RU2795467C2 - Compositions and methods for selective protein expression - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: invention relates to the production of fused proteins, and can be used in medicine for the treatment of cancer in the presence of a stabilizing compound. Recombinantly, fusion proteins are produced containing a conditional expression domain, a domain containing a protein of interest, and a protease-cleavable domain separating two domains.

EFFECT: invention makes it possible to obtain fusion proteins characterized by controlled expression depending on the presence of a stabilizing compound in the medium.

68 cl, 47 dwg, 24 tbl, 29 ex

Description

RELATED APPLICATIONS

This application claims priority based on U.S. Patent Application Serial No: 62/322931, filed April 15, 2016, and U.S. Patent Application Serial No: 62/481094, filed April 3, 2017, the entire contents of each of these applications incorporated herein by reference.

SEQUENCE LIST

This application contains a sequence listing that has been filed electronically in ASCII format and is incorporated herein by reference in its entirety. The specified ASCII copy, created on April 14, 2017, is named N2067-7128WO_SL.txt and has a size of 2326027 bytes.

BACKGROUND OF THE INVENTION

Various constructs have been developed to selectively express a protein of interest. Recently, constructs have been tested containing a domain designed to degrade in the absence of a stabilizing ligand (known in the art as "degrons"). Other constructs contain a domain designed to aggregate in the absence of a disaggregating ligand (eg, an aggregation domain). Such domains can be fused to proteins of interest to selectively express such proteins only in the presence of a stabilizing or deaggregating ligand.

The degrons and aggregation domains known in the art may, in some cases, have certain drawbacks associated with the disruption of the desired function of the protein of interest due to the size and/or conformation of the fusion protein. Such shortcomings may be particularly evident when the protein of interest is a transmembrane protein. Thus, there is a need to improve degron/aggregation domain technology. In addition, there is a need for methods to modify T cells for the treatment of various diseases and conditions, such as, but not limited to, cancer, autoimmune and alloimmune disorders, without permanently modifying or suppressing the immune system.

SUMMARY OF THE INVENTION

In one aspect, the invention relates to fusion proteins comprising two protein domains separated by a heterologous protease cleavage site (e.g., a protease cleavage site that is cleaved by an intracellular or extracellular protease), wherein the first of the protein domains is a conditional expression domain, e.g., a degradation domain or an aggregation domain, and the second protein is the protein of interest, eg, a transmembrane protein (eg, CAR).

In some embodiments, the conditional expression domain is a degradation domain, such as the degradation domain described herein. Without wishing to be bound by a particular theory, in some embodiments, the degradation domain is unstable and/or unable to fold into a stable conformation in the absence of an expression compound, such as a stabilizing compound. The misfolded/unfolded degradation domain may be degraded in intracellular degradation pathways along with other fusion protein domain(s) (see, for example, Figure 25). In the presence of an expression compound, the degradation domain is able to fold into a stable conformation and is less susceptible to degradation in intracellular pathways, for example, compared to the degradation domain in the absence of the expression compound. As a result, the level and/or extent of cell surface expression or extracellular expression of the fusion protein is increased, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or 30-fold, in the presence of an expression compounds compared to those in the absence of the expression compound. In some embodiments, after the degradation domain of the fusion protein assumes the correct conformation, the heterologous cleavage site is exposed, resulting in the removal of the degradation domain and thus the release of the second protein domain.

In other embodiments, the conditional expression domain is an aggregation domain. Without wishing to be bound by a particular theory, in some embodiments, in the absence of an expression compound, e.g., a deaggregating compound, the aggregation domain of the fusion protein binds to one or more other aggregation domains into oligomers and aggregates (see, e.g., Figure 26). The aggregated fusion protein can be sequestered in the cellular compartment in which it has aggregated. In the presence of an expression compound, such as a deaggregating compound, the aggregation domains are separated from each other and the fusion proteins are solubilized (eg, assume a monomeric configuration). As a result, the level and/or extent of cell surface expression or extracellular expression of the fusion protein is increased, for example, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or 30-fold, in the presence of an expression compounds compared to those in the absence of the expression compound. In some embodiments, after the aggregation domain of the fusion protein is solubilized, the heterologous cleavage site is exposed, resulting in the removal of the aggregation domain and thus the release of the second protein domain.

In any of the above aspects and embodiments, the fusion protein comprises a first protein domain that is, or contains, a conditional expression domain, such as a degradation domain or an aggregation domain, and a second protein domain that is, or contains, a protein of interest, such as , a transmembrane protein (eg, CAR), wherein the first and second domains of the fusion protein are separated by a heterologous protease cleavage site (eg, a protease cleavage site that is cleaved by an intracellular or extracellular protease). In some embodiments, a conditional expression domain, such as a degradation or aggregation domain, is located in the N-terminal direction relative to the second protein domain. In specific embodiments, the fusion protein also contains a signal peptide in the N-terminal direction relative to the degradation domain.

In one aspect, the invention provides a fusion protein comprising two protein domains separated by a heterologous protease cleavage site, wherein the first of said protein domains is a conditional expression domain and the second of said protein domains is a transmembrane protein, the conditional expression domain having a first state , associated with the first level of surface expression and/or extracellular expression of the fusion protein, and the second condition associated with the second level of surface expression and/or extracellular expression of the fusion protein, while the second level is increased, for example, at least 2, 3, 4 , 5, 10, 20 or 30 times increased relative to the first level in the presence of an expression compound.

In another aspect, the invention provides a fusion protein comprising two protein domains separated by a heterologous protease cleavage site, wherein the first of said protein domains is a conditional expression domain and the second of said protein domains is a transmembrane protein, wherein the heterologous protease cleavage site is a furin cleavage site, provided that the furin cleavage site does not contain the amino acid sequence SARNRQKR (SEQ ID NO: 981).

In another aspect, the invention provides a fusion protein comprising two protein domains separated by a heterologous protease cleavage site, wherein the first of said protein domains is a conditional expression domain and the second of said protein domains is a chimeric antigen receptor (CAR).

In some embodiments, the conditional expression domain is a degradation domain.

In some embodiments, the conditional expression domain is an aggregation domain.

In some embodiments, the fusion protein comprises two protein domains separated by a heterologous protease cleavage site, wherein the first of said protein domains (herein also referred to as the first protein domain) is, or contains, a degradation domain, e.g., the degradation domain described in herein, and the second of these protein domains (herein also referred to as the second protein domain) is the protein of interest. In one embodiment, the protein of interest is a transmembrane protein, such as CAR.

In some embodiments, the degradation domain is selected from an estrogen receptor (ER) domain, an FKB protein (FKBP) domain, or dihydrofolate reductase (DHFR) domain.

In some embodiments, the degradation domain has a first state associated with a first level of surface expression and/or extracellular expression of the fusion protein and a second state associated with a second level of surface expression and/or extracellular expression of the fusion protein, with the second level elevated, for example, at least 2, 3, 4, 5, 10, 20 or 30 times increased relative to the first level in the presence of a stabilizing compound.

In specific embodiments, the degradation domain is derived from an estrogen receptor. For example, the degradation domain may comprise an amino acid sequence selected from SEQ ID NO: 58, or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity therewith, or SEQ ID NO: 121, or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with it. In some embodiments, the degradation domain comprises an amino acid sequence selected from SEQ ID NO: 58 or SEQ ID NO: 121. If the degradation domain is derived from an estrogen receptor, the stabilizing compound may be selected from bazedoxifene or 4-hydroxy tamoxifen (4-OHT). In some embodiments, the stabilizing compound is bazedoxifene. Tamoxifen and bazedoxifene are FDA approved drugs and thus are safe for human use.

In specific embodiments, the degradation domain is derived from an FKB protein (FKBP). For example, the degradation domain may contain the amino acid sequence of SEQ ID NO: 56 or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with it. In some embodiments, the degradation domain comprises SEQ ID NO: 56. If the degradation domain is derived from FKBP, the stabilizing compound may be Shield-1.

In some embodiments, the degradation domain is derived from dihydrofolate reductase (DHFR). In some embodiments, the degradation domain comprises an amino acid sequence selected from SEQ ID NO: 57 or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with it. In some embodiments, the degradation domain comprises SEQ ID NO: 57. If the degradation domain is derived from DHFR, the stabilizing compound may be trimethoprim.

In other embodiments, the degradation domain is not derived from the FKB protein or the estrogen receptor.

In some embodiments, the fusion protein comprises two protein domains separated by a heterologous protease cleavage site, wherein the first of said protein domains (herein also referred to as the first protein domain) is, or contains, an aggregation domain, e.g., the aggregation domain described in herein, and the second of these protein domains (herein also referred to as the second protein domain) is the protein of interest. In one embodiment, the protein of interest is a transmembrane protein, such as CAR.

In some embodiments, the fusion protein comprises two protein domains separated by a heterologous protease cleavage site, wherein the first of said protein domains is an aggregation domain and the second of said protein domains is a transmembrane protein, the aggregation domain having a first state associated with the first the level of surface expression and/or extracellular expression of the fusion protein, and the second condition associated with the second level of surface expression and/or extracellular expression of the fusion protein, and the second level is increased, for example, at least 2, 3, 4, 5, 10, 20 or 30 times increased, relative to the first level, in the presence of a deaggregating compound.

In some embodiments, the fusion protein comprises two protein domains separated by a heterologous protease cleavage site, wherein the first of said protein domains is an aggregation domain and the second of said protein domains is a transmembrane protein, wherein the heterologous protease cleavage site is a furin cleavage site , provided that the furin cleavage site does not contain the amino acid sequence SARNRQKR (SEQ ID NO: 981).

In some embodiments, the fusion protein comprises two protein domains separated by a heterologous protease cleavage site, wherein the first of said protein domains is an aggregation domain and the second of said protein domains is a chimeric antigen receptor (CAR).

In some embodiments, the implementation of the aggregation domain contains 1, 2, 3, 4 5, 6, 7, 8 or more repeats of the dimerization domain, for example, the domain of homodimerization or heterodimerization.

In some embodiments, the aggregation domain is derived from an FKB protein (FKBP).

In some embodiments, the aggregation domain is an FKBP F36M domain.

In some embodiments, the aggregation domain is derived from a FKB protein (FKBP) and contains an amino acid sequence that is at least 90%, 95%, 97%, 98%, 99%, or 100% identical to any of SEQ ID NOs: 975 or 976.

In some embodiments, the fusion protein also contains a 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, or 10th aggregation domain.

In some embodiments, the 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, or 10th aggregation domain is the same type of aggregation domain as and the first aggregation domain.

In some embodiments, the aggregation domain forms homodimers with the same aggregation domain.

In some embodiments, the fusion protein comprises a plurality of aggregation domains, wherein the plurality includes more than one, eg, two types of aggregation domains, and the first type aggregation domain forms heterodimers with the second type aggregation domain.

In some embodiments, the fusion protein contains 2, 4, 6, 8, or 10 aggregation domains, wherein the fusion protein contains equal numbers of type 1 aggregation domains and type 2 aggregation domains.

In some embodiments, the first type and second type aggregation domains are located in the fusion protein in an alternating order, such as first, second, first, second, or second, first, second, first.

In some embodiments, said antiaggregating compound is selected from FK506, rapamycin, AP22542, AP21998, and Shield-1 if the fusion protein contains an aggregation domain derived from a FKB protein (FKBP), e.g., FKBP F36M.

In some embodiments, said heterologous cleavage site is cleaved by a mammalian intracellular protease.

In some embodiments, said cleavage site is cleaved with a protease selected from the group consisting of furin, PCSK1, PCSK5, PCSK6, PCSK7, cathepsin B, granzyme B, factor XA, enterokinase, genenase, sortase, PreScission protease, thrombin, TEV protease, and elastase 1.

In some embodiments, said cleavage site comprises a polypeptide having a cleavage motif selected from the group consisting of RX(K/R)R consensus motif, RXXX[KR]R consensus motif, RRX consensus motif, I-E-P-D-X consensus motif (SEQ ID NO: 35), Glu/Asp-Gly-Arg, Asp-Asp-Asp-Asp-Lys (SEQ ID NO: 36), Pro-Gly-Ala-Ala-His-Tyr (SEQ ID NO: 37), LPXTG consensus motif /A, Leu-Glu-Val-Phe-Gln-Gly-Pro (SEQ ID NO: 38), Leu-Val-Pro-Arg-Gly-Ser (SEQ ID NO: 40), E-N-L-Y-F-Q-G (SEQ ID NO: 41 ) and [AGSV]-x (SEQ ID NO: 42).

In some embodiments, said cleavage site is cleaved with furin.

In some embodiments, the fusion protein comprises a furin cleavage site selected from RTKR (SEQ ID NO: 123); GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125); GTGAEDPRPSRKRR (SEQ ID NO: 127); LQWLEQQVAKRRTKR (SEQ ID NO: 129); GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131); GTGAEDPRPSRKRRSLG (SEQ ID NO: 133); SLNLTESHNSRKKR (SEQ ID NO: 135) or CKINGYPKRGRKRR (SEQ ID NO: 137).

In some embodiments, the fusion protein contains a furin cleavage site selected from GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or GTGAEDPRPSRKRR (SEQ ID NO: 127).

In some embodiments, the fusion protein contains a furin cleavage site GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125).

In some embodiments, said heterologous protease cleavage site is cleaved by a mammalian extracellular protease.

In some embodiments, said mammalian extracellular protease is selected from the group consisting of factor XA, enterokinase, genenase, sortase, PreScission protease, thrombin, TEV protease, and elastase 1.

In some embodiments, said cleavage site comprises a polypeptide having an amino acid sequence selected from the group consisting of Glu/Asp-Gly-Arg, Asp-Asp-Asp-Asp-Lys (SEQ ID NO: 36), Pro-Gly-Ala -Ala-His-Tyr (SEQ ID NO: 37), LPXTG/A consensus motif, Leu-Glu-Val-Phe-Gln-Gly-Pro (SEQ ID NO: 38), Leu-Val-Pro-Arg-Gly -Ser (SEQ ID NO: 40), E-N-L-Y-F-Q-G (SEQ ID NO: 41) and [AGSV]-x (SEQ ID NO: 42).

In any of the above aspects and embodiments, the heterologous cleavage site is cleaved with furin, PCSK1, PCSK5, PCSK6, PCSK7, cathepsin B, granzyme B, factor XA, enterokinase, genenase, sortase, PreScission protease, thrombin, TEV protease, or elastase 1. For example , the protease cleavage site may comprise a polypeptide having a cleavage motif selected from RX(K/R)R consensus motif, RXXX[KR]R consensus motif, RRX consensus motif, I-E-P-D-X consensus motif (SEQ ID NO: 35), Glu/Asp -Gly-Arg, Asp-Asp-Asp-Asp-Lys (SEQ ID NO: 36), Pro-Gly-Ala-Ala-His-Tyr (SEQ ID NO: 37), LPXTG/A consensus motif, Leu-Glu -Val-Phe-Gln-Gly-Pro (SEQ ID NO: 38), Leu-Val-Pro-Arg-Gly-Ser (SEQ ID NO: 40), E-N-L-Y-F-Q-G (SEQ ID NO: 41) or [AGSV]- x (SEQ ID NO: 42). In specific embodiments, the mammalian extracellular protease is selected from factor XA, enterokinase, genenase, sortase, PreScission protease, thrombin, TEV protease, or elastase 1 (e.g., the cleavage site may contain a polypeptide having an amino acid sequence selected from Glu/Asp-Gly- Arg, Asp-Asp-Asp-Asp-Lys (SEQ ID NO: 36), Pro-Gly-Ala-Ala-His-Tyr (SEQ ID NO: 37), LPXTG/A consensus motif, Leu-Glu-Val- Phe-Gln-Gly-Pro (SEQ ID NO: 38), Leu-Val-Pro-Arg-Gly-Ser (SEQ ID NO: 40), E-N-L-Y-F-Q-G (SEQ ID NO: 41) or [AGSV]-x (SEQ ID NO: 42)).

In some embodiments, the fusion protein described herein contains a furin cleavage site. In some embodiments, the fusion proteins described herein contain any of the furin cleavage sites shown in Table 20. In some embodiments, the fusion proteins described herein contain a furin cleavage site selected from RTKR (SEQ ID NO: 123 ) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRR (SEQ ID NO: 127) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; LQWLEQQVAKRRTKR (SEQ ID NO: 129) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRRSLG (SEQ ID NO: 133) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; SLNLTESHNSRKKR (SEQ ID NO: 135) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; or CKINGYPKRGRKRR (SEQ ID NO: 137) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with it, or GTGAEDPRPSRKRR (SEQ ID NO: 127) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. In some embodiments, the fusion proteins described herein comprise a furin cleavage site GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or a sequence that is at least 90%, 95%, 97%, 98%, or 99% identical to it.

In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from RTKR (SEQ ID NO: 123); GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125); GTGAEDPRPSRKRR (SEQ ID NO: 127); LQWLEQQVAKRRTKR (SEQ ID NO: 129); GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131); GTGAEDPRPSRKRRSLG (SEQ ID NO: 133); SLNLTESHNSRKKR (SEQ ID NO: 135) or CKINGYPKRGRKRR (SEQ ID NO: 137). In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or GTGAEDPRPSRKRR (SEQ ID NO: 127). In some embodiments, the fusion proteins described herein comprise a furin cleavage site GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125).

In some embodiments, a conditional expression domain, such as an aggregation domain or a degradation domain, is N-terminal to said second protein domain or C-terminal to said second protein domain.

In some embodiments, said fusion protein also contains a signal peptide N-terminally relative to said conditional expression domain, such as an aggregation domain or a degradation domain. In some embodiments, the fusion protein also contains a linker located between the signal peptide and the specified conditional expression domain, for example, an aggregation domain or a degradation domain. In some embodiments, the linker is a linker in any of the fusion proteins shown in Tables 23 and 24.

In some embodiments, the fusion protein contains the amino acid sequence of any of the fusion proteins shown in Tables 22, 23, or 24.

In any of the above aspects and embodiments, the second of the protein domains is a transmembrane protein (eg, a transmembrane receptor). In any of the above aspects, the transmembrane receptor may be, for example, a synthetic protein (eg, a chimeric antigen receptor). Chimeric antigen receptors may contain, for example, in the N-terminal to C-terminal direction, an antigen-binding domain, a transmembrane domain, and one or more intracellular signaling domains. The signaling domain may comprise one or more core signaling domains (e.g., the CD3-zeta stimulatory domain) and optionally one or more costimulatory signaling domains (e.g., an intracellular domain from a costimulatory protein selected from CD27, CD28, 4-1BB (CD137) , OX40, GITR, CD30, CD40, ICOS, BAFFR, HVEM, ICAM-1, lymphocyte function-associated antigen 1 (LFA-1), CD2, CDS, CD7, CD287, LIGHT, NKG2C, NKG2D, SLAMF7, NKp80, NKp30, NKp44, NKp46, CD160, B7-H3, or a ligand that specifically binds CD83).

In some of the above embodiments, the antigen binding domain is scFv. In addition, the antigen-binding domain may bind an antigen selected from CD19; CD123; CD22; CD30; CD171; CS-1; lectin-like C-type molecule 1, CD33; epidermal growth factor variant III receptor (EGFRvIII); ganglioside G2 (GD2); ganglioside GD3; a member of the TNF receptor family, B cell maturation antigen (BCMA); Tn antigen ((Tn Ag) or (GalNAcα-Ser/Thr)); prostate specific membrane antigen (PSMA); tyrosine kinase-like orphan receptor 1 (ROR1); Fms-like tyrosine kinase 3 (FLT3); tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; carcinoembryonic antigen (CEA); epithelial cell adhesion molecules (EPCAM); B7H3 (CD276); KIT (CD117); alpha-2 subunits of the interleukin-13 receptor; mesothelin; interleukin-11 receptor alpha subunits (IL-11Ra); prostatic stem cell antigen (PSCA); serine protease 21; vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; platelet growth factor receptor beta (PDGFR-beta); stage-specific embryonic antigen-4 (SSEA-4); CD20; folate receptor alpha; receptor tyrosine-specific protein kinase ERBB2 (Her2/neu); mucin 1 associated with the cell surface (MUC1); epidermal growth factor receptor (EGFR); neuronal adhesion molecules (NCAM); prostases; prostatic acid phosphatase (PAP); mutant elongation factor 2 (ELF2M); aphrine B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAIX); proteasome subunits (prosoma, macropain), type beta, 9 (LMP2); glycoprotein 100 (gp100); an oncogenic fusion protein comprising a rearrangement initiation site (BCR) localization region and Abelson murine leukemia viral oncogene homologue 1 (Abl) (bcr-abl); tyrosinase; aphrin A2 receptor (EphA2); fucosyl GM1; sialyl-Lewis adhesion molecules (sLe); ganglioside GM3; transglutaminase 5 (TGS5); high molecular weight melanoma-associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); folate receptor beta; tumor endothelial marker 1 (TEM1/CD248); antigen related to tumor endothelial marker 7 (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein-coupled receptor class C, group 5, member D (GPRC5D); X chromosome open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); polysialic acid; placenta-specific protein 1 (PLAC1); the hexasaccharide portion of glycoceramide globoH (GloboH); breast differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); hepatitis A virus cell receptor 1 (HAVCR1); adrenoreceptor beta-3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); complex of lymphocytic antigen 6, locus K9 (LY6K); olfactory receptor 51E2 (OR51E2); protein TCR-gamma with an alternative reading frame (TARP); Wilms tumor protein (WT1); testicular cancer antigen 1 (NY-ESO-1); testicular cancer antigen 2 (LAGE-1a); melanoma-associated antigen 1 (MAGE-A1); translocation variant 6 of the ETS gene located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); family X antigens, representative 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); testicular melanoma antigen 1 (MAD-CT-1); testicular melanoma antigen 2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; protein; survivin; telomerase; prostate carcinoma tumor antigen 1, melanoma antigen 1 recognized by T-cells; a protein mutant of the rat sarcoma virus (Ras); human telomerase reverse transcriptase (hTERT); break points during translocation in the case of sarcoma; an inhibitor of apoptosis from melanoma cells (ML-IAP); ERG (transmembrane serine protease 2 (TMPRSS2) and ETS fusion gene); N-acetylglucosamine transferase V (NA17); paired box protein Pax-3 (PAX3); androgen receptor; cyclin B1; a neuroblastoma-derived homologue of the v-myc oncogene of avian myelocytomatosis virus (MYCN); a member of the C family of Ras homologues (RhoC); tyrosinase-related protein 2 (TRP-2); cytochrome P450 1B1 (CYP1B1); a CCCTC-binding factor-like protein (zinc finger protein) recognized by T-cells of squamous cell carcinoma antigen 3 (SART3); paired box protein Pax-5 (PAX5); proacrosin-binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); anchor protein 4 A-kinase (AKAP-4); breakpoints 2 in X in synovial sarcoma (SSX2); receptor for advanced glycosylation end products (RAGE-1); renal ubiquitous protein 1 (RU1); renal ubiquitous protein 2 (RU2); legumain; human papillomavirus E6 protein (HPV E6); human papillomavirus E7 protein (HPV E7); intestinal carboxylesterase; mutant heat shock protein 70-2 (mut hsp70-2); CD79a; CD79b; CD72; leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Fc fragment of the IgA receptor (FCAR or CD89); leukocyte immunoglobulin-like receptors, subfamily A, member 2 (LILRA2); a family of proteins similar to the CD300 molecule, representative f (CD300LF); a family of 12 C-type domain lectins, representative A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); protein 2, like the EGF-like domain-containing mucin-like hormone receptor (EMR2); lymphocyte antigen 75 (LY75); glypican-3 (GPC3); Fc receptor-like protein 5 (FCRL5) or lambda chain-like immunoglobulin polypeptide 1 (IGLL1).

In some embodiments, the fusion protein contains an antigen-binding domain that binds CD19. In some embodiments, the fusion protein comprises an antigen-binding domain comprising an amino acid sequence selected from any of SEQ ID NOs: 356-368 or 381. In some embodiments, the fusion protein comprises a chimeric antigen receptor comprising an amino acid sequence selected from any of SEQ ID NOs. : 897, 902, 907, 912, 917, 922, 927, 932, 937, 942, 947, 952, 956.

In some embodiments, the fusion protein contains an antigen-binding domain that binds CD123. In some embodiments, the fusion protein comprises an antigen-binding domain comprising an amino acid sequence selected from any of SEQ ID NOs: 751, 756, 761, or 766. In some embodiments, the fusion protein comprises a chimeric antigen receptor comprising an amino acid sequence selected from any of SEQ ID NOs: 750, 755, 760 or 765.

In some embodiments, the fusion protein contains an antigen-binding domain that binds BCMA. In some embodiments, the fusion protein comprises an antigen binding domain comprising an amino acid sequence selected from any of SEQ ID NOs: 382, 386, 390, 394, 398, 402, 406, 410, 414, 418, 422, 426, 430, 434, 438, 442, 446, 450, 454, 458, 462, 466, 470, 474, 478, 482, 486, 490, 494, 498, 502, 506, 510, 514, 518, 522, 528, 531, 5 34 or 537. In some embodiments, the fusion protein comprises a chimeric antigen receptor comprising an amino acid sequence selected from any of SEQ ID NOs: 789, 791, 793, 795, 797, 799, 801, 803, 805, 807, 809, 811, 813 , 815, 817, 819, 821, 823, 825, 827, 829, 831, 833, 835, 837, 839, 841, 843, 845, 847, 849, 851, 853, 855, 857 or 859.

In some embodiments, the fusion protein contains an antigen-binding domain that binds CD20. In some embodiments, the fusion protein comprises an antigen-binding domain comprising the amino acid sequence occupying positions 470-712 or 470-939 of SEQ ID NO: 3033. In some embodiments, the fusion protein comprises a chimeric antigen receptor comprising the amino acid sequence of SEQ ID NO: 3033.

Cells, Nucleic Acids and Process for Producing Fusion Proteins

In another aspect, the invention relates to a cell, eg a host cell, comprising any of the above fusion proteins. In some embodiments, the cell, such as a host cell, is an immune cell, such as an immune effector cell. In some embodiments, the cell is a T cell or an NK cell.

In another aspect, the invention relates to a nucleic acid (eg, mRNA or DNA molecule) encoding any of the above fusion proteins. In another aspect, the invention relates to a vector (eg, a viral vector (such as a lentiviral vector)) containing such a nucleic acid. The invention also relates to a viral particle containing such a viral vector.

In another aspect, the invention relates to a cell, eg, a host cell (eg, a human T cell), containing any of the above vectors, nucleic acids, or fusion proteins.

In specific embodiments, the cell also contains a protease capable of cleaving a heterologous protease cleavage site. In specific embodiments, the host cell may also contain a stabilizing compound (e.g., bazedoxifene, Shield-1, or 1 μM 4-OHT (4-hydroxy tamoxifen)), wherein said degradation domain adopts a conformation that promotes degradation in the cell in the absence of said stabilizing compound. .

In some embodiments, in the absence of an expression compound, e.g., a stabilizing compound, the fusion protein is degraded in cellular degradation pathways, e.g., at least 50%, 60%, 70%, 80%, 90% or more of the fusion protein is degraded.

In some embodiments, in the absence of an expression compound, such as a disaggregating compound, the fusion protein is in an aggregated state within the cell, such as the endoplasmic reticulum or cytosol, such as at least 50%, 60%, 70%, 80%, 90% or more of the protein is in an aggregated state.

In some embodiments, said cell also contains an expression compound, such as a stabilizing compound.

In some embodiments, a conditional expression domain, such as a degradation domain, adopts a conformation that is more resistant to degradation in the cell in the presence of an expression compound, such as a stabilizing compound, compared to a conformation in the absence of the expression compound.

In some embodiments, the fusion protein conformation is more susceptible to cleavage at a heterologous protease cleavage site in the presence of an expression compound, eg, a stabilizing compound, compared to a conformation in the absence of the expression compound.

In some embodiments, the level of cell surface expression or extracellular expression of the fusion protein is increased, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or 30 times higher than the level of cell surface expression or extracellular expression. a fusion protein in a cell that does not contain an expression compound, such as a stabilizing compound.

In some embodiments, said cell also contains an expression compound, such as a deaggregating compound.

In some embodiments, a conditional expression domain, such as an aggregation domain, assumes a conformation that is more resistant to oligomerization or aggregation in the presence of an expression compound, such as a deaggregating compound, compared to a conformation in the absence of the expression compound.

In some embodiments, the fusion protein conformation is more susceptible to cleavage at a heterologous protease cleavage site in the presence of an expression compound, eg, a deaggregating compound, compared to a conformation in the absence of an expression compound.

In some embodiments, the level of cell surface expression or extracellular expression of the fusion protein is increased, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or 30 times higher than the level of cell surface expression or extracellular expression. a fusion protein in a cell that does not contain an expression compound, such as a deaggregating compound.

In another aspect, a method for making a fusion protein described herein is disclosed. The method includes obtaining a cell, for example, a host cell described herein, for example, a host cell, containing any of the above vectors, nucleic acids, or fusion proteins, under conditions suitable for expression.

In another aspect, the invention also relates to a method for conditionally expressing a protein of interest. In one embodiment, the protein of interest is a transmembrane protein, such as CAR.

In some embodiments, the invention also relates to a method for conditionally expressing a protein of interest, a transmembrane protein, or a CAR on the surface of a cell (eg, an immune cell, eg, a host cell). The method includes:

obtaining a cell, for example, an immune cell (eg, a host cell) containing a fusion protein or a nucleic acid encoding a fusion protein (eg, any of the fusion proteins described herein);

creating a contact of the fusion protein or a cell containing the specified fusion protein with an expression compound, while:

(a) in the presence of said expression compound, the surface expression of said protein of interest, transmembrane protein, or CAR is increased, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or 30 times greater than the reference value , for example, relative to the level of surface expression of said protein of interest, transmembrane protein, or CAR in the absence of said expression compound; And

(b) in the absence of said expression compound, surface expression of said protein of interest, transmembrane protein, or CAR is significantly reduced, e.g. values, for example, relative to the level of surface expression of the indicated protein of interest, transmembrane protein or CAR in the presence of the expression compound.

In some embodiments, the presence of said expression compound is associated with, for example, causes, a conformational change in the conditional expression domain from a first folded state to a second folded state, wherein the first folded state is more susceptible to degradation, such as cellular degradation or aggregation, as compared to the second folded state.

In some embodiments, the presence of said expression compound results in the exposure of the heterologous protease cleavage site, e.g., to a greater extent, e.g. exposing the protease cleavage site in the absence of said expression compound.

In some embodiments, the invention also provides a method for conditionally expressing a protein, transmembrane protein, or CAR of interest, comprising contacting a cell, such as a host cell and/or a cell described herein, with a stabilizing compound, wherein:

(a) in the presence of said stabilizing compound,

(i) said degradation domain adopts a conformation that is more resistant to degradation in the cell compared to the conformation in the absence of the stabilizing compound,

which results in cleavage of said degradation domain from said protein of interest, transmembrane protein or CAR and expression of said protein of interest, transmembrane protein or CAR; And

(b) in the absence of said stabilizing compound, said degradation domain adopts a conformation that is more susceptible to degradation in the cell than in the presence of the stabilizing compound, resulting in degradation of said protein of interest, transmembrane protein, or CAR.

In some embodiments, said cell is contacted ex vivo with said stabilizing compound.

In some embodiments, said cell is contacted with said stabilizing compound in vivo .

In some embodiments, the invention also provides a method for conditionally expressing a protein, transmembrane protein, or CAR of interest, comprising contacting a cell, such as a host cell and/or a cell described herein, with a deaggregating compound, wherein:

(a) in the presence of said anti-aggregating compound

(i) said aggregation domain adopts a conformation that is more resistant to aggregation or oligomerization compared to a conformation in the absence of a deaggregating compound,

which results in cleavage of said aggregation domain from said protein of interest, transmembrane protein or CAR and expression of said protein of interest, transmembrane protein or CAR; And

(b) in the absence of said antiaggregating compound, said aggregation domain adopts a more aggregating or oligomerizing conformation than in the presence of the antiaggregating compound, resulting in aggregation of said protein of interest, transmembrane protein, or CAR.

In some embodiments, said cell is contacted ex vivo with said antiaggregating compound.

In some embodiments, said cell is contacted with said antiaggregating compound in vivo .

In another aspect, the invention relates to a method of treating a subject having a disease associated with the expression of a tumor antigen, comprising administering to the subject an effective amount of any of the above host cells, wherein the second protein is a chimeric antigen receptor and contains, in the direction from the N-terminus to C-terminally, an antigen-binding domain, a transmembrane domain and one or more intracellular signaling domains, and an antigen-binding domain specifically binds a tumor antigen. In another aspect, the invention relates to a method of treating an autoantibody or alloantibody induced disease or condition comprising administering to a subject an effective amount of said host cell, said second protein being a chimeric antigen receptor and comprising, in N-terminal to C-terminal direction, an antigen-binding domain, a transmembrane domain, and one or more intracellular signaling domains, and said antigen-binding domain specifically binds an antigen specific for said autoantibody- or alloantibody-induced disease. In such methods, the host cell may be either autologous or non-autologous, eg, allogeneic, to the subject. Such methods may also include the step of contacting the host cell, in vivo or ex vivo , with the aforementioned stabilizing compounds.

In some embodiments, the cell is contacted with an expression compound and:

(a) in the presence of said expression compound

(i) said conditional expression domain adopts a conformation more resistant to degradation or aggregation in the cell than in the absence of said expression compound, resulting in said conditional expression domain being cleaved from said chimeric antigen receptor (CAR) and expression of said CAR; And

(b) in the absence of said expression compound, said conditional expression domain assumes a conformation that is more susceptible to degradation or aggregation in the cell than in the presence of said expression compound, resulting in degradation or aggregation of said fusion protein.

In some embodiments, a cell, such as a host cell, is contacted with a stabilizing compound and:

(a) in the presence of said stabilizing compound

(i) said degradation domain assumes a conformation that is more resistant to degradation in the cell than in the absence of said stabilizing compound,

which results in cleavage of said degradation domain from said chimeric antigen receptor (CAR) and expression of said CAR; And

(b) in the absence of said stabilizing compound, said degradation domain assumes a conformation more susceptible to degradation in the cell than in the presence of said stabilizing compound, resulting in degradation of said fusion protein.

In some embodiments, said stabilizing compound is selected from bazedoxifene or 4-hydroxy tamoxifen (4-OHT) if the fusion protein contains a degradation domain derived from the estrogen receptor.

In some embodiments, said stabilizing compound is Shield-1 if the fusion protein contains a degradation domain derived from the FKB protein.

In some embodiments, the cell is contacted with a deaggregating compound and:

(a) in the presence of said anti-aggregating compound

(i) said aggregation domain adopts a conformation that is more resistant to aggregation or oligomerization compared to a conformation in the absence of said antiaggregating compound,

which results in cleavage of said aggregation domain from said chimeric antigen receptor (CAR) and expression of said CAR; And

(b) in the absence of said anti-aggregating compound, said aggregation domain adopts a conformation more prone to aggregation or oligomerization than in the presence of said anti-aggregating compound, resulting in aggregation of said fusion protein.

In some embodiments, said antiaggregating compound is selected from FK506, rapamycin, AP22542, and AP21998 if the fusion protein contains an aggregation domain derived from a FKB protein (FKBP), such as FKBP F36M.

In some embodiments, the autoantibody-induced disease or condition is selected from the group consisting of bullous pemphigoid, acquired epidermolysis bullosa, p200 pemphigoid, linear IgA-dependent bullous dermatosis, other diseases of the pemphigoid group, dermatitis herpetiformis, gluten-sensitive celiac disease, myasthenia gravis, Goodpasture's syndrome, granules hematosis with polyangiitis and other ANCA+ forms of vasculitis, autoimmune encephalitis involving the limbic system, anti-NMDA receptor encephalitis, neuromyelitis of the optic nerve, autoimmune hemolytic anemia, autoantibody-induced target organ damage in lupus and other connective tissue diseases (caused by anti-dsDNA, anti- -Ro and other autoantibodies), Graves' disease and Hashimoto's thyroiditis, production of antibodies against insulin in diabetes, antibodies against insulin receptors in autoimmune hypoglycemia, cryoglobulinemia, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, dermatomyositis, production of antibodies against Fc-epsilon receptors in chronic idiopathic urticaria, anti-folate receptor antibodies, anti-endothelial receptor or anti-adrenergic receptor antibodies in pulmonary arterial hypertension, refractory hypertension, dilated cardiomyopathy, autoinflammatory syndrome, optic neuromyelitis, Goodpasture's syndrome, anti-NMDAR encephalitis, AIHA, ITP, TTP, Graves' disease /Hashimoto's, primary biliary cirrhosis, neonatal lupus, production of maternal autoantibodies causing destruction of T-cells, pulmonary alveolar proteinosis, production of antibodies against folate receptors, chronic inflammatory demyelinating polyneuropathy and idiopathic membranous nephropathy. In some embodiments, the alloantibody-induced disease or condition is an immune response to organ transplantation, blood transfusion, pregnancy, or protein replacement therapy.

In some embodiments, the cancer is mesothelioma (eg, malignant pleural mesothelioma), for example, in a subject that has progressed on at least one previous standard therapy; lung cancer (eg, non-small cell lung cancer, small cell lung cancer, squamous cell lung cancer, or large cell lung cancer); pancreatic cancer (eg, pancreatic ductal adenocarcinoma or metastatic pancreatic ductal adenocarcinoma (PDA), eg, in a subject that has progressed on at least one previous standard therapy); adenocarcinoma of the esophagus, ovarian cancer (e.g., serous epithelial ovarian cancer, e.g., in a subject that has progressed after at least one previous standard therapy regimen), breast cancer, colorectal cancer, bladder cancer, or any combination thereof.

In some embodiments, the tumor antigen expression disease is cancer.

In some embodiments, the disease associated with the expression of the tumor antigen is a hematological cancer, for example, a hematological cancer selected from leukemia or lymphoma.

In some embodiments, the cancer is selected from: chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), multiple myeloma, acute lymphoid leukemia (ALL), Hodgkin's lymphoma, B-cell acute lymphoid leukemia (BALL), T-cell acute lymphoid leukemia (TALL), small cell lymphocytic lymphoma (SLL), B-cell prolymphocytic leukemia, blast plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL associated with chronic inflammation, chronic myeloid leukemia , myeloproliferative neoplasms, follicular lymphoma, follicular lymphoma in children, hairy cell leukemia, small cell or large cell follicular lymphoma, malignant lymphoproliferative conditions, MALT-type lymphoma (extranodal marginal zone lymphoma arising from mucosal associated lymphoid tissue), marginal zone lymphoma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin's lymphoma, plasmablastic lymphoma, neoplasms from plasmacytoid dendritic cells, Waldenström's macroglobulinemia, lymphoma of the marginal zone of the spleen, lymphoma/leukemia of spleen cells, diffuse small cell B-cell lymphoma of the red pulp of the spleen, hairy cell leukemia - a variant, lymphoplasmic lymphomas, diseases heavy chain, plasma cell myeloma, solitary bone plasmacytoma, extraosseous plasmacytoma, nodal marginal zone lymphoma, nodal marginal zone lymphoma in children, primary cutaneous follicular lymphoma, lymphogranulomatosis, primary mediastinal large B-cell lymphoma (thymus), intravascular large B-cell lymphoma, ALK+ large B-cell lymphoma, large B-cell lymphoma arising from HHV8-associated multifocal Castleman's disease, primary effusion lymphoma, B-cell lymphoma, acute myeloid leukemia (AML), or unclassifiable lymphoma.

In some embodiments, the cancer is selected from MCL, CLL, ALL, Hodgkin's lymphoma, AML, or multiple myeloma.

In another aspect, the invention relates to a fusion protein, cell, nucleic acid, viral particle or vector described herein for use as a drug.

In another aspect, the invention provides a fusion protein, cell, nucleic acid, vector, or method as described herein for use in the treatment of a disease in which a tumor antigen is expressed.

Methods and compositions for use in the treatment of autoantibody- or alloantibody-induced disease

In one aspect, the invention relates to methods of treating an autoantibody or alloantibody induced disease or condition in a subject in need thereof, comprising administering an effective amount of a pharmaceutical composition comprising a modified T cell to the subject, wherein the modified T cell contains a nucleic acid containing a suicide a gene, and a nucleic acid encoding a chimeric antigen receptor (CAR) containing an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain. In another aspect, the invention relates to methods of treating an autoantibody or alloantibody induced disease or condition in a subject in need thereof, comprising administering an effective amount of a pharmaceutical composition comprising a modified T cell to the subject, wherein the modified T cell comprises a nucleic acid encoding a domain dimerization and a chimeric antigen receptor (CAR) containing an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain.

In some embodiments, the suicide gene encodes an amino acid sequence selected from the group consisting of SEQ ID NOs: 3005-3007.

In some embodiments, the suicide gene product also contains a dimerization domain containing an amino acid sequence selected from the group consisting of SEQ ID NOS: 3013 and 3014.

In some embodiments, the dimerization domain comprises the amino acid sequence of SEQ ID NO: 980.

In some embodiments, the dimerization domain also contains a furin cleavage site containing the amino acid sequence of SEQ ID NO: 980.

In some embodiments, the CAR also contains a signal peptide.

In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3035.

In some embodiments, administration of an effective amount comprises activating the modified T cell to produce a cytotoxic effect on B cells.

In some embodiments, the method further comprises activating the suicide gene product to induce cell death of the modified T cell.

In some embodiments, activation of the suicide gene product also includes administering a dimerizing agent to promote dimerization of the suicide gene product.

In some embodiments, activation of the suicide gene product occurs after the modified T cell has a cytotoxic effect on B cells.

In some embodiments, activation of the suicide gene product occurs after the subject develops an adverse reaction to the modified T cell.

In some embodiments, the method further comprises suppressing activation of the suicide gene product to suppress cell death of the modified T cell.

In some embodiments, suppressing activation of the suicide gene product also includes administering a solubilizing agent to prevent dimerization of the suicide gene product.

In some embodiments, administration of the solubilizing agent occurs concurrently with administration of the modified T cell and continues until the modified T cell has a cytotoxic effect on B cells.

In some embodiments, administration of the solubilizing agent is terminated after the subject develops an adverse reaction to the modified T cell.

In some embodiments, the CAR anti-B cell binding domain comprises an antibody selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a synthetic antibody, a human antibody, a humanized antibody, a single domain antibody, a single chain variable fragment, and antigen binding fragments thereof.

In some embodiments, the CAR anti-B cell binding domain specifically binds a B cell marker selected from the group consisting of CD19, BCMA, CD20, CD21, CD27, CD38, CD138, and any combination thereof.

In some embodiments, the CAR anti-B cell binding domain specifically binds a B cell marker selected from the group consisting of CD20, CD21, CD27, CD38, CD138, any combination thereof, and at least one surface marker found exclusively on pro-B cell, pre-B cell, immature B cell, mature B cell, memory B cell and plasma cell.

In some embodiments, the intracellular CAR domain contains dual signaling domains.

In some embodiments, the co-stimulatory domain is selected from the group consisting of CD3, CD27, CD28, CD83, CD86, CD127, 4-1BB, 4-1BBL, PD-1, PD-1L, T cell receptor (TCR), any of them. a derivative or variant, any synthetic sequence thereof that has the same functional properties, as well as any combination thereof.

In some embodiments, the method further comprises administering a solubilizing agent to prevent dimerization of the CAR.

In some embodiments, administration of the solubilizing agent occurs concurrently with administration of the modified T cell and continues until the modified T cell has a cytotoxic effect on B cells.

In some embodiments, administration of the solubilizing agent is terminated after the subject develops an adverse reaction to the modified T cell.

In some embodiments, the autoantibody-induced disease or condition is selected from the group consisting of bullous pemphigoid, acquired epidermolysis bullosa, p200 pemphigoid, linear IgA-dependent bullous dermatosis, other diseases of the pemphigoid group, dermatitis herpetiformis, gluten-sensitive celiac disease, myasthenia gravis, Goodpasture's syndrome, granules hematosis with polyangiitis and other ANCA+ forms of vasculitis, autoimmune encephalitis involving the limbic system, anti-NMDA receptor encephalitis, neuromyelitis of the optic nerve, autoimmune hemolytic anemia, autoantibody-induced target organ damage in lupus and other connective tissue diseases (caused by anti-dsDNA, anti- -Ro and other autoantibodies), Graves' disease and Hashimoto's thyroiditis, production of antibodies against insulin in diabetes, antibodies against insulin receptors in autoimmune hypoglycemia, cryoglobulinemia, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, dermatomyositis, production of antibodies against Fc-epsilon receptors in chronic idiopathic urticaria, antibodies against folate receptors, antibodies against endothelial receptors or against adrenergic receptors in pulmonary arterial hypertension, refractory hypertension, dilated cardiomyopathy and autoinflammatory syndrome.

In some embodiments, the alloantibody-induced disease or condition is an immune response to organ transplantation, blood transfusion, pregnancy, or protein replacement therapy.

In some embodiments, the modified T cell is further modified by deletion of a gene selected from the group consisting of T cell receptor (TCR) chain genes, major histocompatibility complex protein, and any combinations thereof.

In some embodiments, the modified T cell is further modified prior to administration to a subject in need thereof.

In some embodiments, the modified T cell is further modified by induction of the CRISPR/Cas system.

In one aspect, the invention relates to a pharmaceutical composition formulated for use in the method described herein, comprising a modified T cell containing a nucleic acid encoding a suicide gene and a nucleic acid encoding a chimeric antigen receptor (CAR) containing anti-B -cellular binding domain, transmembrane domain, costimulatory domain and intracellular signaling domain.

In one aspect, the invention relates to a pharmaceutical composition formulated for use in the method described herein, comprising a modified T cell containing a nucleic acid encoding a dimerization domain and a chimeric antigen receptor (CAR) containing an anti-B-cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain.

In some embodiments, the suicide gene encodes an amino acid sequence selected from the group consisting of SEQ ID NOs: 3005-3007.

In some embodiments, the suicide gene product also contains a dimerization domain containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 3013 and 3014.

In some embodiments, the dimerization domain comprises the amino acid sequence of SEQ ID NO: 980.

In some embodiments, the dimerization domain also contains a furin cleavage site containing the amino acid sequence of SEQ ID NO: 980.

In some embodiments, the CAR also contains a signal peptide.

In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3035.

In some embodiments, the composition also contains an inducing agent for inducing activation of a suicide gene.

In some embodiments, the modified T cell lacks at least one gene encoding the T cell receptor (TCR) chain and major histocompatibility complex protein.

In one aspect, the invention relates to an isolated nucleotide sequence, which is a nucleotide sequence containing (i) a suicide gene containing a nucleotide sequence selected from the group consisting of SEQ ID NOs: 3001-3004, and (ii) a nucleotide sequence encoding a chimeric antigenic a receptor (CAR) containing an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain.

In some embodiments, the isolated nucleotide sequence comprises SEQ ID NO: 3018, 3020, 3024, 3026, 3028, or 3030.

In one aspect, the invention provides an isolated polypeptide comprising (i) an amino acid sequence encoded by a suicide gene, wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs: 3005-3007, and (ii) a chimeric antigen receptor (CAR) comprising an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain.

In some embodiments, the isolated polypeptide comprises the amino acid sequence of SEQ ID NO: 3019, 3021, 3026, 3028, 3030, or 3034.

In one aspect, the invention provides an isolated nucleotide sequence comprising (i) a nucleic acid encoding a dimerization domain and (ii) a chimeric antigen receptor (CAR) comprising an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain.

In some embodiments, the dimerization domain comprises the amino acid sequence of SEQ ID NO: 980.

In some embodiments, the isolated nucleotide sequence comprises SEQ ID NO: 977 or 3032.

In one aspect, the invention provides an isolated polypeptide comprising (i) a dimerization domain and (ii) a chimeric antigen receptor (CAR) comprising an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain.

In some embodiments, the isolated polypeptide comprises the amino acid sequence of SEQ ID NO: 978 or 3033.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the expression of members of the PCSK (proprotein convertase) family in primary human T cells. Expression of members of the PCSK family was measured by qRT-PCR. RNA was isolated from normal donor T cells on days 0, 4 and 11 after stimulation with anti-CD3/anti-CD28 activating beads. In the additional group, 100 U/ml IL-2 was added to the medium during culture and RNA was isolated on day 11.

FIG. 2 is a series of graphs showing compound dependent CAR expression in Jurkat T cells transduced with an anti-CD19 scFv CAR construct fused to the indicated furin degradation domain (FKBP _FD , ERα _FD , or DHFR _FD ), followed by treatment with the appropriate stabilizing compound. FKBP _FD -transduced cells were treated with 1 μM Shield-1 solution; ERα _FD -transduced cells were treated with 1 μM bazedoxifene solution; DHFR _FD -transduced cells were treated with 1 mM trimethoprim (TMP). Expression of anti-CD19 scFv was induced with a stabilizing compound. Black = HT (not transduced cells); gray = construct, no connection; white = construct, with connection.

FIG. 3 is a graph showing the kinetics of CAR expression in Jurkat T cells transduced with an anti-CD19 scFv CAR construct fused to the indicated furin degradation domain (FKBP _FD or ERα _FD ), followed by the addition of a stabilizing compound. FKBP _FD -transduced cells were treated with 1 μM Shield-1 solution and ERα _FD -transduced cells were treated with 1 μM 4-OHT (4-hydroxytamoxifen) solution for the indicated time; and CAR expression was determined by FACS.

FIG. 4 is a series of histograms showing that the ERα _FD furin degron domain can regulate CAR19 expression in a bazedoxifene dependent manner in primary human T cells and that stabilization is enhanced in the presence of IL-2 in vitro . Primary human T cells were transduced with an ERα _FD domain fused to an anti-CD19 scFv CAR construct. 100 U/ml IL-2 was added on day 9 after activation with anti-CD3/CD28 stimulation beads. Bazedoxifene was added on day 10 and CAR expression was determined by FACS on day 11.

FIG. 5 is a pair of graphs showing the kinetics of CAR expression after compound washout in primary T cells transduced with a CAR construct fused to the degradation furin domain. Primary human T cells were transduced with the indicated furin degradation domain (FKBP _FD or ERα _FD ) fused to an anti-CD19 scFv CAR construct. 100 U/ml IL-2 was added on day 9 after activation with anti-CD3/CD28 stimulating beads. Bazedoxifene was added on day 10 and T cells were frozen on day 11. T cells were thawed, washed copiously and cultured for the indicated time periods, followed by determination of CAR expression by FACS.

FIG. 6 is a series of graphs showing that several ERα-targeted drugs stabilize FurOn CART. Jurkat T cells were transduced with an ERα _FD degradation domain fused to an anti-CD19 scFv CAR construct, followed by treatment with the indicated compounds for 24 hours. The ERα-targeting drugs used were: 10 μM 4-OHT, 1 μM bazedoxifene, or 1 μM lasofoxifene.

FIG. 7 is a graph showing bazedoxifene dose-dependent expression of ERα _FD fused to CAR. Primary human T cells were transduced with an ERα _FD degradation domain fused to an anti-CD19 scFv CAR construct or a parental CD19 CAR construct. 100 U/ml IL-2 was added on day 9 after activation with anti-CD3/CD28 stimulating beads and T cells were frozen on day 11. T cells were thawed and cultured with bazedoxifene at the indicated concentrations for 48 hours. CAR expression was determined by FACS.

FIG. 8 is a pair of graphs showing compound-dependent, target-specific killing of FurON CART cells based on ER-alpha. Primary human T cells were transduced with an ERα _FD degradation domain fused to an anti-CD19 scFv CAR construct or a parental CD19 CAR construct. 100 U/ml IL-2 and bazedoxifene were added on day 9 after activation with anti-CD3/CD28 stimulation beads and T cells were frozen on day 11. T cells were thawed and incubated for 20 hours with luciferase-containing target cells of the indicated lines, K562 (CD19-) or NALM6 (CD19+). The percentage of cell destruction was determined by analysis of residual luciferase activity.

FIG. 9 is a pair of graphs showing compound-dependent, target-specific killing of FKBP-based FurON CART cells. Primary human T cells were transduced with the FKBP _FD furin degradation domain fused to an anti-CD19 scFv CAR construct or the parental CD19 CAR construct. 100 U/mL IL-2 and Shield-1 were added on day 9 after activation with anti-CD3/CD28 stimulation beads and T cells were frozen on day 11. T cells were thawed and incubated for 20 hours with luciferase-containing cells. targets of these lines, K562 (CD19-) or NALM6 (CD19+). The percentage of cell destruction was determined by analysis of residual luciferase activity.

FIG. 10 is a pair of graphs showing compound-dependent cytokine production in FurOn CART ER-alpha. Primary human T cells were transduced with the ERα _FD furin degradation domain fused to an anti-CD19 scFv CAR construct or the parental CD19 CAR construct. 100 U/ml IL-2 and bazedoxifene were added on day 9 after activation with anti-CD3/CD28 stimulation beads and T cells were frozen on day 11. T cells were thawed and incubated with target cell lines for 20 hours. Supernatants were collected and analyzed with a set of anti-cytokine antibody beads.

FIG. 11 is a graph showing compound-dependent proliferation of FurOn CART ER-alpha. Primary human T cells were transduced with an ERα _FD degradation domain fused to an anti-CD19 scFv CAR construct or a parental CD19 CAR construct. 100 U/ml IL-2 and bazedoxifene were added on day 9 after activation with anti-CD3/CD28 stimulation beads and T cells were frozen on day 11. T cells were thawed and incubated with target cell lines for 4 days. The number of FurON-CAR T cells was analyzed by FACS.

FIG. 12A-12B are representative immunoblots showing the degree of furin cleavage of the various furin cleavage sites tested in the ERα-FurON constructs for CAR19. Furin cleavage sites tested are:

No. 105 - LQWLEQQVAKRRTKR (SEQ ID NO: 129); No. 106 - GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125); No. 107 - GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131); No. 108 - GTGAEDPRPSRKRRSLG (SEQ ID NO: 133); No. 102 - SLNLTESHNSRKKR (SEQ ID NO: 135); No. 103 - GTGAEDPRPSRKRR (SEQ ID NO: 127); No. 104 - CKINGYPKRGRKRR (SEQ ID NO: 137); No. 73 - RTKR (SEQ ID NO: 123).

FIG. 13 is a table showing that the FurON domain (furin degron) regulates CAR19 expression in a stabilizing compound-dependent manner in human primary T cells, but does not affect cell viability and cell proliferation.

FIG. 14 is a series of line graphs showing that CAR19 with the furin degron domain kills CD19+ tumor cells in a stabilizing compound dose-dependent manner and is no less effective than the parental CAR construct.

FIG. 15 is a bar graph showing that primary human T cells expressing ERαFurON CAR19 secrete IFNγ in the presence of CD19+ tumor cells in a dose-dependent manner with a stabilizing compound and are no less potent than cells with the CAR parent construct.

FIG. 16 is a series of histograms showing that primary human T cells expressing ERαFurON CAR19 proliferate in the presence of tumor CD19+ cells in a dose-dependent manner with a stabilizing compound and are not inferior to cells with the CAR19 parent construct.

FIG. 17 is a series of graphs showing that the FurON domains tested regulate CAR19 expression in Jurkat T cells in a compound-dependent manner, regardless of the number of mutations; and no surface expression of CAR was detected in the absence of a stabilizing compound.

FIG. 18 is a table showing that the FurON domain regulates CAR19 expression in a stabilizing compound dependent and IL-2 dependent manner in human primary T cells. Surface expression of CAR cannot be detected in the absence of the stabilizing compound bazedoxifene when the FurON fragment is fused to CAR19.

FIG. 19A-19B are line graphs showing that CAR T cells expressing FurON CAR19, which has a limited number of mutations in the degron domain, kill CD19+ tumor cells in a stabilizing compound-dependent and target-dependent manner, and are no less effective than cells with the parent construct CAR.

FIG. 20 is a bar graph showing that CAR T cells expressing FurON CAR19, which has a limited number of mutations in the degron domain, secrete cytokines in the presence of CD19+ tumor cells in a stabilizing compound-dependent manner and are not inferior to cells with the parental CAR construct.

FIG. 21 is a bar graph showing that FurON CAR19-containing CD3+ T cells proliferate in the presence of tumor CD19+ cells in a stabilizing compound-dependent manner and are not inferior to cells with the CAR parent construct.

FIG. 22 is a series of graphs showing that the FurON domain regulates CAR123 expression in primary human T cells in a stabilizing compound dependent manner.

FIG. 23 is a series of histograms showing that CAR T cells expressing FurON CAR123 kill tumor CD123+ cells in a stabilizing compound- and target-dependent manner and are no less efficient than cells with the CAR parent construct.

FIG. 24 is a series of histograms showing that CAR T cells expressing FurON CAR123 secrete cytokines in the presence of CD123+ tumor cells in a stabilizing compound-dependent manner and are not inferior to cells with the CAR parent construct.

FIG. 25 is a schematic representation of an exemplary fusion protein containing a degradation domain (degron), a protease cleavage site, and a second protein domain (CAR), as well as reversal of degradation of the fusion protein in the presence of a drug, such as a stabilizing compound.

FIG. 26 is a schematic representation of an exemplary fusion protein containing four copies of an aggregation domain (FKBP12F36M), a protease cleavage site (furin cleavage site), and a second protein domain (scFv with a cytoplasmic tail), and an alteration in fusion protein aggregation in the presence of a compound, e.g. , a deaggregating compound. This figure is an illustration of the onCAR regulatory system, which is another embodiment for controlling cell surface expression and thus CAR function. CAR is expressed downstream of the modified FKBP12 domains, separated by a furin cleavage site. In the absence of a solubilizing compound, CAR molecules spontaneously aggregate in the endoplasmic reticulum and fewer CAR molecules can surface on the T cell, eg no CAR molecules. This results in a reduction in CAR-mediated T cell function, eg, a lack of CAR-mediated T cell function. In the presence of a solubilizing compound, the aggregation domains of CARs are separated and aggregation is prevented. The furin cleavage site, which is N-terminal to the scFv, becomes available for cleavage. After removal of aggregation domains by furin in the late cisternae of the Golgi apparatus, CAR molecules come to the surface of T cells and CAR-mediated function of T cells can be carried out.

FIG. 27 is an illustration of an anti-CD19 or anti-CD20 chimeric antigen receptor suicide switch (inducible caspase-9 or iCasp9 or iC9) construct, called CD19 sCAR or CD20 sCAR, designed to induce complete but transient depletion of B cells. CD19/CD20 sCAR T cells exert their therapeutic effect by depleting B cells after infusion. Subsequent administration of low molecular weight compounds leads to dimerization of caspase-9 and activation of caspase activity, which leads to self-destruction of CD19/CD20 sCAR T cells, which may result in restoration of the B cell population.

FIG. 28 is a schematic of a reversible caspase-9 suicide cassette, which is another embodiment of a caspase-9 suicide cassette. In the CD19/CD20 revCAR system, caspase-9 is constitutively expressed and spontaneously dimerizes, thereby inducing apoptosis by default in CD19 revCAR T cells. In the presence of a small molecule compound that solubilizes caspase-9 molecules (ie, inhibits dimerization), caspase activity is inhibited. Thus, treatment with a low molecular weight solubilizer leads to inhibition of caspase-9 activity during expansion and infusion of revCAR T cells, and removal of a low molecular weight solubilizer leads to activation of caspase-9 and self-destruction of revCAR T cells, as a result of which restoration of the B cell population can occur.

FIG. 29A-29F are a series of graphs showing efficient expression of the CD19 sCAR, CD19revCAR, and CD20 CAR constructs in primary human T cells.

FIG. 30 is a graph showing in vitro specific target killing by CD19 sCAR cells. NALM6 is a B cell line expressing CD19 (gt, wild type). CD19 sCAR T cells killed CD19+ NALM6 cells, while non-transduced (NT) T cells or T cells expressing control sCAR (negative control) did not recognize NALM6 gt cells.

FIG. 31 is a graph showing the specific and robust elimination of CD19 sCAR T cells after caspase-9 suicide switch activation with AP20187. CAR T cells were incubated in the presence of AP20187 at the indicated concentrations for 16 hours at 37°C. Dead cells were detected using a violet live/dead cell stain and quantified by flow cytometry. Only T cells expressing inducible caspase were eliminated (containing FMC63 iC9 or CD19 sCARs and iC9 control CAR). T cells not expressing control CAR were not affected (not transduced, HT, or with control CAR not expressing iC9).

FIG. 32 is a graph showing that CD19 sCAR T cells expressing inducible caspase-9 are effective in vivo . NSG mice were injected with 1×10 ⁶ CD19+ NALM6 cells. Five days later, mice were injected with either CD19 CAR T cells expressing inducible caspase-9 or non-transduced control T cells.

FIG. 33 is a graph showing the detection of CD19 sCAR T cells expressing inducible caspase-9 in blood and spleen by flow cytometry after completion of the in vivo experiment, indicating cell engraftment.

FIG. 34 is a series of graphs showing the results of the kill assay: CD20sCAR, 20revCAR and CD20 onCAR. Chromium release 4-hour assay to assess killing of NALM6 cells engineered to express CD20. Kdt=wild-type K562 cells that are CD20 negative served as a foreign target to demonstrate specific killing. CD20sCAR, 20revCAR and CD20 onCAR show equivalent and specific killing of CD20+ target cells. On-CAR was tested in the presence of 500 nM Shield-1 solution.

FIG. 35 is a series of histograms showing that in the absence of a solubilizing FKBP ligand (eg, shield-1), CAR function is inhibited. Shows the percentage reduction in killing in the absence of shield-1 relative to killing in the presence of 500 nM shield-1. Jeko cells express CD20. At a lower E:M ratio, On-CAR function is strongly inhibited in the absence of FKBP ligand.

FIG. 36 is a series of graphs showing modulation of CAR surface expression by FKBP Shield-1 ligand. CD20 on-CAR T cells were stained for CAR expression and a plot of mean fluorescence intensity (CIF measured by flow cytometry) of the CAR signal versus Shield-1 concentration was plotted. Shield-1 causes a dose-dependent increase in CAR expression. Lack of Shield-1 results in ~60% reduction in CD20 on-CAR expression (lower graph).

FIG. 37 is a series of plotted flow cytometric results showing Shield-1 titration for the CD19rev CAR. CD19rev CAR T cells (~38% transduced) were incubated with Shield-1 at various doses for 24 h to evaluate dose-dependent caspase-9 activation. The remaining CAR+ cells were quantified by flow cytometry. In the CD19rev CAR system, lower doses of Shield-1 resulted in higher caspase-9 activation and increased apoptosis (lower proportion of CAR+ cells).

FIG. 38 is a graph showing in vivo evaluation of apoptosis efficacy in anti-CD19 revCAR T cells. NALM6 cells (expressing click beetle luciferase) that are CD19 positive were injected (iv) into NSG mice on day 0. On day 4, mice were injected with CD19-targeted revCAR, 19sCAR, or extrinsic T cells T cells. Bioluminescence signals from NALM6 cells were quantified at the indicated time points. RevCAR-treated mice were injected twice with 10 mg/kg aquashield-1 at the indicated time points, these injections were expected to be insufficient to keep revCAR T cells alive. Thus, the bioluminescence curves for both revCAR and HT treated mice strongly overlap, indicating sufficient in vivo apoptosis of revCAR T cells.

FIG. 39 is a schematic timeline and graph showing the in vivo efficacy of CD19 revCAR T cells. NALM6 cells (expressing click beetle luciferase) that are CD19 positive were injected (iv) into NSG mice on day 0. On day 4, mice were implanted with osmotic infusion pumps to secrete aquashield-1 at a dose of 20 mg/kg/day. CD19rev CAR T cells were injected 4 hours after successful pump implantation (bottom graph, black arrow). Bioluminescence signals from NALM6 cells were quantified at the indicated time points. The infusion pumps secreted aquashield-1 for 7 days, after which the bioluminescence of NALM6 cells began to increase (curves CD19 revCAR).

FIG. 40 is a series of flow cytometry plots showing that activation of self-destruct leads to peripheral depletion of suicide CAR T cells. Mice were injected with NALM6 cells and 5 days later were injected with CD19 sCAR T cells. Prior to injection of CD19 sCAR, T cells were sorted based on scFV expression. Flow cytometry diagrams show peripheral T cells (CD3+, CD45+) at day 8 and day 26. CD19 sCAR T cells were depleted on day 10 by injection of AP1903 (10 mg/kg). In the case of mice treated with AP1903, the 2 graphs on the left show that T cells are difficult to detect after self-destruct activation, and in the case of mice treated with solvent, the 2 graphs on the right show a stable percentage of T cells.

FIG. 41 is a series of graphs showing that activation of self-destruct leads to peripheral depletion of sCAR T cells. T cell quantification was performed on several mice. Mice were injected with AP1903 on day 10 to deplete sCAR T cells. After administration, the percentage of T cells decreased in the AP1903 receiving group, in contrast to the solvent receiving group.

FIG. 42 is a series of images and graphs showing that self-destruct activation leads to depletion of sCAR T cells in lymphoid organs. Upper panel of images: Mouse spleens were harvested >2 weeks after AP1903 administration and stained for human CD3; in AP1903-treated mice, T cells were not detectable, in contrast to vehicle-treated mice. Bottom graph: Quantitative PCR was performed to detect sCAR T cells in the spleens of mice treated with AP1903 and vehicle, the results show an almost complete absence of sCAR in most mice.

FIG. 43 is a flow chart and graphs showing that using BT (bone marrow, liver, thymus) mice as recipients requires "universal" T cells that lack TCR and MHCI expression. T cells were transduced on day 1 after activation with CD19 sCAR-encoding lentivirus, cells were electroporated with Cas9 guide RNA on day 3 (10 μg/10 ⁶ cells) and again on day 4 with beta-targeted guide RNAs by electroporation. -chain TCR and beta-2-microglobulin. Flow cytometry diagrams show sCAR19 expression in 45.2% of cells 10 days after activation and double knockout of TCR beta chain and beta-2-microglobulin in ~20% of cells. The scheme shows the timeline for obtaining T cells.

FIG. 44 is a schematic diagram of a chronological workflow for the in vivo experiment design of the present invention. Used BT (bone marrow, liver and thymus) mice to evaluate the function of the universal sCAR in a non-cancerous mouse model. Human fetal bone marrow and thymus were implanted into NSG mice at day -91. The survival rate was assessed by flow cytometry on day -27. Universal T cells expressing CD19 sCAR T cells were injected on day 0, B cell depletion was assessed on day 10, and mice were injected with AP1903 (3 daily injections of 10 mg/kg). sCAR survival was assessed by qPCR.

FIG. 45 is a series of flow cytometry plots showing that "universal" sCAR T cells induce peripheral B cell depletion in non-autologous BT (bone marrow, liver and thymus) mice. Generic CAR T cells were able to deplete human B cells in a non-cancerous humanized mouse model. Flow cytometry charts at day 0 and day 10 show a complete absence of CD19-positive cells in the peripheral circulation.

FIG. 46 is a graph showing that universal sCAR T cells can be depleted by AP1903 administration. Quantitative PCR was performed to detect sCAR T cells in the peripheral blood of mice treated with AP1903 and vehicle, the results show an almost complete absence of sCAR in 2/3 of the mice. To determine the number of copies of WPRE in peripheral blood, qPCR was performed with gDNA 4 weeks after the administration of AP1903.

FIG. 47 is a graph showing that CD19+ NALM6 tumor growth was inhibited in mice infused with CART19 or infused with FurON CART19 that received BZA, with or without the addition of IL2.

DETAILED DESCRIPTION

In general, the invention relates to the regulated expression of recombinant fusion proteins. This regulation occurs upon expression of fusion proteins containing the protein of interest fused to a conditional expression domain, such as a degradation domain (often referred to in the art as "degron") or an aggregation domain. Typically, such degradation domains fold into a stable conformation only in the presence of a specific ligand (eg, a soluble ligand or a ligand associated with a fusion protein). In the absence of such a ligand, the degradation domain assumes a disorganized structure, resulting in degradation of the entire fusion protein by natural intracellular mechanisms. Typically, such aggregation domains oligomerize and/or aggregate in the absence of a specific ligand (eg, soluble ligand or ligand bound to a fusion protein), resulting in aggregation and/or sequestration of the entire fusion protein. The invention is based on the understanding that a degradation domain or an aggregation domain can be separated from a protein of interest by a cleavage site (e.g., a protease cleavage site) when expressed under stabilizing conditions (e.g., in the presence of a stabilizing compound) or deaggregating conditions (e.g., in the presence of a deaggregating compound ). Thus, in the absence of a cognate protease, a fusion protein containing a degradation domain will not be degraded only in the presence of a stabilizing compound, and a fusion protein containing an aggregation domain will not be susceptible to aggregation only in the presence of a deaggregating compound. However, once the cleavage site has been cleaved by the cognate protease, the presence of a stabilizing compound or a deaggregating compound is no longer necessary for the protein of interest not to be degraded or aggregated, since it is no longer associated with a degradation domain or an aggregation domain. Thus, at the beginning of expression, the fusion protein containing the degradation domain is susceptible to degradation and the fusion protein containing the aggregation domain is susceptible to aggregation, however, after cleavage, the resulting protein of interest becomes indistinguishable from its non-fusion counterpart.

Thus, the fusion proteins of the invention contain three main elements: a conditional expression domain (eg, a degradation domain or an aggregation domain), a domain containing the protein of interest, and a cleavage domain separating the two domains. Within each of these elements, specific domains are interchangeable and are described below. Notably, the fusion protein can be arranged such that the conditional expression domain is either N-terminal or C-terminal relative to the protein of interest. However, in specific embodiments, the conditional expression domain is located in the N-terminal direction relative to the protein of interest. In such embodiments, if the conditional expression domain is a degradation domain, the degradation domain, being disorganized, makes the entire fusion protein a target for degradation prior to cleavage of the cleavage domain. In the case of a C-terminal fusion, the protease cleavage site must be oriented towards the compartment in which the protease resides. In the particular case of furin, the C-terminal degron must be directed towards the lumen of the endoplasmic reticulum and the Golgi apparatus.

Definitions

As used herein, the term "conditional expression domain" means a fusion protein domain that has a first state and a second state, such as aggregation states or conformational states, such as a stabilization/destabilization state or a correct/misfolded state. The first condition is associated with, causes, or mediates cell surface expression or extracellular expression of one or more (e.g., all) fragments of the fusion protein in the first degree, or at the first level, and the second condition is associated with, causes, or mediates cell surface expression or extracellular expression of one or more (eg, all) fragments of the fusion protein in the second degree, or at the second level. In the absence of an expression junction, when expressed in a cell of interest, most of the fusion protein containing the conditional expression domain is undetectable, both on the cell surface and outside the cell. Conversely, in the presence of an expression compound, surface expression and/or extracellular expression of one or more (eg, all) domains of the fusion protein is substantially increased. Thus, the conditional expression domain has the following characteristics: (1) it is not naturally present in the context of the fusion protein; (2) surface expression and/or extracellular expression is co-translationally or post-translationally regulated; (3) the degree of surface expression and/or extracellular expression is significantly increased in the presence of the expression compound. In embodiments, the conditional expression domain is a degradation domain, such as those described herein. In other embodiments, the conditional expression domain is an aggregation domain, such as those described herein. In embodiments, the fusion protein containing the conditional expression domain contains a chimeric antigen receptor (CAR), for example, as described herein. In embodiments, the fusion protein contains a heterologous protease cleavage site located between the conditional expression domain and the second domain. In such embodiments, in the absence of an expression junction, the protease cleavage site of a large proportion of the fusion proteins is inaccessible to the cognate protease and the fate of the fusion protein in the cell is determined by the conditional expression domain. In the presence of an expression compound, the protease cleavage site of a large proportion of the fusion proteins becomes available to the cognate protease, the conditional expression domain is cleaved from the fusion protein, and the fate of the remaining fusion protein in the cell is no longer affected by the conditional expression domain.

As used herein, the term "aggregation domain" means the domain of a fusion protein causing intracellular aggregation of the fusion protein. In the absence of a disaggregating compound, when expressed in a cell of interest, most of the aggregation domain-containing fusion protein is in aggregates that are, for example, sequestered in the cell prior to reaching the final stages of expression, such as cell surface expression or extracellular secretion. Conversely, in the presence of a deaggregating compound, surface expression and/or extracellular expression of one or more (eg, all) domains of the fusion protein is substantially increased. Thus, the aggregation domain has the following characteristics: (1) it is not naturally present in the context of the fusion protein; (2) surface expression and/or extracellular expression is co-translationally or post-translationally regulated; (3) the degree of surface expression and/or extracellular expression increases significantly in the presence of a deaggregating compound. In embodiments, the aggregation domain comprises one or more, eg 1, 2, 3, 4, 5, 6, 7 or more repeats of the dimerization domain. In embodiments, the dimerization domain is a homodimerization domain. In other embodiments, the dimerization domain is a heterodimerization domain.

As used herein, the term "expression compound" means a compound that, when added to a cell expressing a fusion protein containing a conditional expression domain, binds to the conditional expression domain and results in increased surface and/or extracellular expression of one or more (e.g., all ) fusion protein domains. Expression compounds may be natural or synthetic.

As used herein, the term “disaggregating compound” means a compound that, when added to a cell expressing a fusion protein containing an aggregation domain, binds to an aggregation domain and results in increased surface and/or extracellular expression of one or more (e.g., all) of the domains. fused protein. The antiaggregating compounds may be natural or synthetic.

The term "degradation domain" means a fusion protein domain that assumes a stable conformation when expressed in the presence of a stabilizing compound. In the absence of a stable conformation, when expressed in a cell of interest, most of the degradation domains (and generally any protein to which they are fused) will be degraded by the endogenous cellular machinery. Notably, the degradation domain is not a natural protein domain, but is designed to be unstable in the absence of contact with a stabilizing compound. Thus, a degradation domain has the following characteristics: (1) it is not natural; (2) its expression is regulated co-translationally or post-translationally by increasing or decreasing the degree of degradation; (3) the degree of degradation is significantly reduced in the presence of a stabilizing compound. In some embodiments, the degradation domain does not result in aggregation of the fusion proteins. In some embodiments, in the absence of a stabilizing compound, the degradation domain or other domain of the fusion protein is substantially undetectable in, or on, the cell.

In this document, the terms "deaggregation" and "disaggregation" are used interchangeably.

As used herein, the terms "fusion protein" or "chimeric protein" means a protein created by joining two or more heterologous protein domains into one continuous protein.

The term "heterologous" refers to a domain (eg, a protein domain) that is of a different origin (i.e., not naturally associated with at least one of the other reference domains) than the one or more protein domains to which it is fused. In addition, "heterologous protease cleavage site" means a protease cleavage site that is not cleaved by any fusion protein domain in which it resides.

The term "protease" means a protein that cleaves another protein in the presence of a cleavage site in the protein to be cleaved.

The term "intracellular protease" means a protease that is naturally expressed within the cell of interest.

The term "extracellular protease" means a protease that is naturally expressed in an organism (eg, a mammal) and is secreted or exposed outside of cells (eg, in the blood or on the surface of the skin).

The terms "stabilization compound" or "stabilizing compound" means a compound which, when added to a cell expressing a degradation domain, stabilizes the degradation domain and reduces the extent to which it subsequently degrades. Stabilization compounds or stabilizing compounds may be natural or synthetic.

The grammatical form of the singular noun means "one or more than one" (that is, at least one). By way of example, "element" means one element or more than one element.

The term "about", when applied to a measurable quantity such as quantity, duration, and the like, should include variations of ±20%, or in some cases ±10%, or in some cases ±5%, or in some cases ± 1%, or in some cases ±0.1%, of the specific value, as such variations are suitable for practicing the disclosed methods.

The term "chimeric antigen receptor" or alternatively "CAR" means a recombinant polypeptide construct containing at least an extracellular antigen-binding domain, a transmembrane domain, and a cytoplasmic signaling domain (also referred to herein as an "intracellular signaling domain") containing a functional signaling domain, derived from the stimulatory molecule described below. In some embodiments, the domains in a CAR polypeptide construct are on the same polypeptide chain, eg, they constitute a chimeric fusion protein. In some embodiments, the domains in a CAR polypeptide construct are not contiguous, eg, are on different polypeptide chains, eg, in a regulated chimeric antigen receptor (RCAR).

In one aspect, the stimulatory molecule is a zeta chain associated with a T cell receptor complex. In one aspect, the cytoplasmic signaling domain contains the main signaling domain (eg, the main signaling domain of CD3-zeta). In one aspect, the cytoplasmic signaling domain also contains one or more functional signaling domains derived from at least one costimulatory molecule, described below. In one aspect, the co-stimulatory molecule is selected from 4 1BB (ie, CD137), CD27, ICOS, and/or CD28. In one aspect, a CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain containing a functional signaling domain derived from a stimulatory molecule. In one aspect, a CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain comprising a functional signaling domain derived from a costimulatory molecule and a functional signaling domain derived from a stimulatory molecule. In one aspect, a CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain containing two functional signaling domains derived from one or more co-stimulatory molecules and a functional signaling domain derived from a stimulatory molecule. In one aspect, a CAR comprises a chimeric fusion protein comprising an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain comprising at least two functional signaling domains derived from one or more costimulatory molecules and a functional signaling domain derived from a stimulatory molecule. In one aspect, the CAR optionally contains a leader sequence at the amino-terminus (N-terminus) of the CAR fusion protein. In one aspect, the CAR also contains a leader sequence at the N-terminus of the extracellular antigen-binding domain, with the leader sequence optionally cleaved from the antigen recognition domain (eg, scFv) during cellular processing and localization of the CAR to the cell membrane.

A CAR containing an antigen-binding domain (eg, scFv or TCR) that targets, for example, binds, a specific X antigen, such as those described herein, is also referred to as XCAR, X-CAR, or X-targeted CAR. For example, a CAR containing an antigen binding domain that targets CD19 is referred to as a CD19 CAR.

The term "signaling domain" means a functional portion of a protein that acts to communicate information within the cell to regulate cellular activity through certain signaling pathways by creating second messengers, or by functioning as an effector by responding to such messengers. In some aspects, the signaling domain of the CARs described herein is derived from a stimulatory molecule or a co-stimulatory molecule described herein, or is a synthesized or recombinant signaling domain.

As used herein, the term "antibody" means a protein or polypeptide sequence derived from an immunoglobulin molecule that specifically binds to an antigen. The antibodies may be polyclonal or monoclonal, multi or single chain, or intact immunoglobulins, and may be obtained from natural sources or from recombinant sources. The antibodies may be tetrameric immunoglobulin molecules.

The term "antibody fragment" means at least one portion of an intact antibody, or recombinant variants thereof, and refers to an antigen-binding domain, e.g., the antigen-recognizing variable region of an intact antibody, that is sufficient to allow recognition and specific binding of an antibody fragment to a target, such as an antigen. . Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab') ₂ and Fv fragments, scFv antibody fragments, linear antibodies, single domain antibodies such as sdAb (either VL or VH), camelid VHH domains, and multispecific antibodies formed from antibody fragments, such as a bivalent fragment containing two Fab fragments linked by a disulfide bridge at the hinge region, as well as isolated CDRs or other epitope-binding antibody fragments. The antigen binding fragment can also be incorporated into single domain antibodies, maxibody, minibody, nanobody, intrabody, diabody, triabody, tetrabody, v-NAR, and bis-scFv (see, e.g., Hollinger and Hudson, Nature Biotechnology 23:1126-1136, 2005) . Antigen binding fragments can also be grafted onto scaffolds based on polypeptides such as type III fibronectin (Fn3) (see US Pat. No. 6,703,199, which describes fibronectin polypeptide minibodies).

The term "scFv" means a fusion protein comprising at least one antibody fragment containing a light chain variable region and at least one antibody fragment containing a heavy chain variable region, wherein the light and heavy chain variable regions are adjacent, linked by a short, flexible polypeptide linker, and can be expressed as a single chain polypeptide, while scFv retains the specificity of the intact antibody from which it is derived. Unless otherwise indicated, the scFvs described herein may have the VL and VH variable regions in any order, for example, relative to the N-terminus and C-terminus of the polypeptide, the scFv may contain a VL linker-VH or may contain a VH linker-VL.

As used herein, the term "complementarity determining region" or "CDR" refers to amino acid sequences in the variable regions of an antibody that are responsible for antigen specificity and binding affinity. For example, there are typically three CDRs in each heavy chain variable region (eg, HCDR1, HCDR2, and HCDR3) and three CDRs in each light chain variable region (LCDR1, LCDR2, and LCDR3). The precise boundaries of the amino acid sequence of a particular CDR can be determined using any number of well known systems, including those described in Kabat et al. (1991), "Sequences of Proteins of Immunological Interest" 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (Kabat numbering system), Al-Lazikani et al., (1997) JMB 273, 927-948 (Chothia numbering system), or combinations thereof. According to the Kabat numbering system, in some embodiments, the CDR amino acid residues in the heavy chain variable domain (VH) are numbers 31-35 (HCDR1), 50-65 (HCDR2), and 95-102 (HCDR3); and the amino acid residues of the CDRs in the light chain variable domain (VL) are numbers 24-34 (LCDR1), 50-56 (LCDR2) and 89-97 (LCDR3). According to the Chothia numbering system, in some embodiments, the CDR amino acids in the VH are numbers 26-32 (HCDR1), 52-56 (HCDR2), and 95-102 (HCDR3); and amino acid residues of the CDRs in VL are numbers 26-32 (LCDR1), 50-52 (LCDR2) and 91-96 (LCDR3). According to the combined Kabat and Chothia numbering system, in some embodiments, the CDR regions correspond to amino acid residues that are part of the Kabat CDR, Chothia CDR, or both. For example, in some embodiments, the CDR regions correspond to amino acid residues 26-35 (HCDR1), 50-65 (HCDR2), and 95-102 (HCDR3) in a VH, eg, a mammalian VH, eg, a human VH; and amino acid residues 24-34 (LCDR1), 50-56 (LCDR2) and 89-97 (LCDR3) in VL, eg mammalian VL, eg human VL.

The portion of a CAR of the invention containing an antibody or antibody fragment may exist in various forms in which the antigen binding domain is expressed as part of a contiguous polypeptide chain containing, for example, scFv antibody fragments, linear antibodies, single domain antibodies such as sdAb (either VL, or VH), camelid VHH domains, humanized antibody, bispecific antibody, antibody conjugate (Harlow et al., 1999, in: Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, NY; Harlow et al., 1989, in: Antibodies: A Laboratory Manual, Cold Spring Harbor, New York; Houston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; Bird et al., 1988, Science 242:423-426). In one aspect, the CAR antigen-binding domain of the invention comprises an antibody fragment. In a further aspect, the CAR contains an antibody fragment that is an scFv.

As used herein, the term "binding domain" or "antibody molecule" (also known as "target (e.g., CD19) binding domain") means a protein, such as an immunoglobulin chain or fragment thereof, containing at least one immunoglobulin variable domain sequence. . The term "binding domain" or "antibody molecule" encompasses antibodies and antibody fragments. In one embodiment, the antibody molecule is a multispecific antibody molecule, for example, it contains a plurality of immunoglobulin variable domain sequences, wherein a first immunoglobulin variable domain sequence of the plurality has a binding specificity for a first epitope and a second immunoglobulin variable domain sequence of the plurality has a binding specificity for second epitope. In one embodiment, the multispecific antibody molecule is a bispecific antibody molecule. A bispecific antibody has specificity for no more than two antigens. A bispecific antibody molecule is characterized by a first immunoglobulin variable domain sequence that has a binding specificity for a first epitope and a second immunoglobulin variable domain sequence that has a binding specificity for a second epitope.

The term "antibody heavy chain" means the larger of the two kinds of polypeptide chains present in antibody molecules in their natural conformations, which generally defines the class to which the antibody belongs.

The term "antibody light chain" means the smaller of the two kinds of polypeptide chains present in antibody molecules in their natural conformations. Kappa (κ) and lambda (λ) light chains are the two main isotypes of antibody light chains.

The term "recombinant antibody" means an antibody that is produced using recombinant DNA technology, such as, for example, an antibody expressed in a bacteriophage or yeast expression system. The term should also mean an antibody that is produced by synthesizing a DNA molecule encoding an antibody, and that DNA molecule expresses an antibody protein or an amino acid sequence defining the antibody, wherein the DNA or amino acid sequence is obtained using recombinant DNA or amino acid sequence technology that is available and well known in the field.

As used herein, the term "immunoglobulin" or "Ig" refers to a class of proteins that act as antibodies. Antibodies expressed by B cells are sometimes referred to as BCR (B cell receptor) or antigen receptor. The five members of this class of proteins are IgA, IgG, IgM, IgD, and IgE. IgA is the main antibody present in body secretions such as saliva, tears, breast milk, gastrointestinal secretions, and mucous secretions from the respiratory and genitourinary tracts. IgG is the most common circulating antibody. IgM is the main immunoglobulin produced in the primary immune response in most subjects. It is the most effective immunoglobulin in agglutination, complement fixation, and other humoral responses, and is important in defense against bacteria and viruses. IgD is an immunoglobulin that lacks any of the known antibody functions but can serve as an antigen receptor. IgE is an immunoglobulin that mediates an immediate hypersensitivity reaction by causing the release of mediators from mast cells and basophils when exposed to an allergen.

The term "antigen" or "Ag" means a molecule that elicits an immune response. This immune response may involve either the production of antibodies, or the activation of specific immunologically competent cells, or both. The skilled artisan will appreciate that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. Moreover, antigens can be obtained from recombinant or genomic DNA. The skilled artisan will appreciate that any DNA that contains a nucleotide sequence or partial nucleotide sequence encoding a protein that elicits an immune response thus encodes an "antigen" as used herein. In addition, the person skilled in the art understands that a given antigen need not be encoded by the full nucleotide sequence of a gene alone. Obviously, the present invention includes, but is not limited to, the use of partial nucleotide sequences of more than one gene, and that these nucleotide sequences are assembled in different combinations to encode polypeptides that elicit the desired immune response. In addition, the skilled artisan will appreciate that an antigen need not necessarily be encoded by a "gene". Obviously, the antigen can be created or can be obtained from a biological sample, or can be a macromolecule other than a polypeptide. Such a biological sample may include, but is not limited to, a tissue sample, a tumor sample, a cell or fluid with other biological components.

As used herein, the term "self-antigen" means any self-antigen that is recognized as foreign by the immune system. Self antigens include, but are not limited to, cellular proteins, phosphoproteins, cell surface proteins, cellular lipids, nucleic acids, glycoproteins, including cell surface receptors.

The term "autoantibody" means an antibody that is produced by a B cell specific for a self-antigen.

The term "autoantibody disease" as used herein means a disorder resulting from an immune response in the form of autoantibody production. Autoantibody-induced disease is the result of inadequate and excessive production of autoantibodies. Examples of autoantibody-induced diseases include, but are not limited to, bullous pemphigoid, acquired epidermolysis bullosa, p200 pemphigoid, linear IgA-dependent bullous dermatosis, other pemphigoid diseases, dermatitis herpetiformis, gluten-sensitive celiac disease, myasthenia gravis, Goodpasture's syndrome, granulomatosis with polyangiitis, and others ANCA+ forms of vasculitis, autoimmune encephalitis involving the limbic system, anti-NMDA receptor encephalitis, neuromyelitis of the optic nerve, autoimmune hemolytic anemia, autoantibody-induced target organ damage in lupus and other connective tissue diseases (caused by anti-dsDNA, anti-Ro, and others) autoantibodies), Graves' disease and Hashimoto's thyroiditis, production of antibodies against insulin in diabetes, antibodies against insulin receptors in autoimmune hypoglycemia, cryoglobulinemia, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, dermatomyositis, production of antibodies against Fc-epsilon receptors in chronic idiopathic urticaria, antibodies against folate receptors, antibodies against endothelial receptors or against adrenergic receptors in pulmonary arterial hypertension, refractory hypertension, dilated cardiomyopathy, as well as autoinflammatory syndromes such as IgG4-related disease, among others.

As used herein, the term "autoimmune disease" means a disease or condition resulting from an antibody-mediated autoimmune response to autoantigens. In an autoimmune disease, autoantibodies are produced that are inappropriately and/or overproduced against self antigen or self antigen.

The term "autologous" refers to any material obtained from the same individual to whom it will later be reintroduced.

The terms "antitumor effect" or "antitumor activity" means a biological effect that can manifest itself in many ways, including, but not limited to, for example, a decrease in tumor volume, a decrease in the number of tumor cells, a decrease in the number of metastases, an increase in life expectancy, a decrease in tumor cell proliferation , decrease in the survival of tumor cells or weakening of various physiological symptoms associated with the oncological condition. An "antitumor effect" can also be manifested in the ability of the peptides, polynucleotides, cells and antibodies of the invention to initially prevent the onset of a tumor.

The term "allogeneic" refers to any material derived from another animal of the same species as the individual to whom the material is administered. Two or more individuals are said to be allogeneic to each other when their genes at one or more loci are not identical. In some aspects, allogeneic material from individuals of the same species may differ genetically enough to act as an antigen.

The term "xenogeneic" refers to an implant derived from an animal of a different species.

As used herein, the term "apheresis" refers to an extracorporeal process in which blood from a donor or patient is withdrawn from the donor or patient and passed through a machine that separates the selected specific component(s) and returns the remainder to the donor or patient's circulatory system, e.g., by retransfusion. Thus, in this context, "apheresis sample" means a sample obtained using apheresis.

The term "cleavage" means the destruction of covalent bonds, for example, in the backbone of a nucleic acid molecule, or the hydrolysis of peptide bonds. Cleavage can be initiated in a variety of ways, including, but not limited to, enzymatic or chemical hydrolysis of the phosphodiester bond. Both single-strand cleavage and double-strand cleavage can occur. Double-strand cleavage can occur as a result of two separate single-strand cleavage events. DNA cleavage can result in either blunt ends or stepped ends. In specific embodiments, fusion polypeptides can be used to target cleaved double-stranded DNA.

The terms "cancer" or "tumor" means a disease characterized by the uncontrolled growth of aberrant cells. Cancer includes all types of malignant growth or oncogenic processes, metastatic tissues or malignantly transformed cells, tissues or organs, regardless of the histopathological type or stage of invasion. Cancer cells can spread locally or through the circulatory and lymphatic systems to other parts of the body. Examples of various cancers are described herein and include, but are not limited to, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, kidney cancer, liver cancer, brain cancer , lymphoma, leukemia, lung cancer and the like.

The terms "CRISPR/CAS", "regularly arranged short palindromic repeat array system", or "CRISPR" refer to DNA loci containing short base sequence repeats. Each repeat is followed by short segments of spacer DNA from previous viral exposures. Bacteria and archaea have developed an adaptive immune defense called the CRISPR-CRISPR-associated (Cas) system, which uses short RNAs to direct the degradation of foreign nucleic acids. In bacteria, the CRISPR system provides acquired immunity against invading foreign DNA through RNA-driven DNA cleavage.

In the type II CRISPR/Cas system, short segments of foreign DNA, called "spacers", are integrated into CRISPR genomic loci, and transcribed and processed into short CRISPR RNAs (crRNAs). These crRNAs anneal to trans-activating crRNAs (tracrRNAs) and drive sequence-specific cleavage and silencing of pathogenic DNA by Cas proteins. Recent studies have shown that target recognition by the Cas9 protein requires a seed sequence in crRNA and a conserved protospacer-adjacent dinucleotide motif (PAM) sequence upstream of the crRNA-binding region.

To direct Cas9 to cleave sequences of interest, crRNA-tracrRNA fusion transcripts, hereinafter referred to as "guide RNAs" or "nRNAs", can be constructed from the human polymerase III U6 promoter. CRISPR/CAS-mediated genome editing and regulation has demonstrated transformational potential in basic science, cell engineering, and therapy.

The term "CRISPRi" means a CRISPR system for sequence-specific gene silencing or gene expression inhibition, for example, at the transcriptional level.

As used herein, the term "derived from" indicates a bond between the first and second molecules. It generally refers to the structural similarity between the first molecule and the second molecule, and does not imply or include limitation on the method or source for the first molecule that is derived from the second molecule. For example, in the case of an intracellular signaling domain that is derived from a CD3 zeta molecule, the intracellular signaling domain retains the structure of CD3 zeta sufficiently to perform a necessary function, namely, to be able to generate a signal under appropriate conditions. The term does not imply or include limitation as to the specific method of obtaining an intracellular signaling domain, for example, it does not mean that in order to obtain an intracellular signaling domain, it is necessary to start with a CD3-zeta sequence and delete an undesired sequence or introduce mutations, resulting in an intracellular signaling domain.

The expression "disease associated with the expression of a tumor antigen" includes, but is not limited to, a disease associated with the expression of a tumor antigen described herein, or a condition associated with cells expressing a tumor antigen described herein, including, for example, proliferative diseases such as cancer or an early stage of cancer, or a precancerous condition such as myelodysplasia, myelodysplastic syndrome or preleukemia; or a non-cancerous condition associated with cells that express the tumor antigen described herein. In one aspect, the cancer associated with the expression of a tumor antigen described herein is a hematological cancer. In one aspect, the cancer associated with the expression of the tumor antigen described herein is a solid cancer. Other diseases associated with the expression of the tumor antigen described herein include, but are not limited to, for example, atypical and/or non-classical cancers, early stage cancers, precancerous conditions, or proliferative diseases associated with the expression of the tumor antigen described herein. . Non-cancerous conditions associated with the expression of the tumor antigen described herein include, but are not limited to, for example, autoimmune disease (eg, lupus), inflammatory diseases (allergy and asthma), and transplantation.

The term "conservative sequence modifications" means amino acid modifications that do not significantly affect or alter the binding characteristics of an antibody or an antibody fragment containing an amino acid sequence. Such conservative modifications include amino acid substitutions, additions and deletions. Modifications can be made to an antibody or antibody fragment of the invention by standard methods known in the art, such as site-directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions are substitutions in which an amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains are known in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), non-polar side chains (eg, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta-branched side chains (eg, threonine, valine, isoleucine), and aromatic side chains (eg, tyrosine, phenylalanine, tryptophan , histidine). Thus, one or more amino acid residues in a CAR of the invention may be replaced with other amino acid residues from the same side chain family, and the altered CAR may be tested using the functional assays described herein.

The term "stimulation" means the primary response induced by the binding of a stimulatory molecule (e.g., TCR/CD3 complex or CAR) to a ligand recognized by it (or tumor antigen in the case of CAR) that mediates a signaling event, such as, but not limited to, transmission signaling through the TCR/CD3 complex, or signaling through the corresponding NK receptor or CAR signaling domains. Stimulation may mediate changes in the expression of certain molecules, such as downregulation of TGF-β, and/or reorganization of cytoskeletal structures, and the like.

The term "stimulatory molecule" means a molecule expressed by an immune effector cell (e.g., T cell, NK cell, B cell) that is a cytoplasmic signal sequence(s) that regulates immune effector cell activation in a stimulatory manner for at least some aspects of immune effector cell signaling, for example T cell signaling. In one aspect, a signal is a primary signal that is initiated, for example, upon binding of a TCR/CD3 complex to a peptide-loaded MHC molecule, and which results in a mediated T cell response, including, but not limited to, proliferation, activation, differentiation, and so on. similar. The basic cytoplasmic signaling sequence (also referred to as the "basic signaling domain") that acts in a stimulatory manner may contain a signaling motif known as an immunoreceptor tyrosine activating motif, or ITAM. Examples of ITAM-containing basic cytoplasmic signal sequences that are particularly suitable for use in the invention include, but are not limited to, those derived from CD3-zeta, total FcR-gamma (FCER1G), Fc-gamma RIIa, FcR-beta (Fc -epsilon R1b), CD3-gamma, CD3-delta, CD3-epsilon, CD5, CD22, CD79a, CD79b, CD278 (also known as "ICOS"), FcεRI, DAP10, DAP12 and CD66d. In a particular CAR of the invention, the intracellular signaling domain in any one or more of the CARs of the invention contains an intracellular signal sequence, for example, the basic signal sequence of CD3-zeta. In a particular CAR of the invention, the primary CD3-zeta signal sequence is the sequence shown in SEQ ID NO: 18, or equivalent residues in non-human species, e.g., mouse, rabbit, monkey, great ape, and the like. In a particular CAR of the invention, the primary CD3-zeta signal sequence is the sequence shown in SEQ ID NO: 20, or equivalent residues in non-human species, e.g., mouse, rabbit, monkey, great ape, and the like.

The term "antigen presenting cell" or "APC" means a cell of the immune system, such as a helper cell (e.g., B cell, dendritic cell, and the like) that presents a foreign antigen in complex with major histocompatibility complex (MHC) molecules on its surfaces. T cells can recognize these complexes through T cell receptors (TCRs). APCs process antigens and present them to T cells.

Used in this document, the term "intracellular signaling domain" means the intracellular part of the molecule. The intracellular signaling domain generates a signal that stimulates the immune effector function of a CAR expressing cell, such as a CAR T cell or a CAR expressing NK cell. Examples of an immune effector function, for example, in a CAR T cell or a CAR expressing NK cell, include cytolytic activity and helper activity, including cytokine secretion. Although the entire intracellular signaling domain can be used, in some cases it is not necessary to use the entire chain. Regarding the use of a truncated fragment of the intracellular signaling domain, such a truncated fragment can be used in place of the intact strand, provided that it signals the effector function. Thus, the term "intracellular signaling domain" should include any truncated fragment of an intracellular signaling domain sufficient to signal an effector function.

In one embodiment, the intracellular signaling domain may comprise a basic intracellular signaling domain. Exemplary major intracellular signaling domains include those derived from molecules responsible for basic stimulation, or antigen-dependent stimulation. In one embodiment, the intracellular signaling domain may comprise a costimulatory intracellular domain. Exemplary costimulatory intracellular signaling domains include those derived from molecules responsible for costimulatory signals or antigen-independent stimulation. In one embodiment, the intracellular signaling domain is synthesized or recombinant. For example, in the case of a CAR-expressing immune effector cell, e.g., a CAR T cell or a CAR-expressing NK cell, the major intracellular signaling domain may contain a cytoplasmic T cell receptor sequence, the major intracellular signaling domain may contain a cytoplasmic T cell receptor sequence , and the co-stimulatory intracellular signaling domain may comprise a cytoplasmic sequence from a co-receptor or co-stimulatory molecule.

The main intracellular signaling domain may contain a signal motif known as the immunoreceptor tyrosine activating motif, or ITAM. Examples of ITAM-containing major cytoplasmic signal sequences include, but are not limited to, those derived from CD3-zeta, total FcR-gamma (FCER1G), Fc-gamma RIIa, FcR-beta, CD3-gamma, CD3-delta, CD3- epsilon, CD5, CD22, CD79a, CD79b, CD278 ("ICOS"), FcεRI CD66d, DAP10 and DAP12.

The terms "zeta", or alternatively "zeta chain", "CD3-zeta", or "TCR-zeta", means a protein having GenBank accession no. BAG36664.1, or equivalent residues in non-human species, e.g., mouse, rabbit, monkey, great ape and the like, and the terms "stimulatory zeta domain" or alternatively "CD3 zeta stimulatory domain" or "TCR zeta stimulatory domain" means amino acid residues from the cytoplasmic domain of the zeta chain sufficient to functional transmission of the primary signal required for T-cell activation. In one aspect, the cytoplasmic zeta domain contains residues 52-164 of the GenBank accession no. BAG36664.1 protein, or equivalent residues in non-human species, e.g., mouse, rabbit, monkey, great ape, and the like, which are their functional orthologues. . In one aspect, "zeta stimulatory domain" or "CD3 zeta stimulatory domain" is the sequence shown in SEQ ID NO: 18. In one aspect, "zeta stimulatory domain" or "CD3 zeta stimulatory domain" is the sequence listed in SEQ ID NO: 20. Also provided herein are CD3 zeta domains having one or more mutations in the amino acid sequences described herein, e.g., SEQ ID NO: 20.

The term "costimulatory molecule" refers to a cognate binding partner on a T cell that specifically binds to a costimulatory ligand, thereby mediating a costimulatory response of the T cell, such as, but not limited to, proliferation. Costimulatory molecules are cell surface molecules, other than antigen receptors or their ligands, that are required for an effective immune response. Costimulatory molecules include, but are not limited to, MHC class I molecule, TNF receptor protein, immunoglobulin like protein, cytokine receptor, integrin, lymphocyte activation signaling molecule (SLAM protein), NK cell activating receptor, BTLA, Toll-like receptor, OX40, CD2 , CD7, CD27, CD28, CD30, CD40, CDS, ICAM-1, LFA-1 (CD11a/CD18), 4-1BB (CD137), B7-H3, CDS, ICAM-1, ICOS (CD278), GITR, BAFFR, LIGHT, HVEM (LIGHTR), KIRDS2, SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD19, CD4, CD8-alpha, CD8-beta, IL2R-beta, IL2R-gamma, IL7R-alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, NKG2D, NKG2C, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1 , CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/ Cbp, CD19a, and a ligand that specifically binds to CD83.

A costimulatory intracellular signaling domain, or a costimulatory signaling domain, may be an intracellular portion of a costimulatory molecule. An intracellular signaling domain may comprise the entire intracellular portion or the entire natural intracellular signaling domain of the molecule from which it is derived, or a functional fragment thereof.

The term "4-1BB" means a TNFR superfamily protein having the amino acid sequence of GenBank Accession No. AAA62478.2, or equivalent residues in non-human species, eg, mouse, rabbit, monkey, great ape, and the like; and "co-stimulatory domain 4-1BB" means amino acid residues 214-255 in the protein GenBank Accession No. AAA62478.2, or equivalent residues in non-human species, e.g., mouse, rabbit, monkey, great ape, and the like. In one aspect, the "4-1BB co-stimulatory domain" is the sequence shown in SEQ ID NO: 14, or equivalent residues in non-human species, e.g., mouse, rabbit, monkey, great ape, and the like.

As used herein, the term "immune response" means a cellular response to an antigen that occurs when lymphocytes identify antigenic molecules as foreign and induce antibody production and/or activate lymphocytes to remove the antigen.

When an "immunologically effective amount", "an effective amount to inhibit an autoimmune disease", or a "therapeutic amount" is indicated, the exact amount of the compositions of the present invention to be administered may be determined by the clinician or researcher taking into account individual differences in age, body weight, tumor size, degree of infection, or metastasis, as well as the health status of the patient (subject).

As used herein, the term "immune effector cell" means a cell involved in an immune response, for example, in stimulating an immune effector response. Examples of immune effector cells include T cells, such as alpha/beta T cells and gamma/delta T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, mast cells, and phagocytes of myeloid origin.

As used herein, the terms "immune effector function" or "immune effector response" means a function or response, for example, of an immune effector cell that enhances or stimulates an immune attack on a target cell. For example, an immune effector function or response means a property of a T or NK cell that causes the target cell to be destroyed or inhibited in growth or proliferation. In the case of a T cell, basal stimulation and costimulation are examples of an immune effector function or response.

The term "effector function" means a specialized function of a cell. The effector function of the T cell, for example, may be cytolytic activity or helper activity, including the secretion of cytokines.

The term "coding" means the characteristic property of certain nucleotide sequences in a polynucleotide, such as a gene, cDNA or mRNA, to serve as templates for the synthesis in biological processes of other polymers and macromolecules having either a specific nucleotide sequence (for example, rRNA, tRNA and mRNA), or a certain sequence of amino acids, and the resulting biological properties. Thus, a gene, cDNA, or RNA encodes a protein if the transcription and translation of the mRNA corresponding to that gene results in the formation of a protein in a cell or other biological system. It can be said that both a coding strand whose nucleotide sequence is identical to an mRNA sequence and is usually listed in a sequence listing, and a non-coding strand used as a template for transcription of a gene or cDNA, encode a protein or other product of that gene or cDNA.

Unless otherwise indicated, the term "nucleotide sequence encoding an amino acid sequence" encompasses all nucleotide sequences that are degenerate variants of each other and that encode the same amino acid sequence. The expression "a nucleotide sequence encoding a protein or RNA" may also encompass introns, to the extent that a nucleotide sequence encoding a protein may, in some embodiments, contain intron(s).

The terms "effective amount" or "therapeutically effective amount" are used interchangeably herein and mean the amount of a compound, drug, material or composition described herein effective to achieve a particular biological result.

The term "endogenous" means any material from, or produced within, an organism, cell, tissue, or system.

The term "exogenous" means any material introduced from outside, or produced outside of the body, cell, tissue or system.

The term "expression" means the transcription and/or translation of a particular nucleotide sequence driven by a promoter.

The term "transfer vector" means a chemical compound containing an isolated nucleic acid that can be used to deliver the isolated nucleic acid into a cell. A variety of vectors are known in the art, including, but not limited to, linear polynucleotides, polynucleotides linked to ionic or amphiphilic compounds, plasmids, and viruses. Thus, the term "transfer vector" includes autonomously replicating plasmids or viruses. The term should be construed to also include non-plasmid and non-viral compounds that facilitate the transfer of nucleic acid into cells, such as, for example, a polylysine compound, a liposome, and the like. Examples of viral transfer vectors include, but are not limited to, adenoviral vectors, adeno-associated viral vectors, retroviral vectors, lentiviral vectors, and the like.

The term "expression vector" means a vector containing a recombinant polynucleotide comprising expression control sequences operably linked to the nucleotide sequence to be expressed. The expression vector contains sufficient cis-acting elements for expression; other elements for expression may be provided by the host cell or present in an in vitro expression system. Expression vectors include all vectors known in the art, including cosmids, plasmids (eg, naked or liposome-embedded), and viruses (eg, lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that contain the recombinant polynucleotide.

The term "lentivirus" refers to a genus in the family Retroviridae . Lentiviruses are unique among retroviruses in that they are able to infect non-dividing cells; they can deliver a significant amount of genetic information to the DNA of the host cell, thus they are one of the most efficient gene delivery vectors. HIV, SIV and FIV are examples of lentiviruses.

The term "lentiviral vector" means a vector derived from at least a portion of the lentiviral genome, including in particular the self-inactivating lentiviral vector described in Milone et al., Mol. Ther. 17(8): 1453-1464 (2009). Other examples of lentiviral vectors that can be used in the clinic include, but are not limited to, for example, the ^{LENTIVECTOR®} gene delivery technology from Oxford BioMedica, the LENTIMAX™ vector system from Lentigen, and the like. Non-clinical types of lentiviral vectors are also available and known to those skilled in the art.

The terms "homology" or "identity" means subunit sequence identity between two polymeric molecules, for example between two nucleic acid molecules, for example two DNA molecules or two RNA molecules, or between two polypeptide molecules. When the subunit position in both of the two molecules is occupied by the same monomeric subunit; for example, if a position in each of two DNA molecules is occupied by adenine, those molecules are homologous or identical at that position. Homology between two sequences depends directly on the number of matching or homologous positions; for example, if half (eg, five positions in a polymer ten subunits long) of the positions in two sequences are homologous, then the two sequences are 50% homologous; if 90% of the positions (eg, 9 out of 10) are identical or homologous, then the two sequences are 90% homologous.

"Humanized" forms of non-human (eg, murine) antibodies are chimeric immunoglobulins, immunoglobulin chains, or antibody fragments (such as Fv, Fab, Fab', F(ab') ₂ or other antigen-binding antibody subsequences) that contain the minimum sequence derived from a non-human immunoglobulin. In general, humanized antibodies and antibody fragments are human immunoglobulins (recipient antibody or antibody fragment) in which residues from the complementarity determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as a mouse, rat or rabbit having the desired specificity, affinity and functionality. In some instances, framework region (FR) residues of a human Fv immunoglobulin are replaced with corresponding non-human residues. Moreover, the humanized antibody/antibody fragment may contain residues that are not found in either the recipient antibody or the imported CDR or framework sequences. These modifications may lead to further improvement and optimization of the function of the antibody or antibody fragment. Typically, a humanized antibody or antibody fragment contains substantially all of at least one, and typically two, variable domains in which all or substantially all of the CDRs correspond to those of a non-human immunoglobulin and all or a significant portion of the FRs are regions from the human immunoglobulin sequence. The humanized antibody or antibody fragment may also contain at least a portion of an immunoglobulin constant region (Fc), typically from a human immunoglobulin. For more details, see Jones et al., Nature, 321: 522-525, 1986; Reichmann et al., Nature, 332: 323-329, 1988; Presta, Curr. Op. Struct. Biol., 2:593-596, 1992.

The term "fully human" refers to immunoglobulins, such as an antibody or antibody fragment, in which the entire molecule is human or consists of an amino acid sequence identical to the human form of the antibody or immunoglobulin.

The term "isolated" means modified or extracted from the natural environment. For example, a nucleic acid or peptide naturally present in the body of a living animal is not "isolated", but the same nucleic acid or peptide, partially or completely separated from materials coexisting with it in its natural environment, is "isolated". An isolated nucleic acid or protein may exist in a substantially purified form, or may exist in an environment that is not native to it, such as, for example, a host cell.

In the context of the present invention, the following abbreviations are used for common nucleic acid bases. "A" means adenosine, "C" means cytosine, "G" means guanosine, "T" means thymidine and "U" means uridine.

The terms "operably linked" or "transcriptional control" refer to a functional relationship between a regulatory sequence and a heterologous nucleotide sequence allowing the expression of the latter. For example, the first nucleotide sequence is operably linked to the second nucleotide sequence when the first nucleotide sequence is brought into functional interaction with the second nucleotide sequence. For example, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Functionally related DNA sequences can be contiguous and, for example, if two protein coding regions need to be combined, be in the same reading frame.

The term "parenteral" administration of an immunogenic composition includes, for example, subcutaneous (SC), intravenous (IV), intramuscular (IM) or intrasternal injection, intratumoral or infusion methods of administration.

The terms "nucleic acid" or "polynucleotide" means deoxyribonucleic acids (DNA) or ribonucleic acids (RNA) and their polymers, in single or double stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogs of naturally occurring nucleotides that have binding properties similar to those of a reference nucleic acid and that are metabolized in a manner similar to natural nucleotides. Unless otherwise indicated, a particular nucleotide sequence is also meant to include its conservatively modified variants (eg, with degenerate codon substitutions), alleles, orthologs, SNPs, and complementary sequences, as well as the sequence specified directly. In particular, degenerate codon substitutions can be made by creating sequences in which the third position of one or more selected (or all) codons is replaced by mixed bases and/or deoxyinosine residues (Batzer et al., Nucleic Acid Res. 19:5081 (1991); Ohtsuka et al., J. Biol Chem 260:2605-2608 (1985) and Rossolini et al., Mol Cell Probes 8:91-98 (1994)).

The terms "peptide", "polypeptide" and "protein" are used interchangeably and refer to a compound consisting of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and there is no limit to the maximum number of amino acids that can make up a protein or peptide sequence. Polypeptides include any peptide or protein containing two or more amino acids linked together by peptide bonds. As used herein, the term refers to both short chains, commonly referred to in the art as peptides, oligopeptides, and oligomers, for example, and longer chains, commonly referred to in the art as proteins, of which there are many types. "Polypeptides" include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variant polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The term "polypeptide" includes a natural peptide, a recombinant peptide, or a combination thereof.

The term "promoter" means a DNA sequence recognized by the synthetic apparatus of the cell or introduced by the synthetic apparatus, which is necessary to initiate a specific transcription of a polynucleotide sequence.

The term "promoter/regulatory sequence" means a nucleotide sequence necessary for the expression of a gene product operably linked to a promoter/regulatory sequence. In some cases, this sequence may be a promoter core sequence, and in other cases, this sequence may also include an enhancer sequence and other regulatory elements necessary for expression of the gene product. A promoter/regulatory sequence may, for example, be a sequence that allows the gene product to be expressed in a tissue-specific manner.

The term "constitutive" promoter means a nucleotide sequence which, when operably linked to a polynucleotide encoding or defining a gene product, causes the product to be produced in a cell under most or all physiological conditions in the cell.

The term "inducible" promoter means a nucleotide sequence which, when operably linked to a polynucleotide encoding or defining a gene product, causes the product to be produced in a cell substantially only if an inducer corresponding to the promoter is present in the cell.

The term "tissue-specific" promoter means a nucleotide sequence which, when operably linked to a polynucleotide encoding or defining a gene product, causes the product to be produced in a cell substantially only if the cell is a tissue cell corresponding to that promoter.

The terms "cancer-associated antigen" or "tumor antigen" are used interchangeably to mean a molecule (typically a protein, carbohydrate, or lipid) that is expressed on the surface of a cancer cell, either in its entirety or as a fragment (e.g., MHC/peptide), and which useful for selectively targeting a pharmacological agent to a cancer cell. In some embodiments, the tumor antigen is a marker expressed by both normal cells and cancer cells, such as a lineage marker, such as CD19 on B cells. In some embodiments, a tumor antigen is a cell surface molecule that is overexpressed in a cancer cell relative to a normal cell, e.g., 1-fold overexpression, 2-fold overexpression, 3-fold overexpression, or more, compared to normal cells. In some embodiments, the tumor antigen is a cell surface molecule that is not properly synthesized on the cancer cell, for example, a molecule that has deletions, additions, or mutations compared to a molecule expressed by a normal cell. In some embodiments, the tumor antigen will be expressed exclusively on the cell surface of the cancer cell, in whole or as a fragment (eg, MHC/peptide), and not synthesized, or not expressed, on the surface of a normal cell. In some embodiments, exemplary tumor antigens include: CD19; CD123; CD22; CD30; CD171; CS-1; C-type lectin-like molecule 1, CD33; epidermal growth factor variant III receptor (EGFRvIII); ganglioside G2 (GD2); ganglioside GD3; a member of the TNF receptor family, B cell maturation antigen (BCMA); Tn antigen ((Tn Ag) or (GalNAcα-Ser/Thr)); prostate specific membrane antigen (PSMA); receptor tyrosine kinase-like orphan receptor 1 (ROR1); Fms-like tyrosine kinase 3 (FLT3); tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; carcinoembryonic antigen (CEA); epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); the alpha-2 subunit of the interleukin-13 receptor; mesothelin; interleukin-11 receptor alpha subunit (IL-11Ra); prostatic stem cell antigen (PSCA); serine protease 21; vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; platelet growth factor receptor beta (PDGFR-beta); stage-specific embryonic antigen-4 (SSEA-4); CD20; folate receptor alpha; receptor tyrosine-specific protein kinase ERBB2 (Her2/neu); mucin 1 associated with the cell surface (MUC1); epidermal growth factor receptor (EGFR); neuronal adhesion molecule (NCAM); prostasis; prostatic acid phosphatase (PAP); mutant elongation factor 2 (ELF2M); ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAIX); proteasome subunit (prosoma, macropain), type beta, 9 (LMP2); glycoprotein 100 (gp100); an oncogenic fusion protein comprising a rearrangement initiation site (BCR) localization region and Abelson murine leukemia viral oncogene homologue 1 (Abl) (bcr-abl); tyrosinase; ephrin A2 receptor (EphA2); fucosyl GM1; a sialyl-Lewis adhesion molecule (sLe); ganglioside GM3; transglutaminase 5 (TGS5); high molecular weight melanoma-associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); folate receptor beta; tumor endothelial marker 1 (TEM1/CD248); antigen related to tumor endothelial marker 7 (TEM7R); claudin 6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein-coupled class C receptors, group 5, member D (GPRC5D); X chromosome open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); polysialic acid; placenta-specific protein 1 (PLAC1); the hexasaccharide portion of glycoceramide globoH (GloboH); breast differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); hepatitis A virus cell receptor 1 (HAVCR1); adrenoreceptor beta-3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); complex of lymphocytic antigen 6, locus K9 (LY6K); olfactory receptor 51E2 (OR51E2); protein TCR-gamma with an alternative reading frame (TARP); Wilms tumor protein (WT1); testicular cancer antigen 1 (NY-ESO-1); testicular cancer antigen 2 (LAGE-1a); melanoma-associated antigen 1 (MAGE-A1); translocation variant 6 of the ETS gene located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); family X antigens, representative 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); testicular melanoma antigen 1 (MAD-CT-1); testicular melanoma antigen 2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; protein; survivin; telomerase; prostate carcinoma tumor antigen 1, melanoma antigen 1 recognized by T-cells; a protein mutant of the rat sarcoma virus (Ras); human telomerase reverse transcriptase (hTERT); breakpoints at translocation in case of sarcoma; inhibitor of apoptosis from melanoma cells (ML-IAP); ERG (transmembrane serine protease 2 (TMPRSS2) and ETS fusion gene); N-acetylglucosamine transferase V (NA17); paired box protein Pax-3 (PAX3); androgen receptor; cyclin B1; a neuroblastoma-derived homologue of the avian myelocytomatosis virus (MYCN) v-myc oncogene; a member of the C family of Ras homologues (RhoC); tyrosinase-related protein 2 (TRP-2); cytochrome P450 1B1 (CYP1B1); CCCTC-binding factor-like protein (zinc finger protein), T cell-recognized squamous cell carcinoma antigen 3 (SART3); paired box protein Pax-5 (PAX5); proacrosin-binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); anchor protein 4 A-kinase (AKAP-4); breakpoint 2 in X in synovial sarcoma (SSX2); receptor for advanced glycosylation end products (RAGE-1); renal ubiquitous protein 1 (RU1); renal ubiquitous protein 2 (RU2); legumain; human papillomavirus E6 protein (HPV E6); human papillomavirus E7 protein (HPV E7); intestinal carboxylesterase; mutant heat shock protein 70-2 (mut hsp70-2); CD79a; CD79b; CD72; leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Fc fragment of the IgA receptor (FCAR or CD89); leukocyte immunoglobulin-like receptors, subfamily A, representative 2 (LILRA2); a family of proteins similar to the CD300 molecule, representative f (CD300LF); a family of 12 C-type domain lectins, representative A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); protein 2, similar to the EGF-like domain-containing mucin-like hormone receptor (EMR2); lymphocytic antigen 75 (LY75); glypican-3 (GPC3); Fc receptor-like protein 5 (FCRL5); immunoglobulin lambda chain-like polypeptide 1 (IGLL1); a member of the TNF receptor family; Fms-like tyrosine kinase 3 (FL T3); CD10; CD19; CD20; CD21; CD22; CD23; CD24; CD25; CD37; CD38; CD53; CD72; CD73; CD74; CD75; CD77; CD79a; CD79b; CD80; CD81; CD82; CD83; CD84; CD85; ROR1; BCMA; CD86; CD179b; CD1a; CD1b; CD1c; CD1d; CD2; CD5; CD6; CD9; CD11a; CD11b; CD11c; CD17; CD18; CD26; CD27; CD29; CD30; CD31; CD32a; CD32b; CD35; CD38; CD39; CD40; CD44; CD45; CD45RA; CD45RB; CD45RC; CD45RO; CD46; CD47; CD48; CD49b; CD49c; CD49d; CD50; CD52; CD54; CD55; CD58; CD60a; CD62L; CD63; CD63; CD68CD69; CD70; CD85E; CD85I; CD85J; CD92; CD95; CD97; CD98; CD99; CD100; CD102; CD108; CD119; CD120a; CD120b; CD121b; CD122; CD124; CD125; CD126; CD130; CD132; CD137; CD138; CD139; CD147; CD148; CD150; CD152; CD162; CD164; CD166; CD167a; CD170; CD175; CD175s; CD180; CD184; CD185; CD192; CD196; CD197; CD200; CD205; CD210a; CDw210b; CD212; CD213a1; CD213a2; CD215; CD217; CD218a; CD218b; CD220; CD221; CD224; CD225; CD226; CD227; CD229; CD230; CD232; CD252; CD253; CD257; CD258; CD261; CD262; CD263; CD264; CD267; CD268; CD269; CD270; CD272; CD274; CD275; CD277; CD279; CD283; CD289; CD290; CD295; CD298; CD300a; CD300c; CD305; CD306; CD307a; CD307b; CD307c; CD307d; CD307e; CD314; CD315; CD316; CD317; CD319; CD321; CD327; CD328; CD329; CD338; CD351; CD352; CD353; CD354; CD355; CD357; CD358; CD360; CD361; CD362; CD363; as well as a peptide of any of these antigens, presented in the context of MHC. Particularly preferred antigens include: CD19, CD20, CD22, FcRn5, FcRn2, BCMA, CS-1, CD138, CLDN6, mesothelin, EGFRvIII, CD123, CD33 and CLL-1. In some embodiments, the CARs of the present invention include CARs containing an antigen-binding domain (eg, an antibody or antibody fragment) that binds to an MHC-presented peptide. Typically, peptides derived from endogenous proteins fit into pockets of major histocompatibility complex (MHC) class I molecules and are recognized by T cell receptors (TCRs) on CD8+ T lymphocytes. MHC class I complexes are constitutively expressed by all nucleated cells. In cancer cells, virus-specific and/or tumor-specific peptide/MHC complexes represent a unique class of cell surface targets for immunotherapy. TCR-like antibodies targeting peptides from viral or tumor antigens in the context of human leukocyte antigen (HLA)-A1 or HLA-A2 have been described (see e.g. Sastry et al., J Virol. 2011 85(5):1935- 1942; Sergeeva et al., Blood, 2011 117(16):4262-4272; Verma et al., J Immunol 2010 184(4):2156-2165; Willemsen et al., Gene Ther 2001 8(21):1601 -1608; Dao et al., Sci Transl Med 2013 5(176):176ra33; Tassev et al., Cancer Gene Ther 2012 19(2):84-100). For example, a TCR-like antibody can be identified by screening a library, such as a human scFv phage display library. Accordingly, the present invention provides CARs containing an antigen binding domain that binds to an MHC-presented peptide of a molecule selected from the group consisting of WT1, NY-ESO-1, LAGE-1a, MAGE-A1 and RAGE-1.

The term "flexible polypeptide linker" or "linker" as used herein in the context of scFv means a peptide linker, composed of amino acids such as glycine and/or serine residues, used alone or in combination, that links together a heavy chain variable region. and the variable region of the light chain. In one embodiment, the flexible polypeptide linker is a Gly/Ser linker and contains the amino acid sequence (Gly-Gly-Gly-Ser)n, where n is a positive integer equal to or greater than 1, e.g., n=1, n=2 , n=3, n=4, n=5 and n=6, n=7, n=8, n=9 and n=10 (SEQ ID NO: 28). In one embodiment, flexible polypeptide linkers include, but are not limited to, (Gly ₄ Ser) ₄ (SEQ ID NO: 29) or (Gly ₄ Ser) ₃ (SEQ ID NO: 30). In another embodiment, the linkers include multiple repeats of (Gly ₂ Ser), (GlySer) or (Gly ₃ Ser) (SEQ ID NO: 31). The scope of the invention also includes the linkers described in WO2012/138475, the content of which is incorporated herein by reference.

As used herein, the term "5'cap" (also referred to as RNA cap, RNA 7-methylguanosine cap, or RNA m ⁷ G cap) means a modified guanine nucleotide that has been added "upstream" or at the 5' end of a eukaryotic messenger RNA shortly after the start of transcription. The 5' cap consists of an end group that is linked to the first nucleotide to be transcribed. Its presence is extremely important for ribosome recognition and protection against RNases. The addition of a cap is coupled to transcription and occurs co-transcriptionally, so that there is a mutual influence. Shortly after the start of transcription, the 5' end of the synthesized mRNA is bound by a cap-synthesizing complex associated with RNA polymerase. This enzymatic complex catalyzes the chemical reactions required for mRNA capping. Synthesis occurs as a multi-stage biochemical reaction. The capping fragment can be modified to modulate the functional properties of the mRNA, such as its stability or translation efficiency.

As used herein, the term " in vitro transcribed RNA" means RNA, preferably mRNA, that has been synthesized in vitro . Typically, in vitro transcribed RNA is obtained from an in vitro transcription vector. The in vitro transcription vector contains a template that is used to generate in vitro transcribed RNA.

As used herein, the term "poly(A)" refers to a series of adenosine residues attached to an mRNA during polyadenylation. In a preferred embodiment, the polyA transient expression construct consists of 50-5000 (SEQ ID NO: 32), preferably greater than 64, more preferably greater than 100, most preferably greater than 300 or 400 residues. Poly(A) sequences can be chemically or enzymatically modified to modulate the functional properties of the mRNA, such as localization, stability, or translation efficiency.

As used herein, the term "polyadenylation" refers to the covalent attachment of a polyadenyl moiety, or a modified variant thereof, to a messenger RNA molecule. In eukaryotic organisms, most messenger RNA (mRNA) molecules are polyadenylated at the 3' end. The 3'-poly(A) tail is a long sequence of adenine nucleotides (often several hundred) added to the pre-mRNA by the enzyme polyadenylate polymerase. In higher eukaryotes, a poly(A) "tail" is added to transcripts containing a specific sequence, a polyadenylation signal. The poly(A) tail and its associated protein help protect mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, mRNA export from the nucleus, and translation. Polyadenylation occurs in the nucleus immediately after the transcription of DNA into RNA, but can also occur later in the cytoplasm. After transcription is completed, the mRNA strand is cleaved by the action of the endonuclease complex associated with RNA polymerase. The cleavage site is typically characterized by the presence of the AAUAAA base sequence next to the cleavage site. After mRNA cleavage, adenosine residues are added to the free 3' end at the cleavage site.

As used herein, the term "transient" refers to the expression of an unintegrated transgene for hours, days, or weeks, while the period of expression is less than the period of expression of the gene in the case of its integration into the genome or being in a stable plasmid replicon in the cell - owner.

As used herein, the terms "treat", "treatment" and "therapy" mean the reduction or amelioration of the progression, severity and/or duration of a proliferative disease, or the amelioration of one or more symptoms (preferably one or more overt symptoms) of a proliferative disease resulting from as a result of the introduction of one or more therapeutic agents (for example, one or more therapeutic agents, such as CAR according to the invention). In specific embodiments, the terms "treat", "treatment", and "therapy" mean a reduction in at least one measurable physical parameter of a proliferative disease, such as tumor growth, not necessarily perceivable by the patient. In other embodiments, the terms "treat", "treatment", and "therapy" mean inhibiting the progression of a proliferative disease, either physically, such as stabilizing an overt symptom, physiologically, such as stabilizing a physical parameter, or both. In other embodiments, the implementation of the terms "treat", "treatment" and "therapy" means to reduce or stabilize the size of the tumor or the number of cancer cells.

The term "signaling pathway" refers to the biochemical interaction between different signaling molecules that play a role in transmitting a signal from one part of a cell to another part of the cell. The expression "cell surface receptor" encompasses molecules and complexes of molecules capable of receiving a signal and transmitting a signal across the cell membrane.

The term "subject" should include living organisms in which an immune response can be elicited (eg, mammals, humans). As used herein, the terms "subject" or "patient" may include a human or non-human mammal. Non-human mammals include, for example, livestock and pets such as sheep, cattle, pigs, dogs, cats, and marine mammals. Preferably, the subject is a human.

The term "substantially clear" cell means a cell that is substantially free of other types of cells. A "substantially cleared" cell also means a cell that has been separated from other types of cells with which it is naturally associated in its natural environment. In some cases, a population of "substantially purified" cells means a homogeneous population of cells. In other cases, the term simply means a cell that has been separated from the cells with which it is naturally associated in its natural environment. In some aspects, the cells are cultured in vitro . In other aspects, the cells are not cultured in vitro .

As used herein, the term "suicide gene" means a self-destruction or apoptosis-inducing gene operably linked to a promoter, which may be constitutive or inducible. Examples of a suicide gene include, but are not limited to, the herpes simplex virus thymidine kinase (HSV-TK) gene, the Fas cytoplasmic domain, a caspase such as caspase-8 or caspase-9, cytosine deaminase, E1A, FHIT, as well as other known self-destruct inducing or apoptosis genes.

As used herein, the term "suicide gene product" or "suicide domain" refers to the expression product of a suicide gene.

Used in this document, the term "therapeutic" effect means treatment. The therapeutic effect is obtained by reducing, suppressing, remission or elimination of the disease state.

As used herein, the term "tolerance" or "immune tolerance" means a condition in which a subject has a reduced or no immune response to a specific antigen or group of antigens to which the subject normally responds. Tolerance is achieved under conditions that cause suppression of the immune response, and is not only the absence of an immune response. In one embodiment, tolerance in a subject can be characterized as one or more of the following: decreased level of a specific immunological response (eg, mediated by antigen-specific effector T-lymphocytes, B-lymphocytes, or antibodies); delaying the onset or progression of a specific immunological response; or a reduction in the likelihood of initiation or progression of a specific immunological response, compared to unexposed subjects.

As used herein, the term "prophylaxis" means the prevention, or proactive treatment, of a disease or disease state.

The term "transfection" or "transformation" or "transduction" refers to the process by which an exogenous nucleic acid is transferred or introduced into a host cell. A "transfected" or "transformed" or "transduced" cell is a cell that has been transfected, transformed, or transduced with an exogenous nucleic acid. A cell includes a subject's primary cell and its progeny.

The term "specifically binds" refers to an antibody or ligand that recognizes and binds to an appropriate binding partner protein (e.g., a stimulatory and/or costimulatory molecule present on a T cell) present in a sample, but where the antibody or ligand is substantially do not recognize or bind other molecules in the sample.

As used herein, the term "refractory" refers to a disease, such as cancer, that does not respond to treatment. In embodiments, refractory cancer may be treatment-resistant prior to, or at the start of, treatment. In other embodiments, a refractory cancer may become resistant during treatment. Refractory cancer is also called resistant cancer.

As used herein, the terms "recurrent" or "relapse" means the recurrence or recurrence of a disease (e.g., cancer) or signs and symptoms of a disease, such as cancer, after a period of improvement or response to treatment, e.g., following prior treatment, e.g. , cancer treatment. The initial period of response to treatment may include a decrease in the number of cancer cells to a level below a certain limit, for example, below 20%, 1%, 10%, 5%, 4%, 3%, 2% or 1%. The return of the disease may include an increase in the number of cancer cells to a level above a certain limit, for example, above 20%, 1%, 10%, 5%, 4%, 3%, 2% or 1%. For example, in the context of B-ALL, recurrence of the disease may include, for example, the reappearance of blasts in the blood, bone marrow (>5%), or any extramedullary site of the body, after a complete response to treatment. A complete response, in this context, may include the presence of <5% CM blasts. More generally, in one embodiment, the response (eg, complete response or partial response) may include the absence of detectable MRD (minimal residual disease). In one embodiment, the initial response period to treatment is at least 1, 2, 3, 4, 5, or 6 days; at least 1, 2, 3 or 4 weeks; at least 1, 2, 3, 4, 6, 8, 10 or 12 months; or at least 1, 2, 3, 4 or 5 years.

Ranges: Throughout this application, various aspects of the invention may be presented in range format. It should be understood that the description in range format is for convenience and brevity only, and should not be taken as an inflexible limitation on the scope of the invention. Accordingly, the description of a range is to be understood as specifically including all possible subranges as well as individual numerical values within the range. For example, a description of a range such as 1 to 6 should be understood to include specifically disclosed subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 up to 6, and so on, as well as individual numbers in a given range, such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6. As another example, a range such as 95-99% identity , includes something that has an identity of 95%, 96%, 97%, 98%, or 99%, including subranges such as 96-99%, 96-98%, 96-97%, 97-99%, 97- 98% and 98-99% identity. This rule applies regardless of the latitude of the range.

Fusion proteins

The present invention provides fusion proteins comprising two protein domains separated by a heterologous protease cleavage site (e.g., a protease cleavage site that is cleaved by an intracellular or extracellular protease), the first of the protein domains being a conditional expression domain, such as a degradation domain or a aggregation. In some embodiments, the fusion proteins described herein comprise three main elements: a conditional expression domain, such as a degradation or aggregation domain, a domain containing the protein of interest, and a protease-cleavable domain separating the two domains. These elements can be arranged such that a conditional expression domain, such as a degradation domain or an aggregation domain, is located either N-terminally or C-terminally relative to the protein of interest.

In some embodiments, the fusion protein described herein contains a furin cleavage site. In some embodiments, the fusion proteins described herein contain any of the furin cleavage sites shown in Table 20. In some embodiments, the fusion proteins described herein contain a furin cleavage site selected from RTKR (SEQ ID NO: 123 ); GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRR (SEQ ID NO: 127) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; LQWLEQQVAKRRTKR (SEQ ID NO: 129) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRRSLG (SEQ ID NO: 133) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; SLNLTESHNSRKKR (SEQ ID NO: 135) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; or CKINGYPKRGRKRR (SEQ ID NO: 137) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with it, or GTGAEDPRPSRKRR (SEQ ID NO: 127) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. In some embodiments, the fusion proteins described herein comprise a furin cleavage site GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or a sequence that is at least 90%, 95%, 97%, 98%, or 99% identical to it.

In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from RTKR (SEQ ID NO: 123); GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125); GTGAEDPRPSRKRR (SEQ ID NO: 127); LQWLEQQVAKRRTKR (SEQ ID NO: 129); GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131); GTGAEDPRPSRKRRSLG (SEQ ID NO: 133); SLNLTESHNSRKKR (SEQ ID NO: 135) or CKINGYPKRGRKRR (SEQ ID NO: 137). In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or GTGAEDPRPSRKRR (SEQ ID NO: 127). In some embodiments, the fusion proteins described herein comprise a furin cleavage site GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125).

In some embodiments, the fusion protein described herein comprises a furin degron domain (FurON) that includes two components: a degron, or degradation domain, which is a mutant protein domain that is unable to assume the correct conformation in the absence of a small molecular weight ligand, and a site furin breakdown. The furin degron domain can be fused to a protein of interest that is expressed in the endoplasmic reticulum. The N- and/or C-terminus of a protein of interest can be used as a fusion site, provided that the furin degron domain is directed towards the endoplasmic reticulum lumen. The protein of interest can be either a membrane protein (regardless of the number of transmembrane domains) or a soluble protein. The orientation of the furin cleavage site relative to the degron domain should be such that the cleavage results in separation of the furin degron domain and the protein of interest. In the absence of a small molecule ligand or stabilizing compound, the furin degron domain results in destabilization or degradation of the entire fusion protein. In the presence of a low molecular weight ligand or stabilizing compound, the fusion protein is not degraded. The furin degron domain is mutated such that the affinity for its natural endogenous ligand is eliminated; the affinity for the low molecular weight ligand or stabilizing compound is maintained; and the protein becomes unstable in the absence of the low molecular weight ligand.

In some embodiments, the degron, or degradation domain, is derived from the protein shown in Table 21. In some embodiments, the degron, or degradation domain, is derived from the estrogen receptor. In some embodiments, the degron, or degradation domain, comprises an amino acid sequence selected from SEQ ID NO: 58 or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity therewith, or SEQ ID NO : 121 or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. In some embodiments, the degron, or degradation domain, comprises an amino acid sequence selected from SEQ ID NO: 58 or SEQ ID NO: 121.

In some embodiments, the degron, or degradation domain, is derived from a FKB protein (FKBP). In some embodiments, the degradation domain comprises the amino acid sequence of SEQ ID NO: 56 or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. In some embodiments, the degradation domain comprises the amino acid sequence of SEQ ID NO: 56.

In some embodiments, the degron, or degradation domain, is derived from dihydrofolate reductase (DHFR). In some embodiments, the degradation domain comprises an amino acid sequence selected from SEQ ID NO: 57 or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with it. In some embodiments, the degradation domain comprises an amino acid sequence selected from SEQ ID NO: 57. In some embodiments, the degron, or degradation domain, is not derived from an FKB protein, estrogen receptor, or DHFR.

Proteins of interest

The fusion proteins of the invention may contain virtually any protein of interest. In some preferred embodiments, the protein of interest may be a transmembrane protein (eg, a transmembrane receptor). The fusion protein format of the invention is particularly useful in the case of such transmembrane proteins, since the incorporation of an intact conditional expression domain, e.g. The C-terminus may result in poor regulation of the protein of interest (because, for example, integration into the membrane may result in sufficient stabilization of the protein or degradation domain to avoid degradation and/or aggregation). One example of a class of proteins of interest are the chimeric T cell antigen receptors described in the next section.

Chimeric antigen receptor

In some embodiments, the protein of interest is a chimeric antigen receptor (CAR), wherein the CAR contains an antigen-binding domain (e.g., an antibody or antibody fragment, TCR or TCR fragment) that binds to the tumor antigen described herein, a transmembrane domain (e.g. , the transmembrane domain described herein) and an intracellular signaling domain (e.g., an intracellular signaling domain described herein) (e.g., an intracellular signaling domain containing a costimulatory domain (e.g., a costimulatory domain described herein) and/or a basic signal domain (e.g., the main signal domain described herein) CAR nucleic acid constructs, encoded proteins, vectors containing them, host cells, pharmaceutical compositions, and methods of administration and treatment related to the present invention are described in detail in the publication International Patent Application No. WO2015142675, the entire content of which is incorporated herein by reference.

In some embodiments, the protein of interest is a chimeric antigen receptor (CAR), wherein the CAR contains an antigen-binding domain (e.g., an antibody or antibody fragment, TCR or TCR fragment) that binds to a tumor-specific antigen (e.g., tumor-specific antigen, described herein), a transmembrane domain (e.g., the transmembrane domain described herein), and an intracellular signaling domain (e.g., an intracellular signaling domain described herein) (e.g., an intracellular signaling domain containing a costimulatory domain (e.g., a costimulatory domain , described herein) and/or a major signaling domain (e.g., the major signaling domain described herein.) In some embodiments, the tumor-specific antigen is an antigen present on a stromal cell or myeloid suppressor cell (MDSC). In other aspects, the invention relates to polypeptides encoded by such nucleic acids and host cells containing such nucleic acids and/or polypeptides.

In some embodiments, the CAR molecule comprises at least one intracellular signaling domain selected from a CD137 (4-1BB) signaling domain, a CD28 signaling domain, a CD27 signaling domain, an ICOS signaling domain, a CD3-zeta signaling domain, or any combinations thereof. In some embodiments, the CAR molecule contains at least one intracellular signaling domain selected from one or more costimulatory molecules selected from CD137 (4-1BB), CD28, CD27, or ICOS.

In some aspects, the present invention also provides a method for modifying a T cell with a chimeric antigen receptor (CAR) and a suicide gene. Thus, the present invention relates to a nucleic acid encoding a CAR, or a modified T cell containing a CAR, wherein the CAR contains an antigen-binding domain, a transmembrane domain, and an intracellular domain.

Exemplary CARs are described in US Pat.

Sequences of non-limiting examples of various components that may be part of CAR molecules are shown in Table 2, where "a" means an amino acid sequence and "n" means a nucleic acid encoding the corresponding peptide.

Table 2. Sequences of various CAR components (aa - amino acid sequence, nc - nucleic acid encoding the corresponding protein)

SEQID NO Description Subsequence 1 EF-1, promoter CGTGAGGCTCCGGTGCCCGTCAGTGGGCAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGAGGGGTCGGCAATTGAACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAAGTAGTCGCCGTGAACGTTCTTTTT CGCAACGGGTTTGCCGCCAGAACACAGGTAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGCCTCTTTACGGGTTATGGCCCTTGCGTGCCTTGAATTACTTCCACCTGGCTGCAGTACGTGATTCTTGATCCCGAGCTTCGGGTTGGAAGTGGGTGGGAGAGTTCGAGGCCTTGCGCTTAAGGAGCCCCTTCGCCTCGTGCTTGAGTTGAGGCCTGGCCTGG GCGCTGGGGCCGCCGCGTGCGAATCTGGTGGCACCTTCGCGCCTGTCTCGCTGCTTTCGATAAGTCTCTAGCCATTTAAAATTTTTGATGACCTGCTGCGACGCTTTTTTTCTGGCAAGATAGTCTTGTAAATGCGGGCCAAGATCTGCACACTGGTATTTCGGTTTTTGGGGCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAGCGCACATGTTCGGCGAGGCGG GGCCTGCGAGCGCGGCCACCGAGAATCGGACGGGGGTAGTCTCAAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGCGCCCGTGTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGTCGGCACCAGTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCCCTGCTGCAGGGAGCTCAAAATGGAGGACGCGGCTCTCGGGAGAGCGGGCGGGTGAG TCACCCACACAAAGGAAAAGGGCTTTCCGTCCTCAGCCGTCGCTTCATGTGACTCCACGGAGTACCGGGCGCCGTCCAGGCACCTCGATTAGTTTCCGAGCTTTTGGAGTACGTCGTCTTTAGGTTGGGGGGAGGGTTTTATGCGATGGAGTTTCCCCACACTGAGTGGGTGGAGACTGAAGTTAGGCCAGCTTGGCACTTGATGTAATTCTCCTTGGA ATTTGCCCTTTTTGAGTTTGGATCTTGGTTCATTCTCAAGCCTCAGACAGTGGTTCAAAGTTTTTTTCTTTCCATTTCAGGTGTCGTGA 2 Leader (ak) MALPVTALLLPLALLLHAARP 3 Leader (nk) ATGGCCCTGCCTGTGTGACAGCCCTGCTGCTGCCTCTGGCTCTGCTGCTGCATGCCGCTAGACCC 33 Leader (nk) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccc 4 CD8, joint (ak) TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD 5 CD8, hinge (nk) ACCAGACGCCAGCGCCGCGACCACCAACACCGGCCCACCATCGCGTCGCAGCCCCTGTCCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGAT 6 Ig4, hinge (ak) ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKM 7 Ig4, hinge (nc) GAGAGCAAGTACGGCCCTCCCTGCCCCCCTTGCCCTGCCCCCGAGTTCCTGGGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAGCCCAAGGACACCCTGATGATCAGCCGGACCCCCGAGGTGACCTGTGTGTGTGGTGGACGTGTCCCAGGAGGACCCCGAGGTCCAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCAAGCCCCGGGAG GAGCAGTTCAATAGCACCTACCGGGTGGTGTCCGTGCTGACCGTGCTGCACCAGGACTGGCTGAACGGCAAGGAATACAAGTGTAAGGTGTCCAACAAGGGCCTGCCCAGCAGCATCGAGAAAACCATCAGCAAGGCCAAGGGCCAGCCTCGGGAGCCCCAGGTGTACACCCTGCCCCCTAGCCAAGAGGAGATGACCAAGAACCAGGTGTCCCCTGACCTGCCTGGTGA AGGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCCGAGAACAACTACAAGACCACCCCCCCTGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCCGGCTGACCGTGGACAAGCCGGTGGCAGGAGGGCAACGTCTTTAGCTGCTCCGTGATGCACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGTCCCTGGGCAAGA TG 8 IgD, hinge (ak) RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGRGGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAVQDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGVEEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPSLPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLC EVSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPGSTTFWAWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVSYVTDH 9 IgD, hinge (nc) AGGTGGCCCGAAAGTCCCAAGGCCCAGGCATCTAGTGTTCCTACTGCACAGCCCCAGGCCAGAAGGCAGCCTAGCCAAAGCTACTACTGCACCTGCCACTACGCGCAATACTGGCCGTGGCGGGGAGGAGAAAAAAAAGGAAAGAGAAAGAAGAACAGGAAGAGAGGGAGACCAAGACCCCTGAATGTCCATCCCATACCCAGCCGCTGGGCGTCTATCTCTTGACTCCC GCAGTACAGGACTTGTGGCTTAGAGATAAGGCCACCTTTACATGTTTCGTCGTGGGCTCTGACCTGAAGGATGCCCATTTGACTTGGGAGGTTGCCGGAAAGGTACCCACAGGGGGGTTGAGGAAGGGTTGCTGGAGCGCCATTCCAATGGCTCTCAGAGCCAGCACTCAAGACTCACCCTTCCGAGATCCCTGTGGAACGCCGGGACCTCTGTCACATGTACTCT AAATCATCCTAGCCTGCCCCCACCGTCTGATGGCCCTTAGAGCCAGCCGCCCAGGCACCAGTTAAGCTTAGCCTGAATCTGCTCGCCAGTAGTGATCCCCCAGAGGCCGCCAGCTGGCTCTTATGCGAAGTGTCCGGCTTTAGCCCGCCCAACATCTTGCTCATGTGGCTGGAGGACCAGCGAGAAGTGAACACCAGCGGCTTCGCTCCAGCCCGGCCCCCCCCAGCCGGGTT CTACCACATTCTGGGCCTGGAGTGTCTTAAGGGTCCCAGCACCACCTAGCCCCAGCCAGCCACATACACCTGTGTTGTGTCCCATGAAGATAGCAGGACCCTGCTAAATGCTTCTAGGAGTCTGGAGGTTTCCTACGTGACTGACCATT 10 GS, hinge/linker (ac) GGGGSGGGGS eleven GS, hinge/linker (NK) GGTGGCGGAGGTTCTGGAGGTGGAGGTTCC 12 CD8, TM (ak) IYIWAPLAGTCGVLLLSLVITLYC 13 CD8, TM (nc) ATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGC 34 CD8, TM (nc) ATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGT 14 4-1BB, intracellular domain (ak) KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 15 4-1BB, intracellular domain (nk) AAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTG 118 4-1BB, intracellular domain (nk) aagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactg 16 CD27 (ak) QRRKYRSNKGESPVEPAEPCRYSCPREEEGSTIPIQEDYRKPEPACSP 17 CD27 (nc) AGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGACTTCGCAGCCTATCGCTCC 18 CD3-zeta (ak) RVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 19 CD3-zeta (nc) AGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACAAGCAAGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGACGTGGCCGGGACCCTGAGATGGGGGAAAGCCGAGAAGGAAGACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTG GGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC 119 CD3-zeta (nc) CGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGGAGAAGAAGCCTATAGCGAGATTGG TATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 20 CD3-zeta (ak) RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 21 CD3-zeta (nc) AGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGACGTGGCCGGGACCCTGAGATGGGGGAAAGCCGAGAAGGAAGACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTG GGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC 22 linker GGGGS 23 linker GGTGGCGGAGGTTCTGGAGGTGGAGGTTCC 24 PD-1, extracellular domain (ak) Pgwfldspdrpwnpptfspallvvtegdnatftcsfsntsesfvlnwyrmspsnqtdklaafpedrsqpgqdcrfrvtqlpngrdfhmsvvrarrndsgtylcgaislapkaqikeslraelrvterraevptahpspsprpagqfqtlv 25 PD-1, extracellular domain (NK) Cccggatggtttctggactctccggatcgcccgtggaatcccccaaccttctcaccggcactcttggttgtgactgagggcgataatgcgaccttcacgtgctcgttctccaacacctccgaatcattcgtgctgaactggtaccgcatgagcccgtcaaaccagaccgacaagctcgccgcgtttccggaagatcggtcgcaac cgggacaggattgtcggttccgcgtgactcaactgccgaatggcagagacttccacatgagcgtggtccgcgctaggcgaaacgactccgggacctacctgtgcggagccatctcgctggcgcctaaggcccaaatcaaagagcttgagggccgaactgaggtgaccgagcgcagagctgaggtgccaactgcacatccatcccca tcgcctcggcctgcggggcagtttcagaccctggtc 26 PD-1 CAR (ak) with signal sequence Malpvtalllplalllhaarppgwfldspdrpwnpptfspallvvtegdnatftcsfsntsesfvlnwyrmspsnqtdklaafpedrsqpgqdcrfrvtqlpngrdfhmsvvrarrndsgtylcgaislapkaqikeslraelrvterraevptahpspsprpagqfqtlvtttpaprpptpaptiasqplslrpea crpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydal hmqalppr 27 PD-1 CAR (NK) Atggccctccctgtcactgccctgcttctccccctcgcactcctgctccacgccgctagaccacccggatggtttctggactctccggatcgcccgtggaatcccccaaccttctcaccggcactcttggttgtgactgagggcgataatgcgaccttcacgtgctcgttctccaacacctcgaatcattcgtgctgaactggtaccgcat gagccgtcaaaccagaccgacaagctcgccgcgtttccggaagatcggtcgcaaccgggacaggattgtcggttccgcgtgactcaactgccgaatggcagagacttccacatgagcgtggtccgcgctaggcgaaacgactccgggacctacctgtgcggagccatctcgctggcgcctaaggcccaaatcaaagaga gcttgaggggccgaactgagagtgaccgagcgcagagctgaggtgccaactgcacatccatccccatcgcctcggcctgcggggcagtttcagaccctggtcacgaccactccggcgccgcgcccaccgactccggccccaactatcgcgagccagcccctgtcgctgaggccggaagcatgccgccctgccgccggaggtgctgtg catacccggggattggacttcgcatgcgacatctacatttgggctcctctcgccggaacttgtggcgtgctccttctgtccctggtcatcaccctgtactgcaagcggggtcggaaaaagcttctgtacattttcaagcagcccttcatgaggcccgtgcaaaccacccaggaggaggacggttgctcctgccggttccccgaagaggaaga aggaggttgcgagctgcgcgtgaagttctcccggagcgccgacgccccgcctataagcagggccagaaccagctgtacaacgaactgaacctgggacggcgggaagagtacgatgtgctggacaagcggcgcggccgggaccccgaaatgggcgggaagcctagaagaaagaaccctcaggaaggcctgtataacgagctgcagaag gacaagatggccgaggcctactccgaaattgggatgaagggagagcggcggaggggaaaggggcacgacggcctgtaccaaggactgtccaccgccaccaaggacacatacgatgccctgcacatgcaggcccttccccctcgc 28 linker (Gly-Gly-Gly-Ser)n, where n=1-10 29 linker (Gly4 Ser)4 thirty linker (Gly4 Ser)3 31 linker (Gly3Ser) 32 polyA [a] _50-5000 39 PD-1 CAR (ac) Pgwfldspdrpwnpptfspallvvtegdnatftcsfsntsesfvlnwyrmspsnqtdklaafpedrsqpgqdcrfrvtqlpngrdfhmsvvrarrndsgtylcgaislapkaqikeslraelrvterraevptahpspsprpagqfqtlv tttpaprpptpaptiasqplslrpeacrpaaggavhtrgld facdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr 120 ICOS, intracellular domain (ak) TKKKYSSSVHDPNGEYMFMRAVNTAKKSRLTDVTL 1111 ICOS, intracellular domain (nk) ACAAAAAAGAAGTATTCATCCAGTGTGCACGACCCTAACGGTGAATACATGTTCATGAGAGCAGTGAACACAGCCAAAAAATCCAGACTCACAGATGTGACCCTA 972 ICOS, TM domain (ac) TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDFWLPIGCAAFVVVCILGCILICWL 973 ICOS, TM domain (nk) ACCACGACGCCAGCGCCGCGACCACCAACACCGGCCCACCATCGCGTCGCAGCCCCTGTCCCTGGCCCAGAGGCGTGTGCCGGCAGCGGCGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATTTCTGGTTACCCATAGGATGTGCAGCCTTTGTTGTAGTCTGCATTTTGGGATGCATACTTATTTGTTGGCTT 124 CD28, intracellular domain (aa) RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS 1113 CD28, intracellular domain (nc) AGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGACTTCGCAGCCTATCGCTCC

In specific aspects, the CAR construct comprises an scFv domain, wherein the scFv domain may optionally be preceded by a leader sequence, such as the sequence shown in SEQ ID NO: 2, and optionally followed by a hinge sequence, such as the sequence shown in SEQ ID NO: 4 or SEQ ID NO: 6 or SEQ ID NO: 8 or SEQ ID NO: 10, a transmembrane region such as that shown in SEQ ID NO: 12, an intracellular signaling domain containing any of the sequences of SEQ ID NO : 14, SEQ ID NO: 16, SEQ ID NO: 120 or SEQ ID NO: 124, and a CD3 zeta sequence that contains SEQ ID NO: 18 or SEQ ID NO: 20, for example, wherein the domains are contiguous and are in one reading frame, forming one fusion protein.

In one aspect, exemplary CAR constructs optionally comprise a leader sequence (e.g., the leader described herein), an extracellular antigen-binding domain (e.g., the antigen-binding domain described herein), a hinge (e.g., a hinge region described herein). ), a transmembrane domain (eg, the transmembrane domain described herein), and an intracellular stimulatory domain (eg, the intracellular stimulatory domain described herein). In one aspect, an exemplary CAR construct optionally comprises a leader sequence (e.g., the leader described herein), an extracellular antigen-binding domain (e.g., the antigen-binding domain described herein), a hinge (e.g., a hinge region described herein ), a transmembrane domain (e.g., the transmembrane domain described herein), an intracellular costimulatory signaling domain (e.g., the costimulatory signaling domain described herein), and/or an intracellular major signaling domain (e.g., the major signaling domain described herein ).

An exemplary leader sequence is shown in SEQ ID NO: 2. An exemplary hinge/spacer sequence is shown in SEQ ID NO: 4 or SEQ ID NO: 6 or SEQ ID NO: 8 or SEQ ID NO: 10. An exemplary transmembrane domain sequence is shown in SEQ ID NO: 12. An exemplary sequence of the intracellular signaling domain of the 4-1BB protein is shown in SEQ ID NO: 14. An exemplary sequence of the intracellular signaling domain of CD27 is shown in SEQ ID NO: 16. An exemplary sequence of the intracellular signaling domain of ICOS is given in ID NO: 120. An exemplary CD28 intracellular signaling domain sequence is shown in ID NO: 124. An exemplary CD3-zeta domain sequence is shown in ID NO: 18 or SEQ ID NO: 20.

Nucleotide sequences encoding the desired molecules can be obtained by recombinant methods known in the art, such as, for example, screening libraries from cells expressing the nucleic acid molecule, obtaining the nucleic acid molecule from a vector known to contain it, or by direct isolation from cells and tissues containing it using standard methods. Alternatively, the nucleic acid of interest can be obtained by synthetic methods rather than cloning.

Antigen binding domain

In one aspect, the chimeric antigen receptor (CAR) contains a target-specific binding element, otherwise referred to as an antigen-binding domain. The choice of fragment depends on the type and number of ligands located on the surface of the target cell. For example, an antigen binding domain may be selected or designed to recognize a ligand that acts as a cell surface marker on target cells associated with a particular disease state, such as a tumor antigen associated with a particular cancer (e.g., an antigen binding domain that binds to a tumor antigen). In other embodiments, an antigen binding domain is selected or designed to recognize normal B cells or a subpopulation of B cells to deplete normal B cells or a target population of B cells (eg, an antigen binding domain that binds to a B cell antigen).

An antigen-binding domain can be any domain that binds to an antigen, including, but not limited to, a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a bispecific antibody, a conjugated antibody, a human antibody, a humanized antibody, and a functional fragment thereof, including, but not limited to, a single-domain antibody such as a heavy chain variable domain (VH), a light chain variable domain (VL), and a camelid-derived variable domain (VHH) nanobody, as well as an alternative scaffold known in the art that acts as an antigen-binding domain, for example, a recombinant fibronectin domain, a T-cell receptor (TCR), an affinity-enhanced recombinant TCR, or a fragment thereof, eg, a single chain TCR, and the like. In some cases, it is preferable if the antigen-binding domain is derived from the same species for which the CAR will subsequently be used. For example, for use in humans, a CAR antigen-binding domain containing human or humanized residues in the antigen-binding domain of an antibody or antibody fragment may be preferred.

In some embodiments, the antigen-binding domain of the encoded CAR molecule comprises an antibody, an antibody fragment, scFv, Fv, Fab, (Fab') ₂ , a single domain antibody (SDAB), a VH or VL domain, a camelid VHH domain, or a bifunctional (e.g., bispecific) hybrid antibody (e.g. Lanzavecchia et al., Eur. J. Immunol. 17, 105 (1987)).

In some embodiments, the antigen-binding domain of the encoded CAR molecule contains scFv. In some cases, scFv fragments can be generated in a manner known in the art (see, for example, Bird et al., (1988) Science 242:423-426 and Huston et al., (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). ScFv molecules can be generated by linking the VH and VL regions with flexible polypeptide linkers.

In one aspect, a CAR antigen-binding domain is an antibody scFv fragment that is humanized relative to the murine scFv sequence from which it is derived.

In one aspect, a CAR antigen-binding domain of the invention (eg, scFv) is encoded by a nucleic acid molecule whose sequence has been codon-optimized for expression in a mammalian cell. In one aspect, the entire CAR construct of the invention is encoded by a nucleic acid molecule, the entire sequence of which has been codon-optimized for expression in a mammalian cell. Codon optimization is a consequence of the discovery that the frequency of occurrence of synonymous codons (that is, codons that code for the same amino acid) in coding DNA differs between species. Due to the degeneracy of codons, the same polypeptide can be encoded by different nucleotide sequences. Various methods of codon optimization are known in the art and include, for example, those disclosed in at least US Pat. Cell surface markers, exclusively present on B cells, can act as an antigen that binds to the antigen-binding domain of CAR. An anti-B cell antigen binding domain may include any domain that binds to a B cell and may include, but is not limited to, a monoclonal antibody, a polyclonal antibody, a synthetic antibody, a human antibody, a humanized antibody, a non-human antibody, and any its fragment. Thus, in one embodiment, the antigen binding domain comprises an antibody or a mammalian antibody fragment, such as a single chain variable fragment (scFv). An antigen binding domain may bind one or more antigens, for example, but not limited to, any surface marker exclusively present on a B cell, such as a pro-B cell, a pre-B cell, an immature B cell, a mature B cell, Memory B cell and plasma cell. In one embodiment, the antigen binding domain binds at least one antigen, such as CD19, BCMA, or any combination thereof. In another embodiment, the antigen binding domain binds at least one antigen, such as CD20, CD21, CD27, CD38, CD138, and any combination thereof. In some cases, it is preferable if the antigen-binding domain is derived from the same species for which the CAR will subsequently be used. For example, for use in humans, a CAR antigen-binding domain containing a human antibody, a humanized antibody described elsewhere herein, or a fragment thereof may be preferred.

Tumor antigens

In some embodiments, the antigen-binding domain of a CAR is specifically targeted to a tumor antigen. There are two classes of tumor antigens (tumor antigens, TA) that can be targeted by the CARs of the present invention: (1) a tumor antigen expressed on the surface of cancer cells; and (2) a tumor antigen that is itself intracellular, but a fragment of such antigen (peptide) is present on the surface of cancer cells in the context of MHC (major histocompatibility complex).

In one embodiment, the tumor antigen is expressed on both normal cells and cancer cells, however, it is expressed at a lower level on normal cells. In one embodiment, the method further comprises selecting a CAR that binds a tumor antigen with an affinity that allows a cell engineered to express the CAR to bind to and kill cancer cells expressing the tumor antigen, but kill less than 30%, 25%, 20%, 15 %, 10%, 5%, or less, of normal cells expressing the tumor antigen, for example, as determined in the assay described herein. For example, a kill assay such as flow cytometry using Cr-51 CTL can be used. In one embodiment, the selected CAR has an antigen binding domain having a K _D binding affinity of 10 ^-4 M to 10 ^-8 M, e.g., 10 ^-5 M to 10 -7 M, e.g., ^{10 -6 M} or 10 ^-7 M , for the target antigen. In one embodiment, the selected antigen binding domain has a binding affinity that is at least five times, 10 times, 20 times, 30 times, 50 times, 100 times, or 1000 times less than a reference antibody, e.g., the antibody described herein. document.

Accordingly, a cell can be engineered to express a CAR containing an antigen-binding domain that can be targeted, for example, to bind to any of the following illustrative tumor antigens (tumor antigens): CD123, CD30, CD171, CS-1, CLL-1 (CLECL1) , CD33, EGFRvIII, GD2, GD3, Tn Ag, sTn Ag, Tn-O-glycopeptides, Stn-O-glycopeptides, PSMA, FLT3, FAP, TAG72, CD44v6, CEA, EPCAM, B7H3, KIT, IL-13Ra2, mesothelin , IL-11Ra, PSCA, VEGFR2, LewisY, PDGFR-beta, PRSS21, SSEA-4, folate receptor alpha, ERBB2 (Her2/neu), MUC1, EGFR, NCAM, prostasis, PAP, ELF2M, ephrin B2, IGF-receptor I, CAIX, LMP2, gp100, bcr-abl, tyrosinase, EphA2, fucosyl GM1, sLe, GM3, TGS5, HMWMAA, o-acetyl-GD2, folate receptor beta, TEM1/CD248, TEM7R, CLDN6, TSHR, GPRC5D, CXORF61 , CD97, CD179a, ALK, polysialic acid, PLAC1, GloboH, NY-BR-1, UPK2, HAVCR1, ADRB3, PANX3, GPR20, LY6K, OR51E2, TARP, WT1, NY-ESO-1, LAGE-1a, legumain, HPV E6,E7, MAGE-A1, MAGE A1, ETV6-AML, sperm protein 17, XAGE1, Tie 2, MAD-CT-1, MAD-CT-2, Fos-related antigen 1, p53, p53 mutant, protein, survivin and telomerase, PCTA-1/galectin 8, MelanA/MART1, Ras mutant, hTERT, translocation breakpoints in sarcoma, ML-IAP, ERG (TMPRSS2 ETS fusion gene), NA17, PAX3, androgen receptor, cyclin B1, MYCN, RhoC, TRP-2, CYP1B1, BORIS, SART3, PAX5, OY-TES1, LCK, AKAP-4, SSX2, RAGE-1, human telomerase reverse transcriptase, RU1, RU2, intestinal carboxylesterase, mut hsp70-2, LAIR1 , FCAR, LILRA2, CD300LF, CLEC12A, BST2, EMR2, LY75, GPC3, FCRL5, IGLL1, CD10, CD19, CD20, CD21, CD22, CD23, CD24, CD25, CD37, CD38, CD53, CD72, CD73, CD74, CD75 , CD77, CD79a, CD79b, CD80, CD81, CD82, CD83, CD84, CD85, ROR1, BCMA, CD86, and CD179b. Other B cell antigens that may be targeted by the CARs described herein include: CD1a, CD1b, CD1c, CD1d, CD2, CD5, CD6, CD9, CD11a, CD11b, CD11c, CD17, CD18, CD26, CD27, CD29, CD30, CD31, CD32a, CD32b, CD35, CD38, CD39, CD40, CD44, CD45, CD45RA, CD45RB, CD45RC, CD45RO, CD46, CD47, CD48, CD49b, CD49c, CD49d, CD50, CD52, CD54, CD55, CD58 CD60a , CD126, CD130, CD132, CD137, CD138, CD139, CD147, CD148, CD150, CD152, CD162, CD164, CD166, CD167a, CD170, CD175, CD175s, CD180, CD184, CD185, CD192, CD196, CD197, CD20 0, CD205 , CD210a, CDw210b, CD212, CD213a1, CD213a2, CD215, CD217, CD218a, CD218b, CD220, CD221, CD224, CD225, CD226, CD227, CD229, CD230, CD232, CD252, CD253, CD257, CD258, CD 261, CD262, CD263 , CD264, CD267, CD268, CD269, CD270, CD272, CD274, CD275, CD277, CD279, CD283, CD289, CD290, CD295, CD298, CD300a, CD300c, CD305, CD306, CD307a, CD307b, CD307c, CD307d , CD307e, CD314 , CD315, CD316, CD317, CD319, CD321, CD327, CD328, CD329, CD338, CD351, CD352, CD353, CD354, CD355, CD357, CD358, CD360, CD361, CD362, CD363; .

In some embodiments, the CAR antigen-binding domain targets a tumor antigen associated with a solid tumor, e.g., expressed by a solid tumor cell, herein referred to as a solid tumor associated antigen, e.g., an antigen associated with mesothelioma (e.g., malignant mesothelioma of the pleura), lung cancer (eg, non-small cell lung cancer, small cell lung cancer, squamous cell lung cancer, or large cell lung cancer), pancreatic cancer (eg, pancreatic ductal adenocarcinoma), esophageal adenocarcinoma, ovarian cancer, breast cancer, colorectal cancer, and bladder cancer , or any combination of them. In one embodiment, the disease is pancreatic cancer, eg, metastatic pancreatic ductal adenocarcinoma (PDA), eg, in a subject that has progressed on at least one previous standard therapy. In one embodiment, the disease is mesothelioma (eg, malignant pleural mesothelioma), for example, in a subject that has progressed on at least one previous standard therapy. In one embodiment, the disease is ovarian cancer, eg, serous epithelial ovarian cancer, eg, in a subject that has progressed after at least one previous standard therapy regimen.

Examples of tumor-associated antigens (i.e., solid tumor antigens) include, without limitation: EGFRvIII, mesothelin, GD2, Tn antigen, sTn antigen, Tn-O-glycopeptides, sTn-O-glycopeptides, PSMA, CD97, TAG72, CD44v6, CEA, EPCAM, KIT, IL-13Ra2, legumain, GD3, CD171, IL-11Ra, PSCA, MAD-CT-1, MAD-CT-2, VEGFR2, LewisY, CD24, PDGFR-beta, SSEA-4, folate receptor alpha, ERBB (e.g. ERBB2), Her2/neu, MUC1, EGFR, NCAM, ephrin B2, CAIX, LMP2, sLe, HMWMAA, o-acetyl-GD2, folate receptor beta, TEM1/CD248, TEM7R, FAP, legumain, HPV E6 or E7, ML-IAP, CLDN6, TSHR, GPRC5D, ALK, polysialic acid, Fos-related antigen, neutrophil elastase, TRP-2, CYP1B1, sperm protein 17, human chorionic gonadotropin beta subunit, AFP, thyroglobulin , PLAC1, globoH, RAGE1, MN-CA IX, reverse transcriptase human telomerase, intestinal carboxylesterase, mut hsp 70-2, NA-17, NY-BR-1, UPK2, HAVCR1, ADRB3, PANX3, NY-ESO-1, GPR20, Ly6k, OR51E2, TARP, GFRα4, as well as a peptide of any of these antigens presented on the MHC.

In one embodiment, the CAR antigen binding domain binds to human mesothelin. In one embodiment, the antigen-binding domain is a murine scFv domain that binds to human mesothelin, such as SS1 shown in Table 3. In one embodiment, the antigen-binding domain is a humanized antibody or antibody fragment, such as an scFv domain derived from mouse SS1 scFv. In one embodiment, the antigen binding domain is a human antibody, or antibody fragment, that binds to human mesothelin. Exemplary human scFv domains (and sequences thereof) and mouse SS1 scFv that bind to mesothelin are shown in Table 3. The CDR sequences are underlined. The scFv domain sequences shown in Table 3 include the light chain variable region (VL) and the heavy chain variable region (VH). VL and VH are linked by a linker containing the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 30) (e.g., as shown in scFv SS1 domains) or GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 29) (e.g., as shown in M1, M2, M3, M4, M5 , M6, M7, M8, M9, M10, M11, M12, M13, M14, M15, M16, M17, M18, M19, M20, M21, M22, M23 or M24 scFv domains). The scFv domains shown in Table 3 are in the following orientation: VL-linker-VH.

Table 3. Antigen-binding domains that bind to mesothelin

Tumor antigen Name Amino acid sequence SEQID NO: mesothelin M5
(human) QVQLVQSGAEVEKPGASVKVSCKAS GYTFTDYYMH WVRQAPGQGLEWMG WINPNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYCAS GWDFDY WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSPSSLSASVGDRVTITC RASQSIRYYLS WYQQKPGKAPK LLIY TASILQN GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC LQTYTTPD FGPGTKVEIK 201 mesothelin M11
(human) QVQLQQSGAEVKKPGASVKVSCKAS GYTFTGYYMH WVRQAPGQGLEWMG WINPNSGGTNYAQNFQG RVTMTRDTSISTAYMELRRLRSDDTAVYYCAS GWDFDY WGQGTLVTVSSGGGGSGGGGSGGGGGSGGGGSDIRMTQSPSSLSASVGDRVTITC RASQSIRYYLS WYQQKPGKAP KLLIY TASILQN GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC LQTYTTPD FGPGTKVEIK 202 mesothelin ss1 (mouse) QVQLQQSGPELEKPGASVKISCKASGYSFTGYTMNWVKQSHGKSLEWIGLITPYNGASSYNQKFRGKATLTVDKSSSTAYMDLLSLTSEDSAVYFCARGGYDGRGFDYWGQGTTVTVSSGGGGSGGGGSGGGGSDIELTQSPAIMSASPGEKVTMTCSASSSVSYMHYQQKSGTSPKRWIYDTSKLA SGVPGRFSGSGSGNSYSLTISSVEAEDDATYYCQQWSGYPLTFGAGTKLEI 203 mesothelin M1
(human) QVQLQQQSGAEVKKPGASVKVSCKAS GYTFTGYYMH WVRQAPGQGLEWMG RINPNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSEDTAVYYCAR GRYYGMDV WGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATISC RASQSVSSNFA WYQQRPGQ APRLLIY DASNRAT GIPPRFSGSGSGTDFTLTISSLEPEDFAAYYC HQRSNWLYT FGQGTKVDIK 204 mesothelin M2
(human) QVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYYMH WVRQAPGQGLEWMG WINPNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR DLRRTVVTPRAYYGMDV WGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSTLSASVGDRVTITC QASQDISNSLN WY QQKAGKAPKLLIY DASTLET GVPSRFSGSGSGTDFSFTISSLQPEDIATYYC QQHDNLPLT FGQGTKVEIK 205 mesothelin M3
(human) QVQLVQSGAEVKKPGAPVKVSCKAS GYTFTGYYMH WVRQAPGQGLEWMG WINPNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR GEWDGSYYYDY WGQGTLVTVSSGGGGSGGGGGSGGGGSGGGGSDIVLTQTPSSLSASVGDRVTITC RASQSINTYLN WYQ HKPGKAPKLLIY AASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSFSPLT FGGGTKLEIK 206 mesothelin M4
(human) QVQLVESGGGLVQPGGSLRLSCAAS GFTFSSYWMH WVRQVPGKGLVWVS RINTDGSTTTYADSVEG RFTISRDNAKNTLYLQMNSLRDDDTAVYYCVG GHWAV KASSLE SGVPSRFSGSGSGTEFTLTISSLQPDDFAVYYC QQYGHLPMYT FGQGTKVEIK 207 mesothelin M6
(human) QVQLVQSGAEVKKPGASVKVSCKAS GYTFTSYYMH WVRQAPGQGLEWMG IINPSGGSTSYAQKFQG RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR YRLIAVAGDYYYYGMDV WGQGTMVTVSSGGGGSGGGGSGGGGGSGGGGSDIQMTQSPSSVASVGDRVTITC RASQGVGRW LA WYQQKPGTAPKLLIY AASTLQS GVPSRFSGSGSGTDFTLTINNLQPEDFATYYC QQANSFPLT FGGGTRLEIK 208 mesothelin M7
(human) QVQLVQSGGGVVQPGRSLRLSCAAS GFTFSSYAMH WVRQAPGKGLEWVA VISYDGSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR WKVSSSSPAFDY WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERAILSC RASQSVYTKYLG WYQQK PGQAPRLLIY DASTRAT GIPDRFSGSGSGTDFTLTINRLEPEDFAVYYC QHYGGSPLIT FGQGTRLEIK 209 mesothelin M8
(human) QVQLQQSGAEVKKPGASVKVSCKTS GYPFTGYSLH WVRQAPGQGLEWMG WINPNSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR DHYGGNSLFY WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSSISASVGDTVSITC RASQDSGTWLA WYQQK PGKAPNLLMY DASTLED GVPSRFSGSASGTEFTLTVNRLQPEDSATYYC QQYNSYPLT FGGGTKVDIK 210 mesothelin M9
(human) QVQLVQSGAEVKKPGASVEVSCKAS GYTFTSYYMH WVRQAPGQGLEWMG IINPSGGSTGYAQKFQG RVTMTRDTSTSTVHMELSSLRSEDTAVYYCAR GGYSSSSDAFDI WGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPPSLSASVGDRVTITC RASQDISSALA WYQQKPG TPPKLLIY DASSLES GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQFSSYPLT FGGGTRLEIK 211 mesothelin M10
(human) QVQLVQSGAEVKKPGASVKVSCKAS GYTFTSYGIS WVRQAPGQGLEWMG WISAYNGNTNYAQKLQ GRVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR VAGGIYYYYGMDV WGQGTTITVSSGGGGSGGGGSGGGGSGGGGSDIVMTQTPDSLAVSLGERATISC KSSHVLYNRNNKNYLA WYQQ KPGQPPKLLFY WASTRKS GVPDRFSGSGSGTDFTLTISSLQPEDFATYFC QQTQTFPLT FGQGTRLEIN 212 mesothelin M12
(human) QVQLVQSGAEVKKPGASVKVSCKAS GYTFTGYYMH WVRQAPGQGLEWMG RINPNSGGTNYAQKFQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR TTTSYAFDI WGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSTLSASVGDRVTITC RASQSISTWLA WYQQKPGKA PNLLIY KASTLES GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYNTYSPYT FGQGTKLEIK 213 mesothelin M13
(human) QVQLVQSGGGLVKPGGSLRLSCEAS GFIFSDYYMG WIRQAPGKGLEWVS YIGRSGSSMYYADSVKG RFTFSRDNAKNSLYLQMNSLRAEDTAVYYCAA SPVVAATEDFQH WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQTPATLSLSPGERATLSC RASQSVTSNYLA WYQQKPGQ APRLLLF GASTRAT GIPDRFSGSGSGTDFTLTINRLEPEDFAMYYC QQYGSAPVT FGQGTKLEIK 214 mesothelin M14
(human) QVQLVQSGAEVRAPGASVKISCKAS GFTFRGYYIH WVRQAPGQGLEWMG IINPSGGSRAYAQKFQG RVTMTRDTSTSTSTVYMELSSLRSDDTAMYYCAR TASCGGDCYYLDY WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPPTLSASVGDRVTITC RASENVNIWLA WYQQKPG KAPKLLIY KSSSLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QQYQSYPLT FGGGTKVDIK 215 mesothelin M15
(human) QVQLVQSGGGLVQPGRSLRLSCAAS GFTFDDYAMH WVRQAPGKGLEWVS GISWNSGSIGYADSVK GRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAK DGSSSWSWGYFDY WGQGTLVTVSSGGGGSGGGGSGGGGSSSELTQDPAVSVALGQTVRTTC QGDALRSYYAS WYQQKPGQAPMLVIY GKNNRPS GIPDRFSGSDSGDTASLTITGAQAEDEADYYC NSRDSSGYPV FGTGTKVTVL 216 mesothelin M16
(human) EVQLVESGGGLVQPGRSLRLSCAAS GFTFDDYAMH WVRQAPGKGLEWVS GISWNSGSTGYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYCAK DSSSWYGGGSAFDI WGQGTMVTVSSGGGGSGGGGGSGGGGSSSELTQEPAVSVALGQTVRITC QGDSLRSYYAS WYQQKPGQAPV LVIF GRSRRPS GIPDRFSGSSSGNTASLIITGAQAEDEADYYC NSRDNTANHYV FGTGTKLTVL 217 mesothelin M17
(human) EVQLVESGGGLVQPGRSLRLSCAAS GFTFDDYAMH WVRQAPGKGLEWVS GISWNSGSTGYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYCAK DSSSWYGGGSAFDI WGQGTMVTVSSGGGGSGGGGGSGGGGSSSELTQDPAVSVALGQTVRITC QGDSLRSYYAS WYQQKPGQAPV LVIY GKNNRPS GIPDRFSGSSSGNTASLTITGAQAEDEADYYC NSRGSSGNHYV FGTGTKVTVL 218 mesothelin M18
(human) QVQLVQSGGGLVQPGGSLRLSCAAS GFTFSSYWMH WVRQAPGKGLVWVS RINSDGSSTSYADSVKG RFTISRDNAKNTLYLQMNSLRAEDTAVYYCVR TGWVGSYYYYMDV WGKGTTVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSC RASQSVSSNYLA WYQQK PGQPPRLLIY DVSTRAT GIPARFSGGGSGTDFTLTISSLEPEDFAVYYC QQRSNWPPWT FGQGTKVEIK 219 mesothelin M19
(human) QVQLVQSGGGVVQPGRSLRLSCAAS GFTFSSYGMH WVRQAPGKGLEWVA VISYDGSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK GYSRYYYYGMDV WGQGTTVTVSSGGGGSGGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERAILSC RASQSVYTKYLG WY QQKPGQAPRLLIY DASTRAT GIPDRFSGSGSGTDFTLTINRLEPEDFAVYYC QHYGGSPLIT FGQGTKVDIK 220 mesothelin M20
(human) QVQLVQSGGGLVQPGGSLRLSCAAS GFTFSSYAMS WVRQAPGKGLEWVS AISGSGGSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK REAAAGHDWYFDL WGRGTLVTVSSGGGGSGGGGSGGGGGSGGGGSDIRVTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAP KLLIY AASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSIPLT FGQGTKVEIK 221 mesothelin M21
(human) QVQLVQSWAEVKKPGASVKVSCKAS GYTFTSYYMH WVRQAPGQGLEWMG INPSGGSTSYAQKFQG RVTMTRDTSTSTVYMELSNLRSEDTAVYYCAR SPRVTTGYFDY WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSTLSASVGDRVTITC RASQSISSWLA WYQQKPG KAPKLLIY KASSLE SGVPSRFSGSGSGTEFTLTISSLQPDDFATYYC QQYSSYPLT FGGGTRLEIK 222 mesothelin M22
(human) QVQLVQSGAEVRRPGASVKISCRAS GDTSTRHYIH WLRQAPGQGPEWMG VINPTTGPATGSPAYAQMLQG RVTMTRDTSTRTVYMELRSLRFEDTAVYYCAR SVVGRSAPYYFDY WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITC RASQGISDYS AWYQQ KPGKAPKLLIY AASTLQS GVPSRFSGSGSGTDFTLTISYLQSEDFATYYC QQYYSYPLT FGGGTKVDIK 223 mesothelin M23
(human) QVQLQQSGAEVKKPGASVKVSCKAS GYTFTNYYMH WVRQAPGQGLEWMG IINPSGGYTTYAQKFQG RLTMTRDTSTSTVYMELSSLRSEDTAVYYCAR IRSCGGDCYYFDN WGQGTLVTVSSGGGGSGGGGSDIQLTQSPSTLSASVGDRVTITC RASENVNIWLA WY QQKPGKAPKLLIY KSSSLAS GVPSRFSGSGSGAEFTLTISSLQPDDFATYYC QQYQSYPLT FGGGTKVDIK 224 mesothelin M24
(human) QITLKESGPALVKPTQTLLTTCTFS GFSLSTAGVHVG WIRQPPGKALEWLA LISWADDKRYRPSLRS RLDITRVTSKDQVVLSMTNMQPEDTATYYCAL QGFDGYEAN WGPGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSPSSLSASAGDRVTITC RASRGISSALA WYQQKPGKPPKL LIY DASSLES GVPSRFSGSGSGTDFTLTIDSLEPEDFATYYC QQSYSTPWT FGQGTKVDIK 225

The sequences of the CDR domains of the scFv antigen binding domains for mesothelin shown in Table 3 are shown in Table 4 for the heavy chain variable domains and in Table 5 for the light chain variable domains.

Table 4. Amino acid sequences of the heavy chain (HC) CDR1, CDR2, and CDR3 regions of scFv for human mesothelin

Description HC-CDR1 SEQID NO: HC-CDR2 SEQID NO: H-CDR3 SEQID NO: M5 GYTFTDYYMH 226 WINPNSGGTNYAQKFQG 227 GWDFDY 228 M11 GYTFTGYYMH 229 WINPNSGGTNYAQNFQG 230 GWDFDY 228 SS1 GYSFTGYTMN 231 LITPYNGASSYNQKFRG 232 GGYDGRGFDY 233 M1 GYTFTGYYMH 229 RINPNSGGTNYAQKFQG 234 GRYYGMDV 235 M2 GYTFTGYYMH 229 WINPNSGGTNYAQKFQG 227 DLRRTVVTPRAYYGMDV 236 M3 GYTFTGYYMH 229 WINPNSGGTNYAQKFQG 227 GEWDGSYYYDY 237 M4 GFTFSSYWMH 238 RINTDGSTTTYADSVEG 239 GHWAV 240 M6 GYTFTSYYMH 241 IINPSGGSTSYAQKFQ 242 YRLIAVAGDYYYYGMDV 243 M7 GFTFSSYAMH 244 VISYDGSNKKYYADSVKG 245 WKVSSSSPAFDY 246 M8 GYPFTGYSLH 247 WINPNSGGTNYAQKFQG 227 DHYGGNSLFY 248 M9 GYTFTSYYMH 241 IINPSGGSTGYAQKFQG 249 GGYSSSSDAFDI 250 M10 GYTFTSYGIS 251 WISAYNGNTNYAQKLQ 252 VAGGIYYYYGMDV 253 M12 GYTFTGYYMH 229 RINPNSGGTNYAQKFQG 234 TTTSYAFDI 254 M13 GFIFSDYYMG 255 YIGRSGSSMYYADSVKG 256 SPVVAATEDFQH 257 M14 GFTFRGYYIH 258 IINPSGGSRAYAQKFQG 259 TASCGGDCYYLDY 260 M15 GFTFDDYAMH 261 GISWNSGSIGYADSVK 262 DGSSSWSWGYFDY 263 M16 GFTFDDYAMH 261 GISWNSGSTGYADSVKG 264 DSSSWYGGGSAFDI 265 M17 GFTFDDYAMH 261 GISWNSGSTGYADSVKG 264 DSSSWYGGGSAFDI 265 M18 GFTFSSYWMH 238 RINSDGSSTSYADSVKG 266 TGWVGSYYYYMDV 267 M19 GFTFSSYGMH 268 VISYDGSNKKYYADSVKG 245 GYSRYYYYGMDV 269 M20 GFTFSSYAMS 270 AISGSGGSTYYADSVKG 271 REAAAGHDWYFDL 272 M21 GYTFTSYYMH 241 IINPSGGSTSYAQKFQG 273 SPRVTTGYFDY 274 M22 GDTSTRHYIH 275 VINPTTGPATGSPAYAQMLQG 276 SVVGRSAPYYFDY 277 M23 GYTFTNYYMH 278 IINPSGGYTTYAQKFQG 279 IRSCGGDCYYFDN 280 M24 GFSLSTAGVHVG 281 LISWADDKRYRPSLRS 282 QGFDGYEAN 283

Table 5. Amino acid sequences of the light chain (LC) CDR1, CDR2 and CDR3 regions of scFv for human mesothelin

Description LC-CDR1 SEQID NO: LC-CDR2 SEQID NO: LC-CDR3 SEQID NO: M5 RASQSIRYYLS 284 TASILQN 285 LQTYTTPD 286 M11 RASQSIRYYLS 284 TASILQN 285 LQTYTTPD 286 SS1 SASSSVSYMH 287 DTSKLAS 288 QQWSGYPLT 289 M1 RASQSVSSNFA 290 DASNRAT 291 HQRSNWLYT 292 M2 QASQDISNSLN 293 DASTLET 294 QQHDNLPLT 295 M3 RASQSINTYLN 296 AASSLQS 297 QQSFSPLT 298 M4 RASQSISDRLA 299 KASSLES 300 QQYGHLPMYT 301 M6 RASQGVGRWLA 302 AASTLQS 303 QQANSFLT 304 M7 RASQSVYTKYLG 305 DASTRAT 306 QHYGGSPLIT 307 M8 RASQDSGTWLA 308 DASTLED 309 QQYNSYPLT 310 M9 RASQDISSALA 311 DASSLES 312 QQFSSYPLT 313 M10 KSSHVLYNRNNKNYLA 314 WASTRKS 315 QQTQTFPLT 316 M12 RASQSISTWLA 317 KASTLES 318 QQYNTYSPYT 319 M13 RASQSVTSNYLA 320 GASTRAT 321 QQYGSAPVT 322 M14 RASENVNIWLA 323 KSSSLAS 324 QQYQSYPLT 325 M15 QGDALRSYYAS 326 GKNNRPS 327 NSRDSSGYPV 328 M16 QGDSLRSYYAS 329 GRRRPS 330 NSRDNTANHYV 331 M17 QGDSLRSYYAS 329 GKNNRPS 327 NSRGSSGNHYV 332 M18 RASQSVSSNYLA 333 DVSTRAT 334 QQRSNWPPWT 335 M19 RASQSVYTKYLG 305 DASTRAT 306 QHYGGSPLIT 307 M20 RASQSISSYLN 336 AASSLQS 297 QQSYSIPLT 337 M21 RASQSISSWLA 338 KASSLES 300 QQYSSYPLT 339 M22 RASQGISDYS 340 AASTLQS 303 QQYYSYPLT 341 M23 RASENVNIWLA 323 KSSSLAS 324 QQYQSYPLT 325 M24 RASRGISSALA 342 DASSLES 312 QQSYSTPWT 343

Any known mesothelin binding domain from, for example, a known antibody, bispecific molecule, or CAR may be suitable for use in the CAR of the present invention. For example, the antigen-binding domain for mesothelin is, or can be, derived from antigen-binding regions, eg CDRs or VH and VL, of an antibody, antigen-binding fragment or CAR, as described, for example, in PCT publication WO2015/090230. In embodiments, the antigen-binding domain for mesothelin is, or is derived from, an antigen-binding fragment, e.g., a CDR or VH and VL, an antibody, an antigen-binding fragment, or a CAR, as described in, for example, PCT Publications WO1997/025068, WO1999/028471, WO2005/014652, WO2006/099141, WO2009/045957, WO2009/068204, WO2013/142034, WO2013/040557 or WO2013/063419.

In one embodiment, the mesothelin binding domain comprises one or more (e.g., all three) of Light Chain Complementarity Determining Region 1 (LC CDR1), Light Chain Complementarity Determining Region 2 (LC CDR2), and Light Chain Complementarity Determining Region 3 (LC CDR3). ) a mesothelin binding domain as described herein, such as those listed in Table 3 or 5, and/or one or more (eg, all three) of the heavy chain complementarity determining region 1 (HC CDR1), heavy chain complementarity determining region 2 (HC CDR2) and complementarity determining region 3 of the heavy chain (HC CDR3) of the mesothelin binding domain described herein, for example, are shown in Table 3 or 4. In one embodiment, the mesothelin binding domain contains one, two or all of the LC CDR1, LC CDR2 and LC CDR3 with any of the amino acid sequences shown in Table 5; and one, two or all of HC CDR1, HC CDR2 and HC CDR3 with any of the amino acid sequences shown in Table 4.

In one embodiment, the mesothelin binding domain comprises a light chain variable region as described herein (eg, in Table 3) and/or a heavy chain variable region as described herein (eg, in Table 3). In one embodiment, the mesothelin binding domain is a scFv containing a light chain and a heavy chain with the amino acid sequences shown in Table 3. In one embodiment, the mesothelin binding domain (e.g., scFv) contains: a light chain variable region containing the amino acid sequence having at least one, two, or three modifications (e.g., substitutions, e.g., conservative substitutions), but not more than 30, 20, or 10 modifications (e.g., substitutions, e.g., conservative substitutions) of the amino acid sequence of the light chain variable region given in Table 3, or a sequence having 95-99% identity with the amino acid sequence shown in Table 3; and/or a heavy chain variable region containing an amino acid sequence having at least one, two, or three modifications (e.g., substitutions, e.g., conservative substitutions), but no more than 30, 20, or 10 modifications (e.g., substitutions, substitutions) the amino acid sequence of the heavy chain variable region shown in Table 3, or a sequence having 95-99% identity with the amino acid sequence shown in Table 3.

In one embodiment, the mesothelin binding domain comprises an amino acid sequence selected from any of SEQ ID NOs: 201-225; or an amino acid sequence having at least one, two, or three modifications (eg, substitutions, eg, conservative substitutions), but not more than 30, 20, or 10 modifications (eg, substitutions, eg, conservative substitutions) in any of the above sequences; or a sequence having 95-99% identity with any of the above sequences. In one embodiment, the mesothelin binding domain is scFv and a light chain variable region containing the amino acid sequence described herein, e.g., in Table 3, is linked to a heavy chain variable region containing the amino acid sequence described herein, e.g. , in Table 3, via a linker, such as the linker described herein. In one embodiment, the mesothelin binding domain includes a (Gly4-Ser)n linker, where n is 1, 2, 3, 4, 5, or 6, preferably 4 (SEQ ID NO: 967). The light chain variable region and the heavy chain variable region in the scFv can be, for example, in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region.

In one embodiment, the antigen-binding domain of a CAR, for example the CAR expressed by the cell of the invention, binds to human EGFRvIII. In one embodiment, the antigen binding domain is a murine scFv domain that binds to human EGFRvIII, such as, for example, mu310C. In one embodiment, the antigen binding domain is a humanized antibody or antibody fragment, such as an scFv domain derived from a murine mu31°C scFv. Exemplary humanized scFv domains (and their sequences) as well as murine scFv SS1 that bind to EGFRvIII are shown in Table 6.

In one embodiment, the CAR antigen-binding domain binds to human claudin-6 (CLDN6). In one embodiment, the antigen binding domain is a murine scFv domain that binds to human CLDN6. In one embodiment, the antigen binding domain is a humanized antibody or antibody fragment. Exemplary scFv domains (and their sequences) that bind to CLDN6 are shown in Table 6. The scFv domain sequences shown in Table 6 include the light chain variable region (VL) and the heavy chain variable region (VH). VL and VH are linked by a linker containing the sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 29), for example in the following orientation: VL-linker-VH.

Table 6. Antigen-binding domains that bind to tumor antigen EGFRvIII or CLDN6

Tumor antigen Name Amino acid sequence SEQID NO: EGFRvIII huscFv1 Eiqlvqsgaevkkpgatvkisckgsgfniedyyihwvqqapgkglewmgridpendetkygpifqgrvtitadtstntvymelsslrsedtavyycafrggvywgqgttvtvssggggsggggsggggsggggsdvvmtqspdslavslgeratinckssqslldsdgktylnwlqqkpgqppk rlislvskldsgvpdrfsgsgsgtdftltisslqaedvavyycwqgthfpgtfgggtkveik 344 EGFRvIII huscFv2 Dvvmtqspdslavslgeratincksssqslldsdgktylnwlqqkpgqppkrlislvskldsgvpdrfsgsgsgtdftltisslqaedvavyycwqgthfpgtfgggtkveikggggsggggsggggsggggseiqlvqsgaevkkpgatvkisckgsgfniedyyihwvqqapg kglewmgridpendetkygpifqgrvtitadtstntvymelsslrsedtavyycafrggvywgqgttvtvss 345 EGFRvIII huscFv3 Eiqlvqsgaevkkpgeslrisckgsgfniedyyihwvrqmpgkglewmgridpendetkygpifqghvtisadtsintvylqwsslkasdtamyycafrggvywgqgttvtvssggggsggggsggggsggggsdvvmtqsplslpvtlgqpasisckssqslldsdgktylnwlqqrp gqsprrlislvskldsgvpdrfsgsgsgtdftlkisrveaedvgvyycwqgthfpgtfgggtkveik 346 EGFRvIII huscFv4 Dvvmtqsplslpvtlgqpasisckssqslldsdgktylnwlqqrpgqsprrlislvskldsgvpdrfsgsgsgtdftlkisrveaedvgvyycwqgthfpgtfgggtkveikggggsggggsggggsggggseiqlvqsgaevkkpgeslrisckgsgfniedyyihwvr qmpgkglewmgridpendetkygpifqghvtisadtsintvylqwsslkasdtamyycafrggvywgqgttvtvss 347 EGFRvIII huscFv5 Eiqlvqsgaevkkpgatvkisckgsgfniedyyihwvqqapgkglewmgridpendetkygpifqgrvtitadtstntvymelsslrsedtavyycafrggvywgqgttvtvssggggsggggsggggsggggsdvvmtqsplslpvtlgqpasisckssqslldsdgktylnwlqqrp gqsprrlislvskldsgvpdrfsgsgsgtdftlkisrveaedvgvyycwqgthfpgtfgggtkveik 348 EGFRvIII huscFv6 Eiqlvqsgaevkkpgeslrisckgsgfniedyyihwvrqmpgkglewmgridpendetkygpifqghvtisadtsintvylqwsslkasdtamyycafrggvywgqgttvtvssggggsggggsggggsggggsdvvmtqspdslavslgeratinckssqslldsdgktylnwlqqkpgqppk rlislvskldsgvpdrfsgsgsgtdftltisslqaedvavyycwqgthfpgtfgggtkveik 349 EGFRvIII huscFv7 Dvvmtqspdslavslgeratincksssqslldsdgktylnwlqqkpgqppkrlislvskldsgvpdrfsgsgsgtdftltisslqaedvavyycwqgthfpgtfgggtkveikggggsggggsggggsggggseiqlvqsgaevkkkpgeslrisckgsgfniedyyihwvrqmpgk glewmgridpendetkygpifqghvtisadtsintvylqwsslkasdtamyycafrggvywgqgttvtvss 350 EGFRvIII huscFv8 Dvvmtqsplslpvtlgqpasisckssqslldsdgktylnwlqqrpgqsprrlislvskldsgvpdrfsgsgsgtdftlkisrveaedvgvyycwqgthfpgtfgggtkveikggggsggggsggggsggggseiqlvqsgaevkkpgatvkisckgsgfniedyyihwv qqapgkglewmgridpendetkygpifqgrvtitadtstntvymelsslrsedtavyycafrggvywgqgttvtvss 351 EGFRvIII Mu310C eiqlqqsgaelvkpgasvklsctgsgfniedyyihwvkqrteqglewigridpendetkygpifqgratitadtssntvylqlssltsedtavyycafrggvywgpgttltvssggggsggggsggggshmdvvmtqspltlsvaigqsasisckssqslldsdgktylnwllqrpgqspkrlis lvskldsgvpdrftgsgsgtdftlrisrveaedlgiyycwqgthfpgtfgggtkleik 352 Claudin-6 muMAB 64A EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYNGGTIYNQKFKGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARDYGFVLDYWGQGTTLTVSSGGGGSGGGGSGGGGGSGGGGSQIVLTQSPSIMSVSPGEKVTITCSASSSVSYMHWFQQKPGTSPKLC IYSTSNLASGVPARFSGRGSGTSYSLTISRVAAEDAATYYCQQRSNYPPWTFGGGTKLEIK 353 Claudin-6 mAb206-LCC EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYNGGTIYNQKFKGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARDYGFVLDYWGQGTTLTVSSGGGGSGGGGSGGGGGSGGGGSQIVLTQSPAIMSASPGEKVTITCSASSSVSYLHWFQQKPGTSPKL WVYSTSNLPSGVPARFGGSGSGTSYSLTISRMEAEDAATYYCQQRSIYPPWTFGGGTKLEIK 354 Claudin-6 mAb206-SUBG EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWIGLINPYNGGTIYNQKFKGKATLTVDKSSSTAYMELLSLTSEDSAVYYCARDYGFVLDYWGQGTTLTVSSGGGGSGGGGSGGGGSGGGGSQIVLTQSPSIMSVSPGEKVTITCSASSSVSYMHWFQQKPGTSPKL GIYSTSNLASGVPARFSGRGSGTSYSLTISRVAAEDATYYCQQRSNYPPWTFGGGTKLEIK 355

In one embodiment, the EGFRvIII binding domain comprises one or more (e.g., all three) of light chain complementarity determining region 1 (LC CDR1), light chain complementarity determining region 2 (LC CDR2), and light chain complementarity determining region 3 (LC CDR3). ) the EGFRvIII binding domain described herein, such as those listed in Table 6, and/or one or more (e.g., all three) of the heavy chain complementarity determining region 1 (HC CDR1), the heavy chain complementarity determining region 2 (HC CDR2) and complementarity determining region 3 of the heavy chain (HC CDR3) of the EGFRvIII binding domain described herein, for example, are shown in Table 6.

In one embodiment, the EGFRvIII binding domain comprises a light chain variable region as described herein (eg, in Table 6) and/or a heavy chain variable region as described herein (eg, in Table 6). In one embodiment, the EGFRvIII binding domain is an scFv containing a light chain and a heavy chain with the amino acid sequences shown in Table 6. In one embodiment, an EGFRvIII binding domain (e.g., scFv) contains: a light chain variable region containing the amino acid sequence having at least one, two, or three modifications (e.g., substitutions, e.g., conservative substitutions), but not more than 30, 20, or 10 modifications (e.g., substitutions, e.g., conservative substitutions) of the amino acid sequence of the light chain variable region given in Table 6, or a sequence having 95-99% identity with the amino acid sequence shown in Table 6; and/or a heavy chain variable region containing an amino acid sequence having at least one, two, or three modifications (e.g., substitutions, e.g., conservative substitutions), but no more than 30, 20, or 10 modifications (e.g., substitutions, substitutions) the amino acid sequence of the heavy chain variable region shown in Table 6, or a sequence having 95-99% identity with the amino acid sequence shown in Table 6.

In one embodiment, the EGFRvIII binding domain comprises an amino acid sequence selected from any of SEQ ID NOs: 344-352; or an amino acid sequence having at least one, two, or three modifications (eg, substitutions, eg, conservative substitutions), but not more than 30, 20, or 10 modifications (eg, substitutions, eg, conservative substitutions) in any of the above sequences; or a sequence having 95-99% identity with any of the above sequences. In one embodiment, the EGFRvIII binding domain is scFv and a light chain variable region containing the amino acid sequence described herein, e.g., in Table 6, is linked to a heavy chain variable region containing the amino acid sequence described herein, e.g. , in Table 6, via a linker, such as the linker described herein. In one embodiment, the EGFRvIII binding domain includes a (Gly4-Ser)n linker, where n is 1, 2, 3, 4, 5, or 6, preferably 4 (SEQ ID NO: 967). The light chain variable region and the heavy chain variable region in the scFv can be, for example, in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region.

In one embodiment, the claudin-6 binding domain comprises one or more (e.g., all three) of light chain complementarity determining region 1 (LC CDR1), light chain complementarity determining region 2 (LC CDR2), and light chain complementarity determining region 3 ( LC CDR3) of the claudin-6 binding domain described herein, such as those listed in Table 6, and/or one or more (eg, all three) of the heavy chain complementarity determining region 1 (HC CDR1), complementarity determining region 2 heavy chain (HC CDR2) and complementarity determining region 3 of the heavy chain (HC CDR3) of the claudin-6 binding domain described herein, for example, are shown in Table 6.

In one embodiment, the claudin-6 binding domain comprises a light chain variable region as described herein (eg, in Table 6) and/or a heavy chain variable region as described herein (eg, in Table 6). In one embodiment, the claudin-6 binding domain is an scFv containing a light chain and a heavy chain with the amino acid sequences shown in Table 6. In one embodiment, the claudin-6 binding domain (e.g., scFv) contains: a light chain variable region, containing an amino acid sequence having at least one, two or three modifications (e.g. substitutions, e.g. conservative substitutions), but not more than 30, 20 or 10 modifications (e.g. substitutions, e.g. conservative substitutions) of the light chain variable region amino acid sequence shown in Table 6, or a sequence having 95-99% identity with the amino acid sequence shown in Table 6; and/or a heavy chain variable region containing an amino acid sequence having at least one, two, or three modifications (e.g., substitutions, e.g., conservative substitutions), but no more than 30, 20, or 10 modifications (e.g., substitutions, substitutions) the amino acid sequence of the heavy chain variable region shown in Table 6, or a sequence having 95-99% identity with the amino acid sequence shown in Table 6.

In one embodiment, the claudin-6 binding domain comprises an amino acid sequence selected from any of SEQ ID NOs: 353-355; or an amino acid sequence having at least one, two, or three modifications (eg, substitutions, eg, conservative substitutions), but not more than 30, 20, or 10 modifications (eg, substitutions, eg, conservative substitutions) in any of the above sequences; or a sequence having 95-99% identity with any of the above sequences. In one embodiment, the claudin-6 binding domain is scFv and a light chain variable region containing the amino acid sequence described herein, e.g., in Table 6, is linked to a heavy chain variable region containing the amino acid sequence described herein. , for example, in Table 6, through a linker, for example, the linker described in this document. In one embodiment, the claudin-6 binding domain includes a (Gly4-Ser)n linker, where n is 1, 2, 3, 4, 5, or 6, preferably 4 (SEQ ID NO: 967). The light chain variable region and the heavy chain variable region in the scFv can be, for example, in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region.

In one embodiment, the antigen-binding domain for GD2 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Mujoo et al., Cancer Res. 47(4):1098-1104 (1987); Cheung et al., Cancer Res 45(6):2642-2649 (1985), Cheung et al., J Clin Oncol 5(9):1430-1440 (1987), Cheung et al., J Clin Oncol 16(9 ):3053-3060 (1998), Handgretinger et al., Cancer Immunol Immunother 35(3):199-204 (1992). In some embodiments, the antigen-binding domain for GD2 is an antigen-binding fragment of an antibody selected from mAb 14.18, 14G2a, ch14.18, hu14.18, 3F8, hu3F8, 3G6, 8B6, 60C3, 10B8, ME36.1, and 8H9, see e.g. , WO2012033885, WO2013040371, WO2013192294, WO2013061273, WO2013123061, WO2013074916 and WO201385552. In some embodiments, the antigen-binding domain for GD2 is an antigen-binding fragment of an antibody described in US Patent Application Publication No. 20100150910 or PCT Publication No. WO2011160119.

In one embodiment, the antigen-binding domain for a Tn antigen, sTn antigen, Tn-O-glycopeptide antigen, or sTn-O-glycopeptide antigen is an antigen-binding fragment, e.g., a CDR region, of an antibody described, for example, in US2014/0178365, US8440798 , EP 2083868 A2, Brooks et al., PNAS 107(22):10056-10061 (2010) and Stone et al., OncoImmunology 1(6):863-873(2012).

In one embodiment, the antigen-binding domain for PSMA is an antigen-binding fragment, e.g., CDR regions, of an antibody as described in e.g. Parker et al., Protein Expr Purif 89(2):136-145 (2013), US20110268656 (J591 ScFv) ; Frigerio et al, European J Cancer 49(9):2223-2232 (2013) (scFvD2B); WO2006125481 (mAb 3/A12, 3/E7 and 3/F11), and single chain antibody fragments (scFv A5 and D7).

In one embodiment, the antigen-binding domain for CD97 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, US6846911; de Groot et al., J Immunol 183(6):4127-4134 (2009); or antibodies from R&D:MAB3734.

In one embodiment, the antigen-binding domain for TAG72 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Hombach et al., Gastroenterology 113(4):1163-1170 (1997); and Abcam ab691.

In one embodiment, the antigen-binding domain for CD44v6 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Casucci et al., Blood 122(20):3461-3472 (2013).

In one embodiment, the antigen-binding domain for CEA is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Chmielewski et al., Gastoenterology 143(4):1095-1107 (2012).

In one embodiment, the antigen-binding domain for EPCAM is an antigen-binding fragment, eg, CDR regions, of an antibody selected from MT110, EpCAM-CD3 bispecific Ab (see, eg, clinicaltrials.gov/ct2/show/NCT00635596); edrecolomab; 3622W94; ING-1 and adecatumumab (MT201).

In one embodiment, the antigen-binding domain for a KIT is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, US7915391, US20120288506, and some commercially available antibody catalogues.

In one embodiment, the antigen-binding domain for IL-13Ra2 is an antigen-binding fragment, e.g., CDR regions, of an antibody described in e.g.

In one embodiment, the antigen-binding domain for CD171 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Hong et al., J Immunother 37(2):93-104 (2014).

In one embodiment, the antigen-binding domain for PSCA is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Morgenroth et al., Prostate 67(10):1121-1131 (2007) (scFv 7F5); Nejatollahi et al., J of Oncology 2013(2013), paper ID 839831 (scFv C5-II) and US Patent Publication No. 20090311181.

In one embodiment, the antigen-binding domain for MAD-CT-2 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, PMID: 2450952; US7635753.

In one embodiment, the antigen-binding domain for folate receptor alpha is an antigen-binding fragment, for example, the CDR regions of an IMGN853 antibody, or an antibody described in US20120009181; US4851332, LK26: US5952484.

In one embodiment, the antigen-binding domain for ERBB2 (Her2/neu) is an antigen-binding fragment, such as the CDR regions of a trastuzumab or pertuzumab antibody.

In one embodiment, the antigen-binding domain for MUC1 is an antigen-binding fragment, such as the CDR regions, of the SAR566658 antibody.

In one embodiment, the antigen-binding domain for EGFR is an antigen-binding fragment, for example, the CDR regions of a cetuximab, panitumumab, zalutumumab, nimotuzumab, or matuzumab antibody.

In one embodiment, the antigen-binding domain for NCAM is an antigen-binding fragment, e.g., CDR regions, of antibody clone 2-2B: MAB5324 (EMD Millipore)

In one embodiment, the antigen-binding domain for CAIX is an antigen-binding fragment, eg, CDR regions, of antibody clone 303123 (R&D Systems).

In one embodiment, the antigen-binding domain for Fos-related antigen 1 is an antigen-binding fragment, eg, CDR regions, of the 12F9 antibody (Novus Biologicals).

In one embodiment, the antigen-binding domain for SSEA-4 is an antigen-binding fragment, such as the CDR regions of the MC813 antibody (Cell Signaling), or other commercially available antibodies.

In one embodiment, the antigen-binding domain for PDGFR-beta is an antigen-binding fragment, eg, CDR regions, of the Abcam ab32570 antibody.

In one embodiment, the antigen-binding domain for ALK is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Mino-Kenudson et al., Clin Cancer Res 16(5):1561-1571 (2010).

In one embodiment, the polysialic acid antigen-binding domain is an antigen-binding fragment, e.g., CDR regions, of an antibody as described in, e.g., Nagae et al., J Biol Chem 288(47):33784-33796 (2013).

In one embodiment, the antigen-binding domain for PLAC1 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Ghods et al., Biotechnol Appl Biochem 2013 doi:10,1002/bab.1177.

In one embodiment, the antigen-binding domain for GloboH is an antigen-binding fragment of a VK9 antibody; or an antibody as described in, for example, Kudryashov V et al, Glycoconj J.15(3):243-9 (1998), Lou et al., Proc Natl Acad Sci USA 111(7):2482-2487 (2014); MBr1: Bremer EG et al. J Biol Chem 259:14773-14777 (1984).

In one embodiment, the antigen-binding domain for NY-BR-1 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Jager et al., Appl Immunohistochem Mol Morphol 15(1):77-83 (2007).

In one embodiment, the antigen-binding domain for sperm 17 protein is an antigen-binding fragment, eg, CDR regions, of an antibody described in, eg, Song et al., Target Oncol 2013 Aug 14 (PMID: 23943313); Song et al., Med Oncol 29(4):2923-2931 (2012).

In one embodiment, the antigen-binding domain for TRP-2 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Wang et al., J Exp Med. 184(6):2207-16 (1996).

In one embodiment, the antigen-binding domain for CYP1B1 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Maecker et al, Blood 102 (9): 3287-3294 (2003).

In one embodiment, the antigen-binding domain for RAGE-1 is an antigen-binding fragment, eg, CDR regions, of the MAB5328 antibody (EMD Millipore).

In one embodiment, the antigen-binding domain for human telomerase reverse transcriptase is an antigen-binding fragment, eg, CDR regions, of antibody cat. no.: LS-B95-100 (Lifespan Biosciences).

In one embodiment, the antigen-binding domain for intestinal carboxylesterase is an antigen-binding fragment, eg, CDR regions, of the 4F12 antibody cat. no.: LS-B6190-50 (Lifespan Biosciences).

In one embodiment, the antigen-binding domain for mut hsp70-2 is an antigen-binding fragment, e.g., CDR regions, of an antibody from Lifespan Biosciences: monoclonal, cat. no: LS-C133261-100 (Lifespan Biosciences).

In one embodiment, the antigen-binding domain for MAD-CT-2 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, PMID: 2450952; US7635753.

In one embodiment, the antigen binding domain comprises one, two, three (e.g., all three) of the heavy chain CDR regions, HC CDR1, HC CDR2, and HC CDR3, from the antibody listed above, and/or one, two, three (e.g., all three) from the light chain CDR regions, LC CDR1, LC CDR2 and LC CDR3, from the antibody listed above. In one embodiment, the antigen binding domain comprises a heavy chain variable region and/or a light chain variable region of an antibody listed above.

In some embodiments, the antigen-binding domain of a CAR is targeted to a tumor antigen, which is an antigen expressed on a myeloid tumor (either a surface antigen or presented by an MHC), and a cell containing such a CAR recognizes the myeloid tumor antigen.

In one embodiment, the myeloid tumor antigen is an antigen that is preferentially or specifically expressed on the surface of a myeloid tumor cell.

In one embodiment, the antigen-binding domain of a CAR may be selected to target a population of myeloid tumor cells. Alternatively, if targeting more than one species of myeloid tumor is desired, an antigen-binding domain that targets a myeloid tumor antigen expressed by more than one, eg, all, myeloid tumor species can be selected.

CAR can target the following additional tumor antigens: CD123, CD34, Flt3, CD33 and CLL-1. In embodiments, the tumor antigen is selected from CD123, CD33, and CLL-1. In some embodiments, the tumor antigen is CD123. In some embodiments, the tumor antigen is CD33. In some embodiments, the tumor antigen is CD34. In some embodiments, the tumor antigen is Flt3. In embodiments, the tumor antigen is CLL-1. In embodiments, the antigen-binding domain is targeted to a human antigen.

In one aspect, a CAR antigen-binding domain binds to CD123, eg, human CD123. Any known CD123 binding domain can be used in the invention. In one embodiment, the antigen-binding domain for CD123 is an antigen-binding fragment, such as the CDRs or VH and VL regions, of an antibody, antigen-binding fragment, or CAR, as described, for example, in PCT publication WO2014/130635. In one embodiment, the antigen-binding domain for CD123 is an antigen-binding fragment, such as the CDRs or VH and VL regions, of an antibody, antigen-binding fragment, or CAR, as described, for example, in PCT publication WO2016/028896. In one embodiment, the antigen-binding domain for CD123 is an antigen-binding fragment, e.g., the CDR, antibody, antigen-binding fragment, or CAR regions described in, e.g., PCT publications WO1997/024373, WO2008/127735 (e.g. , 37716 or 32703), WO2014/138805 (e.g. CD123 binding domain from CSL362), WO2014/138819, WO2013/173820, WO2014/144622, WO2001/66139, WO2010/126066 (e.g. CD12 3-binding domain from any of Old4 , Old5, Old17, Old19, New102 or Old6), WO2014/144622, WO2016/028896 or US2009/0252742. In embodiments, the antigen binding domain is, or is derived from, a murine binding domain for human CD123. In embodiments, the antigen binding domain is a humanized antibody or antibody fragment, such as an scFv domain. In one embodiment, the antigen binding domain is a human antibody, or antibody fragment, that binds to human CD123. In embodiments, the antigen binding domain is an scFv domain that contains a light chain variable region (VL) and a heavy chain variable region (VH). VL and VH may be linked by a linker as described herein, eg, containing the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 30), and may be in any orientation, eg, VL-linker-VH or VH-linker-VL.

In some embodiments, the antigen binding domain that binds to CD123 is an scFv domain. In some embodiments, the antigen binding domain that binds to CD123 is the murine scFv domain. In one embodiment, the antigen binding domain that binds to CD123 is a human or humanized scFv domain. Exemplary scFv domains (and sequences thereof) that bind to CLDN6 are shown in Table 19. The scFv domain sequences shown in Table 19 include the light chain variable region (VL) and the heavy chain variable region (VH). VL and VH are linked by a linker containing the sequence GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 29), for example in the following orientation: VL-linker-VH. In one embodiment, the CD123 binding domain comprises an amino acid sequence selected from any of SEQ ID NOs: 751, 756, 761, or 766; or an amino acid sequence having at least one, two, or three modifications (eg, substitutions, eg, conservative substitutions), but not more than 30, 20, or 10 modifications (eg, substitutions, eg, conservative substitutions) in any of the above sequences; or a sequence having 95-99% identity with an amino acid sequence selected from any of SEQ ID NOs: 751, 756, 761, or 766.

In one aspect, the CAR antigen-binding domain binds to CD33, eg, human CD33. Any known CD33 binding domain can be used in the invention. In one embodiment, the antigen-binding domain for CD33 is an antigen-binding fragment, e.g., the CDR or VH and VL regions, of an antibody, antigen-binding fragment, or CAR, as described in, for example, PCT publication WO2016/014576 or US Patent Publication 2016-0096892-A1, in full the contents of which are incorporated herein by reference. In one embodiment, the antigen-binding domain for CD33 is an antigen-binding fragment from, or derived from, gemtuzumab-ozagomycin (e.g., comprising an antigen-binding domain comprising one or more, e.g., one, two, or three CDRs from a heavy chain variable domain and/ or one or more, e.g. one, two or three, CDRs from a light chain variable domain, or a VH or VL sequence, or an scFv from the gemtuzumab-ozagomycin scFv sequence (formerly sold under the name mylotarg), e.g., Bross et al. , Clin Cancer Res 7(6):1490-1496 (2001) (gemtuzumab-ozagomycin, hP67.6). In one embodiment, the antigen-binding domain for CD33 is an antigen-binding fragment from, or derived from (e.g., containing an antigen-binding domain containing one or more, e.g., one, two, or three CDRs from a heavy chain variable domain and/or one or more , for example, one, two or three CDRs from a light chain variable domain, or a VH or VL sequence, or scFv) of an scFv sequence having GenBank Accession No. AM402974.1 (see Wang et al., Mol. Ther., vol. 23:1, pp. 184-191 (2015, document incorporated by reference). In one embodiment, the antigen-binding domain for CD33 is an antigen-binding fragment, e.g., CDR regions, of an antibody described in, e.g., Caron et al., Cancer Res 52(24):6761-6767 (1992) (lintuzumab, HuM195), Lapusan et al., Invest New Drugs 30(3):1121-1131 (2012) (AVE9633), Aigner et al., Leukemia 27(5):1107-1115 (2013) (AMG330, CD33 BiTE), Dutour et al. , Adv hematol 2012:683065 (2012) and Pizzitola et al., Leukemia doi:10,1038/Lue.2014,62 (2014). In embodiments, the antigen binding domain is, or is derived from, a murine binding domain for human CD33. In embodiments, the antigen binding domain is a humanized antibody or antibody fragment, such as an scFv domain. In one embodiment, the antigen binding domain is a human antibody, or antibody fragment, that binds to human CD33. In embodiments, the antigen binding domain is an scFv domain that contains a light chain variable region (VL) and a heavy chain variable region (VH). VL and VH may be linked by a linker as described herein, eg, containing the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 30), and may be in any orientation, eg, VL-linker-VH or VH-linker-VL.

In one aspect, the antigen-binding domain of a CAR binds to CLL-1, eg, human CLL-1. Any known CLL-1 binding domain can be used in the invention. In one embodiment, the antigen-binding domain for CLL-1 is an antigen-binding fragment, such as the CDR or VH and VL regions of an antibody, antigen-binding fragment, or CAR, as described in, for example, PCT Publication WO2016/014535 or US Patent Publication 2016-0051651-A1 , the entire contents of which are incorporated herein by reference. In one embodiment, the antigen binding domain for CLL-1 is an antigen binding fragment, eg, CDR regions, of an antibody available from R&D, ebiosciences, Abcam, eg, PE-CLL1-hu cat#353604 (BioLegend); and PE-CLL1 (CLEC12A) with catalog # 562566 (BD). In embodiments, the antigen binding domain is, or is derived from, a murine binding domain for human CLL-1. In embodiments, the antigen binding domain is a humanized antibody or antibody fragment, such as an scFv domain. In one embodiment, the antigen binding domain is a human antibody, or antibody fragment, that binds to human CLL-1. In embodiments, the antigen binding domain is an scFv domain that contains a light chain variable region (VL) and a heavy chain variable region (VH). VL and VH may be linked by a linker as described herein, eg, containing the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 30), and may be in any orientation, eg, VL-linker-VH or VH-linker-VL.

In some embodiments, the CAR antigen-binding domain is targeted to a B-cell antigen. In one embodiment, the B cell antigen is an antigen that is preferentially or specifically expressed on the surface of a B cell. The antigen can be expressed on the surface of any of the following types of B cells: B cell progenitors (eg, pre-B cells or pro-B cells), early pro-B cells, late pro-B cells, large pre- B cells, small pre-B cells, immature B cells, e.g. "naive" B cells, mature B cells, plasma B cells, plasmablasts, memory B cells, B-1 cells, B-2 cells, marginal zone B cells, follicular B cells, germinal center B cells, or regulatory B cells (B _reg ).

The present invention relates to CARs that can be targeted to the following B cell antigens: CD19; CD123; CD22; CD30; CD171; CS-1; C-type lectin-like molecule 1, CD33; epidermal growth factor variant III receptor (EGFRvIII); ganglioside G2 (GD2); ganglioside GD3; a member of the TNF receptor family, B cell maturation antigen (BCMA); Tn antigen ((Tn Ag) or (GalNAcα-Ser/Thr)); prostate specific membrane antigen (PSMA); receptor tyrosine kinase-like orphan receptor 1 (ROR1); Fms-like tyrosine kinase 3 (FLT3); tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; carcinoembryonic antigen (CEA); epithelial cell adhesion molecule (EPCAM); B7H3 (CD276); KIT (CD117); the alpha-2 subunit of the interleukin-13 receptor; mesothelin; interleukin-11 receptor alpha subunit (IL-11Ra); prostatic stem cell antigen (PSCA); serine protease 21; vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; platelet growth factor receptor beta (PDGFR-beta); stage-specific embryonic antigen-4 (SSEA-4); CD20; folate receptor alpha; receptor tyrosine-specific protein kinase ERBB2 (Her2/neu); mucin 1 associated with the cell surface (MUC1); epidermal growth factor receptor (EGFR); neuronal adhesion molecule (NCAM); prostasis; prostatic acid phosphatase (PAP); mutant elongation factor 2 (ELF2M); ephrin B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAIX); proteasome subunit (prosoma, macropain), type beta, 9 (LMP2); glycoprotein 100 (gp100); an oncogenic fusion protein comprising a rearrangement initiation site (BCR) localization region and Abelson murine leukemia viral oncogene homologue 1 (Abl) (bcr-abl); tyrosinase; ephrin A2 receptor (EphA2); fucosyl GM1; a sialyl-Lewis adhesion molecule (sLe); ganglioside GM3; transglutaminase 5 (TGS5); high molecular weight melanoma-associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); folate receptor beta; tumor endothelial marker 1 (TEM1/CD248); antigen related to tumor endothelial marker 7 (TEM7R); claudin-6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein-coupled class C receptors, group 5, member D (GPRC5D); X chromosome open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); polysialic acid; placenta-specific protein 1 (PLAC1); the hexasaccharide portion of glycoceramide globoH (GloboH); breast differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); hepatitis A virus cell receptor 1 (HAVCR1); adrenoreceptor beta-3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); complex of lymphocytic antigen 6, locus K9 (LY6K); olfactory receptor 51E2 (OR51E2); protein TCR-gamma with an alternative reading frame (TARP); Wilms tumor protein (WT1); testicular cancer antigen 1 (NY-ESO-1); testicular cancer antigen 2 (LAGE-1a); melanoma-associated antigen 1 (MAGE-A1); translocation variant 6 of the ETS gene located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); family X antigens, representative 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); testicular melanoma antigen 1 (MAD-CT-1); testicular melanoma antigen 2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; protein; survivin; telomerase; prostate carcinoma tumor antigen 1, melanoma antigen 1 recognized by T-cells; a protein mutant of the rat sarcoma virus (Ras); human telomerase reverse transcriptase (hTERT); breakpoints at translocation in case of sarcoma; inhibitor of apoptosis from melanoma cells (ML-IAP); ERG (transmembrane serine protease 2 (TMPRSS2) and ETS fusion gene); N-acetylglucosamine transferase V (NA17); paired box protein Pax-3 (PAX3); androgen receptor; cyclin B1; a neuroblastoma-derived homologue of the avian myelocytomatosis virus (MYCN) v-myc oncogene; a member of the C family of Ras homologues (RhoC); tyrosinase-related protein 2 (TRP-2); cytochrome P450 1B1 (CYP1B1); CCCTC-binding factor-like protein (zinc finger protein), T cell-recognized squamous cell carcinoma antigen 3 (SART3); paired box protein Pax-5 (PAX5); proacrosin-binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); anchor protein 4 A-kinase (AKAP-4); breakpoint 2 in X in synovial sarcoma (SSX2); receptor for advanced glycosylation end products (RAGE-1); renal ubiquitous protein 1 (RU1); renal ubiquitous protein 2 (RU2); legumain; human papillomavirus E6 protein (HPV E6); human papillomavirus E7 protein (HPV E7); intestinal carboxylesterase; mutant heat shock protein 70-2 (mut hsp70-2); CD79a; CD79b; CD72; leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Fc fragment of the IgA receptor (FCAR or CD89); leukocyte immunoglobulin-like receptors, subfamily A, representative 2 (LILRA2); a family of proteins similar to the CD300 molecule, representative f (CD300LF); a family of 12 C-type domain lectins, representative A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); protein 2, similar to the EGF-like domain-containing mucin-like hormone receptor (EMR2); lymphocytic antigen 75 (LY75); glypican-3 (GPC3); Fc receptor-like protein 5 (FCRL5); immunoglobulin lambda chain-like polypeptide 1 (IGLL1); a member of the TNF receptor family; Fms-like tyrosine kinase 3 (FL T3); CD10, CD19, CD20, CD21, CD22, CD23, CD24, CD25, CD37, CD38, CD53, CD72, CD73, CD74, CD75, CD77, CD79a, CD79b, CD80, CD81, CD82, CD83, CD84, CD85, ROR1, BCMA, CD86, and CD179b. Other B cell antigens that may be targeted by the CARs described herein include: CD1a, CD1b, CD1c, CD1d, CD2, CD5, CD6, CD9, CD11a, CD11b, CD11c, CD17, CD18, CD26, CD27, CD29, CD30, CD31, CD32a, CD32b, CD35, CD38, CD39, CD40, CD44, CD45, CD45RA, CD45RB, CD45RC, CD45RO, CD46, CD47, CD48, CD49b, CD49c, CD49d, CD50, CD52, CD54, CD55, CD58 CD60a , CD126, CD130, CD132, CD137, CD138, CD139, CD147, CD148, CD150, CD152, CD162, CD164, CD166, CD167a, CD170, CD175, CD175s, CD180, CD184, CD185, CD192, CD196, CD197, CD20 0, CD205 , CD210a, CDw210b, CD212, CD213a1, CD213a2, CD215, CD217, CD218a, CD218b, CD220, CD221, CD224, CD225, CD226, CD227, CD229, CD230, CD232, CD252, CD253, CD257, CD258, CD 261, CD262, CD263 , CD264, CD267, CD268, CD269, CD270, CD272, CD274, CD275, CD277, CD279, CD283, CD289, CD290, CD295, CD298, CD300a, CD300c, CD305, CD306, CD307a, CD307b, CD307c, CD307d , CD307e, CD314 .

In another embodiment, the antigen targeted by the CAR is selected from CD19, BCMA, CD20, CD22, FcRn5, FcRn2, CS-1, and CD138. In one embodiment, the antigen targeted by CAR is CD19. In one embodiment, the antigen targeted by CAR is CD20. In one embodiment, the antigen targeted by CAR is CD22. In one embodiment, the antigen targeted by the CAR is BCMA. In one embodiment, the antigen targeted by the CAR is FcRn5. In one embodiment, the antigen targeted by the CAR is FcRn2. In one embodiment, the antigen targeted by the CAR is CS-1. In one embodiment, the antigen targeted by CAR is CD138.

In one embodiment, the antigen binding domain of a CAR, eg, a CAR expressed by a cell of the invention (eg, a cell that also expresses CAR), can be selected to target a preferred population of B cells. For example, in one embodiment in which targeting of regulatory B cells is desired, an antigen-binding domain is selected that targets a B cell antigen expressed on regulatory B cells but not B cells from other populations, such as plasma B cells. memory cells and B cells. Cell surface markers expressed on regulatory B cells include: CD19, CD24, CD25, CD38, or CD86, or those described in He et al., 2014, J Immunology Research, article ID 215471. If targeting B- cells of more than one species, an antigen-binding domain can be selected that targets a B-cell antigen that is expressed by all of the desired target B-cells.

In one embodiment, the antigen-binding domain of a CAR, such as the CAR expressed by the cell of the invention, binds to CD19. CD19 is present on B cells throughout cell differentiation of a given lineage from the pro/pre-B cell stage to the terminally differentiated plasma cell stage. In one embodiment, the antigen binding domain is a murine scFv domain that binds to human CD19, eg CTL019 (eg, SEQ ID NO: 356). In one embodiment, the antigen binding domain is a humanized antibody or antibody fragment, such as an scFv domain derived from a mouse CTL019 scFv. In one embodiment, the antigen binding domain is a human antibody, or antibody fragment, that binds to human CD19. Exemplary scFv domains (and sequences thereof, eg, CDR, VL and VH region sequences) that bind to CD19 are shown in Table 7 and Table 15A. The scFv domain sequences shown in Table 7 include the light chain variable region (VL) and the heavy chain variable region (VH). VL and VH are linked by a linker containing the sequence GGGGSGGGGSGGGGS (SEQ ID NO: 30), for example in the following orientation: VL-linker-VH.

Table 7. Antigen-binding domains that bind CD19

Antigen Name Amino acid sequence SEQID NO: CD19 muCTL019 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRL TIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS 356 CD19 huscFv1 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSS 357 CD19 huscFv2 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQSSLKSRVTI SKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSS 358 CD19 huscFv3 QVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRL HSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIK 359 CD19 huscFv4 QVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTS RLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIK 360 CD19 huscFv5 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSL KSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSS 361 CD19 huscFv6 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQS SLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSS 362 CD19 huscFv7 QVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLI YHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIK 363 CD19 huscFv8 QVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYQSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRL LIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIK 364 CD19 huscFv9 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYNSSL KSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSS 365 CD19 HuscFv10 QVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYNSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLI YHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIK 366 CD19 HuscFv11 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYNSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSS 367 CD19 HuscFv12 QVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYNSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRL HSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIK 368

The sequences of the CDR domains of the scFv antigen binding domains for CD19 shown in Table 7 are shown in Tables 8 and 15B for the heavy chain variable domains and in Tables 9 and 15C for the light chain variable domains. "ID" means the corresponding SEQ ID NO for each CDR.

Table 8 CDR regions of heavy chain variable domains

Description FW HCDR1 SEQID NO HCDR2 SEQID NO HDDR3 SEQID NO mouse_CART19 GVSLPDYGVS 369 VIWGSETTYYNSALKS 370 HYYYGGSYAMDY 371 humanized_CART19 a VH4 GVSLPDYGVS 369 VIWGSETTYY S S S LKS 372 HYYYGGSYAMDY 371 humanized_CART19 b VH4 GVSLPDYGVS 369 VIWGSETTYY Q S S LKS 373 HYYYGGSYAMDY 371 humanized_CART19 c VH4 GVSLPDYGVS 369 VIWGSETTYYNS S LKS 374 HYYYGGSYAMDY 371

Table 9 Light chain variable CDR regions

Description FW LCDR1 SEQID NO LCDR2 SEQID NO LCDR3 SEQID NO mouse_CART19 RASQDISKYLN 375 HTSRLHS 376 QQGNTLPYT 377 humanized_CART19 a VK3 RASQDISKYLN 375 HTSRLHS 376 QQGNTLPYT 377 humanized_CART19 b VK3 RASQDISKYLN 375 HTSRLHS 376 QQGNTLPYT 377 humanized_CART19 c VK3 RASQDISKYLN 375 HTSRLHS 376 QQGNTLPYT 377

In one embodiment, the antigen binding domain comprises an anti-CD19 antibody or fragment thereof, eg scFv. For example, an antigen binding domain comprises a heavy chain variable domain and a light chain variable domain as shown in Table 10. The linker sequence connecting the heavy chain variable domain and the light chain variable domain can be any of the linker sequences described herein, or alternatively, may be GSTSGSGKPGSGEGSTKG (SEQ ID NO: 378). The light chain variable region and the heavy chain variable region in the scFv can be, for example, in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region.

Table 10 Additional binding domains of the anti-CD19 antibody

Name At VH sequence Sequence VL SJ25-C1 QVQLLESGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYSCARKTISSVVDFYFDYWGQGTTVT (SEQ ID NO: 379) ELVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFYFCQYNRYPYTSGGGTKLEIKRRS (SEQ ID NO: 380) scFv sequence SJ25-C1
scFv QVQLLESGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYSCARKTISSVVDFYFDYWGQGTTVTGSTSGSGKPGSGEGSTKGELVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKPLI YSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFYFCQYNRYPYTSGGGTKLEIKRRS (SEQ ID NO: 381)

In one embodiment, the CD19 binding domain comprises one or more (e.g., all three) of light chain complementarity determining region 1 (LC CDR1), light chain complementarity determining region 2 (LC CDR2), and light chain complementarity determining region 3 (LC CDR3). ) a CD19 binding domain as described herein, such as those listed in Table 7 or 9, and/or one or more (e.g., all three) of the Heavy Chain Complementarity Determining Region 1 (HC CDR1), Heavy Chain Complementarity Determining Region 2 (HC CDR2) and complementarity determining region 3 of the heavy chain (HC CDR3) of the CD19 binding domain described herein, for example, those shown in Table 7 or 8. In one embodiment, the CD19 binding domain contains one, two, or all of the LC CDR1, LC CDR2 and LC CDR3 with any of the amino acid sequences shown in Table 9, the contents of which are incorporated herein by reference; and one, two or all of HC CDR1, HC CDR2 and HC CDR3 with any of the amino acid sequences shown in Table 8.

In one embodiment, the CD19 binding domain comprises a light chain variable region as described herein (eg, in Table 7 or 10) and/or a heavy chain variable region as described herein (eg, in Table 7 or 10). In one embodiment, the CD19 binding domain is an scFv containing a light chain and a heavy chain with the amino acid sequences shown in Table 7 or 10. In one embodiment, the CD19 binding domain (e.g., scFv) contains: a light chain variable region containing an amino acid sequence having at least one, two or three modifications (e.g. substitutions, e.g. conservative substitutions), but not more than 30, 20 or 10 modifications (e.g. substitutions, e.g. conservative substitutions) of the light chain variable region amino acid sequence, shown in Table 7 or 10, or a sequence having 95-99% identity with the amino acid sequence shown in Table 7 or 10; and/or a heavy chain variable region containing an amino acid sequence having at least one, two, or three modifications (e.g., substitutions, e.g., conservative substitutions), but no more than 30, 20, or 10 modifications (e.g., substitutions, substitutions) the amino acid sequence of the heavy chain variable region shown in Table 7 or 10, or a sequence having 95-99% identity with the amino acid sequence shown in Table 7 or 10.

In one embodiment, the CD19 binding domain contains an amino acid sequence selected from any of SEQ ID NOs: 356-368 and 381; or an amino acid sequence having at least one, two, or three modifications (eg, substitutions, eg, conservative substitutions), but not more than 30, 20, or 10 modifications (eg, substitutions, eg, conservative substitutions) in any of the above sequences; or a sequence having 95-99% identity with any of the above sequences. In one embodiment, the CD19 binding domain is scFv and a light chain variable region containing the amino acid sequence described herein, such as in Table 7 or 10, is linked to a heavy chain variable region containing the amino acid sequence described herein. , for example, in Table 7 or 10, through a linker, for example, the linker described in this document. In one embodiment, the CD19 binding domain includes a (Gly4-Ser)n linker, where n is 1, 2, 3, 4, 5, or 6, preferably 4 (SEQ ID NO: 967). The light chain variable region and the heavy chain variable region in the scFv can be, for example, in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region.

Any known CAR, for example, the antigen binding domain for CD19 of any CD19 CAR known in the art, can be used in the present invention to construct a CAR. For example, LG-740; CAR, described in US patent No. 8399645; US patent No. 7446190; Xu et al., Leuk Lymphoma. 2013 54(2):255-260(2012); Cruz et al., Blood 122(17):2965-2973 (2013); Brentjens et al., Blood, 118(18):4817-4828 (2011); Kochenderfer et al., Blood 116(20):4099-102 (2010); Kochenderfer et al., Blood 122(25):4129-39(2013); and 16th Annu Meet Am Soc Gen Cell Ther (ASGCT) (May 15-18, Salt Lake City) 2013, Abst 10. In one embodiment, the antigen binding domain for CD19 is an antigen binding fragment, e.g. an antigen-binding fragment as described, for example, in PCT publication WO2012/079000; PCT publications WO2014/153270; Kochenderfer, JN et al., J. Immunother. 32 (7), 689-702 (2009); Kochenderfer, JN, et al., Blood, 116 (20), 4099-4102 (2010); PCT Publication WO2014/031687; Bejcek, Cancer Research, 55, 2346-2351, 1995; or U.S. Patent No. 7,446,190.

In one embodiment, the antigen-binding domain of a CAR, such as the CAR expressed by the cell of the invention, binds to BCMA. BCMA is predominantly expressed on mature B-lymphocytes. In one embodiment, the antigen binding domain is a murine scFv domain that binds to human BCMA. In one embodiment, the antigen binding domain is a humanized antibody, or antibody fragment, such as an scFv domain, that binds to human BCMA. In one embodiment, the antigen binding domain is a human antibody, or antibody fragment, that binds to human BCMA. Exemplary scFv domains (and sequences thereof, e.g., CDR, VL, and VH region sequences) that bind to BCMA are shown in Table 11, Table 12, Table 13, and Table 14. The scFv domain sequences shown in Table 11 and Table 12 are include a light chain variable region (VL) and a heavy chain variable region (VH). VL and VH are connected by a linker, for example in the following orientation: VH-linker-VL.

Table 11. Antigen-binding domains that bind BCMA

Also shown are the amino acid sequences of the heavy chain variable domain and the light chain variable domain for each scFv.

Name/Description SEQID NO: Subsequence 139109 139109 - ak
scFv domain 382 EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIK 139109 - nk
scFv domain 383 GAAGTGCAATTGGTGGAATCAGGGGGAGACTTGTGCAGCCTGGAGGATCGCTGAGACTGTCATGTGCCGTGTCCGGCTTTGCCCTGTCCAACCACGGGATGTCCTGGGTCCGCCGCGCGCCTGGAAAGGGCCTCGAATGGGTGTCGGGTATTGTGTACAGCGGTAGCACCTACTATGCCGCATCCGTGAAGGGGAGATTCACCCATCAGCCGG GACAACTCCAGGAACACTCTGTACCTCCAAATGAATTCGCTGAGGCCAGAGGACACTGCCATCTACTACTGCTCCGCGCATGGCGGAGAGTCCGACGTCTGGGGACAGGGGACCACCGTGACCGTGTCTAGCGCGTCCGGCGGAGGCGGCAGCGGGGGTCGGGCATCAGGGGGCGGCGGATCGGACATCCAGCTACCCAGTCCCCGAGCTCGCTGTCCGCC TCCGTGGGAGATCGGGTCACCATCACGTGCCGCCCAGCCAGTCGATTCCTCCTACCTGAACTGGTACCAACAGAAGCCCGGAAAAGCCCCGAAGCTTCTCATCTACGCCGCCTCGAGCCTGCAGTCAGGAGTGCCCTCACGGTTTCCCGGCTCCGGTTCCGGTACTGATTTCACCCTGACCATTTCCTCCCTGCAACCGGAGGACTTCGCTACTTACTACTGCCAGCAGTCG TACTCCACCCCTACACTTTCGGACAAGGCACCAAGGTCGAAATCAAG 139109 - ak
vh 384 EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSS 139109 - ak
VL 385 DIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIK 139103 139103 - ak
scFv domain 386 QVQLVESGGGLVQPGRSLRLSCAASGFTFSNYAMSWVRQAPGKGLGWVSGISRSGENTYYADSVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARSPAHYYGGMDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIVLTQSPGTLSLSPGERATLSCRASQSISSSFLAWYQQKPGQAPRLLIYGASRRATGIPDR FSGSGSGTDFTLTISRLEPEDSAVYYCQQYHSSPSWTFGQGTKLEIK 139103 - nk
scFv domain 387 CAAGTGCAACTCGTGGAATCTGGTGGAGACTCGTGCAACCCGGAAGATCGCTTAGACTGTCGTGTGCCGCCAGCGGGTTCACTTTTCTCGAACTACGCGATGTCCTGGGTCCGCCAGGCACCCGGAAAGGACTCGGTTGGGTGTCCGGCATTTCCCGGTCCGGCGAAAATACCTACTACGCCGACTCCGTGAAGGGCCGCTTCACCATCTCAAGGGACAAC AGCAAAAAACACCCTGTACTTGCAAATGAACTCCCTGCGGGATGAAGATACAGCCGTGTACTATTGCGCCCGGTCGCCTGCCCATTACTACGGCGGAATGGACGTCTGGGGACAGGGAACCACTGTGACTGTCAGCAGCGCGTCGGGTGGCGGCGGCTCAGGGGGTCGGGCCTCCGGGGGGGGAGGTCCGACATCGTGCTGACCCAGTCCC CGGGAACCCTGAGCCTGAGCCCGGGAGAGCGCGCGACCCTGTCATGCCGGGCATCCCAAGAGCATTAGCTCCTCCTTTCTCGCCTGGTATCAGCAGAAGCCCGGACAGGCCCCGAGGCTGCTGATCTACGGCGCTAGCAGAAGGGCTACCGGAATCCCAGACCGGTTTCCCGGCTCCGGTTCCGGGACCGATTTCACCCTTACTATCTCGCGCCTGGAACCTGAGGACTCC GCCGTCTACTACTGCCAGCAGTACCACTCATCCCCGTCGTGGACGTTCGGACAGGGCACCAAGCTGGAGATTAAG 139103 - ak
vh 388 QVQLVESGGGLVQPGRSLRLSCAASGFTFSNYAMSWVRQAPGKGLGWVSGISRSGENTYYADSVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARSPAHYYGGMDVWGQGTTVTVSS 139103 - ak
VL 389 DIVLTQSPGTLSLSPGERATLSCRASQSISSSFLAWYQQKPGQAPRLLIYGASRRATGIPDRFSGSGSGTDFTLTISRLEPEDSAVYCQQYHSSPSWTFGQGTKLEIK 139105 139105 - ak
scFv domain 390 QVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCSVHSFLAYWGQGTLVTVSSASGGGGSGGRASGGGGSDIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVP DRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKVEIK 139105 - nk
scFv domain 391 CAAGTGCAACTCGTCGAATCCGGTGGAGTCTGGTCCAACCTGGTAGAAGCCTGAGACTGTCGTGTGCGGCCAGCGGATTACCTTTGATGACTATGCTATGCACTGGGTGCGGCAGGCCCCAGGAAAGGGCCTGGAATGGGTCTGGGGAATTAGCTGGAACTCCGGTCCATTGGCTACGCCGACTCCGTGAAGGGCCGCTTCACCATCTCCCGCGAC AACGCAAAGAACTCCCTGTACTTGCAAATGAACTCGCTCAGGGCTGAGGATACCGCGCTGTACTACTGCTCCGTGCATTCCTTCCTGGCCTACTGGGGACAGGGAACTCTGGTCACCGTGTCGAGCCGCCTCCGGCGGCGGGGGCTCGGGTGGACGGGCCTCGGGCGGAGGGGGTCCGACATCGTGATGACCCAGACCCCGCTGAGCTTGCCCGTGACTCCCG GAGAGCCTGCATCCATCTCCTGCCGGTCATCCAGTCCCTTCTCCACTCCAACGGATACAACTACCTCGACTGGTACCTCCAGAAGCCGGGACAGAGCCCTCAGCTTCTGATCTACCTGGGTCAAATAGAGCCTCAGGAGTGCCGGATCGGTTCAGCGGATCTGGTTCGGGAACTGATTTCACTCTGAAGATTTCCCGCGTGTGGAAGCCGAGGACGTGGGCGTCTACTACT GTATGCAGGCGCTGCAGACCCCCTATACCTTCGGCCAAGGGACGAAAGTGGAGATCAAG 139105 - ak
vh 392 QVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCSVHSFLAYWGQGTLVTVSS 139105 - ak
VL 393 DIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKVEIK 139111 139111 - ak
scFv domain 394 EVQLLESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIVMTQTPLSLSVTPGQPASISCKSSQSLLRNDGKTPLYWYLQKAGQPPQLLIYEVSNRFSG VPDRFSGSGSGTDFTLKISRVEAEDVGAYYCMQNIQFPSFGGGTKLEIK 139111 - nk
scFv domain 395 GAAGTGCAATTGTTGGAATCTGGAGGAGACTTGTGTCAGCCTGGAGGATCACTGAGACTTTCGTGTGCGGTGTCAGGCTTCGCCCTGAGCAACCACGGCATGAGCTGGGTGCGGAGAGCCCCGGGGAAGGGTCTGGAATGGGTGTCCGGGATCGTCTACTCCGGTTCAACTTACTACGCCGCAAGCGTGAAGGTCGCTTCACCATTTCCCGCGATAACTCC CGGAACACCCTGTACCTCCAAATGAACTCCCTGCGGCCCGAGGACACCGCCATCTACTACTGTTCCGCGCATGGAGGAGAGTCCGATGTCTGGGGACAGGGCACTACCGTGACCGTGTCGAGCGCCTCGGGGGAGGAGGCTCCGGCGTCGCCGCCTCCGGGGGGGTGGCAGCGACATTGTGATGACGCAGACTCCACTCTCGCTGTCCGTGACCCCGGGA CAGCCCGCGTCCATCTCGTGCAAGAGCTCCCAGAGCCTGCTGAGGAACGACGGAAAGACTCCTCTGTATTGGTACCTCCAGAAGGCTGGACAGCCCCCGCAACTGCTCATCTACGAAGTGTCAAATCGCTTCTCCGGGGTGCCGGATCGGTTTTCCGGCTCGGGATCGGGCACCGACTTCACCCTGAAAATCTCCAGGGTCGAGGCCGAGGACGTGGGAGCCTACTACTG CATGCAAAACATCCAGTTCCCTTCCTTCGGCGGCGGCACAAAGCTGGAGATTAAG 139111 - ak
vh 396 EVQLLESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSS 139111 - ak
VL 397 DIVMTQTPLSLSVTPGQPASISCKSSQSLLRNDGKTPLYWYLQKAGQPPQLLIYEVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGAYYCMQNIQFPSFGGGTKLEIK 139100 139100 - ak
scFv domain 398 QVQLVQSGAEVRKTGASVKVSCKASGYIFDNFGINWVRQAPGQGLEWMGWINPKNNNTNYAQKFQGRVTITADESTNTAYMEVSSLRSEDTAVYYCARGPYYYQSYMDVWGQGTMVTVSSASGGGGSGGRASGGGGSDIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLNWYLQKPGQSPQLLIYL GSKRASGVPDRFSGSGSGTDFTLHITRVGAEDVGVYYCMQALQTPYTFGQGTKLEIK 139100 - nk
scFv domain 399 CAAGTCCAACTCGTCCAGTCCGGCCGCAGAAGTCAGAAAAACCGGTGCTAGCGTGAAAGTGTCCTGCAAGGCCTCCGGCTACATTTTCGATAACTTCGGAATCAACTGGGTCAGACAGGCCCCGGGCCAGGGGCTGGAATGGATGGGATGGATCAACCCCAAGAACAACAACACCAACTACGCACAGAAGTTCCAGGGCCGCGTGACTATCACCGCCGATGAATCGACCAATA CCGCCTACATGGAGGTGTCCTCCCTGCGTCGGAGGACACTGCCGTGTATTACTGCGCGAGGGGCCCATACTACCAAAGCTACATGGACGTCTGGGGACAGGGAACCATGGTGACCGTGTCATCCGCCTCCGGTGGTGGAGGCTCCGGGGGGCGGGCTTCAGGAGGCGGAGGAAGCGATATTGATGACCCAGACTCCGCTTAGCCTGCCCGTGACT CCTGGAGAACCGGCCTCCATTTCCTGCCGGTCCTCGCAATCACTCCTGCATTCCAACGGTTACAACTACCTGAATTGGTACCTCCAGAAGCCTGGCCAGTCGCCCCAGTTGCTGATCTATCTGGGCTCGAAGCGCGCCTCCGGGGTGCCTGACCGGTTTAGCGGATCTGGGAGCGGCACGGACTTCACTCTTCCACATCACCCGCGTGGGAGCGGAGGACGTGGGAG TGTACTACTGTATGCAGGCGCTGCAGACTCCGTACACATTCGGACAGGGCACCAAGCTGGAGATCAAG 139100 - ak
vh 400 QVQLVQSGAEVRKTGASVKVSCKASGYIFDNFGINWVRQAPGQGLEWMGWINPKNNNTNYAQKFQGRVTITADESTNTAYMEVSSLRSEDTAVYYCARGPYYYQSYMDVWGQGTMVTVSS 139100 - ak
VL 401 DIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLNWYLQKPGQSPQLLIYLGSKRASGVPDRFSGSGSGTDFTLHITRVGAEDVGVYYCMQALQTPYTFGQGTKLEIK 139101 139101 - ak
scFv domain 402 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSDAMTWVRQAPGKGLEWVSVISGSGGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLDSSGYYYARGPRYWGQGTLVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY GASTLASGVPARFSGSGSGTHFTLTINSLQSEDSATYYCQQSYKRASFGQGTKVEIK 139101 - nk
scFv domain 403 CAAGTGCAACTTCAAGAATCAGGCGGAGACTCGTGCAGCCCGGAGGATCATTGCGGCTCTCGTGCGCCGCCTCGGGCTTCACCTTCTCGAGCGACGCCATGACCTGGGTCCGCCAGGCCCCGGGGAAGGGGCTGGAATGGGTGTCTGTGATTTCCGGCTCCGGGGGAACTACGTACTACGCCGATTCCGTGAAAGGTCGCTTCACTATCTCCCGGGACAAC AGCAAGAACACCCTTTATCTGCAAATGAATTCCCTCCGCGCCGAGGACACCGCCGTGTACTACTGCGCCAAGCTGGACTCCTCGGGCTACTATGCCCGGGGTCCGAGATACTGGGGACAGGGAACCCTCGTGACCGTGTCCTCCGCGTCCGGCGGAGGAGGGTCGGGAGGGCGGCCTCCGGCGGCGGCGGTTCGGACATCCAGCTGACCCAGTC CCCATCCTCACTGAGCGCCAAGCGTGGGCGACAGAGTCACCATTACATGCAGGGCGTCCCAGAGCATCAGCTCCTACCTGAACTGGTACCAACAGAAGCCTGGAAAGGCTCCTAAGCTGTTGATCTACGGGGCTTCGACCCTGGCATCCGGGGTGCCCGCGAGGTTTAGCGGAAGCGGTAGCGGCACTCACTTCACTCTGACCATTAACAGCCTCCAGTCCGAGGATTCAGCCACT TACTACTGTCAGCAGTCCTACAAGCGGGCCAGCTTCGGACAGGGCACTAAGGTCGAGATCAAG 139101 - ak
vh 404 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSDAMTWVRQAPGKGLEWVSVISGSGGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLDSSGYYYARGPRYWGQGTLVTVSS 139101 - ak
VL 405 DIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASTLASGVPARFSGSGSGTHFTLTINSLQSEDSATYYCQQSYKRASFGQGTKVEIK 139102 139102 - ak
scFv domain 406 QVQLVQSGAEVKKPGASVKVSCKASGYTFSNYGITWVRQAPGQGLEWMGWISAYNGNTNYAQKFQGRVTMTRNTSISTAYMELSSLRSEDTAVYYCARGPYYYYMDVWGKGTMVTVSSASGGGGSGGRASGGGGSEIVMTQSPLSLPVTPGEPASISCRSSQSLLYSNGYNYVDWYLQKPGQSPQLLIYL GSNRAGVPDRFSGSGSGTDFKLQISRVEAEDVGIYYCMQGRQFPYSFGQGTKVEIK 139102 - nk
scFv domain 407 CAAGTCCAACTGGTCCAGAGCGGTGCAGAAGTGAAGAAGCCCGGAGCGAGCGTGAAAGTGTCCTGCAAGGCTTCCGGGTACACCCTTCTCCAACTACGGCATCACTTGGGTGCGCCAGGCCCCGGGACAGGGCCTGGAATGGATGGGGTGGATTTCCGCGTACAACGGCAATACGAACTACGCTCAGAAGTTCCAGGGTAGAGTGACCATGACTAGGAAC ACCTCCATTTCCACCGCCTACATGGAACTGTCCTCCCTGCGGAGCGAGGACACCGCCGTGTGTACTATTGCGCCCGGGGACCATACTACTACTACTACATGGATGTCTGGGGGAAGGGGACTATGTCACCGTGTCATCCGCCTCGGGAGGCGGCGGATCAGGAGGACGCGCCTCTGGTGGTGGAGGATCGGAGATCGTGATGACCCAGAGCCCTCTCCTTGCCCGTGACT CCTGGGGAGCCCGCATCCATTTCATGCCGGAGCTCCCAGTCACTTCTCTACTCCAACGGCTATAACTACGTGGATTGGTACCTCCAAAAGCCGGGCCAGAGCCCGCAGCTGCTGATCTACCTGGGCTCGAACAGGGCAGCGGAGTGCCTGACCGGTTCTCCGGGTCGGGAAGCGGGACCGACTTCAAGCTGCAAATCTCGAGAGTGGAGGCCGAGGACGTGGGAAT CTACTACTGTATGCAGGGCCGCCAGTTTCCGTACTCGTTCGGACAGGGCACCAAAGTGGAAATCAAG 139102 - ak
vh 408 QVQLVQSGAEVKKPGASVKVSCKASGYTFSNYGITWVRQAPGQGLEWMGWISAYNGNTNYAQKFQGRVTMTRNTSISTAYMELSSLRSEDTAVYYCARGPYYYYMDVWGKGTMVTVSS 139102 - ak
VL 409 EIVMTQSPLSLPVTPGEPASISCRSSQSLLYSNGYNYVDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFKLQISRVEAEDVGIYYCMQGRQFPYSFGQGTKVEIK 139104 139104 - ak
scFv domain 410 EVQLLETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVLTQSPATLSVSPGESATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRASGIPDRFSGSGSG TDFTLTISSLQAEDVAVYYCQQYGSSLTFGGGTKVEIK 139104 - nk
scFv domain 411 GAAGTGCAATTGCTCGAAACTGGAGGAGTCTGGTGCAACCTGGAGGATCACTTCGCCTGTCCTGCGCCGTGTCGGGCTTTGCCCTGTCCAACCATGGAATGAGCTGGGTCCGCCGCGCGCCGGGGAAGGGCCTCGAATGGGTGTCCGGCATCGTCTACTCCGGCTCCACCTACTACGCCGCGTCCGTGAAGGGCCGGTTCACGATTTCACGGGACAACTCG CGGAACACCCTGTACCTCCAAATGAATTCCCTTCGGCCGGAGGATACTGCCATCTACTACTGCTCCGCCCACGGTGGCGAATCCGACGTCTGGGGCCAGGGAACCACCGTGACCGTGTCCAGCGCGTCCGGGGGAGGAGGAAGCGGGGGTAGAGCATCGGGTGGAGGCGGATCAGAGATCGTGCTGACCCAGTCCCCCGCCACCTTGAGCGTGTCACCAGGAGA GTCCGCCACCCTGTCATGCCGCGCCAGCCAGTCCGTGTCCTCCAACCTGGCTTGGTACCAGCAGAAGCCGGGCAGGCCCCTAGACTCCTGATCTATGGGCGTCGACCCGGGCATCTGGAATTCCCGATAGGTTCAGCGGATCGGGCTCGGGCACTGACTTCACTCTGACCATCTCCTCGCTGCAAGCCGAGGACGTGGCTGTGTACTACTGTCAGCAGTACGGAAG CTCCCTGACTTTCGGTGGCGGGACCAAAGTCGAGATTAAG 139104 - ak
vh 412 EVQLLETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSS 139104 - ak
VL 413 EIVLTQSPATLSVSPGESATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASTRASGIPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYGSSLTFGGGTKVEIK 139106 139106 - ak
scFv domain 414 EVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVMTQSPATLSVSPGERATLSCRASQSVSSKLAWYQQKPGQAPRLLFSGASIRATGIPDRGSGSGS GTEFTLTISSLEPEDFAVYYCQQYGSSSWTFGQGTKVEIK 139106 - nk
scFv domain 415 GAAGTGCAATTGGTGGAAACTGGAGGAGACTTGTGCAACCTGGAGGATCATTGAGACTGAGCTGCGCAGTGTCGGGATTCGCCCTGAGCAACCATGGAATGTCCTGGGTCAGAAGGGCCCCTGGAAAAGGCCTCGAATGGGTGTCAGGGATCGTGTACTCCGGTTCCACTTACTACGCCGCCTCCGTGAAGGGCGCTTCACTATCTCACGGGATA ACTCCCGCAATACCCTGTACCTCCAAATGAACAGCCTGCGGCCGGAGGATACCGCCATCTACTACTACTGTTCCGCCCACGGTGGAGAGTCTGACGTCTGGGGCAGGGAACTACCGTGACCGTGTCCTCCGCGTCCGGCGGTGGAGGGAGCGGCGGCCGCGCCAGCGGCGGCGGAGGCTCCGAGATCGTGATGACCCAGAGCCCCGCTACTCTGTCGGTGTCGCCCGGA GAAAGGGCGACCCTGTCCTGCCGGGCGTCGCAGTCCGTGAGCAGCAAGCTGGCTTGGTACCAGCAGAAGCCGGGCCAGGCACCACGCCTGCTTATGTACGGTGCCTCCATTCGGGCCACCGGAATCCCGGACCGGTTCTCGGGGTCGGGGTCCGGTACCGAGTTCACACTGACCATTTCCTCGCTCGAGCCCGAGACTTTGCCGTCTATTACTGCCAGCAG TACGGCCTCCTCCTCATGGACGTTCGGCCAGGGGACCAAGGTCGAAATCAAG 139106 - ak
vh 416 EVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSS 139106 - ak
VL 417 EIVMTQSPATLSVSPGERATLSCRASQSVSSKLAWYQQKPGQAPRLLMYGASIRATGIPDRFSGSGSGTEFTLTISSLEPEDFAVYYCQQYGSSSWTFGQGTKVEIK 139107 139107 - ak
scFv domain 418 EVQLVETGGGVVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSTNLAWYQQKPGQAPRLLIYDASNRATGIPDR FSGGGSGTDFTLTISRLEPEDFAVYYCQQYGSSSPPWTFGQGTKVEIK 139107 - nk
scFv domain 419 GAAGTGCAATTGGTGGAGACTGGAGGAGGAGTGGTGCAACCTGGAGGAAGCCTGAGACTGTCATGCGCGGTGTCGGGCTTTCGCCCTCTCCAACCACGGAATGTCCTGGGTCCGCCGGGCCCCTGGGAAAGGACTTGAATGGGTGTCCGGCATCGTGTACTCGGGTTCCACCTACTACGCGGCCTCAGTGAAGGGCCGGTTTACTATTAGCC GCGACAACTCCAGAAACACACTGTACCTCCAAATGAACTCGCTGCGGCCGGAAGATACCGCTATCTACTACTGCTCCGCCCATGGGGGAGAGTCGGACGTCTGGGGACAGGGCACCACTGTCACTGTGTCCAGCGCCTTCCGGCGGTGGTGGAAGCGGGGGACGGGCCTCAGGAGGCGGTGGCAGCGAGATTGTGCTGACCAGTCCCCCGGGACCCTGAGCCT GTCCCCGGGAGAAAGGGCCACCCTCTCCTGTCGGGCATCCCAGTCCGTGGGGTCTACTAACCTTGCATGGTACCAGCAGAAGCCCGGCCAGGCCCCTCCTGCTGATCTACGACGCGTCCAATAGAGCCACCGGCATCCCGGATCGCTTCAGCGGAGGCGGATCGGGCACCGACTTCACCCTCACCATTTCAAGGCTGGAACCGGAGGACTTCGCCGTGTACTACTGC CAGCAGTATGGTTCGTCCCCACCCTGGACGTTCGGCCAGGGGACTAAGGTCGAGATCAAG 139107 - ak
vh 420 EVQLVETGGGVVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSS 139107 - ak
VL 421 EIVLTQSPGTLSLSPGERATLSCRASQSVGSTNLAWYQQKPGQAPRLLIYDASNRATGIPDRFSGGGSGTDFTLTISRLEPEDFAVYYCQQYGSPPWTFGQGTKVEIK 139108 139108 - ak
scFv domain 422 QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARESGDGMDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQ SGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTLAFGQGTKVDIK 139108 - nk
scFv domain 423 CAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGAAACCTGGAGGATCATTGAGACTGTCATGCGCGGCCTCGGGATTCACGTTCTCCGATTACTACATGAGCTGGATTCGCCAGGCTCCGGGGAAGGGACTGGAATGGGTGTCCTACATTTCCTCATCCGGCTCCACCATCTACTACGCGGACTCCGTGAAGGGGAGATTCACCATTAGCCGCGATAACGCC AAGAACAGCCTGTACCTTTCAGATGAACTCCCTGCGGGCTGAAGATACTGCCGTCTACTACTGCGCAAGGGAGAGCGGAGATGGGATGGACGTCTGGGGACAGGGTACCACTGTGACCGTGTCGTCGGCCTCCGGCGGAGGGGTTCGGGTGGAAGGCCAGCGGCGGCGGAGGCAGCGACATCCAGATGACCCAGTCCCCCTCATCGCTGTCCGCCTC CGTGGGCGACCGCGTCACCATCACATGCCGGGCCTCACAGTCGATCTCCTCCTACCTCAATTGGTATCAGCAGAAGCCCGGAAAGGCCCCTAAGCTTCTGATCTACGCAGCGTCCTCCCTGCAATCCGGGTCCCATCTCGGTTCTCCGGCTCGGGCAGCGGTACCGACTTCACTCTGACCATCTCGAGCCTGCAGCCGGAGACTTCGCCACTTACTACTGTCAGCAAAGC TACACCCTCGCGTTTGGCCAGGGCACCAAAAGTGGACATCAAG 139108 - ak
vh 424 QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARESGDGMDVWGQGTTVTVSS 139108 - ak
VL 425 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTLAFGQGTKVDIK 139110 139110 - ak
scFv domain 426 QVQLVQSGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISSSGNTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSTMVREDYWGQGTLVTVSSASGGGGSGGRASGGGGSDIVLTQSPLSLPVTLGQPASISCKSSESLVHNSGKTYLNWFHQRPGQSPRRLIYEVSNRD SGVPDRFTGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPGTFGQGTKLEIK 139110 - nk
scFv domain 427 CAAGTGCAACTGGTGCAAAGCGGAGGAGGATTGGTCAAACCCGGAGGAAGCCTGAGACTGTCATGCGCGGCTCTCTGGATTCACCTTCTCCGATTACTACATGTCATGGATCAGACAGGCCCCGGGGAAGGGCCTCGAATGGGTGTCCTACATCTCGTCCTCCGGGAACACCATCTACTACGCCGACCGTGAAGGGCCGCTTTACCATTTCCCGACAACGCA AAGAACTCGCTGTACCTTTCAGATGAATTCCCTGCGGGCTGAAGATACCGCGGTGTACTATTGCGCCCGGTCCACTATGGTCCGGGAGGACTACTGGGGACAGGGCACACTCGTGACCGTGTCCAGCGCGAGCGGGGGTGGAGGCAGCGGTGGACGCGCCTCCGGGCGGCGGTTCAGACATCGTGTGCTGACTCAGTCGCCCCTGTCGCTGCCGGTCACCC TGGGCCAACCGGCCTCAATTAGCTGCAAGTCCTCGGAGAGCCTGGTGCACAACTCAGGAAAGACTTACCTGAACTGGTTCCATCAGCGGCCTGGACAGTCCCCACGGAGGCTCATCTATGAAGTGTCCAACAGGGATTCGGGGGTGCCCGACCGCTTCACTGGCTCCGGGTCCGGCACCGACTTCACCTGAAAATCTCCAGAGTGGAAGCCGAGGACGTGGGCGTG TACTACTGTATGCAGGGTACCCACTGGCCTGGAACCTTTGGACAAGGAACTAAGCTCGAGATTAAG 139110 - ak
vh 428 QVQLVQSGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISSSGNTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSTMVREDYWGQGTLVTVSS 139110 - ak
VL 429 DIVLTQSPLSLPVTLGQPASISCKSSESLVHNSGKTYLNWFHQRPGQSPRRLIYEVSNRDSGVPDRFTGSGSGTDFTLKISRVEAEDVGVYYCMQGTHWPGTFGQGTKLEIK 139112 139112 - ak
scFv domain 430 QVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIRLTQSPSPLSASVGDRVTITCQASEDINKFLNWYHQTPGKAPKLLIYDASTLQTGVPSR FSGSGSGTDFTLTINSLQPEDIGTYYCQQYESLPLTFGGGTKVEIK 139112 - nk
scFv domain 431 CAAGTGCAACTCGTGGAATCTGGTGGAGACTCGTGCAACCCGGTGGAAGCCTTAGGCTGTCGTGCGCCGTCAGCGGGTTTGCTCTGAGCAACCATGGAATGTCCTGGGTCCGCCGGGCACCGGGAAAAGGGCTGGAATGGGTGTCCGGCATCGTGTACAGCGGGTCAACCTATTACGCCGCGTCCGTGAAGGGCAGATTCACTATCTCAAGAGACAA CAGCCGGAACACCCTGTACTTGCAAATGAATTCCCTGCGCCCCGAGGACACCGCCATCTACTACTGCTCCGCCCACGGAGGAGAGTCGGACGTGTGGGGCCAGGGAACGACTGTGACTGTGTCCAGCCGCATCAGGAGGGGTGGTTCGGGCGGCCGGGCCTCGGGGGGAGGAGGTTCCGACATTCGGCTGACCCAGTCCCCGTCCCCACTGTCGGCCTCCG TCGGCGACCGCGTGACCATCACTTGTCAGGCGTCCGAGGACATTAACAAGTTCCTGAACTGGTACCACCAGACCCCTGGAAAGGCCCCCAAGCTGCTGATCTACGATGCCTCGACCCTTCAAACTGGAGTGCCTAGCCGGTTCTCCGGGTCCGGCTCCGGCACTGATTTCACTCTGACCATCAACTCATTGCAGCCGGAAGATATCGGACCTACTATTGCCAGCAGTACGAATCC CTCCCGCTCACATTCGGCGGGGGAACCAAGGTCGAGATTAAG 139112 - ak
vh 432 QVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSS 139112 - ak
VL 433 DIRLTQSPSPLSASVGDRVTITCQASEDINKFLNWYHQTPGKAPKLLIYDASTLQTGVPSRFSGSGSGTDFTLTINSLQPEDIGTYYCQQYESLPLTFGGGTKVEIK 139113 139113 - ak
scFv domain 434 EVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSETTLTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQGPRLLIYGASTRATGIPARFSGSGS GTEFTLTISSLQPEDFAVYYCQQYNDWLPVTFGQGTKVEIK 139113 - nk
scFv domain 435 GAAGTGCAATTGGTGGAAACTGGAGGAGACTTGTGCAACCTGGAGGATCATTGCGGCTCATGCGCTGTCTCCGGCTTCGCCCTGTCAAATCACGGGATGTCGTGGGTCAGACGGGCCCCGGGAAAGGGTCTGGAATGGGTGTCGGGGATTGTGTACAGCGGCTCCACCTACTACGCCGCTTCGGTCAAGGGCCGCTTCACTATTTCACGG GACAACAGCCGCAACACCCTCTATCTGCAAATGAACTCTCTCCGCCCGGAGGATACCGCCATCTACTACTGCTCCGCACACGGCGGCGAATCCGACGTGTGTGGGACAGGGAACCACTGTCACCGTGTCGTCCGCATCCGGTGGCGGAGGATCGGGTGGCCGGGCCTCCGGGGGCGGCGGCAGCGAGACTACCCTGACCCAGTCCCCTGCCACTCTGTCCGTGAGCCCG GGAGAGAGAGCCACCCTTAGCTGCCGGGCCAGCCAGAGCGTGGGCTCCAACCTGGCCTGGTACCAGCAGAAGCCAGGACAGGGTCCCAGGCTGCTGATCTACGGAGCCTCCACTCGCGACCGGCATCCCCGCGAGGTTCTCCGGGTCGGGTTCCGGGACCGAGTTCACCCTGACCATCTCCTCCCTCCAACCGGAGGACTTCGCGGTGTACTACTGTCAG CAGTACAACGATTGGCTGCCCGTGACATTTGGACAGGGGACGAAGGTGGAAATCAAA 139113 - ak
vh 436 EVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSS 139113 - ak
VL 437 ETTLTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQGPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQPEDFAVYYCQQYNDWLPVTFGQGTKVEIK 139114 139114 - ak
scFv domain 438 EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSIGSSSLAWYQQKPGQAPRLLFSGASSRASGIPDRMYGS GSGTDFTLTISRLEPEDFAVYYCQQYAGSPPFTFGQGTKVEIK 139114 - nk
scFv domain 439 GAAGTGCAATTGGTGGAATCTGGTGGAGACTTGTGCAACCTGGAGGATCACTGAGACTGTCATGCGCGGTGTCCGGTTTTGCCCTGAGCAATCATGGGATGTCGTGGGTCCGGCGCGCCCCCGGAAAGGGTCTGGAATGGGTGTCGGGTATCGTCTACTCCGGGAGCACTTACTACGCCGCGAGCGTGAAGGGCCGCTTCACCATTTCCCGCGATA ACTCCCGCAACACCCTGTACTTGCAAATGAACTCGCTCCGGCCTGAGGACACTGCCATCTACTACTGCTCCGCACACGGAGGAGAATCCGACGTGTGGGGCCAGGGAACTACCGTGACCGTCAGCAGCGCCTCCGGCGGCGGGGCTCAGGCGGACGGGCTAGCGGCGGCGGTGGCTCCGAGATCGTGCTGACCCAGTCGCCTGGCACTCTTCCGCTGAGCCCCGGGGA AAGGGCACCCTGTCCTGTCGGGCCAGCCAGTCCATTGGATCATCCTCCCTCGCCTGGTATCAGCAGAAACCGGGACAGGCTCCGCGGCTGCTTATGTATGGGGCCAGCTCAAGAGCCTCCGGCATTCCCGACCGGTTCTCCGGGTCCGGTTCCGGCACCGATTTCACCCTGACTATCTCGAGGCTGGAGCCAGAGGACTTCGCCGTGTACTACTGCCAGCAGTA CGCGGGGTCCCCGCCGTTCACGTTCGGACAGGGAACCAAGGTCGAGATCAAG 139114 - ak
vh 440 EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSS 139114 - ak
VL 441 EIVLTQSPGTLSLSPGERATLSCRASQSIGSSSLAWYQQKPGQAPRLLMYGASSRASGIPDRFSGSGSGTDFTLTISRLEPEDFAVYCQQYAGSPPFTFGQGTKVEIK 149362 149362 - ak
scFv domain 442 Qvqlqesgpglvkpsetlsltctvsggsisssyyywgwirqppgkglewigsiyysgsayynpslksrvtisvdtsknqfslrlssvtaadtavyycarhwqewpdafdiwgqgtmvtvssggggsggggsggggsettltqspafmsatpgdkviisckasqdiddamnwyqqkpgeaplfiiq satspvpgipprfsgsgfgtdfsltinniesedaayyfclqhdnfpltfgqgtkleik 149362 - nk
scFv domain 443 caagtgcagcttcaggaaagcggaccgggcctggtcaagccatccgaaactctctccctgacttgcactgtgtctggcggttccatctcatcgtcgtactactactggggctggattaggcagccgcccggaaagggactggagtggatcggaagcatctactattccggctcggcgtactacaaccctagcctcaagtcgagagtgacca tctccgtggatacctccaagaaccagttttccctgcgcctgagctccgtgaccgccgctgacaccgccgtgtactactgtgctcggcattggcaggaatggcccgatgccttcgacatttggggccagggcactatggtcactgtgtgtcatccgggggtggaggcagcgggggaggagggtccgggggggggaggttcagagacaaccttgac ccagtcacccgcattcatgtccgccactccggagacaaggtcatcatctcgtgcaaagcgtcccaggatatcgacgatgccatgaattggtaccagcagaagcctggcgaagcgccgctgttcattatccaatccgcaacctcgcccgtgcctggaatcccaccgcggttcagcggcagcggtttcggaaccgacttttccct gaccattaacaacattgagtccgaggacgccgcctactacttctgcctgcaacacgacaacttccctctcacgttcggccagggaaccaagctggaaatcaag 149362 - ak
vh 444 QVQLQESGPGLVKPSETLSLTCTVSGGSISSSYYYWGWIRQPPGKGLEWIGSIYYSGSAYYNPSLKSRVTISVDTSKNQFSLRLSSVTAADTAVYYCARHWQEWPDAFDIWGQGTMVTVSS 149362 - ak
VL 445 ETTLTQSPAFMSATPGDKVIISCKASQDIDDAMNWYQQKPGEAPLFIIQSATSPVPGIPPRFSGSGFGTDFSLTINNIESEDAAYYFCLQHDNFPLTFGQGTKLEIK 149363 149363 - ak
scFv domain 446 QVNLRESGPALVKPTQTLTLTCTFSGFSLRTSGMCVSWIRQPPGKALEWLARIDWDEDKFYSTSLKTRLTISKDTSDNQVVLRMTNMDPADTATYYCARSGAGGTSATAFDIWGPGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDIYNNLAWFQLKPGSAPRSLAANKSQSGVPSR FSGSASGTDFTLTISSLQPEDFATYYCQHYYRFPYSFGQGTKLEIK 149363 - nk
scFv domain 447 caagtcaatctgcgcgaatccggccccgccttggtcaagcctacccagaccctcactctgacctgtactttctccggcttctccctgcggacttccgggatgtgcgtgtcctggatcagacagcctccgggaaaggccctggagtggctcgctcgcattgactgggatgaggacaagttctactccacctcactcaagaccaggctgaccat cagcaaagatacctctgacaaccaagtggtgctccgcatgaccaacatggacccagccgacactgccacttactactgcgcgaggagcggagcgggcggaacctccgccaccgccttcgatatttggggcccgggtaccatggtcaccgtgtcaagcggaggaggggggtccgggggcggcggttccgggggaggcggatcggacattcagatg actcagtcaccatcgtccctgagcgctagcgtgggcgacagagtgacaatcacttgccgggcatcccaggacatctataacaaccttgcgtggttccagctgaagcctggttccgcaccgcggtcacttatgtacgccgccaacaagagccagtcgggagtgccgtcccggttttccggttcggcctcgggaactgacttcacc ctgacgatctccagcctgcaacccgaggatttcgccacctactactgccagcactactaccgctttccctactcgttcggacagggaaccaagctggaaatcaag 149363 - ak
vh 448 QVNLRESGPALVKPTQTLTLTCTFSGFSLRTSGMCVSWIRQPPGKALEWLARIDWDEDKFYSTSLKTRLTISKDTSDNQVVLRMTNMDPADTATYYCARSGAGGTSATAFDIWGPGTMVTVSS 149363 - ak
VL 449 DIQMTQSPSSLSASVGDRVTITCRASQDIYNNLAWFQLKPGSAPRSLMYAANKSQSGVPSRFSGSASGTDFTLTISSLQPEDFATYYCQHYYRFPYSFGQGTKLEIK 149364 149364 - ak
scFv domain 450 evqlvesggglvkpggslrlscaasgftfssysmnwvrqapgkglewvssisssssyiyyadsvkgrftisrdnaknslylqmnslraEDTAvyycaktiaavyafdiwgqgttvtvssggggsggggsggggseivltqsplslpvtpeepasiscrssqsllhsngynyldwylqkpgqspqll iylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqalqtpytfgqgtkleik 149364 - nk
scFv domain 451 gaagtgcagcttgtcgaatccggggggggactggtcaagccgggcggatcactgagactgtcctgcgccgcgagcggcttcacgttctcctcctactccatgaactgggtccgccaagcccccgggaagggactggaatgggtgtcctctatctcctcgtcgtcgtcctacatctactacgccgactccgtgaagggaaga ttcaccatttcccgcgacaacgcaaagaactcactgtacttgcaaatgaactcactccgggccgaagatactgctgtgtactattgcgccaagactattgccgccgtctacgctttcgacatctggggccagggaaccaccgtgactgtgtgtcgtccggtggtggtggctcgggcggaggaggaagcggcggcggggggtccgagattg tgctgacccagtcgccactgagcctccctgtgacccccgaggaacccgccagcatcagctgccggtccagccagtccctgctccactccaacggatacaattacctcgattggtaccttcagaagcctggacaaagcccgcagctgctcatctacttgggatcaaaccgcgcgtcaggagtgcctgaccggttctccggctcgggcagcgg taccgatttcaccctgaaaatctccagggtggaggcagaggacgtgggagtgtattactgtatgcaggcgctgcagactccgtacacatttgggcagggcaccaagctggagatcaag 149364 - ak
vh 452 EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKTIAAVYAFDIWGQGTTVTVSS 149364 - ak
VL 453 EIVLTQSPLSLPVTPEEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKLEIK 149365 149365 - ak
scFv domain 454 evqlvesggglvkpggslrlscaasgftfsdyymswirqapgkglewvsyisssgstiyyadsvkgrftisrDNAknslylqmnslraEDTAvyycardlrgafdiwgqgtmvtvssggggsggggsggggssyvltqspsvsaapgytatiscggnnigtksvhwyqqkpgqapllvirddsvrp skipgrfsgsnsgnmatltisgvqagdeadfycqvwdsdsehvvfgggtkltvl 149365 - nk
scFv domain 455 gaagtccagctcgtggagtccggcggaggccttgtgaagcctggaggttcgctgagactgtcctgcgccgcctccggcttcaccttctccgactactacatgtcctggatcagacaggccccgggaaagggcctggaatgggtgtcctacatctcgtcgggcagcactatctactacgcggactcagtgaaggggcggtt caccatttcccgggataacgcgaagaactcgctgtatctgcaaatgaactcactgagggccgaggacaccgccgtgtactactgcgcccgcgatctccgcggggcatttgacatctggggacagggaaccatggtcacagtgtccagcggagggggaggatcgggtggcggaggttccgggggtggaggctcctcctacgtgctgact cagagcccaagcgtcagcgctgcgcccggttacacggcaaccatctcctgtggcggaaacaacattgggaccaagtctgtgcactggtatcagcagaagccgggccaagctcccctgttggtgatccgcgatgactccgtgcggcctagcaaaattccgggacggttctccggctccaacagcggcaatatggccactctcaccatctc gggagtgcaggccggagatgaagccgacttctactgccaagtctgggactcagactccgagcatgtggtgttcgggggcggaaccaagctgactgtgctc 149365 - ak
vh 456 EVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDLRGAFDIWGQGTMVTVSS 149365 - ak
VL 457 SYVLTQSPSVSAAPGYTATISCGGNNIGTKSVHWYQQKPGQAPLLVIRDDSVRPSKIPGRFSGSNSGNMATLTISGVQAGDEADFYCQVWDSDSEHVVFGGGTKLTVL 149366 149366 - ak
scFv domain 458 qvqlvqsgaevkkpgasvkvsckpsgytvtshyihwvrrapgqglewmgminpsggvtaysqtlqgrvtmtsdtssstvymelsslrsEDTAmyycaregsgsgwyfdfwgrgtlvtvssggggsggggsggggssyvltqppsvsvspgqtasitcsgdglskkyvswyqqkagqspv vlisrdkerpsgipdrfsgsnsadtatltisgtqamdeadyycqawddttvvfgggtkltvl 149366 - nk
scFv domain 459 caagtgcagctggtgcagagcggggccgaagtcaagaagccgggagcctccgtgaaagtgtcctgcaagccttcgggatacaccgtgacctcccactacattcattgggtccgccgcgcccccggccaaggactcgagtggatgggcatgatcaaccctagcggcggagtgaccgcgtacagccagacgctgcagggacg cgtgactatgacctcggatacctcctcctccaccgtctatatggaactgtccagcctgcggtccgaggataccgccatgtactactgcgcccgggaaggatcaggctccgggtggtatttcgacttctggggaagaggcaccctcgtgtgtgtcatctgggggagggggttccggtggtggcggatcgggaggaggcggttcatcct acgtgctgacccagccaccctccgtgtccgtgagccccggccagactgcatcgattacatgtagcggcgacggcctctccaagaaatacgtgtcgtggtaccagcagaaggccggacagagcccggtggtgctgatctcaagagataaggacggcctagcggaatccggacaggttctcggttccaactccgcggacactgctactctgaccat ctcggggacccaggctatggacgaagccgattactactgccaagcctgggacgacactactgtcgtgtttggagggggcaccaagttgaccgtcctt 149366 - ak
vh 460 QVQLVQSGAEVKKPGASVKVSCKPSGYTVTSHYIHWVRRAPGQGLEWMGMINPSGGVTAYSQTLQGRVTMTSDTSSSTVYMELSSLRSEDTAMYYCAREGSGSGWYFDFWGRGTLVTVSS 149366 - ak
VL 461 SYVLTQPPSVSVSPGQTASITCSGDGLSKKYVSWYQQKAGQSPVVLISRDKERPSGIPDRFSGSNSADTATLTISGTQAMDEADYYCQAWDDTTVVFGGGTKLTVL 149367 149367 - ak
scFv domain 462 QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARAGIAARLRGAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIVMTQSPSSVSASVGDRVIITCRASQGIRNWLAWYQQKPGKAPNLLIYAA SNLQSGVPSRFSGSGSGADFTLTISSLQPEDVATYYCQKYNSAPFTFGPGTKVDIK 149367 - nk
scFv domain 463 caagtgcagcttcaggagagcggcccgggactcgtgaagccgtcccagaccctgtccctgacttgcaccgtgtcgggaggaagcatctcgagcggaggctactattggtcgtggattcggcagcaccctggaaagggcctggaatggatcggctacatctactactccggctcgacctactaacccatcgctgaagtccaga gtgacaatctcagtggacacgtccaagaatcagttcagcctgaagctctcttccgtgactgcggccgacaccgccgtgtactactgcgcacgcgctggaattgccgcccggctgaggggtgccttcgacatttggggacagggcaccatggtcaccgtgtcctccggcggcggaggttccgggggtggaggctcaggaggggg ggtccgacatcgtcatgactcagtcgccctcaagcgtcagcgcgtccgtcggggacagagtgatcatcacctgtcgggcgtcccagggaattcgcaactggctggcctggtatcagcagaagcccggaaaggcccccaacctgttgatctacgccgcctcaaacctccaatccggggtgccgagccgcttcagcggct ccggttcgggtgccgatttcactctgaccatctcctccctgcaacctgaagatgtggctacctactactgccaaaagtacaactccgcaccttttactttcggaccggggaccaaagtggacattaag 149367 - ak
vh 464 QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYYWSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARAGIAARLRGAFDIWGQGTMVTVSS 149367 - ak
VL 465 DIVMTQSPSSVSASVGDRVIITCRASQGIRNWLAWYQQKPGKAPNLLIYAASNLQSGVPSRFSGSGSGADFTLTISSLQPEDVATYYCQKYNSAPFTFGPGTKVDIK 149368 149368 - ak
scFv domain 466 qvqlvqsgaevkkpgssvkvsckasggtfssyaiswvrqapgqglewmggiipifgtanyaqkfqgrvtitadeststaymelsslrsedtavyycarrggyqllrwdvgllrsafdiwgqgtmvtvssggggsggggsggggssyvltqppsvsvapgqtaritcggnnigsksvhwyqq kpgqapvlvlygknnrpsgvpdrfsgsrsgttasltitgaqaedeadyycssrdssgdhlrvfgtgtkvtvl 149368 - nk
scFv domain 467 caagtgcagctggtccagtcgggcgccgaggtcaagaagcccgggagctctgtgaaagtgtcctgcaaggcctccgggggcacctttagctcctacgccatctcctgggtccgccaagcaccgggtcaaggcctggagtggatgggggggaattatccctatcttcggcactgccaactacgcccagaagttccagggacgcgtga ccattaccgcggacgaatccacctccaccgcttatatggagctgtccagcttgcgctcggaagataccgccgtgtactactgcgcccgggaggggtggataccagctgctgagatgggacgtgggcctcctgcggtcggcgttcgacatctggggccagggcactatggtcactgtgtccagcggaggaggcggatcgggaggcggc ggatcagggggaggcggttccagctacgtgctttactcaacccccttcggtgtccgtggccccgggacagaccgccagaatcacttgcggaggaaacaacattgggtccaagagcgtgcattggtaccagcagaagccaggacaggcccctgtgctggtgctctacgggaagaacaatcggcccagcggagtgccggacaggttctcgggtt cacgctccggtacaaccgcttcactgactatcaccggggcccaggcagaggatgaagcggactactgttcctcccgggattcatccggcgaccacctccgggtgttcggaaccggaacgaaggtcaccgtgctg 149368 - ak
vh 468 QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARRGGYQLLRWDVGLLRSAFDIWGQGTMVTVSS 149368 - ak
VL 469 SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVLYGKNNRPSGVPDRFSGSRSGTTASLTITGAQAEDEADYYCSSRDSSGDHLRVFGTGTKVTVL 149369 149369 - ak
scFv domain 470 evqlqqsgpglvkpsqtlsltcaisgdsvssnsaawnwirqspsrglewlgrtyyrskwysfyaislksriiinpdtsknqfslqlksvtpEDTAvyycarsspeglflywfdpwgqgtlvtvsssggdgsggggsggggssseltqdpavsvalgqtiritcqgdslgnyyatwyq qkpgqapvlviygtnnrpsgipdrfsasssgntasltitgaqaedeadyycnsrdssghhllfgtgtkvtvl 149369 - nk
scFv domain 471 gaagtgcagctccaacagtcaggaccggggctcgtgaagccatcccagaccctgtccctgacttgtgccatctcgggagatagcgtgtcatcgaactccgccgcctggaactggattcggcagagcccgtcccgcggactggagtggcttggaaggacctactaccggtccaagtggtactctttctacgcgatctcgctgaag tcccgcattatcattaaccctgatacctccaagaatcagttctccctccaactgaaatccgtcacccccgaggacacagcagtgtattactgcgcacggagcagccccgaaggactgttcctgtattggtttgacccctggggccaggggactcttgtgaccgtgtcgagcggcggagatgggtccggtggcggtggttcggggggcggcgg atcatcatccgaactgacccaggacccggctgtgtccgtggcgctgggacaaaccatccgcattacgtgccagggagactccctgggcaactactacgccacttggtaccagcagaagccggggccaagcccctgtgttggtcatctacgggaccaacaacagaccttccggcatccccgaccggttcagcgcttcgtcctccggcaacactgccagcctgaccatc actggagcgcaggccgaagatgaggccgactactactgcaacagcagagactcctcgggtcatcacctcttgttcggaactggaaccaaggtcaccgtgctg 149369 - ak
vh 472 EVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYSFYAISLKSRIIINPDTSKNQFSLQLKSVTPEDTAVYYCARSSPEGLFLYWFDPWGQGTLVTVSS 149369 - ak
VL 473 SSELTQDPAVSVALGQTIRITCQGDSLGNYYATWYQQKPGQAPVLVIYGTNNRPSGIPDRFSASSSGNTASLTITGAQAEDEADYYCNSRDSSGHHLLFGTGTKVTVL BCMA_EBB-C1978-A4 BCMA_EBB-C1978-A4 - ak
scFv domain 474 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVEGSGSLDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPGTLSLSPGERATLSCRASQSVSSAYLAWYQQKPGQPPRLLISGASTRATGIPD RFGGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSFNGSSLFTFGQGTRLEIK BCMA_EBB-C1978-A4 - nk
scFv domain 475 GAAGTGCAGCTCGTGGAGTCAGGAGGCGGCCTGGTCCAGCCGGGAGGGTCCCTTAGACTGTCATGCGCCGCAAGCGGATTCACTTTCTCCTCCTATGCCATGAGCTGGGTCCGCCAAGCCCCCGGAAAGGACTGGAATGGGTGTCCGCCATCTCGGGGTCTGGAGGCTCAACTTACTACGCTGACTCCGTGAAGGGACGGTTCACCATTAGCCGC GACAACTCCAAGAACACCCTCTACCTCCAAATGAACTCCCTGCGGGCCGAGGATACCGCCGTCTACTACTGCCCAAAGTGGAAGGTTCAGGATCGCTGGACTACTGGGGACAGGGTACTCTCGTGACCGTGTCATCGGGCGGAGGAGGTTCCGGCGGTGGCGGCTCCGGCGGCGGAGGTCGGAGATCGTGATGACCCAGAGCCCTGGTACTCTGAGCC TTTCGCCGGGAGAAAGGGCCACCTGTCCTGCCGCGCTTCCCAATCCGTGTCCTCCGCGTACTTGGCGTGGTACCAGCAGAAGCCGGGACAGCCCCCTCGGCTGCTGATCAGCGGGGCAGCACCCGGGCAACCGGAATCCCAGACAGATTCGGGGGTTCCGGCAGCGGCACAGATTTCACCCTGACTATTTCGAGGTTGGAGCCCGAGACTTTGCGGTG TATTACTGTCAGCACTACGGGTCGTCCTTTAATGGCTCCAGCCTGTTCACGTTCGGACAGGGGACCCGCCTGGAAATCAAG BCMA_EBB-C1978-A4 - ak
vh 476 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVEGSGSLDYWGQGTLVTVSS BCMA_EBB-C1978-A4 - ak
VL 477 EIVMTQSPGTLSLSPGERATLSCRASQSVSSAYLAWYQQKPGQPPRLLISGASTRATGIPDRFGGSGSGTDFTLTISRLEPEDFAVYCQHYGSSFNGSSLFTFGQGTRLEIK BCMA_EBB-C1978-G1 BCMA_EBB-C1978-G1 - ac
scFv domain 478 EVQLVETGGGLVQPGGSLRLSCAASGITFSRYPMSWVRQAPGKGLEWVSGISDSGVSTYYADSAKGRFTISRDNSKNTLFLQMSSLRDEDTAVYYCVTRAGSEASDIWGQGTMVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSNSLAWYQQKPGQAPRLLIYDASSRATGIPDRGSGSGS GTDFTLTISRLEPEDFAIYYCQQFGTSSGLTFGGGTKLEIK BCMA_EBB-C1978-G1 - nk
scFv domain 479 GAAGTGCAACTGGTGGAAACCGGTGGCGGCCTGGTGCAGCCTGGAGGATCATTGAGGCTGTCATGCGCGGCCAGCGGTATTACCTTCTCCCGGTACCCCATGTCCTGGTCAGACAGGCCCCGGGGAAAGGGCTTGAATGGGTGTCCGGGATCTCGGACTCCGGTGTCAGCACTTACTACGCCGACTCCGCCAAGGGACGCTTCACCATTTCCCG GGACAACTCGAAGAACACCCTGTTCCTCCAAATGAGCTCCCTCCGGGACGAGGATACTGCAGTGTACTGCGTGACCCGCGCCGGGTCCGAGGCGTCTGACATTTGGGGACAGGGCACTATGGTCACCGTGTCGTCCGGCGGAGGGGCTCGGGAGGCGGTGGCAGCGGAGGAGGAGGGTCCGAGATCGTGCTGACCCAATCCCCGGCCACCCTCT CGCTGAGCCCTGGAGAAAGGGCAACCTTGTCCTGTCGCGCGAGCCAGTCCGTGAGCAACTCCCTGGCCTGGTACCAGCAGAAGCCCGGACAGGCTCCGAGACTTCTGATCTACGACGCTTCGAGCCGGGCCACTGGAATCCCCGACCGCTTTTCGGGGTCCGGCTCAGGAACCGATTTCACCCTGACAATCTCACGGCTGGAGCCAGAGGATTTCGCCATCTATTACTGCCAGC AGTTCGGTACTTCCTCCGGCCTGACTTTCGGAGGCGGCACGAAGCTCGAAATCAAG BCMA_EBB-C1978-G1 - ac
vh 480 EVQLVETGGGLVQPGGSLRLSCAASGITFSRYPMSWVRQAPGKGLEWVSGISDSGVSTYYADSAKGRFTISRDNSKNTLFLQMSSLRDEDTAVYYCVTRAGSEASDIWGQGTMVTVSS BCMA_EBB-C1978-G1 - ac
VL 481 EIVLTQSPATLSLSPGERATLSCRASQSVSNSLAWYQQKPGQAPRLLIYDASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAIYCQQFGTSSGLTFGGGTKLEIK BCMA_EBB-C1979-C1 BCMA_EBB-C1979-C1 - ac
scFv domain 482 QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAIYYCARATYKRELRYYYGMDVWGQGTMVTVSSGGGGSGGGGSGGGGSEIVMTQSPGTVSLSPGERATLSCRASQSVSSSFLAWYQQKPGQAPRLLIYGA SSRATGIPDRFSGSGSGTDFTLTISRLEPEDSAVYYCQQYHSSPSWTFGQGTRLEIK BCMA_EBB-C1979-C1 - nk
scFv domain 483 CAAGTGCAGCTCGTGGAATCGGGTGGCGGACTGGTGCAGCCGGGGGGCTCACTTAGACTGTCCTGCGCGGCCAGCGGATTCACTTTCTCCTCCTACGCCATGTCCTGGGTCAGACAGGCCCCTGGAAAGGGCCTGGAATGGGTGTCCGCAATCAGCGGCAGCGGCGGCTCGACCTATTACGCGGATTCAGTGAAGGGCAGATTCACCATTTCCCG GGACAACGCCAAGAACTCCTTGTACCTTCAAATGAACTCCCTCCGCGCGGAAGATACCGCAATCTACTACTGCGCTCGGGCCACTTACAAGAGGGAACTGCGCTACTACGGGATGGACGTCTGGGGCCAGGGAACCATGGTCACCGTGTCCAGCGGAGGAGGAGGATCGGGAGGAGGCGGTAGCGGGGTGGAGGGTCGGAGATCGTGATGAC CCAGTCCCCCGGCACTGTGTCGCTGTCCCCCGGCGAACGGGCCACCTGTCATGTCGGCCAGCCAGTCAGTGTCGTCAAGCTTCCTCGCCTGGTACCAGCAGAAACCGGGACAAGCTCCCCGCCTGCTGATCTACGGAGCCAGCAGCCGGGCCACCGGTATTCCTGACCGGTTCTCCGGTTCGGGGTCCGGGACCGACTTTACTCTGACTATCTCTCGCC TCGAGCCAGAGGACTCCGCCGTGTATTACTGCCAGCAGTACCACTCCTCCCCGTCCTGGACGTTCGGACAGGGCACAAGGCTGGAGATTAAG BCMA_EBB-C1979-C1 - ac
vh 484 QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAIYYCARATYKRELRYYYGMDVWGQGTMVTVSS BCMA_EBB-C1979-C1 - ac
VL 485 EIVMTQSPGTVSLSPGERATLSCRASQSVSSSFLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDSAVYCQQYHSSPSWTFGQGTRLEIK BCMA_EBB-C1978-C7 BCMA_EBB-C1978-C7 - ak
scFv domain 486 EVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNTLKAEDTAVYYCARATYKRELRYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPSTLSLSPGESATLSCRASQSVSTTFLAWYQQKPGQAPRLLIYGS SNRTGIPDRFSGSGSGTDFTLTIRRLEPEDFAVYYCQQYHSSPSWTFGQGTKVEIK BCMA_EBB-C1978-C7 - nk
scFv domain 487 GAGGTGCAGCTTGTGGAAACCGGTGGCGGACTGGTGCAGCCCGGAGGAAGCCTCAGGCTGTCGCGCCGCGTCCGGCTTCACCTTCTCCTCGTACGCCATGTCCTGGGTCCGCCAGGCCCCCGGAAAGGGCCTGGAATGGGTGTCCGCCATCTCTGGAAGCGGAGGTTCCACGTACTACGCGGACAGCGTCAAGGGAAGGTTCACAATCTCC CGCGATAATTCGAAGAACACTCTGTACCTTCAAATGAACACCCTGAAGGCCGAGGACACTGCTGTGTACTACTGCGCACGGGCCACCTACAAGAGAGCTCCGGTACTACTACGGAATGGACGTCTGGGGCCAGGGAACTACTGTGACCGTGTCCTCGGGAGGGGGTGGCTCCGGGGGGGCGGCTCCGGCGGAGGCGGTTCCGAGATTGTGCTGACCCC AGTCACCTTCAACTCTGTCGCTGTCCCCGGGAGAGAGCGCTACTCTGAGCTGCCGGGCCAGCCAGTCCGTGTCCACCACCTTCCTCGCCTGGTATCAGCAGAAGCCGGGGCAGGCACCACGGCTCTTGATCTACGGGTCAAGCAACAGCGACCGGAATTCCTGACCGCTTCTCGGGGAGCGGTTCAGGCACCGACTTCACCCTGACTATCCGGCGCCTGGAACCCGA AGATTTCGCCGTGTATTACTGTCAACAGTACCACTCCTCGCCGTCCTGGACCTTTGGCCAAGGAACCAAAGTGGAAATCAAG BCMA_EBB-C1978-C7 - ak
vh 488 EVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNTLKAEDTAVYYCARATYKRELRYYYGMDVWGQGTTVTVSS BCMA_EBB-C1978-C7 - ak
VL 489 EIVLTQSPSTLSLSPGESATLSCRASQSVSTTFLAWYQQKPGQAPRLLIYGSSNRATGIPDRFSGSGSGTDFTLTIRRLEPEDFAVYCQQYHSSPSWTFGQGTKVEIK BCMA_EBB-C1978-D10 BCMA_EBB-C1978-D10 - ac
scFv domain 490 EVQLVETGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCARVGKAVPDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVMTQTPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQ SGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTRLEIK BCMA_EBB-C1978-D10 - nk
scFv domain 491 GAAGTGCAGCTCGTGGAAACTGGAGGTGGACTCGTGCAGCCTGGACGGTCGCTGCGGCTGAGCTGCGCTGCATCCGGCTTCACCTTCGACGATTATGCCATGCACTGGGTCAGACAGGCGCCAGGGAAGGACTTGAGTGGGTGTCCGGTATCAGCTGGAATAGCGGCTCAATCGGATACGCGGACTCCGTGAAGGGAAGGTTCACCATTTCCCGCACACG CCAAGAACTCCCTGTACTTGCAAATGAACAGCCTCCGGGATGAGGACACTGCCGTGTACTACTGCGCCCGCGTCGGAAAAGCTGTGCCCCGACGTCTGGGCCAGGGAACCACTGTGACCGTGTCCAGCGGCGGGGTGGATCGGGCGGTGGAGGTCCGGTGGAGGGGCTCAGATATTGATGACCCAGACCCCCTCGTCCCTGTCCGCCTCGG TCGGCGACCGCGTGACTATCACATGTAGAGCCTCGCAGAGCATCTCCAGCTACCTGAACTGGTATCAGCAGAAGCCGGGGAAGGCCCCGAAGCTCCTGATCTACGCGGCATCATCACTGCAATCGGGAGTGCCGAGCCGGTTTTCCGGGTCCGGCTCCGGCACCGACTTCACGCTGACCATTTCTTCCCTGCAACCCGAGGACTTCGCCACTTACTGCCAGCAGTCCTACTCCAC CCCTTACTCCTTCGGCCAAGGAACCAGGCTGGAAATCAAG BCMA_EBB-C1978-D10 - ac
vh 492 EVQLVETGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCARVGKAVPDVWGQGTTVTVSS BCMA_EBB-C1978-D10 - ac
VL 493 DIVMTQTPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTRLEIK BCMA_EBB-C1979-C12 BCMA_EBB-C1979-C12 - ac
scFv domain 494 EVQLVESGGGLVQPGRSLRLSCTASGFTFDDYAMHWVRQRPGKGLEWVASINWKGNSLAYGDSVKGRFAISRDNAKNTVFLQMNSLRTEDTAVYYCASHQGVAYYNYAMDVWGRGTLVTVSSGGGGSGGGGSGGGGGSEIVLTQSPGTLSLSPGERATLSCRATQSIGSSFLAWYQQRPGQAPRLLIYGAS QRATGIPDRFSGRGSGTDFTLTISRVEPEDSAVYYCQHYESSPSWTFGQGTKVEIK BCMA_EBB-C1979-C12 - nk
scFv domain 495 GAAGTGCAGCTCGTGGAGAGCGGGGGAGGATTGGTGCAGCCCGGAAGGTCCCTGCGGCTCTCCTGCACTGCGTCTGGCTTCACCTTCGACGACTACGCGAATGCACTGGGTCAGACAGCGCCCGGGAAAGGGCCTGGAATGGGTCGCCTCAATCAACTGGAAGGGAAACTCCCTGGCCTATGGCGACAGCGTGAAGGGCCGCTTCGCCATTTCGCGCG ACAACGCCAAGAACACCGTGTTTCTGCAAATGAATTCCCTGCGGACCGAGGATACCGCTGTGTACTACTGCCAGCCACCAGGGCGTGGCATACTATAACTACGCCATGGACGTGTGGGGAAGAGGGACGCTCGTCACCGTGTCCTCCGGGGGCGGTGGATCGGGTGGAGGAGGAAGCGGTGGCGGGGCAGCGAAATCGTGCTGACTCAGAGCCCGGGAACTC TTTCACTGTCCCCGGGAGAACGGGCCACTCTCTCGTGCCGGGCACCCAGTCCATCGGCTCCTCCTTCCTTGCCTGGTACCAGCAGAGGCCAGGACAGGCGCCCCGCCTGCTGATCTACGGTGCTTCCCAACGCGCCACTGGCATTCCTGACCGGTTCAGCGGCAGAGGGTCGGGAACCGATTTCACACTGACCATTTCCCGGGTGGAGCCCGAAGATTCGGCAG TCTACTACTGTCAGCATTACGAGTCCTCCCCTTCATGGACCTTCGGTCAAGGGACCAAAGTGGAGATCAAG BCMA_EBB-C1979-C12 - ac
vh 496 EVQLVESGGGLVQPGRSLRLSCTASGFTFDDYAMHWVRQRPGKGLEWVASINWKGNSLAYGDSVKGRFAISRDNAKNTVFLQMNSLRTEDTAVYYCASHQGVAYYNYAMDVWGRGTLVTVSS BCMA_EBB-C1979-C12 - ac
VL 497 EIVLTQSPGTLSLSPGERATLSCRATQSIGSSFLAWYQQRPGQAPRLLIYGASQRATGIPDRFSGRGSGTDFTLTISRVEPEDSAVYYCQHYESSPSWTFGQGTKVEIK BCMA_EBB-C1980-G4 BCMA_EBB-C1980-G4 - ac
scFv domain 498 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVVRDGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP DRFSGNGSGTDFTLTISRLEPEDFAVYYCQQYGSPPRFTFGPGTKVDIK BCMA_EBB-C1980-G4 - nk
scFv domain 499 GAGGTGCAGTTGGTCGAAAAGCGGGGGCGGGCTTGTGCAGCCTGGCGGATCACTGCGGCTGTCCTGCGCGGCATCAGGCTTCACGTTTTCTTCCTACGCCATGTCCTGGTGCGCCAGGCCCCTGGAAAGGGACTGGAATGGGTGTCCGCGATTTCGGGGTCCGGCGGAGCACCTACTACGCCGATTCCGTGAAGGGCCGCTTCACTATCTCG CGGGACAACTCCAAGAACACCCTCTACCTCCAAATGAATAGCCTGCGGGCCGAGGATACCGCCGTCTACTATTGCGCTAAGGTCGTGGCGCGACGGAATGGACGTGTGGGGACAGGGTACCACCGTGACAGTGTCCTCGGGGGGAGGCGGTAGCGGCGGAGGAGGAAGCGGTGGTGGAGGTTCCGAGATTGTGCTGACTCAATCACCCGCGACCCTGAG CCTGTCCCCCGGCGAAAGGGCCACTCTGTCCTGTCGGGCCAGCCAATCAGTCTCCTCCTCGTACCTGGCCTGGTACCAGCAGAAGCCAGGACAGGCTCCGAGACTCCTTATCTATGGCGCATCCTCCCGCGCCACCGGAATCCCGGATAGGTTCTCGGGAAACGGATCGGGGACCGACTTCACTTCACCATCTCCCGGCTGGAACCGGAGACTTCGCCGTGTACT ACTGCCAGCAGTACGGCAGCCCGCCTAGATTCACTTTCGGCCCCGGCACCAAAAGTGGACATCAAG BCMA_EBB-C1980-G4 - ac
vh 500 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVVRDGMDVWGQGTTVTVSS BCMA_EBB-C1980-G4 - ac
VL 501 EIVLTQSPATLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGNGSGTDFTLTISRLEPEDFAVYYCQQYGSPPRFTFGPGTKVDIK BCMA_EBB-C1980-D2 BCMA_EBB-C1980-D2 - ac
scFv domain 502 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIPQTGTFDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQRPGQAPRLLIYGASSRATG IPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGSPSWTFGQGTRLEIK BCMA_EBB-C1980-D2 - nk
scFv domain 503 GAAGTGCAGCTGCTGGAGTCCGGCGGTGGATTGGTGCAACCGGGGGATCGCTCAGACTGTCCTGTGTGCGGCGTCAGGCTTCACCTTCTCGAGCTACGCCATGTCATGGGTCAGACAGGCCCCTGGAAAGGTCTGGAATGGGTGTCCGCCATTTCCGGGAGCGGGGGATCTACATACTACGCCGATAGCGTGAAGGGCCGCTTCACCATTTCCCG GGACAACTCCAAGAACACTCTCTATCTGCAAATGAACTCCCTCCGCGCTGAGGACACTGCCGTGTACTACTGCGCCAAAATCCCTCAGACCGGCACCTTCGACTACTGGGGACAGGGGACTCTGGTCACCGTCAGCAGCGGTGGCGGAGGTTCGGGGGAGGAGGAAGCGGCGGCGGAGGTCCGAGATTGTGCTGACCAGTCACCCGGCACTTTGTCCCTG TCGCCTGGAGAAAGGGCACCCTTTCCTGCCGGGCATCCCAATCCGTGTCCTCCTCGTACCTGGCCTGGTACCAGCAGAGGCCCGGACAGGCCCCACGGCTTCTGATCTACGGAGCAAGCAGCCGCGCGACCGGTATCCCGGACCGGTTTTCGGGCTCGGGCTCAGGAACTGACTTCACCCTCACCATCTCCCGCCTGGAACCCGAAGATTTCGCTGTGTATTACTGC CAGCACTACGGCAGCTCCCCGTCCTGGACGTTCGGCCAGGGAACTCGGCTGGAGATCAAG BCMA_EBB-C1980-D2 - ac
vh 504 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIPQTGTFDYWGQGTLVTVSS BCMA_EBB-C1980-D2 - ac
VL 505 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQRPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYCQHYGSPSWTFGQGTRLEIK BCMA_EBB-C1978-A10 BCMA_EBB-C1978-A10 - ac
scFv domain 506 EVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTMSRENDKNSVFLQMNSLRVEDTGVYYCARANYKRELRYYYGMDVWGQGTMVTVSSGGGGSGGGGSGGGGSEIVMTQSPGTLSLSPGESATLSCRASQRVASNYLAWYQHKPGQAPSLLIS GASSRATGVPDRFSGSGSGTDFTLAISRLEPEDSAVYYCQHYDSSPSWTFGQGTKVEIK BCMA_EBB-C1978-A10 - nk
scFv domain 507 GAAGTGCAACTGGTGGAAACCGGTGGAGGACTCGTGTCAGCCTGGCGGCAGCCTCCGGCTGAGCTGCGCCGCTTCGGGATTCACCTTTTCCTCCTACGCGATGTCTTGGGTCAGACAGGCCCCCGGAAAGGGGCTGGAATGGGTGTCAGCCATCTCCGGCTCCGGGATCAACGTACTACGCCGACTCCGTGAAAGGCCGGTTCACCATGTCGCGCGAGA ATGACAAGAACTCCGTGTTCCTGCAAATGAACTCCCTGAGGGTGGAGGACACCGGAGTGTACTATTGTGTCGCGCGCCAACTACAAGAGAGAGCTGCGGTACTACTACGGAATGGACGTCTGGGGACAGGGAACTATGGTGACCGTGTCATCCGGTGGAGGGGAAGCGGCGGTGGAGGCAGCGGGGGCGGGGTTCAGAAATTGTCATGACCC AGTCCCCGGGAACTCTTTCCCTCTCCCCCGGGGAATCCGCGACTTTGTCCTGCCGGGCCAGCCAGCGCGTGGCCTCGAACTACCTCGCATGGTACCAGCATAAGCCAGGCCAAGCCCCTTCCCTGCTGATTTCCGGGGCTAGCAGCCGCGCCACTGGCGTGCCGGATAGGTTCTCGGGAAGCGGCTCGGGTACCGATTTCACCCTGGCAATCTCGCGGCTGGAACCG GAGGATTCGGCCGTGTACTACTGCCAGCACTATGACTCATCCCCCTCCTGGACATTCGGACAGGGCACCAAGGTCGAGATCAAG BCMA_EBB-C1978-A10 - ac
vh 508 EVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTMSRENDKNSVFLQMNSLRVEDTGVYYCARANYKRELRYYYGMDVWGQGTMVTVSS BCMA_EBB-C1978-A10 - ac
VL 509 EIVMTQSPGTLSLSPGESATLSCRASQRVASNYLAWYQHKPGQAPSLLISGASSRATGVPDRFSGSGSGTDFTLAISRLEPEDSAVYCQHYDSSPSWTFGQGTKVEIK BCMA_EBB-C1978-D4 BCMA_EBB-C1978-D4 - ak
scFv domain 510 EVQLLETGGGLVQPGGSLRLSCAASGFSFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKALVGATGAFDIWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSLSSNFLAWYQQKPGQAPGLLIYGASNWATGTPDR FSGSGSGTDFTLTITRLEPEDFAVYYCQYYGTSPMYTFGQGTKVEIK BCMA_EBB-C1978-D4 - nk
scFv domain 511 GAAGTGCAGCTGCTCGAAACCGGTGGAGGCTGGTGCAGCCAGGGGCTCCCTGAGGCTTTCATGCGCCGCTAGCGGATTCTCCTTCTCCTCTTACGCCATGTCGTGGGTCCGCCAAGCCCCTGGAAAAGGCCTGGAATGGGTGTCCGCGATTTCCGGGAGCGGAGGTTCGACCTATTACGCCGACTCCGTGAAGGGCCGCTTTACCATCTCCCGGG ATAACTCCAAGAACACTCTGTACCTCCAAATGAACTCGCTGAGAGCCGAGGACACCGCCGTGTATTACTGCGCGAAGGCGCTGGTCGGCGCGACTGGGCATTCGACATCTGGGGACAGGGAACTCTTGTGACCGTGTCGAGCGGAGGCGGCGGCTCCGGCGGAGGAGGGAGCGGGGGCGGTGGTTCCGAAATCGTGTTGACTCAGTCCCCGGGAACCCTGAG CTTGTCACCCGGGGAGCGGGCCACTCTCTCCTGTCGCGCCTCCCAATCGCTCTCATCCAATTTCCTGGCCTGGTACCAGCAGAAGCCCGGACAGGCCCCGGGCCTGCTCATCTACGGCGCTTCAAACTGGGCAACGGGAACCCCTGATCGGTTCAGCGGAAGCGGATCGGGTACTGACTTTACCCTGACCATCACCAGACTGGAACCGGAGACTTCGCCGTGTACT ACTGCCAGTACTACGGCACCTCCCCCATGTACACATTCGGACAGGGTACCAAGGTCGAGATTAAG BCMA_EBB-C1978-D4 - ak
vh 512 EVQLLETGGGLVQPGGSLRLSCAASGFSFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKALVGATGAFDIWGQGTLVTVSS BCMA_EBB-C1978-D4 - ak
VL 513 EIVLTQSPGTLSLSPGERATLSCRASQSLSSNFLAWYQQKPGQAPGLLIYGASNWATGTPDRFSGSGSGTDFTLTITRLEPEDFAVYYCQYYGTSPMYTFGQGTKVEIK BCMA_EBB-C1980-A2 BCMA_EBB-C1980-A2 - ac
scFv domain 514 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCVLWFGEGFDPWGQGTLVTVSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNR ASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVDIK BCMA_EBB-C1980-A2 - nk
scFv domain 515 GAAGTGCAGCTGCTTGAGAGCGGTGGAGGTCTGGTGCAGCCCGGGGGATCACTGCGCCTGTCCTGTGCCGCGTCCGGTTTCACTTTCTCCTCGTACGCCATGTCGTGGGTCAGACAGGCACCGGGAAAGGGACTGGAATGGGTGTCAGCCATTTCGGGTTCGGGGGGCAGCACCACTACTACGCTGACTCCGTGAAGGGCCGGTTCACCATT TCCCGCGACAACTCCAAGAACACCTTGTACCTCCAAATGAACTCCCTGCGGCCGAAGATACCGCCGTGTATTACTGCGTGTGCTGTGGTTCGGAGAGGGATTCGACCCGTGGGGACAAGGAACACTCGTGACTGTGTCATCCGGCGGAGGCGGCAGCGGTGGCGGCGGTTCCGGCGGCGGCGGATCTGACATCGTGTTGACCCAGTCCCCTCTGAGCCTGCCGGTC ACTCCTGGCGAACCAGCCAGCATCTCCTGCCGGTCGAGCCAGTCCCTCCTGCACTCCAATGGGTACAACTACCTCGATTGGTATCTGCAAAAGCCGGGCCAGAGCCCCCAGCTGCTGATCTACCTTGGGTCAAACCGCGCTTCCGGGGTGCCTGATAGATTTCTCCGGGTCCGGGAGCGGAACCGACTTTACCCTGGAAAATCTCGAGGGTGGAGGCCGAGGACGTCGGA GTGTACTACTGCATGCAGGCGCCTCCAGACTCCCCTGACCTTCGGAGGAGGAACGAAGGTCGACATCAAGA BCMA_EBB-C1980-A2 - ac
vh 516 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCVLWFGEGFDPWGQGTLVTVSS BCMA_EBB-C1980-A2 - ac
VL 517 DIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVDIK BCMA_EBB-C1981-C3 BCMA_EBB-C1981-C3 - ac
scFv domain 518 QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVGYDSSGYYRDYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAP RLLIYGTSSRATGISDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGNSPPKFTFGPGTKLEIK BCMA_EBB-C1981-C3 - nk
scFv domain 519 CAAGTGCAGCTCGTGGAGTCAGGCGGAGACTGGTGCAGCCCGGGGCTCCCTGAGACTTTCCTGCGCGGCATCGGGTTTTACCTTCTCCTCCTATGCTATGTCCTGGGTGCGCCAGGCCCCGGGAAAGGGACTGGAATGGGTGTCCGCAATCAGCGGTAGCGGGGGCTCAACATACTACGCCGACTCCGTCAAGGGTCGCTTCACTATTTCC CGGGACAACTCCAAGAATACCCTGTACCTCCAAATGAACAGCCTCAGGGCCGAGGATACTGCCGTGTACTGCGCCAAAAGTCGGATACGATAGCTCCGGTTACTACCGGGACTACTACGGAATGGACGTGTGGGGACAGGGCACCACCGTGACCGTGTCAAGCGGCGGAGGCGGTTCAGGAGGGGAGGCTCCGGCGGTGGAGGTCCGAAATCGTCCT GACTCAGTCGCCTGGCACTCTGTCGTTGTCCCCGGGGGAGCGCGCTACCCTGTCGTGTCGGGCGTCGCAGTCCGTGTCGAGCTCCTACCTCGCGTGTGTACCAGCAGAAGCCCGGACAGGCCCCTAGACTTCTGATCTACGGCACTTCTTCACGCGCCACCGGGATCAGCGACAGGTTCAGCGGCTCCGGCTCCGGGACCGACTTCACCCTGACCATTAGCCGGCTGGAGC CTGAAGATTTCGCCGTGTATTACTGCCAACACTACGGAAACTCGCCGCCAAAGTTCACGTTCGGACCCGGAACCAAGCTGGAAATCAAG BCMA_EBB-C1981-C3 - ac
vh 520 QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVGYDSSGYYRDYYGMDVWGQGTTVTVSS BCMA_EBB-C1981-C3 - ac
VL 521 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGTSSRATGISDRFSGSGSGTDFTLTISRLEPEDFAVYCQHYGNSPPKFTFGPGTKLEIK BCMA_EBB-C1978-G4 BCMA_EBB-C1978-G4 - ak
scFv domain 522 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKMGWSSGYLGAFDIWGQGTTVTVSSGGGGSGGGGSGGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVASSFLAWYQQKPGQAPRLLIYGASGRA TGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGGSPRLTFGGGTKVDIK BCMA_EBB-C1978-G4 - nk
scFv domain 523 GAAGTCCAACTGGTGGAGTCCGGGGGAGGGCTCGTGCAGCCCGGAGGCAGCCTTCGGCTGTCGTGCGCCGCCTCCGGGTTCACGTTCTCATCCTACGCGATGTCGTGGGTCAGACAGGCACCAGGAAAGGGACTGGAATGGGTGTCCGCCATTAGCGGCTCCGGCGGTAGCACCTACTATGCCGACTCAGTGAAGGGAAGGTTCACTATCTCC CGCGACAACAGCAAGAACACCCTGTACCTCCAAATGAACTCTCTGCGGGCCGAGGATACCGCGGTGTACTATTGCGCCAAGATGGGTTGGTCCAGCGGATACTTGGGAGCCTTCGACATTTGGGGACAGGGCACTACTGTGACCGTGTCCTCCGGGGGTGGCGGATCGGGAGGCGGCGGCTCGGGTGGAGGGGTTCCGAAATCGTGTTGAC CCAGTCACCGGGAACCCTCTCGCTGTCCCCGGGAGAACGGGCTACACTGTCATGTAGAGCGTCCCAGTCCGTGGCTTCCTCGTTCCTGGCCTGGTACCAGCAGAAGCCGGGACAGGCACCCCGCCTGCTCATCTACGGAGCCAGCGGCCGGGCGACCGGCATCCCTGACCGCTTCTCCGGTTCCGGCTCGGGCACCGACTTTACTCTGACCATTAGCAGGCTTGAGC CCGAGGATTTTGCCGTGTACTACTGCCAACACTACGGGGGAGCCCTCGCCTGACCTTCGGAGGCGGAACTAAGGTCGATATCAAAA BCMA_EBB-C1978-G4 - ak
vh 524 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKMGWSSGYLGAFDIWGQGTTVTVSS BCMA_EBB-C1978-G4 - ak
VL 525 EIVLTQSPGTLSLSPGERATLSCRASQSVASSFLAWYQQKPGQAPRLLIYGASGRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYCQHYGGSPRLTTFGGGTKVDIK

In some embodiments, additional exemplary CAR constructs are generated using the VH and VL sequences from PCT publication WO2012/0163805 (the contents of which are incorporated herein by reference in their entirety). In some embodiments, additional exemplary CAR constructs are generated using the VH and VL sequences from PCT publication WO2016/014565 (the contents of which are incorporated herein by reference in their entirety). In some embodiments, additional exemplary CAR constructs are generated using the VH and VL sequences from PCT publication WO2014/122144 (the contents of which are incorporated herein by reference in their entirety). In some embodiments, additional exemplary CAR constructs are generated using the CAR and/or VH and VL molecular sequences from PCT Publication WO2016/014789 (the contents of which are incorporated herein by reference in their entirety). In some embodiments, additional exemplary CAR constructs are generated using the CAR and/or VH and VL molecular sequences from PCT Publication WO2014/089335 (the contents of which are incorporated herein by reference in their entirety). In some embodiments, additional exemplary CAR constructs are generated using the CAR and/or VH and VL molecular sequences from PCT Publication WO2014/140248 (the contents of which are incorporated herein by reference in their entirety).

In some embodiments, additional exemplary CAR constructs can also be generated using the VH and VL sequences shown in Table 12. Amino acid sequences of exemplary scFv domains containing VH and VL domains, as well as linker and full length CAR sequences are also shown in Table 12.

Table 12 . Additional exemplary binding domain sequences for BCMA

Name Subsequence SEQID NO: A7D12.2
vh QIQLVQSGPDLKKPGETVKLSCKASGYTFFTNFGMNWVKQAPGKGFKWMAWINTYTGESYFADDFKGRFAFSVETSATTAYLQINNLKTEDTATYFCARGEIYYGYDGGFAYWGQGTLVTVSA 526 A7D12.2
VL DVVMTQSHRFMSTSVGDRVSITCRASQDVNTAVSWYQQKPGQSPKLLIFSASYRYTGVPDRFTGSGSGADFTLTISSVQAEDLAVYYCQQHYSTPWTFGGGTKLDIK 527 A7D12.2
scFv domain QIQLVQSGPDLKKPGETVKLSCKASGYTFFTNFGMNWVKQAPGKGFKWMAWINTYTGESYFADDFKGRFAFSVETSATTAYLQINNLKTEDTATYFCARGEIYYGYDGGFAYWGQGTLVTVSAGGGGSGGGGGSGGGGSDVVMTQSHRFMSTSVGDRVSITCRASQDVNTAVSWYQQKPGQSP KLLIFSASYRYTGVPDRFTGSGSGADFTLTISSVQAEDLAVYYCQQHYSTPWTFGGGTKLDIK 528 C11D5.3
vh QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS 529 C11D5.3
VL DIVLTQSPASLAMSLGKRATISCRASESVSVIGAHLIHWYQQKPGQPPKLLIYLASNLETGVPARFSGSGSGTDFTLTIDPVEEDDVAIYSCLQSRIFPRTFGGGTKLEIK 530 C11D5.3
scFv domain QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPA YAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS 531 C12A3.2
vh QIQLVQSGPELKKPGETVKISCKASGYTFRHYSMNWVKQAPGKGLKWMGRINTESGVPIYADDFKGRFAFSVETSASTAYLVINNLKDEDTASYFCSNDYLYSLDFWGQGTALTVSS 532 C12A3.2
VL DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIYWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK 533 C12A3.2
scFv domain QIQLVQSGPELKKPGETVKISCKASGYTFRHYSMNWVKQAPGKGLKWMGRINTESGVPIYADDFKGRFAFSVETSASTAYLVINNLKDEDTASYFCSNDYLYSLDFWGQGTALTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIYWYQQKPGQPPTLLIQLASNVQ TGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK 534 C13F12.1
vh QIQLVQSGPELKKPGETVKISCKASGYTFTHYSMNWVKQAPGKGLKWMGRINTETGEPLYADDFKGRFAFSLETSASTAYLVINNLKNEDTATFFCSNDYLYSCDYWGQGTTLTVSS 535 C13F12.1
VL DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIYWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK 536 C13F12.1
scFv domain QIQLVQSGPELKKPGETVKISCKASGYTFTHYSMNWVKQAPGKGLKWMGRINTETGEPLYADDFKGRFAFSLETSASTAYLVINNLKNEDTATFFCSNDYLYSCDYWGQGTTLTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIYWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK 537

The sequences of the human scFv CDR domains are shown in Table 13 for the heavy chain variable domains and in Table 14 for the light chain variable domains. "ID" means the corresponding SEQ ID NO for each CDR. The CDRs are given according to the Kabat system, but CDRs corresponding to another numbering system, such as Chothia or the combined Kabat/Chothia system, can easily be derived from the VH and VL sequences above.

Table 13 Heavy chain variable domain CDR regions according to the Kabat numbering system (Kabat et al. (1991), "Sequences of Proteins of Immunological Interest", 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD)

Candidate HCDR1 ID HCDR2 ID HDDR3 ID 139109 NHGMS 538 GIVYSGSTYYAASVKG 539 HGGESDV 540 139103 NYAMS 541 GISRSGENTYYADSVKG 542 SPAHYYGGMDV 543 139105 DYAMH 544 GISWNSGSIGYADSVKG 545 HSFLAY 546 139111 NHGMS 538 GIVYSGSTYYAASVKG 539 HGGESDV 540 139100 NFGIN 547 WINPKNNNTNYAQKFQG 548 GPYYYQSYMDV 549 139101 SDAMT 550 VISGSGGTTYYADSVKG 551 LDSSGYYYARGPRY 552 139102 NYGIT 553 WISAYNGNTNYAQKFQG 554 GPYYYYMDV 555 139104 NHGMS 538 GIVYSGSTYYAASVKG 539 HGGESDV 540 139106 NHGMS 538 GIVYSGSTYYAASVKG 539 HGGESDV 540 139107 NHGMS 538 GIVYSGSTYYAASVKG 539 HGGESDV 540 139108 DYYMS 556 YISSGSTIYYADSVKG 557 ESGDGMDV 558 139110 DYYMS 556 YISSSGNTIYYADSVKG 559 STMVREDY 560 139112 NHGMS 538 GIVYSGSTYYAASVKG 539 HGGESDV 540 139113 NHGMS 538 GIVYSGSTYYAASVKG 539 HGGESDV 540 139114 NHGMS 538 GIVYSGSTYYAASVKG 539 HGGESDV 540 149362 SSYYYWG 561 SIYYSGSAYYNPSLKS 562 HWQEWPDAFDI 563 149363 TSGMCVS 564 RIDWDEDKFYSTSLKT 565 SGAGGTSATAFDI 566 149364 SYSMN 567 SISSSSSYIYYADSVKG 568 TIAAVYAFDI 569 149365 DYYMS 556 YISSGSTIYYADSVKG 557 DLRGAFDI 570 149366 SHYIH 571 MINPSGGVTAYSQTLQG 572 EGSGSGWYFDF 573 149367 SGGYYWS 574 YIYYSGSTYYNPSLKS 575 AGIAARLRGAFDI 576 149368 SYAIS 577 GIIPIFGTANYAQKFQG 578 RGGYQLLRWDVGLLRSAFDI 579 149369 SNSAAWN 580 RTYYRSKWYSFYAISLKS 581 SSPEGLFLYWFDP 582 BCMA_EBB-C1978-A4 SYAMS 583 AISGSGGSTYYADSVKG 584 VEGSGSLDY 585 BCMA_EBB-C1978-G1 RYPMS 586 GISDSGVSTYYADSAKG 587 RAGSEASDI 588 BCMA_EBB-C1979-C1 SYAMS 583 AISGSGGSTYYADSVKG 584 ATYKRELRYYYGMDV 589 BCMA_EBB-C1978-C7 SYAMS 583 AISGSGGSTYYADSVKG 584 ATYKRELRYYYGMDV 589 BCMA_EBB-C1978-D10 DYAMH 544 GISWNSGSIGYADSVKG 545 VGKAVPDV 590 BCMA_EBB-C1979-C12 DYAMH 544 SINWKGNSLAYGDSVKG 591 HQGVAYYNYAMDV 592 BCMA_EBB-C1980-G4 SYAMS 583 AISGSGGSTYYADSVKG 584 VVRDGMDV 593 BCMA_EBB-C1980-D2 SYAMS 583 AISGSGGSTYYADSVKG 584 IPQTGTFDY 594 BCMA_EBB-C1978-A10 SYAMS 583 AISGSGGSTYYADSVKG 584 ANYKRELRYYYGMDV 595 BCMA_EBB-C1978-D4 SYAMS 583 AISGSGGSTYYADSVKG 584 ALVGATGAFDI 596 BCMA_EBB-C1980-A2 SYAMS 583 AISGSGGSTYYADSVKG 584 WFGEGFDP 597 BCMA_EBB-C1981-C3 SYAMS 583 AISGSGGSTYYADSVKG 584 VGYDSSGYYRDYYGMDV 598 BCMA_EBB-C1978-G4 SYAMS 583 AISGSGGSTYYADSVKG 584 MGWSSGYLGAFDI 599 A7D12.2 NFGMN 600 WINTYTGESYFADDFKG 601 GEIYYGYDGGFAY 602 C11D5.3 DYSIN 603 WINTETREPAYAYDFRG 604 DYSYAMDY 605 C12A3.2 HYSMN 606 RINTESGVPIYADDFKG 607 DYLYSLDF 608 C13F12.1 HYSMN 606 RINTEGEPLYADDFKG 609 DYLYSCDY 610

Table 14 Light chain variable CDR regions according to Kabat numbering system (Kabat et al. (1991), "Sequences of Proteins of Immunological Interest", 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD)

Candidate LCDR1 ID LCDR2 ID LCDR3 ID 139109 RASQSISSYLN 611 AASSLQS 612 QQSYSTPYT 613 139103 RASQSISSSFLA 614 GASRRAT 615 QQYHSSPSWT 616 139105 RSSQSLLHSNGYNYLD 617 LGSNRAS 618 MQALQTPYT 619 139111 KSSQSLLRNDGKTPLY 620 EVSNRFS 621 MQNIQFPS 622 139100 RSSQSLLHSNGYNYLN 623 LGSKRAS 624 MQALQTPYT 619 139101 RASQSISSYLN 611 GASTLAS 625 QQSYKRAS 626 139102 RSSQSLLYSNGYNYVD 627 LGSNRAS 618 MQGRQFPYS 628 139104 RASQSVSSNLA 629 GASTRAS 630 QQYGSSLT 631 139106 RASQSVSSKLA 632 GASIRAT 636 QQYGSSSWT 637 139107 RASQSVGSTNLA 638 DASNRAT 639 QQYGSPPWT 640 139108 RASQSISSYLN 611 AASSLQS 612 QQSYTLA 641 139110 KSSELVHNSGKTYLN 642 EVSNRDS 643 MQGTHWPGT 644 139112 QASEDINKFLN 645 DASTLQT 646 QQYESLPLT 647 139113 RASQSVGSNLA 648 GASTRAT 649 QQYNDWLPVT 650 139114 RASQSIGSSSLA 651 GASSRAS 652 QQYAGSPPPFT 653 149362 KASQDIDDAMN 654 SATSPVP 655 LQHDNFPLT 656 149363 RASQDIYNNLA 657 AANKSQS 658 QHYYRFPYS 659 149364 RSSQSLLHSNGYNYLD 617 LGSNRAS 618 MQALQTPYT 619 149365 GGNNGTKSVH 660 DDSVRPS 661 QVWDSDSEHVV 662 149366 SGDGLSKKYVS 663 RDKERPS 664 QAWDDDTTVV 665 149367 RASQGIRNWLA 666 AASNLQS 667 QKYNSAPFT 668 149368 GGNNIGSKSVH 669 GKNNRPS 670 SSRDSSGDHLRV 671 149369 QGDSLGNYYAT 672 GTNNRPS 673 NSRDSSGHHL 674 BCMA_EBB-C1978-A4 RASQSVSSAYLA 675 GASTRAT 649 QHYGSSFNGSSLFT 676 BCMA_EBB-C1978-G1 RASQSVSNSLA 677 DASSRAT 678 QQFGTSSGLT 679 BCMA_EBB-C1979-C1 RASQSVSSSFLA 680 GASSRAT 681 QQYHSSPSWT 616 BCMA_EBB-C1978-C7 RASQSVSTTFLA 682 GSSNRAT 683 QQYHSSPSWT 616 BCMA_EBB-C1978-D10 RASQSISSYLN 611 AASSLQS 612 QQSYSTPYS 684 BCMA_EBB-C1979-C12 RATQSIGSSFLA 685 GASQRAT 686 QHYESSPSWT 687 BCMA_EBB-C1980-G4 RASQSVSSSYLA 688 GASSRAT 681 QQYGSPPRFT 689 BCMA_EBB-C1980-D2 RASQSVSSSYLA 688 GASSRAT 681 QHYGSSPSWT 690 BCMA_EBB-C1978-A10 RASQRVASNYLA 691 GASSRAT 681 QHYDSSPSWT 692 BCMA_EBB-C1978-D4 RASQSLSSNFLA 693 GASNWAT 694 QYYGTSPMYT 695 BCMA_EBB-C1980-A2 RSSQSLLHSNGYNYLD 617 LGSNRAS 618 MQALQTPLT 696 BCMA_EBB-C1981-C3 RASQSVSSSYLA 688 GTSSRAT 697 QHYGNSPPKFT 698 BCMA_EBB-C1978-G4 RASQSVASSFL 699 GASGRAT 700 QHYGGSPRLT 701 A7D12.2 RASQDVNTAVS 702 SASYRYT 703 QQHYSTPWT 704 C11D5.3 RASESVSVIGAHLIH 705 LASNLET 706 LQSRIFPRT 707 C12A3.2 RASESVTILGSHLIY 708 LASNVQT 709 LQSRTIPRT 710 C13F12.1 RASESVTILGSHLIY 708 LASNVQT 709 LQSRTIPRT 710

In one embodiment, the BCMA binding domain comprises one or more (e.g., all three) of Light Chain Complementarity Determining Region 1 (LC CDR1), Light Chain Complementarity Determining Region 2 (LC CDR2), and Light Chain Complementarity Determining Region 3 (LC CDR3). ) a BCMA binding domain as described herein, such as those listed in Table 11, 12, or 14, and/or one or more (e.g., all three) of the Heavy Chain Complementarity Determining Region 1 (HC CDR1), Complementarity Determining Region 2 heavy chain (HC CDR2) and complementarity determining region 3 of the heavy chain (HC CDR3) of the BCMA binding domain described herein, for example, are shown in Table 11, 12 or 13. In one embodiment, the BCMA binding domain contains one, two or all of LC CDR1, LC CDR2 and LC CDR3 with any of the amino acid sequences shown in Table 11, the contents of which are incorporated herein by reference; and one, two or all of HC CDR1, HC CDR2 and HC CDR3 with any of the amino acid sequences shown in Table 11.

In one embodiment, the BCMA binding domain comprises a light chain variable region as described herein (eg, in Table 11 or 12) and/or a heavy chain variable region as described herein (eg, in Table 11 or 12). In one embodiment, the BCMA binding domain is an scFv containing a light chain and a heavy chain with the amino acid sequences shown in Table 11 or 12. In one embodiment, the BCMA binding domain (e.g., scFv) contains: a light chain variable region containing an amino acid sequence having at least one, two or three modifications (e.g. substitutions, e.g. conservative substitutions), but not more than 30, 20 or 10 modifications (e.g. substitutions, e.g. conservative substitutions) of the light chain variable region amino acid sequence, shown in Table 11 or 12, or a sequence having 95-99% identity with the amino acid sequence shown in Table 11 or 12; and/or a heavy chain variable region containing an amino acid sequence having at least one, two, or three modifications (e.g., substitutions, e.g., conservative substitutions), but no more than 30, 20, or 10 modifications (e.g., substitutions, substitutions) the amino acid sequence of the heavy chain variable region shown in Table 11 or 12, or a sequence having 95-99% identity with the amino acid sequence shown in Table 11 or 12.

In one embodiment, the BCMA binding domain contains an amino acid sequence selected from any of SEQ ID NOs: 382, 386, 390, 394, 398, 402, 406, 410, 414, 418, 422, 426, 430, 434, 438, 442, 446, 450, 454, 458, 462, 466, 470, 474, 478, 482, 486, 490, 494, 498, 502, 506, 510, 514, 518, 522, 528, 531, 534 or 5 37; or an amino acid sequence having at least one, two, or three modifications (eg, substitutions, eg, conservative substitutions), but not more than 30, 20, or 10 modifications (eg, substitutions, eg, conservative substitutions) in any of the above sequences; or a sequence having 95-99% identity with any of the above sequences. In one embodiment, the BCMA binding domain is scFv and a light chain variable region containing the amino acid sequence described herein, such as in Table 11 or 12, is linked to a heavy chain variable region containing the amino acid sequence described herein. , for example, in Table 11 or 12, through a linker, for example, the linker described in this document. In one embodiment, the BCMA binding domain includes a (Gly4-Ser)n linker, where n is 1, 2, 3, 4, 5, or 6, preferably 4 (SEQ ID NO: 967). The light chain variable region and the heavy chain variable region in the scFv can be, for example, in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region.

Any known CAR, for example, the BMCA antigen-binding domain of any CAR known in the art, can be used in the present invention to construct a CAR. For example, those described in this document.

In one embodiment, the antigen-binding domain for ROR1 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Hudecek et al., Clin Cancer Res 19(12):3153-3164 (2013); WO2011159847 and US20130101607.

In one embodiment, the antigen-binding domain for CD22 is an antigen-binding fragment, eg, CDR regions, of an antibody as described in, eg, Haso et al., Blood, 121(7): 1165-1174 (2013); Wayne et al., Clin Cancer Res 16(6): 1894-1903 (2010); Kato et al., Leuk Res 37(1):83-88 (2013); Creative BioMart (creativebiomart.net): MOM-18047-S(P).

In one embodiment, the antigen-binding domain for CD20 is an antigen-binding fragment, for example, CDR regions, rituximab, ofatumumab, ocrelizumab, veltuzumab, or GA101 antibodies, or derivatives thereof. In one embodiment, the antigen-binding domain for CD20 is the antigen-binding fragment described in WO2016/164731, the contents of which are incorporated herein by reference in their entirety.

In one embodiment, the antigen binding domain comprises one, two, three (e.g., all three) of the heavy chain CDR regions, HC CDR1, HC CDR2, and HC CDR3, from the antibody listed above, and/or one, two, three (e.g., all three) from the light chain CDR regions, LC CDR1, LC CDR2 and LC CDR3, from the tumor antigen binding antibody listed above. In one embodiment, the antigen-binding domain comprises a heavy chain variable region and/or a light chain variable region of an antibody that binds a tumor antigen listed above.

In one embodiment, the antigen-binding domain of the CAR described herein is a scFv antibody fragment. In one aspect, such an antibody fragment is functional in that it retains an equivalent binding affinity, eg, it binds the same antigen with comparable potency as the IgG antibody from which it is derived. In other embodiments, an antibody fragment has a lower binding affinity, e.g., it binds the same antigen with a lower binding affinity than the antibody from which it is derived, but is functional in that it provides the biological response described herein. In one embodiment, the CAR molecule contains an antibody fragment that has a K _D binding affinity of 10 ^-4 M to 10 ^-8 M, such as 10 ^-5 M to 10 ^-7 M, such as 10 ^-6 M or 10 ^-7 M, for the target antigen. In one embodiment, an antibody fragment has a binding affinity that is at least five times, 10 times, 20 times, 30 times, 50 times, 100 times, or 1000 times less than a reference antibody, e.g., the antibody described herein. .

In one embodiment, the antigen binding domain comprises a non-human antibody or antibody fragment, such as a mouse antibody or antibody fragment.

In another embodiment, the antigen binding domain comprises a humanized antibody or antibody fragment. In some aspects, a non-human antibody is humanized, with specific sequences or regions of the antibody modified to more closely resemble an antibody naturally produced in the human body, or a fragment thereof. In one aspect, the antigen binding domain is humanized relative to the sequence of the mouse antibody or antibody fragment, eg scFv, from which it is derived.

The humanized antibody can be obtained by various methods known in the art, including, but not limited to, CDR grafting (see, for example, European Patent No. EP 239400; International Patent Publication No. WO91/09967 and US Patent Nos. the contents of each of the documents are incorporated herein by reference in their entirety), veneering or surface modification (see, for example, European Patent Nos. EP 592106 and EP 519596; Padlan, 1991, Molecular Immunology, 28(4/5):489- 498; Studnicka et al., 1994, Protein Engineering, 7(6):805-814; and Roguska et al., 1994, PNAS, 91:969-973, the contents of each of which are incorporated herein by reference in their entirety. ), strand shuffling (see, for example, US Pat. No. 5,565,332, the contents of which are incorporated herein by reference in its entirety), as well as methods disclosed, for example, in US Patent Application Publication No. US2005/0042664, US Patent Application Publication No. US2005/0048617, US Patent No. 6407213, US Patent No. 5766886, International Patent Publication No. WO9317105, Tan et al., J. Immunol., 169:1119-25 (2002), Caldas et al., Protein Eng., 13( 5):353-60 (2000), Morea et al., Methods, 20(3):267-79 (2000), Baca et al., J. Biol. Chem., 272(16):10678-84 (1997), Roguska et al., Protein Eng., 9(10):895-904 (1996), Couto et al., Cancer Res., 55 (23 Supp) :5973s-5977s (1995), Couto et al., Cancer Res., 55(8):1717-22 (1995), Sandhu JS, Gene, 150(2):409-10 (1994) and Pedersen et al. , J. Mol. Biol., 235(3):959-73 (1994), the contents of each of the documents are incorporated herein by reference in their entirety. Often, framework residues in framework regions are replaced with corresponding residues from the CDR donor antibody to alter, eg, improve, antigen binding. Such substitutional framework residues are determined by methods well known in the art, for example, by modeling interactions between CDRs and framework residues to identify framework residues important for antigen binding and sequence comparisons to identify unusual framework residues at specific positions. (See, for example, Queen et al., US patent No. 5585089; and Riechmann et al., 1988, Nature, 332:323, the contents of these documents are incorporated herein by reference in their entirety).

A humanized antibody or antibody fragment has one or more amino acid residues retained therein from a non-human source. Such non-human amino acid residues are often referred to as "imported" residues, which are typically derived from an "imported" variable domain. As described herein, humanized antibodies or antibody fragments comprise one or more CDRs of non-human immunoglobulin molecules and framework regions in which the framework amino acid residues are derived wholly or primarily from human germline sequences. Various methods for humanizing antibodies or antibody fragments are well known in the art and can generally be carried out by the method described by Winter et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by replacing CDR regions or rodent CDR sequences with corresponding human antibody sequences, i.e., by CDR grafting (EP 239400; PCT WO91/09967 and US Pat. Nos. 4,816,567; 6,331,415; 5,225,539; 5,530,101; In such humanized antibodies and antibody fragments, substantially less than the entire variable domain of a human antibody is replaced by a corresponding sequence from a non-human species. Humanized antibodies are often human antibodies in which some CDR residues and possibly some framework (FR) residues are replaced by residues from similar regions in rodent antibodies. Humanization of antibodies and antibody fragments can also be accomplished by veneering or surface modification (EP 592106; EP 519596; Padlan, 1991, Molecular Immunology, 28(4/5):489-498; Studnicka et al., Protein Engineering, 7(6) :805-814 (1994); and Roguska et al., PNAS, 91:969-973 (1994)), or chain shuffling (US Pat. No. 5,565,332), the contents of these documents are incorporated herein by reference in their entirety.

The choice of human variable domains, both light and heavy chain, used to obtain humanized antibodies, aimed at reducing antigenicity. In the so-called "best fit" method, the variable domain sequence of a rodent antibody is screened against a complete library of known human variable domain sequences. The human sequence that is closest to the rodent sequence is then selected as the human framework (FR) sequence for the humanized antibody (Sims et al., J. Immunol., 151:2296 (1993); Chothia et al., J. Mol. Biol., 196:901 (1987), the contents of these documents are incorporated herein by reference in their entirety). Another method uses a specific framework sequence derived from the consensus sequence of all human antibodies with a specific subgroup of light or heavy chains. The same framework can be used for several different humanized antibodies (see, for example, Nicholson et al. Mol. Immun. 34 (16-17): 1157-1165 (1997); Carter et al., Proc. Natl. Acad. Sci USA, 89:4285 (1992), Presta et al., J. Immunol., 151:2623 (1993, the contents of these documents are incorporated herein by reference in their entirety). In some embodiments, the framework region, eg all four framework regions, of the heavy chain variable region is derived from the VH4_4-59 germline sequence. In one embodiment, the framework region may have one, two, three, four, or five modifications, such as substitutions, such as an amino acid from the corresponding mouse sequence. In one embodiment, the framework, for example, all four variable light chain frameworks are derived from the VK3_1.25 germline sequence. In one embodiment, the framework region may have one, two, three, four, or five modifications, such as substitutions, such as an amino acid from the corresponding mouse sequence.

In some aspects, the CAR antibody fragment is humanized, retaining high affinity for the target antigen and other favorable biological properties. In one aspect of the invention, humanized antibodies and antibody fragments are generated by analysis of parental sequences and various conceptual humanized products using 3D models of parental and humanized sequences. Three-dimensional immunoglobulin models are readily available and familiar to those skilled in the art. Computer programs are available illustrating and demonstrating possible three-dimensional conformational structures of selected candidate immunoglobulin sequences. The study of such images allows one to analyze the likely role of the residues in the functioning of the candidate immunoglobulin sequence, for example, to analyze residues that affect the ability of the candidate immunoglobulin to bind the target antigen. As a result, FR residues can be selected and combined with recipient and imported sequences such that the desired characteristic of an antibody or antibody fragment, such as increased affinity for the target antigen, is achieved. As a rule, CDR residues directly and most significantly affect antigen binding.

A humanized antibody or antibody fragment may retain antigenic specificity similar to that of the parent antibody, for example, in the present invention, the ability to bind the human tumor antigen described herein. In some embodiments, a humanized antibody or antibody fragment may have increased affinity and/or binding specificity for the tumor antigen described herein. In some embodiments, a humanized antibody or antibody fragment may have lower binding affinity and/or specificity for the tumor antigen described herein or the B cell antigen described herein.

In one aspect, the antigen-binding domain of the invention is characterized by specific functionalities, or properties, of an antibody or antibody fragment. For example, in one aspect, a CAR fragment of the invention containing an antigen-binding domain specifically binds a tumor antigen as described herein.

In one aspect, the antigen binding domain is a fragment, for example, a single chain variable fragment (scFv). In one aspect, the tumor antigen binding domain described herein is a Fv, Fab, (Fab') ₂ or bifunctional (e.g., bispecific) hybrid antibody (e.g., Lanzavecchia et al., Eur. J. Immunol. 17, 105 (1987)). In one aspect, the antibodies and fragments thereof of the invention bind the tumor antigen protein described herein with the affinity of the wild-type antibody or increased affinity.

In some cases, scFv fragments can be generated in a manner known in the art (see, for example, Bird et al., (1988) Science 242:423-426 and Huston et al., (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). ScFv molecules can be generated by linking the VH and VL regions with flexible polypeptide linkers. The scFv molecules contain a linker (eg, Ser-Gly linker) with an optimized length and/or amino acid composition. Linker length can greatly influence the folding and interaction of scFv variable regions. In fact, if a short polypeptide linker (eg, 5-10 amino acids long) is used, intrachain folding is prevented. Interchain folding is also required to bring the two variable regions together to form a functional epitope binding site. For examples of linker orientations and sizes, see, for example, Hollinger et al. 1993 Proc Natl Acad. sci. USA 90:6444-6448, US Patent Application Publication Nos. 2005/0100543, 2005/0175606, 2007/0014794, and PCT Publication Nos. WO2006/020258 and WO2007/024715, the contents of which are incorporated herein by reference.

The scFv fragment may contain a linker length of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25 , 30, 35, 40, 45, 50 or more amino acid residues between its VL and VH regions. The linker sequence may contain any naturally occurring amino acid. In some embodiments, the linker sequence contains the amino acids glycine and serine. In another embodiment, the linker sequence contains a repeat set of glycine and serine residues, such as (Gly ₄ Ser)n, where n is a positive integer equal to or greater than 1 (SEQ ID NO: 22). In one embodiment, the linker may be (Gly ₄ Ser) ₄ (SEQ ID NO: 29) or (Gly ₄ Ser) ₃ (SEQ ID NO: 30). Varying the length of the linker can help maintain or increase activity, resulting in maximum performance in activity assays.

In another aspect, the antigen binding domain is a T cell receptor (“TCR”), a recombinant TCR, or a fragment thereof, such as a single chain TCR (scTCR). Methods for producing such TCRs are known in the art. See, for example, Willemsen RA et al., Gene Therapy 7: 1369-1377 (2000); Zhang T et al., Cancer Gene Ther 11: 487-496 (2004); Aggen et al., Gene Ther. 19(4):365-74 (2012) (literature references incorporated herein by reference). For example, an scTCR can be constructed that contains the Vα and Vβ gene products from a T cell clone linked by a linker (eg, a flexible peptide). This approach is very useful in the case of a cancer-associated target antigen that itself is intracellular, however, a fragment of such an antigen (peptide) is presented on the surface of cancer cells in the context of MHC.

In one aspect, a CAR antigen-binding domain comprises an amino acid sequence that is homologous to the amino acid sequence of an antigen-binding domain described herein, and the antigen-binding domain retains the desired functionality of the antigen-binding domain described herein.

In one specific aspect, the CAR of the invention comprises an antibody fragment. In the following aspect, the antibody fragment contains scFv. In a further aspect, the antibody fragment contains only the heavy chain variable domain (VH).

In various aspects, a CAR antigen-binding domain is constructed by modifying one or more amino acids in one or both variable regions (e.g., VH and/or VL), for example, in one or more CDRs and/or one or more framework regions. In one specific aspect, the CAR of the invention comprises an antibody fragment. In the following aspect, the antibody fragment contains scFv.

Those skilled in the art will appreciate that an antibody or antibody fragment of the invention may be further modified such that it may differ in amino acid sequence (eg, from wild type) but not in the desired activity. For example, in the case of such a protein, additional nucleotide substitutions can be made resulting in amino acid substitutions of "non-essential" amino acid residues. For example, a non-essential amino acid residue in a molecule can be replaced by another amino acid residue from the same family of residues with similar side chains. In another embodiment, an amino acid sequence may be replaced with a structurally similar sequence that differs in the order and/or composition of members of a family of residues with similar side chains, for example, a conservative substitution may be made in which an amino acid residue is replaced with an amino acid residue with a similar side chain.

Families of amino acid residues with similar side chains are known in the art, including residue families with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine , asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (eg, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (eg, threonine, valine, isoleucine), and aromatic side chains (eg tyrosine, phenylalanine, tryptophan, histidine).

The term "percent identity" in the context of two or more nucleotide or polypeptide sequences refers to two or more sequences that are the same. Two sequences are "substantially identical" if two sequences share a certain percentage of amino acid residues, or nucleotides, that are the same (e.g., 60% identity, optionally 70%, 71%, 72%, 73%, 74%, 75 %, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identical over a specific area or, if not specified, over the entire sequence) when compared and aligned for maximum match in the comparison window, or a defined area as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, identity exists over a region that is at least about 50 nucleotides (or 10 amino acids) or more in length, preferably over a region that is 100-500 or 1000 or more nucleotides (or 20, 50, 200 or more amino acids).

When comparing sequences, as a rule, one sequence acts as a reference sequence against which the tested sequences are compared. When using the sequence comparison algorithm, information about the tested and reference sequences is entered into the computer, the coordinates of the subsequences are determined, if necessary, and the parameters of the sequence comparison algorithm program are determined. You can use the program's default settings, or you can set alternative settings. The sequence comparison algorithm then calculates the percent sequence identity for the test sequences relative to the reference sequence, based on the program parameters. Methods for aligning sequences for comparison purposes are well known in the art. Optimal sequence alignment for comparison purposes can be achieved, for example, using the local homology algorithm of Smith-Waterman (1970) Adv. Appl. Math. 2:482c, using the Needleman-Wunsch homology region alignment algorithm, (1970) J. Mol. Biol. 48:443, Pearson-Lipman similarity search, (1988) Proc. Nat'l. Acad. sci. USA 85:2444, by computerized implementation of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by manual alignment and visual inspection (see , for example, Brent et al. , (2003) Current Protocols in Molecular Biology).

Two examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. , (1977) Nuc. Acids Res. 25:3389-3402; and Altschul et al. , (1990) J. Mol. Biol. 215:403-410, respectively. The program for performing BLAST analyzes is publicly available through the National Center for Biotechnology Information.

The percent identity of two amino acid sequences can also be determined using the Myers-Miller algorithm, (1988) Comput. Appl. biosci. 4:11-17) that is included in the ALIGN program (version 2.0) using the PAM120 residue substitution weight table, a deletion extension penalty of 12, and a deletion insertion penalty of 4. In addition, the percent identity of two amino acid sequences can be determined using the algorithm Needleman-Wunsch (1970) J. Mol. Biol. 48:444-453), which is included in the GAP program in the GCG software package (available on the Internet at gcg.com), using either the Blossom 62 matrix or the PAM250 matrix, deletion penalty 16, 14, 12, 10, 8, 6, or 4 and a deletion extension penalty of 1, 2, 3, 4, 5, or 6.

In one aspect of the present invention, amino acid sequence modifications of the parent antibody or fragment (eg, scFv) are contemplated that result in functionally equivalent molecules. For example, the VH or VL of the antigen-binding domain for a tumor antigen described herein, e.g., scFv contained in a CAR, can be modified to conserve at least about 70%, 71%, 72%, 73%, 74%, 75% , 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92 %, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity with the original VH or VL framework region of the antigen binding domain for the tumor antigen described herein, eg scFv. The present invention contemplates modifications to the entire CAR construct, such as modifications to one or more amino acid sequences of the various domains of the CAR construct, to create functionally equivalent molecules. The CAR construct may be modified to conserve at least about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity with the original CAR construct.

Bispecific CARs

In one embodiment, the multispecific antibody molecule is a bispecific antibody molecule. A bispecific antibody has specificity for no more than two antigens. A bispecific antibody molecule has a first immunoglobulin variable domain sequence with binding specificity for a first epitope and a second immunoglobulin variable domain sequence with binding specificity for a second epitope. In one embodiment, the first and second epitopes are on the same antigen, eg, the same protein (or subunit of a multimeric protein). In one embodiment, the first and second epitopes overlap. In one embodiment, the first and second epitopes do not overlap. In one embodiment, the first and second epitopes are on different antigens, such as different proteins (or different subunits of a multimeric protein). In one embodiment, the bispecific antibody molecule comprises a heavy chain variable domain sequence and a light chain variable domain sequence that have a binding specificity for a first epitope, and a heavy chain variable domain sequence and a light chain variable domain sequence that have a binding specificity for a second epitope. . In one embodiment, the bispecific antibody molecule comprises half an antibody having a binding specificity for a first epitope and half an antibody having a binding specificity for a second epitope. In one embodiment, the bispecific antibody molecule comprises half an antibody or fragment thereof with a binding specificity for a first epitope and half an antibody or fragment thereof with a binding specificity for a second epitope. In one embodiment, the bispecific antibody molecule comprises an scFv or fragment thereof with a binding specificity for a first epitope and an scFv or fragment thereof with a binding specificity for a second epitope.

In specific embodiments, the antibody molecule is a multispecific (eg, bispecific or trispecific) antibody molecule. Methods for producing bispecific or heterodimeric antibody molecules are known in the art; including, but not limited to, for example, the "trough in the valley" approach, as described, for example, in US5731168; electrostatically driven Fc pairing as described, for example, in WO09/089004, WO06/106905 and WO2010/129304; the formation of heterodimers using domains obtained by chain replacement (SEED), as described, for example, in WO07/110205; replacement of Fab fragments as described, for example, in WO08/119353, WO2011/131746 and WO2013/060867; creation of a conjugate of two antibodies, for example, by cross-linking antibodies, obtaining a bispecific structure, using a heterobifunctional reagent having a reactive amino group and a reactive sulfhydryl group, as described, for example, in US4433059; obtaining a bispecific antibody by recombining halves of antibodies (heavy-light chain pairs or Fab) from different antibodies in a cycle of reduction and oxidation of disulfide bonds between two heavy chains, as described, for example, in US4444878; the creation of trifunctional antibodies, for example, due to three Fab'-fragments cross-linked through sulfhydryl reactive groups, as described, for example, in US5273743; creation of biosynthetic binding proteins, for example, a pair of scFvs, cross-linked through the C-terminal fragments, preferably by formation of disulfide bonds or chemical cross-linking through reactive amino groups, as described, for example, in US5534254; obtaining bifunctional antibodies, for example, Fab fragments with different binding specificities, dimerized by leucine zippers (eg, c-fos and c-jun), which replaced the constant domain, as described, for example, in US5582996; production of bispecific and oligospecific mono- and oligovalent receptors, e.g., VH-CH1 regions from two antibodies (two Fab fragments) linked via a polypeptide spacer between the CH1 region of one antibody and the VH region of another antibody, usually with linked light chains, as described, for example, in US5591828; creating bespecifically DNA-antibody conjugates, for example, by cross-linking antibodies or Fab fragments through a double-stranded DNA fragment, as described, for example, in US5635602; obtaining bispecific fused proteins, for example, an expression construct containing two scFv fragments with a hydrophilic helical peptide linker between them and a complete constant region, as described, for example, in US5637481; production of multivalent and multispecific binding proteins, for example, a dimer from polypeptides having a first domain with a binding region from the variable region of the Ig heavy chain and a second domain with a binding region from the variable region of the Ig light chain, usually called a diabody (it is also envisaged to create structures of a higher order to obtain bispecific, trispecific or tetraspecific molecules, as described, for example, in US5837242); creation of minibody constructs with linked VL and VH chains, further connected by peptide spacers to the hinge region and the CH3 region of the antibody, which can be dimerized to obtain bispecific/multivalent molecules, as described, for example, in US5837821; making VH and VL domains linked by a short peptide linker (eg, 5 or 10 amino acids) or no linker at all, in any orientation, which can form dimers to form bispecific diabodies; obtaining trimers and tetramers, as described, for example, in US5844094; creating a sequence of VH domains (or VL domains in members of the family) linked by peptide bonds through cross-linking groups at the C-terminus, additionally linked to VL domains, to form a series of FVs (or scFv fragments), as described, for example, in US5864019; and making single chain binding polypeptides having both VH and VL domains linked via a peptide linker, joined into multivalent structures by non-covalent bonds or chemical crosslinking, to form, for example, homobivalent, heterobivalent, trivalent and tetravalent structures using both scFV format and diabody format as described, for example, in US5869620. Additional exemplary multispecific and bispecific molecules and methods for their preparation are described in, for example, US5910573, US5932448, US5959083, US5989830, US6005079, US6239259, US6294353, US6333396, US6476198, US6511663, US66704 53, US6743896, US6809185, US6833441, US7129330, US7183076, US7521056, US7527787 US2002004587A1, US2002076406A1, US2002103345A1, US2003207346A1, US2003211078A1, US2004219643A1, US2004220388A1, US200 US2005003403A1, US2005004352A1, US2005069552A1, US2005079170A1, US2005100543A1, US2005136049A1, US2005136051A1, US2005163782A1, US 2005266425A1 , US2006083747A1 , US2006120960A1 , US2006204493A1 , US2006263367A1 US2007128150A1 US2007141049A1 US2007154901A1 US2007274985A1 US2008050370A1 US2008069820A1 US2008152645A1 US2008171855A1 US2009148905A1, US2009155275A1, US2009162359A1, US2009162360A1, US2009175851A1, US2009 175867A1, US2009232811A1, US2009234105A1, US2009263392A1, US2009274649A1, EP346087A2, WO0006605A2, WO02072635A2 WO2007137760A2, WO2008119353A1, WO2009021754A2, WO2009068630A1, WO91 03493A1, WO9323537A1, WO9409131A1, WO9412625A2, WO9509917A1, WO9637621A2, WO9964460A1. The contents of all of the above applications are incorporated herein by reference in their entirety.

In each antibody or antibody fragment (eg, scFv) of the bispecific antibody molecule, the VH may be before or after the VL. In some embodiments, the upstream antibody or antibody fragment (e.g., scFv) is arranged so that its VH (VH ₁ ) is in front of its VL (VL ₁ ), and the downstream antibody or antibody fragment (e.g., scFv) arranged so that its VL (VL ₂ ) is in front of its VH (VH ₂ ), resulting in the entire bispecific antibody molecule having the structure VH ₁ -VL ₁ -VL ₂ -VH ₂ . In other embodiments, an upstream antibody or antibody fragment (e.g., scFv) is organized such that its VL (VL ₁ ) is in front of its VH (VH ₁ ), and the downstream antibody or antibody fragment (e.g., scFv) arranged so that its VH (VH ₂ ) is before its (VL ₂ ), resulting in the entire molecule of the bispecific antibody having the structure VL ₁ -VH ₁ -VH ₂ -VL ₂ . Optionally, the linker is between two antibodies or antibody fragments (eg, scFv), for example, between VL ₁ and VL ₂ if the construct has the structure VH ₁ -VL ₁ -VL ₂ -VH ₂ , or between VH ₁ and VH ₂ if the construct has the structure VL ₁ -VH ₁ -VH ₂ -VL ₂ . The linker may be a linker as described herein, for example a (Gly ₄ -Ser)n linker where n is 1, 2, 3, 4, 5 or 6, preferably 4 (SEQ ID NO: 967). Typically, the linker between two scFvs should be long enough to avoid mismatch between the domains of two scFvs. Optionally, the linker is located between the VL and VH regions of the first scFv. Optionally, the linker is located between the VL and VH regions of the second scFv. In constructs having multiple linkers, any two or more linkers may be the same or different. Accordingly, in some embodiments, a bispecific CAR comprises VL, VH regions, and optionally one or more linkers in the structure described herein.

In one aspect, the chimeric antigen receptor comprises a bispecific antigen-binding domain, a transmembrane domain (eg, as described herein), and an intracellular signaling domain (eg, as described herein). In embodiments, the bispecific antigen-binding domain comprises a first sequence of an immunoglobulin variable domain, e.g., scFv (or contains light chain CDRs and/or heavy chain CDRs from scFv described herein) that binds an antigen, e.g., described herein ( e.g., a CD19 binding domain or a BCMA binding domain as described herein, e.g., in Table 6 or Table 12), and a second immunoglobulin variable domain sequence, e.g., scFv (or contains light chain CDR regions and/or heavy chain CDR regions). chain from an scFv described herein) that has binding specificity for one or more of the antigens described herein, e.g., contains an scFv described herein, e.g., containing a mesothelin binding domain or an EGFRvIII binding domain (e.g., given in Table 2 or Table 5). In embodiments, the bispecific antigen binding domain comprises the CD19 binding domain described herein and the mesothelin binding domain described herein. In embodiments, the bispecific antigen binding domain comprises the BCMA binding domain described herein and the mesothelin binding domain described herein. In embodiments, the bispecific antigen binding domain comprises the CD19 binding domain described herein and the EGFRvIII binding domain described herein. In embodiments, the bispecific antigen binding domain comprises the BCMA binding domain described herein and the EGFRvIII binding domain described herein. In another aspect, the invention relates to a cell (e.g., a population of cells), e.g., an immune effector cell, e.g., a T cell or an NK cell, e.g., as described herein, which is engineered to express (e.g., contains) a bispecific CAR as described herein, for example, a bispecific CAR containing the two antigen-binding domains described herein. Without wishing to be bound by a particular theory, it is believed that cells expressing such bispecific CARs (eg, containing two antigen-binding domains, such as those described herein) can be used in the methods and compositions described herein.

Chimeric TCR

In one aspect, the antigen-binding domains described herein, such as antibodies and antibody fragments, such as those shown in the Tables herein, can be grafted onto one or more T cell receptor ("TCR") chain constant domains, such as alpha- TCR chains or TCR beta chains to produce a chimeric TCR that has binding specificity for the tumor antigen described herein. Without wishing to be bound by a particular theory, it is believed that chimeric TCRs will signal through the TCR complex upon antigen binding. For example, a scFv for mesothelin or CD19, or a fragment thereof, such as the VL domain or VH domain disclosed herein, can be grafted onto a constant domain, such as at least a portion of the extracellular constant domain, the transmembrane domain, and the cytoplasmic domain of the TCR chain, for example, TCR alpha chains and/or TCR beta chains. As another example, the CDRs of an antibody or antibody fragment, e.g., the CDRs of any of the antibodies or antibody fragments listed in the Tables herein, can be grafted onto the alpha and/or beta chain of a TCR to produce a chimeric TCR that binds specifically with the tumor antigen described herein. For example, the LCDR regions disclosed herein may be grafted onto a TCR alpha chain variable domain, and the HCDR regions disclosed herein may be grafted onto a TCR beta chain variable domain, or vice versa. Such chimeric TCRs can be prepared by methods known in the art (e.g., Willemsen RA et al., Gene Therapy 2000; 7: 1369-1377; Zhang T et al., Cancer Gene Ther 2004; 11: 487-496; Aggen et al., Gene Ther. 2012 Apr;19(4):365-74).

transmembrane domain

With regard to the transmembrane domain, in various embodiments, the implementation of the CAR can be designed to contain a transmembrane domain that is associated with an extracellular domain of the CAR, for example, an antigen-binding domain. The transmembrane domain may contain one or more additional amino acids adjacent to the transmembrane region, e.g., one or more amino acids associated with the extracellular region of the protein from which the transmembrane domain is derived (e.g., 1, 2, 3, 4, 5, 6, 7, 8 , 9, 10, or up to 15 amino acids from the extracellular region), and/or one or more additional amino acids associated with the intracellular region of the protein from which the transmembrane domain is derived (e.g., 1, 2, 3, 4, 5, 6, 7 , 8, 9, 10, or up to 15 amino acids from the intracellular region). In one aspect, a transmembrane domain is a domain that is associated with one of the other CAR domains, such as a transmembrane domain from the same protein as an intracellular signaling domain, such as a costimulatory domain. In some cases, the transmembrane domain may be selected or modified by amino acid substitutions to prevent such domains from binding to transmembrane domains of the same or other surface membrane proteins, for example, to minimize interactions with other members of the receptor complex. In one aspect, the transmembrane domain is capable of homodimerizing with another CAR on the cell surface of a CAR-expressing cell. In another aspect, the amino acid sequence of the transmembrane domain can be modified or altered to minimize interactions with the binding domains of a natural binding partner present on the same CAR-expressing cell.

The transmembrane domain can be obtained from either a natural or recombinant source. If the source is natural, the domain can be derived from any membrane-bound or transmembrane protein. In one aspect, the transmembrane domain is capable of signaling to the intracellular domain(s) upon binding of the CAR to a target. A transmembrane domain particularly useful in this invention may comprise at least a transmembrane region(s), e.g., T cell receptor alpha, beta or zeta chains, CD28, CD27, CD3epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154. In some embodiments, a transmembrane domain may comprise at least a transmembrane region(s), e.g., KIRDS2, OX40, CD2, CD27, LFA-1 (CD11a, CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD40, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD160, CD19, IL2R-beta, IL2R-gamma, IL7Rα, ITGA1, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, TNFR2, DNAM1 (CD226) , SLAMF4 (CD244, 2B4), CD84, CD96 (tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150 , IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, PAG/Cbp, NKG2D, NKG2C.

In some instances, the transmembrane domain may be linked to an extracellular region of a CAR, eg, a CAR antigen-binding domain, via a hinge, eg, a human protein hinge. For example, in one embodiment, the hinge can be a human Ig (immunoglobulin) hinge, such as an IgG4 hinge, or a CD8a hinge. In one embodiment, the hinge or spacer comprises (e.g., consists of) the amino acid sequence of SEQ ID NO: 4. In one aspect, the transmembrane domain comprises (e.g., consists of) the transmembrane domain of SEQ ID NO: 12.

In one aspect, the hinge or spacer comprises an IgG4 hinge. For example, in one embodiment, the hinge or spacer comprises a hinge with the amino acid sequence of SEQ ID NO: 6. In some embodiments, the hinge or spacer comprises a hinge encoded by the nucleotide sequence of SEQ ID NO: 7. In one aspect, the hinge or spacer comprises an IgD hinge. For example, in one embodiment, the hinge or spacer comprises a hinge with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the hinge or spacer comprises a hinge encoded by the nucleotide sequence of SEQ ID NO: 9.

In one aspect, the transmembrane domain may be recombinant, in which case it will contain predominantly hydrophobic residues such as leucine and valine. In one aspect, a triplet of phenylalanine, tryptophan and valine residues can be located at each end of the recombinant transmembrane domain.

Optionally, a short oligo- or polypeptide linker, 2-10 amino acids in length, can link the transmembrane domain and the cytoplasmic region of the CAR. A particularly suitable linker may be a glycine-serine doublet. For example, in one aspect, the linker contains the amino acid sequence GGGGSGGGGS (SEQ ID NO: 10). In some embodiments, the linker is encoded by the nucleotide sequence GGTGGCGGAGGTTCTGGAGGTGGAGGTTCC (SEQ ID NO: 11).

In one aspect, the hinge or spacer comprises a KIR2DS2 hinge.

Cytoplasmic domain

The cytoplasmic domain, or region, of CAR contains an intracellular signaling domain. The intracellular signaling domain is generally responsible for the activation of at least one of the normal effector functions of the immune cell into which the CAR has been introduced. The term "effector function" means a specialized function of a cell. The effector function of the T cell, for example, may be cytolytic activity or helper activity, including the secretion of cytokines. Thus, the term "intracellular signaling domain" refers to a protein fragment that signals an effector function and directs the cell to perform a specialized function. Although it is generally possible to use the entire intracellular signaling domain, in many cases it is not necessary to use the entire chain. If a truncated fragment of the intracellular signaling domain can be used, such a truncated fragment can be used in place of the intact strand, provided that it signals the effector function. Thus, the term "intracellular signaling domain" should include any truncated fragment of an intracellular signaling domain sufficient to signal an effector function.

Examples of intracellular signaling domains for use in the CARs of the invention include cytoplasmic T cell receptor (TCR) and co-receptor sequences that act together to initiate signaling upon antigen binding to the receptor, as well as any derivative or variant of such sequences, and any recombinant sequence having the same functionality.

It is known that signals generated by the TCR alone are insufficient for full T cell activation, and that a secondary and/or co-stimulatory signal is also required. Thus, T cell activation can be said to be mediated by two different kinds of cytoplasmic signaling sequences: those that initiate antigen-dependent primary activation via TCRs (major intracellular signaling domains), and those that act in an antigen-independent manner, providing a secondary or costimulatory signal (secondary cytoplasmic domain, eg, costimulatory domain).

The main signaling domain regulates the primary activation of the TCR complex in either a stimulatory or inhibitory manner. The main intracellular signaling domains that act in a stimulatory manner may contain signaling motifs known as immunoreceptor tyrosine activating motifs, or ITAMs.

Examples of ITAM-containing major intracellular signaling domains that are particularly suitable for use in the invention include TCR-zeta, FcR-gamma, FcR-beta, CD3-gamma, CD3-delta, CD3-epsilon, CD5, CD22, CD79a, CD79b , CD278 (also known as "ICOS"), FcεRI, DAP10, DAP12 and CD66d. In one embodiment, the CAR of the invention contains an intracellular signaling domain, eg, the main CD3 zeta signaling domain, eg, the CD3 zeta sequence described herein.

In one embodiment, the core signaling domain contains a modified ITAM domain, such as a mutant ITAM domain, that has altered (eg, increased or decreased) activity compared to the native ITAM domain. In one embodiment, the main signaling domain is a main intracellular signaling domain containing a modified ITAM, for example, a main intracellular signaling domain containing an optimized and/or truncated ITAM. In one embodiment, the main signaling domain contains one, two, three, four or more ITAM motifs.

The CAR intracellular signaling domain may contain the CD3-zeta signaling domain alone, or in combination with any other desired intracellular signaling domain(s) useful in the context of the CAR of the invention. For example, a CAR intracellular signaling domain may contain a portion of the CD3-zeta chain and a co-stimulatory signaling domain. The costimulatory signaling domain is a CAR fragment containing the intracellular domain of a costimulatory molecule. A co-stimulatory molecule is a cell surface molecule, other than the antigen receptor or its ligands, that is required for an effective lymphocyte response to an antigen. Examples of such molecules include CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen 1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7- H3, as well as a ligand that specifically binds to CD83, and the like. For example, costimulation of CD27 has been shown to increase the proliferation, effector function, and survival of human CAR T cells in vitro , as well as to increase human T cell persistence and antitumor activity in vivo (Song et al. Blood. 2012; 119(3): 696-706). Additional examples of such costimulatory molecules include MHC class I molecule, TNF receptor protein, immunoglobulin-like protein, cytokine receptor, integrin, lymphocyte activation signaling molecule (SLAM protein), NK cell-activating receptor, BTLA, Toll-like receptor, OX40, CD2, CD7 , CD27, CD28, CD30, CD40, CDS, ICAM-1, LFA-1 (CD11a/CD18), 4-1BB (CD137), B7-H3, CDS, ICAM-1, ICOS (CD278), GITR, BAFFR, LIGHT, HVEM (LIGHTR), KIRDS2, SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD19, CD4, CD8-alpha, CD8-beta, IL2R-beta, IL2R-gamma, IL7R-alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA- 1, ITGB7, NKG2D, NKG2C, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/Cbp, CD19a, as well as a ligand that specifically binds to CD83.

The intracellular signal sequences in the cytoplasmic CAR fragment of the invention may be linked to each other in a random or specific manner. Optionally, a short oligo- or polypeptide linker, eg 2-10 amino acids long (eg 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids), can bind intracellular signal sequences. In one embodiment, a glycine-serine doublet can be used as a suitable linker. In one embodiment, one amino acid, eg alanine, glycine, can be used as a suitable linker.

In one aspect, an intracellular signaling domain is designed to contain two or more, eg 2, 3, 4, 5 or more, costimulatory signaling domains. In one embodiment, two or more, eg 2, 3, 4, 5 or more co-stimulatory signaling domains are separated by a linker molecule, eg the linker molecule described herein. In one embodiment, the intracellular signaling domain contains two costimulatory signaling domains. In some embodiments, the linker molecule is a glycine residue. In some embodiments, the linker is an alanine residue.

In one aspect, an intracellular signaling domain is designed to contain a CD3-zeta signaling domain and a CD28 signaling domain. In one aspect, the intracellular signaling domain is designed to contain the CD3-zeta signaling domain and the 4-1BB signaling domain. In one aspect, the 4-1BB signaling domain is the signal domain of SEQ ID NO: 14. In one aspect, the CD3-zeta signal domain is the signal domain of SEQ ID NO: 18.

In one aspect, an intracellular signaling domain is designed to contain a CD3-zeta signaling domain and a CD27 signaling domain. In one aspect, the CD27 signal domain comprises the amino acid sequence of SEQ ID NO: 16. In one aspect, the CD27 signal domain is encoded by the nucleotide sequence of SEQ ID NO: 17.

In one aspect, an intracellular signaling domain is designed to contain a CD3-zeta signaling domain and a CD28 signaling domain. In one aspect, the CD28 signal domain comprises the amino acid sequence of SEQ ID NO: 124. In one aspect, the CD28 signal domain is encoded by the nucleotide sequence of SEQ ID NO: 1113.

In one aspect, an intracellular signaling domain is designed to contain a CD3-zeta signaling domain and an ICOS signaling domain. In one aspect, the ICOS signal domain comprises the amino acid sequence of SEQ ID NO: 120. In one aspect, the ICOS signal domain is encoded by the nucleotide sequence of SEQ ID NO: 1111.

In one aspect, a cell of the invention, e.g., as described herein, e.g., a cell expressing two different CARs, has CARs each containing an antigen-binding domain that binds the target antigen described herein, a transmembrane domain, a major signaling domain and a costimulatory signaling domain. In embodiments of the above aspect, the co-stimulatory domains of two different CARs may be the same or different. In embodiments, one or more of the two different CARs contain more than one co-stimulatory signaling domain. In other aspects, a cell of the invention, e.g., as described herein, e.g., a cell expressing two different CARs, has a first CAR containing an antigen-binding domain that binds the target antigen described herein, a transmembrane domain, a major signaling domain, but not containing a costimulatory signaling domain, and a second CAR containing an antigen-binding domain that binds the target antigen described herein, a transmembrane domain, and a costimulatory signaling domain, but not containing the main signaling domain.

In one aspect, a CAR expressing cell as described herein, e.g., a cell expressing two different CARs, may also have a different, e.g., third, CAR, e.g., a different CAR containing a different antigen binding domain, e.g., for the same target or a different target (eg, a target other than the tumor antigen described herein or another tumor antigen described herein). For example, in one embodiment in which a cell of the invention expresses a third CAR containing an antigen-binding domain that binds a second tumor target antigen, the third CAR contains an antigen-binding domain for a target expressed on the same type of cancer cell as the tumor antigen, being the target of the first or second CAR. In one embodiment, a CAR-expressing cell has a first CAR that targets a first tumor antigen and contains an intracellular signaling domain containing a co-stimulatory signaling domain but not a major signaling domain, and a third CAR that targets a second, distinct, tumor antigen and contains an intracellular signaling domain containing the main signaling domain but not the costimulatory signaling domain. Without wishing to be bound by a particular theory, placing a costimulatory signaling domain, e.g., 4-1BB, CD28, CD27, or OX-40, on the first CAR and a major signaling domain, e.g., CD3-zeta, on the third CAR may limit CAR activity to only cells on which both targets are expressed. In one embodiment, a cell of the invention has a first CAR containing an antigen binding domain that binds a target antigen described herein, a transmembrane domain, and a costimulatory domain, and a second CAR that targets a different target antigen (e.g., an antigen expressed on that the same type of cancer cell as the first target antigen) and contains an antigen-binding domain, a transmembrane domain and a basic signaling domain. In another embodiment, the cell of the invention has (i.e., is genetically programmed to express) a first CAR containing an antigen-binding domain that binds the target antigen described herein, a transmembrane domain, and a major signaling domain, and a second CAR that targets a tumor antigen, different from the first target antigen (eg, an antigen expressed on the same type of cancer cell as the first target antigen) and contains an antigen-binding domain for the antigen, a transmembrane domain, and a co-stimulatory signaling domain. In another embodiment, a cell of the invention has (i.e., is genetically programmed to express) a first CAR containing an antigen-binding domain that binds the target antigen described herein, a transmembrane domain, a co-stimulatory signaling domain, and a major signaling domain, and a second CAR that targets to a tumor antigen other than the first target antigen (e.g., an antigen expressed on the same type of cancer cell as the first target antigen) and contains an antigen-binding domain for the antigen, a transmembrane domain, a costimulatory signaling domain, and a basic signaling domain. In embodiments where both the first and second CARs contain a costimulatory signaling domain, the costimulatory signaling domains of the first CAR and the second CAR can be derived from the same protein, e.g., from the costimulatory protein described herein, e.g., 4-1BB, CD28, or ICOS. In other embodiments, the costimulatory signaling domains of the first CAR and the second CAR may be derived from different proteins, e.g., the first CAR contains the costimulatory signaling domain described herein, e.g., from 4-1BB, and the second CAR contains a different costimulatory signaling domain, described in this document, for example, from CD28.

In one embodiment, a CAR-expressing cell has a CAR containing an antigen-binding domain that binds the target antigens described herein and inhibits CAR. In one embodiment, the inhibitory CAR comprises an antigen-binding domain that binds an antigen present on normal cells but not cancer cells, e.g., normal cells that also express tumor antigens that are targeted by a CAR containing an antigen-binding domain that binds the target antigen. In one embodiment, the inhibitory CAR comprises an antigen-binding domain, a transmembrane domain, and an intracellular domain of an inhibitory molecule. For example, the intracellular domain of an inhibitory CAR may be the intracellular domain of PD-1, PD-L1, CTLA4, TIM3, LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, CD80, CD86, B7-H3 (CD276), B7- H4 (VTCN1), HVEM (TNFRSF14 or CD270), KIR, A2aR, MHC class I, MHC class II, GAL9, adenosine, or TGF-beta.

In one embodiment, the antigen-binding domains of different CARs may be such that the antigen-binding domains do not interact with each other. For example, a cell expressing the first and second CARs may contain the antigen-binding domain of the first CAR, e.g., as a fragment, e.g., scFv, that does not bind to the antigen-binding domain of the second CAR, e.g., the antigen-binding domain of the second CAR, which is VHH.

In some embodiments, the antigen-binding domain comprises single-domain antigen-binding (SDAB) molecules, including molecules whose complementarity-determining regions are part of a single-domain polypeptide. Examples include, but are not limited to, heavy chain variable domains binding molecules naturally lacking light chains, single domains derived from conventional 4 chain antibodies, recombinant domains, and single domain scaffolds other than those derived from antibodies. The SDAB molecules can be any single domain molecules known in the art or any future one. SDAB molecules can be derived from any species, including, but not limited to, mouse, human, camel, llama, lamprey, fish, shark, goat, rabbit, and cattle. The term also includes naturally occurring single domain antibody molecules in species other than camelids and sharks.

In one aspect, the SDAB molecule can be derived from an immunoglobulin variable region found in fish, such as derived from an immunoglobulin isotype known as a novel antigen receptor (NAR) found in shark sera. Methods for making single domain molecules derived from the NAR variable region ("IgNAR") are described in WO03/014161 and Streltsov (2005) Protein Sci. 14:2901-2909.

In another aspect, the SDAB molecule is a naturally occurring single domain antigen binding molecule known as a heavy chain devoid of light chains. Such single domain molecules are disclosed in WO9404678 and Hamers-Casterman, C. et al. (1993) Nature 363:446-448, for example. For clarity, this variable domain derived from a heavy chain molecule naturally devoid of a light chain is referred to herein as a VHH or nanobody to distinguish it from conventional VH from four chain immunoglobulins. Such a VHH molecule can be obtained from camelids such as the camel, llama, dromedary, alpaca, and guanaco. And species other than camelids can produce heavy chain molecules that are naturally devoid of light chains; such VHHs are within the scope of the invention.

SDAB molecules can be recombinant, CDR-grafted, humanized, camelid, lacking immunogenicity, and/or produced in vitro (eg, selected by phage display).

It has also been found that in the case of cells having a plurality of chimeric membrane-embedded receptors containing antigen-binding domains, interaction between the antigen-binding domains of the receptors may be undesirable, for example, because it inhibits the ability of one or more of the antigen-binding domains to bind the antigen it recognizes. Accordingly, the present document discloses cells having first and second non-natural chimeric membrane-immersed receptors containing antigen-binding domains whose interaction is minimized. Also disclosed herein are nucleic acids encoding first and second non-natural chimeric membrane-embedded receptors containing antigen-binding domains whose interaction is minimized, as well as methods for making and using such cells and nucleic acids. In one embodiment, the antigen-binding domain in one of said first and said second non-natural chimeric membrane-embedded receptors contains scFv, and in the other contains one VH domain, for example, one VH domain of camelids, sharks or lampreys, or one VH domain derived from from a human or mouse antibody sequence.

In another aspect, the CAR-expressing cell described herein may additionally express another agent, for example, an agent that increases the activity of the CAR-expressing cell. For example, in one embodiment, the agent may be an agent that inhibits an inhibitory molecule. Inhibitory molecules, such as PD-1, in some embodiments, may reduce the ability of a CAR-expressing cell to mount an immune effector response. Examples of inhibitory molecules include PD-1, PD-L1, CTLA4, TIM3, CEACAM (e.g. CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, CD80 , CD86, B7-H3 (CD276), B7-H4 (VTCN1), HVEM (TNFRSF14 or CD270), KIR, A2aR, MHC class I, MHC class II, GAL9, adenosine, and TGF-beta.

In one embodiment, an agent that inhibits an inhibitory molecule, for example, is a molecule described herein, for example, an agent containing a first polypeptide, for example, an inhibitory molecule associated with a second polypeptide, which transmits a positive signal to a cell, for example, an intracellular signaling domain described in this document. In one embodiment, the agent comprises a first polypeptide, e.g., an inhibitory molecule such as PD-1, PD-L1, CTLA4, TIM3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG3, VISTA , BTLA, TIGIT, LAIR1, CD160, 2B4, CD80, CD86, B7-H3 (CD276), B7-H4 (VTCN1), HVEM (TNFRSF14 or CD270), KIR, A2aR, MHC Class I, MHC Class II, GAL9, adenosine and TGF-beta, or a fragment of any of them (for example, at least part of the extracellular domain of any of them), and a second polypeptide that is an intracellular signaling domain described herein (for example, containing a co-stimulatory domain (for example, 41BB , CD27, or CD28, such as described herein) and/or a major signaling domain (eg, the CD3-zeta signaling domain described herein)). In one embodiment, the agent comprises a first PD-1 polypeptide or fragment thereof (e.g., at least a portion of the PD-1 extracellular domain) and a second intracellular signaling domain polypeptide described herein (e.g., the CD28 signaling domain described herein, and/or the CD3-zeta signaling domain described herein). PD-1 is an inhibitory member of the CD28 receptor family, which also includes CD28, CTLA-4, ICOS, and BTLA. PD-1 is expressed on activated B cells, T cells and myeloid cells (Agata et al. 1996 Int. Immunol 8:765-75). Two PD-1 ligands, PD-L1 and PD-L2, have been shown to down-regulate T cell activation when bound to PD-1 (Freeman et al. 2000 J Exp Med 192:1027-34; Latchman et al. 2001 Nat Immunol 2:261-8 Carter et al 2002 Eur J Immunol 32:634-43). PD-L1 is abundant in human cancers (Dong et al. 2003 J Mol Med 81:281-7; Blank et al. 2005 Cancer Immunol. Immunother 54:307-314; Konishi et al. 2004 Clin Cancer Res 10: 5094). Immune suppression can be reversed by inhibiting the local interaction of PD-1 with PD-L1.

In one embodiment, the agent comprises an extracellular domain (ECD) of an inhibitory molecule, e.g., programmed cell death protein 1 (PD-1), fused to a transmembrane domain and an intracellular signaling domain, such as 41BB and CD3-zeta (herein also referred to as PD -1CAR). In one embodiment, the PD-1 CAR, when used in combination with the XCAR described herein, improves T cell persistence. In one embodiment, the CAR is a PD-1 CAR comprising the extracellular domain of PD-1 underlined in SEQ ID NO: 26. In one embodiment, the PD-1 CAR comprises the amino acid sequence of SEQ ID NO: 26. In one embodiment, PD- 1 CAR contains the amino acid sequence of SEQ ID NO: 39.

In one embodiment, the agent has a nucleotide sequence encoding a PD-1 CAR, such as the PD-1 CAR described herein. In one embodiment, the nucleotide sequence for PD-1 CAR is shown in SEQ ID NO: 27 in Table 1, with the sequence for PD-1 ECD underlined.

In another aspect, the present invention relates to a population of CAR-expressing cells. In some embodiments, the population of CAR-expressing cells contains a mixture of cells expressing different CARs. For example, in one embodiment, a population of CAR T cells may include a first cell expressing a CAR containing an antigen-binding domain for a CAR of an antigen described herein and a second cell expressing a CAR containing a different antigen-binding domain, e.g., an antigen-binding domain for another antigen. described herein, for example, an antigen-binding domain for the tumor antigen described herein, which is different from the tumor antigen bound by the antigen-binding domain of the CAR expressed by the first cell. As another example, a population of CAR-expressing cells may include a first cell expressing a CAR containing an antigen-binding domain for a tumor antigen described herein and a second cell expressing a CAR containing an antigen-binding domain for a target other than the tumor antigen described in this document. In one embodiment, the population of CAR-expressing cells includes, for example, a first cell expressing a CAR containing a primary intracellular signaling domain and a second cell expressing a CAR containing a secondary signaling domain.

In another aspect, the present invention relates to a population of cells in which at least one cell expresses a CAR containing an antigen-binding domain for the tumor antigen described herein, and the second cell expresses another agent, for example, an agent that increases the activity of a CAR-expressing cell . For example, in one embodiment, the agent may be an agent that inhibits an inhibitory molecule. In some embodiments, inhibitory molecules, such as PD-1, may decrease the ability of a CAR-expressing cell to mount an immune effector response. Examples of inhibitory molecules include PD-1, PD-L1, CTLA4, TIM3, CEACAM (e.g. CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, CD80 , CD86, B7-H3 (CD276), B7-H4 (VTCN1), HVEM (TNFRSF14 or CD270), KIR, A2aR, MHC class I, MHC class II, GAL9, adenosine, and TGF-beta. In one embodiment, an agent that inhibits an inhibitory molecule, for example, is a molecule described herein, for example, an agent containing a first polypeptide, for example, an inhibitory molecule associated with a second polypeptide, which transmits a positive signal to the cell, for example, intracellular signaling domain described in this document. In one embodiment, the agent comprises a first polypeptide, e.g., an inhibitory molecule such as PD-1, PD-L1, CTLA4, TIM3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG3, VISTA , BTLA, TIGIT, LAIR1, CD160, 2B4, CD80, CD86, B7-H3 (CD276), B7-H4 (VTCN1), HVEM (TNFRSF14 or CD270), KIR, A2aR, MHC Class I, MHC Class II, GAL9, adenosine and TGF-beta, or a fragment of any of them, and a second polypeptide that is an intracellular signaling domain described herein (for example, containing a costimulatory domain (for example, 41BB, CD27, OX40 or CD28, for example, described herein ) and/or a major signaling domain (eg, the CD3-zeta signaling domain described herein)). In one embodiment, the agent comprises a first PD-1 polypeptide or fragment thereof and a second intracellular signaling domain polypeptide described herein (e.g., the CD28 signaling domain described herein and/or the CD3-zeta signaling domain described herein) .

In one aspect, the present invention provides methods comprising administering a population of CAR-expressing cells, eg, a mixture of cells expressing different CARs, in combination with another agent, eg, a kinase inhibitor such as the kinase inhibitor described herein. In another aspect, the present invention relates to methods comprising administering a cell population in which at least one cell expresses a CAR containing an antigen-binding domain for a tumor antigen described herein and the second cell expresses another agent, e.g. CAR-expressing cell, in combination with another agent, for example, a kinase inhibitor, such as a kinase inhibitor described herein.

Illustrative CAR molecules

The CAR molecules disclosed herein may contain a binding domain that binds to a target, such as the target described herein; a transmembrane domain, such as the transmembrane domain described herein; and an intracellular signaling domain, such as the intracellular domain described herein. In embodiments, the binding domain comprises a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2), and a heavy chain complementarity determining region 3 (HC CDR3) of the heavy chain binding domain described herein, and/ or light chain complementarity determining region 1 (LC CDR1), light chain complementarity determining region 2 (LC CDR2), and light chain complementarity determining region 3 (LC CDR3) of the light chain binding domain described herein.

In other embodiments, the CAR molecule is a CD19 CAR molecule as described herein, eg a CD19 CAR molecule as described in US-2015-0283178-A1, eg CTL019. In embodiments, the CD19 CAR contains the amino acid, or has the nucleotide, sequence shown in US-2015-0283178-A1, the content of the document is incorporated herein by reference, or a sequence substantially identical to it (for example, at least 85% , 90%, 95% or more identical).

In one embodiment, a CAR T cell that specifically binds to CD19 has the USAN designation TISAGENLECLEUCEL-T. CTL019 is produced by genetic modification of T cells mediated by stable introduction by transduction of a self-inactivating, replication-deficient lentiviral (LV) vector containing the CTL019 transgene under the control of the EF1-alpha promoter. CTL019 may be a mixture of transgene positive and negative T cells that are delivered to the subject based on the percentage of transgene positive T cells.

In one embodiment, the CAR19 molecule contains (eg, consists of) the amino acid sequence shown in Table 15A or Table 3 in International Patent Publication No. WO2014/153270, filed March 15, 2014; the contents of which are incorporated herein by reference. Amino acid and nucleotide sequences encoding CD19 CAR molecules and antigen binding domains (eg, containing one, two, three VH CDRs; and one, two, three VL CDRs according to the Kabat or Chothia system) are given in WO2014/153270. In embodiments, the CD19 CAR contains the amino acid, or has the nucleotide sequence set forth in WO2014/153270, the contents of the document incorporated herein by reference, or a sequence substantially identical to any of the above sequences (e.g., at least 85% 90%, 95% or more identical to any of the above CD19 CAR sequences). In one embodiment, the CAR molecule contains (eg, consists of) an amino acid sequence selected from any of SEQ ID NOs: 897, 902, 907, 912, 917, 922, 927, 932, 937, 942, 947, 952, 956; or an amino acid sequence having at least one, two, three, four, five, 10, 15, 20, or 30 modifications (e.g., substitutions, e.g. conservative substitutions), but no more than 60, 50, or 40 modifications (e.g., substitutions eg conservative substitutions) amino acid sequence selected from any of SEQ ID NOs: 897, 902, 907, 912, 917, 922, 927, 932, 937, 942, 947, 952, 956; or an amino acid sequence having 85%, 90%, 95%, 96%, 97%, 98%, 99% identity with an amino acid sequence selected from any of SEQ ID NOs: 897, 902, 907, 912, 917, 922, 927, 932, 937, 942, 947, 952, 956.

In one embodiment, the mouse scFv parental sequence is the CAR19 construct shown in PCT publication WO2012/079000 (the contents of which are incorporated herein by reference) and listed herein in Table 15A. In one embodiment, the anti-CD19 binding domain is the scFv described in WO2012/079000 and listed herein in Table 15A.

In one embodiment, the CD19 CAR contains the amino acid sequence shown in SEQ ID NO: 12 in PCT publication WO2012/079000. In an embodiment, the amino acid sequence is:

MALPVTALLLPLALLLHAARPdiqmtqttsslsaslgdrvtiscrasqdiskylnwyqqkpdgtvklliyhtsrlhsgvpsrfsgsgsgtdysltisnleqediatyfcqqgntlpytfgggtkleitggggsggggsggggsevklqesgpglvapsqslsvtctvsgvslpdygv swirqpprkglewlgviwgsettyynsalksrltiikdnsksqvflkmnslqtddtaiyycakhyyyggsyamdywgqgtsvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpe eeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr (SEQ ID NO: 891), or a sequence substantially identical to it (e.g., at least 85%, 90%, or 95% or more identical to it), with or without the content of the signal peptide sequence, indicated by capital letters .

In an embodiment, the amino acid sequence is:

diqmtqttsslsaslgdrvtiscrasqdiskylnwyqqkpdgtvklliyhtsrlhsgvpsrfsgsgsgtdysltisnleqediatyfcqqgntlpytfgggtkleitggggsggggsggggsevklqesgpglvapsqslsvtctvsgvslpdygvswirqpprkglewlgviw gsettyynsalksrltiikdnsksqvflkmnslqtddtaiyycakhyyyggsyamdywgqgtsvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeeggcelrvkfsrsadapay kqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr (SEQ ID NO: 892), or a sequence substantially homologous to it (e.g., at least 85%, 90% or 95% or more identical to it).

In embodiments, the CAR molecule is a CD19 CAR molecule as described herein, e.g., a humanized CAR molecule as described herein, e.g., a humanized CD19 CAR molecule in Table 15A or containing the CDR regions shown in Tables 15B and 15C.

In embodiments, the CAR molecule is a CD19 CAR molecule as described herein, e.g., a mouse CAR molecule as described herein, e.g., a mouse CD19 CAR molecule in Table 15A or containing the CDR regions shown in Tables 15B and 15C.

In some embodiments, the CAR molecule comprises one, two and/or three CDRs from the heavy chain variable region, and/or one, two and/or three CDRs from the light chain variable region of the murine or humanized CD19 CAR in Tables 15B and 15C.

In one embodiment, the antigen binding domain comprises one, two, three (e.g., all three) of the heavy chain CDR regions, HC CDR1, HC CDR2, and HC CDR3, from the antibody listed above, and/or one, two, three (e.g., all three) from the light chain CDR regions, LC CDR1, LC CDR2 and LC CDR3, from the antibody listed above. In one embodiment, the antigen binding domain comprises a heavy chain variable region and/or a light chain variable region of an antibody listed or described herein.

Exemplary CD19 CARs include any of the CD19 CARs or anti-CD19 binding domains described herein, e.g., in one or more of the tables (e.g., Table 15A) provided herein (e.g., or the anti-CD19 CARs described in Xu et al Blood 123.24(2014):3750-9 Kochenderfer et al Blood 122.25(2013):4129-39, Cruz et al Blood 122.17(2013):2965-73, NCT00586391, NCT01087294 , NCT02456350, NCT00840853, NCT02659943, NCT02650999, NCT02640209, NCT01747486, NCT02546739, NCT02656147, NCT02772198, NCT00709033, NCT02081937 NCT00924326 NCT02735083 NCT02794246 NCT02746952 NCT01593696 NCT02134262 NCT01853631 NCT02443831 NCT02277522 NCT02348216 CT02030834, NCT02624258, NCT02625480 NCT02030847 NCT02644655 NCT02349698 NCT02813837 NCT02050347 NCT01683279 NCT02529813 NCT02537977 NCT02799550 NCT02672501 NCT01430390, NCT02146924, NCT02051257, NCT02431988, NCT01815749, N CT02153580, NCT01865617, NCT02208362 , NCT02685670, NCT02535364, NCT02631044, NCT02728882, NCT02735291, NCT01860937, NCT02822326, NCT02737085, NCT02465983, NCT02132624, NCT02782351 NCT01493453, NCT02652910, NCT02247609, NCT01029366, NCT01626495, NCT02721407, NCT01044069, NCT00422383, NCT01680991, NCT02794961, the content of each incorporated herein by reference in its entirety.

Exemplary CD19 CAR and antigen binding domain constructs that can be used in the methods described herein are shown in Table 15A. The sequences of the light and heavy chain CDR regions according to the Kabat system are bold and underlined and are also shown in Tables 15A-C. Portions of the signal sequence and the histidine tag are also underlined. In embodiments, the CD19 CAR sequences and their antigen-binding fragments do not include a signal sequence and/or a histidine tag sequence.

In embodiments, the CD19 CAR contains an anti-CD19 binding domain (e.g., a murine or humanized anti-CD19 binding domain), a transmembrane domain, and an intracellular signaling domain, wherein said anti-CD19 binding domain contains a heavy chain complementarity determining region 1 (HC CDR1) , complementarity determining region 2 of the heavy chain (HC CDR2) and complementarity determining region 3 of the heavy chain (HC CDR3) of any of the amino acid sequences of the anti-CD19 binding domain of the heavy chain shown in Table 15A-C, or a sequence of at least 85% , 90%, 95% or more identical to them (for example, having less than 5, 4, 3, 2 or 1 amino acid substitutions, for example, conservative substitutions).

In one embodiment, the anti-CD19 binding domain comprises the light chain variable region described herein (e.g., in Table 15A) and/or the heavy chain variable region described herein (e.g., Table 15A), or the sequences at least 85%, 90%, 95% or more identical to them.

In one embodiment, the encoded anti-CD19 binding domain is a scFv containing a light chain and a heavy chain with the amino acid sequences shown in Table 5, or sequences at least 85%, 90%, 95% or more identical to them.

In one embodiment, a human or humanized anti-CD19 binding domain (e.g., scFv) contains: a light chain variable region containing an amino acid sequence having at least one, two, or three modifications (e.g., substitutions, e.g., conservative substitutions), but not more than 30, 20 or 10 modifications (e.g. substitutions, e.g. conservative substitutions) of the light chain variable region amino acid sequence shown in Table 15A, or a sequence at least 85%, 90%, 95% or more identical to it ; and/or a heavy chain variable region containing an amino acid sequence having at least one, two, or three modifications (e.g., substitutions, e.g., conservative substitutions), but no more than 30, 20, or 10 modifications (e.g., substitutions, substitutions) the amino acid sequence of the heavy chain variable region shown in Table 15A, or a sequence at least 85%, 90%, 95% or more identical to it.

In one embodiment, the CAR molecule contains an antigen-binding domain for CD19 (e.g., a murine, human, or humanized antibody, or an antibody fragment that specifically binds to CD19), a transmembrane domain, and an intracellular signaling domain (e.g., an intracellular signaling domain containing a costimulatory domain and/ or the main signaling domain).

Exemplary CAR19 molecules are shown in Table 15A (as well as Table 7). The CAR molecules in Table 15A contain an antigen-binding domain for CD19, for example, the amino acid sequence of any antigen-binding domain for CD19 shown in Table 7 or 10.

Table 15A. Illustrative CD19 CAR molecules

Name SEQID NO: Subsequence CAR1 CAR1,
scFv domain 893 EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSS 103101
CAR1,
Soluble scFv - nk 894 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaa aggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagccaccaccatcatcaccatcaccat 103101
CAR1,
Soluble scFv - ak 895 MALPVTALLLPLALLLHAARP eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyys sslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss hhhhhhh 104875
CAR1,
Whole - nk 896 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaa aggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcg tcgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactactcaaga ggaggacggctgttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaa agaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 104875
CAR1,
Whole - ak 897 MALPVTALLLPLALLLHAARPeivmtqspatlslspgeratlsc rasqdiskyln wyqqkpgqaprlliy htsrlhs giparfsgsgsgtdytltisslqpedfavyfc qqgntlpyt fgqgtkleikggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslp dygv s wirqppgkglewig viwgsettyyssslks rvtiskdnsknqvslklssvtaadtavyycak hyyyggsyamdy wgqgtlvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscr fpeeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR2 CAR2,
scFv domain 898 eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyy qsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss 103102
CAR2,
Soluble scFv - nk 899 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactaccaatcatccctcaagtcacgcgtcaccatctcaa aggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagccaccaccatcatcaccatcaccat 103102
CAR2,
Soluble scFv - ak 900 MALPVTALLLPLALLLHAARP eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyy qsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss hhhhhhh 104876
CAR2,
Whole - nk 901 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactaccaatcatccctcaagtcacgcgtcaccatctcaa aggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcg tcgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactactcaaga ggaggacggctgttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaa agaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 104876
CAR2,
Whole - ak 902 MALPVTALLLPLALLLHAARPeivmtqspatlslspgeratlsc rasqdiskyln wyqqkpgqaprlliy htsrlhs giparfsgsgsgtdytltisslqpedfavyfc qqgntlpyt fgqgtkleikggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslp dygv s wirqppgkglewig viwgsettyyqsslks rvtiskdnsknqvslklssvtaadtavyycak hyyyggsyamdy wgqgtlvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcs crfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR3 CAR3,
scFv domain 903 qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyssslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlli yhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik 103104
CAR3,
Soluble scFv - nk 904 atggctctgcccgtgaccgcactcctcctgccactggctctgctgcttcacgccgctcgcccacaagtccagcttcaagaatcagggcctggtctggtgaagccatctgagactctgtccctcacttgcaccgtgagcggagtgtccctcccagactacggagtgagctggattagacagcctcccggaaagggactggagtggatc ggagtgatttggggtagcgaaaccacttactattcatcttccctgaagtcacgggtcaccatttcaaaggataactcaaagaatcaagtgagcctcaagctctcatcagtcaccgccgctgacaccgccgtgtattactgtgccaagcattactactatggagggtcctacgccatggactactggggccagggaactctggtcactgtgtcatctggtggagga ggtagcggaggaggcgggagcggtggaggtggctccgaaatcgtgatgacccagagccctgcaaccctgtccctttctcccggggaacgggctaccctttcttgtcgggcatcacaagatatctcaaaatacctcaattggtatcaacagaagccgggacaggcccctaggcttcttatctaccacacctctcgcctgcatagcgggattc ccgcacgctttagcgggtctggaagcgggaccgactacactctgaccatctcatctctccagcccgaggacttcgccgtctacttctgccagcagggtaacaccctgccgtacaccttcggccagggcaccaagcttgagatcaaacatcaccaccatcatcaccatcac 103104
CAR3,
Soluble scFv - ak 905 MALPVTALLLPLALLLHAARP qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyssslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlli yhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik hhhhhhh 104877
CAR3 - Whole - nk 906 atggctctgcccgtgaccgcactcctcctgccactggctctgctgcttcacgccgctcgcccacaagtccagcttcaagaatcagggcctggtctggtgaagccatctgagactctgtccctcacttgcaccgtgagcggagtgtccctcccagactacggagtgagctggattagacagcctcccggaaagggactggagtggatc ggagtgatttggggtagcgaaaccacttactattcatcttccctgaagtcacgggtcaccatttcaaaggataactcaaagaatcaagtgagcctcaagctctcatcagtcaccgccgctgacaccgccgtgtattactgtgccaagcattactactatggagggtcctacgccatggactactggggccagggaactctggtcactgtgtcatctggtggagga ggtagcggaggaggcgggagcggtggaggtggctccgaaatcgtgatgacccagagccctgcaaccctgtccctttctcccggggaacgggctaccctttcttgtcgggcatcacaagatatctcaaaatacctcaattggtatcaacagaagccgggacaggcccctaggcttcttatctaccacacctctcgcctgcatagcgggattc ccgcacgctttagcgggtctggaagcgggaccgactacactctgaccatctcatctctccagcccgaggacttcgccgtctacttctgccagcagggtaacaccctgccgtacaccttcggccagggcaccaagcttgagatcaaaaccactactcccgctccaaggccacccacccctgccccgaccatcgcctctcagccgctttccctgcgt ccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagagg aggacggctgttcatgccggttcccagaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaaga atccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 104877
CAR3,
Whole - ak 907 MALPVTALLLPLALLLHAARPqvqlqesgpglvkpsetlsltctvsgvslp dygvs wirqppgkglewig viwgsettyyssslks rvtiskdnsknqvslklssvtaadtavyycak hyyyggsyamdy wgqgtlvtvssggggsggggsggggseivmtqspatlslspgeratlsc rasq diskyln wyqqkpgqaprlliy htsrlhs giparfsgsggtdytltisslqpedfavyfc qqgntlpyt fgqgtkleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscr fpeeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR4 CAR4,
scFv domain 908 qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyqsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprll iyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik 103106
CAR4,
Soluble scFv - nk 909 atggctctgcccgtgaccgcactcctcctgccactggctctgctgcttcacgccgctcgcccacaagtccagcttcaagaatcagggcctggtctggtgaagccatctgagactctgtccctcacttgcaccgtgagcggagtgtccctcccagactacggagtgagctggattagacagcctcccggaaagggactggagtggatc ggagtgatttggggtagcgaaaccacttactatcaatcttccctgaagtcacgggtcaccatttcaaaggataactcaaagaatcaagtgagcctcaagctctcatcagtcaccgccgctgacaccgccgtgtattactgtgccaagcattactactatggagggtcctacgccatggactactggggccagggaactctggtcactgtgtcatctggtggagga ggtagcggaggaggcgggagcggtggaggtggctccgaaatcgtgatgacccagagccctgcaaccctgtccctttctcccggggaacgggctaccctttcttgtcgggcatcacaagatatctcaaaatacctcaattggtatcaacagaagccgggacaggcccctaggcttcttatctaccacacctctcgcctgcatagcgggattc ccgcacgctttagcgggtctggaagcgggaccgactacactctgaccatctcatctctccagcccgaggacttcgccgtctacttctgccagcagggtaacaccctgccgtacaccttcggccagggcaccaagcttgagatcaaacatcaccaccatcatcaccatcac 103106
CAR4,
Soluble scFv - ak 910 MALPVTALLLPLALLLHAARP qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyqsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprll iyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik hhhhhhh 104878
CAR4,
Whole - nk 911 atggctctgcccgtgaccgcactcctcctgccactggctctgctgcttcacgccgctcgcccacaagtccagcttcaagaatcagggcctggtctggtgaagccatctgagactctgtccctcacttgcaccgtgagcggagtgtccctcccagactacggagtgagctggattagacagcctcccggaaagggactggagtggatc ggagtgatttggggtagcgaaaccacttactatcaatcttccctgaagtcacgggtcaccatttcaaaggataactcaaagaatcaagtgagcctcaagctctcatcagtcaccgccgctgacaccgccgtgtattactgtgccaagcattactactatggagggtcctacgccatggactactggggccagggaactctggtcactgtgtcatctggtggagga ggtagcggaggaggcgggagcggtggaggtggctccgaaatcgtgatgacccagagccctgcaaccctgtccctttctcccggggaacgggctaccctttcttgtcgggcatcacaagatatctcaaaatacctcaattggtatcaacagaagccgggacaggcccctaggcttcttatctaccacacctctcgcctgcatagcgggattc ccgcacgctttagcgggtctggaagcgggaccgactacactctgaccatctcatctctccagcccgaggacttcgccgtctacttctgccagcagggtaacaccctgccgtacaccttcggccagggcaccaagcttgagatcaaaaccactactcccgctccaaggccacccacccctgccccgaccatcgcctctcagccgctttccctgcgt ccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagagg aggacggctgttcatgccggttcccagaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaaga atccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 104878
CAR4,
Whole - ak 912 MALPVTALLLPLALLLHAARPqvqlqesgpglvkpsetlsltctvsgvslp dygvs wirqppgkglewig viwgsettyyqsslks rvtiskdnsknqvslklssvtaadtavyycak hyyyggsyamdy wgqgtlvtvssggggsggggsggggseivmtqspatlslspgeratlsc ras qdiskyln wyqqkpgqaprlliy htsrlhs giparfsgsgsgtdytltisslqpedfavyfc qqgntlpyt fgqgtkleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcs crfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR5 CAR5,
scFv domain 913 eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwg settyyssslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss 99789
CAR5,
Soluble scFv - nk 914 atggccctcccagtgaccgctctgctgctgcctctcgcacttcttctctccatgccgctcggcctgagatcgtcatgacccaaagccccgctaccctgtccctgtcacccggcgaggggcaaccctttcatgcaggccagccaggacatttctaagtacctcaactggtatcagcagaagccagggcaggctcctcgcctgctgat ctaccacaccagccgcctccacagcggtatccccgccagattttccgggagcgggtctggaaccgactacaccctcaccatctctctctgcagcccgaggatttcgccgtctatttctgccagcaggggaatactctgccgtaccaccttcggtcaaggtaccaagctggaaatcaagggaggcggaggatcaggcggtggcggaagcggag gaggtggctccggaggaggaggttcccaagtgcagcttcaagaatcaggacccggacttgtgaagccatcagaaaccctctccctgacttgtaccgtgtccggtgtgagcctccccgactacggagtctcttggattcgccagcctccggggaagggtcttgaatggattggggtgatttggggatcagagactacttactactctctcatcactta agtcacgggtcaccatcagcaaagataatagcaagaaccaagtgtcacttaagctgtcatctgtgaccgccgctgacaccgccgtgtactattgtgccaaacattactattacggagggtcttatgctatggactactggggacaggggaccctggtgactgtctctagccatcaccatcaccaccatcatcac 99789
CAR5,
Soluble scFv - ak 915 MALPVTALLLPLALLLHAARP eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwg settyyssslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss hhhhhhh 104879
CAR5,
Whole - nk 916 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagcggcggaggcgggagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactcttcatccctcaagtcac gcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccag cctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcc tgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggc gggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 104879
CAR5,
Whole - ak 917 MALPVTALLLPLALLLHAARPeivmtqspatlslspgeratlsc rasqdiskyln wyqqkpgqaprlliy htsrlhs giparfsgsgsgtdytltisslqpedfavyfc qqgntlpyt fgqgtkleikggggsggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslp dygvs wirqppgkglewig viwgsettyyssslks rvtiskdnsknqvslklssvtaadtavyycak cscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR6 car6,
scFv domain 918 eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwg settyyqsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss 99790
car6,
Soluble scFv - nk 919 atggccctcccagtgaccgctctgctgctgcctctcgcacttcttctctccatgccgctcggcctgagatcgtcatgacccaaagccccgctaccctgtccctgtcacccggcgaggggcaaccctttcatgcaggccagccaggacatttctaagtacctcaactggtatcagcagaagccagggcaggctcctcgcctgctgat ctaccacaccagccgcctccacagcggtatccccgccagattttccgggagcgggtctggaaccgactacaccctcaccatctctctctgcagcccgaggatttcgccgtctatttctgccagcaggggaatactctgccgtaccaccttcggtcaaggtaccaagctggaaatcaagggaggcggaggatcaggcggtggcggaagcggag gaggtggctccggaggaggaggttcccaagtgcagcttcaagaatcaggacccggacttgtgaagccatcagaaaccctctccctgacttgtaccgtgtccggtgtgagcctccccgactacggagtctctcttggattcgccagcctccggggaagggtcttgaatggattggggtgatttggggatcagagactacttactaccagtcatcact taagtcacgggtcaccatcagcaaagataatagcaagaaccaagtgtcacttaagctgtcatctgtgaccgccgctgacaccgccgtgtactattgtgccaaacattactattacggagggtcttatgctatggactactggggacaggggaccctggtgactgtctctagccatcaccatcaccaccatcatcac 99790
car6,
Soluble scFv - ak 920 MALPVTALLLPLALLLHAARP eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwg settyyqsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss hhhhhhh 104880
car6,
Whole - nk 921 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagcggaggcggagggagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactaccaatcatccctcaagtcacg cgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcc tctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcct gtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgg gaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 104880
car6,
Whole - ak 922 MALPVTALLLPLALLLHAARPeivmtqspatlslspgeratlsc rasqdiskyln wyqqkpgqaprlliy htsrlhs giparfsgsgsgtdytltisslqpedfavyfc qqgntlpyt fgqgtkleikggggsggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslp dygvs wirqppgkglewig viwgsettyyqsslks rvtiskdnsknqvslklssvtaadtavyycak gcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR7 CAR7,
scFv domain 923 qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyssslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqap rlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik 100796
CAR7,
Soluble scFv - nk 924 atggcactgcctgtcactgccctcctgctgcctctggccctccttctgcatgccgccaggccccaagtccagctgcaagagtcaggacccggactggtgaagccgtctgagactctctcactgacttgtaccgtcagcggcgtgtccctccccgactacggagtgtcatggatccgccaacctcccgggaaagggcttgaatggattggtg tcatctggggttctgaaaccacctactactcatcttccctgaagtccagggtgaccatcagcaaggataattccaagaaccaggtcagccttaagctgtcatctgtgaccgctgctgacaccgccgtgtattactgcgccaagcactactactattacggaggaagctacgctatggactattggggacagggcactctcgtgactgtgagcagcggcggtggag ggtctggaggtggaggatccggtggtggtgggtcaggcggaggagggagcgagattgtgatgactcagtcaccagccaccctttctctttcacccggcgagagagcaaccctgagctgtagagccagccaggacatttctaagtacctcaactggtatcagcaaaaccggggcaggcccctcgcctcctgatctaccatacctcacgcctt cactctggtatccccgctcggtttagcggatcaggatctggtaccgactacactctgaccatttccagcctgcagccagaagatttcgcagtgtatttctgccagcagggcaatacccttccttacaccttcggtcagggaaccaagctcgaaatcaagcaccatcaccatcatcaccaccat 100796
CAR7,
Soluble scFv - ak 925 MALPVTALLLPLALLLHAARP qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyssslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqap rlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik hhhhhhh 104881
CAR7,
Whole - nk 926 atggctctgcccgtgaccgcactcctcctgccactggctctgctgcttcacgccgctcgcccacaagtccagcttcaagaatcagggcctggtctggtgaagccatctgagactctgtccctcacttgcaccgtgagcggagtgtccctcccagactacggagtgagctggattagacagcctcccggaaagggactggagtggatc ggagtgatttggggtagcgaaaccacttactattcatcttccctgaagtcacgggtcaccatttcaaaggataactcaaagaatcaagtgagcctcaagctctcatcagtcaccgccgctgacaccgccgtgtattactgtgccaagcattactactatggagggtcctacgccatggactactggggccagggaactctggtcactgtgtcatctggtggagga ggtagcggaggaggcgggagcggtggaggtggctccggaggtggcggaagcgaaatcgtgatgacccagagccctgcaaccctgtccctttctcccggggaacgggctaccctttcttgtcgggcatcacaagatatctcaaaatacctcaattggtatcaacagaagccgggacaggcccctaggcttcttatctaccacacctctcg cctgcatagcgggattcccgcacgctttagcgggtctggaagcgggaccgactacactctgaccatctcatctctccagcccgaggacttcgccgtctacttctgccagcagggtaacaccctgccgtacaccttcggccagggcaccaagcttgagatcaaaaccactactccgctccaaggccacccacccctgccccgaccatcgcctctcag ccgctttccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcct gtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgg gaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 104881
CAR7,
Whole - ak 927 MALPVTALLLPLALLLHAARPqvqlqesgpglvkpsetlsltctvsgvslp dygvs wirqppgkglewig viwgsettyyssslks rvtiskdnsknqvslklssvtaadtavyycak hyyyggsyamdy wgqgtlvtvssggggsggggsggggsggggseivmtqspatlslspgeratlsc rasqdiskyln wyqqkpgqaprlliy htsrlhs giparfsgsgsgtdytltisslqpedfavyfc qqgntlpyt fgqgtkleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedg cscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR8 car8,
scFv domain 928 qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyqsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgq aprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik 100798
car8,
Soluble scFv - nk 929 atggcactgcctgtcactgccctcctgctgcctctggccctccttctgcatgccgccaggccccaagtccagctgcaagagtcaggacccggactggtgaagccgtctgagactctctcactgacttgtaccgtcagcggcgtgtccctccccgactacggagtgtcatggatccgccaacctcccgggaaagggcttgaatggattggtg tcatctggggttctgaaaccacctactaccagtcttccctgaagtccagggtgaccatcagcaaggataattccaagaaccaggtcagccttaagctgtcatctgtgaccgctgctgacaccgccgtgtattactgcgccaagcactactattacggaggaagctacgctatggactattggggacagggcactctcgtgactgtgagcagcggcggt ggagggtctggaggtggaggatccggtggtggtgggtcaggcggaggagggagcgagattgtgatgactcagtcaccagccaccctttctctttcacccggcgagagagcaaccctgagctgtagagccagccaggacatttctaagtacctcaactggtatcagcaaaaaccggggcaggcccctcgcctcctgatctaccatacctcacg ccttcactctggtatccccgctcggtttagcggatcaggatctggtaccgactacactctgaccatttccagcctgcagccagaagatttcgcagtgtatttctgccagcagggcaatacccttccttacaccttcggtcagggaaccaagctcgaaatcaagcaccatcaccatcatcatcaccac 100798
car8,
Soluble scFv - ak 930 MALPVTALLLPLALLLHAARP qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyqsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgq aprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik hhhhhhh 104882
car8,
Whole - nk 931 atggctctgcccgtgaccgcactcctcctgccactggctctgctgcttcacgccgctcgcccacaagtccagcttcaagaatcagggcctggtctggtgaagccatctgagactctgtccctcacttgcaccgtgagcggagtgtccctcccagactacggagtgagctggattagacagcctcccggaaagggactggagtggatc ggagtgatttggggtagcgaaaccacttactatcaatcttccctgaagtcacgggtcaccatttcaaaggataactcaaagaatcaagtgagcctcaagctctcatcagtcaccgccgctgacaccgccgtgtattactgtgccaagcattactactatggagggtcctacgccatggactactggggccagggaactctggtcactgtgtcatctggtggagga ggtagcggaggaggcgggagcggtggaggtggctccggaggcggtgggtcagaaatcgtgatgacccagagccctgcaaccctgtccctttctcccggggaacgggctaccctttcttgtcgggcatcacaagatatctcaaaatacctcaattggtatcaacagaagccgggacaggcccctaggcttcttatctaccacacctctcg cctgcatagcgggattcccgcacgctttagcgggtctggaagcgggaccgactacactctgaccatctcatctctccagcccgaggacttcgccgtctacttctgccagcagggtaacaccctgccgtacaccttcggccagggcaccaagcttgagatcaaaaccactactccgctccaaggccacccacccctgccccgaccatcgcctctcag ccgctttccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcct gtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgg gaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 104882
car8,
Whole - ak 932 MALPVTALLLPLALLLHAARPqvqlqesgpglvkpsetlsltctvsgvslp dygvs wirqppgkglewig viwgsettyyqsslks rvtiskdnsknqvslklssvtaadtavyycak hyyyggsyamdy wgqgtlvtvssggggsggggsggggsggggseivmtqspatlslspgeratls c rasqdiskyln wyqqkpgqaprlliy htsrlhs giparfsgsgsgtdytltisslqpedfavyfc qqgntlpyt fgqgtkleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeed gcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR9 car9,
scFv domain 933 eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwg settyynsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss 99789
car9,
Soluble scFv - nk 934 atggccctcccagtgaccgctctgctgctgcctctcgcacttcttctctccatgccgctcggcctgagatcgtcatgacccaaagccccgctaccctgtccctgtcacccggcgaggggcaaccctttcatgcaggccagccaggacatttctaagtacctcaactggtatcagcagaagccagggcaggctcctcgcctgctgat ctaccacaccagccgcctccacagcggtatccccgccagattttccgggagcgggtctggaaccgactacaccctcaccatctctctctgcagcccgaggatttcgccgtctatttctgccagcaggggaatactctgccgtaccaccttcggtcaaggtaccaagctggaaatcaagggaggcggaggatcaggcggtggcggaagcggag gaggtggctccggaggaggaggttcccaagtgcagcttcaagaatcaggacccggacttgtgaagccatcagaaaccctctccctgacttgtaccgtgtccggtgtgagcctccccgactacggagtctcttggattcgccagcctccggggaagggtcttgaatggattggggtgatttggggatcagagactacttactacaattcatcact taagtcacgggtcaccatcagcaaagataatagcaagaaccaagtgtcacttaagctgtcatctgtgaccgccgctgacaccgccgtgtactattgtgccaaacattactattacggagggtcttatgctatggactactggggacaggggaccctggtgactgtctctagccatcaccatcaccaccatcatcac 99789
car9,
Soluble scFv - ak 935 MALPVTALLLPLALLLHAARP eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwg settyynsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss hhhhhhh 105974
car9,
Whole - nk 936 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagcggaggcggtgggagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactacaactcatccctcaagtcac gcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccag cctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcc tgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggc gggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 105974
car9,
Whole - ak 937 MALPVTALLLPLALLLHAARPeivmtqspatlslspgeratlsc rasqdiskyln wyqqkpgqaprlliy htsrlhs giparfsgsgsgtdytltisslqpedfavyfc qqgntlpyt fgqgtkleikggggsggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslp dygvs wirqppgkglewig viwgsettyynsslks rvtiskdnsknqvslklssvtaadtavyycak cscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR10 CAR10,
scFv domain 938 qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyynsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqap rlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik 100796
CAR10,
Soluble scFv - nk 939 atggcactgcctgtcactgccctcctgctgcctctggccctccttctgcatgccgccaggccccaagtccagctgcaagagtcaggacccggactggtgaagccgtctgagactctctcactgacttgtaccgtcagcggcgtgtccctccccgactacggagtgtcatggatccgccaacctcccgggaaagggcttgaatggattggtg tcatctggggttctgaaaccacctactacaactcttccctgaagtccagggtgaccatcagcaaggataattccaagaaccaggtcagccttaagctgtcatctgtgaccgctgctgacaccgccgtgtattactgcgccaagcactactattacggaggaagctacgctatggactattggggacagggcactctcgtgactgtgagcagcggcggtgg agggtctggaggtggaggatccggtggtggtgggtcaggcggaggagggagcgagattgtgatgactcagtcaccagccaccctttctctttcacccggcgagagagcaaccctgagctgtagagccagccaggacatttctaagtacctcaactggtatcagcaaaaaccggggcaggcccctcgcctcctgatctaccatacctcacgcc ttcactctggtatccccgctcggtttagcggatcaggatctggtaccgactacactctgaccatttccagcctgcagccagaagatttcgcagtgtatttctgccagcagggcaatacccttccttacaccttcggtcagggaaccaagctcgaaatcaagcaccatcaccatcatcaccaccat 100796
CAR10,
Soluble scFv - ak 940 MALPVTALLLPLALLLHAARP qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyynsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqap rlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik hhhhhhh 105975
CAR10,
Whole - nk 941 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagcggaggcggtgggagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactacaactcatccctcaagtcac gcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccag cctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcc tgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggc gggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 105975
CAR10,
Whole - ak 942 MALPVTALLLPLALLLHAARPEIVMTQSPATLSLSPGERATLSC RASQDISKYLN WYQQKPGQAPRLLIY HTSRLHS GIPARFSGSGSGTDYTLTISSLQPEDFAVYFC QQGNTLPYT FGQGTKLEIKGGGGSGGGGSGGGGSGGGGSQVQLQSETESGPGLVKPLLSLTTCTVSGVSLP DYGVS WIRQ PPGKGLEWIG VIWGSETTYYNSSLKS RVTISKDNSKNQVSLKLSSVTAADTAVYYCAK HYYYGGSYAMDY WGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKRVKRSADAPA YKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CAR11 CAR11,
scFv domain 943 eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyn sslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss 103101
CAR11,
Soluble scFv - nk 944 Atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactacaattcatccctcaagtcacgcgtcaccatctca aaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagccaccaccatcatcaccatcaccat 103101
CAR11,
Soluble scFv - ak 945 MALPVTALLLPLALLLHAARP eivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlliyhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleikggggsggggsggggsqvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyyn sslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvss hhhhhhh 105976
CAR11,
Whole - nk 946 atggctctgcccgtgaccgcactcctcctgccactggctctgctgcttcacgccgctcgcccacaagtccagcttcaagaatcagggcctggtctggtgaagccatctgagactctgtccctcacttgcaccgtgagcggagtgtccctcccagactacggagtgagctggattagacagcctcccggaaagggactggagtggatc ggagtgatttggggtagcgaaaccacttactataactcttccctgaagtcacgggtcaccatttcaaaggataactcaaagaatcaagtgagcctcaagctctcatcagtcaccgccgctgacaccgccgtgtattactgtgccaagcattactactatggagggtcctacgccatggactactggggccagggaactctggtcactgtgtcatctggtggaggagg tagcggaggaggcgggagcggtggaggtggctccgggaggtggcggaagcgaaatcgtgatgacccagagccctgcaaccctgtccctttctcccggggaacgggctaccctttcttgtcgggcatcacaagatatctcaaaatacctcaattggtatcaacagaagccgggacaggccctaggcttcttctaccacacctctcgcc tgcatagcgggattcccgcacctttagcgggtctggaagcgggaccgactacactctgaccatctcatctctccagcccgaggacttcgccgtctacttctgccagcagggtaacaccctgccgtacaccttcggccagggcaccaagcttgagatcaaaaccactactcccgctccaaggccacccacccctgccccgaccatcgcctctcagcc gctttccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgctgtacatctttaagcaacccttcatgaggcctg tgcagactactcaagaggaggacggctgttcatgccggttcccagaggagggaaggcggctgcgaactgcgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagaggaggtacgacgtgctggacaagcggagaggacgggacccagaaatgggcggga agccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 105976
CAR11,
Whole - ak 947 MALPVTALLLPLALLLHAARPQVQLQESGPGLVKPSETLSLTCTVSGVSLP DYGVS WIRQPPGKGLEWIG VIWGSETTYYNSSLKS RVTISKDNSKNQVSLKLSSVTAADTAVYYCAK HYYYGGSYAMDY WGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERATLSC RAS QDISKYLN WYQQKPGQAPRLLIY HTSRLHS GIPARFSGSGSGTDYTLTISSLQPEDFAVYFC QQGNTLPYT FGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADA PAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CAR12 car12,
scFv domain 948 qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyynsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlli yhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik 103104
car12,
Soluble scFv - nk 949 atggctctgcccgtgaccgcactcctcctgccactggctctgctgcttcacgccgctcgcccacaagtccagcttcaagaatcagggcctggtctggtgaagccatctgagactctgtccctcacttgcaccgtgagcggagtgtccctcccagactacggagtgagctggattagacagcctcccggaaagggactggagtggatc ggagtgatttggggtagcgaaaccacttactataactcttccctgaagtcacgggtcaccatttcaaaggataactcaaagaatcaagtgagcctcaagctctcatcagtcaccgccgctgacaccgccgtgtattactgtgccaagcattactactatggagggtcctacgccatggactactggggccagggaactctggtcactgtgtcatctggtggaggagg tagcggaggaggcgggagcggtggaggtggctccgaaatcgtgatgacccagagccctgcaaccctgtccctttctcccggggaacgggctaccctttcttgtcgggcatcacaagatatctcaaaatacctcaattggtatcaacagaagccgggacaggcccctaggcttcttatctaccacacctctcgcctgcatagcgggattccc gcacgctttagcgggtctggaagcgggaccgactacactctgaccatctcatctctccagcccgaggacttcgccgtctacttctgccagcagggtaacaccctgccgtacaccttcggccagggcaccaagcttgagatcaaacatcaccaccatcatcaccatcac 103104
car12,
Soluble scFv - ak 950 MALPVTALLLPLALLLHAARP qvqlqesgpglvkpsetlsltctvsgvslpdygvswirqppgkglewigviwgsettyynsslksrvtiskdnsknqvslklssvtaadtavyycakhyyyggsyamdywgqgtlvtvssggggsggggsggggseivmtqspatlslspgeratlscrasqdiskylnwyqqkpgqaprlli yhtsrlhsgiparfsgsgsgtdytltisslqpedfavyfcqqgntlpytfgqgtkleik hhhhhhh 105977
car12,
Whole - nk 951 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttct gatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtgg aggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactacaactcatccctcaagtcacgcgtcaccatctcaa aggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcg tcgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactactcaaga ggaggacggctgttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaa agaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 105977
car12,
Whole - ak 952 MALPVTALLLPLALLLHAARPEIVMTQSPATLSLSPGERATLSC RASQDISKYLN WYQQKPGQAPRLLIY HTSRLHS GIPARFSGSGSGTDYTLTISSLQPEDFAVYFC QQGNTLPYT FGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLP DYGVS WIRQPPGKG LEWIG VIWGSETTYYNSSLKS RVTISKDNSKNQVSLKLSSVTAADTAVYYCAK HYYYGGSYAMDY WGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQG QNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR CTL019 CTL019,
Soluble scFv-His-label - nc 953 atggccctgcccgtcaccgctctgctgctgccccttgctctgcttcttcatgcagcaaggccggacatccagatgacccaaaccacctcatccctctctgcctctcttggagacagggtgaccatttcttgtcgcgccagccaggacatcagcaagtatctgaactggtatcagcagaagccggacggaaccgtgaagctcctgatctac catacctctcgcctgcatagcggcgtgccctcacgcttctctctggaagcggatcaggaaccgattattctctcactatttcaaatcttgagcaggaagatattgccacctatttctgccagcagggtaataccctgccctacaccttcggaggagggaccaagctcgaaatcaccggtggaggaggcagcggcggtggagggtctggtggaggtgg ttctgaggtgaagctgcaagaatcaggccctggacttgtggccccttcacagtccctgagcgtgacttgcaccgtgtccggagtctccctgcccgactacggagtgtcatggatcagacaacctccacggaaaggactggaatggctcggtgtcatctggggtagcgaaactacttactacaattcagccctcaaaagcaggctgactattatcaag gacaacagcaagtcccaagtctttcttaagatgaactcactccagactgacgacaccgcaatctactattgtgctaagcactactactacggaggatcctacgctatggattactggggacaaggtacttccgtcactgtctcttcacaccatcatcaccatcaccatcac CTL019,
Soluble scFv-His-label - ak 954 MALPVTALLLPLALLLHAARP diqmtqttsslsaslgdrvtiscrasqdiskylnwyqqkpdgtvklliyhtsrlhsgvpsrfsgsgsgtdysltisnleqediatyfcqqgntlpytfgggtkleitggggsggggsggggsevklqesgpglvapsqslsvtctvsgvslpdygvswirqpprkglewlgviw gsettyynsalksrltiikdnsksqvflkmnslqtddtaiyycakhyyyggsyamdywgqgtsvtvss hhhhhhh CTL019,
Whole - nk 955 atggccttaccagtgaccgccttgctcctgccgctggccttgctgctccacgccgccaggccggacatccagatgacacagactacatcctccctgtctgcctctctgggagacagagtcaccatcagttgcagggcaagtcaggacattagtaaatatttaaattggtatcagcagaaaccagatggaactgttaaactcctgatctaccata catcaagattacactcaggagtcccatcaaggttcagtggcagtgggtctggaacagattattctcaccattagcaacctggagcaagaagatattgccacttactttgccaacagggtaatacgcttccgtacacgttcggaggggggaccaagctggagatcacaggtggcggtggctcgggcggtggtgggtcgggtggcggcggatctgaggtgaa actgcaggagtcaggacctggcctggtggcgccctcacagagcctgtccgtcacatgcactgtctcaggggtctcattacccgactatggtgtaagctggattcgccagcctccacgaaagggtctggagtggctgggagtaatatggggtagtgaaaccacatactataattcagctctcaaatccagactgaccatcatcaaggacaactccaagagccaagtt ttcttaaaaatgaacagtctgcaaactgatgacacagccatttactactgtgccaaacattattactacggtggtagctatgctatggactactggggccaaggaacctcagtcaccgtctcctcaaccacgacgccagcgccgcgaccaccaacaccggcgcccaccatcgcgtcgcagcccctgtccctgcgcccagaggcgtgccggcca gcggcggggggcgcagtgcacacgaggggggctggacttcgcctgtgatatctacatctgggcgcccttggccgggacttgtggggtccttctcctgtcactggttatcaccctttactgcaaacggggcagaaagaaactcctgtatatattcaaacaaccatttatgaccagtacaaactactcaagaggaagatggctgtagctgccgat ttccagaagaagaagaagggaggatgtgaactgagagtgaagttcagcaggagcgcagacgcccccgcgtacaagcagggccagaaccagctataacgagctcaatctaggacgaagagaggagtacgatgttttggacaagagacgtggccgggaccctgagatgggggggaaagccgagaaggaagaaccctcaggaaggcctgtacaatgaactgcagaa agataagatggcggaggcctacagtgagattgggatgaaaggcgagcgccggaggggcaaggggcacgatggcctttaccagggtctcagtacagccaccaaggacacctacgacgcccttcacatgcaggccctgccccctcgc CTL019,
Whole - ak 956 MALPVTALLLPLALLLHAARPdiqmtqttsslsaslgdrvtiscrasqdiskylnwyqqkpdgtvklliyhtsrlhsgvpsrfsgsgsgtdysltisnleqediatyfcqqgntlpytfgggtkleitggggsggggsggggsevklqesgpglvapsqslsvtctvsgvslpdygv swirqpprkglewlgviwgsettyynsalksrltiikdnsksqvflkmnslqtddtaiyycakhyyyggsyamdywgqgtsvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpe eeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CTL019,
scFv domain 957 diqmtqttsslsaslgdrvtiscrasqdiskylnwyqqkpdgtvklliyhtsrlhsgvpsrfsgsgsgtdysltisnleqediatyfcqqgntlpytfgggtkleitggggsggggsggggsevklqesgpglvapsqslsvtctvsgvslpdygvswirqpprkglewlgviw gsettyynsalksrltiikdnsksqvflkmnslqtddtaiyycakhyyyggsyamdywgqgtsvtvss mCAR1,
scFv 983 QVQLLESGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYSCARKTISSVVDFYFDYWGQGTTVTGGGSGGGSGGGSGGGSELVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPK PLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQYNRYPYTSFFFTKLEIKRRS mCAR1,
Whole - ak 984 QVQLLESGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYSCARKTISSVVDFYFDYWGQGTTVTGGGSGGGSGGGSGGGSELVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPK PLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQYNRYPYTSFFFTKLEIKRRSKIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELN LGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR mCAR2 scFv 985 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTI IKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSE mCAR2
CAR - ak 986 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTI IKDNSKSQVFLKMNSLQTDDTAIY YCAKHYYYGGSYAMDYWGQGTSVTVSSESKYGPPCPPCPMFWVLVVVGGVLACYSLLVTVAFIIFWVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLY NELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRL mCAR2,
Whole - ak 987 DIQMTQTT SSLSASLGDR VTISCRASQD ISKYLNWYQQ KPDGTVKLLI YHTSRLHSGV PSRFSGSGSG TDYSLTISNL EQEDIATYFC QQGNTLPYTF GGGTKLEITG STSGSGKPGS GEGSTKGEVK LQESGPGLVA PSQSLSVTCT VSGVSLPDYG VSWIRQPPRK GLEWLGVIWG SETTY YNSAL KSRLTIIKDN SKSQVFLKMN SLQTDDTAIY YCAKHYYYGG SYAMDYWGQG TSVTVSSESK YGPPCPPCPM FWVLVVVGGV LACYSLLVTV AFIIFWVKRG RKKLLYIFKQ PFMRPVQTTQ EEDGCSCRFE EEEGGCELRV KFSRSADAPA YQQGQNQLYN ELNLGRREEY D VLDKRRGRD PEMGGKPRRK NPQEGLYNEL QKDKMAEAYS EIGMKGERRR GKGHDGLYQG LSTATKDTYD ALHMQALPPR LEGGGEGRGS LLTCGDVEEN PGPRMLLLVT SLLLCELPHP AFLLIPRKVC NGIGIGEFKD SLSINATNIK HFKNCTSISG DLHILPVAFR GDSFTHTPPL DPQELDILKT VKEITGFLLI QAWPENRTDL HAFENLEIIR GRTKQHGQFS LAVVSLNITS LGLRSLKEIS DGDVIISGNK NLCYANTINW KKLFGTSGQK TKIISNRGEN SCKATGQVCH ALCSPEGCWG PEPRDCVSCR NVSRGRECVD KCN LLEGEPR EFVENSECIQ CHPECLPQAM NITCTGRGPD NCIQCAHYID GPHCVKTCPA GVMGENNTLV WKYADAGHVC HLCHPNCTYG CTGPGLEGCP TNGPKIPSIA TGMVGALLLL LVVALGIGLF M mCAR3,
scFv 988 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTI IKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS mCAR3,
Whole - ak 989 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTI IKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSAAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREE YDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR SSJ25-C1,
VH sequence 379 QVQLLESGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYSCARKTISSVVDFYFDYWGQGTTVT SSJ25-C1,
VL sequence 380 ELVLTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFYFCQYNRYPYTSGGGTKLEIKRRS

In some embodiments, the CD19 CAR, or binding domain, contains the amino acid sequence CTL019, or is encoded by the CTL019 nucleotide sequence shown in Table 5, with or without a leader sequence or histidine tag, or a sequence substantially identical to it (for example, by at least 85%, 90%, 95% or more identical).

In some embodiments, the CDRs are specified according to the Kabat numbering system, the Chothia numbering system, or a combination thereof.

The sequences of the humanized scFv CDR domains are shown in Table 15B for heavy chain variable domains and in Table 15C for light chain variable domains. "ID" means the corresponding SEQ ID NO for each CDR.

Table 15B . Heavy chain variable domain CDR regions (according to the Kabat numbering system)

Candidate FW HCDR1 SEQ
ID HCDR2 SEQ
ID HDDR3 SEQ
ID mouse_CART19 DYGVS 958 VIWGSETTYYNSALKS 959 HYYYGGSYAMDY 960 humanized_CART19 a VH4 DYGVS 958 VIWGSETTYY S S S LKS 961 HYYYGGSYAMDY 960 humanized_CART19 b VH4 DYGVS 958 VIWGSETTYY Q S S LKS 962 HYYYGGSYAMDY 960 humanized_CART19 c VH4 DYGVS 958 VIWGSETTYYNS S LKS 963 HYYYGGSYAMDY 960

Table 15C Light chain variable domain CDR regions (according to the Kabat numbering system)

Candidate FW LCDR1 SEQ
ID LCDR2 SEQ
ID LCDR3 SEQ
ID mouse_CART19 RASQDISKYLN 964 HTSRLHS 965 QQGNTLPYT 966 humanized_CART19 a VK3 RASQDISKYLN 964 HTSRLHS 965 QQGNTLPYT 966 humanized_CART19 b VK3 RASQDISKYLN 964 HTSRLHS 965 QQGNTLPYT 966 humanized_CART19 c VK3 RASQDISKYLN 964 HTSRLHS 965 QQGNTLPYT 966

In one embodiment, a CAR is a CAR molecule comprising an antigen-binding domain for BCMA (e.g., a mouse, human, or humanized antibody, or an antibody fragment that specifically binds to BCMA, e.g., human BCMA), a transmembrane domain, and an intracellular signaling domain (e.g., an intracellular signaling domain containing a costimulatory domain and/or a core signaling domain).

Exemplary CAR molecules are listed in Table 16 or Table 1 in WO2016/014565 or are also listed here. The CAR molecules in Table 16 contain an antigen-binding domain for BCMA, for example, the amino acid sequence of any antigen-binding domain for BCMA shown in Table 11 or 12.

Table 16 Exemplary CAR molecules. The sequences are given with the leader sequence.

Name/Description SEQID NO: Subsequence 139109 139109 - ak
Whole CAR 789 MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGK APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNL GRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139109 - nk
Whole CAR 790 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAATTGGTGGAATCAGGGGGAGGACTTGTGTCAGCCTGGAGGATCGCTGAGACTGTCATGTGCCGTGTCCGGCTTTGCCCTGTCCAACCACGGGATGTCCTGGGTCCGCCGCGCGCCTGGAAAGGGCCTCGAATGGGTGTCGGGTATTG TGTACAGCGGTAGCACCTACTATGCCGCATCCGTGAAGGGGAGATTACCATCAGCCGGGACAACTCCAGGAACACTCTGTACCTCCAAATGAATTCGCTGAGGCCAGAGGACACTGCCATCTACTACTGCTCCGCGCATGGCGGAGAGTCCGACGTCTGGGGACAGGGGACCACCGTGACCGTGTCTAGCGCGTCCGGCGGAGGCGGCAGCGGGGGTCGGGCAT CAGGGGGCGGCGGATCGGACATCCAGCTCACCCAGTCCCCGAGCTCGCTGTCCGCCTCCGTGGGAGATCGGGTCACCATCACGTGCCGCGCCAGCCAGTCGATTTCCTCCTACCTGAACTGGTACCAACAGAAGCCCGGAAAAGCCCCGAAGCTTCTCATCTACGCCGCCTCGAGCCTGCAGTCAGGAGTGCCCTCACGGTTCTCCGGCTCCGGTTCCGGTACTGA TTTCACCCTGACCATTTCCTCCCTGCAACCGGAGACTTCGCTACTTACTACTGCCAGCAGTCGTACTCCACCCCTACACTTTCGGACAAGGCACCAAGGTCGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTC GCCTGCGATATCTACATTTGGGCCCTCTGGCTGGTACTTGCGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCCGCAGCGCA GATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGC AAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139103 139103 - ak
Whole CAR 791 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGRSLRLSCAASGFTFSNYAMSWVRQAPGKGLGWVSGISRSGENTYYADSVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARSPAHYYGGMDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIVLTQSPGTLSLSPGERATLSCRASQSISSSFLAWYQQK PGQAPRLLIYGASRRATGIPDRFSGSGSGTDFTLTISRLEPEDSAVYYCQQYHSSPSWTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELN LGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139103 - nk
Whole CAR 792 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGCAACCCGGAAGATCGCTTAGACTGTCGTGTGCCGCCAGCGGGTTCACTTTCTCGAACTACGCGATGTCCTGGTCCGCCAGGCACCCGGAAAGGGACTCGGTTGGGTGTCCGGCATTTCCCGG TCCGGCGAAAATACCTACTACGCCGACTCCGTGAAGGGCCGCTTCACCATCTCAAGGGACAACAGCAAAAACACCCTGTACTTGCAAATGAACTCCCTGCGGGATGAAGATACAGCCGTGTACTATTGCGCCCGGTCGCCTGCCCATTACTACGGCGGAATGGACGTCTGGGGACAGGGAACCACTGTGACTGTCAGCAGCGCGTCGGGTGGCGGCGGCTCAGGG GGTCGGGCCTCCGGGGGGGGAGGGTCCGACATCGTGCTGACCCAGTCCCCGGGAACCCTGAGCCTGAGCCCGGGAGAGCGCGCGACCCTGTCATGCCGGGCATCCCAGAAGCATTAGCTCCTCCTTTCTCGCCTGGTATCAGCAGAAGCCCGGACAGGCCCCGAGGCTGCTGATCTACGGCGCTAGCAGAAGGGCTACCGGAATCCCAGACCGGTTCTCC GGCTCCGGTTCCGGGACCGATTTCACCCTTACTATCTCGCGCCTGGAACCTGAGGACTCCGCCGTCTACTACTGCCAGCAGTACCACTCATCCCCGTCGTGGACGTTCGGACAGGGCACCAAGCTGGAGATTAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGCATGTAGACCCGCAGCTGGTGGGC CGTGCATACCCGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGGA ACTGCGCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGG TATGAAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139105 139105 - ak
Whole CAR 793 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCSVHSFLAYWGQGTLVTVSSASGGGGSGGRASGGGGSDIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPG QSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNEL NLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139105 - nk
Whole CAR 794 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTGCAACTCGTCGAATCCGGTGGAGGTCTGGTCCAACCTGGTAGAAGCCTGAGACTGTCGTGTGCGGCCAGCGGATTCACCTTTGATGACTATGCTATGCACTGGTGCGGCAGGCCCCAGGAAAGGGCCTGGAATGGGTGTCGGGAATTAGCTG GAACTCCGGGTCCATTGGCTACGCCGACTCCGTGAAGGGCCGCTTCACCATCTCCCGCGACAACGCAAAGAACTCCCTGTACTTGCAAATGAACTCGCTCAGGGCTGAGGATACCGCGCTGTACTACTGCTCCGTGCATTCCTTCCTGGCCTACTGGGGACAGGGAACTCTGGTCACCGTGTCGAGCCCTCCGGCGGCGGGGCTCGGGTGGACGGGCCTCGGGC GGAGGGGGGTCCGACATCGTGATGACCCAGACCCCGCTGAGCTTGCCCGTGACTCCCGGAGAGCCTGCATCCATCTCCTGCCGGTCATCCCAAGTCCCTTCTCCACTCCAACGGATACAACTACCTCGACTGGTACCTCCAGAAGCCGGGACAGAGCCCTCAGCTTCTGATCTACCTGGGGTCAAATAGAGCCTCAGGAGTGCCGGATCGGTTCAGCGGATCTGGTT CGGGAACTGATTTCACTCTGAAGATTTCCCGCGTGGAAGCCGAGGACGTGGGCGTCTACTACTGTATGCAGGCGCTGCAGACCCCCTATACCTTCGGCCAAGGGACGAAAGTGGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGG GTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAATTC AGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGAAGCCGCGCAGAAAGAATCCCCAAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAAC GCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139111 139111 - ak
Whole CAR 795 MALPVTALLLPLALLLHAARPEVQLLESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIVMTQTPLSLSVTPGQPASISCKSSQSLLRNDGKTPLYWYLQK AGQPPQLLIYEVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGAYYCMQNIQFPSFGGGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNL GRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139111 - nk
Whole CAR 796 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAATTGTTGGAATCTGGAGGAGGACTTGTGTCAGCCTGGAGGATCACTGAGACTTTCGTGTGCGGTGTCAGGCTTCGCCCTGAGCAACCACGGCATGAGCTGGGTGCGGAGAGCCCCGGGGAAGGGTCTGGAATGGGTGTCCGGGATCGTCTACT CCGGTTCAACTTACTACGCCGCAAGCGTGAAGGGTCGCTTCACCATTTCCCGCGATAACTCCCGGAACACCCTGTACCTCCAAATGAACTCCCTGCGGCCCGAGGACACCGCCATCTACTACTGTTCCGCCGCATGGAGGAGTCCGATGTCTGGGGACAGGGCACTACCGTGACCGTGTCGAGCGCCTCGGGGGGAGGAGGCTCCGGCGGTCGCGCCCTCCGGGG GGGGTGGCAGCGACATTGTGGACGCAGACTCCACTCTCGCTGTCCGTGACCCCGGGACAGCCCGTCCATCTCGTGCAAGAGCTCCCAGAGCCTGCTGAGGAACGACGGAAAGACTCCTCTGTATTGGTACCTCCAGAAGGCTGGACAGCCCCCGCAACTGCTCATCTACGAAGTGTCAAATCGCTTCTCCGGGGTGCCGGATCGGTTTTCCGGCTCGGGATCGG GCACCGACTTCACCCTGAAAATCTCCAGGGTCGAGGCCGAGGACGTGGGAGCCTACTACTGCATGCAAAACATCCAGTTCCCTTCCTTCGGCGGCGGCACAAAGCTGGAGATTAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGCATGTAGACCCGCAGCTGGTGGGCCGTGCATACCCGGGGTC TTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCC GCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCA GAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139100 139100 - ak
Whole CAR 797 MALPVTALLLPLALLLHAARPQVQLVQSGAEVRKTGASVKVSCKASGYIFDNFGINWVRQAPGQGLEWMGWINPKNNNTNYAQKFQGRVTITADESTNTAYMEVSSLRSEDTAVYYCARGPYYYQSYMDVWGQGTMVTVSSASGGGGSGGRASGGGGSDIVMTQTPLSLPVTPGEPASISCRSSQSLLHSNGYNYLNW YLQKPGQSPQLLIYLGSKRASGVPDRFSGSGSGTDFTLHITRVGAEDVGVYYCMQALQTPYTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQ NQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139100 - nk
Whole CAR 798 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTCCAACTCGTCCAGTCCGGCGCAGAAGTCAGAAAAACCGGTGCTAGCGTGAAAGTGTCCTGCAAGGCCTCCGGCTACATTTTCGATAACTTCGGAATCAACTGGGTCAGACAGGCCCCGGGCCAGGGGCTGGAATGGATGGGATGGATCAACCCCAAGAACAA CAACACCAACTACGCACAGAAGTTCCAGGGCCGCGTGACTATCACCGCCGATGAATCGACCAATACCGCCTACATGGAGGTGTCCTCCCTGCGGTCGGAGGACACTGCCGTGTATTACTGCGCGAGGGGCCCATACTACCAAAGCTACATGGACGTCTGGGGACAGGGAACCATGGTGACCGTGTCATCCGCCTCCGGTGGTGGAGGCTCCGGGGGGCGGG CTTCAGGAGGCGGAGGAAGCGATATTGTGATGACCCAGACTCCGCTTAGCCTGCCCGTGACTCCTGGAGAACCGGCCTCCATTTCCTGCCGGTCCTCGCAATCACTCCTGCATTCCAACGGTTACAACTACCTGAATTGGTACCTCCAGAAGCCTGGCCAGTCGCCCCAGTTGCTGATCTATCTGGGCTCGAAGCGCGCCTCCGGGGTGCCTGACCGGTTTAGCGGATCTG GGAGCGGCACGGACTTCACTCTCCACATCACCCGCGTGGGAGCGGAGGACGTGGGAGTGTACTGTATGCAGGCGCCTGCAGACTCCGTACACATTCGGACAGGGCACCAAGCTGGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGCATGTAGACCCGCAGCTGGTGGGGCCGTG CATACCCGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTCAAGAGGAGGACGGCTGTTGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGC GCGTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATG AAAGGGGAACGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139101 139101 - ak
Whole CAR 799 MALPVTALLLPLALLLHAARPQVQLQESGGGLVQPGGSLRLSCAASGFTFSSDAMTWVRQAPGKGLEWVSVISGSGGTTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKLDSSGYYYARGPRYWGQGTLVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLN WYQQKPGKAPKLLIYGASTLASGVPARFSGSGSGTHFTLTINSLQSEDSATYYCQQSYKRASFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQ LYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139101 - nk
Whole CAR 800 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTGCAACTTCAAGAATCAGGCGGAGGACTCGTGCAGCCCGGAGGATCATTGCGGCTCTCGTGCGCCGCCTCGGGCTTCACCTTCTCGAGCGACGCCATGACCTGGGTCCGCCAGGCCCCGGGGAAGGGGCTGGAATGGTGTCTGTGATTTCCGGCTCCG GGGGAACTACGTACTACGCCGATTCCGTGAAAGGTCGCTTCACTATCTCCCGGGACAACAGCAAGAACACCCTTTATCTGCAAATGAATTCCCTCCGCGCCGAGGACACCGCCGTGTACTACTGCGCCAAGCTGGACTCCTCGGGCTACTACTATGCCCGGGGTCCGAGATACTGGGGACAGGGAACCCTCGTGTGACCGTGTCCTCCGCGTCCGGCGGAGGAGGG TCGGGAGGGCGGGCCCTCCGGCGGCGGCGGTTCGGACATCCAGCTGACCCAGTCCCCATCCTCACTGAGCGCAAGCGTGTGGGCGACAAGAGTCACCATTACATGCAGGGCGTCCCAGAGCATCAGCTCCTACCTGAACTGGTACCAACAGAAGCCTGGAAAGGCTCCTAAGCTGTTGATCTACGGGGCTTCGACCCTGGCATCCGGGGTGCCCGCGAGGTTTAGCGGA AGCGGTAGCGGCACTCACTTCACTCTGACCATTAACAGCCTCCAGTCCGAGGATTCAGCCACTTACTACTGTCAGCAGTCCTACAAGCGGGCCAGCTTCGGACAGGGCACTAAGGTCGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATAC CCGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGTCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCAGAGGAGGAGGAAGGCGGCTGGAACTGCGCG TGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAG GGGAACGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139102 139102 - ak
Whole CAR 801 MALPVTALLLPLALLLHAARPQVQLVQSGAEVKKPGASVKVSCKASGYTFSNYGITWVRQAPGQGLEWMGWISAYNGNTNYAQKFQGRVTMTRNTSISTAYMELSSLRSEDTAVYYCARGPYYYMDVWGKGTMVTVSSASGGGGSGGRASGGGGSEIVMTQSPLSLPVTPGEPASISCRSSQSLLYSNGYNYVDW YLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFKLQISRVEAEDVGIYYCMQGRQFPYSFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQ NQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139102 - nk
Whole CAR 802 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTCCAACTGGTCCAGAGCGGTGCAGAAGTGAAGAAGCCCGGAGCGAGCCGTGAAAGTGTCCTGCAAGGCTTCCGGGTACACCTTCTCCAACTACGGCATCACTTGGGTGCGCCAGGCCCCGGGACAGGGCCTGGAATGGATGGGGTGGATTTCCGCG TACAACGGCAATACGAACTACCGCTCAGAAGTTCCAGGGTAGAGTGACCATGACTAGGAACACCCATTTCCACCGCCTACATGGAACTGTCCTCCCTGCGGAGCGAGGACACCGCCGTGTACTATTGCGCCCGGGGACCATACTACTACTACTACATGGATGTCTGGGGGAAGGGGACTATGGTCACCGTGTCATCCGCCTCGGGAGGCGGCGGATCAGGAGGACGCGCC TCTGGTGGTGGAGGATCGGAGATCGTGATGACCCAGAGCCCTCTCCTTGCCCGTGACTCCTGGGGAGCCCGCATCCATTTCATGCCGGAGCTCCCAGTCACTTCTCTACTCCAACGGCTATAACTACGTGGATTGGTACCTCCAAAAGCCGGGCCAGAGCCCGCAGCTGCTGATCTACCTGGGCTCGAACAGGGCCAGCGGAGTGCCTGACCGGTTCTCCGGGTCG GGAAGCGGGACCGACTTCAAGCTGCAAATCTCGAGAGTGGAGGCCGAGGACGTGGGAATCTACTGTATGCAGGGCCGCCAGTTTCCGTACTCGTTCGGACAGGGCACCAAAGTGGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCAT ACCCGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGC GTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCGAAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAA AGGGGAACCGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139104 139104 - ak
Whole CAR 803 MALPVTALLLPLALLLHAARPEVQLLETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVLTQSPATLSVSPGESATLSCRASQSVSSNLAWYQQKPGQAPRL LIYGASTRASGIPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYGSSLTFGGGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDV LDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139104 - nk
Whole CAR 804 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAATTGCTCGAAACTGGAGGAGGTCTGGTGCAACCTGGAGGATCACTTCGCCTGTCCTGCGCCGTGTCGGCTTTGCCCTGTCCAACCATGGAATGAGCTGGGTCCGCCGCGCGCCGGGGAAGGGCCTCGAATGGGTGTCCGGCATCGTCTACTCC GGCTCCCACCTACTACGCCGCGTCCGTGAAGGGCCGGTTCACGATTTCACGGGACAACTCGCGGAACACCCTGTACCTCCAAATGAATTCCCTTCGGCCGGAGGATACTGCCATCTACTACTGCTCCGCCCACGGTGGCGAATCCGACGTCTGGGGCCAGGGAACCACCGTGACCGTGTCCAGCGCGTCCGGGGGAGGAGGAAGCGGGGGTAGAGCATCGGGTGGA GGCGGATCAGAGATCGTGCTGACCAGTCCCCCGCCACCTTGAGCGTGTCACCAGGAGAGTCCGCCACTGTCATGCCGCCAGCCAGTCCGTGTCCTCCAACCTGGCTTGGTACCAGCAGAAGCCGGGGCAGGCCCCTAGACTCCTGATCTATGGGGCGTCGACCCGGGCATCTGGAATTCCCGATAGGTTCAGCGGATCGGGCTCGGGCACTGACTTCACT CTGACCATCTCCTCGCTGCAAGCCGAGGACGTGGCTGTGTACTGTCAGCAGTACGGAAGCTCCCTGACTTTCGGTGGCGGGACCAAAGTCGAGATTAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGCATGTAGACCCGCAGCTGGTGGGCCGTGCATACCCGGGGTCTTGACTTCGCCTGC GATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGTCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGTGAAATTCAGCCGCAGCGCAGATGCT CCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAGG CCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139106 139106 - ak
Whole CAR 805 MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVMTQSPATLSVSPGERATLSCRASQSVSSKLAWYQQKPGQAPRL LMYGASIRATGIPDRFSGSGSGTEFTLTISSLEPEDFAVYYCQQYGSSSWTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDV LDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139106 - nk
Whole CAR 806 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAATTGGTGGAAACTGGAGGAGGACTTGTGCAACCTGGAGGATCATTGAGACTGAGCTGCGCAGTGTCGGATTCGCCCTGAGCAACCATGGAATGTCCTGGGTCAGAAGGGCCCCTGGAAAAGGCCTCGAATGGGTGTCAGGGATCGTGT ACTCCGGTTCCACTTACTACGCCGCCTCCGTGAAGGGGCGCTTCACTATCTCACGGGATAACTCCCGCAATACCCTGTACCTCCAAATGAACAGCCTGCGGCCGGAGGATACCGCCATCTACTACTACTGTTCCGCCCACGGTGGAGAGTCTGACGTCTGGGGCCAGGGAACTACCGTGACCGTGTCCTCCGTCCGGCGGTGGAGGGAGCGGCGGCCGCGCCAGCGGCG GCGGAGGCTCCGAGATCGTGATGACCCAGAGCCCCGCTACTCTGTCGTGTCGCCCGGAGAAAGGGCGACCCTGTCCTGCCGGGCGTCGCAGTCCGTGTGCAGCAAGCTGGCTTGGTACCAGCAGAAGCCGGCCAGGCACCACGCCTGCTTATGTACGGTGCCTCCATTCGGGCCACCGGAATCCCGGACCGGTTCTCGGGGTCGGGGTCCGGTACC GAGTTCACACTGACCATTTCCTCGCTCGAGCCCGAGGACTTTGCCGTCTATTACTGCCAGCAGTACGGCTCCTCCTCATGGACGTTCGGCCAGGGGACCAAGGTCGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTC TTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAATTCAGCC GCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCA GAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139107 139107 - ak
Whole CAR 807 MALPVTALLLPLALLLHAARPEVQLVETGGGVVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVGSTNLAWYQQKPG QAPRLLIYDASNRATGIPDRFSGGGSGTDFTLTISRLEPEDFAVYYCQQYGSPPWTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELN LGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139107 - nk
Whole CAR 808 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAATTGGTGGAGACTGGAGGAGGAGTGGTGCAACCTGGAGGAAGCCTGAGACTGTCATGCGCGGTGTCGGGCTTCGCCCTCTCCAACCACGGAATGTCCTGGGTCCGCCGGGCCCCTGGGAAAGGACTTGAATGGGTGTCCGGCATCG TGTACTCGGGTTCCACCTACTACGCGGCCTCAGTGAAGGGCCGGTTTACTATTAGCCGCGACAACTCCAGAAACACACTGTACCTCCAAATGAACTCGCTGCGGCCGGAAGATACCGCTATCTACTACTGCTCCGCCCATGGGGGAGAGTCGGACGTCTGGGGACAGGGCACCACTGTCACTGTGTCCAGCGCTTCCGGGTGGTGGAAGCGGGGGACGGG CCTCAGGAGGCGGTGGCAGCGAGATTGTGCTGACCCAGTCCCCCGGGACCCTGAGCCTGTCCCCGGGAGAAAGGGCCACCCTCTCCTGTCGGGCATCCCAGTCCGTGGGGTCTACTAACCTTGCATGGTACCAGCAGAAGCCCGGCCAGGCCCCTCGCCTGCTGATCTACGACGCGTCCAATAGAGCCACCGGCATCCCGGATCGCTTCAGCGGAGGCGGATC GGGCACCGACTTCACCCTCACCATTTCAAGGCTGGAACCGGAGGACTTCGCCGTGTACTGCCAGCAGTATGGTTCGTCCCCACCCTGGACGTTCGGCCAGGGGACTAAGGTCGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCC GGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCTCTGGCTGGTACTTGCGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCTGTG AAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGG GGAACGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139108 139108 - ak
Whole CAR 809 MALPVTALLLPLALLLHAARPQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARESGDGMDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQMTQSPSSLSASVGDRVTITCRASQsissyLNWYQQ KPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTLAFGQGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNEL NLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139108 - nk
Whole CAR 810 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGAAACCTGGAGGATCATTGAGACTGTCATGCGCGGCCTCGGGATTCACGTTCTCCGATTACTACATGAGCTGGATTCGCCAGGCTCCGGGGAAGGGACTGGAATGGGTGTCCTACATTTCCTCATCCGG CTCCACCATCTACTACGCGGACTCCGTGAAGGGGAGATTCACCATTAGCCGCGATAACGCCAAGAACAGCCTGTACCTTTCAGATGAACTCCCTGCGGGCTGAAGATACTGCCGTCTACTACTGCGCAAGGGAGAGCGGAGATGGGATGGACGTCTGGGGACAGGGTACCACTGTGACCGTGTCGTCGGCTCCGGCGGAGGGGGTTCGGGTGGAAGGGCC AGCGGCGGCGGAGGCAGCGACATCCAGATGACCCAGTCCCCCTCATCGCTGTCCGCCTCCGTGGGCGACCGCGTCACCATCACATGCCGGGCCTCACAGTCGATCTCCTCCTACCTCAATTGGTATCAGCAGAAGCCCGGAAAGGCCCCTAAGCTTCTGATCTACGCAGCGTCCTCCCTGCAATCCGGGGTCCCATCTCGGTTCTCCGGCTCGGGCAGCGGTACCG ACTTCACTCTGACCATCTCGAGCCTGCAGCCGGAGACTTCGCCACTTACTACTGTCAGCAAAGCTACACCCTCGCGTTTGGCCAGGGCACCAAAAGTGGACATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGCCT GCGATATCTACATTTGGGCCCCTTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGTGAAATTCAGCCAGCGCAGATG CTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGAAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAAAG GCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139110 139110 - ak
Whole CAR 811 MALPVTALLLPLALLLHAARPQVQLVQSGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLEWVSYISSSGNTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSTMVREDYWGQGTLVTVSSASGGGGSGGRASGGGGSDIVLTQSPLSLPVTLGQPASISCKSSESLVHNSGKTYLNWF HQRPGQSPRRLIYEVSNRDSGVPDRFTGSGSGTDFTLKISRVEEAEDVGVYYCMQGTHWPGTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLY NELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139110 - nk
Whole CAR 812 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTGCAACTGGTGCAAAGCGGAGGAGGATTGGTCAAACCCGGAGGAAGCCTGAGACTGTCATGCGCGGCCTCTGGATTCACCTTCTCCGATTACTACATGTCATGGATCAGACAGGCCCCGGGGAAGGGCCTCGAATGGGTGTCCTACATCTCGTCCTCC GGGAACACCATCTACTACGCCGACAGCGTGAAGGGCCGCTTTACCATTTCCCGCAAACGCAAAGAACTCGCTGTACCTTTCAGATGAATTCCCTGCGGGCTGAAGATACCGCGGTGTACTATTGCGCCCGGTCCACTATGGTCCGGGAGGACTACTGGGGACAGGGCACACTCGTGACCGTGTCCAGCGCGAGCGGGGTGGAGGCAGCGGTGGACGCGCCTCCG GCGGCGGCGGTTCAGACATCGTGCTGACTCAGTCGCCCCTGTCGCTGCCGGTCACCCTGGGCCAACCGGCCTCAATTAGCTGCAAGTCCTCGGAGAGCCTGGTGCACAACTCAGGAAAGACTTACCTGAACTGGTTCCATCAGCGGCCTGGACAGTCCCCACGGAGCTCATCTATGAAGTGTCCAACAGGGATTCGGGGTGCCCGACCGCTTCACTGGCTCCG GGTCCGGCACCGACTTCACCTTGAAAATCTCCAGAGTGGAAGCCGAGGACGTGGGCGTGTACTGTATGCAGGGTACCCACTGGCCTGGAACCTTTGGACAAGGAACTAAGCTCGAGATTAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCAT ACCCGGGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGC GTGAAATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCGAAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAA AGGGGAACCGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139112 139112 - ak
Whole CAR 813 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIRLTQSPSPLSASVGDRVTITCQASEDINKFLNWYHQTPGK APKLLIYDASTLQTGVPSRFSGSGSGTDFTLTINSLQPEDIGTYYCQQYESLPLTFGGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNL GRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139112 - nk
Whole CAR 814 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTGCAACTCGTGGAATCTGGTGGAGGACTCGTGCAACCCGGTGGAAGCCTTAGGCTGTCGTGCGCCGTCAGCGGGTTTGCTCTGAGCAACCATGGAATGTCCTGGGTCCGCCGGGCACCGGGAAAAGGGCTGGAATGGGTGTCCGGCATCGTGTA CAGCGGGTCAACCTATTACGCCGCGTCCGTGAAGGGCAGATTCACTATCTCAAGAGACAACAGCCGGAACACCCTGTACTTGCAAATGAATTCCCTGCGCCCCGAGGACACCGCCATCTACTACTGCTCCGCCCACGGAGGAGTCGGACGTGTGGGGCAGGGAACGACTGTGACTGTGTCCAGCGCATCAGGAGGGGTGGTTCGGGCGGCCGGGCCTCGGG GGGAGGAGGTTCCGACATTCGGCTGACCCAGTCCCCGTCCCCACTGTCGGCCTCCGTCGGCGACCGTGTGACCATCACTTGTCAGGCGTCCGAGGACATTAACAAGTTCCTGAACTGGTACCACCAGACCCCTGGAAAGGCCCCCAAGCTGCTGATCTACGATGCCTCGACCCTTCAAACTGGAGTGCCTAGCCGGTTTCCGGGTCCGGCTCCGGCACTGATTTCACT CTGACCATCAACTCATTGCAGCCGGAAGATATCGGACCTACTATTGCCAGCAGTACGAATCCCTCCCGCTCACATTCGGCGGGGAACCAAGGTCGAGATTAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGGTCTTGACTTCGC CTGCGATATCTACATTTGGGCCCCTTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCCGTGAAATTCAGCCGCAGCGCAGA TGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACGCAGAAGAGGCAA AGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139113 139113 - ak
Whole CAR 815 MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSETTLTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQGP RLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQPEDFAVYYCQQYNDWLPVTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEY DVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139113 - nk
Whole CAR 816 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAATTGGTGGAAACTGGAGGAGGACTTGTGCAACCTGGAGGATCATTGCGGCTCTCATGCGCTGTCTCCGGCTTCGCCCTGTCAAATCACGGGATGTCGTGGGTCAGACGGGCCCCGGGAAAGGGTCTGGAATGGGTGTCGGGGATTG TGTACAGCGGCTCCACCTACTACGCCGCTTCGGTCAAGGGCCGCTTCACTATTTCACGGGACAACAGCCGCAACACCCTCTATCTGCAAATGAACTCTCTCCGCCCGGAGGATACCGCCATCTACTACTGCTCCGCACACGGCGGCGAATCCGACGTGTGGGGACAGGGAACCACTGTCACCGTGTCGTCCGCATCCGGTGGCGGAGGATCGGGTGGCCGGGCCTCCG GGGGCGGCGGCAGCGAGACTACCCTGACCCAGTCCCCTGCCACTCTGTCCGTGAGCCCGGGAGAGAGAGCCACCCTTAGCTGCCGGGCCAGCCAGAGCGTGGGCTCCAACCTGGCCTGGTACCAGCAGAAGCCAGGACAGGGTCCCAGGCTGCTGATCTACGGAGCCTCCACTCGCGCGACCGGCATCCCCGCGAGGTTCCCGGGTCGGGTTCCGGGACC GAGTTCACCCTGACCATCTCCTCCCTCCAACCGGAGGACTTCGCGGTGTACTACTGTCAGCAGTACAACGATTGGCTGCCCGTGACATTTGGACAGGGGACGAAGGTGGAAATCAAAACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCG GGGTCTTGACTTCGCCTGCGATATCTACATTTGGGCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGGAACTGCGCGTGAA ATTCAGCCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGG GAACGCAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 139114 139114 - ak
Whole CAR 817 MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSIGSSSLAWYQQKPGQAP RLLMYGASSRASGIPDRFSGSGTDFTLTISRLEPEDFAVYYCQQYAGSPPFTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEY DVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 139114 - nk
Whole CAR 818 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAATTGGTGGAATCTGGTGGAGGACTTGTGCAACCTGGAGGATCACTGAGACTGTCATGCGCGGTGTCCGGTTTTGCCCTGAGCAATCATGGGATGTCGTGGGTCCGGCGCCCCCCGGAAAGGGTCTGGAATGGGTGTCGGGTATCG TCTACTCCGGGAGCACTTACTACGCCGCGAGCGTGAAGGGCCGCTTCACCATTTCCCGCGATAACTCCCGCAACACCCTGTACTTGCAAATGAACTCGCTCCGGCCTGAGGACACTGCCATCTACTACTGCTCCGCACACGGAGGAGAATCCGACGTGTGTGGGCCAGGGAACTACCGTGACCGTCAGCAGCGCTCCGGCGGCGGGGCTCAGGCGGACGGGCTAGCGGCGGC GGTGGCTCCGAGATCGTGCTGACCCAGTCGCCTGGCACTCTCTCGCTGAGCCCCGGGGAAAGGCAACCCTGTCCTGTCGGGCCAGCCAGTCCATTGGATCATCCTCCCTCGCCTGGTATCAGCAGAAACCGGGACAGGCTCCGCGTGCTTATGTATGGGGCAGCTCAAGAGCCTCCGGCATTCCCGACCGGTTCTCCGGGTCCGGTTCCGGCACC GATTTCACCCTGACTATCTCGAGGCTGGAGCCAGAGGACTTCGCCGTGTACTACTGCCAGCAGTACGCGGGGTCCCCGCCGTTCACGTTCGGACAGGGAACCAAGGTCGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAGCATGTAGACCCGCAGCTGGTGGGGCCGTGCATACCCGGGG TCTGACTTCGCCTGCGATATCTACATTTGGGCCCCTCTGGCTGGTACTTGCGGGGTCCTGCTGCTTTCACTCGTGATCACTCTTTACTGTAAGCGCGGTCGGAAGAAGCTGCTGTACATCTTTAAGCAACCCTTCATGAGGCCTGTGCAGACTACTCAAGAGGAGGACGGCTGTTCATGCCGGTTCCCAGAGGAGGAGGAAGGCGGCTGCGAACTGCGCGTGAAATTCAG CCGCAGCGCAGATGCTCCAGCCTACAAGCAGGGGCAGAACCAGCTCTACAACGAACTCAATCTTGGTCGGAGAGAGGAGTACGACGTGCTGGACAAGCGGAGAGGACGGGACCCAGAAATGGGCGGGAAGCCGCGCAGAAAGAATCCCCAAGAGGGCCTGTACAACGAGCTCCAAAAGGATAAGATGGCAGAAGCCTATAGCGAGATTGGTATGAAAGGGGAACG CAGAAGAGGCAAAGGCCACGACGGACTGTACCAGGGACTCAGCACCGCCACCAAGGACACCTATGACGCTCTTCACATGCAGGCCCTGCCGCCTCGG 149362 149362 -ak
Whole CAR 819 malpvtalllplalllhaarpqvqlqesgpglvkpsetlsltctvsggsisssyyywgwirqppgkglewigsiyysgsayynpslksrvtisvdtsknqfslrlssvtaadtavyycarhwqewpdafdiwgqgtmvtvssggggsggggsggggsettltqspafmsatpgdkviisckasqdiddam nwyqqkpgeaplfiiqsatspvpgipprfsgsgfgtdfsltinniesedaayyfclqhdnfpltfgqgtkleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeee ggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr 149362 - nk
Whole CAR 820 atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccaagtgcagcttcaggaaagcggaccgggcctggtcaagccatccgaaactctctccctgacttgcactgtgtctggcggttccatctcatcgtcgtactactactactggggctggattaggcagccgcccggaaagggactggagtgg atcggaagcatctactattccggctcggcgtactacaaccctagcctcaagtcgagagtgaccatctccgtggatacctccaagaaccagttttccctgcgcctgagctccgtgaccgccgctgacaccgccgtgtactactgtgctcggcattggcaggaatggcccgatgccttcgacatttggggccagggcactatggtcactgtgt catccgggggtggaggcagcgggggaggagggtccggggggggaggttcagagacaaccttgacccagtcacccgcattcatgtccgccactccggagacaaggtcatcatctcgtgcaaagcgtcccaggatatcgacgatgccatgaattggtaccagcagaagcctggcgaagcgccgctgttcattatccaatccgcaacctcgccc gtgcctggaatcccaccgcggttcagcggcagcggtttcggaaccgacttttccctgaccattaacaacattgagtccgaggacgccgcctactactacttctgcctgcaacacgacaacttccctctcacgttcggccagggaaccaagctggaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcct ctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctg tgcagactactcaagaggaggacggctgttcatgccggttcccagaggagggaaggcggctgcgaactgcgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagaggaggtacgacgtgctggacaagcggagaggacgggacccagaaatgggcggga agccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 149363 149363 - ak
Whole CAR 821 malpvtalllplallllhaarpqvnlresgpalvkptqtltltctfsgfslrtsgmcvswirqppgkalewlaridwdedkfystslktrltiskdtsdnqvvlrmtnmdpadtatyycarsgaggtsatafdiwgpgtmvtvssggggsggggsggggsdiqmtqspsslsasvgdrvtitcras qdiynnlawfqlkpgsaprslmyaanksqsgvpsrfsgsasgtdftltisslqpedfatyycqhyyrfpysfgqgtkleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeee ggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr 149363 - nk
Whole CAR 822 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccaagtcaatctgcgcgaatccggccccgccttggtcaagcctacccagaccctcactctcggcttctccctgcggacttccgggatgtgcgtgtcctggatcagacagcctccgggaaaggccctggag tggctcgctcgcattgactgggatgaggacaagttctactccacctcactcaagaccaggctgaccatcagcaaagatacctctgacaaccaagtggtgctccgcatgaccaacatggacccagccgacactgccacttactactgcgcgaggagcggagcgggcggaacctccgccaccgccttcgatatttggggcccgggtaccatggtcaccgtgt caagcgggagggaggggggtccgggggcggcggttccgggggaggcggatcggacattcagatgactcagtcaccatcgtccctgagcgctagcgtgggcgacagagtgacaatcacttgccgggcatcccaggacatctctataacaaccttgcgtggttccagctgaagcctggttccgcaccgcggtcacttatgtacgccgccaac aagagccagtcgggagtgccgtcccggttttccggttcggcctcgggaactgacttcaccctgacgatctccagcctgcaacccgaggatttcgccacctactactgccagcactactaccgctttccctactcgttcggcacagggaaccaagctggaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcc tctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcct gtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgg gaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 149364 149364 - ak
Whole CAR 823 malpvtalllplalllhaarpevqlvesggglvkpggslrlscaasgftfssysmnwvrqapgkglewvssisssssyiyyadsvkgrftisrdnaknslylqmnslraedtavyycaktiaavyafdiwgqgttvtvssggggsggggsggggseivltqsplslpvtpeepasiscrssqsllhsngynyl dwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqalqtpytfgqgtkleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeegg celrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr 149364 - nk
Whole CAR 824 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaagtgcagcttgtcgaatccggggggggactggtcaagccggggcggatcactgagactgtcctgcgccgcgagcggcttcacgttctcctcctactccatgaactgggtccgccaagcccccgggaagggactggaatgggg tgtcctctatctcctcgtcgtcgtcctacatctactacgccgactccgtgaagggaagattcaccatttcccgcgacaacgcaaagaactcactgtacttgcaaatgaactcactccggccgaagatactgctgtgtactattgcgccaagactattgccgccgtctacgctttcgacatctggggccagggaaccaccgtgactgtg tcgtccggtggtggtggctcggccggagggaagcggcggcggggggtccgagattgtgctgacccagtcgccactgagcctccctgtgacccccgaggaacccgccagcatcagctgccggtccagccagtccctgctccactccaacggatacaattacctcgattggtaccttcagaagcctggacaaagcccgcagctgctcatct acttgggatcaaaccgcgcgtcaggagtgcctgaccggttctccggctcgggcagcggtaccgatttcaccctgaaaatctccagggtggaggcagaggacgtgggagtgtattactgtatgcaggcgctgcagactccgtacacatttgggcagggcaccaagctggagatcaagaccactaccccagcaccgaggccacccaccccggctcct accatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttta agcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacg ggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 149365 149365 - ak
Whole CAR 825 malpvtalllplalllhaarpevqlvesggglvkpggslrlscaasgftfsdyymswirqapgkglewvsyisssgstiyyadsvkgrftisrdnaknslylqmnslraedtavyycardlrgafdiwgqgtmvtvsssggggsggggsggggssyvltqspsvsaapgytatiscggnnigtksvhwyqqkp gqapllvirddsvrpskipgrfsgsnsgnmatltisgvqagdeadfycqvwdsdsehvvfgggtkltvltttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeeggcelrvkfs rsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr 149365 - nk
Whole CAR 826 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaagtccagctcgtggagtccggcggaggccttgtgaagcctggaggttcgctgagactgtcctgcgccgcctccggcttcaccttctccgactactacatgtcctggatcagacaggccccgggaaagggcctggaatgg gtgtcctacatctcgtcatcgggcagcactatctactacgcggactcagtgaaggggcggttcaccatttcccgggataacgcgaagaactcgctgtatctgcaaatgaactcactgagggccgaggacaccgccgtgtactactgcgcccgcgatctccgcggggcatttgacatctggggacagggaaccatggtcacagtgtccagc ggagggggaggatcgggtggcggaggttccggggtggaggctcctcctacgtgctgactcagagcccaagcgtcagcgctgcgcccggttacacggcaaccatctcctgtggcggaaacaacattgggaccaagtctgtgcactggtatcagcagaagccgggccaagctcccctgttggtgatccgcgatgactccgt gcggcctagcaaaattccgggacggttctccggctccaacagcggcaatatggccactctcaccatctcgggagtgcaggccggagatgaagccgacttctactgccaagtctgggactcagactccgagcatgtggtgttcgggggcggaaccaagctgactgtgctcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccag cctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcc tgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggc gggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 149366 149366 - ak
Whole CAR 827 malpvtalllplalllhaarpqvqlvqsgaevkkpgasvkvsckpsgytvtshyihwvrrapgqglewmgminpsggvtaysqtlqgrvtmtsdtssstvymelsslrsedtamyycaregsgsgwyfdfwgrgtlvtvssggggsggggsggggssyvltqppsvsvspgqtasitcsgdglsk kyvswyqqkagqspvvlisrdkerpsgipdrfsgsnsadtatltisgtqamdeadyycqawddttvvfgggtkltvltttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeeggcel rvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr 149366 - nk
Whole CAR 828 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccaagtgcagctggtgcagagcggggccgaagtcaagaagccgggggcctccgtgaaagtgtcctgcaagccttcgggatacaccgtgacctcccactacattcattgggtccgccgcgccccggccaaggactcgagt ggatgggcatgatcaaccctagcggcggagtgaccgcgtacagccagacgctgcagggacgcgtgactatgacctcggatacctcctcctccaccgtcttatggaactgtccagcctgcggtccgaggataccgccatgtactactgcgcccgggaaggatcaggctccgggtggtattcgacttctggggaagaggcaccctcgt gactgtgtcatctgggggaggggttccggtggtggcggatcgggaggaggcggttcatcctacgtgctgacccagccaccctccgtgtccgtgagccccggccagactgcatcgattacatgtagcggcgacggcctctctccaagaaatacgtgtcgtggtaccagcagaaggccggacagagcccggtggtgctgatctcaagagataagg agcggcctagcggaatcccggacaggttctcggttccaactccgcggacactgctactctgaccatctcggggacccaggctatggacgaagccgattactactgccaagcctgggacgacactactgtcgtgttggagggggcaccaagttgaccgtccttaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtcc ctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcag actactcaagaggagaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgc gcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 149367 149367 - ak
Whole CAR 829 malpvtalllplallllhaarpqvqlqesgpglvkpsqtlsltctvsggsissggyywswirqhpgkglewigyiyysgstyynpslksrvtisvdtsknqfslklssvtaadtavyycaragiaarlrgafdiwgqgtmvtvssggggsggggsggggsdivmtqspssvsasvgdrviitcrasq girnwlawyqqkpgkapnlliyaasnlqsgvpsrfsgsgsgadftltisslqpedvatyycqkynsapftfgpgtkvdiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpee eeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr 149367 - nk
Whole CAR 830 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccaagtgcagcttcaggagagcggcccgggactcgtgaagccgtcccagaccctgtccctgacttgcaccgtgtcgggaggaagcatctcgagcggaggctactattggtcgtggattcggcagcaccctggaaaggg cctggaatggatcggctacatctactactccggctcgacctactacaacccatcgctgaagtccagagtgacaatctcagtggacacgtccaagaatcagttcagcctgaagctctcttccgtgactgcggccgacaccgccgtgtactactgcgcacgcgctggaattgccgcccggctgaggggtgccttcgacatttggggacagggca ccatggtcaccgtgtcctccggcggcggaggttccgggggtggaggctcaggaggaggggggtccgacatcgtcatgactcagtcgccctcaagcgtcagcgcgtccgtcggggacagagtgatcatcacctgtcgggcgtcccagggaattcgcaactggctggcctggtatcagcagaagcccggaaaggccccca acctgttgatctacgccgcctcaaacctccaatccggggtgccgagccgcttcagcggctccggttcggggtgccgatttcactctgaccatctcctccctgcaacctgaagatgtggctacctactactgccaaaagtacaactccgcaccttttactttcggaccggggaccaaagtggacattaagaccactaccccagcaccgaggccacccaccccggctcc taccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctt taagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggac gggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg 149368 149368 - ak
Whole CAR 831 malpvtalllplallllhaarpqvqlvqsgaevkkpgssvkvsckasggtfssyaiswvrqapgqglewmggiipifgtanyaqkfqgrvtitadeststaymelsslrsedtavyycarrggyqllrwdvgllrsafdiwgqgtmvtvvssggggsggggsggggssyvltqppsvsvapgqtarit cggnnigsksvhwyqqkpgqapvlvlygknnrpsgvpdrfsgsrsgttasltitgaqaedeadyycssrdsssgdhlrvfgtgtkvtvltttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqtt qeedgcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr 149368 - nk
Whole CAR 832 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccaagtgcagctggtccagtcgggcgccgaggtcaagaagcccgggagctctgtgaaagtgtcctgcaaagcctccggggggcacctttagctcctacgccatctcctgggtccgccaagcaccgggtcaaggcctggagt ggatggggggaattatccctatcttcggcactgccaactacgcccagaagttccagggacgcgtgaccattaccgcggacgaatccacctccaccgcttatatggagctgtccagcttgcgctcggaagataccgccgtgtactactgcgcccgggaggggtggataccagctgctgagatgggacgtgggcctcctgcggtcggcgttc gacatctggggccagggcactatggtcactgtgtccagcggaggaggcggatcgggaggcggcggatcagggggaggcggttccagctacgtgctttactcaacccccttcggtgtccgtggccccgggacagaccgccagaatcacttgcggaggaaacaacattgggtccaagagcgtgcattggtaccagcagaagccaggacaggcccctg tgctggtgctctctacgggaagaacaatcggcccagcggagtgccggacaggttctcgggttcacgctccggtacaaccgcttcactgactatcaccggggcccaggcagaggatgaagcggactactactgttcctcccgggattcatccggcgaccacctccgggtgttcggaaccggaacgaaggtcaccgtgctgaccactaccccagcaccga ggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaaga agctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgct ggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccg ccctcgg 149369 149369 - ak
Whole CAR 833 malpvtalllplallllhaarpevqlqqsgpglvkpsqtlsltcaisgdsvssnsaawnwirqspsrglewlgrtyyrskwysfyaislksriiinpdtsknqfslqlksvtpedtavyycarsspeglflywfdpwgqgtlvtvssggdgsggggsggggssseltqdpavsvalgqtiritcq gdslgnyyatwyqqkpgqapvlviygtnnrpsgipdrfsasssgntasltitgaqaedeadyycnsrdssghhllfgtgtkvtvltttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcs crfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr 149369 - nk
Whole CAR 834 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaagtgcagctccaacagtcaggaccggggctcgtgaagccatcccagaccctgtccctgacttgtgccatctcgggagatagcgtgtcatcgaactccgccgcctggaactggattcggcagagcccgtcccgcggact ggagtggcttggaaggacctactaccggtccaagtggtactctttctacgcgatctcgctgaagtcccgcattatcattaaccctgatacctccaagaatcagttctccctccaactgaaatccgtcacccccgaggacacagcagtgtattactgcgcacggagcagccccgaaggactgttcctgtattggtttgacccctggggccaggggactctt gtgaccgtgtcgagcggcggagatgggtccggtggcggtggttcggggggcggcggatcatcatccgaactgacccaggacccggctgtgtccgtggcgctgggacaaaccatccgcattacgtgccagggagactccctgggcaactactacgccacttggtaccagcagaagccgggccaagcccctgtgttggtcatctacgggaccaacaac agaccttccggcatccccgaccggttcagcgcttcgtcctccggcaacactgccagcctgaccatcactggagcgcaggccgaagatgaggccgactactactactgcaacagcagagactcctcggtcatcacctcttgttcggaactggaaccaaggtcaccgtgctgaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccag cctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcc tgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggc gggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1978-A4 BCMA_EBB-C1978-A4 - ak
Whole CART 835 MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVEGSGSLDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVMTQSPGTLSLSPGERATLSCRASQSVSSAYLAWYQQK PGQPPRLLISGASTRATGIPDRFGGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSFNGSSLFTFGQGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELN LGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1978-A4 - nk
Whole CART 836 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAGCTCGTGGAGTCAGGAGGCGGCCTGGTCCAGCCGGGAGGGTCCCTTAGACTGTCATGCGCCGCAAGCGGATTCACTTTCTCCTCCTATGCCATGAGCTGGGTCCGCCAAGCCCCCGGAAAGGGACTGGAATGGGTGTCCGCCATCTCGGG GTCTGGAGGCTCAACTTACTACGCTGACTCCGTGAAGGGACGGTTCACCATTAGCCGCGACAACTCCAAGAACACCCTCTACCTCCAAATGAACTCCCTGCGGGCCGAGGATACCGCCGTCTACTACTGCGCCAAAAGTGGAAGGTTCAGGATCGCTGGACTACTGGGGACAGGGTACTCTCGTGACCGTGTCATCGGGCGGAGGAGGTTCCGGCGGTGGCGGC TCCGGCGGCGGAGGGTCGGAGATCGTGATGACCCAGAGCCCTGGTACTCTGAGCCTTTCGCCGGGAGAAAGGGCACCCTGTCCTGCCGCGCTTCCCAATCCGTGTCCTCCGCGTACTTGGCGTGGTACCAGCAGAAGCCGGGACAGCCCCCTCGGCTGCTGATCAGCGGGGCAGCACCCGGGCAACCGGAATCCCAGACAGATTCGGGGGTTCCG GCAGCGGCACAGATTTCACCCTGACTATTTCGAGGTTGGAGCCCGAGGACTTTGCGGTGTATTACTGTCAGCACTACGGTCGTCCTTTAATGGCTCCAGCCTGTTCACGTTCGGACAGGGGACCCGCCTGGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagct ggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttc ccagagggaggaggaaggcggctgcgaactgcgcgtgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggggcctgtacaacga gctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1978-G1 BCMA_EBB-C1978-G1 - ac
Whole CART 837 MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAASGITFSRYPMSWVRQAPGKGLEWVSGISDSGVSTYYADSAKGRFTISRDNSKNTLFLQMSSLRDEDTAVYYCVTRAGSEASDIWGQGTMVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSNSLAWYQQKPGQAPRL LIYDASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAIYYCQQFGTSSGLTFGGGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEY DVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1978-G1 - nk
Whole CART 838 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAACTGGTGGAAACCGGTGGCGGCCTGGTGCAGCCTGGAGGATCATTGAGGCTGTCATGCGCGGCCAGCGGTATTACCTTCTCCCGGTACCCCATGTCCTGGGTCAGACAGGCCCCGGGGAAAGGGCTTGAATGGGTGTCCGGGATC TCGGACTCCGGTGTCAGCACTTACTACGCCGACTCCGCCAAGGGACGCTTCACCATTTCCCGGGACAACTCGAAGAACACCCTGTTCCTCCAAATGAGCTCCCTCCGGGACGAGGATACTGCAGTGTACTGCGTGACCCGCGCCGGGTCCGAGGCGTCTGACATTTGGGGACAGGGCACTATGGTCACCGTGTCGTCCGGCGGAGGGGGCTCGGGAGGCG GTGGCAGCGGAGGAGGAGGGTCCGAGATCGTGCTGACCCAATCCCCGGCCACCCTCTCGCTGAGCCCTGGAGAAAGGCAACCTTGTCCTGTCGCGCGAGCCAGTCCGTGAGCAACTCCCTGGCCTGGTACCAGCAGAAGCCCGGACAGGCTCCGAGACTTCTGATCTACGACGCTTCGAGCCGGGCCACTGGAATCCCCGACCGCTTTTCGGGGTCCGGCTCAGGA ACCGATTTCACCCTGACAATCTCACGGCTGGAGCCAGAGGATTTCGCCATCTATTACTGCCAGCAGTTCGGTACTTCCTCCGGCCTGACTTTCGGAGGCGGCACGAAGCTCGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagctggtggggccgtgcatacccggggt cttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgc gaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaagatggcagaag cctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1979-C1 BCMA_EBB-C1979-C1 - ac
Whole CART 839 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAIYYCARATYKRELRYYYGMDVWGQGTMVTVSSGGGGSGGGGSGGGGSEIVMTQSPGTVSLSPGERATLSCRASQSVSSSFL AWYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDSAVYYCQQYHSSPSWTFGQGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQN QLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1979-C1 - nk
Whole CART 840 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTGCAGCTCGTGGAATCGGTGGCGGACTGGTGCAGCCGGGGGGCTCACTTAGACTGTCCTGCGCGGCAGCGGATTCACTTTCTCCTCCTACGCCATGTCCTGGGTCAGACAGGCCCCTGGAAAGGGCCTGGAATGGGTGTCCGCAATCAGC GGCAGCGGCGGCTCGACCTATTACGCGGATTCAGTGAAGGGCAGATTCACCATTTCCCGGGACAACGCCAAGAACTCCTTGTACCTTCAAATGAACTCCCTCCGCGCGGAAGATACCGCAATCTACTACTGCGCTCGGGCCACTTACAAGAGGGAACTGCGCTACTACTACGGGATGGACGTCTGGGCCAGGGAACCATGGTCACCGTGTCCAGCGGAGGAGGAGGA TCGGGAGGAGGCGGTAGCGGGGGTGGAGGGTCGGAGATCGTGATGACCCAGTCCCCCGGCACTGTGTCGCTGTCCCCCGGCGAACGGCCACCCTGTCATGTCGGGCCAGCCAGTCAGTGTCGTCAAGCTTCCTCGCCTGGTACCAGCAGAAACCGGGACAAGCTCCCCCTGCTGATCTACGGAGCCAGCAGCCGGGCCACCGGTATT CCTGACCGGTTCTCCGGTTCGGGGTCCGGGACCGACTTTTTACTCTGACTATCTCTCGCCTCGAGCCAGAGGACTCCGCCGTGTATTACTGCCAGCAGTACCACTCCTCCCCGTCCTGGACGTTCGGACAGGGCACAAGGCTGGAGATTAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccg cagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagagggaggacggctgttcatgcc ggttcccagagggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgta caacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1978-C7 BCMA_EBB-C1978-C7 - ak
Whole CART 841 MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNTLKAEDTAVYYCARATYKRELRYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPSTLSLSPGESATLSCRASQSVSTTFLAW YQQKPGQAPRLLIYGSSNRATGIPDRFSGSGSGTDFTLTIRRLEPEDFAVYYCQQYHSSPSWTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQ LYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1978-C7 - nk
Whole CART 842 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAGTGCAGCTTGTGGAAACCGGTGGCGGACTGGTGCAGCCCGGAGGAAGCCTCAGGCTGTCCTGCGCCGCGTCCGGCTTCACCTTCCTCGTACGCCATGTCCTGGGTCCGCCAGGCCCCCGGAAAGGGCCTGGAATGGGTGTCCGCCATCTCT GGAAGCGGAGGTTCCACGTACTACGCGGACAGCGTCAAGGGAAGGTTCACAATCTCCCGCGATAATTCGAAGAACACTCTGTACCTTCAAATGAACACCCTGAAGGCCGAGGACACTGCTGTGTACTGCGCACGGGCCACCTACAAGAGAGAGCTCCGGTACTACTACGGAATGGACGTCTGGGGCCAGGGAACTACTGTGACCGTGTCCTCGGGAGGGGG TGGCTCCGGGGGGGCGGCTCCGGCGGAGGCGGTTCCGAGATTGTGCTGACCCAGTCACCTTCAACTCTGTCGCTGTCCCCGGGAGAGAGCGCTACTCTGAGCTGCCGGGCCAGCCAGTCCGTGTCCACCACCTTCCTCGCCTGGTATCAGCAGAAGCCGGGCAGGCACCACGGCTCTTGATCTACGGGTCAAGCAACAGAGCGACCGGAATTCCTGACC GCTTCTCGGGGAGCGGTTCAGGCACCGACTTCACCCTGACTATCCGGCCTGGAACCCGAAGATTTCGCCGTGTATTACTGTCAACAGTACCACTCCTCGCCGTCCTGGACCTTTGGCCAAGGAACCAAAGTGGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagctgg tggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttccca gaggaggaggaaggcggctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgag ctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1978-D10 BCMA_EBB-C1978-D10 - ac
Whole CART 843 MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCARVGKAVPDVWGQGTTVTVSSGGGGGSGGGGSGGGGSDIVMTQTPSSLSASVGDRVTITCRASQsissyLNWYQQK PGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNEL NLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1978-D10 - nk
Whole CART 844 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAGCTCGTGGAAACTGGAGGTGGACTCGTGTCAGCCTGGACGGTCGCTGCGGCTGAGCTGCGCTGCATCCGGCTTCACCTTCGACGATTATGCCATGCACTGGTCAGACAGGCGCCAGGGAAGGACTTGAGTGGGTGTCCGGTATCAGCTGGAATAGC GGCTCAATCGGATACGCGGACTCCGTGAAGGGAAGGTTCACCATTTCCCGCGACAACGCCAAGAACTCCCTGTACTTGCAAATGAACAGCCTCCGGGATGAGGACACTGCCGTGTACTACTGCGCCCGCGTCGGAAAAGCTGTGCCCGACGTCTGGGGCCAGGGAACCACTGTGACCGTGTCCAGCGGCGGGGTGGATCGGGCGTGTGGAGGTCCG GTGGAGGGGCTCAGATATTGTGATGACCCAGACCCCCTCGTCCCTGTCCGCCTCGGTCGGCGACCGCGTGACTATCACATGTAGAGCCTCGCAGAGCATCTCCAGCTACCTGAACTGGTATCAGCAGAAGCCGGGAAGGCCCCGAAGCTCCTGATCTACGCGGCATCATCACTGCAATCGGGAGTGCCGAGCCGGTTTTCCGGGTCCGGCTCCGGCACCGACTTCAC GCTGACCATTTCTTCCCTGCAACCCGAGGACTTCGCCACTTACTGCCAGCAGTCCTACTCCACCCTTACTCCTTCGGCCAAGGAACCAGGCTGGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctg cgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaa attcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtat gaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1979-C12 BCMA_EBB-C1979-C12 - ac
Whole CART 845 MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGRSLRLSCTASGFTFDDYAMHWVRQRPGKGLEWVASINWKGNSLAYGDSVKGRFAISRDNAKNTVFLQMNSLRTEDTAVYYCASHQGVAYYNYAMDVWGRGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRATQSIGSSFLAWY QQRPGQAPRLLIYGASQRATGIPDRFSGRGSGTDFTLTISRVEPEDSAVYYCQHYESSPSWTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYN ELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1979-C12 - nk
Whole CART 846 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAGCTCGTGGAGAGCGGGGGAGGATTGGTGCAGCCCGGAAGGTCCCTGCGGCTCTCCTGCACTGCGTCTGGCTTCACCTTCGACGACTACGCGATGCACTGGTCAGACAGCGCCCGGGAAAGGGCCTGGAATGGGTCGCCTCAATCAACTG GAAGGGAAACTCCCTGGCCTATGGCGACAGCGTGAAGGGCCGCTTCGCCATTTCGCGCGACAACGCCAAGAACACCGTGTTTCTGCAAATGAATTCCCTGCGGACCGAGGATACCGCTGTGTACTACTGCGCCAGCCACCAGGGCGTGGCATACTATAACTACGCCATGGACGTGTGGGAAGAGGGACGCTCGTCACCGTGTCCTCCGGGGGCGGTGGATCGGGTGGA GGAGGAAGCGGTGGCGGGGGCAGCGAAATCGTGCTGACTCAGAGCCCGGGAACTCTTTCACTGTCCCCGGGAGAACGGGCCACTCTCTCGTGTGCCGGGCACCCAGTCCATCGGCTCCTCCTTCCTTGCCTGGTACCAGCAGAGGCCAGGACAGGCGCCCCGCCTGCTGATCTACGGTGCTTCCCAACGCGCCACTGGCATTCCTGACCGGTTCAGCGGCAGAG GGTCGGGAACCGATTTCACACTGACCATTTCCCGGGTGGAGCCCGAAGATTCGGCAGTCTACTGTCAGCATTACGAGTCCTCCCCTTCATGGACCTTCGGTCAAGGGACCAAAGTGGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagctggtggggccgtg catacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaccggctgttcatgccggttcccagaggagggaggaa ggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggata agatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1980-G4 BCMA_EBB-C1980-G4 - ac
Whole CART 847 MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVVRDGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSSYLAWYQQK PGQAPRLLIYGASSRATGIPDRFSGNGSGTDFTLTISRLEPEDFAVYYCQQYGSPPRFTFGPGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNL GRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1980-G4 - nk
Whole CART 848 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAGTGCAGTTGGTCGAAAGCGGGGGCGGGCTTGTGCAAGCCTGGCGGATCACTGCGGCTGTCCTGCGCGGCATCAGGCTTCACGTTTTCTTCCTACGCCATGTCCTGGGTGCGCCAGGCCCCTGGAAAGGGACTGGAATGGGTGTCCGCGAT TTCGGGGTCCGGCGGGAGCACCTACTACGCCGATTCCGTGAAGGGCCGCTTCACTATCTCGCGGGACAACTCCAAGAACACCCTCTACCTCCAAATGAATAGCCTGCGGGCCGAGGATACCGCCGTCTACTATTGCGCTAAGGTCGTGCGGCGACGGAATGGACGTGTGGGGACAGGGTACCACCGTGACAGTGTCCTCGGGGGGAGGCGGTAGCGGCGGA GGAGGAAGCGGTGGTGGAGGTTCCGAGATTGTGCTGACTCAATCACCCGCGACCCTGAGCCTGTCCCCCGGCGAAAGGGCCACTCTGTCCTGTCGGCCAGCCAATCAGTCTCCTCCTCGTACCTGGCCTGGTACCAGCAGAAGCCAGGACAGGCTCCGAGACTCCTTATCTATGGCGCATCCTCCCGCGCCACCGGAATCCCGGATAGTTCTCGGGAAACG GATCGGGGACCGACTTCACTCTCACCATCTCCCGGCTGGAACCGGAGGACTTCGCCGTGTACTACTGCCAGCAGTACGGCAGCCCGCCTAGATTCACTTTCGGCCCCGGCACCAAAGTGGACATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagctggtggggccgtgcataccc ggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggacggctgttcatgccggttcccagaggaggaggaaggcgg ctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatgg cagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1980-D2 BCMA_EBB-C1980-D2 - ac
Whole CART 849 MALPVTALLLPLALLLHAARPEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKIPQTGTFDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQ RPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSPSWTFGQGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELN LGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1980-D2 - nk
Whole CART 850 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAGCTGCTGGAGTCCGGCGGTGGATTGGTGCAACCGGGGGGATCGCTCAGACTGTCCTGTGCGGCGTCAGGCTTCACCTTCTCGAGCTACGCCATGTCATGGGTCAGACAGGCCCCTGGAAAGGTCTGGAATGGGTGTCCGCCATTTCC GGGAGCGGGGGATCTACATACTACGCCGATAGCGTGAAGGGCCGCTTCACCATTTCCCGGGACAACTCCAAGAACACTCTCTATCTGCAAATGAACTCCCTCCGCTGAGGACACTGCCGTGTACTACTGCCAAAATCCCTCAGACCGGCACCTTCGACTACTACTGGGGACAGGGGACTCTGGTCACCGTCAGCAGCGGTGGCGGAGGTTCGGGGGGAGGAGGA AGCGGCGGCGGAGGGTCCGAGATTGTGCTGACCCAGTCACCCGGCACTTTGTCCCTGTCGCCTGGAGAAAGGGCACCCTTTCCTGCCGGGCATCCCAATCCGTGTCCTCCTCGTACCTGGCCTGGTACCAGCAGAGGCCCGGACAGGCCCCACGGCTTCTGATCTACGGAGCAAGCAGCCGCGCGACCGGTATCCCGGACCGGTTTTCGGGCTCGGC TCAGGAACTGACTTCACCCTCACCATCTCCCGCCTGGAACCCGAAGATTTCGCTGTGTATTACTGCCAGCACTACGGCAGCTCCCCGTCCTGGACGTTCGGCCAGGGAACTCGGCTGGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagctggtggggccgtgcatacccgggg tcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctg cgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcaga agcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1978-A10 BCMA_EBB-C1978-A10 - ac
Whole CART 851 MALPVTALLLPLALLLHAARPEVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTMSRENDKNSVFLQMNSLRVEDTGVYYCARANYKRELRYYYGMDVWGQGTMVTVSSGGGGSGGGGSGGGGSEIVMTQSPGTLSLSPGESATLSCRASQRVASNYLA WYQHKPGQAPSLLISGASSRATGVPDRFSGSGSGTDFTLAISRLEPEDSAVYYCQHYDSSPSWTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQ LYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1978-A10 - nk
Whole CART 852 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAACTGGTGGAAACCGGTGGAGGACTCGTGTCAGCCTGGCGGCAGCCTCCGGCTGAGCTGCGCCGCTTCGGGATTCACCTTTTCCCTACGCGATGTCTTGGTCAGACAGGCCCCCGGAAAGGGGCTGGAATGGGTGTCAGCCATCTCCGGC TCCGGCGGATCAACGTACTACGCCGACTCCGTGAAAGGCCGGTTCACCATGTCGCGCGAGAATGACAAGAACTCCGTGTTCCTGCAAATGAACTCCCTGAGGTGGAGGACACCGGAGTGTACTATTGTGCGCGCGCCAACTACAAGAGAGAGCTGCGGTACTACTACGGAATGGACGTCTGGGGACAGGGAACTATGTGACCGTGTCATCCGGTGGAGGG GAAGCGGCGGTGGAGGCAGCGGGGGCGGGGGTTCAGAAATTGTCATGACCCAGTCCCCGGGAACTCTTTCCCTCTCCCCCGGGGAATCCGCGACTTTGTCCTGCCGGGCCAGCCAGCGCGTGGCCTCGAACTACCTCGCATGGTACCAGCATAAGCCAGGCCAAGCCCCTTCCCTGCTGATTTCCGGGGCTAGCAGCCGCGCCACTGGCGTGCCGGATAG GTTCTCGGGAAGCGGCTCGGGTACCGATTTCACCCTGGCAATCTCGCGGCTGGAACCGGAGGATTCGGCCGTGTACTACTGCCAGCACTATGACTCATCCCCCTCCTGGACATTCGGACAGGGCACCAAGGTCGAGATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagctggt ggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccaga ggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagct ccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1978-D4 BCMA_EBB-C1978-D4 - ak
Whole CART 853 MALPVTALLLPLALLLHAARPEVQLLETGGGLVQPGGSLRLSCAASGFSFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKALVGATGAFDIWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSLSSNFLAWYQQKPG QAPGLLIYGASNWATGTPDRFSGSGSGTDFTLTITRLEPEDFAVYYCQYYGTSPMYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNL GRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1978-D4 - nk
Whole CART 854 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAGCTGCTCGAAACCGGTGGAGGGCTGGTGCAGCCAGGGGGCTCCCTGAGGCTTTCATGCGCCGCTAGCGGATTCTCCTTCTCCTCTTACGCCATGTCGTGGGTCCGCCAAGCCCCTGGAAAAGGCCTGGAATGGGTGTCCGCGATTTCCGGGA GCGGAGGTTCGACCTATTACGCCGACTCCGTGAAGGGCCGCTTTACCATCTCCCGGGATAACTCCAAGAACACTCTGTACCTCCAAATGAACTCGCTGAGAGCCGAGGACACCGCCGTGTATTACTGCGCGAAGGCGCTGGTCGGCGCGACTGGGCATTCGACATCTGGGGACAGGGAACTCTTGTGACCGTGTCGAGCGGAGGCGGCGGCTCCGGCGGAGGAGG GAGCGGGGGCGGTGGTTCCGAAATCGTGTTGACTCAGTCCCCGGGAACCCTGAGCTTGTCACCCGGGGAGCGGGCCACTCTCTCCTGTCGCGCCTCCCAATCGCTCTCATCCAATTTCCTGGCCTGGTACCAGCAGAAGCCCGGACAGGCCCCGGGCCTGCTCATCTACGGCGCCTTCAAACTGGGCAACGGGAACCCCTGATCGGTTCAGCGGAAGCGGA TCGGGTACTGACTTTACCCTGACCATCACCAGACTGGAACCGGAGGACTTCGCCGTGTACTACTGCCAGTACTACGGCACCTCCCCCATGTACACATTCGGACAGGGTACCAAGGTCGAGATTAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagctggtggggccgtgcat acccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggacggggctgttcatgccggttcccagaggaggaggaagg cggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaagggataaga tggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1980-A2 BCMA_EBB-C1980-A2 - ac
Whole CART 855 MALPVTALLLPLALLLHAARPEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCVLWFGEGFDPWGQGTLVTVSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQ KPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQ LYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1980-A2 - nk
Whole CART 856 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTGCAGCTGCTTGAGAGCGGTGGAGGTCTGGTGCAGCCCGGGGGATCACTGCGCCTGTCCTGTGCCGCGTCCGGTTTCACTTTCTCCTCGTACGCCATGTCGTGGGTCAGACAGGCACCGGGAAAGGGACTGGAATGGGTGTCAGCCATTTCG GGTTCGGGGGGCAGCACCCTACTACGCTGACTCCGTGAAGGGCCGGTTCACCATTTCCCGCGACAACTCCAAGAACACCTTGTACCTCCAAATGAACTCCCTGCGGGCCGAAGATACCGCCGTGTATTACTGCGTGCTGTGGTTCGGAGAGGGATTCGACCCGTGGGGACAAGGAACACTCGTGACTGTGTCATCCGGCGGAGGCGGCAGCGGTGGCGGCGG TTTCCGGCGGCGGCGGATCTGACATCGTGTTGACCCAGTCCCCTCTGAGCCTGCCGGTCACTCCTGGCGAACCAGCCAGCATCTCCTGCCGTCGAGCCAGTCCCTCCTGCACTCCAATGGGTACAACTACCTCGATTGGTATCTGCAAAAGCCGGGCCAGAGCCCCCAGCTGCTGATCTACCTTGGGTCAAACCGCGCTTCCGGGTGCCTGATAGATTTCCGGGTC CGGGAGCGGAACCGACTTTTACCCTGAAAATCTCGAGGGTGGAGGCCGAGGACGTCGGAGTGTACTACTGCATGCAGGCGCCTCCAGACTCCCCTGACCTTCGGAGGAGGAACGAAGGTCGACATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcagctggtggggccgtg catacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaccggctgttcatgccggttcccagaggagggaggaa ggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggata agatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1981-C3 BCMA_EBB-C1981-C3 - ac
Whole CART 857 MALPVTALLLPLALLLHAARPQVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVGYDSSGYYRDYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQS VSSSYLAWYQQKPGQAPRLLIYGTSSRATGISDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGNSPPKFTFGPGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQ GQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1981-C3 - nk
Whole CART 858 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCCAAGTGCAGCTCGTGGAGTCAGGCGGAGGACTGGTGCAGCCCGGGGGCTCCCTGAGACTTTCCTGCGCGGCATCGGGTTTTACCTTCTCCTCCTATGCTATGTCCTGGGTGCGCCAGGCCCCGGGAAAGGGACTGGAATGGGTGTCCGCAATCAGC GGTAGCGGGGGCTCAACATACTACGCCGACTCCGTCAAGGGTCGCTTCACTATTTCCCGGGACAACTCCAAGAATACCCTGTACCTCCAAATGAACAGCCTCAGGGCCGAGGATACTGCCGTGTACTGCGCCAAAGTCGGATACGATAGCTCCGGTTACTACCGGGACTACTACGGAATGGACGTGTGGGGACAGGGCACCACCGTGACCGTGTCAAGCGGCGGA GGCGGTTCAGGAGGGGGAGGCTCCGGCGGTGGAGGTCCGAAATCGTCCTGACTCAGTCCTGGCACTCTGTCGTTGTCCCCGGGGGAGCGCGCTACCCTGTCGTGTCGGGCGTCGCAGTCCGTGTCGAGCTCCTACCTCGCGTGGTACCAGCAGAAGCCCGGACAGGCCCCTAGACTTCTGATCTACGGCACTTCTTCACGCGCCACCGGGATCAG CGACAGGTTCAGCGGCTCCGGCTCCGGGACCGACTTCACCCTGACCATTAGCCGGCTGGAGCCTGAAGATTTCGCCGTGTATTACTGCCAACACTACGGAAACTCGCCGCCAAAGTTCACGTTCGGACCCGGAACCAAGCTGGAAATCAAGACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgcag ctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggagaggacggctgttcatgccggtt cccagaggagaggagaaggcggctgcgaactgcgcgtgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggggcctgtacaac gagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg BCMA_EBB-C1978-G4 BCMA_EBB-C1978-G4 - ak
Whole CART 859 MALPVTALLLPLALLLHAARPEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKMGWSSGYLGAFDIWGQGTTVTVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVASSFLAWYQ QKPGQAPRLLIYGASGRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGGSPRLTGGGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYN ELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR BCMA_EBB-C1978-G4 - nk
Whole CART 860 ATGGCCCTCCCTGTCACCGCCCTGCTGCTTCCGCTGGCTCTTCTGCTCCACGCCGCTCGGCCCGAAGTCCAACTGGTGGAGTCCGGGGGAGGGCTCGTGCAGCCCGGAGGCAGCCTTCGTGTCGTGCGCCGCCTCCGGGTTCACGTTCTCATCCTACGCGATGTCGTGGGTCAGACAGGCACCAGGAAAGGGACTGGAATGGGTGTCCGCCATTA GCGGCTCCGGCGGTAGCACCTACTATGCCGACTCAGTGAAGGGAAGGTTCACTATCTCCCGCGCAAACAGCAAGAACACCCTGTACCTCCAAATGAACTCTCTGCGGGCCGAGGATACCGCGGTGTACTATTGCGCCAAGATGGGTTGGTCCAGCGGATACTTGGGAGCCTTCGACATTTGGGGACAGGGCACTACTGTGACCGTGTCCTCCGGGGTGGCG GATCGGGAGGCGGCGGCTCGGGTGGAGGGGTTCCGAAATCGTGTTGACCCAGTCACCGGGAACCCTCTCTGTGTCCCCGGGAGAACGGGCTACACTGTCATGTAGAGCGTCCCAGTCCGTGGCTTCCTCGTTCCTGGCCTGGTACCAGCAGAAGCCGGGACAGGCACCCCGCCTGCTCATCTACGGAGCCAGCGGCCGGGCGACCGGCATCCCT GACCCGCTTCTCCGGTTCCGGCTCGGGCACCGACTTTACTCTGACCATTAGCAGGCTTGAGCCCGAGGATTTTGCCGTGTACTACTGCCAACACTACGGGGGAGCCCTCGCCTGACCTTCGGAGGCGGAACTAAGGTCGATATCAAAACCACTACCCCAGCACCGAGGCCACCCACCCCGGCTCCTACCATCGCCTCCCAGCCTCTGTCCCTGCGTCCGGAggcatgtagacccgca gctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggagaggacggctgttcatgccgg ttcccagagggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtaca acgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg

In one embodiment, the CAR contains (eg, consists of) the amino acid sequence shown in Table 16 or Table 1 in WO2016/014565, or as provided herein. In one embodiment, the CAR contains (e.g., consists of) an amino acid sequence selected from any of SEQ ID NOs: 789, 791, 793, 795, 797, 799, 801, 803, 805, 807, 809, 811, 813, 815 , 817, 819, 821, 823, 825, 827, 829, 831, 833, 835, 837, 839, 841, 843, 845, 847, 849, 851, 853, 855, 857, 859; or an amino acid sequence having at least one, two, three, four, five, 10, 15, 20, or 30 modifications (e.g., substitutions, e.g. conservative substitutions), but no more than 60, 50, or 40 modifications (e.g., substitutions , for example, conservative substitutions) amino acid sequence selected from any of SEQ ID NOs: 789, 791, 793, 795, 797, 799, 801, 803, 805, 807, 809, 811, 813, 815, 817, 819, 821 , 823, 825, 827, 829, 831, 833, 835, 837, 839, 841, 843, 845, 847, 849, 851, 853, 855, 857, 859; or an amino acid sequence having 85%, 90%, 95%, 96%, 97%, 98%, 99% identity with an amino acid sequence selected from any of SEQ ID NOs: 789, 791, 793, 795, 797, 799, 801 803 805 807 809 811 813 815 817 819 821 823 825 827 829 831 833 835 837 839 841 843 845 847 8 49, 851, 853, 855, 857, 859.

In one embodiment, the CAR molecule contains an antigen-binding domain for mesothelin (e.g., a murine, human, or humanized antibody, or an antibody fragment that specifically binds to mesothelin), a transmembrane domain, and an intracellular signaling domain (e.g., an intracellular signaling domain containing a costimulatory domain and/ or the main signaling domain).

Exemplary mesothelin-targeting CAR molecules are described herein and shown in Table 17. The CAR molecules in Table 17 contain an antigen-binding domain for mesothelin, e.g., the amino acid sequence of any of the antigen-binding domains for mesothelin shown in Table 3. The leader sequence is shown in bold and underlined, CDR regions underlined and the linker sequence between the heavy and light chains of the antigen-binding region is shaded in grey.

Table 17 Exemplary CAR Molecules

Name Amino acid sequence SEQID NO: M5 CAR MALPVTALLLPLALLLHAARP QVQLVQSGAEVEKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVMTRDTSISTAYMELSRLRSDDTAVYYCASGWDFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSPSSLSASVGDRVTITCRASQSIRYYLSWYQQKPGKAPKLLIYTASILQNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQTYTTPDFGPGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR RGKGHDGLYQGLSTATKDTYDALHMQALPPR 724 M11CAR MALPVTALLLPLALLLHAARP QVQLQQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQNFQGRVMTRDTSISTAYMELRRLRSDDTAVYYCASGWDFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIRMTQSPSSLSASVGDRVTITCRASQSIRYYLSWYQQKPGKAPKLLIYTASILQNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQTYTTPDFGPGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR RGKGHDGLYQGLSTATKDTYDALHMQALPPR 725 SS1CAR MALPVTALLLPLALLLHAARP QVQLQQSGPELEKPGASVKISCKASGYSFTGYTMNWVKQSHGKSLEWIGLITPYNGASSYNQKFRGKATLTVDKSSSTAYMDLLSLTSEDSAVYFCARGGYDGRGFDYWGQGTTVTVSSGGGGSGGGGSGGGGSDIELTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASGVPGRFSGSGSGNSYSLTISSVEAEDDATYYCQQWSGYPLTFGAGTKLEITTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPA 726 M1CAR MALPVTALLLPLALLLHAARP QVQLQQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGRINPNSGGTNYAQKFQGRVMTRDTSISTAYMELSRLRSEDTAVYYCARGRYYGMDVWGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERATISCRASQSVSSNFAWYQQRPGQAPRLLIYDASNRATGIPPRFSGSGSGTDFTLTISSLEPEDFAAYYCHQRSNWLYTFGQGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 727 M2 CAR MALPVTALLLPLALLLHAARP QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVMTRDTSISTAYMELSRLRSDDTAVYYCARDLRRTVVTPRAYYGMDVWGQGTTTVVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSTLSASVGDRVTITCQASQDISNSLNWYQQKAGKAPKLLIYDASTLETGVPSRFSGSGSGTDFSFTISSLQPEDIATYYCQQHDNLPLTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 728 M3 CAR MALPVTALLLPLALLLHAARP QVQLVQSGAEVKKPGAPVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVMTRDTSISTAYMELSRLRSDDTAVYYCARGEWDGSYYYDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVLTQTPSSLSASVGDRVTITCRASQSINTYLNWYQHKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSFSPLTFGGGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 729 M4 CAR MALPVTALLLPLALLLHAARP QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQVPGKGLVWVSRINTDGSTTTYADSVEGRFTISRDNAKNTLYLQMNSLRDDDTAVYYCVGGHWAVWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCRASQSISDRLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFAVYYCQQYGHLPMYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 730 M6 CAR MALPVTALLLPLALLLHAARP QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARYRLIAVAGDYYYYGMDVWGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVGRWLAWYQQKPGTAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTINNLQPEDFATYYCQQANSFLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 731 M7CAR MALPVTALLLPLALLLHAARP QVQLVQSGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWKVSSSSPAFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPATLSLSPGERAILSCRASQSVYTKYLGWYQQKPGQAPRLLIYDASTRATGIPDRFSGSGSGTDFTLTINRLEPEDFAVYYCQHYGGSPLITFGQGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 732 M8 CAR MALPVTALLLPLALLLHAARP QVQLQQSGAEVKKPGASVKVSCKTSGYPFTGYSLHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVMTRDTSISTAYMELSRLRSDDTAVYYCARDHYGGNSLFYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSSISASVGDTVSITCRASQDSGTWLAWYQQKPGKAPNLLMMYDASTLEDGVPSRFSGSASGTEFTLTVNRLQPEDSATYYCQQYNSYPLTFGGGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 733 M9 CAR MALPVTALLLPLALLLHAARP QVQLVQSGAEVKKPGASVEVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTGYAQKFQGRVTMTRDTSTSTVHMELSSLRSEDTAVYYCARGGYSSSSDAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPPSLSASVGDRVTITCRASQDISSALAWYQQKPGTPPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFSSYPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 734 M10CAR MALPVTALLLPLALLLHAARP QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARVAGGIYYYYGMDVWGQGTTITVSSGGGGSGGGGSGGGGSGGGGSDIVMTQTPDSLAVSLGERATISCKSSHVLYNRNNKNYLAWYQQKPGQPPKLLFYWASTRKSGVPDRFSGSGSGTDFTLTISSLQPEDFATYFCQQTQTFPLTFGQGTRLEINTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR RGKGHDGLYQGLSTATKDTYDALHMQALPPR 735 M12CAR MALPVTALLLPLALLLHAARP QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGRINPNSGGTNYAQKFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARTTTSYAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSTLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPNLLIYKASTLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNTYSPYTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 736 M13CAR MALPVTALLLPLALLLHAARP QVQLVQSGGGLVKPGGSLRLSCEASGFIFSDYYMGWIRQAPGKGLEWVSYIGRSGSSMYYADSVKGRFTFSRDNAKNSLYLQMNSLRAEDTAVYYCAASPVVAATEDFQHWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQTPATLSLSPGERATLSCRASQSVTSNYLAWYQQKPGQAPRLLLFGASTRATGIPDRFSGSGSGTDFTLTINRLEPEDFAMYYCQQYGSAPVTFGQGTKLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 737 M14 CAR MALPVTALLLPLALLLHAARP QVQLVQSGAEVRAPGASVKISCKASGFTFRGYYIHWVRQAPGQGLEWMGIINPSGGSRAYAQKFQGRVTMTRDTSTSTVYMELSSLRSDDTAMYYCARTASCGGDCYYLDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPPTLSASVGDRVTITCRASENVNIWLAWYQQKPGKAPKLLIYKSSSLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQQYQSYPLTFGGGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 738 M15 CAR MALPVTALLLPLALLLHAARP QVQLVQSGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKDGSSSWSWGYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSSSELTQDPAVSVALGQTVRTTCQGDALRSYYASWYQQKPGQAPMLVIYGKNNRPSGIPDRFSGSDSGDTASLTITGAQAEDEADYYCNSRDSSGYPVFGTGTKVTVLTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR RGKGHDGLYQGLSTATKDTYDALHMQALPPR 739 M16 CAR MALPVTALLLPLALLLHAARP EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSTGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDSSSWYGGGSAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSSSELTQEPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIFGRRRPSGIPDRFSGSSSGNTASLIITGAQAEDEADYYCNSRDNTANHYVFGTGTKLTVLTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR RGKGHDGLYQGLSTATKDTYDALHMQALPPR 740 M17CAR MALPVTALLLPLALLLHAARP EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSTGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDSSSWYGGGSAFDIWGQGTMVTVSSGGGGSGGGGSGGGGSSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRGSSGNHYVFGTGTKVTVLTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERR RGKGHDGLYQGLSTATKDTYDALHMQALPPR 741 M18 CAR MALPVTALLLPLALLLHAARP QVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLVWVSRINSDGSSTSYADSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCVRTGWVGSYYYYMDVWGKGTTTVVSSGGGGSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQPPRLLIYDVSTRATGIPARFSGGGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPWTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 742 M19 CAR MALPVTALLLPLALLLHAARP QVQLVQSGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGYSRYYYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSGGGGSEIVMTQSPATLSLSPGERAILSCRASQSVYTKYLGWYQQKPGQAPRLLIYDASTRATGIPDRFSGSGSGTDFTLTINRLEPEDFAVYYCQHYGGSPLITFGQGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 743 M20CAR MALPVTALLLPLALLLHAARP QVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKREAAAGHDWYFDLWGRGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIRVTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPLTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 744 M21CAR MALPVTALLLPLALLLHAARP QVQLVQSWAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSNLRSEDTAVYYCARSPRVTTGYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYSSYPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGE RRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 745 M22CAR MALPVTALLLPLALLLHAARP QVQLVQSGAEVRRPGASVKISCRASGDTSTRHYIHWLRQAPGQGPEWMGVINPTTGPATGSPAYAQMLQGRVTMTRDTSTRTVYMELRSLRFEDTAVYYCARSVVGRSAPYYFDYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGISDYSAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISYLQSEDFATYYCQQYYSYPLTFGGGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 746 M23CAR MALPVTALLLPLALLLHAARP QVQLQQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGIINPSGGYTTYAQKFQGRLTMTRDTSTSTVYMELSSLRSEDTAVYYCARIRSCGGDCYYFDNWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQLTQSPSTLSASVGDRVTITCRASENVNIWLAWYQQKPGKAPKLLIYKSSSLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQQYQSYPLTFGGGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 747 M24 CAR MALPVTALLLPLALLLHAARP QITLKESGPALVKPTQTLLTTCTFSGFSLSTAGVHVGWIRQPPGKALEWLALISWADDKRYRPSLRSRLDITRVTSKDQVVLSMTNMQPEDTATYYCALQGFDGYEANWGPGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIVMTQSPSSLSASAGDRVTITCRASRGISSALAWYQQKPGKPPKLLIYDASSLESGVPSRFSGSGSGTDFTLTIDSLEPEDFATYYCQQSYSTPWTFGQGTKVDIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMK GERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 748

In one embodiment, the CAR molecule that binds mesothelin contains (eg, consists of) the amino acid sequence shown in Table 17 or Table 2 in International Patent Publication No. WO2015/090230, filed December 19, 2014; the contents of which are incorporated herein by reference. In one embodiment, the CAR molecule comprises (eg, consists of) an amino acid sequence selected from any of SEQ ID NOs: 724-748; or an amino acid sequence having at least one, two, three, four, five, 10, 15, 20, or 30 modifications (e.g., substitutions, e.g. conservative substitutions), but no more than 60, 50, or 40 modifications (e.g., substitutions eg conservative substitutions) amino acid sequence selected from any of SEQ ID NOs: 724-748; or an amino acid sequence having 85%, 90%, 95%, 96%, 97%, 98%, 99% identity with an amino acid sequence selected from any of SEQ ID NOs: 724-748.

In one embodiment, the CAR molecule contains an antigen-binding domain for EGFRvIII (e.g., a murine, human, or humanized antibody, or antibody fragment that specifically binds to EGFRvIII), a transmembrane domain, and an intracellular signaling domain (e.g., an intracellular signaling domain containing a costimulatory domain and/ or the main signaling domain).

Exemplary CAR molecules targeting EGFRvIII are described herein and listed in Table 18 or Table 2 in WO/2014/130657, or described in WO2016/014789.

Table 18. Exemplary humanized CAR constructs. The sequences are shown with the leader sequence and the CDR regions are underlined. The abbreviation "nc" means a nucleic acid and "ak" means an amino acid sequence.

Name SEQID NO: Subsequence CAR 1 CAR 1 - Whole - nk 769 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagatccagctggtgcagtcgggagctgaagtcaaaaagcctggcgcaaccgtcaagatctcgtgcaaaggatcagggttcaacatcgaggactactacatccattgggtgcaacaggcacccggaaaaaggcctgg agtggatggggaggattgacccagaaaatgacgaaaccaagtacggaccgatcttccaaggacgggtgaccatcacggctgacacttcactaacaccgtctacatggaactctcgagccttcgctcggaagataccgcggtgtactactgcgcctttagaggtggagtctactggggacaagggactaccgtcaccgtgtcgtcagg tggcggaggatcaggcggaggcggctccggtggagagggaagcggaggaggtggctccgacgtggtgatgacgcagtcaccggactccttggcggtgagcctgggtgaacgcgccactatcaactgcaagagctcccagagcttgctggactccgatggaaagacttatctcaattggctgcaacagaagcctggccagccgccaaagagact catctcactggtgagcaagctggatagcggagtgccagatcggttttcgggatcgggctcaggcaccgacttcaccctgactatttcctccctccaagccgaggatgtggccgtctactactactgttggcaggggactcacttcccggggaccttcggtggaggcactaaggtggagatcaaaaccactaccccagcaccgaggccacccaccccggctcctac catcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaag caacccttcatgaggcctgtgcagactactcaagggaggacggctgttcatgccggttcccagagggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggg acccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR 1 - Whole - ak 770 malpvtalllplalllhaarpeiqlvqsgaevkkpgatvkisckgsgfnie dyyih wvqqapgkglewmg ridpendetkygpifqg rvtitadtstntvymelsslrsedtavyycaf rggv ywgqgttvtvssggggsggggsggggsggggsdvvmtqspdslavslgeratinc kssqs lldsdgktyln wlqqkpgqppkrlis lvsklds gvpdrfsgsgsgtdftltisslqaedvavyyc wqgthfpgt fgggtkveiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttq eedgcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR 2 CAR 2 - Whole - nk 771 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgacgtggtcatgactcaaagcccagattccttggctgtctcccttggagaaagagcaacgatcaattgcaaaagctcgcagtccctgttggactccgatggaaaaacctacctcaactggctgcagcagaagccgggacaaccacca aagcggctgatttccctcgtgtccaagctggacagcggcgtgccggatcgcttctcgggcagcggctcgggaaccgattttactctcactatttcgtcactgcaagcggaggacgtggcggtgtattactgctggcagggcactcacttcccgggtacttttggtggaggtaccaaagtcgaaatcaagggtggaggcggga gcggaggaggcgggtcgggaggaggaggatcgggtggcgggaggctcagaaatccagctggtgcagtcaggtgccgaagtgaagaagcctggggccacggtgaagatctcgtgcaaggggagcggattcaacatcgaggattactacatccattgggtgcaacaggcccctggcaaagggctggaatggatgggaaggatcgaccccgagaat gacgagactaagtacggcccgatcttccaaggacgggtgaccatcactgcagacacttcaaccaacaccgtctacatggaactctcctcgctgcgctccgaggacaccgccgtgtactactgtgctttcagaggaggagtctactggggacagggaacgaccgtgaccgtcagctcaaccactaccccagcaccgaggccacccaccccggct cctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatct ttaagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagagg acgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctgacgctcttcacatgcaggccctgccgcctcgg CAR 2 - Whole - ak 772 malpvtalllplalllhaarpdvvmtqspdslavslgeratinc kssqslldsdgktyln wlqqkpgqppkrlis lvsklds gvpdrfsgsgsgtdftltisslqaedvavyyc wqgthfpgt fgggtkveikggggsggggsggggsggggseiqlvqsgaevkkpgatvkisck gsgfnie dyyih wvqqapgkglewmg ridpendetkygpifqg rvtitadtstntvymelsslrsedtavyyca frggvy wgqgttvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgc scrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR 3 CAR 3 - Whole - nk 773 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgaaatccagctggtgcaaagcggagccgaggtgaagaagcccggagaatccctgcgcatctcgtgtaagggttccggctttaacatcgaggattactacatccactgggtgagacagatgccgggcaaaggtctggaatggatgggcc gcatcgacccggagaacgacgaaaccaaatacggaccaatcttccaaggacatgtgactatttccgcggatacctccatcaacactgtctacttgcagtggagctcgctcaaggcgtcggataccgccatgtactactgcgcattcagagggaggtgtgtactggggccagggcactacggtcaccgtgtcctcgggaggtggagggtcagg aggcgggaggctcgggcggtggaggatcaggcggagagggaagcgatgtggtcatgactcaatccccactgtcactgcctgtcactctggggcaaccggcttccatctcatgcaagtcaagccaatcgctgctcgactccgacggaaaaacctacctcaattggcttcagcagcgcccaggccagtcgcctcggaggctgatct cactcgtgtcgaagcttgactccggggtgccggatcggtttagcggaagcggatcggggaccgacttcacgttgaagattagccgggtggaagccgaggacgtgggagtctattactgctggcaggggacccacttcccggggactttcggaggaggcaccaaagtcgagattaagaccactaccccagcaccgaggccacccaccccggctcctaccatcg cctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaaccc ttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggaccaagcggagaggacggacccaga aatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgcttcacatgcaggccctgccgcctcgg CAR 3 - Whole - ak 774 malpvtalllplalllhaarpeiqlvqsgaevkkpgeslrisckgsgfnie dyyih wvrqmpgkglewmg ridpendetkygpifqg hvtisadtsintvylqwsslkasdtamyycaf rggvy wgqgttvtvssggggsggggsggggsggggsdvvmtqsplslpvtlgqpasisc kssq slldsdgktyln wlqqrpgqsprrlis lvsklds gvpdrfsgsgsgtdftlkisrveaedvgvyyc wqgthfpgt fgggtkveiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqtt qeedgcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR 4 CAR 4 - Whole - nk 775 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgacgtcgtcatgacccaatcccctctccctgccggtcaccctgggtcagccggcgtcgatctcatgcaaaagctcacagtccctgctggattcggacggaaaaacctacttgaactggctccaacagaggccggggtcag tcccctcgcagactgatctcgctggtgagcaagctcgactcgggtgtgccggatcggttctccgggtcaggatcgggcaccgactttacgctcaagatttcgaagagtggaggccgaggatgtgggagtgtactattgctggcagggcacgcatttccccgggacctttggaggcgggactaaggtggaaatcaagggaggt ggcggatcaggcggaggaggcagcggcggaggtggatcaggaggcggagggtcagagatccagctggtccaaagcggagcagaggtgaagaagccaggcgagtcccttcgcatttcgtgcaaagggagcggcttcaacattgaagattactacatccactgggtgcggcaaatgccaggaaagggtctggaatggatgggacggatcgaccca gaaaatgatgaaactaagtacggaccgatcttccaaggacacgtcactatctccgcggacacttcgatcaacaccgtgtacctccagtggagcagcttgaaagcctccgacaccgctatgtactactgtgccttccgcggaggagtctactggggacaggggactactgtgaccgtgtcgtccaccactaccccagcaccgaggccac ccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctcttactgtaagcgcggtcggaagaagctg ctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggaca agcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctc gg CAR 4 - Whole - ak 776 malpvtalllplallllhaarpdvvmtqsplslpvtlgqpasisc kssqslldsdgktyln wlqqrpgqsprrlis lvsklds gvpdrfsgsgsgtdftlkisrveaedvgvyyc wqgthfpgt fgggtkveikggggsggggsggggsggggseiqlvqsgaevkkpge slrisckgsgfnie dyyih wvrqmpgkglewmg ridpendetkygpifqg hvtisadtsintvylqwsslkasdtamyycaf rggvy wgqgttvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttq eedgcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR 5 CAR 5 - Whole - nk 777 atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggcccgaaatccagctcgtgcagagcggagccgaggtcaagaaaccgggtgctaccgtgaagatttcatgcaagggatcgggcttcaacatcgaggattactacatccactgggtgcagcaggcaccaggaaaaggacttgaatggatgggccggatcgacccggaaaatgacgagactaagtacggccctatcttccaaggacgggtgacgatcaccgcagacactagcaccaacaccgtctatatggaactctcgtccctgaggtccgaagatactgccgtgtactactgtgcgtttcgcggaggtgtgtactggggacagggtaccaccgtcaccgtgtcatcgggcggtggaggctccggtggaggagggtcaggaggcggtggaagcggaggaggcggcagcgacgtggtcatgactcaatcgccgctgtcgctgcccgtcactctgggacaacccgcgtccatcagctgcaaatcctcgcagtcactgcttgactccgatggaaagacctacctcaactggctgcagcaacgcccaggccaatccccaagacgcctgatctcgttggtgtcaaagctggactcaggggtgccggaccggttctccgggagcgggtcgggcacggatttcactctcaagatctccagagtggaagccgaggatgtgggagtctactactgctggcagggaacccatttccctggaacttttggcggaggaactaaggtcgagattaaaaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR 5 - Whole - ak 778 malpvtalllplalllhaarpeiqlvqsgaevkkpgatvkisckgsgfnie dyyih wvqqapgkglewmg ridpendetkygpifqg rvtitadtstntvymelsslrsedtavyycaf rggvy wgqgttvtvssggggsggggsggggsggggsdvvmtqsplslpvtlgqpasisc kss qsllldsdgktyln wlqqrpgqsprrlis lvsklds gvpdrfsgsgsgtdftlkisrveaedvgvyyc wqgthfpgt fgggtkveiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvq ttqeedgcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR 6 CAR6-
Whole - nk 779 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagattcagctcgtgcaatcgggagcggaagtcaagaagccaggagagtccttgcggatctcatgcaagggtagcggctttaacatcgaggattactacatccactgggtgaggcagatgccggggaagggactcgaatggatgggacggat cgacccagaaaacgacgaaactaagtacggtccgatcttccaaggccatgtgactattagcgccgatacttcaatcaataccgtgtatctgcaatggtcctcattgaaagcctcagataccgcgatgtactactgtgctttcagagggaggggtctactggggacagggaactaccgtgactgtctcgtccggcggaggcgggtca ggaggtggcggcagcggaggaggagggtccggcggaggtgggtccgacgtcgtgatgacccagagccctgacagcctggcagtgagcctgggcgaaagagctaccattaactgcaaatcgtcgcagagcctgctggactcggacggaaaaacgtacctcaattggctgcagcaaaagcctggccagccaccgaagcg ccttatctcactggtgtcgaagctggattcgggagtgcccgatcgcttctccggctcgggatcgggtactgacttcaccctcactatctcctcgcttcaagcagaggacgtggccgtctactactgctggcagggaacccactttccgggaaccttcggcggagggacgaaagtggagatcaagaccactaccccagcaccgaggccacccaccgggg ctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacat ctttaagcaacccttcatgaggcctgtgcagactactactcaagaggaccgctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggaga ggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR6-
Whole - ak 780 malpvtalllplalllhaarpeiqlvqsgaevkkpgeslrisckgsgfnie dyyih wvrqmpgkglewmg ridpendetkygpifqg hvtisadtsintvylqwsslkasdtamyycaf rggvy wgqgttvtvsssggggsggggsggggsggggsdvvmtqspdslavslgeratinc kssqsllds dgktyln wlqqkpgqppkrlis lvsklds gvpdrfsgsgsgtdftltisslqaedvavyyc wqgthfpgt fgggtkveiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedg cscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR 7 CAR 7
Whole - nk 781 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgacgtggtgatgactcagtcgcctgactcgctggctgtgtcccttggagagcggggccactatcaattgcaagtcatcccagtcgctgctggattccgacgggaaaacctacctcaattggctgcagcaaaaac cgggacagcctccaaagcggctcatcagcctggtgtccaagttggacagcggcgtgccagaccgcttctccggttcgggaagcggtactgatttcacgctgaccatctcatccctccaagcggaggatgtggcagtctactactactgttggcagggcacgcattttccgggcacttttggaggagggaccaaggtcgaaatcaagggaggaggtggct cgggcggaggaggctcgggaggaggaggatcaggaggcggtggaagcgagattcaactggtccagagcggcgcagaagtcaagaagccgggtgaatcgctcagaatctcgtgcaaaggatcgggattcaacatcgaggactactacattcactgggtcagacaaatgccgggcaaagggctggaatggatggggaggatcgaccccgaaaac gatgaaaccaagtacggaccaatcttccaagggcacgtgaccatttcggcggacacctcaatcaacactgtgtacctccagtggagctcacttaaggccagcgataccgccatgtactattgcgctttccgcggaggggtgtactggggacagggcactactgtgaccgtgtcatccaccactaccccagcaccgaggccacccaccccggctcctac catcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaag caacccttcatgaggcctgtgcagactactcaagggaggacggctgttcatgccggttcccagagggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggg acccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR 7
Whole - ak 782 malpvtalllplalllhaarpdvvmtqspdslavslgeratinc kssqslldsdgktyln wlqqkpgqppkrlis lvsklds gvpdrfsgsgsgtdftltisslqaedvavyyc wqgthfpgt fgggtkveikggggsggggsggggsggggseiqlvqsgaevkkpgeslrisckgs gfnie dyyih wvrqmpgkglewmg ridpendetkygpifqg hvtisadtsintvylqwsslkasdtamyycaf rggvy wgqgttvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgc scrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR 8 CAR 8 - Whole - nk 783 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgatgtggtcatgacgcagtcaccactgtccctccccgtgacccttggacagccagcgtcgattagctgcaagtcatcccaatccctgctcgattcggatggaaagacctatctcaactggctgcagcaaagacccggtcagag ccctaggagactcatctcgttggtgtcaaagctggacagcggagtgccggaccggttttccggttcgggatcggggacggacttcactctgaagatttcacggggtggaagctgaggatgtgggagtgtactactgctggcagggaacccatttccctggcacttttggcggaggaactaaggtcgaaatcaagggaggaggtggctcgggaggagg cggatcgggcggaggcgggagcggcggagggggtccgaaatccaacttgtccagtcaggagccgaagtgaagaaaccgggagccaccgtcaaaatcagctgtaagggatcgggattcaatatcgaggactactacatccactgggtgcagcaagctccgggcaaaggactggagtggatggggcgcatcgacccagagaacgacgaaaccaa atacggcccgatcttccaagggcgggtgaccatcaccgcggacacctcaactaacactgtgtacatggagctgagctccctgcgctccgaagatactgcagtctactactgcgccttccgcggtggtgtgtactggggacagggcaccactgtgactgtcagctcgaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctc ccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatga ggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatg ggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR 8 - Whole - ak 784 malpvtalllplalllhaarpdvvmtqsplslpvtlgqpasisc kssqslldsdgktyln wlqqrpgqsprrlis lvsklds gvpdrfsgsgsgtdftlkisrveaedvgvyyc wqgthfpgt fgggtkveikggggsggggsggggsggggseiqlvqsgaevkkpga wgqgttvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqtt qeedgcscrfpeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR 9 Mouse anti-EGFRvIII, clone 3C10 CAR 9 - Whole - nk 785 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagatccagctccaacagagcggagccgaactggtcaaaccggggcgtcggtgaagttgtcatgcactggatcgggcttcaacatcgaggattactacatccactgggtcaagcaacgcaccgagcaggggctggaatggatcggacgg atcgaccccgaaaacgatgaaaccaagtacgggcctatcttccaaggacgggccaccattacggctgacacgtcaagcaataccgtctacctccagctttccagcctgacctccgaggacactgccgtgtactactgcgccttcagaggagaggcgtgtactggggaccaggaaccactttgaccgtgtccagcggaggcggtggatcaggagga ggaggctcaggcggtggcggctcgcacatggacgtggtcatgactcagtccccgctgaccctgtcggtggcaattggacagagcgcatccatctcgtgcaagagctcacagtcgctgctggattccgacggaaagacttatctgaactggctgctccaaagaccagggcaatcaccgaaacgccttatctccctggtgtcgaaactcgact cgggtgtgccggatcggtttaccggtagcgggtccggcacggacttcactctccgcatttcgagggtggaagcggaggatctcgggatctactactgttggcagggaacccacttccctgggacttttggaggcggaactaagctggaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtcc ctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcag actactcaagaggagaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgc gcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR 9 - Whole - ak 786 malpvtalllplalllhaarpeiqlqqsgaelvkpgasvklsctgsgfnie dyyih wvkqrteqglewig ridpendetkygpifqg ratitadtssntvylqlssltsedtavyyca frggvy wgpgttltvssggggsggggsggggshmdvvmtqspltlsvaigqsasisc kssqslldsdg ktyln wllqrpgqspkrlis lvsklds gvpdrftgsgsgtdftlrisrveaedlgiyyc wqgthfpgt fgggtkleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscr fpeeeeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR10 Anti-EGFRvIII, clone 139 CAR 10 - Whole - nk 787 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgatatccaaatgactcagagcccttcatccctgagcgccagcgtcggagacagggtgaccatcacgtgccgggcatcccaaggcattagaaataacttggcgtggtatcagcaaaaaccaggaaaggccccgaagcgcct gatctacgcggcctccaaccttcagtcaggagtgccctcgcgcttcaccgggagcggtagcggaactgagtttacccttatcgtgtcgtccctgcagccagaggacttcgcgacctactactgcctccagcatcactcgtacccgttgacttcgggaggcggaaccaaggtcgaaatcaaacgcactggctcgacgtca gggtccggtaaaccgggatcgggagaaggatcggaagtccaagtgctggagagcggaggcggactcgtgcaacctggcgggtcgctgcggctcagctgtgccgcgtcggggttttactttcagctcgtacgctatgtcatgggtgcggcaggctccgggaaaggggctggaatgggtgtccgctatttccggctc gggtggaagcaccaattacgccgactccgtgaagggacgcttcaccatctcacgggataactccaagaatactctgtacctccagatgaactcgctgagagccgaggacaccgcagtgtactactgcgcagggtcaagcggctggtccgaatactggggacagggcaccctcgtcactgtcagctccaccactaccccagcaccgaggccacccaccccggctcc taccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctt taagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggac gggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR 10 - Whole - ak 788 malpvtalllplallllhaarpdiqmtqspsslsasvgdrvtitcrasqgirnnlawyqqkpgkapkrliyaasnlqsgvpsrftgsgsgteftlivsslqpedfatyyclqhhsypltsgggtkveikrtgstsgsgkpgsgegsevqvlesggglvqpggslrlscaasgftfssyamswvrqapgk glewvsaisgsggstnyadsvkgrftisrdnskntlylqmnslraedtavyycagssgwseywgqgtlvtvsstttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpeeeeggcelrvkfsrsada paykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr

In one embodiment, a CAR molecule that binds EGFRvIII contains (e.g., consists of) the amino acid sequence shown in Table 18. In one embodiment, a CAR that binds EGFRvIII contains (e.g., consists of) an amino acid sequence selected from any of SEQ ID NOs: 770, 772, 774, 776, 778, 780, 782, 784, 786, 788; or an amino acid sequence having at least one, two, three, four, five, 10, 15, 20, or 30 modifications (e.g., substitutions, e.g. conservative substitutions), but no more than 60, 50, or 40 modifications (e.g., substitutions eg conservative substitutions) of an amino acid sequence selected from any of SEQ ID NOs: 770, 772, 774, 776, 778, 780, 782, 784, 786, 788; or an amino acid sequence having 85%, 90%, 95%, 96%, 97%, 98%, 99% identity with an amino acid sequence selected from any of SEQ ID NOs: 770, 772, 774, 776, 778, 780, 782, 784, 786, 788.

In one embodiment, the CAR molecule contains an antigen-binding domain for CD123 (e.g., a murine, human, or humanized antibody, or antibody fragment that specifically binds to CD123), a transmembrane domain, and an intracellular signaling domain (e.g., an intracellular signaling domain containing a costimulatory domain and/ or the main signaling domain). Exemplary CAR molecules targeting CD123 include those shown in Table 19 and those shown in Tables 2, 6 and 9 in WO2016/028896. Other exemplary CAR molecules that target CD123 are described in WO/2014/130635 (eg Table 1 in WO/2014/130635). Other exemplary CAR molecules that target CD123 are described in WO/2014/144622.

In one embodiment, a CAR molecule that binds CD123 contains (e.g., consists of) the amino acid sequence shown in Table 19. In one embodiment, a CAR that binds CD123 contains (e.g., consists of) an amino acid sequence selected from any of SEQ ID NOs: 750, 755, 760, 765; or an amino acid sequence having at least one, two, three, four, five, 10, 15, 20, or 30 modifications (e.g., substitutions, e.g. conservative substitutions), but no more than 60, 50, or 40 modifications (e.g., substitutions eg conservative substitutions) amino acid sequence selected from any of SEQ ID NOs: 750, 755, 760, 765; or an amino acid sequence having 85%, 90%, 95%, 96%, 97%, 98%, 99% identity with an amino acid sequence selected from any of SEQ ID NOs: 750, 755, 760, 765.

Table 19 Exemplary CAR Sequences

Name SEQ ID Subsequence CAR123-2 - nk 749 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggat gggatggatcaaccctaattcgggcggaactaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtct catcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgctgccgctt cgagcttgcaaagcggggtgccatccagattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccag cctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcc tgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggc gggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR123-2 - ak 750 malpvtalllplalllhaarpqvqlvqsgaevkkpgasvkvsckasgytftgyymhwvrqapgqglewmgwinpnsggtnyaqkfqgrvtltrdtsistvymelsrlrsddtavyycardmnilatvpfdiwgqgtmvtvssggggsggggsggggsdiqmtqspsslsasvgdrvtitcrasqsis sylnwyqqkpgkapklliyaasslqsgvpsrfsgsgsgtdftltvnslqpedfatyycqqgdsvpltfgggtrleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpee eeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR123-2
scFv 751 malpvtalllplalllhaarpqvqlvqsgaevkkpgasvkvsckasgytftgyymhwvrqapgqglewmgwinpnsggtnyaqkfqgrvtltrdtsistvymelsrlrsddtavyycardmnilatvpfdiwgqgtmvtvssggggsggggsggggsdiqmtqspsslsasvgdrvtitcrasqsis sylnwyqqkpgkapklliyaasslqsgvpsrfsgsgsgtdftltvnslqpedfatyycqqgdsvpltfgggtrleik CAR123-2
vh 752 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSS CAR123-2
VL 753 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIK CAR123-3 - nk 754 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccaagtccaactcgttcaatccggcgcagaagtcaagaagccaggagcatcagtgaaagtgtcctgcaaagcctcaggctacatcttcacgggatactacatccactgggtgcgccaggctccgggccagggccttgagtggatgggctgg atcaaccctaactctgggggaaccaactacgctcagaagttccaggggagggtcactatgactcgcgatacctccatctccactgcgtacatggaactctcgggactgagatccgacgatcctgccgtgtactactgcgcccgggacatgaacatcttggcgaccgtgccgttgacatttggggacagggcaccctcgtcactgtgtcgagcgg tggaggaggctcggggggtggcggatcaggagggggaggaagcgacatccagctgactcagagcccatcgtcgttgtccgcgtcggtgggggatagagtgaccattacttgccgcgccagccagagcatctcatcatatctgaattggtaccagcagaagcccggaaaggccccaaaactgctgatctacgctgcaagcagcctccaatcgggagt gccgtcacggttctccgggtccggttcgggaactgactttaccctgaccgtgaattcgctgcaaccggaggatttcgccacgtactactgtcagcaaggagactccgtgccgctgaccttcggtggaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtcc ctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcag actactcaagaggagaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgc gcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR123-3 - ak 755 malpvtalllplalllhaarpqvqlvqsgaevkkpgasvkvsckasgyiftgyyihwvrqapgqglewmgwinpnsggtnyaqkfqgrvtmtrdtsistaymelsglrsddpavyycardmnilatvpfdiwgqgtlvtvssggggsggggsggggsdiqltqspsslsasvgdrvtitcrasqsiss ylnwyqqkpgkapklliyaasslqsgvpsrfsgsgsgtdftltvnslqpedfatyycqqgdsvpltfgggtkveiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpee eeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR123-3
scFv 756 malpvtalllplalllhaarpqvqlvqsgaevkkpgasvkvsckasgyiftgyyihwvrqapgqglewmgwinpnsggtnyaqkfqgrvtmtrdtsistaymelsglrsddpavyycardmnilatvpfdiwgqgtlvtvssggggsggggsggggsdiqltqspsslsasvgdrvtitcrasqsiss ylnwyqqkpgkapklliyaasslqsgvpsrfsgsgsgtdftltvnslqpedfatyycqqgdsvpltfgggtkveik CAR123-3
vh 757 QVQLVQSGAEVKKPGASVKVSCKASGYIFTGYYIHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSGLRSDDPAVYYCARDMNILATVPFDIWGQGTLVTVSS CAR123-3
VL 758 DIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTKVEIK CAR123-4 - nk 759 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccaagtccaactccaacagtcaggcgcagaagtgaaaaagagcggtgcatcggtgaaagtgtcatgcaaagcctcgggctacaccttcactgactactatatgcactggctgcggcaggcaccgggacagggacttgagtggatggga tggatcaacccgaattcaggggactaactacgcgcagaagttccaggggagagtgaccctgacgagggacacctcaatttcgaccgtctacatggaattgtcgcgcctgagatcggacgatactgctgtgtactactgtgcccgcgacatgaacatcctcgcgactgtgccttttgatatctggggacaggggactatggtcaccg tttcctccgcttccggtggcggaggctcgggaggccgggcctccggtggaggaggcagcgacatccagatgactcagagcccttcctcgctgagcgcctcagtgggagatcgcgtgaccatcacttgccgggccagccagtccatttcgtcctacctcaattggtaccagcagaagccgggaaaaggcgcccaagctcttgat ctacgctgcgagctccctgcaaagcggggtgccgagccgattctcgggttccggctcgggaaccgacttcactctgaccatctcatccctgcaaccagaggactttgccacctactactgccaacaaggagattctgtcccactgacgttcggcggaggaaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatc gcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaac ccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacggaccca gaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR123-4 - ak 760 malpvtalllplalllhaarpqvqlqqsgaevkksgasvkvsckasgytftdyymhwlrqapgqglewmgwinpnsgdtnyaqkfqgrvtltrdtsistvymelsrlrsddtavyycardmnilatvpfdiwgqgtmvtvssasggggsggrasggggsdiqmtqspsslsasvgdrvtitcrasq sissylnwyqqkpgkapklliyaasslqsgvpsrfsgsgsgtdftltisslqpedfatyycqqgdsvpltfgggtkveiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyck CAR123-4
scFv 761 MALPVTALLLPLALLLHAARPQVQLQQSGAEVKKSGASVKVSCKASGYTFTDYYMHWLRQAPGQGLEWMGWINPNSGDTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSASGGGGSGGRASGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGDSVPLTFGGGTKVEIK CAR123-4
vh 762 WGQGTMVTVSS CAR123-4
VL 763 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGDSVPLTFGGGTKVEIK CAR123-1 - nk 764 atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccaagtccaactcgtccagtcaggagcggaagtcaagaagcccggagcgtcagtcaaagtgtcatgcaaagcctcgggctacactttcactgggtactacatgcactgggtgcgccaggctccaggacagggactggaatggatggga tggatcaacccgaactccggtggcaccaattacgcccagaagttccaggggagggtgaccatgactcgcgacacgtcgatcagcaccgcatacatggagctgtcaagactccggtccgacgatactgccgtgtactactgcgcacgggacatgaacattctggccaccgtgccttttgacatctggggtcagggaactatggttaccgtgtcctctggt ggaggcggctccggcggggggggaagcgggaggcggtggaagcgacattcagatgacccagtcgccttcatccctttcggcgagcgtgggagatcgcgtcactatcacttgtcggggcctcgcagtccatctccacctacctcaattggtaccagcagaagccaggaaaagcaccgaatctgctgatctacgccgcgttttcc ttgcaatcgggagtgccaagcagattcagcggatcgggatcaggcactgatttcaccctcaccatcaactcgctgcaaccggaggattcgctacgtactattgccaacaaggagacagcgtgccgctcaccttcggcggagggactaagctggaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccag cctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcc tgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggc gggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg CAR123-1 - ak 765 malpvtalllplalllhaarpqvqlvqsgaevkkpgasvkvsckasgytftgyymhwvrqapgqglewmgwinpnsggtnyaqkfqgrvtmtrdtsistaymelsrlrsddtavyycardmnilatvpfdiwgqgtmvtvssggggsggggsggggsdiqmtqspsslsasvgdrvtitcrasq sistylnwyqqkpgkapnlliyaafslqsgvpsrfsgsgsgtdftltinslqpedfatyycqqgdsvpltfgggtkleiktttpaprpptpaptiasqplslrpeacrpaaggavhtrgldfacdiyiwaplagtcgvlllslvitlyckrgrkkllyifkqpfmrpvqttqeedgcscrfpe eeeggcelrvkfsrsadapaykqgqnqlynelnlgrreeydvldkrrgrdpemggkprrknpqeglynelqkdkmaeayseigmkgerrrgkghdglyqglstatkdtydalhmqalppr CAR123-1
scFv 766 malpvtalllplalllhaarpqvqlvqsgaevkkpgasvkvsckasgytftgyymhwvrqapgqglewmgwinpnsggtnyaqkfqgrvtmtrdtsistaymelsrlrsddtavyycardmnilatvpfdiwgqgtmvtvssggggsggggsggggsdiqmtqspsslsasvgdrvtitcrasq sistylnwyqqkpgkapnlliyaafslqsgvpsrfsgsgsgtdftltinslqpedfatyycqqgdsvpltfgggtkleik CAR123-1
vh 767 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSS CAR123-1
VL 768 DIQMTQSPSSLSASVGDRVTITCRASQSISTYLNWYQQKPGKAPNLLIYAAFSLQSGVPSRFSGSGSGTDFTLTINSLQPEDFATYYCQQGDSVPLTFGGGTKLEIK

In one embodiment, the CAR molecule contains an antigen-binding domain for CD33 (e.g., a murine, human, or humanized antibody, or an antibody fragment that specifically binds to CD33), a transmembrane domain, and an intracellular signaling domain (e.g., an intracellular signaling domain containing a costimulatory domain and/ or the main signaling domain). Exemplary CAR molecules targeting CD33 are described herein and are listed in WO2016/014576, for example, in Table 2 in WO2016/014576.

In one embodiment, the CAR molecule contains an antigen-binding domain for CLL-1 (e.g., a mouse, human, or humanized antibody, or an antibody fragment that specifically binds to CLL-1), a transmembrane domain, and an intracellular signaling domain (e.g., an intracellular signaling domain containing co-stimulatory domain and/or main signaling domain). Exemplary CAR molecules targeting CLL-1 are described herein and are listed in WO/2016/014535, for example, in Table 2 in WO2016/014535.

CAR with natural killer cell receptor (NKR) components

In one embodiment, the CAR molecule described herein contains one or more components of the cell's natural killer receptor (NKR). The NKR component may be a transmembrane domain, a hinge domain, or a cytoplasmic domain from any of the following natural killer cell receptors: the cell's immunoglobulin-like natural killer receptor (KIR), e.g. , KIR2DS3, KIR2DS4, DIR2DS5, KIR3DL1/S1, KIR3DL2, KIR3DL3, KIR2DP1 and KIR3DP1; mediating cytotoxicity cell receptor - natural killer (NCR), for example, NKp30, NKp44, NKp46; lymphocyte activation signaling molecule (SLAM) families of immune cell receptors, eg CD48, CD229, 2B4, CD84, NTB-A, CRACC, BLAME and CD2F-10; Fc receptor (FcR), eg CD16 and CD64; as well as Ly49 receptors, for example, LY49A, LY49C. CAR molecules containing the NKR components described herein can interact with an adapter molecule or an intracellular signaling domain such as DAP12. Exemplary configurations and sequences of CAR molecules containing NKR elements are described in International Patent Publication No. WO2014/145252, the contents of which are incorporated herein by reference.

Cleaved CAR

In some embodiments, a cleaved CAR is used in the CAR-expressing cell described herein. The split CAR approach is described in more detail in patent publications WO2014/055442 and WO2014/055657, the contents of which are incorporated herein by reference. Briefly, a cleaved CAR system includes a cell expressing a first CAR containing a first antigen-binding domain and a co-stimulatory domain (eg, 41BB), while the cell also expresses a second CAR containing a second antigen-binding domain and an intracellular signaling domain (eg, CD3-zeta). When the cell encounters the first antigen, the co-stimulatory domain is activated and the cell proliferates. When the cell encounters the second antigen, the intracellular signaling domain is activated and cytolytic activity is triggered. Thus, a CAR-expressing cell is fully activated only in the presence of both antigens. In embodiments, the first antigen-binding domain recognizes an antigen as described herein, eg, is an antigen-binding domain as described herein, and a second antigen-binding domain recognizes a second antigen as described herein.

Exemplary characteristics of transiently expressed CARs of the invention

In some embodiments, it is useful if the antigen-binding domain is operably linked to another CAR domain, such as a transmembrane domain or an intracellular domain, both of which are described elsewhere herein, for expression in a cell. In one embodiment, a nucleic acid encoding an antigen-binding domain is operably linked to a nucleic acid encoding a transmembrane domain and a nucleic acid encoding an intracellular domain.

A spacer domain can be inserted between the antigen binding domain and the CAR transmembrane domain, or between the intracellular domain and the CAR transmembrane domain. As used herein, the term "spacer domain" generally refers to any oligo- or polypeptide that binds a transmembrane domain to either an antigen-binding domain or an intracellular domain in a polypeptide chain. In one embodiment, the spacer domain may contain up to 300 amino acids, preferably 10-100 amino acids, and most preferably 25-50 amino acids. In another embodiment, a short oligo- or polypeptide linker, preferably 2 to 10 amino acids in length, can link the transmembrane domain and the intracellular domain of CAR. An exemplary linker includes a glycine-serine doublet.

In some embodiments, the CAR also contains a signal peptide. In one embodiment, the signal peptide contains a nucleotide sequence containing ATGGCCTTACCAGTGACCGCCTTGCTCCTGCCTGGCCTTGCTGCTCCACGCCGCCAGGCCG or SEQ ID NO: 3034. In another embodiment, the signal peptide contains an amino acid sequence containing MALPVTALLLPLALLLHAARP or SEQ ID NO: 3035.

In some embodiments, the CAR also contains a dimerization domain, such as a dimerization domain from FKBP or a similar molecule. In such an embodiment, the presence of CAR molecules on the surface of the modified T cell is prevented due to spontaneous aggregation of CAR molecules in the cytoplasm or other internal areas in the cell.

In another embodiment, the dimerization domain comprises a nucleotide sequence containing CGGGGCGTGCAGGTTGAGACAATTTCCCCAGGAGATGGGCGAACGTTCCCCAAGCGCGGACAGACATGCGTTGTGCACTACACAGGAATGTTGGAGGACGGAAAGAAAATGGACAGTTCAAGAGATCGGAACAAACCATTCAAATTCATGTTGGGAAAACAGGAAGTGATACGGGGCTGGGAAGAGG GTGTAGCGCAAATGTCCGTTGGTCAACGAGCAAAACTCACGATAAGTCCCGATTATGCTTACGGCGCCAACCGGTCACCCGGGCATCATACCGCCTCATGCGACTTTGGTCTTTGATGTGGAGCTGTTGAAACTTGAAACTCGCGGAGTACAGGTTGAAACAATATCACCCGGGGACGGGCGGACTTTTCCGAAGAGAGGTCAGACCTGCGTCGTCCATTATACCGG TATGCTGGAGGACGGAAAGAAAATGGACAGCTCACGGACCGAAATAAACCATTCAAATTTATGTTGGGAAACAAGAGGTTATCAGGGGCTGGGAGGAGGGTGTGGCCCAGATGTCTGTCGTCAGCGCGCGAAACTCACAATCTCTCCGGATTATGCGTATGGGGCGACAGGGCATCCGGGAATTATCCCCCCACGCTACCTTGGTTTTCGAT GTTGAGCTTCTGAAGTTGGAGACCAGAGGAGTTCAAGTGGAGACAATATCTCCTGGGGATGGACGGACGTTCCCCAAGCGCGGCCAGACCTGTGTAGTCCACTACACAGGGATGCTTGAAGACGGAAAAAAGATGGATAGCAGTAGAGATCGCAACAAACCATTTAAGTTCATGCTGGGGAAGCAGGAAGTAATACGCGGCTGGGAGGAAGGCGTGGCACAGATGAGTGTT GGTCAACGGGCCAAACTTACTATTTCTCCCGATTATGCGTATGGAGCCACCGGGCACCCTGGCATTATCCCACCCCATGCCACATTGGTTTTTGACGTTGAATTGCTTAAATTGGAGACCAGGGGAGTCCAAGTGGAAACAATATCACCGGGGGATGGTCGGACTTTTCCTAAAAGGGGCCAAACCTGTGTAGTCCATTATACCGGAATGCTCGAAGACGGAAAGAAA ATGGACTCTTCTAGAGACCGCAATAAGCCCTTCAAGTTCATGTTGGGTAAGCAAGAGGTGATCCGGGGCTGGGAAGAGGGGGTCGCTCAAATGTCCGTCGGTCAGCGAGCTAAACTGACTATTTCCCCAGACTACGCATATGGAGCGACTGGCCACCCCGGTATTATTCCTCCCCATGCGACTCTCGTGTTTCGACGTAGAACTCTTGAAATTGGAAACG or SEQ ID NO : 3015.

In another such embodiment, the dimerization domain comprises an amino acid sequence comprising RGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLG KQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLETRGVQVETISPGDGRTFPKRGQTCVVHYT GMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLET or SEQ ID NO: 980 (given elsewhere in this document).

Solubilizing the dimerization domains with a solubilizing agent introduced into the cell or animal containing the cell prevents dimerization and allows the construct to pass through the secretory system where it is processed by furin cleavage to express functional CAR on the cell surface.

In the presence of a solubilizing agent, the CAR molecules are separated and aggregation is prevented. The introduction of a solubilizing agent prevents the dimerization or aggregation of the CAR molecules and allows the CAR molecules to be presented on the surface of the T cell. In one embodiment, the furin cleavage site contains a nucleotide sequence containing TCAGCCCGGAACAGGCGGAAGAGA or SEQ ID NO: 3016. In another embodiment, the furin cleavage site contains the amino acid sequence SARNRRKR or SEQ ID NO: 3017.

Composition

In one embodiment, the invention provides an isolated nucleotide sequence comprising a nucleotide sequence comprising a suicide gene comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 3001-3004; and a nucleotide sequence encoding a CAR containing an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain. In some embodiments, the isolated nucleotide sequence comprises SEQ ID NO: 3018, 3020, 3024, 3026, 3028, or 3030.

In one embodiment, the invention provides an isolated polypeptide comprising the amino acid sequence encoded by the suicide gene, the amino acid sequence being selected from the group consisting of SEQ ID NOs: 3005-3007; and a CAR containing an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain. In some embodiments, the isolated polypeptide comprises the amino acid sequence of SEQ ID NO: 3019, 3021, 3026, 3028, 3030, or 3034.

In another embodiment, the invention provides an isolated nucleotide sequence comprising a nucleic acid encoding a dimerization domain and a CAR comprising an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain. In some embodiments, the dimerization domain contains the amino acid sequence of SEQ ID NO: 980. In other embodiments, the isolated nucleotide sequence contains SEQ ID NO: 977 or 3032.

In another embodiment, the invention provides an isolated polypeptide comprising a dimerization domain and a CAR comprising an anti-B cell binding domain, a transmembrane domain, a co-stimulatory domain, and an intracellular signaling domain. In some embodiments, the isolated polypeptide comprises the amino acid sequence of SEQ ID NO: 978 or 3033.

Signal peptide

In some preferred embodiments, the fusion proteins of the invention also contain a signal peptide. Signal peptides are useful if you want the protein to pass through the secretory pathway. In preferred embodiments, the signal peptide will be designed to be present at the extreme N-terminus of the fusion protein. Exemplary signal peptides are listed below:

CD8: MALPVTALLLPLALLLHAARP (SEQ ID NO: 2)

GMCSFR: MLLLVTSLLLCELPHPAFLLIP (SEQ ID NO: 43)

IL2: MYRMQLLSCIALSLALVTNS (SEQ ID NO: 44)

Ig K chain: MAQVKLQESGTELAKPGAAVK (SEQ ID NO: 45)

NPC2: MRFLAATFLLLALSTAAQA (SEQ ID NO: 46)

LAMB1: MGLLQLLAFSFLALCRARVRA (SEQ ID NO: 1114)

P3IP1: MLLAWVQAFLVSNMLLAEAYG (SEQ ID NO: 1115)

DMKN: MKFQGPPLLLALCLGSGEA (SEQ ID NO: 1116)

TPA: MDAMKRGLCCVLLLCGAVFVSP (SEQ ID NO: 1117)

PCSK9: MGTVSSRRSWWPLPLLLLLLLLGPAGARAQEDED (SEQ ID NO: 1118)

KDEL (SEQ ID NO: 47) or KKXX and derivatives at the extreme C-terminus of the protein of interest can be designed if the protein of interest is an ER resident protein. These sequences must be included along with the signal peptide.

Proteins of interest can be engineered to have glycosylation patterns for internalization via the mannose-6-phosphate receptor and targeting into the endosomal/lysosomal system. They must be included in the protein of interest itself if it is a protein that is permanently present in the compartment. The consensus sequence for N-glycosylation is Asn-X-Ser/Thr, where X is any amino acid except proline (Pro), serine (Ser), and threonine (Thr).

In embodiments that require proteins of interest to be targeted to the peroxisome, the fusion protein can be designed to contain a C-terminal peroxisome targeting signal (eg, PTS1:-SKL).

Cleavage sites

Each fusion protein of the invention contains a cleavage site. The cleavage site may be a self-cleavage site and/or a protease cleavage site. The cleavage site can be designed to be cleaved by any site-specific protease that is expressed in the cell of interest (whether by recombinant expression or endogenous expression) at a level sufficient to cleave a conditional expression domain, such as a degradation domain or an aggregation domain. In important aspects of the invention, the protease cleavage site is chosen to correspond to a protease naturally (or due to genetic modification of the cell) present in the cellular compartment associated with the expression of the protein of interest. That is, the intracellular targeting of the protease should overlap, or partially overlap, with the intracellular targeting of the protein of interest containing the conditional expression domain used, eg, a degradation domain or an aggregation domain. For example, if the protein of interest is on the cell surface, an enzyme to cleave it can be added exogenously to the cell.

If the protein of interest is in the endosomal/lysosomal system, a protease cleavage site for an enzyme resident in these compartments can be used. Such protease/consensus motifs include, for example,

Furin: RX(K/R)R consensus motif

PCSK1: RX(K/R)R consensus motif

PCSK5: RX(K/R)R consensus motif

PCSK6: RX(K/R)R consensus motif

PCSK7: RXXX[KR]R consensus motif

Cathepsin B: RRX

Granzyme B: I-E-P-D-X (SEQ ID NO: 35)

Factor XA: Ile-Glu/Asp-Gly-Arg

Enterokinase: Asp-Asp-Asp-Asp-Lys (SEQ ID NO: 36)

Genenase: Pro-Gly-Ala-Ala-His-Tyr (SEQ ID NO: 37)

Sortase: LPXTG/A

PreScission protease: Leu-Glu-Val-Phe-Gln-Gly-Pro (SEQ ID NO: 38)

Thrombin: Leu-Val-Pro-Arg-Gly-Ser (SEQ ID NO: 40)

TEV protease: E-N-L-Y-F-Q-G (SEQ ID NO: 41)

Elastase 1: [AGSV]-x (SEQ ID NO: 42).

In some embodiments, the fusion protein described herein contains a furin cleavage site. In some embodiments, the fusion proteins described herein contain any of the furin cleavage sites shown in Table 20.

In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from RTKR (SEQ ID NO: 123) or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with her; GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRR (SEQ ID NO: 127) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; LQWLEQQVAKRRTKR (SEQ ID NO: 129) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; GTGAEDPRPSRKRRSLG (SEQ ID NO: 133) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; SLNLTESHNSRKKR (SEQ ID NO: 135) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it; or CKINGYPKRGRKRR (SEQ ID NO: 137) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it.

In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from RTKR (SEQ ID NO: 123); GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125); GTGAEDPRPSRKRR (SEQ ID NO: 127); LQWLEQQVAKRRTKR (SEQ ID NO: 129); GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131); GTGAEDPRPSRKRRSLG (SEQ ID NO: 133); SLNLTESHNSRKKR (SEQ ID NO: 135) or CKINGYPKRGRKRR (SEQ ID NO: 137).

In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with it, or GTGAEDPRPSRKRR (SEQ ID NO: 127) or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it.

In some embodiments, the fusion proteins described herein comprise a furin cleavage site selected from GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) or GTGAEDPRPSRKRR (SEQ ID NO: 127).

In some embodiments, the fusion proteins described herein comprise a furin cleavage site GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125).

Table 20 . Illustrative furin cleavage sites

Amino acid sequence Nucleotide sequence Furin cleavage site 1 RTKR (SEQ ID NO: 123) cgtactaaaaga (SEQ ID NO: 1112) Furin cleavage site 2 GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) ggaaccggcgcggaagacccccggccctcggaagcgaaggtccctcggagacgtgggt (SEQ ID NO: 126) Furin cleavage site 3 GTGAEDPRPSRKRR (SEQ ID NO: 127) ggaaccggcgcggaagacccccggccctccaggaagcgaagg (SEQ ID NO: 128) Furin cleavage site 4 LQWLEQQVAKRRTKR (SEQ ID NO: 129) ctgcaatggctggagcagcaggtggcgaagcggagaactaagcgg (SEQ ID NO: 130) Furin cleavage site 5 GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131) ggcacaggtgccgaggaccctcggccaagccgcaaaaggaggtcacttggcggc (SEQ ID NO: 132) Furin cleavage site 6 GTGAEDPRPSRKRRSLG (SEQ ID NO: 133) ggaaccggagcagaagatcccagaccaagccggaaaaggcggtccctgggt (SEQ ID NO: 134) Furin cleavage site 7 SLNLTESHNSRKKR (SEQ ID NO: 135) agtctcaatttgactgagtcacacaattcggaagaaaagg (SEQ ID NO: 136) Furin cleavage site 8 CKINGYPKRGRKRR (SEQ ID NO: 137) tgcaagatcaacggctaccctaagaggggcagaaagcggcgg (SEQ ID NO: 138)

CONDITIONAL EXPRESSION DOMAIN

A fusion protein of the invention may contain a conditional expression domain. In some embodiments, the conditional expression domain has a first state and a second state, eg, aggregation states or conformational states, eg, stabilization/destabilization states or correct/misfolded states. The first condition is associated with, causes, or mediates cell surface expression or extracellular expression of one or more (e.g., all) fragments of the fusion protein in the first degree, or at the first level, and the second condition is associated with, causes, or mediates cell surface expression or extracellular expression of one or more (eg, all) fragments of the fusion protein in the second degree, or at the second level. In one embodiment, the second state is characterized by a level or degree that is, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or 30 times greater than the degree or level in the first state. In one embodiment, one of the conditions, such as a second condition, is associated with, maintained, or caused by the presence of an expression compound. In one embodiment, the presence of an expression compound may be associated with, cause, or mediate a change in a physical property, e.g., a second state is associated with a change in the level of a physical property, e.g., the presence of an expression compound is associated with, cause, or mediate a transition from a first state with a first physical property value. property to a second state with a second physical property value, for example, the property may include molecular weight, stability, absorption at a selected wavelength, reactivity with another molecule, or solubility. In one embodiment, the presence of an expression compound can be associated with, cause or mediate a transition from a first folding state to a second folding state, e.g. , less prone to degradation than the first state; or from a first folding state, which is characterized by a first level of degradation, to a second folding state, which is characterized by a second, lower level of degradation, for example, in the cell of interest. In one embodiment, the presence of an expression compound may be associated with, cause or mediate dissociation or disaggregation of the first and second conditional expression domains, e.g., from a higher order association to a lower order association, such as from dimers to monomers, or from tetramers to lower order structures, such as dimers or monomers. In one embodiment, the presence of an expression compound may be associated with, cause or mediate a change in solubility, e.g., the second state is associated with a higher level of solubility, e.g., the presence of an expression compound is associated with, causes, or mediates a transition from a first state of lower solubility to the second state with higher solubility. In one embodiment, the presence of an expression compound can be associated with, cause or mediate a transition from a first state of localization or compartmentalization of one or more or all of the fusion protein fragments to a second state of localization or compartmentalization of one or more or all of the fusion protein fragments, for example, from the Golgi apparatus or ER to another compartment or site, such as the cytosol, membrane, cell surface, or extracellular space.

In one embodiment, the presence of an expression compound can be associated with, cause or mediate a transition from a first folding state to a second folding state, e.g. , less prone to degradation than the first state; or from a first folding state, which is characterized by a first level of degradation, to a second folding state, which is characterized by a second, lower level of degradation, for example, in the cell of interest.

In one embodiment, one of the conditions, such as a second condition, is associated with, causes, or mediates a cleavage at a cleavage site. Without wishing to be bound by a particular theory, it is believed that in some embodiments, cleavage results in, or is associated with, cellular surface expression or extracellular expression of one or more (eg, all) fusion protein fragments. In one embodiment, in the absence of an expression compound, when expressed in a cell of interest, the fusion protein, e.g. at the first level, e.g. steric cleavage hindrance provided by another fragment, such as a conditional expression domain. Conversely, in the presence of an expression compound, surface expression and/or extracellular expression of one or more (e.g., all) domains of the fusion protein shifts to a second level that is higher than the first level, e.g., significantly higher, e.g., 2, 3, 4 , 5 or 10 times higher than the first level, or more, for example, at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 300, 400, 500, 600, 700, 800, 900 or 1000% more than the first level. Thus, in one embodiment, the conditional expression domain has the following characteristics: (1) it is not naturally present in the context of the fusion protein, eg, it is recombinant or engineered; (2) surface expression and/or extracellular expression is co-translationally or post-translationally regulated; (3) the degree of surface expression and/or extracellular expression is significantly increased in the presence of the expression compound.

In one embodiment, the addition of an expression compound, such as a disaggregating compound or a stabilizing compound, to a population of cells, such as host cells or cells containing the fusion proteins described herein, causes a subpopulation of cells to transition from a first state to a second state, such as , aggregation states, or conformational states, for example, stabilization/destabilization states or correct/misfolded states described herein. In one embodiment, in the absence of an expression compound, such as a disaggregating compound or a stabilizing compound, less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the cells in the population have a second state, or more, or exactly 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% of the cells in the population have the first state. In one embodiment, in the presence of an expression compound, such as a disaggregating compound or a stabilizing compound, more than or exactly 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the cells in the population have a second state, and less than 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% of the cells in the population have the first state. The percentage of cells in a population having a certain state can be determined using the methods described in the specification, for example, in Figure 4.

In embodiments, the conditional expression domain is a degradation domain, such as those described herein. In other embodiments, the conditional expression domain is an aggregation domain, such as those described herein. In one embodiment, the conditional expression domain does not contain a degradation domain. In one embodiment, the conditional expression domain does not contain an aggregation domain. In embodiments, the conditional expression domain-containing fusion protein comprises a transmembrane protein, eg, a chimeric antigen receptor (CAR), eg, as described herein. In some embodiments, the conditional expression domain is a degradation domain. In some embodiments, the conditional expression domain is an aggregation domain.

Aggregation domains

In some embodiments, the conditional expression domain is an aggregation domain. Methods for obtaining aggregation domains that cause intracellular aggregation in the absence of an expression compound, such as a deaggregating compound, are known in the art and are described in more detail below.

The present invention encompasses aggregation domains derived from any naturally occurring protein. Preferably, the fusion proteins of the invention will contain an aggregation domain for which no antiaggregating compound is naturally expressed or present in the cellular compartments of the cell of interest. For example, if the fusion protein is to be expressed in T cells, it is preferable to choose an aggregation domain that pairs with a deaggregating compound not naturally present in T cells. Thus, the aggregation domain, when expressed in the cell of interest, will only be disaggregated in the presence of the disaggregating compound. Notably, this property can be achieved either by modifying the aggregation domain to lose binding to the naturally expressed/present antiaggregant compound (in which case the aggregation domain will only disaggregate in the presence of the synthetic compound), or by expressing the aggregation domain in a compartment where there is no a naturally expressed/present ligand (eg, the aggregation domain may be derived from a species other than the species in which the fusion protein will be expressed).

Pairs domain aggregation-disaggregation connection can be obtained from any natural or synthetic protein. Deaggregating compounds can be any natural or synthetic compounds. In particular embodiments, the anti-aggregating compounds will be existing prescription or over-the-counter drugs. Examples of proteins that can be modified to have the properties of an aggregation domain are given below along with the corresponding antiaggregating compounds.

In one embodiment, the aggregation domain is a dimerization domain, eg derived from a FKB protein (FKBP). In some embodiments, the aggregation domain comprises an amino acid sequence selected from SEQ ID NO: 975, or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity therewith, or SEQ ID NO: 976, or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. In some embodiments, the aggregation domain comprises an amino acid sequence selected from SEQ ID NO: 979, or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity therewith, or SEQ ID NO: 980, or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. If the aggregation domain is derived from FKBP, the antiaggregating compound may be selected from AP21998 or AP22542, known in the art and described in Rollins et al. 2000, PNAS vol. 97 no. 13, 7096-7101, WO/2000/023600, and Rivera, VM, et al. (2000) Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum. Science 287:826-30. Each of these references is incorporated by reference in its entirety. Without being bound by a particular theory, FKBP domains having F36M substitutions assemble into dimers. FKBP F36M dimers can be dissociated, eg disaggregated, by adding a ligand, eg FK506, rapamycin, AP22542, AP21998 or Shield-1.

GVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKK F DSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLE (SEQ ID NO: 975)

GVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLE (SEQ ID NO: 976)

RGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKFDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPD YAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEV IRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPPHATLVFDVELLKLET (SEQ ID NO: 979)

RGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPD YAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEV IRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLET (SEQ ID NO: 980).

In another embodiment, the aggregation domain is derived from the UVR8 protein. UVR8 is a plant photoreceptor protein (Chen et al. 2013. J. Cell. Biol. v201 no. 4:631-640; Rizzini, L., et al. 2011. Science. 332:103-106; Christie, JM, et al 2012 Science 335:1492-1496; Wu, D. et al 2012 Nature 484:214-219. Each of these references is incorporated by reference in its entirety. UVR8 constitutively forms photolabile homodimers that dissociate upon absorption of ultraviolet B (UVB) radiation (280-320 nm). In one embodiment, the aggregation domain is derived from the UVR8 domain and the antiaggregating compound is the appropriate dose of UVB radiation. In one embodiment, an appropriate dose of UVB radiation is sufficient to dissociate at least 25%, 50%, 75%, or 100% of the UVR8 homodimers. In one embodiment, the appropriate dose of UVB is minimally toxic to the cell containing the fusion protein.

In some embodiments, a fusion protein of the present invention contains multiple, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10 or more copies of a conditional expression domain, e.g., an aggregation domain or a degradation domain. In some embodiments, the implementation of the fusion protein of the present invention contains many, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more aggregation domains.

In some embodiments, each of the plurality of aggregation domains is a copy of the same aggregation domain. Such aggregation domains will bind to each other to form homooligomers, eg homodimers.

In some embodiments, a fusion protein of the present invention comprises a plurality, eg, more than one, of aggregation domains, wherein the plurality includes more than one type of aggregation domain, eg, a first type and a second type. In some embodiments, the implementation of the first type of aggregation domain connects, for example, binds, and promotes oligomerization or aggregation, with a second type of aggregation domain; such an association is a heteromeric association or heterooligomerization of aggregation domains, eg into heterodimers. In some embodiments, the implementation of the fusion protein of the present invention contains two, four, six or eight aggregation domains, while the fusion protein contains at least one aggregation domain of each type, for example, the first type and the second type. In one embodiment, a fusion protein comprising a plurality of aggregation domains, wherein the plurality includes more than one type of aggregation domain, eg, type one and type two, contains the same number of each type of aggregation domain. In some embodiments, in which the fusion protein contains four or more (e.g., six, eight, ten or more) aggregation domains, the aggregation domains are located in an alternating order in the fusion protein, e.g., type 1, type 2, type 1, 2 type. In some embodiments where the fusion protein contains four or more (e.g., six, eight, ten or more) aggregation domains, the aggregation domains are block-located in the fusion protein, e.g., type 1, type 1, type 2, type 2 domains. In some embodiments, the first type aggregation domain does not perceptibly merge with other copies of the first type aggregation domain, and the second type aggregation domain perceptibly does not merge with other copies of the second type aggregation domain. In some embodiments, the first type aggregation domain only visibly combines with other copies of the first type aggregation domain, and the second type aggregation domain only visibly combines with other copies of the second type aggregation domain.

In some embodiments, the expression compound, e.g., a disaggregating compound, is AP21998 or AP22542 (chemical structures are provided herein; AP21998 and AP22542 are the same to the left of the dotted line and different to the right of the dotted line) . The preparation and use of AP21998 and AP22542 is known in the art and is described in Rollins et al. 2000, Amara, JF, et al. (1997) Proc. Natl. Acad. sci. USA 94, 10618-10623, Clackson, T., et al. (1998) Proc. Natl. Acad. sci. USA 95, 10437-10442 and Yang, W., et al. (2000) J. Med. Chem. 43, 1135-1142. Each of these references is incorporated by reference in its entirety.

In some embodiments, the expression compound, eg, the antiaggregant compound, is FK506 (tacrolimus) or rapamycin (sirolimus). In some embodiments, the conditional expression domain, eg, the aggregation domain, is derived from FKBP and the expression compound, eg, a deaggregating compound, is FK506 (tacrolimus) or rapamycin (sirolimus). The preparation and use of FK506 and rapamycin is known in the art.

In some embodiments, an expression compound, such as a deaggregating compound, inhibits interaction between aggregation domains. In some embodiments, in which the antiaggregating compound is FK506, rapamycin, AP22542, or AP21998, the antiaggregating compound inhibits interaction between fusion proteins containing an aggregation domain derived from FKBP F36M.

An exemplary aggregation domain-disaggregating compound pair was prepared and presented herein (SEQ ID NOs: 977 (nucleic acid) and 978 (amino acid sequence)). This aggregation domain is the FKBP F36M domain described in "A ligand-reversible dimerization system for controlling protein-protein interactions", Rollins et al. PNAS vol. 97 no. 13, 7096-7101 and WO/2000/023600. Each of these references is incorporated by reference in its entirety.

Nucleotide sequence of CD19bbz on-CAR, CD19 on-CAR (SEQ ID NO: 977)

Signal peptide-conditional aggregation domains (4 repeats)-furin site-FMC63bbz

ATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACGCCGCCAGGCCGGGATCCCGGGGCGTGCAGGTTGAGACAATTTCCCCAGGAGATGGGCGAACGTTCCCCAAGCGCGGACAGACATGCGTTGTGCACTACACAGGAATGTTGGAGGACGGAAAGAAAATGGACAGTTCAAGAGATCGGAACAAACCATTCAAATTCATGTTGG GAAAACAGGAAGTGATACGGGGCTGGGAAGAGGGTGTAGCGCAAATGTCCGTTGGTCAACGAGCAAAACTCACGATAAGTCCCGATTATGCTTACGGCGCCAACCGGTCACCCGGGCATCATACCGCCTCATGCGACTTTGGTCTTTGATGTGGAGCTGTTGAAACTTGAAACTCGCGGAGTACAGGTTGAAACAATATCACCCGGGGACGGGCGGACTTTTCCGAAG AGAGGTCAGACCTGCGTCGTCCATTATACCGGTATGCTGGAGGACGGAAAGAAAATGGACAGCTCACGGGACCGAAATAAACCATTCAAATTTATGTTGGGAAACAAGAGGTTATCAGGGGCTGGGAGGAGGTGTGTGGCCCAGATGTCTGTCGTCAGCGCGCGAAACTCACAATCTCTCCGGATTATGCGTATGGGGCGACAGGGCATCCGG GAATTATCCCTCCCCACGCTACCTTGGTTTTCGATGTTGAGCTTCTGAAGTTGGAGACCAGAGGAGTTCAAGTGGAGACAATATCTCCTGGGGATGGACGGACGTTTCCCCAAGCGCGGCCAGACCTGTGTAGTCCACTACACAGGGATGCTTGAAGACGGAAAAAAGATGGATAGCAGTAGAGATCGCAACAAACCATTTAAGTTCATGCTGGGGAAGCAAGGAAGTAATACGCG GCTGGGAGGAAGGCGTGGCACAGATGAGTGTTGGTCAACGGGCCAAACTTACTATTTCTCCCGATTATGCGTATGGAGCCACCGGGCACCCTGGCATTATCCCACCCCATGCCACATTGGTTTTTGACGTTGAATTGCTTAAATTGGAGACCAGGGGAGTCCAAGTGGAAACAATATCACCGGGGATGGTCGGACTTTTCCTAAAAAGGGGCCAAACCTGTGTAG TCCATTATACCGGAATGCTCGAAGACGGAAAGAAAATGGACTCTTCTAGAGACCGCAATAAGCCTTTCAAGTTCATGTTGGGTAAGCAAGAGGTGATCCGGGGCTGGGAAGAGGGGTCGCTCAAATGTCCGTCGTCAGCGAGCTAAACTGACTATTTCCCCAGACTACGCATATGGAGCGACTGGCCACCCCGGTATTATTCCCTCCCCATGCGACTCTCGTGTTC GACGTAGAACTCTTGAAATTGGAAACGTCAGCCCGGAACAGGCGGAAGAGAGGATCCGACATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTGGGAGACAGAGTCACCATCAGTTGCAGGGCAAGTCAGGACATTAGTAAATATTTAAATTGGTATCAGCAGAAACCAGATGGAACTGTTAAACTCCTGATCTACCATACATCAAGATTACACTCAGGAGTCCCATCAAG GTTCAGTGGCAGTGGGTCTGGAACAGATTATTCTCTCACCATTAGCAACCTGGAGCAAGAAGATATTGCCACTTACTTTTGCCAACAGGGTAATACGCTTCCGTACACGTTCGGAGGGGGGACTAAGTTGGAAATAACAGGTGGCGGTGGCTCGGGCGGTGGTGGGTCGGGTGGCGGCGGATCTGAGGTGAAACTGCAGGAGTCAGGACCTGGCCTG GTGGCGCCCTCACAGAGCCTGTCCGTCACATGCACTGTCTCAGGGGTCTCATTACCCGACTATGTGTAAGCTGGATTCGCCAGCCTCCACGAAAGGTCTGGAGTGGCTGGGAGTAATATGGGGTAGTGAAACCACATACTATAATTCAGCTCTCAAATCCAGACTGACCATCATCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTGCAAACTGATGACA CAGCCATTTACTACTGTGCCAAACATTATTACTACGGTGGTAGCTATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAGCTAGCACCACGACGCCAGCGCCGCGACCACCAACACCGGCCCACCATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGCGCAGTGCACACGAGGGGCTGGACTTCGCCT GTGATTCCGGAATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGC AGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGG GCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAA

Amino acid sequence of CD19bbz on-CAR (SEQ ID NO: 978)

Signal peptide-conditional aggregation domains (4 repeats)-furin site-FMC63bbz

MALPVTALLLPLALLLHAARPGS RGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPD YAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEV IRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPPHATLVFDVELLKLET SARNRRKR GSDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSASTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDSGIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEY DVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRZ

Degradation domains

In some embodiments, the conditional expression domain is a degradation domain. Methods for obtaining degradation domains that are selectively stable in the presence of a stabilizing compound are well known in the art and are described in more detail below. Several such domain-stabilizing compound pairs have been made to date and are described herein. These include FKBP-based degradation domains (eg, using the stabilizing compound "Shield") described in "A Rapid, Reversible, and Tunable Method to Regulate Protein Function in Living Cells Using Synthetic Small Molecules'', Banaszynski, L. A.; Chen, L.-C.; Maynard-Smith, L. A.; Ooi, A. G. L.; Wandless, T. J. Cell, 2006, 126, 995-1004; DHFR-based domains (eg, using trimethoprim as a stabilizing compound) described in "A general chemical method to regulate protein stability in the mammalian central nervous system. Iwamoto, M.; Bjorklund, T.; Lundberg, C.; Kirik, D.; Wandless, T. J. Chemistry & Biology, 2010, 17, 981-988; and alpha estrogen receptor-based domains (eg, using 4-OHT as a stabilizing compound) described in "Destabilizing domains derived from the human estrogen receptor" by Y Miyazaki, H Imoto, L-c Chen, TJ Wandless J. Am. Chem. soc. 2012, 134, 3942-3945. Each of these references is incorporated by reference in its entirety.

The present invention encompasses degradation domains derived from any naturally occurring protein. Preferably, the fusion proteins of the invention will contain a degradation domain for which there is no ligand naturally expressed in the cell compartments of interest. For example, if the fusion protein is to be expressed in T cells, it is preferable to choose a degradation domain for which there is no naturally expressed ligand in T cells. Thus, a degradation domain, when expressed in a cell of interest, will only be stabilized in the presence of an exogenously added compound. Notably, this property can be achieved either by modifying the degradation domain to lose the binding of the naturally expressed ligand (in which case the degradation domain will only be stable in the presence of the synthetic compound), or by expressing the degradation domain in a compartment lacking the naturally expressed ligand. ligand (eg, the degradation domain may be derived from a species other than the species in which the fusion protein will be expressed).

The degradation domain-stabilizing compound pairs can be derived from any natural or synthetic protein. The stabilizing compounds may be any natural or synthetic compounds. In particular embodiments, the stabilizing compounds will be existing prescription or over-the-counter drugs. Examples of proteins that can be modified to have degradation domain properties are shown in Table 21 below, along with appropriate stabilizing compounds.

In some embodiments, the degradation domain is derived from the protein shown in Table 21.

In some embodiments, the degradation domain is derived from an estrogen receptor (ER). In some embodiments, the degradation domain comprises an amino acid sequence selected from SEQ ID NO: 58, or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity therewith, or SEQ ID NO: 121, or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. In some embodiments, the degradation domain comprises an amino acid sequence selected from SEQ ID NO: 58 or SEQ ID NO: 121. If the degradation domain is derived from an estrogen receptor, the stabilizing compound may be selected from bazedoxifene or 4-hydroxy tamoxifen (4-OHT). In some embodiments, the stabilizing compound is bazedoxifene. Tamoxifen and bazedoxifene are FDA approved drugs and thus are safe for human use.

In some embodiments, the degradation domain is derived from an FKB protein (FKBP). In some embodiments, the degradation domain comprises the amino acid sequence of SEQ ID NO: 56 or a sequence having at least 90%, 95%, 97%, 98% or 99% identity with it. In some embodiments, the degradation domain comprises the amino acid sequence of SEQ ID NO: 56. If the degradation domain is derived from FKBP, the stabilizing compound may be Shield-1.

In some embodiments, the degradation domain is derived from dihydrofolate reductase (DHFR). In some embodiments, the degradation domain comprises an amino acid sequence selected from SEQ ID NO: 57 or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with it. In some embodiments, the degradation domain comprises an amino acid sequence selected from SEQ ID NO: 57. If the degradation domain is derived from DHFR, the stabilizing compound may be trimethoprim.

In some embodiments, the degradation domain is not derived from the FKB protein, estrogen receptor, or DHFR.

Table 21 . Exemplary Proteins for Obtaining Degradation Domains

Type Drug activity Medicinal Examples Oxidoreductase Aldehyde dehydrogenase Inhibitor Disulfiram Monoamine oxidase (MAO) MAO-A inhibitor tranylcypromine, moclobemide MAO-B inhibitor Tranylcypromine Cyclooxygenase (COX) COX1 inhibitor Acetylsalicylic acid, profens, acetaminophen and dipyrone (as arachidonilamides) COX2 inhibitor Acetylsalicylic acid, profens, acetaminophen and dipyrone (as arachidonilamides) Vitamin K epoxide reductase Inhibitor warfarin, phenprocoumon Aromatase Inhibitor Exemestane Lanosterol demethylase (fungal) Inhibitor Antifungal azoles Lipoxygenases Inhibitor Mesalazine 5-lipoxygenase inhibitor Zileuton Thyroid peroxidase Inhibitor Thiouracils Iodthyronine-5'-deiodinase Inhibitor Propylthiouracil Inosine monophosphate dehydrogenase Inhibitor Mycophenolate mofetil HMG-CoA reductase Inhibitor Statins α-5-testosterone reductase Inhibitor Finasteride, dutasteride Dihydrofolate reductase (bacterial) Inhibitor Trimethoprim Dihydrofolate reductase (human) Inhibitor methotrexate, pemetrexed Dihydrofolate reductase (parasitic) Inhibitor Proguanil Dihydroorotate reductase Inhibitor Leflunomide Enoyl reductase (mycobacterial) Inhibitor Isoniazid Squalene epoxidase (fungal) Inhibitor Terbinafine Δ-14 reductase (fungal) Inhibitor Amorolfine Xanthine oxidase Inhibitor Allopurinol 4-hydroxyphenylpyruvate dioxygenase Inhibitor Nitisinone Ribonucleoside diphosphate reductase Inhibitor Hydroxyurea Transferases Protein kinase C Inhibitor Miltefosine Bacterial peptidyl transferase Inhibitor Chloramphenicol Catecholamine- O -methyltransferase Inhibitor Entacapon RNA polymerase (bacterial) Inhibitor Ansamycins Reverse transcriptases (viral) Competitive inhibitors Zidovudine Allosteric inhibitors Efavirenz DNA polymerase Inhibitor acyclovir, suramin GABA transaminase Inhibitor Valproic acid, vigabatrin Tyrosine kinases PDGFR/ABL/KIT inhibitor Imatinib EGFR inhibitor Erlotinib β-VEGFR2/PDGFR/KIT/FLT3 Sunitinib β-VEGFR2/PDGFR/RAF Sorafenib Glycinamide ribonucleotide formyl transferase Inhibitor Pemetrexed Phosphoenolpyruvate transferase (MurA, bacterial) Inhibitor Fosfomycin Human cytosolic branched-chain amino acid aminotransferase (hBCATc) Inhibitor Gabapentin Hydrolases (proteases) Aspartyl proteases (viral) HIV protease inhibitor Saquinavir, indinavir Hydrolases (serine proteases) Non-specific Non-specific inhibitors Aprotinin Bacterial serine protease Direct inhibitor β-lactams Bacterial serine protease Indirect inhibitor Glycopeptides Bacterial lactamases Direct inhibitor Sulbactam Human antithrombin Activator Heparins Human plasminogen Activator Streptokinase Human coagulation factor Activator Factor IX Complex, Factor VIII Human Factor Xa Inhibitor Fondaparinux Hydrolases (metaloproteases) Human ACE Inhibitor Captopril Human HRD Inhibitor Cilastatin Human carboxypeptidase A (Zn) Inhibitor Penicillamine Human enkephalinase Inhibitor Racecadotril Hydrolases (others) 26S proteasome Inhibitor Bortezomib Esterases AChE inhibitor Physostigmine AChE reactivators Obidoxim PDE inhibitor Caffeine PDE3 inhibitor Amrinone, milrinone PDE4 inhibitor Papaverine PDE5 inhibitor Sildenafil HDAC inhibitor Valproic acid HDAC3/HDAC7 inhibitor Carbamazepine Glycosidases (viral) α-glycosidase inhibitor Zanamivir, oseltamivir Glycosidases (human) α-glycosidase inhibitor Acarbose Lipases Gastrointestinal lipase inhibitor Orlistat Phosphatases Calcineurin inhibitor Cyclosporine Inositol polyphosphate phosphatase inhibitor lithium ions GTPases Rac1 inhibitor 6-Thio-GTP (metabolite of azathioprine) Phosphorylases Bacterial C55 lipid phosphate dephosphorylase inhibitor Bacitracin Liase DOPA decarboxylase Inhibitor Carbidopa carbonic anhydrase Inhibitor Acetazolamide Histidine decarboxylase Inhibitor Tritoqualin Ornithine decarboxylase Inhibitor Eflornithine Soluble guanylate cyclase Activator Esters of nitric acid, molsidomine Isomerases Alanine-racemase Inhibitor D-cycloserine DNA gyrases (bacterial) Inhibitor Fluoroquinolones Topoisomerases Topoisomerase I inhibitor Irinotecan Topoisomerase II inhibitor etoposide 8,7-isomerase (fungal) Inhibitor Amorolfine Ligases (also known as synthases) Dihydropteroate synthase Inhibitor Sulfonamides Thymidylate synthase (fungal and human) Inhibitor Fluorouracil Thymidylate synthase (human) Inhibitor methotrexate, pemetrexed Phosphofructokinase Inhibitor Antimony compounds mTOR Inhibitor Rapamycin Heme-containing polymerase ( Plasmodium ) Inhibitor Antimalarial quinolines β-1,3--D-glucan synthase (fungal) Inhibitor Caspofungin Glucosylceramide synthase Inhibitor Miglustat substrate medicinal substance Asparagine Asparaginase urat Rasburicase (urate oxidase) VAMP-synaptobrevin, SNAP25, syntaxin Botulinum neurotoxin light chain (Zn-endopeptidase) Type Drug activity Examples of drugs Ligand-gated ion channel receptors GABA _A receptors Barbiturate binding site agonists Barbiturate Benzodiazepine binding site agonists Benzodiazepines Benzodiazepine binding site agonists flumazenil Acetylcholine receptors Nicotinic receptor agonists Pirantel (from Angiostrongylus ), levamisole Stabilizing nicotinic receptor antagonists Alcuronium Depolarizing nicotinic receptor antagonists Suxamethonium Allosteric modulators of nicotinic receptors Galantamine Glutamate receptors (ionotropic) NMDA subtype antagonists memantine NMDA subtype expression modulators Acamprosate Phencyclidine-binding site antagonists of the NMDA subtype Ketamine G-protein coupled receptors Acetylcholine receptors Muscarinic receptor agonists Pilocarpine Muscarinic receptor antagonists Tropane derivatives Muscarinic _M3 receptor antagonists Darifenacin Adenosine receptors Agonists adenosine Adenosine A ₁ receptor agonists Lignans from valerian Adenosine A ₁ receptor antagonists caffeine, theophylline Adenosine receptor adenosine A _2A caffeine, theophylline Adrenoreceptors Agonists Adrenaline, norepinephrine, ephedrine α ₁ and α ₂ receptor agonists Xylometazoline Antagonists of α ₁ -receptors Ergotamine Agonists of α ₂ receptors, central Methyldopa (as methylnorepinephrine) β-adrenergic antagonists Isoprenaline β ₁ receptor antagonists propranolol, atenolol β ₂ receptor agonists Salbutamol β ₂ receptor antagonists propranolol Angiotensin receptors AT ₁ receptor antagonists Sartans calcium-sensing receptors Agonists Strontium ions Allosteric activators cinacalcet Cannabinoid receptors CB ₁ and CB ₂ receptor agonists Dronabinol Cysteinyl-leukotriene receptors Antagonists Montelukast dopamine receptors Dopamine receptor subtype direct agonists dopamine, levodopa D ₂ , D ₃ and D ₄ agonists Apomorphine D ₂ , D ₃ and D ₄ antagonists Chlorpromazine, fluphenazine, haloperidol, metoclopramide, ziprasidone Endothelin receptors (ET _A , ET _B ) Antagonists Bosentan GABA _B receptors Agonists Baclofen Glucagon receptors Agonists Glucagon Glucagon-like peptide 1 receptor Agonists Exenatide Histamine receptors Antagonists of H ₁ -histamine receptors Diphenhydramine _H2 -histamine receptor antagonists Cimetidine Opioid receptors μ-opioid receptor agonists Morphine, buprenorphine μ-, κ- and δ-opioid receptor antagonists Naltrexone κ-opioid receptor antagonists Buprenorphine Neurokinin receptors NK ₁ receptor antagonists Aprepitant Prostanoid receptors Agonists misoprostol, sulprostone, iloprost Prostamide receptors Agonists Bimatoprost Purinergic receptors P ₂ Y ₁₂ receptor antagonists Clopidogrel Serotonin receptors Subtype-specific (partial) agonists Ergometrine, ergotamine Partial 5-HT _1A receptor agonists Buspirone 5-HT _1B/1D receptor agonists Triptans 5-HT _2A receptor antagonists Quetiapine, ziprasidone 5-HT ₃ receptor antagonists Granisetron Partial 5- _HT4 agonists Tegaserod Vasopressin receptors Agonists Vasopressin V ₁ receptor agonists Terlipressin V ₂ receptor agonists Desmopressin OT receptor agonists Oxytocin OT receptor antagonists Atosiban Cytokine receptors Class I cytokine receptors Growth hormone receptor antagonists Pegvisomancer Erythropoietin receptor agonists Erythropoietin Granulocyte colony-stimulating factor receptor agonists Filgrastim Granulocyte-macrophage colony-stimulating factor receptor agonists Molgramostim Interleukin-1 receptor antagonists Anakinra Interleukin-2 receptor antagonists Aldesleukin TNFα receptors Mimetics (soluble) etanercept Integrin receptors Glycoprotein IIb/IIIa receptor Antagonists Tirofiban Receptors associated with tyrosine kinase insulin receptor Direct agonists Insulin insulin receptor Sensitizers biguanides Nuclear receptors (steroid hormone receptors) Mineralocorticoid receptor Agonists Aldosterone Antagonists Spironolactone Glucocorticoid receptor Agonists Glucocorticoids progesterone receptor Agonists Gestagens estrogen receptor Agonists Estrogens (Partial) antagonists Clomiphene Antagonists fulvestrant Modulators Tamoxifen, Raloxifene Androgen receptor agonists Testosterone Antagonists Cyproterone acetate Vitamin D receptor Agonists Retinoids ACTH receptors Agonists Tetracosactide (also known as cosinotropin) Nuclear receptors (others) α-retinoic acid receptor (RAR) agonists Isotretinoin β-RAR agonists Adapalene, Isotretinoin γ-RAR agonists Adapalene, Isotretinoin Peroxisome proliferator-activated receptor (PPAR) α-PPAR agonists Fibrates γ-PPAR agonists Glitazones thyroid hormone receptors Agonists L-thyroxine Potential dependent Ca ²⁺ channels Are common Inhibitor Oxcarbazepine In Schistosoma sp. Inhibitor Praziquantel L-type channels Inhibitor Dihydropyridines, diltiazem, lercanidipine, pregabalin, verapamil T-channels Inhibitor Succinimides K ⁺ channels Epithelial K ⁺ channels Opener Inhibitor Diazoxide, Minoxidil Nateglinide, sulfonylurea Potential-gated K ⁺ channels Inhibitor Amiodarone Na ⁺ channels Epithelial Na ⁺ channels (ENaC) Inhibitor Amiloride, bupivacaine, lidocaine, procainamide, quinidine Voltage-gated Na ⁺ channels Inhibitor Carbamazepine, flecyanide, lamotrigine, phenytoin, propafenone, topiramate, valproic acid Ryanodine-inositol-1,4,5-triphosphate Ca receptor family ²⁺ channels (RIR-CaC) Ryanodine receptors Inhibitor Dantrolene Receptor family of transient voltage-dependent Ca ²⁺ channels (TRP-CC) TRPV1 receptors Inhibitor Acetaminophen (as arachidonilamide) Cl ^- channels Cl ^- channel Inhibitor (mast cell) opener (parasitic) Cromolyn sodium, ivermectin Cation-chlorine co-transporter (CCC) family Thiazide-sensitive NaCl symporter inhibitor, human Thiazide diuretics Inhibitor of bumetanide-sensitive NaCl/KCl symporters, human Furosemide Na ⁺ /H ⁺ antiporters Inhibitor Amiloride, triamterene Proton pumps Ca ²⁺ -dependent ATPase inhibitor (PfATP6; Plasmodia ) Artemisinin and derivatives H ⁺ /K ⁺ ATPase Inhibitor Omeprazole Na ⁺ /K ⁺ ATPase Inhibitor cardiac glycosides Eukaryotic (putative) sterol transporters (EST) family Niemann-Pick C1 (NPC1L1) transporter inhibitor ezetimibe Neurotransmitter/Na ⁺ symporter family (NSS) Serotonin/Na ⁺ symporter inhibitor Cocaine, tricyclic antidepressants, paroxetine Norepinephrine/Na ⁺ symporter inhibitor Bupropion, venlafaxine Dopamine/Na ⁺ symporter inhibitor Tricyclic antidepressants, cocaine, amphetamines Vesicular Monoamine Transporter Inhibitor Reserpine Nucleic acids DNA and RNA Alkylation Chlorambucil, cyclophosphamide, decarbazine complexation Cisplatin Intercalation Doxorubicin Oxidative degradation Bleomycin chain breaks Nitroimidazoles RNA Interaction with 16S-rRNA Aminoglycoside anti-infective agents Interaction with 23S-rRNA Macrolide anti-infectives 23S-rRNA/tRNA/2-polypeptide complex Oxazolidinone anti-infectives Spindle Development inhibition Vinca alkaloids Inhibition of disaggregation Taxanes Mitosis inhibition - Colchicine Ribosome 30S subunit (bacterial) Inhibitors Tetracyclines 50S subunit (bacterial) Inhibitors Lincosamides, quinupristin-dalfopristin

Degradation domains can be generated from known proteins (eg, those listed in the table above) by any of a variety of standard methods known in the art. As a rule, such methods include, firstly, the creation of a library of interest, including proteins obtained, for example, from a natural protein. Second, cells or cell populations expressing proteins from individual library constructs are selected based on whether the expression of the protein derivative depends on the presence of the desired stabilizing compound. The derivation and selection process can be repeated over many cycles as needed to identify a suitable candidate.

For example, a library can be generated by rational protein design based on testing of various structures and the expected affinity of the protein domain for the selected compound. Alternatively, the library can be generated by random mutagenesis of the target protein. In any case, for example, Jurkat cells can be transduced with a lentiviral library derived from the constructs. The Jurkat cells can then be subjected to a round of FACS sorting to eliminate cells constitutively expressing the protein of interest. In the next step, sorted cells are incubated with the selected compound for 24 hours and positive cells are sorted by FACS. They are propagated by cloning single cells. Thereafter, individual transduced clones will be evaluated for their ability to induce expression of the protein of interest in a compound-dependent manner.

Suicide genes and domains

The present invention partially utilizes CAR technology in methods for selectively removing or activating modified T cells from a subject after adoptive transfer. In one embodiment, a modified CAR T cell is selectively removed from a subject, causing activation of the suicide domain in the modified T cell. In another embodiment, a modified T cell in a subject is selectively activated by actively preventing the modified CAR T cell from apoptosis during therapy. In another embodiment, a modified T cell in a subject is selectively activated to allow cell surface expression of the CAR construct.

Some of the potential side effects of recognition of non-target cells by CAR T cells can be overcome by co-expression of the suicide gene in the CAR T cell. In addition, CAR T cells can be selectively removed after targeting B cells to eliminate them in order to treat autoantibody- or alloantibody-induced diseases or conditions.

The invention relates to an isolated nucleic acid containing a suicide gene. Examples of suicide genes include, but are not limited to, the herpes simplex virus thymidine kinase (HSV-TK) gene, Fas cytoplasmic domain, caspase such as caspase-8 or caspase-9, cytosine deaminase, E1A, FHIT, as well as other known self-destructive or apoptosis genes (Straathof et al., 2005, Blood 105:4247-4254; Cohen et al., 1999, Leuk. Lymphoma 34:473-480; Thomis et al., 2001, Blood 97:1249-1257; Tey et al., 2007, Biol Blood Marrow Transplant 13:913-924 and Di Stasi et al., 2011, N. Engl. J. Med. 365:1673-1683).

The suicide gene may be operably linked to a promoter, such as an inducible promoter sequence. Examples of inducible promoters include, but are not limited to, the heat shock protein promoter, the tetracycline-regulated promoter, the steroid-regulated promoter, the metal-regulated promoter, the estrogen receptor-regulated promoter, as well as other promoters known in the art. In one aspect, the invention provides an isolated nucleotide sequence which is a nucleotide sequence comprising a suicide gene and a nucleic acid encoding a chimeric antigen receptor. In another aspect, the invention relates to an isolated nucleotide sequence, which is a nucleotide sequence comprising a suicide gene and a nucleic acid encoding a chimeric antigen receptor. In one embodiment, the suicide gene comprises a nucleic acid selected from the group consisting of ATGCTCGAGGGGGTTCAGGTGGAGACTATCAGCCCGGGCGACGGACGGACATTCCCAAAGCGCGGGCAGACGTGTGTGTGTGCATTACACCGGGATGCTTGAGGACGGAAAGAAAGTGGACTCTTCCCGAGACCGAAATAAACCATTCAAGTTCATGTTGGGCAAGCAGGAGG TTATCAGAGGGTGGGAGGAGGGCGTCGCTCAGATGAGTGTCGGACAGAGGGCCAAGCTCACGATCTCCCCTGATTACGCCTACGGGGCAACTGGTCACCCCGGAATCATCCCCCCTCACGCAACCCTCGTGTTCGACGTCGAGCTGCTCAAACTGGAATCAGGCGGAGGCAGTGGCGCCTAGCGGGTTTGGCGATGTCGGTGCCCTTGAAAGCTTGAGGA AATGCCGATCTCGCTTACATCTTGAGCATGGAGCCCTGTGGGCACTGTCTGATCATCAACAATGTTAACTTTTGCCGGGAGTCCGGCCTGCGCACACGCACAGGCTCCAACATTGACTGCGAAAAACTTCGAAGGAGGTTTAGCTCTCTGCATTTCATGGTAGAGGTGAAGGGGGATCTGACCGCCAAGAAAATGGTTCTCGCCCTTCTCGAGCTTGCGCAGCAGGACCATG GAGCGCTTGACTGTTGTGTCGTTGTGATACTGAGCCATGGCTGTCAGGCTTCCCATCTCCAGTTTCCAGGGGCCGTGTACGGAACCGATGGATGCCCTGTGTCAGTTGAAAAGATCGTAAACATCTTTAACGGAACATCTTGCCCGAGCCTCGGCGGTAAACCGAAGCTTTTTTTATCCAGGCCTGCGGCGGTGAACAGAAAGATCATGGCTTCGAGGTTGCCAGTACC AGCCCTGAAGACGAATCCCCCGGGTCAAATCCTGAACCAGATGCGACCCCTTTCAGGAAGGACTCCGCACTTTTTGACCAGCTTGACGCCATTTCCTCCCTGCCAACACCTTCCGACATATTTGTAAGCTACTCCACCTTTCCAGGATTCGTGAGCTGGCGCGACCCAAAATCCGGCAGTTGGTATGTTGAAACCCTGGACGATATTTTCGAACAATGGCCCACAGTGAGGACCTGGC AGTCCCTTCTTCTGCGCGTAGCCAATGCCGTGTCAGTCAAAGGGATTTACAAGCAGATGCCAGGCTGCTTTAATTTCCTGCGCAAGAAACTGTTTTTAAAGACCAGT or SEQ ID NO: 3001;

CGGACGGACATTCCCAAAGCGCGGGCAGACGTGTGTGGTGCATTACACCGGGATGCTTGAGGACGGAAAGAAAGTGGACTCTTCCCGAGACCGAAATAAACCATTCAAGTTCATGTTGGGCAAGCAGGAGGTTATCAGAGGGTGGGAGGAGGGCGTCGCTCAGATGAGTGTCGGACAGAGGGCCAAGCTCACGATCTCCCCTGATTACGCCTACGGGG CAACTGGTCACCCCGGAATCATCCCCCCTCACGCAACCCTCGTGTTCGACGTCGAGCTGCTCAAACTGGAATCAGGCGGAGGCAGTGGCGGGTTTGGCGATGTCGGTGCCCTTGAAAGCTTGAGAGGAAATGCCGATCTCGCTTACATCTTGAGCATGGAGCCCTGTGGGCACTGTCTGATCATCAACAATGTTAACTTTTGCCGGAGTCCGGCCTGCGCACACGCACAGG CTCCAACATTGACTGCGAAAAAACTTCGAAGGAGTTTAGCTCTCTGCATTTCATGGTAGAGGTGAAGGGGGATCTGACCGCCAAGAAAATGGTTCTCGCCCTTCTCGAGCTTGCGCAGCAGGACCATGGAGCGCTTGACTGTTGTGTCGTTGTGATACTGAGCCATGGCTGTCAGGCTTCCCATCTCCAGTTTCAGGGGCCGTGTACGGAACCGATGGATGCCCTGTG TCAGTTGAAAAGATCGTAAACATCTTTAACGGAACATCTTGCCCGAGCCTCGGCGGTAAACCGAAGCTTTTTTTATCCAGGCCTGCGGCGGTGAACAGAAAGATCATGGCTTCGAGGTTGCCAGTACCAGCCCTGAAGACGAATCCCCCGGGTCAAATCCTGAACCAGATGCGACCCCTTTCAGGAAGGACTCCGCACTTTTGACCAGCTTGACGCCATTTCCTCCCTGCCAA CACCTTCCGACATATTTGTAAGCTACTCCACCTTTCCAGGATTCGTGAGCTGGCGCGACCCAAAATCCGGCAGTTGGTATGTTGAAACCCTGGACGATATCTTCGAACAATGGGCCCACAGTGAGGACCCTGCAGTCCCTTCTTCTGCGTAGCCAATGCCGTGTCAGTCAAAGGGATTTACAAGCAGATGCCAGGCTGCTTTAATTTCCTGCGCAAGAAACTGTTTTAAGACCAG TTGAGTCGACGGAGGAGGAG or SEQ ID NO: 3002;

GGGGTTCAGGTGGAGACTATCAGCCCGGGCGACGGACGGACATTCCCAAAGCGCGGGCAGACGTGTGTGGTGCATTACACCGGGATGCTTGAGGACGGAAAGAAAGTGGACTCTTCCCGAGACCGAAATAAACCATTCAAGTTCATGTTGGGCAAGCAGGAGGTTATCAGAGGGTGGGAGGAGGGCGTCGCTCAGATGAGTGTCGGACAGAGGGC CAAGCTCACGATCTCCCCTGATTACGCCTACGGGGCAACTGGTCACCCCGGAATCATCCCCCCTCACGCAACCCTCGTGTTCGACGTCGAGCTGCTCAAACTGGAATCAGGCGGAGGCAGTGGCGGGTTTGGCGATGTCGTGCCCTTGAAAGCTTGAGAGGAAATGCCGATCTCGCTTACATCTTGAGCATGGAGCCCTGTGGGCACTGTCTGATCATCAACAATGTTAACT TTTGCCGGGAGTCCGGCCTGCGCACACGCACAGGCTCCAACATTGACTGCGAAAACTTCGAAGGAGTTTAGCTCTCTGCATTTCATGGTAGAGGTGAAGGGGGATCTGACCGCCAAGAAAATGGTTCTCGCCCTTCTCGAGCTTGCGCAGCAGGACCATGGAGCGCTTGACTGTTGTGTCGTTGTGATACTGAGCCATGGCTGTCAGGCTTCCCATCTCCAGTTTCC AGGGGCCGTGTACGGAACCGATGGATGCCCTGTGTCAGTTGAAAAGATCGTAAACATCTTTAACGGAACATCTTGCCCGAGCCTCGGCGGTAAACCGAAGCTTTTTTTTTATCCAGGCCTGCGGCGGTGAACAGAAAGATCATGGCTTCGAGGTTGCCAGTACCAGCCCTGAAGACGAATCCCCCGGGTCAAATCCTGAACCAGATGCGACCCCTTTCAGGAAGGACTCC GCACTTTTTGACCAGCTTGACGCCATTTCCTCCCTGCCAACACCTTCCGACATATTTGTAAGCTACTCCACCTTTCCAGGATTCGTGAGCTGGCGCGACCCAAAATCCGGCAGTTGGTATGTTGAAACCCTGGACGATATCTTCGAACAATGGCCCACAGTGAGGACCTGCAGTCCCTTCTTCTGCGCGTAGCCAATGCCGTGTCAGTCAAAGGGATTTACAAGCAGATGCCAGGCTGC TTTAATTTCCTGCGCAAGAAACTGTTTTTTAAGACCAGTTGA or SEQ ID NO: 3003; And

AGAGGCGTGCAGGTGGAAACCATCTCTCCCGGCGACGGCAGAACCTTCCCTAAGAGGGGCCAGACCTGCGTGGTGCACTACACCGGCATGCTGGAAGATGGCAAGAAGATGGACAGCTCCCGGGACCGGAACAAGCCCTTCAAGTTCATGCTGGGCAAGCAGGAAGTGATCCGGGGCTGGGAAGAGGGCGTGGCACAGATGTCTGTGGGCCAGAGAGCCAAG CTGACCATCAGCCCCGATTACGCCTACGGCCCACAGGCCACCCTGGCATCATTCCTCCACACGCCACACTGGTGTTCGATGTGGAACTGCTGAAGCTGGAAACCCGGGGAGTGCAGGTGGAAACAATCAGCCCTGGCGACGGCCGGACCTTTCCAAAACGGGGACAGACATGTGTGGTGCATTATACAGGGATGCTGGAAGATGGGAAAAAAATGGATAGCAGCCGCGA CCGCAACAAACCTTTTAAGTTTATGCTGGGGAAACAGGAAGTGATTAGAGGCTGGGAAGAGGGGTGGCACAGATGAGCGTGGGACAGCGGGCCAAACTGACAATCTCCCCCGACTATGCCTATGGGGCCACCGGACACCCCGGAATCATCCCAACCTCATGCTACCCTGGTGTTTGACGTGGAACTGCTGAAACTGGAAACAAGCGGCGGAGGCAGCGGCGGC TTTGGAGATGTGGGAGCCCTGGAAAGCCTGCGGGGCAATGCCGATCTGGCCTACATCCTGAGCATGGAACCCTGCGGCCACTGCCTGATTATCAACAACGTGAACTTCTGCAGAGAGAGCGGCCTGCGGACCAGAACCGGCAGCAACATCGACTGCGAGAAGCTGCGGCGGAGATTCAGCAGCCTGCACTTCATGGTGGAAGTGAAGGGGGACCTGACCGCCAAAAAAATG GTGCTGGCTCTGCTGGAACTGGCCCAGCAGGATCATGGCGCCCTGGACTGTTGCGTGGTCGTGATCCTGAGCCACGGCTGCCAGGCCAGCCATCTGCAGTTTCCCGGCGCTGTGTATGGCACCGATGGCTGCCCTGTGTCCGTGGAAAAGATCGTGAATATCTTCAACGGCACCAGCTGCCCCAGCCTGGGCGGAAAGCCTAAGCTGTTCTTTATTCAAGCCTGTGGG GGCGAGCAGAAGGACCACGGATTTGAGGTGGCCAGCACCTCCCCCGAGGATGAGAGCCCTGGCAGCAACCCCTGAGCCTGACGCCACCCCATTCCAGGAAGGACTGCGGACCTTCGACCAGCTGGACGCCATCTCTAGCCTGCCCACCCCCAGCGACATCTTCGTGTCCTACAGCACCTTCCCTGGCTTTGTGTCCTGGCGGGACCCAAGTCCGGCTCTTGGTACGTGGAAA or SEQ ID NO: 3004.

In another embodiment, the suicide gene encodes an amino acid sequence selected from the group consisting of

MLEGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLESGGGSGASGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLEL or SE Q ID NO: 3005;

GVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLESGGGSGGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLELAQQ or SEQ ID NO : 3006; And

RGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPD YAYGATGHPGIIIPPHATLVFDVELLKLETSGGGSGGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLELAQQDHGALDCCVVVILSHGCQASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVASTSPEDES PGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSGSWYVETLDDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTS or SEQ ID NO: 3007. In another embodiment, the suicide gene has an inducible promoter.

In some embodiments, the suicide gene is in an expression vector. In an exemplary embodiment, the present invention relates to a vector containing a nucleotide sequence containing a suicide gene containing SEQ ID NOs: 3001, 3002, 3003 or 3004. The expression vector may also include other genes, such as a chimeric antigen receptor and/or a CRISPR system, described in other sections of this document.

The invention also relates to a cell containing a suicide gene. In an illustrative aspect, the present invention provides a modified cell comprising a nucleic acid comprising a suicide gene encoding an amino acid sequence selected from the group consisting of SEQ ID NOs: 3005, 3006 and 3007 and a nucleic acid encoding a chimeric antigen receptor. In another aspect, the present invention provides a modified cell comprising a nucleic acid comprising a suicide gene selected from the group consisting of SEQ ID NOs: 3001, 3002, 3003 and 3004 and a nucleic acid encoding a chimeric antigen receptor. In one embodiment, the suicide gene encodes an amino acid sequence selected from the group consisting of SEQ ID NOs: 3005, 3006, and 3007. In another embodiment, the suicide gene has an inducible promoter.

In one embodiment, the modified CAR T cell contains the nucleic acid encoding the suicide gene as a sequence separate from the CAR construct described elsewhere herein. For example, HSV-TK, i-Casp9, Fas cytoplasmic domain or caspase can be included in genetically modified T cells separately from the CAR construct. In another embodiment, the modified CAR T cell contains the suicide gene in the same construct as the CAR-encoding nucleic acids. In this embodiment, the nucleic acid containing the suicide gene may be located upstream or downstream of the CAR-encoding nucleic acids.

In one embodiment, expression of a suicide gene is activated in a cell upon contact of the cell with an inducing agent introduced into the cell or a mammal having the cell. The inducer then activates the inducible promoter to express the suicide gene. In such an embodiment, an inducing agent is administered to a subject to induce expression of a suicide gene.

In another embodiment, the suicide gene product expressed from the suicide gene is activated by an activating agent, such as a dimerizing agent. For example, a dimerizing agent such as AP20187 stimulates the dimerization and activation of caspase-9 molecules.

In some embodiments with constitutive expression of the suicide gene, expression of the suicide gene can be turned off in a cell upon contact of the cell with an inhibitory agent introduced into the cell or a mammal having the cell. The inhibitory agent selectively turns off expression. For example, caspase-9 is constitutively expressed in a cell and the addition of an inhibitory agent suppresses the expression or activation of caspase-9. In one embodiment, an inhibitory agent is administered to a subject to suppress the expression of a suicide gene.

In some embodiments with constitutive expression of a suicide gene, activation of the suicide gene product can be suppressed in a cell by contacting the cell with an inhibitory agent, such as a solubilizing agent, introduced into the cell or a mammal having the cell. The inhibitory agent suppresses the activation of the suicide gene product, for example by preventing the dimerization of caspase-9 molecules. In one embodiment, a solubilizing agent is administered to a subject to suppress activation of a suicide gene product.

In some aspects, the suicide gene is not immunogenic to a cell containing the suicide gene or a host having the suicide gene. While thymidine kinase (TK) may be used, it may be immunogenic. Alternatively, examples of suicide genes that are not immunogenic to the host include caspase-9, caspase-8, and cytosine deaminase genes.

In another embodiment, the expression of the suicide gene is in tandem with the expression of one or more dimerization domains that cause the fusion protein containing the suicide domain and the dimerization domain to aggregate, preventing cell surface expression and hence the functioning of the suicide gene.

In another embodiment, the nucleotide sequence encoding the dimerization domain associated with the suicide gene comprises a nucleotide sequence selected from the group consisting of

GGAAGCGGCGCCACCAATTTCAGCCTGCTGAAACAGGCCGGCGACGTGGAAGAGAACCCTGGCCCT or SEQ ID NO: 3008;

AGTGGCTCCGGCGCAACAAATTTCTCCTTGCTGAAACAGGCAGGCGACGTTGAGGAAAATCCCGGCCCA or SEQ ID NO: 3009;

GGCTCCGGCGCAACAAATTTCTCCTTGCTGAAACAGGCAGGCGACGTTGAGGAAAATCCCGGCCCA or SEQ ID NO: 3010;

GGGGTTCAGGTGGAGACTATCAGCCCGGGCGA or SEQ ID NO: 3011; And

GGCTCCGGCGCAACAAATTTCTCCTTGCTGAAACAGGCAGGCGACGTTGAGGAAAATCCCGGCCCA or SEQ ID NO: 3012.

In another such embodiment, the dimerization domain associated with the suicide domain comprises an amino acid sequence selected from the group consisting of GSGATNFSLLKQAGDVEENPGP or SEQ ID NO: 3013; and RKRRGSGATNFSLLKQAGDVEENPGP or SEQ ID NO: 3014.

Solubilization of the dimerization domains with a solubilizing agent introduced into the cell or mammal having the cell prevents aggregation and allows the construct to pass through the secretory system.

As described herein, the present invention relates to a method for modifying a T cell with a chimeric antigen receptor (CAR) and a suicide gene. Thus, the present invention relates to a nucleic acid encoding a CAR, or a modified T cell containing a CAR, wherein the CAR contains an antigen-binding domain, a transmembrane domain, and an intracellular domain.

One or more domains, or fragments of domains, CARs may be human. In one embodiment, the present invention relates to a fully human CAR. The nucleotide sequences encoding the desired domains can be obtained by recombinant methods known in the art, such as, for example, screening libraries from cells expressing the gene, obtaining the gene from a vector known to contain it, or by direct isolation from cells and tissues containing it using standard methods. Alternatively, the gene of interest can be obtained by synthetic methods rather than cloning.

Examples of CARs are provided in US Pat.

Nucleic acid and vectors

In another aspect, the invention relates to a nucleic acid encoding any of the fusion proteins described herein, or a vector containing such a nucleic acid. In one embodiment, the vector is selected from a DNA vector, an RNA vector, a plasmid, a lentiviral vector, an adenoviral vector, or a retroviral vector. In one embodiment, the vector is a lentiviral vector.

In some embodiments, the nucleic acids described herein contain a sequence encoding a furin cleavage site. In some embodiments, nucleic acids described herein comprise any of SEQ ID NOs: 1112, 126, 128, 130, 132, 134, 136, or 138, or a sequence having at least 90%, 95%, 97% , 98% or 99% identity with her. In some embodiments, the nucleic acids described herein comprise any of SEQ ID NOs: 1112, 126, 128, 130, 132, 134, 136, or 138. In some embodiments, the nucleic acids described herein comprise SEQ ID NO: 126 or SEQ ID NO: 128. In some embodiments, the nucleic acids described herein comprise SEQ ID NO: 126.

In some embodiments, the nucleic acids described herein contain a sequence encoding a conditional expression domain, such as an aggregation domain or a degradation domain. In some embodiments, the implementation of the nucleic acids described herein contain a sequence encoding an aggregation domain derived from FKBP, for example, FKBP F36M. In some embodiments, the nucleic acids described herein contain a sequence encoding a degradation domain derived from the estrogen receptor (ER). In some embodiments, the nucleic acids described herein comprise SEQ ID NO: 1110 or SEQ ID NO: 122, or a sequence having at least 90%, 95%, 97%, 98%, or 99% identity with it. In some embodiments, the nucleic acids described herein comprise SEQ ID NO: 1110 or SEQ ID NO: 122. In some embodiments, the nucleic acids described herein comprise SEQ ID NO: 122.

The present invention also provides vectors into which the DNA of the present invention is inserted. Vectors derived from retroviruses such as lentivirus are suitable tools for achieving long-term gene transfer because they allow long-term stable integration of the transgene and its propagation in daughter cells. Lentiviral vectors have an additional advantage over other vectors derived from onco-retroviruses such as murine leukemia viruses in that they can transduce non-dividing cells such as hepatocytes. They also have the additional advantage of low immunogenicity. The retroviral vector may also be, for example, a retroviral gamma vector. The gamma retroviral vector may include, for example, a promoter, a packaging signal (ψ), a primer binding site (PBS), one or more (eg, two) long terminal repeats (LTRs), and a transgene of interest, for example, a gene encoding CAR. The gamma retroviral vector may be devoid of viral structural genes such as gag , pol and env . Exemplary gamma retroviral vectors include murine leukemia virus (MLV), spleen necrosis virus (SFFV), and myeloproliferative sarcoma virus (MPSV), as well as vectors derived therefrom. Other gamma-retroviral vectors are described, for example, in Tobias Maetzig et al., "Gammaretroviral Vectors: Biology, Technology and Application", Viruses. Jun 2011; 3(6): 677-713.

In another embodiment, the vector containing the nucleic acid encoding the desired fusion protein of the invention is an adenoviral vector (A5/35). In another embodiment, expression of nucleic acids encoding chimeric molecules can be accomplished using transposons such as sleeping beauty, crisper, CAS9, and zinc finger nucleases. See below June et al. 2009 Nature Reviews Immunology 9,10: 704-716, the content of the publication is incorporated herein by reference.

Nucleic acid can be cloned into a variety of vectors. For example, the nucleic acid can be cloned into a vector, including, but not limited to, a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replicable vectors, probe vectors, and sequencing vectors.

Disclosed herein are methods for producing an in vitro transcribed RNA chimeric molecule. The present invention also encompasses an RNA construct encoding a chimeric molecule that can be directly transfected into a cell. The method of obtaining mRNA for use in transfection may include in vitro transcription (IVT) of the template with specially designed primers, followed by the addition of polyA, to obtain a construct containing a 3'- and 5'-untranslated sequence ("UTR"), 5'-cap and/or an internal ribosome binding site (IRES), a nucleic acid to be expressed, and a polyA tail, typically 50-5000 bases long (SEQ ID NO: 32). The RNA obtained in this way can be efficiently transfected into different cell types. In one aspect, the matrix contains sequences for CAR.

Nucleic acid constructs encoding fusion protein containing CAR

The present invention also relates to nucleic acid molecules encoding a fusion protein, for example, as described herein, containing a domain that contains one or more CAR constructs that target the antigen described herein. In one aspect, a nucleic acid molecule is provided as a messenger RNA transcript. In one aspect, a nucleic acid molecule is provided as a DNA construct.

Accordingly, in one aspect, the invention relates to a nucleic acid molecule encoding a fusion protein, for example, as described herein, containing a chimeric antigen receptor (CAR), wherein the CAR contains an antigen-binding domain that binds to the antigen described herein, a transmembrane domain (e.g., the transmembrane domain described herein) and an intracellular signaling domain (e.g., the intracellular signaling domain described herein) containing a stimulatory domain, e.g., a costimulatory signaling domain (e.g., the costimulatory signaling domain described herein) and /or the main signaling domain (eg, the main signaling domain described herein, for example, the zeta chain described herein). In one embodiment, the transmembrane domain is the transmembrane domain of a protein selected from the group consisting of T cell receptor alpha, beta, or zeta chain, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154. In some embodiments, the transmembrane domain may comprise at least the transmembrane region(s) of, e.g., KIRDS2, OX40, CD2, CD27, LFA-1 (CD11a, CD18), ICOS (CD278), 4-1BB (CD137), GITR , CD40, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD160, CD19, IL2R-beta, IL2R-gamma, IL7Rα, ITGA1, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6 , VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, NKG2D, NKG2C, TNFR2 , DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, PAG/Cbp, NKG2D and NKG2C.

In one embodiment, the transmembrane domain contains the sequence of SEQ ID NO: 12 or a sequence having 95-99% identity with it. In one embodiment, the antigen-binding domain is linked to the transmembrane domain by a hinge region, such as the hinge described herein. In one embodiment, the hinge region contains SEQ ID NO: 4 or SEQ ID NO: 6, or SEQ ID NO: 8, or SEQ ID NO: 10, or a sequence having 95-99% identity therewith. In one embodiment, the isolated nucleic acid molecule further comprises a sequence encoding a costimulatory domain. In one embodiment, the costimulatory domain is a functional signaling domain of a protein selected from the group consisting of OX40, CD27, CD28, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278) and 4-1BB (CD137 ). Additional examples of such costimulatory molecules include CDS, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD160, CD19, CD4, CD8-alpha, CD8-beta, IL2R- beta, IL2R-gamma, IL7R-alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, NKG2D, NKG2C, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (tactile), CEACAM1, CRTAM , Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/Cbp, NKG2D and NKG2C. In one embodiment, the intracellular signaling domain comprises a functional 4-1BB signaling domain and a functional CD3-zeta signaling domain. In one embodiment, the intracellular signaling domain comprises the sequence of SEQ ID NO: 14, 16, 120, or 124, or a sequence having 95-99% identity with them, and the sequence of SEQ ID NO: 18 or SEQ ID NO: 20, or a sequence, having 95-99% identity with them, while the sequences that make up the intracellular signaling domain are expressed in the same reading frame and in the form of a single polypeptide chain.

In another aspect, the invention relates to an isolated nucleic acid molecule encoding a fusion protein, for example, as described herein, containing a domain that contains a CAR construct containing the leader sequence of SEQ ID NO: 2, an scFv domain described herein, a hinge region with SEQ ID NO: 4 or SEQ ID NO: 6 or SEQ ID NO: 8 or SEQ ID NO: 10 (or a sequence having 95-99% identity therewith), a transmembrane domain containing the sequence of SEQ ID NO: 12 ( or a sequence having 95-99% identity with it), a 4-1BB co-stimulatory domain containing the sequence of SEQ ID NO: 14, a CD27 co-stimulatory domain containing the sequence of SEQ ID NO: 16 (or a sequence having 95-99% identity with it ), an ICOS co-stimulatory domain containing the sequence of SEQ ID NO: 120 (or a sequence having 95-99% identity with it) or a CD28 co-stimulatory domain containing the sequence of SEQ ID NO: 124, as well as a CD3-zeta stimulatory domain containing the sequence of SEQ ID NO: 18 or SEQ ID NO: 20 (or a sequence having 95-99% identity therewith).

Nucleotide sequences encoding the desired molecules can be obtained by recombinant methods known in the art, such as, for example, screening libraries from cells expressing the gene, obtaining the gene from a vector known to contain it, or isolating directly from cells and tissues containing it using standard methods. Alternatively, the gene of interest can be obtained by synthetic methods rather than cloning.

The present invention also relates to vectors into which the nucleic acid of the present invention is inserted. Vectors derived from retroviruses such as lentivirus are suitable tools for achieving long-term gene transfer because they allow long-term stable integration of the transgene and its propagation in daughter cells. Lentiviral vectors have an additional advantage over other vectors derived from onco-retroviruses such as murine leukemia viruses in that they can transduce non-dividing cells such as hepatocytes. They also have the additional advantage of low immunogenicity.

In another embodiment, the vector containing a nucleic acid encoding a fusion protein, for example as described herein, containing a domain that contains a CAR of the invention, is an adenoviral vector (A5/35). In another embodiment, expression of CAR-encoding nucleic acids can be accomplished using transposons such as sleeping beauty, crisper, CAS9, and zinc finger nucleases. See belowet al. 2009 Nature Reviews Immunology 9,10:704-716, the content of the publication is incorporated herein by reference.

Briefly, expression of natural or synthetic nucleic acids encoding a fusion protein, for example, as described herein, containing a domain that contains a CAR, is generally accomplished by operably linking a nucleic acid encoding a CAR polypeptide or fragments thereof to a promoter and incorporating the construct into expression vector. Vectors may be suitable for replication and integration in eukaryotic cells. Typical cloning vectors contain transcription and translation terminators, initiation sequences and promoters useful in regulating the expression of the desired nucleic acid sequence.

The expression constructs of the present invention can also be used for nucleic acid immunization and gene therapy using standard gene delivery protocols. Gene delivery methods are known in the art. See, for example, US Pat. Nos. 5,399,346; 5,580,859; In another embodiment, the invention relates to a gene therapy vector.

Nucleic acid can be cloned into a variety of vectors. For example, the nucleic acid can be cloned into a vector, including, but not limited to, a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replicable vectors, probe vectors, and sequencing vectors.

In addition, the expression vector may be introduced into the cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Sambrook et al., 2012, MOLECULAR CLONING: A LABORATORY MANUAL, volumes 1-4, Cold Spring Harbor Press, NY, and other virology and molecular biology manuals. Viruses useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno-associated viruses, herpesviruses, and lentiviruses. Typically, a suitable vector contains an origin of replication that is functional in at least one organism, a promoter sequence, convenient sites for restriction endonucleases, and one or more selectable markers (e.g., WO 01/96584; WO 01/29058 and US Pat. No. 6,326,193) .

Various virus-based systems have been developed to transfer genes into mammalian cells. For example, retroviruses provide a convenient platform for gene delivery systems. The selected gene can be inserted into a vector and packaged into retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to the subject's cells either in vivo or ex vivo . Many retroviral systems are known in the art. In some embodiments, adenoviral vectors are used. A variety of adenoviral vectors are known in the art. In one embodiment, lentiviral vectors are used.

Additional promoter elements, such as enhancers, regulate the frequency of transcription initiation. As a rule, they are located in the area located at 30-110 b.p. upstream of the transcription start site, although many promoters have also been shown to contain functional elements downstream of the transcription start site. The space between promoter elements is often flexible so that promoter function is maintained when the elements are flipped or moved relative to each other. In the thymidine kinase (tk) promoter, the space between promoter elements can be extended up to 50 bp before activity begins to decline. Depending on the promoter, the individual elements seem to act either together or independently to activate transcription. Illustrative promoters include the CMV IE, EF-1α, ubiquitin C, or phosphoglycerokinase (PGK) gene promoters.

An example of a promoter capable of allowing expression of a nucleic acid molecule encoding a fusion protein, such as the one described herein, containing a domain that contains a CAR, in a mammalian T cell, is the EF1a promoter. The natural EF1a promoter controls the expression of the alpha subunit of the elongation factor 1 complex, which is responsible for the enzymatic delivery of aminoacyl-tRNA to the ribosome. The EF1a promoter has been widely used in mammalian expression plasmids and has been shown to be effective in directing the expression of a fusion protein, such as that described herein, containing a domain that contains a CAR, from nucleic acid molecules cloned into a lentiviral vector. See, for example, Milone et al., Mol. Ther. 17(8): 1453-1464 (2009). In one aspect, the EF1a promoter contains the sequence shown in SEQ ID NO: 1.

Another example of a promoter is the cytomegalovirus (CMV) immediate early promoter sequence. This promoter sequence is a strong constitutive promoter sequence capable of conferring high levels of expression on any polynucleotide sequence operably linked to it. However, other constitutive promoter sequences can also be used, including, but not limited to, the simian virus 40 early promoter (SV40), the mouse mammary tumor virus (MMTV) promoter, the human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, the MoMuLV, avian leukemia virus promoter, Epstein-Barr virus immediate early promoter, Rous sarcoma virus promoter, as well as human gene promoters such as, but not limited to, actin promoter, myosin promoter, elongation factor 1α promoter, hemoglobin promoter, and creatine kinase promoter. Moreover, the invention should not be limited to the use of constitutive promoters. Inducible promoters are also provided by the present invention. The use of inducible promoters allows one to have a molecular switch capable of turning on expression of an operably linked polynucleotide sequence when such expression is desired, or turning off expression when expression is undesired. Examples of inducible promoters include, but are not limited to, the metallothioneine promoter, the glucocorticoid promoter, the progesterone promoter, and the tetracycline promoter.

Another example of a promoter is the phosphoglycerate kinase (PGK) promoter. In embodiments, it may be desirable to use a truncated PGK promoter (e.g., a PGK promoter with one or more, e.g., 1, 2, 5, 10, 100, 200, 300, or 400 nucleotide deletions compared to the wild-type PGK promoter sequence). The nucleotide sequences of exemplary PGK promoters are shown below.

PGK DT promoter

ACCCCTCTCTCCAGCCACTAAGCCAGTTGCTCCCTCGGCTGACGGCTGCACGCGAGGCCTCCGAACGTCTTACGCCTTGTGGCGCCCCGTCCTTGTCCCGGTGTGATGGCGGGTGTGGGGCGGAGGGCGTGGCGGGGAAGGGCCGGCGACGAGAGCCGCGGGACGACTCGTCGGCGATAACCGGTGTCGGGTAGCGCCAGCCGCGCGACG GTAACGAGGGACCGCGACAGGCAGACCGCTCCCATGATCACTCTGCACGCCGAAGGCAAATAGTGCAGGCCGTGCGGCGCTTGGCGTTCCTTGGAAGGGCTGAATCCCCGCCTCGTCCTTCGCAGCGGCCCCCCGGGTGTTCCCATCGCCGCTTCTAGGCCCACTGCGACGCTTGCCTGCACTTCTTACACGCTCTGGGTCCCAGCCGCGCGCGACGCAAAGGGCCTTGGTG CGGGTCTCGTCGGCGCAGGGACGCGTTTGGGTCCCGACGGAACCTTTTCCGCGTTGGGGTTGGGGCACCATAAGCT (SEQ ID NO: 185)

Illustrative truncated PGK promoters:

PGK100:

ACCCCTCTCTCCAGCCACTAAGCCAGTTGCTCCCTCGGCTGACGGCTGCACGCGAGGCCTCCGAACGTCTTACGCCTTGTGGCGCCCGTCCTTGTCCCGGGTGTGATGGCGGGGTG (SEQ ID NO: 186)

PGK200:

ACCCCTCTCTCCAGCCACTAAGCCAGTTGCTCCCTCGGCTGACGGCTGCACGCGAGGCCTCCGAACGTCTTACGCCTTGTGGCGCCCCGTCCTTGTCCCGGTGTGATGGCGGGTGTGGGGCGGAGGGCGTGGCGGGGAAGGGCCGGCGACGAGAGCCGCGGGACGACTCGTCGGCGATAACCGGTGTCGGGTAGCGCCAGCCGCGCGACG GTAACG (SEQ ID NO: 187)

PGK300:

ACCCCTCTCTCCAGCCACTAAGCCAGTTGCTCCCTCGGCTGACGGCTGCACGCGAGGCCTCCGAACGTCTTACGCCTTGTGGCGCCCCGTCCTTGTCCCGGTGTGATGGCGGGTGTGGGGCGGAGGGCGTGGCGGGGAAGGGCCGGCGACGAGAGCCGCGGGACGACTCGTCGGCGATAACCGGTGTCGGGTAGCGCCAGCCGCGCGACG GTAACGAGGGACCGCGACAGGCAGACGCTCCCATGATCACTCTGCACGCCGAAGGCAAATAGTGCAGGCCGTGCGGCGCTTGGCGTTCCTTGGAAGGGCTGAATCCCCG (SEQ ID NO: 188)

PGK400:

ACCCCTCTCTCCAGCCACTAAGCCAGTTGCTCCCTCGGCTGACGGCTGCACGCGAGGCCTCCGAACGTCTTACGCCTTGTGGCGCCCCGTCCTTGTCCCGGTGTGATGGCGGGTGTGGGGCGGAGGGCGTGGCGGGGAAGGGCCGGCGACGAGAGCCGCGGGACGACTCGTCGGCGATAACCGGTGTCGGGTAGCGCCAGCCGCGCGACG GTAACGAGGGACCGCGACAGGCAGACCGCTCCCATGATCACTCTGCACGCCGAAGGCAAATAGTGCAGGCCGTGCGGCGCTTGGCGTTCCTTGGAAGGCTGAATCCCCGCCTCGTCCTTCGCAGCGGCCCCCCGGGTGTTCCCATCGCCGCTTCTAGGCCCACTGCGACGCTTGCCTGCACTTCTTACACGCTCTGGGTCCCAGCCG (SEQ ID NO: 189)

The vector may also contain, for example, a signal sequence to facilitate secretion, a polyadenylation signal and a transcription terminator (for example, from the bovine growth hormone (BGH) gene), an element that allows episomal replication and replication in prokaryotic cells (for example, the SV40 origin of replication and ColE1 or others known in the art), and/or elements allowing selection (eg, ampicillin resistance gene and/or zeocin resistance marker).

To evaluate the expression of a fusion protein, such as that described herein, containing a domain that contains a CAR polypeptide or fragments thereof, an expression vector introduced into a cell may also contain either a selectable marker gene or a reporter gene, or both, to facilitate identification and selecting expressing cells from a population of cells that are transfected or infected with viral vectors. In other aspects, the selectable marker may be on a separate DNA fragment and used in a co-transfection procedure. Both selectable markers and reporter genes can be flanked by appropriate regulatory sequences allowing expression in host cells. Useful selectable markers include, for example, antibiotic resistance genes such as neo and the like.

Reporter genes are used to identify potentially transfected cells and to evaluate the functionality of regulatory sequences. Typically, a reporter gene is a gene that is not present or expressed in the recipient's body or tissue and which encodes a polypeptide whose expression appears as a readily detectable trait, such as enzymatic activity. The reporter gene expression is analyzed at the appropriate time after the introduction of the DNA into the recipient cells. Suitable reporter genes may include genes encoding luciferase, beta-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or a green fluorescent protein gene (eg, Ui-Tei et al., 2000 FEBS Letters 479: 79-82). Appropriate expression systems are well known and can be obtained using known methods or purchased commercially. Typically, a construct with a minimal 5' flanking region that exhibits the maximum level of reporter gene expression is designated as the promoter. Such promoter regions can be linked to a reporter gene and used to evaluate means for the ability to modulate promoter-driven transcription.

In some embodiments, a vector containing a nucleotide sequence encoding a fusion protein described herein, for example, a fusion protein containing a CAR molecule described herein, may further contain a second nucleotide sequence encoding a polypeptide, for example, an agent that increases the activity of the fusion a protein, for example as described herein, containing a domain that contains a CAR molecule. In some embodiments, a single nucleic acid molecule or a vector containing said nucleic acid molecule encodes multiple fusion proteins, such as those described herein, each containing a CAR containing domain described herein. In some embodiments, the nucleic acid encoding the first fusion protein is under regulatory control (eg, the promoter described herein) separate from the control of the nucleic acid encoding the second fusion protein (eg, the promoter described herein). In other embodiments, two or more nucleotide sequences are encoded by a single nucleic acid molecule in the same reading frame and as a single polypeptide chain. In this aspect, two or more fusion proteins, such as those described herein, each containing a CAR containing domain, may, for example, be separated by one or more peptide cleavage sites (eg, an autocleavage site or a substrate for an intracellular protease). Examples of peptide cleavage sites include the following sites where GSG residues are optional:

T2A: (GSG) E G R G S L L T C G D V E E N P G P (SEQ ID NO: 190)

P2A: (GSG) A T N F S L L K Q A G D V E E N P G P (SEQ ID NO: 191)

E2A: (GSG) Q C T N Y A L L K L A G D V E S N P G P (SEQ ID NO: 192)

F2A: (GSG) V K Q T L N F D L L K L A G D V E S N P G P (SEQ ID NO: 193).

Methods for introducing genes into a cell and expressing them are known in the art. In the context of an expression vector, the vector can be readily introduced into a host cell, such as a mammalian, bacterial, yeast or insect cell, by any method known in the art. For example, the expression vector can be transferred into the host cell by physical, chemical, or biological means.

Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. Methods for obtaining cells containing vectors and/or exogenous nucleic acids are well known in the art. See, for example, Sambrook et al., 2012, MOLECULAR CLONING: A LABORATORY MANUAL, volumes 1-4, Cold Spring Harbor Press, NY. The preferred method for introducing a polynucleotide into a host cell is calcium phosphate transfection or electroporation.

Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors. The use of viral vectors, and in particular retroviral vectors, has become the most widely used method for introducing genes into mammalian cells, such as human cells. Other viral vectors may be derived from lentiviruses, poxviruses, herpes simplex virus I, adenoviruses, adeno-associated viruses, and the like. See, for example, U.S. Patent Nos. 5,350,674 and 5,585,362.

Chemical methods for introducing a polynucleotide into a host cell include the use of colloidal dispersion systems such as macromolecular complexes, nanocapsules, microspheres, granules, and lipid-based systems, including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (eg, an artificial membrane vesicle). Other modern methods of targeted delivery of nucleic acids are available, such as the delivery of polynucleotides with targeted nanoparticles or other suitable submicron delivery systems.

In the case where a non-viral delivery system is used, an exemplary delivery vehicle is a liposome. The use of lipid preparations is contemplated for introducing nucleic acids into a host cell ( in vitro , ex vivo or in vivo ). In another aspect, the nucleic acid may be associated with a lipid. The lipid-bound nucleic acid can be encapsulated in the aqueous interior of the liposome, embedded in the lipid bilayer of the liposome, attached to the liposome through a binding molecule that is linked to both the liposome and the oligonucleotide, enclosed in the liposome, complexed with the liposome, be dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, suspended in a lipid, contained in micelles or complexed with micelles, or otherwise associated with a lipid. Lipid, lipid/DNA, or lipid/expression vector compositions are not limited to a specific structure in solution. For example, they can be in a bilayer structure, in the form of micelles, or have a "destroyed" structure. They may also simply be dispersed in solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances that can be natural or synthetic. For example, lipids include fatty droplets naturally present in the cytoplasm, as well as a class of compounds including long chain aliphatic hydrocarbons and their derivatives such as fatty acids, alcohols, amines, amino alcohols, and aldehydes.

Lipids suitable for use can be obtained from commercial sources. For example, dimyristyl phosphatidylcholine ("DMPC") can be purchased from Sigma, St. Louis, MO; dicetyl phosphate (“DCP”) available from K & K Laboratories (Plainview, NY); cholesterol ("Choi") can be purchased from Calbiochem-Behring; dimyristyl phosphatidylglycerol (“DMPG”) and other lipids can be purchased from Avanti Polar Lipids, Inc. (Birmingham, A.L.). Lipid matrix solutions in chloroform or chloroform/methanol can be stored at about -20°C. Chloroform is used as the only solvent because it evaporates faster than methanol. "Liposome" is a general term encompassing a plurality of single and multilayer lipid vesicles that form when closed lipid bilayers or aggregates are formed. Liposomes can be characterized as vesicular structures with a phospholipid bilayer membrane and an internal aqueous environment. Multilayer liposomes have several lipid layers separated by an aqueous medium. They form spontaneously when phospholipids are suspended in excess aqueous solution. The lipid components undergo a self-redistribution stage, followed by the formation of closed structures and the capture of water and solutes between the lipid bilayers (Ghosh et al., 1991 Glycobiology 5: 505-10). However, compositions having structures in solution other than conventional vesicular structures are also contemplated. For example, lipids can adopt a micelle structure or simply exist as heterogeneous aggregates of lipid molecules. Lipofectamine-nucleic acid complexes are also provided.

Regardless of the method used to introduce exogenous nucleic acids into a host cell or otherwise expose the cell to an inhibitor of the present invention, various assays can be used to confirm the presence of a recombinant DNA sequence in a host cell. Such assays include, for example, "molecular biology" assays well known to those skilled in the art, such as Southern and Northern blotting, RT-PCR, and PCR; "biochemical" assays, such as detecting the presence or absence of a particular peptide, for example, by immunological methods (ELISA and Western blotting), or assays described herein to identify agents within the scope of the invention.

The present invention also relates to a vector containing a nucleic acid molecule encoding a fusion protein, such as described herein, containing a domain that contains CAR. In one embodiment, the vector contains a CAR-encoding nucleic acid molecule, such as described herein. In one embodiment, the vector contains two CAR-encoding nucleic acid molecules. In one aspect, one or more CAR vectors (e.g., a vector containing a first CAR encoding nucleic acid molecule and a vector containing a second CAR encoding nucleic acid molecule, or a vector containing both the first and second CAR encoding nucleic acids ) can be directly transduced into a cell, such as a T cell or NK cell. In one aspect, the vector is a cloning or expression vector, e.g., a vector including, but not limited to, one or more plasmids (e.g., expression plasmids, cloning vectors, minicircles, minivectors, double microchromosomes), retroviral, and lentiviral vector constructs. In one aspect, the vector is capable of expressing a CAR construct in mammalian immune effector cells (eg, T cells, NK cells).

In one embodiment, when stable expression of one or more (e.g., one or two) fusion proteins, such as those described herein, each containing a CAR-containing domain is desired, a vector containing one or more (e.g., one or two ) CAR-encoding nucleic acid molecules are transduced into an immune effector cell. For example, immune effector cells with stable expression of two fusion proteins, such as those described herein, each containing a CAR containing domain, can be generated using lentiviral vectors. Cells stably expressing two fusion proteins, such as those described herein, each containing a CAR containing domain, express CAR for at least 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 3 months, 6 months, 9 months or 12 months after transduction.

In one embodiment, when transient expression of one or more (e.g., one or two) fusion proteins, such as those described herein, is desired, each containing a CAR-containing domain, one or more (e.g., one or two) encoding the fusion the protein of the nucleic acid molecule is transfected into an immune effector cell. One or more (e.g., one or two) nucleic acid molecules encoding fusion proteins, such as those described herein, containing a domain that contains a CAR, may be a vector containing one or more (e.g., one or two) CAR- encoding nucleic acid molecules, or in vitro transcribed RNA of one or more (eg one or two) CARs. In vitro transcribed CAR RNAs and methods for transfection into immune effector cells are further described below. Cells transiently expressing one or more (e.g., one or two) CARs express one or more (e.g., one or two) CARs for 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 days after transfection.

RNA transfection

Disclosed herein are methods for producing in vitro transcribed RNA encoding a fusion protein, for example as described herein, containing a domain that contains CAR. The present invention also encompasses an RNA construct encoding a fusion protein, for example as described herein, containing a domain that contains a CAR that can be directly transfected into a cell. The method of obtaining mRNA for use in transfection may include in vitro transcription (IVT) of the template with specially designed primers, followed by the addition of polyA, to obtain a construct containing a 3'- and 5'-untranslated sequence ("UTR"), 5'-cap and/or an internal ribosome binding site (IRES), a nucleic acid to be expressed, and a polyA tail, typically 50-5000 bases long (SEQ ID NO: 32). The RNA obtained in this way can be efficiently transfected into different cell types. In one aspect, the matrix contains sequences for CARs.

In one aspect, a fusion protein, for example as described herein, containing a domain that contains a CAR, of the present invention is encoded by a messenger RNA (mRNA). In one aspect, an mRNA encoding a CAR as described herein is introduced into a T cell or NK cell.

In one embodiment, an in vitro transcribed RNA encoding a fusion protein, for example as described herein, containing a domain that contains CAR, can be introduced into a cell in a transient transfection form. RNA is produced by in vitro transcription using a polymerase chain reaction (PCR) template. DNA of interest from any source can be directly translated by PCR into a template for in vitro mRNA synthesis using appropriate primers and RNA polymerase. The DNA source can be, for example, genomic DNA, plasmid DNA, phage DNA, cDNA, a synthetic DNA sequence, or any other suitable DNA source. The desired template for in vitro transcription is a fusion protein template, for example as described herein, containing a domain that contains the CAR described herein. For example, a template for CAR RNA contains a sequence for an extracellular region containing a single chain variable domain of an antibody for an antigen described herein; a hinge region (eg, the hinge region described herein), a transmembrane domain (eg, the transmembrane domain described herein, such as the transmembrane domain of CD8a); and a cytoplasmic region that contains an intracellular signaling domain, such as the intracellular signaling domain described herein, such as containing a CD3-zeta signaling domain and a 4-1BB signaling domain.

In one embodiment, the DNA used for PCR contains an open reading frame. The DNA may be from a naturally occurring DNA sequence from the genome of an organism. In one embodiment, the nucleic acid may contain some or all of the 5' and/or 3' untranslated regions (UTRs). A nucleic acid may contain exons and introns. In one embodiment, the DNA used for PCR is a human nucleic acid sequence. In another embodiment, the DNA used for PCR is a human nucleic acid sequence containing 5' and 3' UTRs. Alternatively, the DNA may be an artificial DNA sequence that is not normally expressed in naturally occurring organisms. An exemplary artificial DNA sequence is a sequence containing gene fragments ligated together to form an open reading frame encoding a fusion protein. The DNA fragments ligated together may be from the same organism or from more than one organism.

PCR is used to create a template for in vitro transcription of mRNA, which is used for transfection. PCR methods are well known in the art. Primers for use in PCR are designed to contain regions that are substantially complementary to regions of DNA used as a template for PCR. As used herein, the term "substantially complementary" refers to nucleotide sequences where most or all of the bases in the primer sequence are complementary, or one or more bases are non-complementary or mismatch. Significantly complementary sequences can be annealed or hybridized to the selected target DNA under the annealing conditions used for PCR. Primers can be designed to be substantially complementary to any portion of the template DNA. For example, primers can be designed to amplify a nucleic acid fragment that is normally transcribed in cells (open reading frame), including the 5' and 3' UTRs. Primers can also be designed to amplify a nucleic acid fragment that encodes a particular domain of interest. In one embodiment, primers are designed to amplify a human cDNA coding region, including all or part of the 5' and 3' UTRs. Primers useful for PCR can be prepared by synthetic methods well known in the art. "Forward primers" are primers containing a region of nucleotides that are substantially complementary to nucleotides on the DNA template that are upstream of the DNA sequence to be amplified. Used in this document, the term "upper" means the location in the direction 5' from the DNA sequence to be amplified, in relation to the coding strand. "Reverse primers" are primers containing a region of nucleotides that are substantially complementary to nucleotides on the double-stranded DNA template that are downstream of the DNA sequence to be amplified. Used in this document, the term "below" means the location in the direction of 3' from the DNA sequence to be amplified, in relation to the coding strand.

Any DNA polymerase used for PCR can be used in the methods disclosed herein. The reagents and polymerase are commercially available from a variety of sources.

You can also use chemical structures that have the ability to increase the stability and/or efficiency of translation. The RNA preferably contains 5' and 3' UTRs. In one embodiment, the 5'-UTR is from one to 3000 nucleotides in length. The length of the 5'- and 3'-UTR sequences added to the coding region can be varied in a variety of ways, including, but not limited to, designing PCR primers that anneal to different regions of the UTR. Using this approach, the person skilled in the art can change the length of the 5'- and 3'-UTR as needed to achieve optimal translation efficiency after transfection of the transcribed RNA.

The 5' and 3' UTRs can be natural, endogenous 5' and 3' UTRs from the nucleic acid of interest. Alternatively, UTR sequences that are not endogenous to the nucleic acid of interest can be added by including UTR sequences in the forward and reverse primers, or by otherwise modifying the template. The use of UTR sequences that are not endogenous to the nucleic acid of interest may be useful in altering the stability and/or efficiency of RNA translation. For example, it is known that AU-rich elements in 3'-UTR sequences can decrease mRNA stability. Thus, the 3'-UTR can be selected or designed to enhance the stability of the transcribed RNA based on the properties of the UTR, well known in the art.

In one embodiment, the 5'-UTR may contain a Kozak sequence from an endogenous nucleic acid. Alternatively, if a 5'UTR that is not endogenous to the nucleic acid of interest is added by PCR as described above, the Kozak consensus sequence can be altered by adding the 5'UTR sequence. Kozak sequences may increase the efficiency of translation of some RNA transcripts, but do not appear to be necessary for the efficient translation of all RNAs. The need for Kozak sequences for many mRNAs is known in the art. In other embodiments, the 5'-UTR may be a 5'-UTR from the RNA of a virus whose RNA genome is stable in cells. In other embodiments, various nucleotide analogs can be used in the 3' or 5' UTR to block the degradation of mRNA by exonucleases.

To enable the synthesis of RNA from a DNA template without the need for gene cloning, a transcription promoter must be attached to the DNA template upstream of the sequence to be transcribed. When a sequence acting as a promoter for RNA polymerase is added to the 5' end of the forward primer, the RNA polymerase promoter becomes incorporated into the PCR product upstream of the open reading frame to be transcribed. In one preferred embodiment, the promoter is a T7 polymerase promoter, as described elsewhere herein. Other useful promoters include, but are not limited to, the T3 and SP6 RNA polymerase promoters. Consensus nucleotide sequences for the T7, T3 and SP6 promoters are known in the art.

In a preferred embodiment, the mRNA has both a 5' cap and a 3' poly(A) tail, which determine ribosome binding, translation initiation, and cellular stability of the mRNA. On a circular DNA template, such as plasmid DNA, RNA polymerase creates a long concatemeric product that is not suitable for expression in eukaryotic cells. Transcription of plasmid DNA linearized at the 3'-UTR end results in normal-sized mRNA that is not efficient in transfecting eukaryotic cells, even if it is polyadenylated after transcription.

On a linear DNA template, T7 RNA polymerase can extend the 3' end of the transcript beyond the last base of the template (Schenborn and Mierendorf, Nuc Acids Res., 13:6223-36 (1985); Nacheva and Berzal-Herranz, Eur. J Biochem., 270:1485-65 (2003).

A common method for incorporating polyA/T regions into a DNA template is molecular cloning. However, a polyA/T sequence included in plasmid DNA can cause plasmid instability, whereby plasmid DNA templates derived from bacterial cells are often heavily contaminated with deletions and other aberrations. This makes cloning procedures not only cumbersome and time-consuming, but often unreliable. As a consequence, there is an urgent need for a method that allows the construction of DNA templates with a polyA/T 3' region without cloning.

The polyA/T segment of the transcribed DNA template can be obtained during PCR by using a reverse primer containing a polyT tail, e.g. 100T tail (SEQ ID NO: 968) (size can be 50-5000 T (SEQ ID NO : 974)), or after PCR by any other method, including, but not limited to, DNA ligation or in vitro recombination. Poly(A) "tails" also ensure the stability of RNA molecules and help reduce their degradation. Generally, the length of the poly(A) tail is positively correlated with the stability of the transcribed RNA. In one embodiment, the poly(A) "tail" contains from 100 to 5000 adenosine residues (SEQ ID NO: 82).

The poly(A) tails of RNA molecules can be further extended after in vitro transcription using a poly(A) polymerase such as E. coli polyA polymerase (E-PAP). In one embodiment, increasing the length of the poly(A) "tail" from 100 nucleotides to 300-400 nucleotides (SEQ ID NO: 969) results in an approximately twofold increase in the efficiency of RNA translation. In addition, the attachment of different chemical groups to the 3'-end can lead to an increase in mRNA stability. Such an attached fragment may contain modified/artificial nucleotides, aptamers and other compounds. For example, ATP analogs can be incorporated into the poly(A) tail using a poly(A) polymerase. ATP analogs can further increase the stability of RNA.

5' caps also provide stability to RNA molecules. In a preferred embodiment, the RNA molecules produced by the methods disclosed herein contain a 5' cap. The 5'-cap is introduced by methods known in the art and described herein (Cougot, et al., Trends in Biochem. Sci., 29:436-444 (2001); Stepinski, et al., RNA, 7:1468 -95 (2001); Elango, et al., Biochim. Biophys. Res. Commun., 330:958-966 (2005)).

RNA molecules produced by the methods disclosed herein may also contain an internal ribosome entry site (IRES) sequence. The IRES sequence can be any viral, chromosomal or engineered sequence that initiates cap-independent binding of the ribosome to mRNA and promotes translation initiation. Any solute suitable for cell electroporation may be included, which includes cell permeability and viability enhancing factors such as sugars, peptides, lipids, proteins, antioxidants, and surfactants.

RNA can be introduced into target cells using any of a variety of different methods, such as commercially available methods that include, but are not limited to, electroporation (Amaxa Nucleofector-II (Amaxa Biosystems, Cologne, Germany)), (ECM 830 (BTX ) (Harvard Instruments, Boston, Mass.) or Gene Pulser II (BioRad, Denver, Colo.), Multiporator (Eppendort, Hamburg Germany), cationic liposome-mediated transfection using lipofection, polymer encapsulation, peptide-mediated transfection, or biolistic delivery systems particles such as "gene guns" (see, for example, Nishikawa, et al. Hum Gene Ther., 12(8):861-70 (2001).

Non-viral delivery methods

In some aspects, non-viral methods may be used to deliver a nucleic acid encoding a chimeric molecule or fusion protein described herein to a cell or tissue or body of a subject.

In some embodiments, the non-viral method includes the use of a transposon (also referred to as a transposition element). In some embodiments, a transposon is a DNA fragment that can be inserted into a region of the genome, such as a DNA fragment that is capable of self-replication and inserting a copy of itself into the genome, or a DNA fragment that can be cut from a longer nucleic acid and inserted into another region of the genome. For example, a transposon contains a DNA sequence consisting of inverted repeats flanking the genes to be transposed.

In some embodiments, cells, e.g., T or NK cells, are obtained that express a chimeric molecule or fusion protein, e.g., as described herein, e.g., using a combination of gene insertion with SBTS and genetic editing with a nuclease (e.g., nucleases zinc fingers (ZFN), transcription activator-like effector nucleases (TALEN), the CRISPR/Cas system, or engineered homing endonuclease meganuclease).

In some embodiments, the use of a non-viral delivery method allows cells, such as T or NK cells, to be reprogrammed and the cells to be administered to a subject by direct infusion. The advantages of non-viral vectors include, but are not limited to, ease and relatively low cost of obtaining sufficient quantities to meet patient needs, storage stability, and lack of immunogenicity.

Host cells

The present invention also provides cells, eg, immune effector cells (eg, a population of cells, eg, a population of immune effector cells), containing a nucleic acid molecule, a fusion protein molecule, or a vector, eg, as described herein. In some embodiments, the proposed cells contain a fusion protein, for example, as described herein, containing a domain that contains CAR, a nucleic acid molecule encoding a fusion protein containing a domain that contains CAR, or a vector containing it.

In some aspects, immune effector cells, such as T cells or NK cells, can be obtained from a blood sample obtained from a subject using various methods known to the skilled person, such as ficoll™ gradient separation. In one preferred aspect, cells from the circulating blood of an individual are obtained by apheresis. The apheresis product typically contains lymphocytes, including T cells, monocytes, granulocytes, B cells, other nucleated white blood cells, erythrocytes, and platelets. In one aspect, cells harvested at apheresis can be washed to remove a plasma fraction and placed in an appropriate buffer or medium for subsequent processing steps. In one embodiment, cells are washed with phosphate buffered saline (PBS). In an alternative embodiment, the wash solution is free of calcium and may be free of magnesium, or may be free of many, if not all, of the divalent cations.

The initial stages of activation in the absence of calcium can lead to increased activation. As will be appreciated by those skilled in the art, the washing step can be performed by methods known in the art, such as using a semi-automated "flow through" centrifuge (e.g., Cobe 2991 cell processor, Baxter CytoMate, or Haemonetics Cell Saver 5) according to the manufacturer's instructions. After washing, cells can be resuspended in various biocompatible buffers such as, for example, Ca-free, Mg-free PBS, PlasmaLyte A, or other buffered or unbuffered saline. Alternatively, unwanted components from the apheresis sample can be removed and the cells directly resuspended in culture medium.

It is recognized that culture media containing 5% or less, e.g. 2%, human AB serum can be used in the methods of this application and known culture media and compositions can be used, e.g., those described in Smith et al ., " Ex vivo expansion of human T cells for adoptive immunotherapy using the novel Xeno-free CTS Immune Cell Serum Replacement” Clinical & Translational Immunology (2015) 4, e31; doi:10.1038/cti.2014.31.

In one aspect, T cells are isolated from peripheral blood lymphocytes by lysing erythrocytes and depleting monocytes, such as by Percoll™ gradient centrifugation or flow elution centrifugation.

The methods described herein may include, for example, selecting a specific subset of immune effector cells, e.g., T cells, which is a population depleted of regulatory T cells, depleted of CD25+ cells, using, for example, a negative selection method. , such as described in this document. Preferably, the population depleted of regulatory T cells contains less than 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1% CD25+ cells.

In one embodiment, regulatory T cells, eg, CD25+ T cells, are removed from the population using an anti-CD25 antibody or fragment thereof, or a CD25 binding ligand, IL-2. In one embodiment, an anti-CD25 antibody, or fragment thereof, or a CD25 binding ligand, is conjugated to a substrate, such as a bead, or otherwise applied to a substrate, such as a bead. In one embodiment, an anti-CD25 antibody or fragment thereof is conjugated to a substrate as described herein.

In one embodiment, regulatory T cells, eg, CD25+ T cells, are removed from the population using a CD25 depleting reagent from Miltenyi™. In one embodiment, the ratio of cells to CD25 depleting reagent is 1e7 cells per 20 µl, or 1e7 cells per 15 µl, or 1e7 cells per 10 µl, or 1e7 cells per 5 µl, or 1e7 cells per 2.5 µl, or 1e7 cells for 1.25 µl. In one embodiment, for example, more than 500 million cells/ml are used to deplete regulatory T cells, eg, deplete CD25+ cells. In a further aspect, a cell concentration of 600, 700, 800, or 900 million cells/mL is used.

In one embodiment, the population of immune effector cells to be depleted includes about 6×10 ⁹ CD25+ T cells. In other aspects, the population of immune effector cells to be depleted includes from about 1x10 ⁹ to 1x 10 ¹⁰ CD25+ T cells, as well as any integer value in between. In one embodiment, the resulting regulatory T cell-depleted population contains 2x10 ⁹ regulatory T cells, e.g., CD25+ cells, or less (e.g., 1x10 ⁹ 5x10 ⁸ 1x10 ⁸ .5 ×10 ⁷ , 1×10 ⁷ or less CD25+ cells).

In one embodiment, regulatory T cells, eg, CD25+ cells, are removed from the population using a CliniMAC system with a depletion tubing set, such as, for example, 162-01 tubing. In one embodiment, the CliniMAC system is used with parameters such as DEPLETION2.1, for example.

Without wishing to be bound by a particular theory, reducing the level of immune cell negative regulators (e.g., reducing the number of unwanted immune cells, e.g., T _REG cells) in a subject prior to apheresis or during production of cells expressing a fusion protein, e.g., as described herein, contains a domain , which contains CAR, can reduce the risk of relapse in the subject. For example, methods for depleting T _REG cells are well known in the art. Methods for reducing the number of T _REG cells include, but are not limited to, the use of cyclophosphamide, an anti-GITR antibody (an anti-GITR antibody described herein), CD25 depletion, and combinations thereof.

In some embodiments, production methods include reducing (eg, depleting) T _REG cells prior to producing a cell expressing a fusion protein, eg, as described herein, containing a domain that contains CAR. For example, preparation methods include contacting a sample, such as an apheresis sample, with an anti-GITR antibody and/or an anti-CD25 antibody (or fragment thereof, or CD25 binding ligand), for example, to deplete T _REG cells prior to obtaining preparation of a CAR-expressing cell (eg, T cells, NK cells).

In one embodiment, the subject is pre-treated with one or more therapeutic agents that reduce the number of T _REG cells prior to harvesting the cells to obtain a cell preparation expressing a fusion protein, such as the one described herein, containing a domain that contains a CAR, resulting in reducing the risk of relapse in a subject when treated with cells expressing a fusion protein, for example as described herein, containing a domain that contains CAR. In one embodiment, methods for reducing the number of T _REG cells include, but are not limited to, administering to the subject one or more of cyclophosphamide, an anti-GITR antibody, a CD25-depleting agent, or a combination thereof. Administration of one or more of cyclophosphamide, an anti-GITR antibody, a CD25-depleting agent, or a combination thereof may occur before, during, or after infusion of the CAR-expressing cell preparation.

In one embodiment, the subject is pre-treated with cyclophosphamide prior to harvesting cells to obtain a CAR-expressing cell preparation, resulting in a reduced risk of relapse in the subject when treated with cells expressing a fusion protein, such as the one described herein, containing a domain that contains CAR. In one embodiment, the subject is pre-treated with an anti-GITR antibody prior to harvesting cells to obtain a CAR-expressing cell preparation, resulting in a reduced risk of relapse in the subject when treated with CAR-expressing cells.

In one embodiment, the population of cells to be removed is not regulatory T cells or tumor cells, but cells that otherwise adversely affect proliferation and/or function of CAR T cells, e.g., cells expressing CD14, CD11b, CD33 , CD15, or other markers expressed by potentially immunosuppressive cells. In one embodiment, it is envisaged that such cells will be removed simultaneously with regulatory T cells and/or tumor cells, or after said depletion, or in another order.

The methods described herein may include more than one selection step, such as more than one depletion step. Enrichment of a T cell population by negative selection can be accomplished with a combination of antibodies directed to surface markers unique to the negatively selected cells. One way is to sort and/or select cells by negative magnetic immune adhesion or flow cytometry, where a cocktail of monoclonal antibodies directed to cell surface markers present on negatively selected cells is used. For example, for negative enrichment for CD4+ cells, the monoclonal antibody cocktail typically includes antibodies to CD14, CD20, CD11b, CD16, HLA-DR, and CD8.

The methods described herein may further include removing from a population of cells expressing a tumor antigen, e.g., a tumor antigen that does not include CD25, e.g., CD19, CD30, CD38, CD123, CD20, CD14, or CD11b, to obtain a population of regulatory T cells, e.g. CD25+ depleted and tumor antigen depleted, which are suitable for expression of a fusion protein, e.g., as described herein, containing a domain that contains a CAR, e.g., the CAR described herein . In one embodiment, tumor antigen-expressing cells are removed at the same time as regulatory T cells, eg, CD25+ cells. For example, an anti-CD25 antibody, or fragment thereof, and an antibody against a tumor antigen, or fragment thereof, can be attached to the same substrate, such as a bead that can be used to remove cells, or an anti-CD25 antibody, or fragment thereof. , and an antibody against a tumor antigen, or a fragment thereof, can be attached to different beads, the mixture of which can be used to remove cells. In other embodiments, the removal of regulatory T cells, eg, CD25+ cells, and the removal of tumor antigen-expressing cells are performed sequentially, eg, in any order.

Also provided are methods comprising removing from a population of cells expressing an immune checkpoint inhibitor, e.g., the immune checkpoint inhibitor described herein, e.g., one or more cell species of PD-1+ cells, LAG3+ cells, and TIM3+ cells, to obtain cell populations depleted of regulatory T cells, eg depleted of CD25+ cells, and depleted of cells expressing an immune checkpoint inhibitor, eg depleted of PD-1+, LAG3+ and/or TIM3+ cells. Exemplary immune checkpoint inhibitors include B7-H1, B7-1, CD160, P1H, 2B4, PD-1, TIM3, CEACAM (e.g. CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG3, TIGIT, CTLA -4, BTLA and LAIR1. In one embodiment, cells expressing an immune checkpoint inhibitor are removed at the same time as regulatory T cells, eg, CD25+ cells. For example, an anti-CD25 antibody, or fragment thereof, and an anti-immune checkpoint inhibitor antibody, or fragment thereof, can be attached to the same bead that can be used to remove cells, or an anti-CD25 antibody, or fragment thereof, and the anti-immune checkpoint inhibitor antibody, or fragment thereof, can be attached to different beads, the mixture of which can be used to remove cells. In other embodiments, removal of regulatory T cells, eg, CD25+ cells, and removal of inhibitor-expressing immune checkpoint cells are performed sequentially, eg, in any order.

The methods described herein may include a positive selection step. For example, T cells can be isolated by incubation with anti-CD3/anti-CD28 (eg 3×28) antibody conjugated beads, such as ^DYNABEADS® M-450 CD3/CD28 T, for a period of time sufficient to produce a positive selection of the desired T cells. In one embodiment, the time period is about 30 minutes. In the following embodiment, the time period is from 30 minutes to 36 hours or longer, as well as all integer values in between. In a further embodiment, the time period is at least 1, 2, 3, 4, 5, or 6 hours. In another embodiment, the time period is from 10 to 24 hours, such as 24 hours. Longer incubation times can be used to isolate T cells when T cells are present in low numbers compared to other cell types, for example, when isolating tumor-infiltrating lymphocytes (TIL) from tumor tissue, or from the blood of individuals with immune deficiency. In addition, the use of longer incubation times may increase the efficiency of CD8+ T cell uptake. Thus, by simply shortening or prolonging the time, T cells are allowed to bind to CD3/CD28 beads and/or by increasing or decreasing the bead to T cell ratio (as described hereinafter), selection can be made preferably at in favor or not in favor of T cell subpopulations at the start or at other times during the culture. In addition, by increasing or decreasing the ratio of anti-CD3 and/or anti-CD28 antibodies on the beads or other surface, selection can be made preferentially or against T cell subpopulations at the start of culture or at other desired time points.

In one embodiment, a population of T cells can be selected that express one or more of IFNγ, TNFα, IL-17A, IL-2, IL-3, IL-4, GM-CSF, IL-10, IL-13, granzyme B and perforin, or other relevant molecules, such as other cytokines. Methods for screening cells for expression can be used, for example the methods described in PCT Publication No. WO 2013/126712.

When selecting the desired population of cells by positive or negative selection, the concentration of cells and surfaces (for example, particles such as granules) can be varied. In some aspects, it may be desirable to greatly reduce the volume in which the beads and cells are mixed together (eg, increase the concentration of cells) to maximize contact between cells and beads. For example, in one aspect, a concentration of 10 billion cells/ml, 9 billion cells/ml, 8 billion cells/ml, 7 billion cells/ml, 6 billion cells/ml, or 5 billion cells/ml is used. In one aspect, a concentration of 1 billion cells/mL is used. In yet another aspect, a cell concentration of 75, 80, 85, 90, 95, or 100 million cells/ml is used. In the following aspects, concentrations of 125 or 150 million cells/ml can be used.

The use of high concentrations can lead to increased cell yield, cell activation and cell proliferation. In addition, the use of high cell concentrations allows more efficient capture of cells that may weakly express target antigens of interest, such as CD28-negative T cells, or cells from specimens where many tumor cells are present (such as leukemic blood, tumor tissue, and etc). Such cell populations may be of therapeutic value and it may be desirable to obtain them. For example, the use of a high concentration of cells allows for more efficient selection of CD8+ T cells, which typically have weaker expression of CD28.

In a related aspect, it may be desirable to use lower concentrations of cells. By significantly diluting the mixture of T cells and surfaces (eg, particles such as beads), the interaction between particles and cells is minimized. This allows the selection of cells that express in large quantities the desired antigens that bind to the particles. For example, CD4+ T cells express CD28 at a higher level and are more efficiently captured than CD8+ T cells at low concentrations. In one aspect, the cell concentration used is 5×10 ⁶ /ml. In other aspects, the concentration used can be from about 1×10 ⁵ /ml to 1×10 ⁶ /ml, as well as any intermediate integer value.

In other aspects, the cells can be incubated on a rotator for different periods of time at different speeds, either at 2-10°C or at room temperature.

T cells to be stimulated can also be frozen after the washing step. Without wishing to be bound by a particular theory, the step of freezing and then thawing results in a more homogeneous preparation by removing granulocytes and, to some extent, monocytes from the cell population. After a washing step in which plasma and platelets are removed, the cells can be suspended in a freezing solution. While many freezing solutions and settings are known in the art that will be useful in this context, one method involves using PBS containing 20% DMSO and 8% human serum albumin, or culture media containing 10% dextran 40 and 5% dextrose. , 20% human serum albumin and 7.5% DMSO, or 31.25% plasmalite A, 31.25% dextrose 5%, 0.45% NaCl, 10% dextran 40 and 5% dextrose, 20% human serum albumin and 7.5% DMSO, or other suitable cell freezing medium containing, for example, gespan and plasmalite A; the cells are then frozen to -80° C. at a rate of 1° per minute and stored in the vapor phase in a liquid nitrogen tank. You can use other methods of controlled freezing, as well as uncontrolled immediate freezing at -20°C or in liquid nitrogen.

In some aspects, cryopreserved cells are thawed and washed as described herein and left to stand for one hour at room temperature before being activated using the methods of the present invention.

It is also contemplated within the context of the invention to collect blood or apheresis product samples from a subject during a period of time prior to when the expanded cells described herein may be needed. Because of this, the source of cells to be expanded can be collected at any desired time point, and the desired cells, such as T cells, isolated and frozen for later use in immune effector cell therapy for a number of diseases or conditions in which benefit from immune effector cell therapy such as those described herein. In one aspect, the blood sample or apheresis product is obtained from a generally healthy subject. In some aspects, a blood sample or apheresis product is obtained from a generally healthy subject who is at risk of developing a disease but who has not yet developed a disease, and the cells of interest are isolated and frozen for later use. In some aspects, T cells can be expanded, frozen and used at a later time. In some aspects, samples are collected from a patient shortly after the diagnosis of the specific disease described herein, but prior to any treatment. In a further aspect, cells are isolated from a blood sample or apheresis product obtained from a subject prior to any number of appropriate treatments including, but not limited to, treatment with agents such as natalizumab, efalizumab, antiviral agents, chemotherapy, radiation therapy, immunosuppressive agents such as such as cyclosporine, azathioprine, methotrexate, mycophenolate and FK506, antibodies or other immunoablative agents such as campath, anti-CD3 antibodies, cytoxan, fludarabine, cyclosporine, FK506, rapamycin, mycophenolic acid, steroids, FR901228 and irradiation.

In a further aspect of the present invention, T cells are obtained from a patient immediately after treatment that leaves the subject with functional T cells. In this respect, it has been found that after certain cancer therapies, particularly immune-damaging drugs, shortly after treatment during a period when patients typically recover from treatment, the quality of the resulting T cells can be optimal or improved in terms of their ability to propagate ex vivo . Likewise, after ex vivo manipulation using the methods described herein, these cells may be in a preferred state for better survival and propagation in vivo . Thus, it is within the context of the present invention to harvest blood cells, including T cells, dendritic cells, or other cells of the hematopoietic lineage, during this recovery step. Additionally, in some aspects, mobilization (e.g., mobilization with GM-CSF) and conditioning regimens can be used to create conditions in a subject's body that favor repopulation, recycling, regeneration, and/or multiplication of particular cell types, in particular over a period of time. period of time after therapy. Exemplary cell types include T cells, B cells, dendritic cells, and other cells of the immune system.

In one embodiment, immune effector cells expressing a fusion protein, e.g., as described herein, containing a domain that contains a CAR molecule, e.g., the CAR molecule described herein, are obtained from a subject who has received a low, immunostimulatory dose of an mTOR inhibitor. In one embodiment, a population of immune effector cells, e.g., T cells, to be genetically modified to express CAR is harvested after a sufficient period of time, or after sufficient administration of a low, immunostimulatory dose of an mTOR inhibitor, such that the level of PD-1-negative immune effector cells, e.g. T cells, or the ratio of PD-1 negative immune effector cells, e.g. T cells/PD-1 positive immune effector cells, e.g. T cells, in the subject, or derived from the subject, by at least temporarily, is elevated.

In other embodiments, a population of immune effector cells, e.g., T cells, that have been or will be genetically modified to express a fusion protein, e.g., as described herein, containing a domain that contains CAR, can be treated ex vivo by contacting an amount an mTOR inhibitor that increases the number of PD-1 negative immune effector cells, eg T cells, or increases the ratio of PD-1 negative immune effector cells, eg T cells/PD-1 positive immune effector cells, eg T -cells.

In one embodiment, the T cells in the population are diacylglycerol kinase (DGK) deficient. DGK-deficient cells include cells that do not express DGK RNA or protein, or have reduced or inhibited DGK activity. DGK-deficient cells can be generated by genetic methods, for example by introducing RNAi, eg siRNA, shRNA, miRNA, to reduce or prevent DGK expression. Alternatively, DGK-deficient cells can be obtained by treatment with the DGK inhibitors described herein.

In one embodiment, the T cells in the population are deficient in Ikaros. Ikaros-deficient cells include cells that do not express Ikaros RNA or protein, or have reduced or inhibited Ikaros activity. Ikaros-deficient cells can be obtained by genetic methods, for example, by introducing RNAi, for example, siRNA, shRNA, miRNA, to reduce or prevent the expression of Ikaros. Alternatively, Ikaros-deficient cells can be obtained by treatment with Ikaros inhibitors, such as lenalidomide.

In embodiments, the T cells in the population are DGK-deficient and Ikaros-deficient, eg, do not express DGK and Ikaros, or have reduced or inhibited DGK and Ikaros activity. Such DGK and Ikaros deficient cells can be obtained by any of the methods described herein.

In one embodiment, the NK cells are obtained from a subject. In another embodiment, the NK cells are an NK cell line, for example, the NK-92 cell line (Conkwest).

Additional expressed agents

In another embodiment, an immune effector cell expressing a fusion protein, e.g., as described herein, containing a domain that contains a CAR as described herein, may also express another agent, e.g., an agent that increases the activity of a CAR-expressing cell. For example, in one embodiment, the agent may be an agent that inhibits an inhibitory molecule. Examples of inhibitory molecules include PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g. CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG-3, VISTA, BTLA, TIGIT, LAIR1 , CD160, 2B4, and TGFR-beta, such as those described herein. In one embodiment, an agent that inhibits an inhibitory molecule comprises a first polypeptide, such as an inhibitory molecule, linked to a second polypeptide that positively signals the cell, such as an intracellular signaling domain as described herein. In one embodiment, the agent contains a first polypeptide, e.g., an inhibitory molecule such as PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5) , LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, or TGFR-beta, or a fragment of any of them, and a second polypeptide that is an intracellular signaling domain described herein (for example, containing a co-stimulatory domain (for example , 41BB, CD27, or CD28, e.g., as described herein) and/or a major signaling domain (e.g., the CD3-zeta signaling domain described herein).In one embodiment, the agent comprises a first PD-1 polypeptide or fragment thereof, and a second intracellular signaling domain polypeptide as described herein (eg, the CD28, CD27, OX40, or 4-IBB signaling domain as described herein and/or the CD3-zeta signaling domain as described herein).

In one embodiment, an immune effector cell expressing a fusion protein, e.g., as described herein, containing a domain that contains the CAR described herein, may also contain a second fusion protein, e.g., as described herein, containing a domain that contains CAR, eg, a second CAR containing a different antigen binding domain, eg, for the same target (eg, the target described above) or a different target. In one embodiment, the second CAR contains an antigen binding domain for a target expressed on the same type of cancer cell as the target for the first CAR. In one embodiment, a CAR-expressing immune effector cell has a first CAR that targets a first antigen and contains an intracellular signaling domain that contains a co-stimulatory signaling domain but not a major signaling domain, and a second CAR that targets a second, distinct, antigen and contains an intracellular signaling domain. domain containing the main signaling domain, but not the costimulatory signaling domain.

Without wishing to be bound by a particular theory, placing a co-stimulatory signaling domain, e.g., 4-1BB, CD28, CD27, or OX-40, on the first CAR and a major signaling domain, e.g. which both targets are expressed. In one embodiment, a CAR-expressing immune effector cell has a first CAR containing an antigen-binding domain that targets, for example, the target described above, a transmembrane domain, and a costimulatory domain, and a second CAR that targets an antigen other than the antigen that the first CAR is targeted (eg, an antigen expressed on the same type of cancer cell as the first target) and contains an antigen-binding domain, a transmembrane domain, and a major signaling domain. In another embodiment, a CAR-expressing immune effector cell has a first CAR containing an antigen-binding domain that targets, for example, the target described above, a transmembrane domain and a major signaling domain, and a second CAR that targets an antigen other than the antigen that the first CAR is targeted (eg, an antigen expressed on the same type of cancer cell as the first target) and contains an antigen-binding domain for the antigen, a transmembrane domain, and a costimulatory signaling domain.

In one embodiment, a CAR-expressing immune effector cell has a CAR as described herein, eg, a CAR for the target described above, and an inhibitory CAR. In one embodiment, the inhibitory CAR contains an antigen-binding domain that binds an antigen present on normal cells but not cancer cells, eg, normal cells that also express the target. In one embodiment, the inhibitory CAR comprises an antigen-binding domain, a transmembrane domain, and an intracellular domain of an inhibitory molecule. For example, the intracellular domain of an inhibitory CAR may be the intracellular domain of PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, or TGFR-beta.

In one embodiment, an immune effector cell (e.g., T cell, NK cell) has a first CAR containing an antigen-binding domain that binds to the tumor antigen described herein and a second CAR containing the extracellular domain of PD-1 or a fragment thereof. .

In one embodiment, the cell also contains the inhibitory molecule described above.

In one embodiment, the second CAR in the cell is an inhibitory CAR, wherein the inhibitory CAR comprises an antigen-binding domain, a transmembrane domain, and an intracellular domain of an inhibitory molecule. The inhibitory molecule can be selected from one or more of: PD-1, PD-L1, CTLA-4, TIM-3, LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, TGFR-beta, CEACAM-1, CEACAM-3, and CEACAM-5. In one embodiment, the second CAR molecule contains the extracellular domain of PD-1 or a fragment thereof.

In embodiments, the second CAR molecule in the cell also contains an intracellular signaling domain containing a basic signaling domain and/or an intracellular signaling domain.

In other embodiments, the intracellular signaling domain in the cell comprises a core signaling domain containing a functional CD3-zeta domain and a costimulatory signaling domain containing a functional 4-1BB domain.

In one embodiment, the second CAR molecule in the cell contains the amino acid sequence of SEQ ID NO: 26.

In specific embodiments, the antigen-binding domain of the first CAR molecule contains scFv and the antigen-binding domain of the second CAR molecule does not contain scFv. For example, the antigen-binding domain of the first CAR molecule contains scFv, and the antigen-binding domain of the second CAR molecule contains the camelid VHH domain.

Cleaved CAR

In some embodiments, a cleaved CAR is used in a CAR-expressing cell. The split CAR approach is described in more detail in patent publications WO2014/055442 and WO2014/055657. Briefly, a cleaved CAR system includes a cell expressing a first CAR containing a first antigen-binding domain and a costimulatory domain (e.g., 41BB), while the cell also expresses a second CAR containing a second antigen-binding domain and an intracellular signaling domain (e.g., CD3-zeta). When the cell encounters the first antigen, the co-stimulatory domain is activated and the cell proliferates. When the cell encounters the second antigen, the intracellular signaling domain is activated and cytolytic activity is triggered. Thus, a CAR-expressing cell is fully activated only in the presence of both antigens.

Expression of multiple CARs

In one aspect, a cell expressing a fusion protein, for example, as described herein, containing a domain that contains a CAR, described herein, may also contain a second fusion protein, for example, as described herein, containing a domain that contains a CAR, for example , a second CAR that contains a different antigen-binding domain, e.g., for the same target or a different target (e.g., for a target other than the cancer-associated antigen described herein, or for another cancer-associated antigen described herein) . In one embodiment, the second CAR contains an antigen-binding domain for a target expressed on the same type of cancer cell as the cancer-associated antigen. In one embodiment, a CAR-expressing cell has a first CAR that targets a first antigen and contains an intracellular signaling domain containing a co-stimulatory signaling domain but not a primary signaling domain, and a second CAR that targets a second, distinct antigen and contains an intracellular signaling domain. domain containing the main signaling domain, but not the costimulatory signaling domain. Without wishing to be bound by a particular theory, placing a co-stimulatory signaling domain, e.g., 4-1BB, CD28, CD27, or OX-40, on the first CAR and a major signaling domain, e.g. which both targets are expressed. In one embodiment, a CAR-expressing cell has a first CAR for a cancer-associated antigen containing an antigen-binding domain that binds the target antigen described herein, a transmembrane domain, and a costimulatory domain, and a second CAR that targets a different target antigen ( for example, an antigen expressed on the same type of cancer cell as the first target antigen) and contains an antigen-binding domain, a transmembrane domain, and a basic signaling domain. In another embodiment, a CAR-expressing cell has a first CAR containing an antigen-binding domain that binds the target antigen described herein, a transmembrane domain, and a major signaling domain, and a second CAR that targets an antigen other than the first target antigen ( for example, an antigen expressed on the same type of cancer cell as the first target antigen) and contains an antigen-binding domain for the antigen, a transmembrane domain, and a co-stimulatory signaling domain.

In some embodiments, the invention relates to first and second CARs, wherein the antigen-binding domain of one of said first CAR and said second CAR does not contain a light chain variable domain and a heavy chain variable domain. In some embodiments, the antigen-binding domain of one of said first CAR and said second CAR is scFv and the other is non-scFv. In some embodiments, the antigen-binding domain of one of said first CAR and said second CAR contains a single VH domain, e.g., a single camelid, shark, or lamprey VH domain, or a single VH domain derived from a human or mouse antibody sequence. In some embodiments, the antigen-binding domain of one of said first CAR and said second CAR comprises a nanobody. In some embodiments, the antigen-binding domain of one of said first CAR and said second CAR comprises a camelid VHH domain.

allogeneic cells

In the embodiments described herein, the immune effector cell may be an allogeneic immune effector cell, such as a T cell or NK cell. For example, the cell may be an allogeneic T cell, e.g., an allogeneic T cell lacking expression of a functional T cell receptor (TCR) and/or human leukocyte antigen (HLA), e.g., HLA class I and/or HLA class II, or beta-2 microglobulin (B2M).

A T cell lacking a functional TCR may, for example, be engineered such that it will not express any functional TCR on its surface, engineered such that it will not express one or more of the subunits that make up a functional TCR, such as TRAC , TRBC1, TRBC2, CD3E, CD3G, or CD3D, or designed to produce very small amounts of functional TCR on its surface. Alternatively, the T cell may express a heavily damaged TCR, for example, by expressing mutant or truncated forms of one or more of the TCR subunits. The term "substantially damaged TCR" means that the TCR will not elicit an adverse immune response in the host.

The T cell described herein can, for example, be engineered such that it does not express functional HLA on its surface. For example, the T cell described herein can be engineered such that cell surface expression of an HLA, such as HLA class I and/or HLA class II, or an HLA subunit or expression regulator, such as B2M, is reduced.

The T cell described herein can, for example, be engineered such that it does not express functional B2M on its surface. For example, the T cell described herein can be engineered such that the surface expression of B2M in such a cell is reduced.

In some embodiments, the T cell may lack a functional TCR and a functional HLA, such as HLA class I and/or HLA class II.

Modified T cells lacking functional TCR and/or HLA expression can be generated by any suitable method, including knocking out or knocking out one or more TCR or HLA subunits. For example, TCR and/or HLA can be knocked down in a T cell using siRNA, shRNA, regularly spaced short palindromic repeats (CRISPR), effector nuclease like transcription activators (TALEN), or zinc finger endonuclease (ZFN). ).

In some embodiments, the implementation of the allogeneic cell may be a cell that does not express or expresses at a low level of an inhibitory molecule, obtained, for example, by any of the methods described herein. For example, the cell may be a cell that does not express or low-express an inhibitory molecule, for example, that can reduce the ability of a CAR-expressing cell to mount an immune effector response. Examples of inhibitory molecules include PD-1, PD-L1, CTLA4, TIM3, CEACAM (e.g. CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 and TGFR -beta. Inhibition of the inhibitory molecule, for example, by inhibition at the level of DNA, RNA or protein, can lead to optimization of the functioning of the CAR-expressing cell. In embodiments, an inhibitory nucleic acid, e.g., an inhibitory nucleic acid, e.g., dsRNA, e.g., siRNA or shRNA, regularly spaced short palindromic repeats (CRISPR), an effector nuclease like transcription activators (TALEN), or an endonuclease " Zinc Fingers (ZFN), such as those described herein.

siRNA and shRNA

In some embodiments, TCR expression and/or HLA or B2M expression can be inhibited by a siRNA or shRNA that targets a nucleic acid encoding a TCR and/or HLA in a T cell.

CRISPR

As used herein, the terms "CRISPR" or "CRISPR for TCR and/or HLA" or "CRISPR for TCR and/or HLA inhibition" means a set of short palindromic repeats regularly arranged in groups, or a system containing such a set of repeats. Used in this document, the term "Cas" means CRISPR-associated protein. "CRISPR/Cas" means a system derived from CRISPR and Cas that can be used to suppress or mutate a TCR and/or HLA or B2M gene.

Artificial CRISPR/Cas systems that inhibit TCR and/or HLA can be made using technology known in the art, such as that described in US Patent Publication No. 20140068797, and Cong (2013) Science 339: 819-823. Other artificial CRISPR/Cas systems that inhibit TCR and/or HLA that are known in the art can also be prepared, for example, as described in Tsai (2014) Nature Biotechnol., 32:6 569-576, US Pat. No. 8,871,445 , 8865406, 8795965, 8771945 and 8697359.

TALEN

The terms "TALEN" or "TALEN for HLA and/or TCR" or "TALEN for inhibition of HLA and/or TCR" means an effector nuclease like transcription activators, an artificial nuclease that can be used to edit the HLA or B2M gene and/or TCR.

TALEN is produced artificially by fusing the DNA-binding domain of the TAL effector with a DNA-cleaving domain. Transcription activator-like effectors (TALE) can be designed to bind any desired DNA sequence, including an HLA or TCR gene fragment. By combining TALE with a DNA cleaving domain, a restriction enzyme can be obtained that is specific for any desired DNA sequence, including an HLA or TCR sequence. They can then be introduced into a cell where they can be used to edit the genome. Boch (2011) Nature Biotech. 29:135-6; and Boch et al. (2009) Science 326: 1509-12; Moscow et al. (2009) Science 326: 3501.

TALENs specific for sequences in HLA or TCR can be constructed using any method known in the art, including various schemes using modular components. Zhang et al. (2011) Nature Biotech. 29:149-53; Geibler et al. (2011) PLoS ONE 6: e19509.

Zinc finger nuclease for HLA and/or TCR inhibition

The terms "ZFN" or "zinc finger nuclease" or "ZFN for HLA and/or TCR" or "ZFN for HLA and/or TCR inhibition" means zinc finger nuclease, an artificial nuclease that can be used for editing HLA gene and/or TCR or B2M.

ZFNs specific for sequences in HLA and/or TCR can be constructed using any method known in the art. See, for example, Provasi (2011) Nature Med. 18:807-815; Torikai (2013) Blood 122: 1341-1349; Cathomen et al. (2008) Mol. Ther. 16:1200-7; Guo et al. (2010) J. Mol. Biol. 400:96; US Patent Publication 2011/0158957; and US Patent Publication 2012/0060230.

Telomerase expression

Without wishing to be bound by a particular theory, in some embodiments, the therapeutic T cell has a short persistence in the patient due to shortened telomeres in the T cell; accordingly, transfection of the telomerase gene can lead to lengthening of T-cell telomeres and improvement of T-cell persistence in the patient's body. See Carl June, "Adoptive T cell therapy for cancer in the clinic", Journal of Clinical Investigation, 117:1466-1476 (2007). Thus, in one embodiment, an immune effector cell, eg, a T cell, ectopically expresses a telomerase subunit, eg, a telomerase catalytic subunit, eg TERT, eg hTERT. In some aspects, this invention relates to a method for obtaining a CAR-expressing cell, including contacting the cell with a nucleic acid encoding a telomerase subunit, for example, a telomerase catalytic subunit, for example, TERT, for example, hTERT. The cell may be brought into contact with the nucleic acid before, simultaneously with, or after contact with the construct encoding the CAR.

Reproduction and activation

Immune effector cells, such as T cells, can be activated and propagated, in general, using the methods described in, for example, US Pat. 7172869, 7,232,566; 7,175,843; 5,883,223; 6,905,874;

France), а также можно использовать другие методы, общеизвестные в данной области (Berg et al., Transplant Proc. 30(8):3975-3977, 1998; Haanen et al., J. Exp. Med. 190(9):13191328, 1999; Garland et al., J. Immunol Meth. 227(1-2):53-63, 1999).Typically, a population of immune effector cells, such as cells depleted of regulatory T cells, can be expanded by bringing the cells into contact with a surface anchored to an agent that stimulates the CD3/TCR complex-associated signal and a ligand that stimulates the costimulatory molecule on the surface of T cells. In particular, T cell populations can be stimulated as described herein, for example, by contact with an anti-CD3 antibody or antigen-binding fragment thereof, or an anti-CD2 antibody immobilized on a surface, or by contact with a protein kinase C activator (for example , bryostatin) in combination with a calcium ionophore. To costimulate a helper molecule on the surface of T cells, a ligand is used that binds the helper molecule. For example, a population of T cells can be contacted with an anti-CD3 antibody and an anti-CD28 antibody under conditions suitable to promote T cell proliferation. To stimulate the proliferation of either CD4+ T cells or CD8+ T cells, an anti-CD3 antibody and an anti-CD28 antibody can be used. Examples of anti-CD28 antibodies that can be used include 9.3, B-T3, XR-CD28 (Diaclone,

France) and other methods well known in the art can also be used (Berg et al., Transplant Proc. 30(8):3975-3977, 1998; Haanen et al., J. Exp. Med. 190(9): 13191328, 1999; Garland et al., J. Immunol Meth. 227(1-2):53-63, 1999).

In some aspects, the primary stimulatory signal and the co-stimulatory signal for the T cell may be provided according to different protocols. For example, the means providing each signal may be in solution or associated with a surface. In case they are surface bound, the agents may be bound to the same surface (ie, in a "cis" arrangement) or to different surfaces (ie, in a "trans" arrangement). Alternatively, one agent may be associated with the surface and the other agent may be in solution. In one aspect, the agent providing the co-stimulatory signal is associated with the cell surface and the agent providing the primary activation signal is in solution or associated with the surface. In some aspects, both agents may be in solution. In one aspect, the agents may be in dissolved form and then cross-linked to a surface, such as a cell expressing Fc receptors, or an antibody or other binder that will bind to the agents. In this regard, see, for example, US Patent Application Publication Nos. 20040101519 and 20060034810 for descriptions of artificial antigen presenting cells (aAPCs) that are provided by the present invention for use in T cell activation and expansion.

In one aspect, the two agents are immobilized on the beads, either on the same bead, i.e., "cis", or on different beads, i.e., "trans". As an example, the agent providing the main activation signal is an anti-CD3 antibody or antigen-binding fragment thereof, and the agent providing the costimulatory signal is an anti-CD28 antibody or antigen-binding fragment thereof; and both agents are co-immobilized on the same bead in equivalent molecular amounts. In one aspect, a 1:1 ratio of all bead-bound antibodies is used to expand CD4+ T cells and grow T cells. In some aspects of the present invention, a ratio of bead-bound anti-CD3:CD28 antibodies is used such that there is an increase in T cell expansion compared to that observed using a 1:1 ratio. In one particular aspect, there is an increase of about 1-3 times over the multiplication observed when using a 1:1 ratio. In one aspect, the ratio of anti-CD3:CD28 antibodies associated with the beads is in the range from 100:1 to 1:100, including all integer values in between. In one aspect of the present invention, more anti-CD28 antibodies than anti-CD3 antibodies bind to the particles, ie, the anti-CD3:CD28 ratio is less than one. In specific aspects of the invention, the ratio of anti-CD28 antibody to anti-CD3 antibody associated with beads is greater than 2:1. In one specific aspect, a 1:100 ratio of anti-CD3:CD28 bead-bound antibodies is used. In one aspect, a 1:75 ratio of anti-CD3:CD28 bead-bound antibodies is used. In a further aspect, a 1:50 ratio of anti-CD3:CD28 bead-bound antibodies is used. In one aspect, a 1:30 ratio of anti-CD3:CD28 bead-bound antibodies is used. In one preferred aspect, a 1:10 ratio of anti-CD3:CD28 bead-bound antibodies is used. In one aspect, a 1:3 ratio of anti-CD3:CD28 bead-bound antibodies is used. In another aspect, a 3:1 ratio of anti-CD3:CD28 bead-bound antibodies is used.

Particle to cell ratios ranging from 1:500 to 500:1, including all integer values in between, can be used to stimulate T cells or other target cells. As will be understood by those skilled in the art, the ratio of particles to cells may depend on the size of the particles compared to the target cell. For example, small granules may bind only a few cells, while larger granules may bind a large number of cells. In specific aspects, the ratio of cells to particles is in the range of 1:100 to 100:1, including all intermediate integer values, and in the following aspects, a ratio of 1:9 to 9:1, including all intermediate integer values, can also be used for stimulation T cells. The ratio of anti-CD3 and anti-CD28 bound particles to T cells that results in T cell stimulation may vary as noted above, however specific preferred values include 1:100, 1:50, 1:40, 1 :30, 1:20, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1 , 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1 and 15:1, with one preferred ratio of at least 1:1 particles and T cells. In one aspect, a particle to cell ratio of 1:1 or less is used. In one particular aspect, the preferred particle:cell ratio is 1:5. In the following aspects, the ratio of particles and cells may vary depending on the day of stimulation. For example, in one aspect, the ratio of particles to cells is from 1:1 to 10:1 on the first day, and then additional particles are added to the cells every day or every other day for up to 10 days, with a final ratio ranging from 1:1 up to 1:10 (based on the number of cells per day of addition). In one specific aspect, the particle to cell ratio is 1:1 on the first day of stimulation and adjusted to 1:5 on the third and fifth days of stimulation. In one aspect, the particles are added daily or every other day, with a final ratio of 1:1 on the first day and 1:5 on the third and fifth days of stimulation. In one aspect, the particle to cell ratio is 2:1 on the first day of stimulation and adjusted to 1:10 on the third and fifth days of stimulation. In one aspect, the particles are added daily or every other day, with a final ratio of 1:1 on the first day and 1:10 on the third and fifth days of stimulation. One skilled in the art will appreciate that various other ratios may be suitable for use in the present invention. In particular, the ratio will vary depending on the size of the particles, as well as the size and type of cells. In one aspect, the most typical ratios used are in the range of 1:1, 2:1 and 3:1 on the first day.

In further aspects of the present invention, cells such as T cells are combined with agent-coated beads, the beads and cells are subsequently separated, and then the cells are cultured. In an alternative aspect, the agent-coated beads and cells are not separated but cultured together before culturing. In a further aspect, the beads and cells are first concentrated by the application of a force, such as a magnetic force, which results in enhanced ligation of cell surface markers, whereby stimulation of the cells is induced.

As an example, cell surface proteins can be ligated by bringing paramagnetic beads to which anti-CD3 and anti-CD28 antibodies are bound (3×28 beads) into contact with T cells. In one aspect, cells (eg, 10 ⁴ -10 ⁹ T cells) and beads (eg, ^DYNABEADS® M-450 CD3/CD28 T paramagnetic beads in a 1:1 ratio) are pooled in a buffer, eg, PBS (free of divalent cations). such as calcium and magnesium). Again, those skilled in the art will appreciate that any concentration of cells can be used. For example, target cells may be very rare in a sample, representing only 0.01% of the sample, or the entire sample (ie, 100%) may be target cells of interest. Accordingly, any number of cells is provided in the context of the present invention. In some aspects, it may be desirable to significantly reduce the volume in which the particles and cells are mixed together (ie, increase the concentration of cells) to ensure maximum cell-particle contact. For example, in one aspect, a concentration of about 10 billion cells/ml, 9 billion cells/ml, 8 billion cells/ml, 7 billion cells/ml, 6 billion cells/ml, 5 billion cells/ml, or 2 billion cells/ml is used. In one aspect, a concentration of greater than 100 million cells/mL is used. In a further aspect, a cell concentration of 10, 15, 20, 25, 30, 35, 40, 45, or 50 million cells/ml is used. In yet another aspect, a cell concentration of 75, 80, 85, 90, 95, or 100 million cells/ml is used. In the following aspects, concentrations of 125 or 150 million cells/ml can be used. The use of high concentrations can lead to increased cell yield, cell activation and cell proliferation. In addition, the use of high cell concentrations allows more efficient capture of cells that may weakly express target antigens of interest, such as CD28-negative T cells. Such cell populations may be of therapeutic value and may be desirable in certain aspects. For example, the use of a high concentration of cells allows more efficient selection of CD8+ T cells, which usually have a weaker expression of CD28.

In one embodiment, cells transduced with a nucleic acid encoding a fusion protein, e.g., as described herein, containing a domain that contains a CAR, e.g., a CAR described herein, are propagated, e.g., by the method described herein. In one embodiment, the cells are expanded in culture over a period of time from several hours (e.g., about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 18, 21 hours) to about 14 days (e.g., , 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days). In one embodiment, the cells are propagated over a period of 4-9 days. In one embodiment, cells are propagated over a time period of 8 days or less, such as 7, 6, or 5 days. In one embodiment, the cells are expanded in culture for 5 days and the resulting cells are more active than the same cells expanded in culture for 9 days under the same culture conditions. Activity can be determined, for example, based on various functions of T cells, for example, proliferation, destruction of target cells, production of cytokines, activation, migration, or a combination thereof. In one embodiment, cells expanded for 5 days have at least a one-, two-, three-, or four-fold increase in cell doubling upon antigen challenge compared to the same cells expanded in culture for 9 days at those same cultivation conditions. In one embodiment, cells are expanded in culture for 5 days and the resulting cells produce higher levels of pro-inflammatory cytokines, e.g., levels of IFN-γ and/or GM-CSF, compared to the same cells expanded in culture for 9 days under the same culture conditions. In one embodiment, cells expanded for 5 days experience at least a one-, two-, three-, five-, ten-fold, or greater increase in pg/ml of pro-inflammatory cytokine production, e.g., levels of IFN-γ and /or GM-CSF, compared to the same cells expanded in culture for 9 days under the same culture conditions.

It may also be desirable to run multiple cycles of stimulation so that the T cell culture time can be 60 days or more. Conditions suitable for culturing T cells include appropriate media (e.g., minimal essential or RPMI 1640 or X-vivo 15, (Lonza)), which may contain factors necessary for proliferation and viability, including serum (e.g., fetal bovine or human serum), interleukin-2 (IL-2), insulin, IFN-γ, IL-4, IL-7, GM-CSF, IL-10, IL-12, IL-15, TGFβ and TNFα, or any other cell growth supplements known to the skilled artisan. Other cell growth supplements include, but are not limited to, surfactant, plasmanate, and reducing agents such as N-acetylcysteine and 2-mercaptoethanol. Media may include RPMI 1640, AIM-V, DMEM, MEM, α-MEM, F-12, X-Vivo 15 and X-Vivo 20, Optimizer, supplemented with amino acids, sodium pyruvate and vitamins, either without serum or with adding an appropriate amount of serum (or plasma), or a certain set of hormones and/or amount of cytokine(s), which is sufficient for the growth and reproduction of T-cells. Antibiotics, for example, penicillin and streptomycin, are only included in experimental cultures and not in cell cultures that will be infused into a subject. The target cells are kept under conditions necessary to support growth, eg at the appropriate temperature (eg 37° C.) and atmospheric composition (eg air plus 5% CO ₂ ).

In one embodiment, cells are expanded in an appropriate medium (e.g., the medium described herein) containing one or more interleukins, resulting in at least 200-fold (e.g., 200-fold, 250-fold, 300-fold, 350-fold) increase in the number of cells during the 14-day propagation period, for example, when measured by the method described herein, such as flow cytometry. In one embodiment, cells are propagated in the presence of IL-15 and/or IL-7 (eg, IL-15 and IL-7).

In embodiments, the methods described herein, e.g., methods for obtaining a cell expressing a fusion protein, e.g., as described herein, containing a domain that contains a CAR, comprise removing regulatory T cells, e.g., CD25+ T cells, from a population of cells, for example, using an anti-CD25 antibody or fragment thereof, or a CD25 binding ligand, IL-2. Methods for removing regulatory T cells, eg, CD25+ T cells, from a population of cells are described herein. In embodiments, the methods, e.g., production methods, further comprise contacting a population of cells (e.g., a population of cells in which regulatory T cells, such as CD25+ T cells, have been depleted; or populations of cells that have previously been contacted with anti-CD25 antibody, fragment or CD25 binding ligand) with IL-15 and/or IL-7. For example, a population of cells (eg, that have previously been exposed to an anti-CD25 antibody, fragment thereof, or CD25 binding ligand) is expanded in the presence of IL-15 and/or IL-7.

In some embodiments, a cell expressing a fusion protein, e.g., as described herein, containing a domain that contains the CAR described herein, is contacted with a composition comprising an interleukin-15 (IL-15) polypeptide, an interleukin receptor alpha subunit polypeptide -15 (IL-15Ra), or a combination of an IL-15 polypeptide and an IL-15Ra polypeptide, eg hetIL-15, in the process of obtaining a CAR-expressing cell, eg ex vivo . In embodiments, the CAR-expressing cell described herein is contacted with an IL-15 polypeptide-containing composition during the production of the CAR-expressing cell, for example, ex vivo . In embodiments, a CAR-expressing cell as described herein is contacted with a composition comprising a combination of an IL-15 polypeptide and an IL-15Ra polypeptide during the production of a CAR-expressing cell, for example, ex vivo . In embodiments, the CAR-expressing cell described herein is contacted with a composition containing hetIL-15 during the production of the CAR-expressing cell, for example, ex vivo .

In one embodiment, a cell expressing a fusion protein, eg, as described herein, containing a domain that contains the CAR described herein, is contacted with a composition containing hetIL-15 during ex vivo propagation. In one embodiment, the CAR-expressing cell described herein is contacted with an IL-15 polypeptide-containing composition during ex vivo propagation. In one embodiment, the CAR-expressing cell described herein is contacted with a composition containing both an IL-15 polypeptide and an IL-15Ra polypeptide during ex vivo propagation. In one embodiment, such contact results in the survival and proliferation of a subpopulation of lymphocytes, eg, CD8+ T cells.

T cells that have been stimulated for different times may exhibit different characteristics. For example, typical peripheral blood mononuclear cells derived from blood or apheresis products have a population of helper T cells (TH, CD4+) that is larger than a population of cytotoxic or suppressor T cells (TC, CD8+). Ex vivo expansion of T cells by stimulation of CD3 and CD28 receptors results in a T cell population that up to about 8-9 days consists predominantly of TH cells, while after about 8-9 days the T cell population contains a much larger population of TC cells. Accordingly, depending on the goal of treatment, infusion into a subject of a population of T cells consisting predominantly of TH cells may be advantageous. Similarly, if a subset of antigen-specific TC cells has been isolated, it may be beneficial to expand that subset to a greater extent.

Moreover, in addition to the CD4 and CD8 markers, other phenotypic markers also vary significantly, but largely reproducibly, during cell division. Thus, this reproducibility allows the preparation of activated T cells to be tailored for specific purposes.

Once a fusion protein, for example as described herein, containing a domain that contains a CAR as described herein, is constructed, various assays can be used to evaluate the activity of the molecule, such as, but not limited to, the ability to proliferate T cells. after antigen stimulation, maintain T-cell proliferation in the absence of re-stimulation, as well as anti-cancer activity in appropriate in vitro and animal models. Assays for evaluating the effects of CARs of the present invention are described in more detail below.

Western blot analysis of the expression of a fusion protein, such as that described herein, containing a domain that contains CAR, can be used in primary T cells to detect the presence of monomers and dimers. See, for example, Milone et al ., Molecular Therapy 17(8): 1453-1464 (2009). Briefly, T cells (1:1 mixture of CD4 ⁺ and CD8 ⁺ T cells) expressing CAR are expanded in vitro for more than 10 days, followed by lysis and electrophoresis in SDS-PAGE under reducing conditions. CARs containing a full-length TCR-ζ cytoplasmic domain and an endogenous TCR-ζ chain are detected by Western blotting using an anti-TCR-ζ chain antibody. The same sets of T cells are used for SDS-PAGE analysis under non-reducing conditions to assess the formation of covalently bonded dimers.

In vitro expansion of T cells containing a fusion protein, eg, as described herein, containing a domain that contains CAR, eg, CAR ⁺ T cells, following antigen challenge can be measured by flow cytometry. For example, a mixture of CD4 ⁺ and CD8 ⁺ T cells stimulate αCD3/αCD28 aAPC, followed by transduction with lentiviral vectors expressing GFP under the control of promoters to be analyzed. Exemplary promoters include those for the CMV IE, EF-1α, ubiquitin C, or phosphoglycerokinase (PGK) genes. GFP fluorescence was assessed on day 6 of culture in subgroups of CD4 ⁺ and/or CD8 ⁺ T cells by flow cytometry. See, for example, Milone et al ., Molecular Therapy 17(8): 1453-1464 (2009). Alternatively, a mixture of CD4 ⁺ and CD8 ⁺ T cells are stimulated with αCD3/αCD28 coated magnetic beads on day 0 and transduced with CAR on day 1 using a bicistronic lentiviral vector expressing CAR along with eGFP using a 2A ribosome escape sequence. Cultures are restimulated with either cancer-associated antigen as described herein, K562 cells (K562 expressing cancer-associated antigen as described herein), wild-type (K562 wild-type) K562 cells, or K562 cells expressing hCD32 and 4- 1BBL, in the presence of anti-CD3 and anti-CD28 antibodies (K562-BBL-3/28) after washing. Exogenous IL-2 is added to the cultures every other day at a concentration of 100 IU/ml. The number of GFP ⁺ T cells is determined by flow cytometry, counting the number of granules. See, for example, Milone et al ., Molecular Therapy 17(8): 1453-1464 (2009).

The persistence of T cells containing a fusion protein, eg, as described herein, containing a domain that contains CAR, eg, CAR ⁺ T cells, in the absence of restimulation can also be measured. See, for example, Milone et al ., Molecular Therapy 17(8): 1453-1464 (2009). Briefly, mean T cell volume (fl) was measured on day 8 of culture using a Coulter Multisizer III particle counter, Nexcelom Cellometer Vision or Millipore Scepter, followed by stimulation with αCD3/αCD28 coated magnetic beads on day 0 and transduction with indicated CARs on day 1.

Animal models can also be used to measure CART activity. For example, a xenotransplantation model that uses human specific for the cancer-associated antigen described herein CAR ⁺ T cells to treat primary human pre-B-ALL in immunodeficient mice can be used. See, for example, Milone et al ., Molecular Therapy 17(8): 1453-1464 (2009). Briefly, after developing ALL, mice are randomly assigned to treatment groups. Different numbers of cancer-associated antigen-specific CAR-containing T cells were co-injected in a 1:1 ratio into B-ALL-bearing NOD-SCID-γ ^-/- mice. The copy number of the cancer-associated antigen-specific CAR vector in mouse spleen DNA was assessed at different time points after T-cell injection. Animals are evaluated for signs of leukemia at weekly intervals. The number of B-ALL blast cells containing the cancer-associated antigen described herein in peripheral blood is measured in mice injected with T cells with CAR for the cancer-associated antigen described herein or sham-transduced T cells . Survival curves for animal groups are compared using a log-rank test. In addition, it is also possible to analyze the absolute amount of CD4 ⁺ and CD8 ⁺ T cells in peripheral blood 4 weeks after the injection of T cells into NOD-SCID-γ ^-/- mice. Mice are injected with leukemia cells and 3 weeks later are injected with T cells engineered to express CAR with a bicistronic lentiviral vector encoding eGFP-coupled CAR. T cells are normalized to 45-50% GFP ⁺ T cells by mixing with mock transduced cells prior to injection, as confirmed by flow cytometry. Animals are assessed for signs of leukemia at 1 week intervals. Survival curves for groups of animals injected with CAR ⁺ T cells are compared using a log-rank test.

You can evaluate the dependence of the response to treatment from the dose of the fused protein, for example, described in this document containing a domain that contains CAR. See, for example, Milone et al ., Molecular Therapy 17(8): 1453-1464 (2009). For example, peripheral blood is collected 35-70 days after the onset of leukemia in mice injected on day 21 with CAR T cells, an equivalent number of mock-transduced T cells, or no T cells. Randomly selected mice from each group are bled to determine the peripheral blood count of ALL blast cells containing the cancer-associated antigen described herein and then sacrificed on days 35 and 49. The remaining animals are evaluated on days 57 and 70.

Methods for assessing cell proliferation and cytokine production have previously been described in, for example, Milone et al ., Molecular Therapy 17(8): 1453-1464 (2009). Briefly, the assessment of CAR-mediated proliferation is performed in microtiter plates by mixing washed T cells with K562 cells expressing the cancer-associated antigen described herein (K19) or CD32 and CD137 (KT32-BBL) at a final ratio of T -cell: K562, making up 2:1. K562 cells are irradiated with gamma radiation prior to use. Anti-CD3 (clone OKT3) and anti-CD28 (clone 9.3) monoclonal antibodies are added to cultures with KT32-BBL cells as a positive control to stimulate T cell proliferation as these signals support long-term expansion of CD8 ⁺ T cells ex vivo . T cells are counted in cultures using CountBright™ fluorescent beads (Invitrogen, Carlsbad, CA) and flow cytometry according to the manufacturer's instructions. CAR ⁺ T cells are determined by GFP expression in the case of T cells genetically modified with lentiviral vectors expressing eGFP-2A associated CAR. CAR+ T cells not expressing GFP are detected using a biotinylated recombinant cancer associated antigen protein described herein and an avidin-PE secondary conjugate. Simultaneously determine the expression of CD4+ and CD8 ⁺ on T-cells using specific monoclonal antibodies (BD Biosciences). Cytokine quantitation was performed on supernatants collected 24 hours after restimulation using a Human TH1/TH2 Cytokine Cytometry Bead Kit (BD Biosciences, San Diego, CA) according to the manufacturer's instructions. Fluorescence is determined on a FACScalibur flow cytometer and the data is analyzed according to the manufacturer's instructions.

Cytotoxicity can be assessed by a standard ⁵¹ Cr release assay. See, for example, Milone et al ., Molecular Therapy 17(8): 1453-1464 (2009). Briefly, target cells (K562 cells and primary pro-B-ALL cells) are loaded with ⁵¹ Cr (as NaCrO4, New England Nuclear, Boston, MA) at 37° C. for 2 hours with vigorous agitation, washed twice with complete medium RPMI and put into the wells of microtiter plates. Effector T cells are mixed in wells with target cells in complete RPMI medium at different ratios of effector cell:target cell (E:T). Additional wells are also prepared containing only medium (spontaneous release, SR) or 1% Triton X-100 detergent solution (total release, TR). After 4 hours of incubation at 37°C, collect the supernatant from each well. The release of ⁵¹ Cr is then measured using a gamma counter (Packard Instrument Co., Waltham, MA). Each sample is performed at least in triplicate and percent lysis is calculated by the formula: % lysis=(ER - SR)/(TR - SR) where ER is the average amount of ⁵¹ Cr released for each experimental condition.

Imaging techniques can be used to evaluate specific targeting and proliferation of CARs in animal tumor models. Such assays are described, for example, in Barrett et al ., Human Gene Therapy 22: 1575-1586 (2011). Briefly, NOD/SCID/γc ^−/− (NSG) mice are given iv injection of NALM6 cells followed by T cells 7 days later 4 hours after electroporation of the CAR constructs. T cells are stably transfected with a lentiviral firefly luciferase expression construct, and bioluminescence in mice is visualized. Alternatively, the therapeutic efficacy and specificity of a single injection of CAR ⁺ T cells into NALM6 tumor xenograft mice can be measured as follows: NSG mice are injected with NALM6 cells transduced to stably express firefly luciferase, followed by a single tail T vein injection 7 days later. -cells into which the CAR constructs of the present invention were introduced by electroporation. Animals are imaged at different time points after injection. For example, heat maps of the photon density of firefly luciferase-positive leukemia cells can be obtained from representative mice on day 5 (2 days before treatment) and day 8 (24 hours after CAR ⁺ PBL administration).

Other assays, including those described in the Examples section of this document, as well as those known in the art, can also be used to evaluate the CARs described herein.

Methods for obtaining CAR-expressing cells

In another aspect, the invention relates to a method for producing a cell (e.g., an immune effector cell or a population thereof) comprising introducing (e.g., transducing) into a cell, e.g., a T cell or an NK cell described herein, a vector containing a nucleic acid encoding a fusion protein, eg, as described herein, containing a domain that contains a CAR, eg, CAR, as described herein; or a nucleic acid encoding a CAR molecule, such as the CAR described herein.

The cell in the methods is an immune effector cell (eg, a T cell or an NK cell, or a combination thereof). In some embodiments, the cell in the methods is deficient in diacylglycerol kinase (DGK) and/or Ikaros.

In some embodiments, introducing a nucleic acid molecule encoding a CAR comprises transducing a vector containing a nucleic acid molecule encoding a fusion protein, for example, as described herein, containing a domain that contains a CAR, or transfecting a nucleic acid molecule encoding a CAR, wherein a nucleic acid molecule is an in vitro transcribed RNA.

In some embodiments, the method further comprises:

obtaining a population of immune effector cells (eg, T cells or NK cells); And

removal of regulatory T cells from the population, resulting in a population depleted of regulatory T cells;

wherein steps a) and b) are performed prior to the introduction of a nucleic acid encoding a fusion protein, for example, as described herein, containing a domain that contains CAR, into the cell population.

In embodiments of the methods, the regulatory T cells are CD25+ T cells and are removed from the cell population using an anti-CD25 antibody or fragment thereof. The anti-CD25 antibody, or fragment thereof, can be conjugated to a substrate, such as a bead.

In other embodiments, the regulatory T cell-depleted population obtained in step (b) contains less than 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1 % CD25+ cells.

In other embodiments, the method further comprises removing from a population of cells expressing a non-CD25 tumor antigen to obtain a population of cells depleted of regulatory T cells and tumor antigen expressing cells prior to the introduction of a nucleic acid encoding a fusion protein, e.g., as described in herein, containing a domain that contains CAR, into a population of cells. The tumor antigen may be selected from CD19, CD30, CD38, CD123, CD20, CD14 or CD11b, or combinations thereof.

In other embodiments, the method further comprises removing from a population of cells expressing an immune checkpoint inhibitor to obtain a population of cells depleted in regulatory T cells and cells expressing an inhibitory molecule, prior to the introduction of a nucleic acid encoding a fusion protein, such as that described herein. , containing a domain that contains CAR, into a population of cells. The immune checkpoint inhibitor can be selected from PD-1, LAG-3, TIM3, B7-H1, CD160, P1H, 2B4, CEACAM (e.g., CEACAM-1, CEACAM-3, and/or CEACAM-5), TIGIT, CTLA-4, BTLA and LAIR1.

The following embodiments described herein include obtaining a population of immune effector cells. The resulting immune effector cell population can be selected based on the expression of one or more of CD3, CD28, CD4, CD8, CD45RA and/or CD45RO. In specific embodiments, the immune effector cell population produced is CD3+ and/or CD28+ cells.

In specific embodiments of the method, the method further comprises expanding the cell population after the introduction of a nucleic acid molecule encoding a fusion protein, for example, as described herein, containing a domain that contains CAR.

In embodiments, the cell population is expanded for 8 days or less.

In specific embodiments, a cell population is expanded in culture for 5 days and the resulting cells are more active than the same cells expanded in culture for 9 days under the same culture conditions.

In other embodiments, a population of cells expanded in culture for 5 days has at least a one-, two-, three-, or four-fold increase in cell doubling upon antigen challenge compared to the same cells expanded in culture for 9 days. days under the same cultivation conditions.

In other embodiments, a cell population is expanded in culture for 5 days and the resulting cells produce higher levels of the pro-inflammatory cytokines IFN-γ and/or GM-CSF, compared to the same cells expanded in culture for 9 days at the same cultivation conditions.

In other embodiments, the cell population is expanded by culturing the cells in the presence of an agent that stimulates the CD3/TCR complex-associated signal and/or a ligand that stimulates a co-stimulatory molecule on the cell surface. The agent may be a bead conjugated to an anti-CD3 antibody or fragment thereof and/or an anti-CD28 antibody or fragment thereof.

In other embodiments, the cell population is expanded in an appropriate medium containing one or more interleukins, resulting in at least a 200-fold, 250-fold, 300-fold, or 350-fold increase in cell numbers over a 14-day expansion period, e.g. , when measured by flow cytometry.

In other embodiments, the cell population is expanded in the presence of IL-15 and/or IL-7.

In particular embodiments, the method also includes cryopreserving the cell population after an appropriate expansion period.

In other embodiments, the production method disclosed herein also includes contacting a population of immune effector cells with a nucleic acid encoding a telomerase subunit, such as hTERT. The nucleic acid encoding the telomerase subunit may be DNA.

The present invention also relates to a method for obtaining a population of RNA-modified cells, such as cells described herein, such as immune effector cells (eg, T cells, NK cells) transiently expressing exogenous RNA. The method includes in vitro introduction of a transcribed RNA or synthetic RNA into a cell, wherein the RNA contains a nucleic acid encoding a fusion protein, for example as described herein, containing a domain that contains the CAR molecule described herein.

In another aspect, the invention relates to a method for conferring anti-tumor immunity in a subject, comprising administering to the subject an effective amount of a cell containing a fusion protein, such as that described herein, containing a domain that contains a CAR molecule, such as a cell expressing a CAR molecule described herein. document. In one embodiment, the cell is an autologous T cell or NK cell. In one embodiment, the cell is an allogeneic T cell or NK cell. In one embodiment, the subject is a human.

In one aspect, the invention relates to a population of autologous cells that are transfected or transduced with a vector containing a nucleic acid molecule encoding a fusion protein, for example, as described herein, containing a domain that contains a CAR molecule, for example, as described herein. In one embodiment, the vector is a retroviral vector. In one embodiment, the vector is a self-inactivating lentiviral vector, as described elsewhere in this document. In one embodiment, the vector is delivered (e.g., by transfection or electroporation) into a cell, e.g., a T cell or NK cell, wherein the vector contains a nucleic acid molecule encoding a CAR of the present invention described herein, which is transcribed as a molecule mRNA, and the CAR of the present invention is translated from an RNA molecule and expressed on the cell surface.

In another aspect, the present invention relates to a population of cells expressing a fusion protein, eg, as described herein, containing a domain that contains a CAR, eg, CAR-expressing immune effector cells (eg, T cells or NK cells). In some embodiments, the population of CAR-expressing cells is a mixture of cells expressing different CARs. For example, in one embodiment, a population of CAR-expressing immune effector cells (e.g., T cells or NK cells) may include a first cell expressing a CAR containing an antigen-binding domain that binds to the first tumor antigen described herein, and a second a cell expressing a CAR containing a different antigen-binding domain that binds to the second tumor antigen described herein. As another example, a population of CAR-expressing cells may include a first cell expressing a CAR containing an antigen-binding domain that binds to a tumor antigen described herein and a second cell expressing a CAR containing an antigen-binding domain for a target other than the tumor antigen. described in this document. In one embodiment, the population of CAR-expressing cells includes, for example, a first cell expressing a CAR containing a primary intracellular signaling domain and a second cell expressing a CAR containing a secondary signaling domain, such as a costimulatory signaling domain.

In another aspect, the present invention relates to a population of cells, wherein at least one cell in the population expresses a fusion protein, for example, as described herein, containing a domain that contains a CAR containing an antigen-binding domain that binds to a tumor antigen described herein. document, and the second cell expresses another agent, for example, an agent that increases the activity of a CAR-expressing cell. For example, in one embodiment, the agent may be an agent that inhibits an inhibitory molecule. Examples of inhibitory molecules include PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g. CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG-3, VISTA, BTLA, TIGIT, LAIR1 , CD160, 2B4 and TGFR-beta. In one embodiment, an agent that inhibits an inhibitory molecule, for example, is a molecule described herein, for example, an agent that contains a first polypeptide, for example, an inhibitory molecule associated with a second polypeptide, which transmits a positive signal to the cell, for example, intracellular the signaling domain described herein. In one embodiment, the agent contains a first polypeptide, e.g. an inhibitory molecule such as PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g. CEACAM-1, CEACAM-3 and/or CEACAM-5) , LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, or TGFR-beta, or a fragment of any of them, and a second polypeptide that is an intracellular signaling domain described herein (for example, containing a co-stimulatory domain (for example , 41BB, CD27, or CD28, e.g., as described herein) and/or a major signaling domain (e.g., the CD3-zeta signaling domain described herein).In one embodiment, the agent comprises a first PD-1 polypeptide or fragment thereof, and a second intracellular signaling domain polypeptide as described herein (eg, the CD28, CD27, OX40, or 4-IBB signaling domain as described herein and/or the CD3-zeta signaling domain as described herein).

In one embodiment, a nucleic acid molecule encoding a fusion protein, eg as described herein, containing a domain that contains a CAR molecule of the present invention, eg as described herein, is expressed as an mRNA molecule. In one embodiment, genetically modified CAR-expressing cells of the present invention, e.g., immune effector cells (e.g., T cells, NK cells), can be obtained by transfection or electroporation of an RNA molecule encoding the desired CARs (e.g., without the sequence vector), in a cell. In one embodiment, the CAR molecule of the present invention is translated from the RNA molecule after it has been introduced into the cell and expressed on the surface of the recombinant cell.

A method for producing mRNA for use in transfection involves in vitro transcription (IVT) of a template with specially designed primers, followed by the addition of polyA, to produce a construct containing a 3' and 5' untranslated sequence ("UTR") (e.g., 3' and / or 5' UTR described herein), 5'-cap (for example, 5'-cap, described herein) and/or internal ribosome binding site (IRES) (for example, IRES described herein), a nucleic acid to be expressed and a polyA tail, typically 50-5000 bases long (SEQ ID NO: 32). The RNA obtained in this way can be efficiently transfected into different cell types. In one aspect, the template contains sequences for a fusion protein, such as that described herein, containing a domain that contains a CAR. In one embodiment, a vector with an RNA fusion protein, eg, as described herein, containing a domain that contains a CAR, is transduced into a cell, eg, a T cell or NK cell, by electroporation.

In one embodiment, a fusion protein, e.g., as described herein, containing a domain that contains a CAR, is introduced into immune effector cells (e.g., T cells, NK cells), e.g., using in vitro transcription, and the subject (e.g., , human) receives an initial administration of immune effector cells (e.g., T cells, NK cells) of the invention expressing a fusion protein, e.g., as described herein, containing a domain that contains CAR, and one or more subsequent administrations of immune effector cells (e.g., T cells, NK cells) of the invention expressing a fusion protein, e.g., as described herein, containing a domain that contains a CAR, with one or more subsequent administrations performed in less than 15 days, e.g., 14 , 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 days after previous administration. In one embodiment, more than one administration of CAR immune effector cells (e.g., T cells, NK cells) of the invention is administered to a subject (e.g., human) per week, e.g., 2, 3, or 4 administrations of immune effector cells with CAR (eg T cells, NK cells) of the invention. In one embodiment, the subject (e.g., human subject) receives more than one administration of CAR immune effector cells (e.g., T cells, NK cells) per week (e.g., 2, 3, or 4 administrations per week) (herein also use the term "cycle"), followed by a week without the introduction of CAR immune effector cells (e.g., T cells, NK cells), and then the subject receives one or more additional injections of CAR immune effector cells (e.g., T cells , NK cells) (eg, more than one administration of immune effector cells with CAR (eg, T cells, NK cells) per week). In another embodiment, the subject (e.g., human subject) receives more than one cycle of CAR immune effector cell administrations (e.g., T cells, NK cells) and the time interval between all cycles is less than 10, 9, 8, 7, 6, 5, 4 or 3 days. In one embodiment, CAR immune effector cells (eg, T cells, NK cells) are administered every other day, 3 injections per week. In one embodiment, the CAR immune effector cells (eg, T cells, NK cells) of the invention are administered for at least two, three, four, five, six, seven, eight, or more weeks.

In one aspect, CAR-expressing cells are generated using lentiviral viral vectors, such as lentivirus. Cells, such as CART, obtained in this way will have a stable expression of CAR.

In one aspect, CAR-expressing cells, eg CART, are generated using a viral vector, such as a gamma retroviral vector, eg, the gamma retroviral vector described herein. CARTs generated using such vectors may have stable CAR expression.

In one aspect, CARTs are transiently expressed with CAR vectors 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 days after transduction. Transient expression of CAR can be accomplished by delivery of the vector with CAR RNA. In one aspect, the CAR RNA is transduced into a T cell by electroporation.

A potential problem that may occur in patients treated with immune effector cells (eg, T cells, NK cells) transiently expressing CARs (particularly murine scFv-bearing CARTs) is anaphylaxis after multiple doses of the drug.

Without being bound by a particular theory, it is believed that such an anaphylactic reaction may occur in a patient as a result of the development of a humoral response in the form of anti-CAR antibodies, that is, anti-CAR antibodies having the IgE isotype. It is believed that in the antibody-producing cells of the patient there is a switch from the IgG isotype (which does not cause anaphylaxis) to the IgE isotype when there is a ten to fourteen day break in antigen exposure. If a patient is at high risk of developing an immune response in the form of anti-CAR antibody production during a short-term course of CAR therapy (eg, in the case of RNA transduction), interruptions in CART infusion should not last more than ten to fourteen days.

Protein Conditional Expression Methods and Therapeutic Applications

Also provided herein are methods for conditionally expressing a fusion protein (eg, containing a CAR polypeptide). Such methods may include contacting a host cell containing any of the fusion proteins described herein, or a nucleic acid encoding such a fusion protein, with an expression compound, such as a deaggregating compound or a stabilizing compound.

In the presence of a stabilizing compound, the degradation domain of the fusion protein assumes a conformation that is resistant to degradation in the cell, and the protease cleaves the protease cleavage site in the fusion protein, resulting in the degradation domain being cleaved from the target protein and expression of the target protein. In the absence of a stabilizing compound, the degradation domain of the fusion protein assumes a conformation that allows degradation in the cell, resulting in degradation of the fusion protein. In some embodiments, the host cell is contacted with the stabilizing compound in vivo . In some embodiments, the host cell is contacted ex vivo with a stabilizing compound.

In the presence of a deaggregating compound, the aggregation domain of the fusion protein assumes an oligomerization (e.g., dimerization) resistant conformation, causing the fusion protein to become monomeric and accessible to the protease and the protease cleaving the protease cleavage site in the fusion protein, resulting in cleavage of the aggregation domain from the desired protein and the expression of the desired protein. In the absence of a disaggregating compound, the aggregation domain of the fusion protein assumes a dimerizable conformation, whereby the fusion protein becomes oligomeric, eg dimeric, eg aggregated. The oligomeric, eg, dimeric, eg, aggregated state prevents the fusion protein from moving between cellular compartments or being secreted. The oligomeric, eg, dimeric, eg, aggregated state is inaccessible to the protease. In some embodiments, the host cell is contacted with a deaggregating compound in vivo . In some embodiments, the host cell is contacted ex vivo with a deaggregating compound.

The stabilizing compound may be selected based on the degradation domain. For example, if the degradation domain is derived from an estrogen receptor, the stabilizing compound may be selected from bazedoxifene or 4-hydroxy tamoxifen (4-OHT). Tamoxifen and bazedoxifene are FDA approved drugs and thus are safe for human use. If the degradation domain is derived from the FKB protein, the stabilizing compound may be Shield-1.

The disaggregating compound may be selected based on the aggregation domain. For example, if the aggregation domain is derived from FKBP, the antiaggregating compound may be selected from FK506, rapamycin, AP22542, or AP21998.

In another aspect, the present invention provides methods comprising administering a fusion protein of the invention as a therapeutic agent. Typically, such administration will be in the form of administering to the subject host cells (eg, autologous or allogeneic host cells) expressing a fusion protein of the invention. Accordingly, by administering an appropriate stabilizing compound (either in vivo or ex vivo ), the expression of the therapeutic agent (ie, the protein remaining after cleavage of the degradation domain) can be controlled. Accordingly, by administering an appropriate antiaggregating compound (either in vivo or ex vivo ), the expression of the therapeutic agent (ie, the protein remaining after cleavage of the aggregation domain) can be regulated. Thus, the expression of known synthetic therapeutic proteins or transmembrane receptors (eg, a fusion protein, eg, as described herein, containing a domain that contains the CAR molecule described herein) can be regulated. In one embodiment, the subject has a disease described herein, for example, the subject has a cancer, for example, the subject has a cancer expressing a target antigen described herein. In one embodiment, the subject is a human.

Provided herein are methods of treating a subject having a tumor antigen expression disorder by administering to the subject an effective amount of a host cell containing any of the fusion proteins described herein or a nucleic acid encoding such a fusion protein. In some embodiments, the fusion protein comprises a chimeric antigen receptor (CAR) that contains, in an N-terminal to C-terminal direction, an antigen-binding domain that specifically binds a tumor antigen, a transmembrane domain, and one or more intracellular signaling domains. In some embodiments, the host cell is autologous to the subject. In some embodiments, the implementation of the host cell is allogeneic for the specified subject. In some embodiments, the host cell is contacted with an expression compound, such as a stabilizing compound or a deaggregating compound. In the presence of a stabilizing compound, the degradation domain of the fusion protein assumes a conformation resistant to degradation in the cell, and the protease cleaves the protease cleavage site in the fusion protein, resulting in the degradation domain being cleaved from the target protein and expression of the target protein. In the absence of a stabilizing compound, the degradation domain of the fusion protein assumes a conformation that allows degradation in the cell, resulting in degradation of the fusion protein. In the presence of a disaggregating compound, the aggregation domain of the fusion protein assumes an oligomerization or aggregation resistant conformation and the protease cleaves the protease cleavage site in the fusion protein, resulting in the cleavage of the aggregation domain from the desired protein and expression of the desired protein. In the absence of a disaggregating compound, the aggregation domain of the fusion protein assumes a conformation allowing oligomerization or aggregation, resulting in aggregation of the fusion protein.

In another aspect, the invention relates to a method of treating a subject having a disease associated with the expression of a cancer-associated antigen described herein, comprising administering to the subject an effective amount of a cell containing a fusion protein containing a CAR molecule, for example, a fusion protein containing a CAR molecule, described in this document.

In another aspect, the invention relates to a method of treating a subject having a disease associated with the expression of a tumor antigen (for example, an antigen described herein), comprising administering to the subject an effective amount of a cell, for example, an immune effector cell (for example, a population of immune effector cells), containing a fusion protein containing a CAR molecule, while the CAR molecule contains an antigen-binding domain, a transmembrane domain and an intracellular domain, and the specified intracellular domain contains a co-stimulatory domain and / or the main signal domain, while the specified antigen-binding domain binds to the tumor antigen associated with the disease, for example, a tumor antigen as described herein.

In a related aspect, the invention relates to a method of treating a subject having a disease associated with the expression of a tumor antigen. The method includes administering to a subject an effective amount of a cell, e.g., an immune effector cell (e.g., a population of immune effector cells) containing a fusion protein containing a CAR molecule, in combination with an immune cell efficiency enhancing agent, wherein the immune cell efficiency enhancing agent is selected from one or more of:

(i) a protein phosphatase inhibitor;

(ii) a kinase inhibitor;

(iii) a cytokine;

(iv) an immune inhibitory molecule inhibitor; or

(v) an agent that reduces the level or activity of a T _REG cell.

In another aspect, the invention relates to a composition comprising an immune effector cell (e.g., a population of immune effector cells) containing a fusion protein containing a CAR molecule (e.g., a fusion protein containing a CAR molecule described herein) for use in the treatment of a subject, having a disease associated with the expression of a tumor antigen, for example, the disease described herein.

In specific embodiments of any of the above methods or uses, the disease associated with the tumor antigen, e.g., the tumor antigen described herein, is selected from a proliferative disease, such as cancer or early stage cancer, or a precancerous condition, myelodysplasia, myelodysplastic syndrome, or preleukemia, or a non-cancerous condition associated with the expression of a tumor antigen described herein. In one embodiment, the disease is a cancer as described herein, for example, a cancer as described herein as associated with a target as described herein. In one embodiment, the disease is a hematological cancer. In one embodiment, the hematologic cancer is leukemia. In one embodiment, the cancer is selected from the group consisting of one or more types of acute leukemia, including, but not limited to, B-cell acute lymphoid leukemia (BALL), T-cell acute lymphoid leukemia (TALL), acute lymphoid leukemia (ALL) ; one or more types of chronic leukemia, including, but not limited to, chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL); additional hematologic cancers or hematologic conditions, including, but not limited to, B-cell prolymphocytic leukemia, blast plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell or large cell follicular lymphoma, malignant lymphoproliferative conditions, MALT-type lymphoma, mantle cell lymphoma, marginal zone cell lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenström's macroglobulinemia and "preleukemia", which are a diverse set of hematological conditions united by inefficient production (or dysplasia) of myeloid blood cells; in addition, diseases associated with the expression of the tumor antigen described herein include, but are not limited to, atypical and/or non-classical cancers, early stage cancers, precancerous conditions, or proliferative diseases in which the tumor antigen described herein is expressed. ; as well as any combination of them. In another embodiment, the disease associated with the tumor antigen described herein is a solid tumor.

In specific embodiments, the methods or uses are carried out in combination with an immune effector cell efficiency enhancing agent, such as the agent described herein.

In any of the above methods and uses, the disease associated with tumor antigen expression is selected from the group consisting of proliferative disease, precancerous condition, cancer, as well as non-cancerous conditions associated with tumor antigen expression.

The cancer may be a hematologic cancer, for example, a cancer selected from one or more of chronic lymphocytic leukemia (CLL), acute leukemia, acute lymphoid leukemia (ALL), B-cell acute lymphoid leukemia (BALL), T-cell acute lymphoid leukemia (TALL), chronic myelogenous leukemia (CML), B-cell prolymphocytic leukemia, blast plasmacytoid dendritic cell neoplasms, Burkitt's lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, small or large follicular lymphoma, malignant lymphoproliferative conditions , MALT-type lymphomas, mantle cell lymphomas, marginal zone lymphomas, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasms, Waldenström's macroglobulinemia, or preleukemia.

The cancer can also be selected from colon cancer, rectal cancer, renal cell carcinoma, liver cancer, non-small cell lung carcinoma, small intestine cancer, esophageal cancer, melanoma, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, skin cancer. or intraocular malignant melanoma, endometrial cancer, ovarian cancer, rectal cancer, anus cancer, gastric cancer, testicular cancer, endometrial cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, non-Hodgkin's disease lymphoma, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethra cancer, penis cancer, pediatric solid tumors, bladder cancer, kidney or ureter cancer, renal pelvis carcinoma, neoplasms in the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brainstem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell carcinoma, T-cell lymphoma, environmental cancer, combinations of these cancers, and metastatic foci of these types of cancer.

In specific embodiments of the methods or uses described herein, the cell is administered in combination with an agent that enhances cell performance, e.g., one or more of a protein phosphatase inhibitor, a kinase inhibitor, a cytokine, an immune inhibitory molecule inhibitor, or an agent that reduces the level or activity of T _REG cells.

In specific embodiments of the methods or uses described herein, the protein phosphatase inhibitor is an SHP-1 inhibitor and/or an SHP-2 inhibitor.

In other embodiments of the methods or uses described herein, the kinase inhibitor is selected from one or more of a CDK4 inhibitor, a CDK4/6 inhibitor (eg, palbociclib), a BTK inhibitor (eg, ibrutinib or RN-486), an mTOR inhibitor ( for example, rapamycin or everolimus (RAD001)), an MNK inhibitor, or a dual P13K/mTOR inhibitor. In one embodiment, the BTK inhibitor does not reduce or inhibit the kinase activity of interleukin-2 inducible kinase (ITK).

In other embodiments of the methods or uses described herein, the agent that inhibits an immune inhibitory molecule includes an antibody or antibody fragment that inhibits a nucleic acid, CRISPR-like short palindromic repeats, an effector nuclease like transcription activators ( TALEN), or zinc finger endonuclease (ZFN), inhibiting the expression of the inhibitory molecule.

In other embodiments of the methods or uses described herein, the agent that reduces the level or activity of a T _REG cell is selected from cyclophosphamide, an anti-GITR antibody, CD25 depletion, or a combination thereof.

In specific embodiments of the methods or uses described herein, the immune inhibitory molecule is selected from the group consisting of PD-1, PD-L1, CTLA-4, TIM-3, LAG-3, VISTA, BTLA, TIGIT, LAIR1 , CD160, 2B4, TGFR-beta, CEACAM-1, CEACAM-3 and CEACAM-5.

In other embodiments, the agent that inhibits the inhibitory molecule comprises a first polypeptide containing the inhibitory molecule or a fragment thereof and a second polypeptide that transmits a positive signal to the cell, and wherein the first and second polypeptides are expressed on CAR-containing immune cells, wherein (i ) the first polypeptide includes PD-1, PD-L1, CTLA-4, TIM-3, LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, TGFR-beta, CEACAM-1, CEACAM-3 and CEACAM-5, or their fragment; and/or (ii) the second polypeptide comprises an intracellular signaling domain containing a basic signaling domain and/or a costimulatory signaling domain. In one embodiment, the main signaling domain contains a functional CD3-zeta domain; and/or the costimulatory signaling domain comprises a functional domain of a protein selected from 41BB, CD27 and CD28.

In other embodiments, the cytokine is selected from IL-7, IL-15, IL-18, or IL-21, or combinations thereof.

In other embodiments, an immune effector cell containing a fusion protein and a second agent, such as any of the combination therapies disclosed herein (eg, an immune effector cell performance enhancing agent), are administered substantially simultaneously or sequentially.

In other embodiments, an immune cell containing a fusion protein is administered in combination with a molecule that targets GITR and/or modulates GITR function. In specific embodiments, a molecule that targets GITR and/or modulates GITR function is administered prior to the introduction of a CAR-expressing cell or cell population, or prior to apheresis.

In one embodiment, a lymphocyte infusion, eg an allogeneic lymphocyte infusion, is used to treat cancer, wherein the infused lymphocytes comprise at least one CAR expressing cell of the present invention. In one embodiment, autologous lymphocyte infusion is used in the treatment of cancer, wherein the infused autologous lymphocytes comprise at least one CAR-expressing cell as described herein.

In one embodiment, the cell is a T cell and the T cell is diacylglycerol kinase (DGK) deficient. In one embodiment, the cell is a T cell and the T cell is Ikaros deficient. In one embodiment, the cell is a T cell and the T cell is deficient in both DGK and Ikaros.

In one embodiment, the method comprises administering to a cell expressing a fusion protein containing the CAR molecule described herein, in combination with an agent that increases the activity of a CAR-expressing cell, wherein the agent is a cytokine, e.g., IL-7, IL-15 , IL-18, IL-21, or a combination thereof. The cytokine can be delivered in conjunction with the administration of the CAR expressing cell, for example, simultaneously with or shortly after the administration of the cell. Alternatively, the cytokine can be delivered over an extended period of time after administration of the CAR-expressing cell, for example, after evaluating the subject's response to the CAR-expressing cell. In one embodiment, the cytokine is administered to the subject simultaneously (e.g., administered on the same day) or shortly after administration (e.g., administered 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days after administration) of the cells or a population of cells according to any one of paragraphs. 61-80. In other embodiments, the cytokine is administered to the subject after an extended period of time (e.g., at least 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks or more) after administration of the cell or cell population according to any one of paragraphs. 61-80, or after evaluating the subject's response to the cell.

In other embodiments, cells expressing a fusion protein containing a CAR molecule are administered in combination with an agent that ameliorates one or more side effects associated with administration of a cell expressing a CAR molecule. Side effects associated with administration of a CAR expressing cell can be selected from cytokine release syndrome (CRS) or hemophagocytic lymphohistiocytosis (HLH).

In embodiments of any of the above methods or uses, cells expressing a CAR molecule are administered in combination with an agent that treats a disease associated with tumor antigen expression, such as any of the second or third therapies disclosed herein. Additional illustrative combinations include one or more of the following.

In another embodiment, a cell expressing a CAR molecule, eg, as described herein, can be administered in combination with another agent, eg, a kinase inhibitor and/or an immune checkpoint inhibitor, as described herein. In one embodiment, the cell expressing the CAR molecule may also express another agent, such as an agent that increases the activity of the CAR-expressing cell.

For example, in one embodiment, the agent that increases the activity of a CAR-expressing cell may be an agent that inhibits an inhibitory molecule (eg, an immune inhibitory molecule). Examples of inhibitory molecules include PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g. CEACAM-1, CEACAM-3 and/or CEACAM-5), LAG-3, VISTA, BTLA, TIGIT, LAIR1 , CD160, 2B4 and TGFR-beta.

In one embodiment, the agent that inhibits the inhibitory molecule is an inhibitory nucleic acid such as dsRNA, siRNA, or shRNA. In embodiments, the inhibitory nucleic acid is linked to a nucleic acid encoding a component of a CAR molecule. For example, an inhibitory molecule may be expressed on a CAR-expressing cell.

In another embodiment, an agent that inhibits an inhibitory molecule, for example, is a molecule described herein, for example, an agent that contains a first polypeptide, for example, an inhibitory molecule associated with a second polypeptide, which transmits a positive signal to the cell, for example, intracellular the signaling domain described herein. In one embodiment, the agent contains a first polypeptide, e.g. an inhibitory molecule such as PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g. CEACAM-1, CEACAM-3 and/or CEACAM-5) , LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 or TGFR-beta, or a fragment of any of them (for example, at least part of the extracellular domain of any of them), and a second polypeptide that is an intracellular signaling domain described herein (e.g., containing a co-stimulatory domain (e.g., 41BB, CD27, or CD28, e.g., described herein) and/or a major signaling domain (e.g., the CD3-zeta signaling domain described herein). In one in an embodiment, the agent comprises a first PD-1 polypeptide or fragment thereof (e.g., at least a portion of the extracellular domain of PD-1), and a second intracellular signaling domain polypeptide described herein (e.g., the CD28 signaling domain described herein, and /or the CD3-zeta signaling domain described herein).

In one embodiment, a cell of the invention, such as a T cell or NK cell, is administered to a subject who has previously received a stem cell transplant, such as an autologous stem cell transplant.

In one embodiment, a cell of the present invention, such as a T cell or NK cell, is administered to a subject who has previously received a dose of melphalan.

In one embodiment, a cell expressing a fusion protein containing a CAR molecule, such as the CAR molecule described herein, is administered in combination with an agent that enhances the performance of the cell expressing the CAR molecule, such as the agent described herein.

In one embodiment, cells expressing a fusion protein containing a CAR molecule, such as the CAR molecule described herein, are administered in combination with a low, immunostimulatory dose of an mTOR inhibitor. Without wishing to be bound by a particular theory, it is believed that administration of a low, immunostimulatory dose (eg, a dose that is insufficient to completely suppress the immune system, but sufficient to improve immune function) is accompanied by a decrease in PD-1 positive T cells or an increase in PD- 1-negative cells. PD-1 positive T cells, but not PD-1 negative T cells, can be depleted by interaction with cells expressing a PD-1 ligand, such as PD-L1 or PD-L2.

In one embodiment, this approach can be used to optimize the performance of the CAR cells described herein in a subject. Without wishing to be bound by a particular theory, it is believed that in one embodiment, the performance of endogenous, unmodified immune effector cells, eg, T cells or NK cells, is improved. Without wishing to be bound by a particular theory, it is believed that in one embodiment, the performance of a cell expressing a CAR for a target antigen is improved. In other embodiments, cells, e.g., T cells or NK cells, that have been, or will be, genetically modified to express CAR, can be treated ex vivo by contact with an amount of an mTOR inhibitor that results in an increase in PD-1-negative immune effector cells, eg T cells, or an increase in the ratio of PD-1 negative immune effector cells, eg T cells/PD-1 positive immune effector cells, eg T cells.

In one embodiment, administration of a low, immunostimulatory dose of an mTOR inhibitor, such as an allosteric inhibitor, such as RAD001, or a catalytic inhibitor, is started prior to administration of a CAR expressing cell as described herein, such as a T cell or NK cell. In one embodiment, the CAR cells are administered after a sufficient period of time following administration, or a sufficient number of administrations, of doses of the mTOR inhibitor such that the number of PD-1 negative immune effector cells, e.g., T cells or NK cells, is either the ratio of PD-1 negative immune effector cells, eg T cells/PD-1 positive immune effector cells, eg T cells, at least temporarily increased.

In one embodiment, a cell, such as a T cell or NK cell, to be genetically modified to express CAR is harvested after a sufficient period of time following administration, or a sufficient number of administrations, of a low, immunostimulatory dose of an mTOR inhibitor such that the amount PD-1 negative immune effector cells, eg T cells or NK cells, or PD-1 negative immune effector cells, eg T cells/PD-1 positive immune effector cells, eg T cells , in the subject or in a sample obtained from the subject, at least temporarily increased.

In one embodiment, a cell expressing a fusion protein containing a CAR molecule, e.g., the CAR molecule described herein, is administered in combination with an agent that ameliorates one or more of the side effects associated with administration of the cell expressing the CAR molecule, e.g., an agent described in this document.

In one embodiment, a cell expressing a fusion protein containing a CAR molecule, e.g., the CAR molecule described herein, is administered in combination with an agent that treats a disease associated with a cancer-associated antigen described herein, e.g., an agent described in this document.

In one embodiment, a cell expressing two or more fusion proteins containing CAR molecules, such as those described herein, is administered to a subject in need thereof for cancer treatment. In one embodiment, a cell population comprising a cell expressing a fusion protein containing a CAR, such as described herein, is administered to a subject in need thereof for cancer treatment.

In one embodiment, a cell expressing a fusion protein containing a CAR molecule, such as the CAR molecule described herein, is administered at the doses and/or using the administration regimens described herein.

In one embodiment, a fusion protein containing a CAR molecule is introduced into immune effector cells (e.g., T cells, NK cells), e.g., using in vitro transcription, and the subject (e.g., human) receives an initial administration of cells containing the fusion a protein containing a CAR molecule and one or more subsequent injections of cells containing a fusion protein containing a CAR molecule, with one or more subsequent injections performed in less than 15 days, for example, 14, 13, 12, 11, 10, 9 , 8, 7, 6, 5, 4, 3 or 2 days after the previous administration. In one embodiment, more than one injection of cells containing a fusion protein containing a CAR molecule is performed on a subject (e.g., a human) per week, for example, 2, 3, or 4 injections of cells containing a fusion protein containing a CAR molecule are performed per week. In one embodiment, a subject (e.g., a human subject) receives more than one injection of cells containing a fusion protein containing a CAR molecule per week (e.g., 2, 3, or 4 injections per week) (the term "cycle" is also used herein) ), followed by a week without administration of cells containing a fusion protein containing a CAR molecule, and then the subject receives one or more additional injections of cells containing a CAR molecule (for example, more than one injection of cells containing a CAR molecule per week). In another embodiment, the subject (e.g., human subject) receives more than one cycle of administrations of cells containing a fusion protein containing a CAR molecule, and the time interval between all cycles is less than 10, 9, 8, 7, 6, 5, 4, or 3 days. In one embodiment, cells containing a fusion protein containing a CAR molecule are administered every other day, 3 injections per week. In one embodiment, cells containing a fusion protein containing a CAR molecule are administered for at least two, three, four, five, six, seven, eight or more weeks.

In one embodiment, cells expressing a fusion protein containing a CAR molecule, such as the CAR molecule described herein, are administered as first line therapy for a disease, such as cancer, such as the cancer described herein. In another embodiment, cells expressing a fusion protein containing a CAR molecule, e.g., the CAR molecule described herein, are administered as second, third, fourth line therapy for a disease, e.g., cancer, e.g., the cancer described herein.

In one embodiment, a population of cells described herein is administered.

In another aspect, the invention relates to a cell expressing a fusion protein containing the CAR molecule described herein for use as a drug in combination with a kinase inhibitor and/or immune checkpoint inhibitor described herein. In another aspect, the invention provides a kinase inhibitor and/or immune checkpoint inhibitor described herein for use as a drug in combination with a cell expressing the CAR molecule described herein.

In another aspect, the invention relates to a cell expressing a fusion protein containing the CAR molecule described herein, for use in combination with a cytokine, for example, IL-7, IL-15 and/or IL-21, described herein, in treatment of a disease associated with the expression of a tumor antigen that is a target for CAR. In another aspect, the invention provides a cytokine described herein for use in combination with a cell expressing a fusion protein comprising a CAR molecule described herein in the treatment of a disease associated with the expression of a CAR-targeted tumor antigen.

In another aspect, the invention relates to a cell expressing a fusion protein containing the CAR molecule described herein for use in combination with a kinase inhibitor and/or immune checkpoint inhibitor described herein in the treatment of a disease associated with the expression of a tumor antigen. , which is a target for CAR. In another aspect, the invention provides a kinase inhibitor and/or an immune checkpoint inhibitor described herein for use in combination with a cell expressing a fusion protein comprising the CAR molecule described herein in the treatment of a disease associated with the expression of a tumor antigen. , which is a target for CAR.

In another aspect, the present invention provides a method comprising administering a fusion protein comprising a CAR molecule, such as the CAR molecule described herein, or a cell containing a nucleic acid encoding a fusion protein comprising a CAR molecule, such as the CAR molecule described in this document. In one embodiment, the subject has the disease described herein, eg, the subject has cancer, eg, the subject has cancer and has tumor-supporting cells that express the tumor-supporting antigen described herein. In one embodiment, the subject is a human.

In one embodiment of the methods or uses described herein, a fusion protein containing a CAR molecule is administered in combination with another agent. In one embodiment, the agent may be a kinase inhibitor, such as a CDK4/6 inhibitor, a BTK inhibitor, an mTOR inhibitor, an MNK inhibitor, or a dual PI3K/mTOR inhibitor, and combinations thereof. In one embodiment, the kinase inhibitor is a CDK4 inhibitor, e.g., a CDK4 inhibitor as described herein, e.g., a CD4/6 inhibitor, such as, e.g., 6-acetyl-8-cyclopentyl-5-methyl-2-(5- piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3- d ]pyrimidin-7-one hydrochloride (also called palbociclib or PD0332991). In one embodiment, the kinase inhibitor is a BTK inhibitor, such as a BTK inhibitor described herein, such as, for example, ibrutinib. In one embodiment, the kinase inhibitor is an mTOR inhibitor, such as an mTOR inhibitor described herein, such as, for example, rapamycin, a rapamycin analog, OSI-027. An mTOR inhibitor may be, for example, an mTORC1 inhibitor and/or an mTORC2 inhibitor, such as an mTORC1 inhibitor and/or an mTORC2 inhibitor as described herein. In one embodiment, the kinase inhibitor is an MNK inhibitor, such as an MNK inhibitor as described herein, such as, for example, 4-amino-5-(4-fluoroanilino)-pyrazolo[3,4- d ]pyrimidine. The MNK inhibitor may be, for example, an inhibitor of MNK1a, MNK1b, MNK2a and/or MNK2b. The dual PI3K/mTOR inhibitor can be, for example, PF-04695102.

In one embodiment of the methods or uses described herein, the kinase inhibitor is a CDK4 inhibitor selected from aloisin A; flavopyridol or HMR-1275, 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methyl-4-piperidinyl]-4-chromenone; crizotinib (PF-02341066; 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methyl-3-pyrrolidinyl]-4H-1-benzopyran- 4-one hydrochloride (P276-00);1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy] -N- [4-(trifluoromethyl )phenyl]-1H-benzimidazol-2-amine (RAF265), indiesulam (E7070), roscovitine (CYC202), palbociclib (PD0332991), dinacyclib (SCH727965), N-[5-[[(5- tert- butyloxazole-2 -yl)methyl]thio]thiazol-2-yl]piperidine-4-carboxamide (BMS 387032);4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4- d ][2]benzazepin-2-yl]amino]-benzoic acid (MLN8054);5-[3-(4,6-difluoro-1H-benzimidazol-2-yl)-1H-indazol-5-yl]-N -ethyl-4-methyl-3-pyridinemethanamine (AG-024322);4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid N-(piperidin-4-yl)amide (AT7519);4- [2-methyl-1-(1-methylethyl)-1H-imidazol-5-yl] -N- [4-(methylsulfonyl)phenyl]-2-pyrimidinamine (AZD5438) and XL281 (BMS908662).

In one embodiment of the methods or uses described herein, the kinase inhibitor is a CDK4 inhibitor such as palbociclib (PD0332991) and palbociclib is administered at a dose of about 50 mg, 60 mg, 70 mg, 75 mg, 80 mg, 90 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg (for example, 75 mg, 100 mg, or 125 mg) daily for a period of time, for example, daily for 14 -21 days of a 28 day cycle or daily for 7-12 days of a 21 day cycle. In one embodiment, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more cycles of palbociclib administration are used.

In one embodiment of the methods or uses described herein, the kinase inhibitor is a BTK inhibitor selected from ibrutinib (PCI-32765); GDC-0834; RN-486; CGI-560; CGI-1764; HM-71224; CC-292; ONO-4059; CNX-774 and LFM-A13. In one embodiment, the BTK inhibitor does not reduce or inhibit the kinase activity of interleukin-2-inducible kinase (ITK) and is selected from GDC-0834; RN-486; CGI-560; CGI-1764; HM-71224; CC-292; ONO-4059; CNX-774 and LFM-A13.

In one embodiment of the methods or uses described herein, the kinase inhibitor is a BTK inhibitor, e.g., ibrutinib (PCI-32765), and ibrutinib is administered at a dose of about 250 mg, 300 mg, 350 mg, 400 mg, 420 mg , 440 mg, 460 mg, 480 mg, 500 mg, 520 mg, 540 mg, 560 mg, 580 mg, 600 mg (eg, 250 mg, 420 mg, or 560 mg) daily for a period of time, such as daily at for a 21 day cycle or daily for a 28 day cycle. In one embodiment, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more cycles of ibrutinib are used.

In one embodiment of the methods or uses described herein, the kinase inhibitor is a BTK inhibitor that does not inhibit ITK kinase activity, e.g., RN-486, and RN-486 is administered at a dose of about 100 mg, 110 mg, 120 mg , 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg ) daily for some period of time, such as daily for a 28-day cycle. In one embodiment, 1, 2, 3, 4, 5, 6, 7 or more cycles of RN-486 administration are used.

In one embodiment of the methods or uses described herein, the kinase inhibitor is an mTOR inhibitor selected from temsirolimus; ridaforolimus (1R,2R,4S)-4-[(2R)-2-[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28Z,30S,32S,35R) -1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30 ,3,1,0 ^4,9 ]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl dimethylphosphinate, also known as AP23573 and MK8669; everolimus (RAD001); rapamycin (AY22989); simapimoda; (5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxyphenyl)methanol (AZD8055); 2-amino-8-[ trans -4-(2-hydroxyethoxy)cyclohexyl]-6-(6-methoxy-3-pyridinyl)-4-methylpyrido[2,3- d ]pyrimidin-7(8H)-one ( PF04691502) and N ² -[1,4-dioxo-4-[[4-(4-oxo-8-phenyl-4H-1-benzopyran-2-yl)morpholinium-4-yl]methoxy]butyl]-L -arginylglycyl-L-α-aspartyl-L-serine (SEQ ID NO: 264), internal salt (SF1126), and XL765.

In one embodiment of the methods or uses described herein, the kinase inhibitor is an mTOR inhibitor, such as rapamycin, and rapamycin is administered at a dose of about 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg (eg 6 mg) daily for a period of time, eg daily for a 21 day cycle or daily for a 28 day cycle. In one embodiment, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more cycles of rapamycin are used. In one embodiment, the kinase inhibitor is an mTOR inhibitor, such as everolimus, and everolimus is administered at a dose of about 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg (eg 10 mg) daily for a period of time, eg daily for a 28 day cycle. In one embodiment, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more cycles of everolimus are used.

In one embodiment of the methods or uses described herein, the kinase inhibitor is an MNK inhibitor selected from CGP052088; 4-amino-3-(p-fluorophenylamino)pyrazolo[3,4- d ]pyrimidine (CGP57380); cercosporamide; ETC-1780445-2 and 4-amino-5-(4-fluoroanilino)pyrazolo[3,4- d ]pyrimidine.

In one embodiment of the methods or uses described herein, the kinase inhibitor is a dual phosphatidylinositol 3-kinase (PI3K) and mTOR inhibitor selected from 2-amino-8-[trans-4-(2-hydroxyethoxy)cyclohexyl ]-6-(6-methoxy-3-pyridinyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one (PF-04691502); N-[4-[[4-(dimethylamino)-1-piperidinyl]carbonyl]phenyl]-N'-[4-(4,6-di-4-morpholinyl-1,3,5-triazin-2-yl )phenyl]urea (PF-05212384, PKI-587); 2-methyl-2-{4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl] phenyl}propanenitrile (BEZ-235); apitolisib (GDC-0980, RG7422); 2,4-difluoro-N-{2-(methyloxy)-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl}benzenesulfonamide (GSK2126458); 8-(6-methoxypyridin-3-yl)-3-methyl-1-(4-(piperazin-1-yl)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]quinoline-2 (3H)-one maleic acid (NVP-BGT226); 3-[4-(4-morpholinylpyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol (PI-103); 5-(9-isopropyl-8- methyl-2-morpholino-9H-purin-6-yl)pyrimidin-2-amine (VS-5584, SB2343) and N-[2-[(3,5-dimethoxyphenyl)amino]quinoxalin-3-yl]-4 -[(4-methyl-3-methoxyphenyl)carbonyl]aminophenylsulfonamide (XL765).

In one embodiment of the methods or uses described herein, a cell containing a fusion protein described herein is administered to a subject in combination with a protein tyrosine phosphatase inhibitor, e.g., a protein tyrosine phosphatase inhibitor described herein. In one embodiment, the protein tyrosine phosphatase inhibitor is an SHP-1 inhibitor, such as an SHP-1 inhibitor described herein, such as, for example, sodium stibogluconate. In one embodiment, the protein tyrosine phosphatase inhibitor is an SHP-2 inhibitor.

In one embodiment of the methods or uses described herein, a cell containing a fusion protein described herein is administered in combination with another agent, and the agent is a cytokine. The cytokine may be, for example, IL-7, IL-15, IL-21, or a combination thereof. In another embodiment, a cell containing a fusion protein described herein is administered in combination with an immune checkpoint inhibitor, eg, an immune checkpoint inhibitor described herein. For example, in one embodiment, the immune checkpoint inhibitor inhibits an inhibitory molecule selected from PD-1, PD-L1, CTLA-4, TIM-3, CEACAM (e.g., CEACAM-1, CEACAM-3 and/or CEACAM-5) , LAG-3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 and TGFR-beta.

In one aspect, the fusion protein described herein can be used to kill normal cells expressing the tumor antigen described herein, i.e., it is suitable for use as a cell conditioning therapy prior to cell transplantation. In one aspect, the normal cell expressing the tumor antigen described herein is a normal stem cell and the cell transplant is a stem cell transplant.

Methods of treating conditions caused by autoantibodies or alloantibodies

The present invention relates to methods for treating autoantibody or alloantibody induced diseases or conditions in a subject by targeting B cells, including autoantibody or alloantibody producing B cells, modified T cells directed against B cells. In one embodiment, after B cells have been depleted of modified T cells or after an adverse reaction to modified T cells has occurred, the modified T cells are selectively ablated from the subject by activating the suicide gene that has been introduced into the modified T cells.

In one aspect, the invention relates to a method of treating an autoantibody or alloantibody induced disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of a pharmaceutical composition comprising a modified T cell. The modified T cell contains a nucleic acid containing a suicide gene and a nucleic acid encoding a chimeric antigen receptor containing an anti-B cell binding domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain.

In one embodiment, the method further comprises inducing expression of the suicide gene to produce a suicide gene product that kills the modified T cell. In one such embodiment, administration of an inducing agent causes the expression of a suicide gene. In another embodiment, induction of suicide gene expression occurs after the modified T cell has a cytotoxic effect on B cells, or after the subject has begun to experience an adverse reaction to the modified T cell.

In another embodiment, the method further comprises activating the suicide gene product to induce death of the modified T cell. In one such embodiment, administration of an activating agent is used to promote dimerization of the suicide gene product to activate the suicide gene product. In another embodiment, activation of the suicide gene product occurs after the modified T cell has a cytotoxic effect on B cells, or after the subject begins to experience an adverse reaction to the modified T cell, or after a therapeutic effect has been achieved.

In another embodiment, the method further comprises inhibiting suicide gene expression to inhibit death of the modified T cell. In one such embodiment, administration of an inhibitory agent results in inhibition of the expression of the suicide gene. In another embodiment, administration of the inhibitory agent is concurrent with administration of the modified T cell, continued while the modified T cell is cytotoxic to B cells, and may be discontinued once the subject develops an adverse reaction to the modified T cell.

In another embodiment, the method includes suppressing the activation of the suicide gene product to suppress the death of the modified T cell. In one such embodiment, administration of a solubilizing agent prevents dimerization of the suicide gene product to prevent activation of the suicide gene product. In another embodiment, administration of the solubilizing agent is concurrent with administration of the modified T cell, continued while the modified T cell is cytotoxic to B cells, and may be discontinued after the subject develops an adverse reaction to the modified T cell or after a therapeutic response has been reached. effect.

In another embodiment, the method further comprises administering a solubilizing agent to prevent dimerization of the CAR, wherein the CAR is linked to a dimerization domain, such as the dimerization domain of FKBP or the like. In such an embodiment, CAR molecules spontaneously aggregate in the cytoplasm or other internal zone, thereby preventing the presentation of CAR molecules on the surface of the modified T cell. In another embodiment, administration of the solubilizing agent is concurrent with administration of the modified T cell, continued while the modified T cell has a cytotoxic effect on B cells, and may be discontinued after the subject develops an adverse reaction to the modified T cell or after a therapeutic response has been reached. effect.

The modified T cells can be administered to an animal, preferably a mammal, even more preferably a human, to suppress an immune response, such as those that are common in an autoimmune disease or condition, or in an alloantibody-induced disease or condition.

In addition, the modified T cells of the present invention can be used to treat any condition in which it is desirable to reduce or otherwise inhibit the immune response, especially the cell-mediated immune response, to treat or attenuate the disease. In one aspect, the invention relates to the treatment of a condition, such as an autoantibody or alloantibody induced disease, in a subject, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a modified T cell as described herein.

Examples of diseases caused by autoanthils or conditions include, but without restriction, bullous pomfigoid, acquired bullet epidermolysis, p200 pemphigoid, lineman Iga-dependent bullous dermatosis, other diseases of the pemphigoid disease group, herpetiform dermatitis, glueen-sensitive virgin soil, mysteen, targetpasser syndrome, granulomatia syndrome, granul Z with polyangititis and other ANCA+ forms of vasculitis, autoimmune encephalitis involving the limbic system, anti-NMDA receptor encephalitis, neuromyelitis of the optic nerve, autoimmune hemolytic anemia, autoantibody-induced target organ damage in lupus and other connective tissue diseases (caused by anti-dsDNA, anti-Ro and other autoantibodies), Graves' disease and Hashimoto's thyroiditis, production of antibodies against insulin in diabetes, antibodies against insulin receptors in autoimmune hypoglycemia, cryoglobulinemia, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, dermatomyositis, production of antibodies against Fc-epsilon receptors in chronic idiopathic urticaria, antibodies against folate receptors, antibodies against endothelial receptors or against adrenergic receptors in pulmonary arterial hypertension, refractory hypertension, dilated cardiomyopathy, and autoinflammatory syndrome.

Examples of an alloantibody-induced disease or condition include, but are not limited to, immune response to organ transplantation, blood transfusion and production of antibodies specific for HLA and/or β2-donor microglobulin, sensitization during pregnancy by blood group or Rh antigens, or protein replacement therapy, for example, factor VIII, α-L-iduronidase, collagen type VII, and so on, including, but not limited to, replacement proteins listed in Gorzelany, et al. (Sci. Transl. Med., 5(178):178s10, 2013).

In one embodiment, the disease or condition is pemphigus. Longitudinal analysis of B cell repertoires in patients with pemphigus during treatment showed that patients with pemphigus relapse with the same anti-Dsg B cell clones seen in active disease. Taken together, these data indicate that a single but indeed complete depletion of B cells resulting in the elimination of anti-Dsg B cell clones by targeting a pan B cell marker such as CD20 or alternatively CD19 may lead to complete healing of patients with pemphigus. Pathological clones will be eliminated and the healthy B-cell repertoire will be reformed, and another rare tolerance disorder is unlikely to recur.

By analogy, the same approach should also be effective for any B-cell- or antibody-mediated disease; for example, diseases caused by alloantibodies resulting from blood transfusion or sensitization during pregnancy, HLA donor-specific alloantibodies complicating organ transplantation, and alloantibodies resulting from protein replacement therapy in genetic diseases. Even if alloantibodies reappear due to repeated alloantigen exposure, periodically repeated treatment to completely, but temporarily, eliminate B cells (and, as a result, alloantibodies) will be useful in such diseases.

Pharmaceutical compositions

Pharmaceutical compositions of the present invention may contain any fusion protein, a nucleic acid encoding such a fusion protein as described herein, and one or more pharmaceutically or physiologically acceptable carriers, diluents, or excipients. Such compositions may contain buffers such as neutral buffered saline, phosphate buffered saline, and the like; carbohydrates such as glucose, mannose, sucrose or dextrans, mannitol; proteins; polypeptides or amino acids such as glycine; antioxidants; chelating agents such as EDTA or glutathione; adjuvants (eg aluminum hydroxide); and preservatives. In one aspect, the compositions of the present invention are formulated for intravenous administration.

The pharmaceutical compositions of the present invention may be administered in a manner appropriate to the disease to be treated (or prevented). The number and frequency of administrations will be determined by such factors as the health of the patient and the type and severity of the patient's disease, although appropriate doses may be determined in clinical trials.

In one aspect, the invention relates to a pharmaceutical composition formulated for use in the method described herein, which contains a modified T cell containing a nucleic acid encoding a suicide gene and a nucleic acid encoding a chimeric antigen receptor containing an anti-B cell binding domain, transmembrane domain, costimulatory domain, and intracellular signaling domain.

In another aspect, the invention relates to a pharmaceutical composition formulated for use in the method described herein, which contains a modified T cell containing a nucleic acid encoding a dimerization domain and a chimeric antigen receptor (CAR) containing an anti-B cell binding domain , a transmembrane domain, a costimulatory domain, and an intracellular signaling domain.

In one embodiment, the pharmaceutical composition is substantially free of, e.g., does not contain detectable levels, of a contaminant, e.g., selected from the group consisting of endotoxin, mycoplasma, replication competent lentivirus (RCL), p24, VSV-G nucleic acid, HIV gag, anti-CD3/anti-CD28 antibody coated residual beads, mouse antibodies, pooled human serum, bovine serum albumin, bovine serum, culture media components, vector packaging cells or plasmid components, bacteria and fungi. In one embodiment, the bacterium is at least one bacterium selected from the group consisting of Alcaligenes faecalis , Candida albicans , Escherichia coli , Haemophilus influenza , Neisseria meningitides , Pseudomonas aeruginosa , Staphylococcus aureus , Streptococcus pneumonia , and Group A Streptococcus pyogenes.

If an "immunologically effective amount", "tumor effective amount", "tumor inhibiting effective amount", or "therapeutic amount" is indicated, the exact amount of the compositions of the present invention to be administered may be determined by the clinician, taking into account individual differences in age, body weight, tumor size. , the degree of infection or metastasis, as well as the health status of the patient (subject). In general, it can be noted that a pharmaceutical composition containing immune effector cells (eg, T cells, NK cells) described herein can be administered at a dose of 10 ⁴ -10 ⁹ cells/kg body weight, in some cases 10 ⁵ -10 ⁶ cells/kg of body weight, including all intermediate integer values in these ranges. T cell compositions can also be administered at these doses multiple times. Cells can be administered using the infusion method commonly used in immunotherapy (see, for example, Rosenberg et al., New Eng. J. of Med. 319:1676, 1988).

In some aspects, it may be desirable to administer activated immune effector cells (e.g., T cells, NK cells) to a subject, followed by repeated blood collection (or apheresis), activation of immune effector cells (e.g., T cells, NK cells) from the blood in accordance with the present invention and re-infusion of these activated and expanded immune effector cells (eg, T cells, NK cells) to the patient. This process can be repeated many times every few weeks. In specific aspects, immune effector cells (eg, T cells, NK cells) can be activated from a collected blood volume of 10 cm ³ to 400 cm ³ . In specific aspects, immune effector cells (eg, T cells, NK cells) are activated from a blood volume of 20 cm ³ , 30 cm ³ , 40 cm 3 , 50 cm ³ , 60 cm ^{3 ,} 70 cm ³ , 80 cm ³ , 90 cm ³ or 100 cm ³ .

Administration of the compositions to a subject may be by any convenient means, including aerosol inhalation, injection, ingestion, transfusion, implantation, or transplantation. The compositions described herein can be administered to a patient by transarterial, subcutaneous, intradermal, intratumoral, intranodal, intramedullary, intramuscular, intravenous (IV) injection, or intraperitoneally. In one aspect, the cell compositions of the present invention are administered to a patient by intradermal or subcutaneous injection. In one aspect, the cell compositions of the present invention are administered by intravenous injection. Immune effector cell compositions (eg, T cells, NK cells) can be injected directly into a tumor, lymph node, or site of infection.

In a specific illustrative aspect, subjects may be subjected to leukapheresis, wherein leukocytes are harvested, enriched, or depleted ex vivo to select and/or isolate cells of interest, eg, T cells. These isolated T cells can be expanded by methods known in the art and processed to introduce one or more CAR constructs of the invention, thereby creating a CAR T cell of the invention. Subjects who need it can then receive standard treatment with high dose chemotherapeutic agents, followed by peripheral blood stem cell transplantation. In specific aspects, after or simultaneously with transplantation, subjects receive an infusion of expanded CAR T cells of the present invention. In an additional aspect, the expanded cells are administered before or after surgery.

The doses of the above therapeutic agents administered to a patient will vary depending on the particular condition being treated and the recipient being treated. Dose scaling for human administration can be performed in accordance with the practice accepted in the art.

EXAMPLES

Example 1: Materials and methods for examples 1-13.

Constructs

The following constructs, shown in Table 22, were used in examples 1-13.

It should be noted that the invention encompasses both heavy and light chain orientations.

Table 22. Sequences of the various constructs (signal peptide used in bold; furin cleavage sites underlined)

construct Protein sequence DNA sequence ER _mut _Furin_Flexi-12 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL RTKR IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVPCSGGGSGGGSGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS (SEQ ID NO: 48) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactccgtactaaaaga (SEQ ID NO: 49) linker GGGSGGGSGGGSRNLPV (SEQ ID NO: 52) gtggtggcggtggaagcggcggtggcggaagcggcggtggcggcagcagaaacctccccgtgg (SEQ ID NO: 53) FKBP L106P GVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKPE (SEQ ID NO: 56) DHFR R12Y/G27S/Y100I ISLIAALAVDYVIGMENAMPWNLPADLAWFKRNTLNKPVIMGRHTWESIGRPLPGRKNIILSSQPSTDDRVTWVKSVDEAIAACGDVPEIMVIGGGRVIEQFLPKAQKLYLTHIDAEVEGDTHFPDYEPDDWESVFSEFHDADAQNSHSYCFEILERR (SEQ ID NO: 57) ER T371A_L384M_M421G_N519S_G521R_Y537S RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL (SEQ ID NO: 1119) CG#c43
FKBP _mut _HA_Furin_CAR19 MALPVTALLLPLALLLHAARP GVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKPEYPYDVPDYAFPVD RTKR EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 59) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccggagtgcaggtggaaaccatctccccaggagaacgggcgcaccttccccaagcgcggccagacctgtgtggtgcactacaccgggatgcttgaagatggaaagaaagtcgattcctccgggacagaaacaagccctttaag tttatgctaggcaagcaggaggtgatccgaggctgggaagaaggggttgcccagatgagtgtgggtcagagagccaaactgactatatctccagattatgcctatggtgccactgggcacccaggcatcccaccacatgccactctcgtcttcgatgtggagcttctaaaaccggaatacccttatgatgttcctgattatgctttccccg tggatcgtactaaaagagaaattgtgatgacccagtcacccgccactcttagccttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtag cggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccggtcttgtgaagccatca gaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgca gccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggt cttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgc gaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaagatggcagaag cctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 60) CG#c44
FKBP _mut _HA_Furinmut_CAR19 MALPVTALLLPLALLLHAARP (SEQ ID NO: 61) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccggagtgcaggtggaaaccatctccccaggagaacgggcgcaccttccccaagcgcggccagacctgtgtggtgcactacaccgggatgcttgaagatggaaagaaagtcgattcctccgggacagaaacaagccctttaag tttatgctaggcaagcaggaggtgatccgaggctgggaagaaggggttgcccagatgagtgtgggtcagagagccaaactgactatatctccagattatgcctatggtgccactgggcacccaggcatcccaccacatgccactctcgtcttcgatgtggagcttctaaaaccggaatacccttatgatgttcctgattatgctttccccg tggatgctactaaaagagaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacagctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagc ggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccggtcttgtgaagccatcaga aactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcag ccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtct tgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggagaggaggaaggcggctgcga actgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcc tatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 62) CG#c45
DHFR _mut _HA_Furin_CAR19 MALPVTALLLPLALLLHAARP ISLIAALAVDYVIGMENAMPWNLPADLAWFKRNTLNKPVIMGRHTWESIGRPLPGRKNIILSSQPSTDDRVTWVKSVDEAIAACGDVPEIMVIGGGRVIEQFLPKAQKLYLTHIDAEVEGDTHFPDYEPDDWESVFSEFHDADAQNSHSYCFEILERRYPYDVPDYAFPVD RTKR EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 63) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccatctctctctgattgccgctctggccgtggactacgtgatcgggatggaaaacgctatgccatggaatctgcccgccgatctggcttggttcaagaggaacaccctgaacaagccagtgatcatgggcagacacacttgggagtcca ttggccggcccctgcctggacgcaagaacatcattctgagctcccagccctctaccgacgacagggtgacatgggtgaaaagtgtggacgaagccattgccgcttgcggagatgtgcccgagatcatggtcatcggcggagggagagtgatcgagcagttcctgcctaaggcccagaaactgtacctgactcacattgacgctgaggt ggaaggggacacccattttcctgattatgagccagacgattgggaaagcgtgttctccgagttcacgacgccgatgctcagaactctcatagtttattgctttgagatcctggaaaggagatacccttatgttcctgattatgctttccccgtggatcgtactaaaagagaaattgtgtgatgacccagtcacccgccactcttagcc tttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctg tctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgtgagcggagtgtctctccccgattacggggt gtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacg caatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcgg ggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcagg ggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgta ccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 64) CG#c46
DHFR _mut _HA_Furinmut_CAR19 MALPVTALLLPLALLLHAARP (SEQ ID NO: 65) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccatctctctctgattgccgctctggccgtggactacgtgatcgggatggaaaacgctatgccatggaatctgcccgccgatctggcttggttcaagaggaacaccctgaacaagccagtgatcatgggcagacacacttgggagtcca ttggccggcccctgcctggacgcaagaacatcattctgagctcccagccctctaccgacgacagggtgacatgggtgaaaagtgtggacgaagccattgccgcttgcggagatgtgcccgagatcatggtcatcggcggagggagagtgatcgagcagttcctgcctaaggcccagaaactgtacctgactcacattgacgctgaggt ggaaggggacacccattttcctgattatgagccagacgattgggaaagcgtgttctccgagttcacgacgccgatgctcagaactctcatagtttattgctttgagatcctggaaaggagatacccttatgttcctgattatgctttccccgtggatgctactaaaagagaaattgtgtgacccagtcacccgccactcttagcct ttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgt ctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtg tcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgca atggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcgggg tcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaaggggg cagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaggtaagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtacca gggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 66) CG#c47
ER _mut _HA_FurinCAR19 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLYPYDVPDYAFPVD RTKR EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 67) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactctacccttatgatgttcctgattat gctttccccgtggatcgtactaaaagagaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccagg ttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttg tgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccgggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatct gtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtg catacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaccggctgttcatgccggttcccagaggagggaggaa ggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggata agatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 68) CG#c48
ER _mut _HA_FurinMmut_CAR19 MALPVTALLLPLALLLHAARP (SEQ ID NO: 69) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactctacccttatgatgttcctgattat gctttccccgtggatgctactaaaagagaaattgtgatgacccagtcacccgccacttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggaccaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggtt cagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgt gaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctg tgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcat acccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggacggggctgttcatgccggttcccagaggaggaggaagg cggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaagggataaga tggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 70) CG#c71
FKBP _mut _HA_noFurin_CAR19 MALPVTALLLPLALLLHAARP (SEQ ID NO: 71) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccggagtgcaggtggaaaccatctccccaggagaacgggcgcaccttccccaagcgcggccagacctgtgtggtgcactacaccgggatgcttgaagatggaaagaaagtcgattcctccgggacagaaacaagccctttaag tttatgctaggcaagcaggaggtgatccgaggctgggaagaaggggttgcccagatgagtgtgggtcagagagccaaactgactatatctccagattatgcctatggtgccactgggcacccaggcatcccaccacatgccactctcgtcttcgatgtggagcttctaaaaccggaatacccttatgatgttcctgattatgctttccccg tggatgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccg actacccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactg acttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgattggggctctgagactactactactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccg tgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcc tgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgt gaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattgg tatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 72) CG#c72
_ERmut _HA_noFurinCAR19 MALPVTALLLPLALLLHAARP (SEQ ID NO: 73) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactctacccttatgatgttcctgattat gctttccccgtggatgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacagctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcgg atctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaa actctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactactactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagcc gacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtctt gacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggagaggacggctgttcatgccggttcccagaggagggaaggcggctgcgaact gcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgccgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaaagatggcagaagccta tagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 74) CG#c73
ER _mut _noHa_FurinCAR19 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL RTKR EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 75) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactccgtactaaaagaagaaattgt gatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatca gctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgag cggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcg ctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacat ttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgca gcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacg cagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 76) CG#c74
ER _mut _noHa_noFurin CAR19 MALPVTALLLPLALLLHAARP (SEQ ID NO: 77) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgaaattgtgatgacccagt cacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcag ccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtct ctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactatta tggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctct ggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatg ctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaa ggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 78) ER _mut .Furin CAR19=Alt1 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL SLNLTESHNSRKKR EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 103) agtctcaatttgactgagtcacacaattcggaagaaaagg (SEQ ID NO: 104) ER _mut .Furin CAR19=Alt2 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRR EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 105) gggacgggagctgaggatccacgacccagcagaaagcgacgg (SEQ ID NO: 106) ER _mut .Furin CAR19=Alt3 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL CKINGYPKRGRKRR EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 107) tgcaagatcaacggctaccctaagaggggcagaaagcggcgg (SEQ ID NO: 108) ER _mut .Furin CAR19=Alt4 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL LQWLEQQVAKRRTKR EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 109) ctgcaatggctggagcagcaggtggcgaagcggagaactaagcgg (SEQ ID NO: 110) ER _mut .Furin CAR19=Alt5 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 111) ggaaccggcgcggaagacccccggccctcggaagcgaaggtccctcggagacgtgggt (SEQ ID NO: 112) ER _mut .Furin CAR19=Alt6 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGG EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 113) ggcacaggtgccgaggaccctcggccaagccgcaaaaggaggtcacttggcggc (SEQ ID NO: 114) ER _mut .Furin CAR19=Alt7 MALPVTALLLPLALLLHAARP RSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLG EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 115) ggaaccggagcagaagatccgaccaagccggaaaaggcggtccctgggt (SEQ ID NO: 116)

General Methods

The following general materials and methods were used for the assays described in Examples 1-13.

Receiving CAR Constructs

The scFvs used in the CAR constructs that were evaluated in Example 3 were independently synthesized based on the anti-CD19 scFv sequence above. scFv was cloned in the heavy to light chain direction, with a flexible linker connecting the VH and VL domains (e.g., GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 29)) into a vector scaffold containing the CD8 hinge region along with a 4-1BB molecule and a CD3- zeta. In this construct, upstream of the scFv, an N-terminal furin cleavage site fused to a destabilization domain was added. The proteins used in the furin-degron constructs that were evaluated in Examples 4-5 were independently synthesized based on publicly available sequence data. In this construct, upstream of the protein sequence, an N-terminal furin cleavage site fused to a destabilization domain was added.

Cell lines and cell transduction

Jurkat cells were obtained from ATCC and maintained in the medium according to the supplier's recommendations. Jurkat cells were transduced by spinoculation with lentiviral supernatant from pELPS-transfected 293T cells using regulatable plasmid DNA of the furin domain protein.

Cancer cells

Cell lines NALM6 and K562 were obtained from ATCC and maintained in the medium in accordance with the recommendations of the supplier. To obtain a bioluminescent model for T-cell killing assays, all cells were transduced with a lentiviral luciferase construct and maintained by antibiotic selection.

flow cytometry

Cells were isolated from in vitro culture, washed once in PBS supplemented with 0.5% bovine serum albumin, and stained on ice using either biotinylated L protein, followed by incubation with a fluorochrome-conjugated streptavidin reagent, or an antibody recognizing a particular target antigen. . In all assays, a population of interest was selected based on forward and side scatter characteristics, followed by singlet separation, and live cells were selected. Flow cytometry was performed on a four-laser Fortessa unit (Becton-Dickinson).

Compound handling

In all cases, either 4-OHT or Shield-1 was resuspended in ethanol. Trimethoprim (TMP) was resuspended in DMSO. In all cases where concentrations are not indicated, compounds were added for a total of 24 hours prior to analysis by flow cytometry. 3 μM 4-OHT (ERα), 1 μM Shield-1 (FKBP) or 100 μM TMP (ecDHFR) was used.

Analysis for destruction

Briefly, luciferase gene-transduced target cell lines of the indicated lines were incubated at the indicated ratios with effector CD19CAR or CD19CAR-FurON T cells for 18 hours. Residual luciferase activity was measured by adding Bright-Glo (Promega), on a fluorescent reader (Envision). Percent kill was calculated using negative controls.

Secretion of cytokines

Effector and target cells were incubated at a ratio of 3:1 in RPMI medium containing 10% FBS for 18 hours. The supernatant was analyzed using a 3-plex kit according to the manufacturer's instructions (Invitrogen).

Example 2: Furin is the most highly expressed proprotein convertase in primary human T cells

Literature suggests that furin (FUR; PACE; PCSK3; SPC1) has a broad expression profile (Seidah, et al., Nature Reviews Drug Discovery 11, 367-383 (May 2012)). The expression of members of the proprotein convertase family was analyzed by qRT-PCR. RNA was obtained from normal donor T cells on days 0, 4 and 11 after stimulation with anti-CD3/anti-CD28 activating beads. In the additional group, 100 U/ml IL-2 was added during culture and RNA was harvested on day 11. The data obtained show that after activation with anti-CD3/anti-CD28 beads, furin mRNA is expressed at a higher level than mRNA of other representatives family of proprotein convertases (FIG. 1).

Example 3 Compound Controlled CD19 CAR Expression

Jurkat T cells were transduced with a furin degron domain (FKBP _FD , ERα _FD , or DHFR _FD ) fused to an anti-CD19 scFv CAR construct, followed by treatment with the appropriate compound. FKBP _FD -transduced cells were treated with 1 μM Shield-1 solution. ERα _FD -transduced cells were treated with 1 μM bazedoxifene solution. DHFR _FD -transduced cells were treated with 1 mM TMP. Expression of anti-CD19 scFv is induced in the presence of the compound (FIG. 2). Black=NT; gray = construct, no connection; white = construct, with connection. These data show that several degron domains, when combined with a furin cleavage domain, result in a distinct, compound-dependent regulation of CAR 19 expression.

Example 4 Kinetics of CAR Expression in Jurkat Cells after Compound Addition

Jurkat T cells were transduced with the indicated furin degron domains (FKBP _FD or ERα _FD ) fused to an anti-CD19 scFv CAR construct. These cells were treated with either 1 μM Shield-1 solution or 1 μM 4-OHT solution for the indicated time period and CAR expression was determined by FACS. The data obtained show that the induction of expression when using CAR 19 with furin degrone occurs shortly after the addition of the compound and is stable throughout the treatment period with the compound (FIG. 3).

Example 5 Compound-Inducible CAR Expression in Primary Human T Cells

Primary human T cells were transduced with an ERα furin degron domain (ERα _FD domain) fused to an anti-CD19 scFv CAR construct. 100 U/ml IL-2 was added on day 9 after activation with anti-CD3/CD28 stimulating beads. Bazedoxifene was added on day 10, and CAR expression was determined by FACS on day 11. These data indicate that the furin degron domain (e.g., ERα _FD domain) can regulate CAR 19 expression in a compound-dependent manner in primary human T cells (FIG. 4) and that stabilization is enhanced in the presence of IL-2 in vitro (FIG. 4).

Example 6 Kinetics of CAR Expression After Compound Washout in Primary T Cells

Primary human T cells were transduced with the indicated furin degron domain (FKBP _FD or ERα _FD ) fused to an anti-CD19 scFv CAR construct. 100 U/ml IL-2 was added on day 9 after activation with anti-CD3/CD28 stimulating beads. Bazedoxifene was added on day 10 and T cells were frozen on day 11. T cells were thawed, washed copiously and cultured for the indicated time, followed by determination of CAR expression by FACS. The data obtained show that the removal of the connection leads to a decrease in the expression of CAR 19 when using the furin degron domain (FIG. 5).

Example 7: Several ER-alpha Targeting Drugs Stabilize ER-alpha FurON CART

Jurkat T cells were transduced with an ERα _FD degradation domain fused to an anti-CD19 scFv CAR construct, followed by treatment with the indicated compounds for 24 hours. Compounds were used at the following concentrations: 10 μM for 4-OHT, 1 μM for bazedoxifene, or 1 μM for lasofoxifene. These data indicate that several ER-alpha-targeting compounds can induce CAR19 expression using the estrogen receptor-based furin degron (FurON) system (FIG. 6).

Example 8: Dose dependence of bazedoxifene in human T cells

Primary human T cells were transduced with the ERα _FD furin degron domain fused to an anti-CD19 scFv CAR construct or the parental CD19 CAR construct. 100 U/ml IL-2 was added on day 9 after activation with anti-CD3/CD28 stimulating beads and T cells were frozen on day 11. T cells were thawed and cultured with bazedoxifene at the indicated concentrations for 48 hours. CAR expression was determined by FACS. The data obtained indicate that physiologically relevant concentrations of bazedoxifene can stabilize CAR19 expression with furin degron at a level similar to that in parental CAR19 cells (FIG. 7).

Example 9 Compound-Dependent Target-Specific Cell Killing with FurON CART ER-alpha

Primary human T cells were transduced with the ERα _FD furin degron domain fused to an anti-CD19 scFv CAR construct or the parental CD19 CAR construct. 100 U/mL IL-2 and bazedoxifene were added on day 9 after activation with anti-CD3/CD28 stimulation beads and T cells were frozen on day 11. T cells were thawed and incubated for 20 hours with luciferase containing target cells of the indicated lines K562 (CD19-) or NALM6 (CD19+). The percentage kill was determined by analyzing the residual luciferase activity. These data show that CAR19 with the estrogen receptor-based furin degron domain induces specific killing of CD19+ tumor cells in a compound-dependent manner and is as effective as the parental CAR19 (FIG. 8).

Example 10 Compound-Dependent Target-Specific Cell Killing with FKBP FurON CART

Primary human T cells were transduced with the FKBP _FD furin degron domain fused to the anti-CD19 scFv CAR construct or the parental CD19 CAR construct. 100 U/mL IL-2 and Shield-1 were added on day 9 after activation with anti-CD3/CD28 stimulation beads and T cells were frozen on day 11. T cells were thawed and incubated for 20 hours with luciferase-containing cells. targets of the indicated K562 (CD19-) or NALM6 (CD19+) lines. The percentage kill was determined by analyzing the residual luciferase activity. These data show that CAR19 with the FKBP-based furin degron domain induces specific killing of CD19+ tumor cells in a compound-dependent manner and is as effective as the parental CAR19 (FIG. 9).

Example 11 Compound-Dependent Cytokine Production ER-alpha FurON CART

Primary human T cells were transduced with the ERα _FD furin degron domain fused to an anti-CD19 scFv CAR construct or the parental CD19 CAR construct. 100 U/ml IL-2 and bazedoxifene were added on day 9 after activation with anti-CD3/CD28 stimulating beads, and T cells were frozen on day 11. T cells were thawed and incubated for 20 hours with target cell lines. Supernatants were collected and analyzed by the method of multiplex analysis of cytokines with microspheres. These data show that estrogen receptor-based furin degron domain CAR19 induces specific cytokine production in the presence of CD19+ tumor cells in a compound-dependent manner and is as effective as parental CAR19 (FIG. 10).

Example 12 Compound-Dependent Proliferation of FURON CART ER-alpha

Primary human T cells were transduced with the ERα _FD furin degron domain fused to an anti-CD19 scFv CAR construct or the parental CD19 CAR construct. 100 U/ml IL-2 and bazedoxifene were added on day 9 after activation with anti-CD3/CD28 stimulation beads and T cells were frozen on day 11. T cells were thawed and incubated with target cell lines for 4 days. The number of FurON-CAR T cells was analyzed by FACS. The data obtained show that CAR19 with the estrogen receptor furin degron domain induces specific proliferation in the presence of CD19+ tumor cells in a compound-dependent manner and is as effective as the parental CAR19 (FIG. 11).

Example 13: materials and methods for examples 14-26.

The following general materials and methods were used for the assays described in examples 14-26.

FurON constructs

In some embodiments, the fusion protein described herein comprises a furin degron domain (FurON) that includes two components: a degron, or degradation domain, which is a mutant protein domain that is unable to assume the correct conformation in the absence of a small molecular weight ligand, and a site furin breakdown. The furin degron domain can be fused to a protein of interest that is expressed in the endoplasmic reticulum. The N- and/or C-terminus of the protein of interest can be used as a fusion site provided that the furin degron domain is directed towards the lumen of the endoplasmic reticulum. The protein of interest can be either a membrane protein (regardless of the number of transmembrane domains) or a soluble protein. The orientation of the furin cleavage site relative to the degron domain should be such that the cleavage results in separation of the furin degron domain and the protein of interest. In the absence of a small molecule ligand or stabilizing compound, the furin degron domain results in destabilization or degradation of the entire fusion protein. In the presence of a low molecular weight ligand or stabilizing compound, the fusion protein is not degraded. The furin degron domain is mutated such that the affinity for its natural endogenous ligand is eliminated; the affinity for the low molecular weight ligand or stabilizing compound is maintained; and the protein becomes unstable in the absence of the low molecular weight ligand.

Several constructs with different mutations and different furin cleavage sites in the furin degron domain were generated and fused to the N-terminus of an anti-CD19 scFV CAR or an anti-CD123 scFV CAR. Regardless of the orientation of the scFV heavy and light chains, furin degron domain fusion occurs between the leader signal peptide and the scFV. The selected mutant protein in the furin degron domain was a truncated version of the estrogen receptor alpha. The small molecule ligands chosen to stabilize the furin degron domain belong to the family of selective estrogen receptor modulators or inhibitors.

The efficiency of the furin degron domain in destabilizing or stabilizing CAR structure was evaluated in the absence or presence of a low molecular weight ligand. The effector function of a CAR T cell fused with the furin degron domain was also assessed in the absence or presence of a low molecular weight ligand and compared with a cell containing the parental CAR19 construct. Cells were normalized to the same percentage of CAR-expressing cells, supplemented with non-transduced T cells (HT) from the same source of expanded donor T cells. Normalized populations were then used in co-culture assays to measure CAR-mediated cytolytic function, cytokine production and proliferation.

Obtaining FurON CAR constructs

The scFvs used in the CAR constructs that were evaluated in the examples were independently synthesized based on the anti-CD19 or anti-CD123 scFV sequences above. scFv cloned in light to heavy chain direction (anti-CD19) or heavy to light chain direction (anti-CD123), with a flexible linker connecting the VH and VL domains (e.g., GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 29)), into a vector framework containing the CD8 hinge region along with a 4-1BB molecule and a CD3-zeta molecule. In this construct, upstream of the scFv, an N-terminal furin cleavage site fused to a destabilization domain was added. All constructs were received in a lentiviral vector. The sequences of the various FurON CAR constructs and their components are shown in Table 23.

Table 23. Sequences of FurON CAR constructs and their components

Amino acid sequence DNA sequence ER1 DT
(305ak-549ak) SLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQL LLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLLLEMLDAHRL (SEQ ID NO: 970) tcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgactct gcacgaccaagtgcacctcctggaatgcgcctggctggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgcgcaaccagggaaaatgcgtggaagggatggtcgagattttcgacatgctgctcgccacctcttcccggttccggatgat gaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctga gccacatccggcacatgtcgaacaaggggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtacgatctgctcctggaaatgctggacgcgcacagactc (SEQ ID NO: 971) ERmut1 (6 mutations) SLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQL LLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL (SEQ ID NO: 58) tcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccct gcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatga tgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattct gagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactc (SEQ ID NO: 1110) ERmut2 (4 mutations) SLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQL LLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL (SEQ ID NO: 121) tcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccct gcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatga tgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattct gagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactc (SEQ ID NO: 122) Furin cleavage site 1 RTKR (SEQ ID NO: 123) cgtactaaaaga (SEQ ID NO: 1112) Furin cleavage site 2 GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125) ggaaccggcgcggaagacccccggccctcggaagcgaaggtccctcggagacgtgggt (SEQ ID NO: 126) Furin cleavage site 3 GTGAEDPRPSRKRR (SEQ ID NO: 127) ggaaccggcgcggaagacccccggccctccaggaagcgaagg (SEQ ID NO: 128) Furin cleavage site 4 LQWLEQQVAKRRTKR (SEQ ID NO: 129) ctgcaatggctggagcagcaggtggcgaagcggagaactaagcgg (SEQ ID NO: 130) Furin cleavage site 5 GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131) ggcacaggtgccgaggaccctcggccaagccgcaaaaggaggtcacttggcggc (SEQ ID NO: 132) Furin cleavage site 6 GTGAEDPRPSRKRRSLG (SEQ ID NO: 133) ggaaccggagcagaagatcccagaccaagccggaaaaggcggtccctgggt (SEQ ID NO: 134) Furin cleavage site 7 SLNLTESHNSRKKR (SEQ ID NO: 135) agtctcaatttgactgagtcacacaattcggaagaaaagg (SEQ ID NO: 136) Furin cleavage site 8 CKINGYPKRGRKRR (SEQ ID NO: 137) tgcaagatcaacggctaccctaagaggggcagaaagcggcgg (SEQ ID NO: 138) Leader sequence/Signal peptide (SP) MALPVTALLLPLALLLHAARP (SEQ ID NO: 139) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccc (SEQ ID NO: 140) SP-Linker 1-ERmut1-Furin cleavage site 1-CD19 CAR1 MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLRTKREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGGSGGGQVQLQES GPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKGRRKKLLYIFKQPFMRPVQTT QEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 141) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactccgtactaaaagaagaaattgt gatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatca gctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgag cggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcg ctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacat ttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgca gcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatctttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacg cagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 142) SP-Linker 1-ERmut1-Furin cleavage site 2-CD19 CAR1 (construct 106) MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 143) a agcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccac gacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 144) SP-Linker 1-ERmut1-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGG GSGGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 145) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaccc ccggccctccaggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctgg aatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggac cgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcact gaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctgg tggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttccca gaggaggaggaaggcggctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgag ctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 146) SP-Linker 1-ERmut1-Furin cleavage site 3-CD19 CAR1 (construct 103) MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 147) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacg acccagcagaaagcgacgggaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacagctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtag cggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccggtcttgtgaagccatca gaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgca gccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggt cttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgc gaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaagatggcagaag cctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 148) SP-Linker 1-ERmut1-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 149) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacg acccagcagaaagcgacgggaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacagctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtag cggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccggtcttgtgaagccatca gaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgca gccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggt cttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgc gaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaag cctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 150) SP-Linker 1-ERmut2-Furin cleavage site 1-CD19 CAR1 MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLRTKREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGGSGGGQVQLQES GPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKGRRKKLLYIFKQPFMRPVQTT QEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 151) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactccgtactaaaagagaaattgt gatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatca gctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgag cggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcg ctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacat ttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgca gcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatctttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacg cagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 152) SP-Linker 1-ERmut2-Furin cleavage site 2-CD19 CAR1 (construct 130) MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISK DNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 153) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaccc ccggccctccaggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctgg aatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggac cgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcact gaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctgg tggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttccca gaggaggaggaaggcggctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgag ctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 154) SP-Linker 1-ERmut2-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGG GSGGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 155) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaccc ccggccctccaggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctgg aatccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggac cgggtcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcact gaaactgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctgg tggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttccca gaggaggaggaaggcggctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgag ctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 156) SP-Linker 1-ERmut2-Furin cleavage site 3-CD19 CAR1 MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 157) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcGggacgggagctgaagatccacg acccagcagaaagcgacgggaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacagctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtag cggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccggtcttgtgaagccatca gaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgca gccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggt cttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgc gaactgcgcgtgaaattcagccgcagcgcagatgctccagcctacaagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaagatggcagaag cctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 158) SP-Linker 1-ERmut2-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 159) c agcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccac gacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 160) SP-Linker 1-ERmut1-Furin cleavage site 1-CD123 CAR MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLRTKRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGG GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFK (SEQ ID NO: 161) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactccgtactaaaagacaagtgcaact cgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccaggggagagtgactctgactcgggatacct ccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttcggacattcagatgacccagtccccat cctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgctgctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaac agcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgctttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttc gcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgc gtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgaga ttggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 162) SP-Linker 1-ERmut1-Furin cleavage site 2-CD123 CAR (construct 119) MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 163) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaccc ccggccctccaggaagcgaaggtccctcggagaacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctaccctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggg cggaactaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggag gaggcggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtg ccatccagattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgga ggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgctcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaaggagaggac ggctgttcatgccggttcccagaggaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatcccca agagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 164) SP-Linker 1-ERmut1-Furin cleavage site 3-CD123 CAR (construct 122) MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVS SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 165) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccccggtcgtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaccc ccggccctccaggaagcgaaggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaag ttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcgga ggttcggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcagg ctcaggaaccgacttcaccctgaccgtgaacagcctgaccgtgaacagcctccagccggaggactttgccacttactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggt ggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccaga ggaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagct ccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 166) SP-Linker 1-ERmut2-Furin cleavage site 1-CD123 CAR MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLRTKRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGG GGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFK (SEQ ID NO: 167) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactccgtactaaaagacaagtgcaact cgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccaggggagagtgactctgactcgggatacct ccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttcggacattcagatgacccagtccccat cctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgctgctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaac agcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgctttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttc gcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcgc gtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgaga ttggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 168) SP-Linker 1-ERmut2-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 169) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaccc ccggccctccaggaagcgaaggtccctcggagaacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctaccctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggg cggaactaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggag gaggcggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtg ccatccagattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgga ggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgctcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaaggagaggac ggctgttcatgccggttcccagaggaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatcccca agagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 170) SP-Linker 1-ERmut2-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVS SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 171) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacggggagctgaagatccacg acccagcagaaagcgacggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacggggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagtt ccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggagg ttcggacattcagatgacccagtccccagcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggct caggaaccgacttcaccctgaccgtgaacagcctgaccgtgaacagcctccagccggaggactttgccacttactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgg ggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagagg aggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctcca aaaggtaagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 172) SP-Linker 1-ERmut1-Furin cleavage site 1-BCMA CAR MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLRTKREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGGRASGGGGSDI QLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQE EDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 173) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactccgtactaaaagagaagtgcaat tggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactatgccgcatccgtgaaggggagattcacca tcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggcggatcggacatccagctcacccagtcc ccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggttccggtactgatttcaccctgaccatttcc tccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgact tcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgc gcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaagatggcagaagcctatagc gagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 174) SP-Linker 1-ERmut1-Furin cleavage site 2-BCMA CAR (construct 164) MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 175) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaccc ccggccctcggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggta ttgtgtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactcgggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagc gggggtcgggcatcagggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggag tgccctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtcc ggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagagga ggacggctgttcatgccggttcccagaggaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaat ccccaagaggggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 176) SP-Linker 1-ERmut1-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSG GRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPF (SEQ ID NO: 177) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcGggacgggagctgaagatccacg acccagcagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacct actatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggc ggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttccggctcc ggttccggtactgatttcaccctgaccatttcctccctgcaaccgggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctgg tggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttccca gaggaggaggaaggcggctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgag ctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 178) SP-Linker 1-ERmut2-Furin cleavage site 1-BCMA CAR MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLRTKREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGGRASGGGGSDI QLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQE EDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 179) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactccgtactaaaagagaagtgcaat tggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactatgccgcatccgtgaaggggagattcacca tcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggcggatcggacatccagctcacccagtcc ccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggttccggtactgatttcaccctgaccatttcc tccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgact tcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgc gcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaagatggcagaagcctatagc gagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 180) SP-Linker 1-ERmut2-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 181) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaccc ccggccctcggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggta ttgtgtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactcgggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagc gggggtcgggcatcagggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggag tgccctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtcc ggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactactcaagagga ggacggctgttcatgccggttcccagaggaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaat ccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 182) SP-Linker 1-ERmut2-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPRSSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSG GRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPF MRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 183) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccggtcgTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctgg cggaccgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaa aatgcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacc cttatccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacggggagctgaagatccacg acccagcagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacct actatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggc ggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttccggctcc ggttccggtactgatttcaccctgaccatttcctccctgcaaccgggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctgg tggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttccca gaggaggaggaaggcggctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgag ctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 184)

Cell lines and cell transduction

Jurkat cells were obtained from ATCC and maintained in the medium according to the supplier's recommendations. Jurkat cells were transduced by spinoculation with lentiviral supernatant from 293T cells transfected with various plasmid DNAs.

Cancer cells

Cell lines NALM6, K562, Molm13 were obtained from ATCC and maintained in the medium in accordance with the recommendations of the supplier. To obtain a bioluminescent model for T-cell killing assays, all cells were transduced with a lentiviral luciferase construct and maintained by antibiotic selection.

Compound handling

4-hydroxy tamoxifen (4-OHT) was resuspended in ethanol. Bazedoxifene and raloxifene were resuspended in DMSO. In all cases where concentrations are not indicated, compounds were added at a concentration of 1 μM for 24 hours prior to analysis by flow cytometry.

flow cytometry

Cells were isolated from in vitro culture, washed once in PBS supplemented with 0.5% bovine serum albumin, and stained on ice using either biotinylated L protein, followed by incubation with a fluorochrome-conjugated streptavidin reagent, or an antibody recognizing a particular target antigen. . In all assays, a population of interest was selected based on forward and side scatter characteristics, followed by singlet separation, and live cells were selected. Flow cytometry was performed on a four-laser Fortessa unit (Becton-Dickinson).

Tumor cell killing assay

Briefly, luciferase gene-transduced target cell lines of these lines were co-cultured at the indicated ratios with effector CD19CAR, FurON-CD19CAR, CD123CAR, FurON-CD123 CAR T cells for 20 hours in the presence or absence of bazedoxifene. Residual luciferase activity was measured by adding Bright-Glo (Promega) on a fluorescent reader (Envision). Percent kill was calculated using negative controls.

Secretion of cytokines

Effector cells and luciferase gene-transduced target cells of these lines were co-cultured at a ratio of 3:1 in RPMI medium containing 10% FBS for 20 hours in the presence or absence of bazedoxifene. The supernatant was analyzed using a 3-plex kit according to the manufacturer's instructions (Invitrogen).

Proliferation assay

Effector cells and irradiated target cells were co-cultured for 4 days in the presence or absence of bazedoxifene. Cells were then harvested, washed and stained with anti-CD3 antibody and/or L protein reagent to detect surface expression of CAR. Cells were then washed, resuspended in FACS buffer, and a fixed volume of calibrated Absolute Counting Beads microsphere suspension was added to each sample. Samples were analyzed on a Fortessa FACS analyzer and the same number of events in the discrimination window for Counting Beads were collected for all samples.

Example 14 Evaluation of different furin cleavage sites in the furin degron domain in the context of CAR19 (anti-CD19 scFv CAR)

Gene fragments containing the furin degron domain fused to the anti-CD19 scFv CAR and to the preceding T7 promoter were subjected to in vitro transcription/translation. The differences between the gene fragments lie in the furin cleavage sites created, according to the abstract. In vitro synthesized proteins were incubated with furin as indicated at 37° C. for 1 hour. Samples were applied to SDS-PAGE under reducing conditions and analyzed by immunoblotting using an anti-CD3ζ antibody.

FIG. 12A-12B show the degree of furin cleavage of the various furin cleavage sites tested in the context of CAR19. Furin cleavage sites tested are: No. 105 - LQWLEQQVAKRRTKR (SEQ ID NO: 129); No. 106 - GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125); No. 107 - GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131); No. 108 - GTGAEDPRPSRKRRSLG (SEQ ID NO: 133); No. 102 - SLNLTESHNSRKKR (SEQ ID NO: 135); No. 103 - GTGAEDPRPSRKRR (SEQ ID NO: 127); No. 104 - CKINGYPKRGRKRR (SEQ ID NO: 137); No. 73 - RTKR (SEQ ID NO: 123). A gene fragment derived from parental CAR19 was used as a control (control) and no cleavage was observed (FIGS. 12A-12B).

Example 15 Compound-Inducible CAR Expression in Primary Human T Cells

Primary human T cells were transduced with a furin degron domain fused to an anti-CD19 scFv CAR construct (construct #106). Non-transduced T cells (HT) and parental CAR19 were used as controls. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7, bazedoxifene (BZA) was added on day 8. Prior to cell freezing, CAR expression was determined on day 10 by FACS using protein L staining. Cell number, size and viability were also assessed.

The data showed that the furin degron domain regulates CAR19 expression in a stabilizing compound dependent manner in human primary T cells, with the MIF (mean fluorescence intensity) of the CAR being lower than that of the parental CAR construct (FIG. 13). In addition, the furin degron domain had no effect on cell viability and cell proliferation (FIG. 13).

Example 16 FurON Compound-Dependent CAR-Mediated Tumor Killing

Primary human T cells were transduced with a furin degron domain fused to an anti-CD19 scFv CAR (construct #106). Non-transduced T cells (HT) were used as controls. The CAR19 parent construct was included as a reference for full functional CAR activity. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7, bazedoxifene was added on day 8 (CD19 CAR+ and FurON 106+ samples) or not added (CD19 CAR and FurON 106 samples). Cells were frozen on day 10. T cells were thawed and co-cultured with luciferase-containing target cells of the indicated lines (CD19+ NALM6 cells or CD19-K562 cells) and bazedoxifene for 20 hours. CAR T cells were normalized to the same percentage of CAR expressing cells. Tumor lysis in percent was determined by analyzing the residual luciferase activity.

The data obtained showed that CAR19 with the furin degron domain induces the killing of CD19+ tumor cells in a stabilizing compound dose-dependent manner and is as effective as the parental CAR construct (FIG. 14).

Example 17 Compound and Tumor Dependent Cytokine Secretion Induced by FurON CAR

Primary human T cells were transduced with a furin degron domain fused to an anti-CD19 scFv CAR (construct 106). Non-transduced T cells (HT) were used as controls. The CAR19 parent construct was included as a reference for full functional CAR activity. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7, bazedoxifene (BAZ) was added on day 8 (CD19 CAR+BAZ and FurON 106+BAZ samples) or not added (CD19 CAR and FurON 106 samples). Cells were frozen on day 10. T cells were thawed and co-cultured with luciferase-containing NALM6 cells, CD19+ target cells for 20 hours, and bazedoxifene as indicated. CAR T cells were normalized to the same percentage of CAR expressing cells. Supernatants were collected and evaluated for IFNγ levels.

The data obtained showed that primary human T cells expressing ERαFurON CAR19 secrete IFNγ in the presence of CD19+ tumor cells in a dose-dependent manner of the stabilizing compound and are non-inferior to cells with the CAR19 parent construct (FIG. 15).

Example 18 Compound and Tumor Dependent Cell Proliferation with FurON CAR

Primary human T cells were transduced with a furin degron domain fused to an anti-CD19 scFv CAR (construct 106). Non-transduced T cells (HT) were used as controls. The CAR19 parent construct was included as a reference for full functional CAR activity. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7, bazedoxifene (Baz) was added on day 8 (CD19 CAR+BAZ and FurON 106+BAZ samples) or not added (CD19 CAR and FurON 106 samples). Cells were frozen on day 10. T cells were thawed and co-cultured with luciferase-containing target cells of the indicated lines (NALM6 CD19+ cells or K562 CD19- cells) and bazedoxifene. CAR T cells were normalized to the same percentage of CAR expressing cells. After 4 days, the samples were analyzed by FACS, and 3000 events in the discrimination window for Counting Beads were collected for all samples.

The data obtained showed that primary human T cells expressing ERαFurON CAR19 proliferate in the presence of tumor CD19+ cells in a stabilizing compound-dependent manner and are not inferior to cells with the CAR19 parent construct (FIG. 16).

Example 19 Compound-Inducible CAR Expression in Jurkat T Cells

Jurkat T cells were transduced with one of two furin degron domains fused to anti-CD19 scFv CAR constructs. The two constructs share the same furin cleavage sequence but differ in the number of mutations in the degradation domain (ERmut1 or ERmut2 shown in Table 23). The high mutated construct was FurON CART19 #106 (with ERmut1); and the construct with fewer mutations was FurON CART19 #130 (with ERmut2). The transduced cells were incubated with 4-OH tamoxifen, bazedoxifene or raloxifene at the indicated concentrations for 42 hours. The expression of anti-CD19 scFv was determined by FACS using protein L.

The data obtained showed that the tested furin degron domains can regulate the expression of CAR19 in a stabilizing compound-dependent manner, regardless of the number of mutations; and no surface expression of CAR was detected in the absence of compound (FIG. 17).

Example 20 Compound-Inducible CAR Expression in Human Primary T Cells

Primary human T cells were transduced with a furin degron domain fused to an anti-CD19 scFv CAR construct (construct #130). Non-transduced T cells (HT) and parental CAR19 were used as controls. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7, or no bazedoxifene (BZA) was added on day 8. Prior to cell freezing, CAR expression was determined on day 10 by FACS using protein L staining.

The data obtained showed that the FurON domain - containing a limited number of mutations in the degron domain - regulates the expression of CAR19 in a stabilizing compound and IL-2 dependent manner in human primary T cells (FIG. 18). In addition, no surface expression of CAR was detected in the absence of the stabilizing compound bazedoxifene when the FurON fragment was fused to CAR19 (FIG. 18).

Example 21 FurON Compound-Dependent CAR-Mediated Tumor Killing

Primary human T cells were transduced with a furin degron domain fused to an anti-CD19 scFv CAR construct (construct #130). Non-transduced T cells (HT) were used as controls. The CAR19 parent construct was included as a reference for full functional CAR activity. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7. Bazedoxifene (BZA) was added on day 8 to a portion of the FurON 130 BZA sample so that CAR expression could be determined on day 10 by FACS using protein L staining before cells were frozen. T cells were thawed and co-cultured with luciferase-containing target cell lines (NALM6 CD19+ cells or K562 CD19 cells) for 20 hours in the presence or absence of bazedoxifene. Different ratios of CART ("effector") and target cells were used, as indicated by the x-axis in FIG. 19A-19B. CAR T cells were normalized to the same percentage of CAR expressing cells. Tumor lysis in percent was determined by analyzing the residual luciferase activity.

The data obtained showed that CAR T cells expressing FurON CAR19, containing a limited number of mutations in the degron domain, killed tumor CD19+ cells in a stabilizing compound- and target-dependent manner and were as efficient as cells with the parental CAR construct (FIG. 19A -19B).

Example 22 Compound-Dependent and Tumor-Dependent Cytokine Secretion Induced by FurON CAR

Primary human T cells were transduced with a furin degron domain fused to an anti-CD19 scFv CAR construct (construct #130). Non-transduced T cells (HT) were used as controls. The CAR19 parent construct was included as a reference for full functional CAR activity. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7. Bazedoxifene (BZA) was added on day 8 to a portion of the FurON 130 BZA sample so that CAR expression could be determined on day 10 by FACS using protein L staining before cells were frozen. Cells were frozen on day 10. T cells were thawed and co-cultured with luciferase-containing target cells of this line (CD19+ NALM6 cells) for 20 hours at a 5:1 effector:target ratio in the presence or absence of bazedoxifene. CAR T cells were normalized to the same percentage of CAR expressing cells. The supernatant was collected and evaluated for IFNγ levels.

The data obtained showed that CAR T cells expressing FurON CAR19 containing a limited number of mutations in the degron domain secrete cytokines in the presence of tumor CD19+ cells in a stabilizing compound-dependent manner and are not inferior to cells with the parental CAR construct (FIG. 20).

Example 23 Compound-Dependent and Tumor-Dependent T Cell Proliferation

Primary human T cells were transduced with a furin degron domain fused to an anti-CD19 scFv CAR (construct #130). Non-transduced T cells (HT) were used as controls. The CAR19 parent construct was included as a reference for full functional CAR activity. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7. Bazedoxifene was added on day 8 to a portion of the FurON 130 BZA sample so that CAR expression could be determined on day 10 by FACS using protein L staining before cells were frozen. Cells were frozen on day 10. T cells were thawed and co-cultured with luciferase-containing target cell lines of the indicated lines for 4 days in the presence or absence of bazedoxifene. CAR T cells were normalized to the same percentage of CAR expressing cells. After 4 days, the samples were analyzed by FACS, and 3000 events in the discrimination window for Counting Beads were collected for all samples.

The data obtained showed that CD3+ T cells containing FurON CAR19 proliferated in the presence of CD19+ tumor cells in a stabilizing compound-dependent manner and were not inferior to cells with the CAR parent construct (FIG. 21).

Example 24 Compound Inducible Expression of CAR123 in Primary Human T Cells

Primary human T cells were transduced with a furin degron domain fused to an anti-CD123 scFv CAR construct. Non-transduced T cells (HT) and parental CAR123 were used as controls. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7, bazedoxifene (BZA) was added on day 8 (Furon123+BZA), or not added (Furon123). Prior to cell freezing, CAR expression was determined on day 10 by FACS using protein L staining.

The data obtained showed that the FurON domain regulates CAR123 expression in primary human T cells in a stabilizing compound-dependent manner (FIG. 22).

Example 25 Compound-Dependent CAR123-Mediated Tumor Killing

Primary human T cells were transduced with a furin degron domain fused to an anti-CD123 scFv CAR construct. Non-transduced T cells (HT) were used as controls. The CAR123 parent construct was included as a reference for full functional CAR activity. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7, bazedoxifene (BZA) was added on day 8 (FurON123+ BZA) or not added (FurON123). Prior to cell freezing, CAR expression was determined on day 10 by FACS using protein L staining. T cells were thawed and co-cultured with luciferase-containing target cell lines of the indicated lines for 20 hours in the presence or absence of bazedoxifene. Molm13 is a CD123+ cell line; very low expression of CD123+ is observed in K562 cells. Different ratios of CART and target cells were used, as indicated by the x-axis (E:M ratios) in FIG. 25. CAR T cells were normalized to the same percentage of CAR expressing cells. Tumor lysis in percent was determined by analyzing the residual luciferase activity.

The data showed that CAR T cells expressing FurON CAR123 killed tumor CD123+ cells in a stabilizing compound- and target-dependent manner and were as efficient as cells with the CAR parent construct (FIG. 23).

Example 26: Compound-Dependent and Tumor-Dependent Cytokine IFNγ Secretion by Cells with FurON CAR123

Primary human T cells were transduced with a furin degron domain fused to an anti-CD123 scFv CAR. Non-transduced T cells (HT) were used as controls. The CAR123 parent construct was included as a reference for full functional CAR activity. Cells were expanded for 10 days in the presence of anti-CD3/CD28 stimulating beads. 100 U/ml IL-2 was added on day 7, bazedoxifene (BZA) was added on day 8 (FurON123+ BZA) or not added (FurON123). Cells were frozen on day 10. T cells were thawed and co-cultured with luciferase-containing target cell lines of the indicated lines for 20 hours at a 5:1 effector to target ratio in the presence or absence of bazedoxifene. Molm13 is a CD123+ cell line; very low expression of CD123+ is observed in K562 cells. The supernatant was collected and evaluated for IFNγ levels.

The data obtained showed that CAR T cells expressing FurON CAR123 secrete cytokines in the presence of CD123+ tumor cells in a stabilizing compound-dependent manner and are non-inferior to cells with the CAR parent construct (FIG. 24).

Example 27: FurON CART19 is effective against CD19+ tumor cells in an animal model only when administered with bazedoxifene

cell line

NALM6 (RRID: CVCL_0092) is a human leukemia cell line that is derived from peripheral blood cells of a 19-year-old human with acute lymphoblastic leukemia (ALL) relapsed in 1976. Cells were grown in RMPI medium containing 10% fetal bovine serum . The cells of this line are grown in suspension in tissue culture flasks. Cells of this line persist and proliferate in mice upon intravenous implantation. NALM6 cells have been modified to express luciferase so that tumor cell growth can also be monitored by imaging mice.

Mice

6 week old NSG mice (NOD.Cg- Prkdc ^scid Il2rg ^{tm 1 Wjl} /SzJ) were obtained from Jackson Laboratory. Animals were allowed to acclimate in the NIBR animal housing for at least 3 days prior to the experiment. Animals were handled in accordance with Novartis Laboratory Animal Care and Use Commission (ACUC) rules and guidelines. Animal identification electronic transponders were implanted in the left flank of the animals one day before tumor implantation.

Tumor implantation

Log phase NALM6 cells were harvested and washed in 50 ml Falcon tubes at 1200 rpm for 5 minutes, once in growth medium and then twice in cold sterile PBS. Cells were resuspended in PBS at a concentration of 5×10 ⁶ /ml, placed on ice and immediately injected into mice. Tumor cells were injected intravenously in a volume of 200 μl through the tail vein. Model NALM6 cells endogenously express CD19 and thus can be used to test the in vivo efficacy of CD19-targeted CAR T cells. In this model, the tumor grows well when intravenously implanted in mice and can be visualized to determine tumor burden.

Obtaining CART19 and FurON CART19 cells for in vivo studies

CAR T cells were obtained from apheresis blood samples from healthy donors whose "naive" T cells were obtained by negative selection for T cells, CD4+ and CD8+ lymphocytes. These cells were activated by adding anti-CD3/CD28 beads ( ^Dynabeads® Human T-Expander CD3/CD28, Thermo Fisher Scientific) at a ratio of 1:3 (T cells:beads) to T cell medium (RPMI 1640, 10 % heat-inactivated fetal calf serum (FBS), 2 mM L-glutamine, 1x penicillin/streptomycin mixture, 100 µM non-essential amino acids, 1 mM sodium pyruvate, 10 mM Hepes, and 55 µM 2-mercaptoethanol) at 37°C, 5% CO ₂ . T cells were cultured at a density of 4×10 ⁶ T cells (HT) or 5×10 ⁶ (CART19 and FurON CART19) in 1 ml of medium per well of a 24-well plate. After 24 hours, when the T cells were in the blast stage, 0.5 ml of unconcentrated, or smaller volumes of concentrated, viral supernatant was added; T cells were transduced with a multiplicity of infection (MOI) of 5. T cells began to divide logarithmically, which was monitored by measuring the number of cells per ml, and T cells were diluted with fresh medium every two days. On day 7, cultures were supplemented with 100 U/ml IL2 (Peprotech, Rocky Hill, NJ) and 1 μM bazedoxifene. On day 9, 1 μM bazedoxifene was added. On day 10, cells were harvested and the percentage of transduced cells (expressing CD19-specific CAR on the cell surface) was determined by flow cytometry on a Fortessa FACS analyzer (BD). Viral transduction results showed similar transduction efficiency; the surface expression of FurON CAR19 (mean fluorescence intensity, MIF) was lower than in the case of CART19. All CAR T cells were obtained under research-grade manufacturing conditions (i.e., not for clinical use).

Treatment with CART19 or FurON CART19 cells

CD19+ NALM6 tumor cells expressing luciferase were infused into NSG mice. Seven days later, tumor burden was determined by whole body bioluminescence, animals were randomized into treatment groups (5 mice per group) and infused with PBS (solvent), CART19 (1×10 ⁶ or 5×10 ⁶ CAR+ T cells), FurON CART19 cells (5×10 ⁶ CAR+ T cells) or non-transduced T cells (HT), intravenously via the lateral tail vein. All animals received the same dose of total T cells (16.4×10 ⁶ cells/mouse). Animals in some treatment groups were treated with bazedoxifene (BZA), bazedoxifene plus interleukin 2 (BZA/IL2), or vehicle as indicated. BZA was administered for 10 days (single dose of 200 mg/kg; po). IL2 was administered for 5 days, paused for two days, and reintroduced for 3 days (single dose 18×10 ⁶ IU/kg; i.p.). Tumor growth and animal health were monitored over time. A plot of mean bioluminescence intensity for all treatment groups is shown in FIG. 27; the arrow indicates when the administration of BZA and IL2 was stopped.

results

As shown in FIG. 47, while tumors continued to develop in mice used as negative controls and FurON CART19 alone, tumor growth was inhibited in mice infused with CART19 or infused with FurON CART19 and BZA alone or BZA plus IL2. After cessation of bazedoxifene and IL2 administration, only constitutively active CART19 at the highest dose was able to control tumor growth. BZA has previously been shown to have no effect on NALM6 tumor cell growth at the same doses and dosing regimens (data not shown). Thus, FurON CART19 in the presence of bazedoxifene showed comparable tumor inhibitory activity as the positive control CART19.

Example 28: Additional FurON CAR Sequences

Table 24. Sequences of additional FurON CAR constructs and their components

Amino acid sequence DNA sequence Leader sequence/Signal peptide (SP) MALPVTALLLPLALLLHAARP (SEQ ID NO: 139) atggccctccctgtcaccgccctgctgcttccgctggctcttctgctccacgccgctcggccc (SEQ ID NO: 140) SP-Linker 2-ERmut1-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGS GGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKK (SEQ ID NO: 990) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccctcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggaccg cgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgcg tggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatccat ctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaacccccggccctcca ggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacgctcctcgccttctgatctaccacaccagccggctccattctggaatccctg ccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtct tgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgt catctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccg tgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggagg aaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaag gataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1050) SP-Linker 2-ERmut2-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGS GGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKK (SEQ ID NO: 991) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccctcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggaccg cgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgcg tggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatccat ctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaacccccggccctcca ggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacgctcctcgccttctgatctaccacaccagccggctccattctggaatccctg ccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtct tgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgt catctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccg tgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggagg aaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaag gataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1051) SP-Linker 2-ERmut1-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGGSGGGGSGGGGS QVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFK (SEQ ID NO: 992) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccctcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggaccg cgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgcg tggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatccat ctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccagcaga aagcgacgggaaattgtgatgacccagtcacccgccactcttagccttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatctgg gaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactcttt cactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgacacc gccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgactt cgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgcg cgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcg agattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1052) SP-Linker 2-ERmut2-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGGSGGGGSGGGGS QVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFK (SEQ ID NO: 993) c agcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccac gacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1053) SP-Linker 2-ERmut1-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 994) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccctcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggaccg cgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgcg tggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatccat ctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaacccccggccctcca ggaagcgaaggtccctcggagacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacggggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaacta actacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggct cgggaggcggaggttcggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagatt ctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagac ccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcat gccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggggcct gtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1054) SP-Linker 2-ERmut2-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 995) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggccct cgggaagcgaaggtccctcggagacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaact aactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcgg ctcgggaggcggaggttcggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaaggcgcctaagctgctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccaga ttctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtag acccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgtt catgccggttcccagaggagaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcc tgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1055) SP-Linker 2-ERmut1-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSG GGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 996) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccctcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggaccg cgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgcg tggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatccat ctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagaacccccggccctcca ggaagcgaaggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccaggggaga gtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttcggac attcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcaggaac cgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgt gcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagagggaggacggctgttcatgccggttcccagaggagggagga aggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaagga (SEQ ID NO: 1056) SP-Linker 2-ERmut2-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSG GGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 997) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccagca gaaagcgacggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccaggggaga gtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttcggac attcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcaggaac cgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgt gcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagagggaggacggctgttcatgccggttcccagaggagggagga aggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaagga (SEQ ID NO: 1057) SP-Linker 2-ERmut1-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 998) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggccct cgggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtg tacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggt cgggcatcaggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccct cacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccgggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcat gtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggct gttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagag (SEQ ID NO: 1058) SP-Linker 2-ERmut2-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 999) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggccct cgggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtg tacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggt cgggcatcaggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccct cacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccgggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcat gtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggct gttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagag (SEQ ID NO: 1059) SP-Linker 2-ERmut1-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRA SGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMR PVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1000) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcGggacgggagctgaagatccacgacccagca gaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactatgcc gcatccgtgaaggggagattcaccatcagccgggacaactcgggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggcggat cggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggttccgg tactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggcc gtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagga ggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaa aggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1060) SP-Linker 2-ERmut2-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKA GLTLQQQQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRA SGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMR PVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1001) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccagca gaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactatgcc gcatccgtgaaggggagattcaccatcagccgggacaactcgggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggcggat cggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggttccgg tactgatttcaccctgaccatttcctccctgcaaccgggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggcc gtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagga ggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaa aggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1061) SP-Linker 3-ERmut1-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGG GSGGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1002) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgattcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatgggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccgcaggctcctcgccttctgatctaccacaccagccggctccattctggaatcc ctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggg tcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaact gtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgggg ccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggag gaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaa aaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1062) SP-Linker 3-ERmut2-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGG GSGGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1003) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgattcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatgggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccgcaggctcctcgccttctgatctaccacaccagccggctccattctggaatcc ctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggg tcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaact gtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgggg ccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggag gaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaa aaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1063) SP-Linker 3-ERmut1-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1004) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgattcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatgggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccag cagaaagcgacgggaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacagctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggat ctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaact ctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccgggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccga caccgccgtgtactattgcgctaagcattactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttg acttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactg cgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgccagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaagatggcagaagcctatag cgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1064) SP-Linker 3-ERmut2-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1005) c agcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccac gacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1065) SP-Linker 3-ERmut1-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1006) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgattcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatgggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcgga actaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggc ggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatcca gattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatg Tags: ttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggg cctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1066) SP-Linker 3-ERmut2-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1007) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgatTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctccaggaagcgaaggtccctcggagaacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcggcgg aactaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggagg cggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccat ccagattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcat gtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggct gttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagag (SEQ ID NO: 1067) SP-Linker 3-ERmut1-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVS SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 1008) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgattcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatgggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttttgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccagg ggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacagggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttc ggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcagg aaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggcc gtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagga ggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaa aggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1068) SP-Linker 3-ERmut2-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVS SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 1009) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgatTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgaccca gcagaaagcgacggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccagg ggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacagggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttc ggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcagg aaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggcc gtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagga ggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaa aggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1069) SP-Linker 3-ERmut1-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1010) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgatTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctcgggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattg tgtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcggg ggtcgggcatcagggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtg ccctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccgggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgga ggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgctcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaaggagaggac ggctgttcatgccggttcccagaggaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatcccca agagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1070) SP-Linker 3-ERmut2-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1011) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgatTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctcgggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattg tgtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcggg ggtcgggcatcagggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtg ccctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccgggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgga ggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgctcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaaggagaggac ggctgttcatgccggttcccagaggaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatcccca agagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1071) SP-Linker 3-ERmut1-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSG GRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPF MRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1012) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgatTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcGggacgggagctgaagatccacgaccca gcagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactat gccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggc ggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggtt ccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgg ggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagagg aggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctcca aaaggtaagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1072) SP-Linker 3-ERmut2-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPDSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSG GRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPF MRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1013) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgatTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgaccca gcagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactat gccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggc ggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggtt ccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgg ggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagagg aggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctcca aaaggtaagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1073) SP-Linker 4-ERmut1-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGG GSGGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1014) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaactcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggccct cgggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccct gccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggt cttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactg tcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggcc gtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagga ggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaa aggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1074) SP-Linker 4-ERmut2-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGG GSGGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1015) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaactcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggccct cgggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaatccct gccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggt cttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactg tcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggcc gtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagga ggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaa aggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1075) SP-Linker 4-ERmut1-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1016) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaactcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccagca gaaagcgacgggaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacagctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggatct gggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaactct ttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccgaca ccgccgtgtactattgcgctaagcattactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgact tcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactgc gcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaagatggcagaagcctatagc gagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1076) SP-Linker 4-ERmut2-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1017) c agcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccac gacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1077) SP-Linker 4-ERmut1-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1018) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaactcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggccct cgggaagcgaaggtccctcggagacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaact aactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcgg ctcgggaggcggaggttcggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaaggcgcctaagctgctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccaga ttctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtag acccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgtt catgccggttcccagaggagagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcc tgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1078) SP-Linker 4-ERmut2-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1019) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaacTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcgga actaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggc ggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatcca gattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatg Tags: ttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggg cctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1079) SP-Linker 4-ERmut1-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVS SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 1020) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaactcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttctccgaagccagcatgatgggcctgttgactaacctggcggacc gcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatgc gtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttatcca tctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggccct cggaagcgaaggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccagggg agagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttcgg acattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcagga accgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccg tgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggagg aaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaag gataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1080) SP-Linker 4-ERmut2-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVS SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 1021) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaacTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccag cagaaagcgacggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccagggg agagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttcgg acattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcagga accgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccg tgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggagg aaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaag gataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1081) SP-Linker 4-ERmut1-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1022) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaacTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgt gtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcggggg tcgggcatcaggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgcc ctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggagg catgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacgg ctgttcatgccggttcccagaggaggagaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccagaa gggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1082) SP-Linker 4-ERmut2-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1023) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaacTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgt gtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcggggg tcgggcatcaggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgcc ctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggagg catgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacgg ctgttcatgccggttcccagaggaggagaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccagaa gggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1083) SP-Linker 4-ERmut1-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSG GRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPF MRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1024) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaacTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcGggacgggagctgaagatccacgacccag cagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactatg ccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggcgg atcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggttcc ggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgggg ccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggag gaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaa aaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1084) SP-Linker 4-ERmut2-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSG GRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPF MRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1025) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccaacTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccag cagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactatg ccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggcgg atcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggttcc ggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgggg ccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggag gaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaa aaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1085) SP-Linker 5-ERmut1-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGG GSGGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1026) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctcgggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaat ccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccg ggtcttgtgaagccatcagaaactctttcactgacttgtgtgtgagcggagtgtctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactctcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaa actgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgg ggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagagg aggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctcca aaaggtaagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1086) SP-Linker 5-ERmut2-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGG GSGGGGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1027) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctcgggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacaggctcctcgccttctgatctaccacaccagccggctccattctggaat ccctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccg ggtcttgtgaagccatcagaaactctttcactgacttgtgtgtgagcggagtgtctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactctcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaa actgtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgg ggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagagg aggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctcca aaaggtaagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1087) SP-Linker 5-ERmut1-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1028) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgaccca gcagaaagcgacgggaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacagctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcgg atctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaa actctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccgggggaagggtctggaatggattggagtgatttggggctctgagactactactactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagcc gacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtctt gacttcgcctgcgatatctacatttggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagagggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaact gcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaaagatggcagaagccta tagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1088) SP-Linker 5-ERmut2-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGGG GSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIF KQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1029) c agcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccac gacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1089) SP-Linker 5-ERmut1-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1030) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctccaggaagcgaaggtccctcggagaacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcggcgg aactaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggagg cggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccat ccagattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcat gtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggct gttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagag (SEQ ID NO: 1090) SP-Linker 5-ERmut2-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1031) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctccaggaagcgaaggtccctcggagaacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcggcgg aactaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggagg cggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccat ccagattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcat gtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggct gttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagag (SEQ ID NO: 1091) SP-Linker 5-ERmut1-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVS SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 1032) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctccaggaagcgaaggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacggggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttcca ggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggtt cggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctca ggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgggg ccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggag gaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaa aaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1092) SP-Linker 5-ERmut2-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVS SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 1033) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgaccca gcagaaagcgacggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccagg ggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacagggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttc ggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcagg aaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggcc gtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagga ggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaa aggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1093) SP-Linker 5-ERmut1-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1034) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctcgggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattg tgtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcggg ggtcgggcatcagggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtg ccctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccgggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgga ggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgctcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaaggagaggac ggctgttcatgccggttcccagaggaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatcccca agagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1094) SP-Linker 5-ERmut2-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1035) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccgg ccctcgggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattg tgtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcggg ggtcgggcatcagggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtg ccctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccgggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgga ggcatgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgctcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaaggagaggac ggctgttcatgccggttcccagaggaggagggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatcccca agagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1095) SP-Linker 5-ERmut1-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSG GRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPF (SEQ ID NO: 1036) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcGggacgggagctgaagatccacgaccca gcagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactat gccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggc ggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggtt ccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgg ggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagagg aggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctcca aaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1096) SP-Linker 5-ERmut2-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPESLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHLMA KAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSG GRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPF MRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1037) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggcccgagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcgg accgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaat gcgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacaccctta tccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgaccca gcagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactat gccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggc ggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggtt ccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgg ggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagagg aggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctcca aaaggtaagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1097) SP-Linker 6-ERmut1-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPQSLALSLLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGG GGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 1038) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccgcaggctcctcgccttctgatctaccacaccagccggctccattctggaatcc ctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggg tcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaact gtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgggg ccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggag gaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaa aaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1098) SP-Linker 6-ERmut2-Furin cleavage site 2-CD19 CAR2 MALPVTALLLPLALLLHAARPQSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRSLGDVGEIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGG GGSGGGGSQVQLQESGPGLVKPSETLSLTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRG (SEQ ID NO: 1039) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtgaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccgcaggctcctcgccttctgatctaccacaccagccggctccattctggaatcc ctgccaggttcagcggtagcggatctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggg tcttgtgaagccatcagaaactctttcactgacttgtactgtgagcggagtgtctccccgattacggggtgtcttggatcagacagccaccggggaagggtctggaatggattggagtgatttggggctctgagactactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaact gtcatctgtgaccgcagccgacaccgccgtgtactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgggg ccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggag gaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaa aaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1099) SP-Linker 6-ERmut1-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPQSLALSLLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGG GGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLY (SEQ ID NO: 1040) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccag cagaaagcgacgggaaattgtgatgacccagtcacccgccactcttagcctttcacccggtgagcgcgcaaccctgtcttgcagagcctcccaagacatctcaaaataccttaattggtatcaacagaagcccggacagctcctcgccttctgatctaccacaccagccggctccattctggaatccctgccaggttcagcggtagcggat ctgggaccgactacaccctcactatcagctcactgcagccagaggacttcgctgtctatttctgtcagcaagggaacaccctgccctacacctttggacagggcaccaagctcgagattaaaggtggaggtggcagcggaggaggtgggtccggcggtggaggaagccaggtccaactccaagaaagcggaccgggtcttgtgaagccatcagaaact ctttcactgacttgtactgtgagcggagtgtctctccccgattacggggtgtcttggatcagacagccaccgggggaagggtctggaatggattggagtgatttggggctctgagactacttactactcttcatccctcaagtcacgcgtcaccatctcaaaggacaactctaagaatcaggtgtcactgaaactgtcatctgtgaccgcagccga caccgccgtgtactattgcgctaagcattactattgcgctaagcattactattatggcgggagctacgcaatggattactggggacagggtactctggtcaccgtgtccagcaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccgtgcatacccggggtcttg acttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactcttttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggaggaaggcggctgcgaactg cgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgccagaaagaatccccaagagggcctgtacaacgagctccaaaaggtaagatggcagaagcctatag cgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1100) SP-Linker 6-ERmut2-Furin cleavage site 3-CD19 CAR2 MALPVTALLLPLALLLHAARPQSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREIVMTQSPATLSLSPGERATLSCRASQDISKYLNWYQQKPGQAPRLLIYHTSRLHSGIPARFSGSGSGTDYTLTISSLQPEDFAVYFCQQGNTLPYTFGQGTKLEIKGGGGSGGGSGG GGSQVQLQESGPGLVKPSETLSLTTCTVSGVSLPDYGVSWIRQPPGKGLEWIGVIWGSETTYYSSSLKSRVTISKDNSKNQVSLKLSSVTAADTAVYYCAKHYYYGGSYAMDYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLY (SEQ ID NO: 1041) c agcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccac gacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1101) SP-Linker 6-ERmut1-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPQSLALSLLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1042) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcgga actaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggc ggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatcca gattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatg Tags: ttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggg cctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1102) SP-Linker 6-ERmut2-Furin cleavage site 2-CD123 CAR MALPVTALLLPLALLLHAARPQSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY AASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYD VLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1043) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcgga actaactacgcacagaagttccaggggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggc ggctcgggaggcggaggttcggacattcagatgacccagtccccatcctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatcca gattctcgggatcaggctcaggaaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatg Tags: ttcatgccggttcccagaggagaggaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagaggg cctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1103) SP-Linker 6-ERmut1-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPQSLALSLLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVT VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCK (SEQ ID NO: 1044) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagtcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttttgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccagg ggagagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacagggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttc ggacattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcagg aaccgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggcc gtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggagga ggaaggcggctgcgaactgcgcgctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaa aggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1104) SP-Linker 6-ERmut2-Furin cleavage site 3-CD123 CAR MALPVTALLLPLALLLHAARPQSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRRQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTLTRDTSISTVYMELSRLRSDDTAVYYCARDMNILATVPFDIWGQGTMVT VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTVNSLQPEDFATYYCQQGDSVPLTFGGGTRLEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCK (SEQ ID NO: 1045) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccag cagaaagcgacggcaagtgcaactcgtccaaagcggagcggaagtcaagaaacccggagcgagcgtgaaagtgtcctgcaaagcctccggctacacctttacgggctactacatgcactgggtgcgccaggcaccaggacagggtcttgaatggatgggatggatcaaccctaattcgggcggaactaactacgcacagaagttccagggg agagtgactctgactcgggatacctccatctcaactgtctacatggaactctcccgcttgcggtcagatgatacggcagtgtactactgcgcccgcgacatgaatatcctggctaccgtgccgttcgacatctggggacaggggactatggttactgtctcatcgggcggtggaggttcaggaggaggcggctcgggaggcggaggttcgg acattcagatgacccagtccccatcctctctgtcggccagcgtcggagatagggtgaccattacctgtcgggcctcgcaaagcatctcctcgtacctcaactggtatcagcaaaagccgggaaaggcgcctaagctgctgatctacgccgcttcgagcttgcaaagcggggtgccatccagattctcgggatcaggctcagga accgacttcaccctgaccgtgaacagcctccagccggaggactttgccacttactactgccagcagggagactccgtgccgcttactttcggggggggtacccgcctggagatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtggggccg tgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggaggagg aaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaaaag gataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1105) SP-Linker 6-ERmut1-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPQSLALSLLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDTHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1046) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgt gtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcggggg tcgggcatcaggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgcc ctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggagg catgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacgg ctgttcatgccggttcccagaggaggagaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccagaa gggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1106) SP-Linker 6-ERmut2-Furin cleavage site 2-BCMA CAR MALPVTALLLPLALLLHAARPQSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRL GTGAEDPRPSRKRRSLGDVG EVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGSGGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVP SRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPE MGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1047) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcggaaccggcgcggaagacccccggcc ctcggaagcgaaggtccctcggagacgtgggtgaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgt gtacagcggtagcacctactatgccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcggggg tcgggcatcaggggcggcggatcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgcc ctcacggttctccggctccggttccggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccgggagg catgtagacccgcagctggtggggccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatctttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacgg ctgttcatgccggttcccagaggaggagaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccagaa gggcctgtacaacgagctccaaaaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1107) SP-Linker 6-ERmut1-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPQSLALSLLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLALHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSSKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGS GGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQ PFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1048) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctggccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgtccaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcGggacgggagctgaagatccacgacccag cagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactatg ccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggcgg atcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggttcc ggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgggg ccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggag gaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaa aaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1108) SP-Linker 6-ERmut2-Furin cleavage site 3-BCMA CAR MALPVTALLLPLALLLHAARPQSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINWAKRVPGFVDLTLHDQVHLLECAWMEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEGGVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLDKITLIHL MAKAGLTLQQQHQRLAQLLLILSHIRHMSNKRMEHLYSMKCKNVVPLSDLLLEMLDAHRLGTGAEDPRPSRKRREVQLVESGGGLVQPGGSLRLSCAVSGFALSNHGMSWVRRAPGKGLEWVSGIVYSGSTYYAASVKGRFTISRDNSRNTLYLQMNSLRPEDTAIYYCSAHGGESDVWGQGTTVTVSSASGGGGS GGRASGGGGSDIQLTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQ PFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 1049) atggccctccctgtcaccgccctgctgcttccgctggctcttgctccacgccgctcggccccagTcgttggcactttccctgactgccgaccagatggtgtccgcccttctggacgccgagcctccaattctgtactcggagtacgatccgactcgcccgttccgaagccagcatgatggcctgttgactaacctggcggac cgcgagttggtgcacatgattaactgggctaagcgggtgccgggcttcgtggacctgaccctgcacgaccaagtgcacctcctggaatgcgcctggatggaaatcctcatgatcggcctcgtgtggagatccatggagcatcccggaaagctcctgtttgcacccaacctcctgcttgatcgcaaccagggaaaatg cgtggaagggggtgtcgagattttcgacatgctgctcgccacctcttcccggttccggatgatgaatctgcagggagaagagttcgtgtgtctgaagtcaatcatcctgctgaactccggggtctataccttcctgagctcgaccctcaagtcactggaggaaaaagaccacatccatcgcgtgctcgataagatcaccgacacccttat ccatctcatggcgaaggctggactgaccctgcaacagcagcaccagaggctggcccagttgctgctgattctgagccacatccggcacatgtcgaacaagaggatggaacacctgtacagcatgaagtgcaagaacgtcgtgcctctgtccgatctgctcctggaaatgctggacgcgcacagactcgggacgggagctgaagatccacgacccag cagaaagcgacgggaagtgcaattggtggaatcagggggaggacttgtgcagcctggaggatcgctgagactgtcatgtgccgtgtccggctttgccctgtccaaccacgggatgtcctgggtccgccgcgcgcctggaaagggcctcgaatgggtgtcgggtattgtgtacagcggtagcacctactatg ccgcatccgtgaaggggagattcaccatcagccgggacaactccaggaacactctgtacctccaaatgaattcgctgaggccagaggacactgccatctactactgctccgcgcatggcggagagtccgacgtctggggacaggggaccaccgtgaccgtgtctagcgcgtccggcggaggcggcagcgggggtcgggcatcagggggcggcgg atcggacatccagctcacccagtccccgagctcgctgtccgcctccgtgggagatcgggtcaccatcacgtgccgcgccagccagtcgatttcctcctacctgaactggtaccaacagaagcccggaaaagccccgaagcttctcatctacgccgcctcgagcctgcagtcaggagtgccctcacggttctccggctccggttcc ggtactgatttcaccctgaccatttcctccctgcaaccggaggacttcgctacttactactgccagcagtcgtactccaccccctacactttcggacaaggcaccaaggtcgaaatcaagaccactaccccagcaccgaggccacccaccccggctcctaccatcgcctcccagcctctgtccctgcgtccggaggcatgtagacccgcagctggtgggg ccgtgcatacccggggtcttgacttcgcctgcgatatctacatttgggcccctctggctggtacttgcggggtcctgctgctttcactcgtgatcactctttactgtaagcgcggtcggaagaagctgctgtacatcttttaagcaacccttcatgaggcctgtgcagactactcaagaggaggacggctgttcatgccggttcccagaggag gaggaaggcggctgcgaactgcgcgtgaaattcagccgcagcgcagatgctccagcctaccagcaggggcagaaccagctctacaacgaactcaatcttggtcggagagaggagtacgacgtgctggacaagcggagaggacgggacccagaaatgggcgggaagccgcgcagaaagaatccccaagagggcctgtacaacgagctccaa aaggataagatggcagaagcctatagcgagattggtatgaaaggggaacgcagaagaggcaaaggccacgacggactgtaccagggactcagcaccgccaccaaggacacctatgacgctcttcacatgcaggccctgccgcctcgg (SEQ ID NO: 1109)

Example 29: Temporary controlled complete depletion of B-cells

The following is a description of the materials and methods used in these experiments.

Creation of CAR constructs containing suicide genes . For the FMC63 (anti-CD19) single chain variable fragment (scFv) constructs, a previously described vector (pRRLSIN.cPPT. WPRE gene of interest with human EF1-alpha gene promoter) was used, which was modified to express caspase-9 as follows:

1. For the expression of inducible caspase-9 at the 3' position of the FMC63-bbz CAR, the transmembrane domain and cytoplasmic tail were removed by EcoRV and SalI cleavage and replaced with a block of genes (IDT) encoding the same transmembrane domain and cytoplasmic tail, for followed by site 2A and FKBP12F36V, followed by a short GS linker and the domain of the caspase-9 promolecule.

2. For expression of inducible caspase-9 at the 5' position of the FMC63-bbz CAR, the signal peptide and part of the FMC63 scFv were removed by cleavage with XbaI and Tth111I and replaced with a block of genes (IDT) encoding the same inducible caspase-9 domain as described in 1 followed by the 2A site and the sequence encoding the previously deleted part of the original plasmid.

3. For the expression of reversible caspase-9 at the 3' position of the FMC63-bbz CAR, the transmembrane domain and cytoplasmic tail were removed by cleavage with EcoRV and SalI and replaced with a block of genes (geneart, Thermofisher) encoding the same transmembrane domain and cytoplasmic tail. followed by site 2A and 2 repeats of FKBP12F36M, followed by a short GS linker (SGGGS, SEQ ID NO:3036) and a caspase-9 promolecule domain.

4. For human CD20 scFv expression, the FMC63 scFv and CD8 hinge were removed from the constructs described in 1-3 and replaced with a codon-optimized gene block (IDT) encoding the amino acid sequence of veltuzumab.

Create CAR constructs containing conditional aggregation domains . To express conditional aggregation domains at the 5' position from the FMC63-bbz CAR, the plasmid was cut with BamHI between the signal peptide and scFv, and a block of genes (geneart) encoding 4 FKBP12F36M repeats followed by a furin recognition sequence was inserted between the signal peptide and scFv.

Obtaining lentiviruses. Pseudotyped lentiviral VSV-G particles were generated using a 4th generation packaging system. 293T cells were transfected at 90% confluency with a mixture of pRRLSIN.cPPT.EF1α-gene of interest.WPRE, envelope plasmid pMD2.G (Addgene No. 12252), packaging plasmids pRSVRev (Addgene No. 12253) and pMDLgm/pRRE (Addgene No. 12251) in complex with Lipofectamine 2000 (Life Technologies). The supernatant containing lentivirus was collected after 24 and 48 hours, filtered through a 0.4 μm PES membrane, concentrated at 12000 x g for 12 hours at 4°C and stored at -80°C.

Stimulation and expansion of primary human T cells . Primary human T cells were cultured in RPMI 1640 with 10% EBS, 10 mM HEPES, 1% penicillin/streptomycin. Total T cells (CD4 ⁺ and CD8 ⁺ ) were stimulated with anti-CD3 and anti-CD28 beads (Dynabeads, Life Technologies) at a bead:cell ratio of 3:1. 100 IU/ml interleukin 2 was added to the culture medium. 24 hours after stimulation, 10 ⁶ T cells were transduced with lentiviral particles encoding different CAR constructs or control constructs, or were sham transduced. T cell expansion was monitored for 8-12 days by measuring cell volume and concentration (Beckman Coulter counter). Cell surface expression of the CAR constructs was confirmed by flow cytometry (BD LSRII) with polyclonal antibodies against human or mouse immunoglobulin heavy and light chains. CAR staining was carried out for 25 minutes at room temperature. All staining procedures were carried out under saturation conditions. For some experiments, transduced T cells were pre-frozen in 90% FBS and 10% DMSO. Experiments were performed when the cells were at rest after stimulation (ie, volume <450 fl).

In vitro cytotoxicity and cytokine production assays . In vitro killing of NALM6 cells was tested in a ⁵¹ Cr release assay. 5×10 ⁵ target cells were loaded with 50 μCi Na ₂ ⁵¹ CrO ₄ (Perkin Elmer) for 90-120 minutes, washed twice and resuspended in phenol red free medium with 5% FBS. CAR-containing, control CAR, or mock-transduced T cells (8-10 days after initial activation) were co-incubated with loaded target cells for 4 hours at various effector:target (E:M) ratios, and chromium release into the supernatant was measured in tablet counter MicroBeta2 (Perkin Elmer). Spontaneous release from target cells (without effector cells) was analyzed in the same volume, and the maximum release was determined by lysis of target cells with SDS at a final concentration of 5%. Percent specific lysis=[(experimental release - spontaneous release)/(maximum release - spontaneous release)]*100. All experiments were performed in at least 3 replicas.

Elimination of CD19 CAR T cells . CD19 sCAR T cells were incubated in the presence of the indicated concentrations of AP20187 for 16 hours at 37°C. Dead cells were detected with violet live/dead cell dye and quantified by flow cytometry.

CD19 sCAR T cells retain biological efficacy in vivo . Mice were pretreated with IVIG (Privigen, CSL Behring) at 600 mg/kg IV for 2 days to block FcγR on monocytes and neutrophils. NSG mice were then injected with 1×10 ⁶ CD19+ NALM6 cells expressing click beetle luciferase to detect bioluminescence. Five days later, mice were injected with either 5×10 ⁶ CD19 CAR T cells expressing inducible caspase-9 or non-transduced control T cells. Peripheral blood was collected from the retroorbital sinus and B cell presence and T cell engraftment were determined by flow cytometry using BD TruCOUNT tubes (BD Biosciences) according to the manufacturer's instructions. Bioluminescence was assessed on days 5, 6, 7, 10, 13 and 18 after B-cell injection, which was combined with intraperitoneal administration of IVIG (600 mg/kg). Mice were euthanized for organ harvesting according to local IACUC regulations, and bone marrow, spleen, and blood samples were evaluated by flow cytometry.

The following is a description of the results of the experiment.

Depletion of B cells, if it is 100%, should result in healing of pemphigus vulgaris (PV) and other antibody-mediated diseases, since pathogenic B cells must be eliminated and an entirely new repertoire of B cells must be formed. Given the many checkpoints that prevent autoimmunity, it is unlikely that autoreactive B cells will reappear.

The advantage of the CD19 CAR T cell approach is that it is a versatile approach to treat any B cell or antibody mediated disease and has been clinically proven to be highly effective in depleting CD19 ⁺ B cells. Thus, it is not necessary to know the target antigen in the case of a particular disease. This therapeutic approach can be applied to any disease in which B cells or the antibodies they produce lead to an autoimmune condition or disease. In addition, CD19 CAR can be used to eliminate alloantibodies to non-self proteins that prevent functional rescue in genetic diseases, such as antibodies against HLA or beta-2-microglobulin due to organ transplantation, antibodies against blood group antigens or Rh due to blood transfusion or pregnancy, or against factor VIII, α-L-iduronidase and many other proteins that are used in the clinic or are being developed for replacement therapy.

CD19 CAR T cells have been shown to be effective in depleting B cells in human clinical trials, with no significant off-target cytotoxicity, although B cell depletion is permanent resulting in lifelong immunosuppression. CD20 is also a clinical target for B cell depletion. Thus, incorporation of a suicide gene into an anti-CD19 or anti-CD20 CAR (sCAR) construct, or selective activation of CART function (through reversible suicide cassette or conditional CAR expression) would allow temporal control of CAR-mediated B-cell depletion as an important intervention. security.

An example of a suicide gene in sCAR includes a human caspase-9 fusion protein with a modified human FK binding protein that allows conditional dimerization upon exposure to a synthetic dimerizing drug such as AP1903. After dimerization, caspase-9 becomes activated, leading to the death of cells expressing the suicide gene. Thus, infusion of CD19 sCAR T cells will lead to complete depletion of B cells, resulting in cure of the B cell or antibody mediated disease. Subsequent activation of the suicide gene by AP1903, AP20187, or a similar agent will result in the elimination of sCAR T cells, allowing the B cell population to recover, thus restoring normal immune function. An example of a reversible suicide gene in revCAR includes a human caspase-9 fusion protein with a modified human FK binding protein that dimerizes by default and causes death of cells expressing the suicide gene. When the dimerization domains are solubilized, caspase-9 activity is inhibited and cell death is prevented, allowing the CAR T cell to perform its function. An example of an on-CAR regulatory system includes a CAR fusion protein with modified human FK-binding protein domains that dimerizes by default and causes protein aggregation and degradation in the cell's secretory system. Solubilization of the dimerization domains allows for the exit and processing of CARs in the secretory system of the cell, including furin cleavage of CARs from the FKBP domains, which allows for functional cell surface expression of CARs.

In order to evaluate these approaches for temporal control of CAR T cell function, several constructs were created; for one embodiment, one suicide gene construct before CAR and one suicide gene construct after CAR (FIG. 27). For another embodiment, a construct with a reversible suicide gene (either before or after CAR) (FIG. 28). For another embodiment, regulatory onCAR (FIG. 26). Primary human T cells were shown to efficiently express CD19 sCAR, CD19 revCAR and CD20 CAR (FIGS. 29A-29F), and CD19 sCAR T cells showed specific cytotoxicity against their intended targets (FIG. 30). In addition, primary human T cells expressing CD19 sCAR were specifically killed after activation of the switch to self-destruct by AP20187 in vitro , while non-transduced T cells were not killed after treatment with AP20187 (FIG. 31). In addition, CD19 sCAR T cells remained effective in eliminating CD19 ⁺ B cells in an in vivo mouse model (FIG. 32) and engrafted well (FIG. 33).

As seen from the results of the cell killing assay in FIG. 34, CD20 sCAR, CD20 revCAR and CD20 onCAR showed equivalent and specific killing of CD20+ target cells. On-CAR was tested in the presence of 500 nM Shield-1.

As seen in FIG. 35, in the absence of a FKBP solubilizing ligand (eg, shield-1), CAR function is inhibited. At a lower E:M ratio, On-CAR function is strongly inhibited if the FKBP ligand is not present.

As seen in FIG. 36, CAR surface expression can be modulated by the FKBP Shield-1 ligand. Shield-1 causes a dose-dependent increase in CAR expression, while the absence of Shield-1 results in a ~60% decrease in CD20 on-CAR expression.

As seen in FIG. 37, Shield-1 was titrated in the CD19rev CAR system and lower doses of Shield-1 resulted in higher caspase-9 activation and increased apoptosis.

As seen in FIG. 38, in vivo evaluation of apoptosis efficiency in anti-CD19 revCAR T cells showed sufficient in vivo apoptosis of revCAR T cells (FIG. 38). The in vivo efficacy of CD19 revCAR T cells was also evaluated (FIG. 39).

As seen in FIG. 40, 41 and 42, suicide gene activation resulted in peripheral depletion of suicide CAR T cells (eg, depletion of sCAR T cells in lymphoid organs in FIG. 42).

The chronological sequence of actions for obtaining a T cell according to the present invention is schematically depicted in FIG. 43, and the chronological sequence of steps in the design of the in vivo experiment of the present invention is shown schematically in FIG. 44.

As shown in FIG. 45, "generic" sCAR T cells can deplete peripheral B cells in non-autologous BT mice and human B cells in a non-cancer humanized mouse model. In addition, in FIG. 46 shows that universal sCAR T cells can be depleted when exposed to AP1903.

The corresponding sequences for some of the experimental results presented in this paper are given below:

CD19 scar:

Suicide gene followed by CD19 CAR (nc)

Suicide gene followed by CD19 CAR (ak)

CD19 CAR followed by a suicide gene (nc)

CD19 CAR followed by a suicide gene (ak)

CD20 CAR and sCAR:

CD20bbz CAR (NK and AK)

CD20 CAR followed by a suicide gene (nk and ak)

suicide gene followed by CD20 CAR (nk and ak)

CD19 revCAR:

CD19 CAR followed by a reversible suicide cassette (nc and ak)

CD19onCAR:

CD19 on-CAR (NK and AK)

CD20 revCAR:

CD20 CAR followed by a reversible suicide cassette (nc and ak)

CD20onCAR:

CD20 on-CAR (NK and AK)

Suicide gene = inducible caspase-9 (activates apoptosis when dimerized with small molecular weight activators)

Site 2A=ribosome exit site

CD19 CAR containing CD8 transmembrane domain, CD137 cytoplasmic signaling domains and CD3-zeta (CD3-zeta is also referred to as CD247, collectively CD137-CD3-zeta is also referred to as bbz)

Inducible caspase-9-2A - CD19bbz, nucleotide sequence (SEQ ID NO: 3018)

ATGCTCGAGGGGGTTCAGGTGGAGACTATCAGCCCGGGCGACGGACGGACATTCCCAAAGCGCGGGCAGACGTGTGTGGTGCATTACACCGGGATGCTTGAGGACGGAAAGAAAGTGGACTCTTCCCGAGACCGAAATAAACCATTCAAGTTCATGTTGGGCAAGCAGGAGGTTATCAGAGGGTGGGAGGAGGGCGTCGCTCAGATGAGTGTCGGACAGAGGGCCAAGCTCACGATCTCCCCTGATTACGCCTACGGGGCAACTGGTCACCCCGGAATCATCCCCCCTCACGCAACCCTCGTGTTCGACGTCGAGCTGCTCAAACTGGAATCAGGCGGAGGCAGTGGCGCTAGCGGGTTTGGCGATGTCGGTGCCCTTGAAAGCTTGAGAGGAAATGCCGATCTCGCTTACATCTTGAGCATGGAGCCCTGTGGGCACTGTCTGATCATCAACAATGTTAACTTTTGCCGGGAGTCCGGCCTGCGCACACGCACAGGCTCCAACATTGACTGCGAAAAACTTCGAAGGAGGTTTAGCTCTCTGCATTTCATGGTAGAGGTGAAGGGGGATCTGACCGCCAAGAAAATGGTTCTCGCCCTTCTCGAGCTTGCGCAGCAGGACCATGGAGCGCTTGACTGTTGTGTCGTTGTGATACTGAGCCATGGCTGTCAGGCTTCCCATCTCCAGTTTCCAGGGGCCGTGTACGGAACCGATGGATGCCCTGTGTCAGTTGAAAAGATCGTAAACATCTTTAACGGAACATCTTGCCCGAGCCTCGGCGGTAAACCGAAGCTTTTTTTTATCCAGGCCTGCGGCGGTGAACAGAAAGATCATGGCTTCGAGGTTGCCAGTACCAGCCCTGAAGACGAATCCCCCGGGTCAAATCCTGAACCAGATGCGACCCCTTTCCAGGAAGGACTCCGCACTTTTGACCAGCTTGACGCCATTTCCTCCCTGCCAACACCTTCCGACATATTTGTAAGCTACTCCACCTTTCCAGGATTCGTGAGCTGGCGCGACCCAAAATCCGGCAGTTGGTATGTTGAAACCCTGGACGATATTTTCGAACAATGGGCCCACAGTGAGGACCTGCAGTCCCTTCTTCTGCGCGTAGCCAATGCCGTGTCAGTCAAAGGGATTTACAAGCAGATGCCAGGCTGCTTTAATTTCCTGCGCAAGAAACTGTTTTTTAAGACCAGT GGCTCCGGCGCAACAAATTTCTCCTTGCTGAAACAGGCAGGCGACGTTGAGGAAAATCCCGGCCCA ATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACGCCGCCAGGCCGGACATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTGGGAGACAGAGTCACCATCAGTTGCAGGGCAAGTCAGGACATTAGTAAATATTTAAATTGGTATCAGCAGAAACCAGATGGAACTGTTAAACTCCTGATCTACCATACATCAAGATTACACTCAGGAGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGAACAGATTATTCTCTCACCATTAGCAACCTGGAGCAAGAAGATATTGCCACTTACTTTTGCCAACAGGGTAATACGCTTCCGTACACGTTCGGAGGGGGGACTAAGTTGGAAATAACAGGTGGCGGTGGCTCGGGCGGTGGTGGGTCGGGTGGCGGCGGATCTGAGGTGAAACTGCAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCACAGAGCCTGTCCGTCACATGCACTGTCTCAGGGGTCTCATTACCCGACTATGGTGTAAGCTGGATTCGCCAGCCTCCACGAAAGGGTCTGGAGTGGCTGGGAGTAATATGGGGTAGTGAAACCACATACTATAATTCAGCTCTCAAATCCAGACTGACCATCATCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTGCAAACTGATGACACAGCCATTTACTACTGTGCCAAACATTATTACTACGGTGGTAGCTATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAA

Inducible caspase-9-2A- CD19bbz amino acid sequence (SEQ ID NO: 3019)

MLEGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLESGGGSGASGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLEL AQQDHGALDCCVVVILSHGCQASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVASTSPEDESPGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSGSWYVETLDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTSGSGATNFSLLKQAGDVEENPGPMALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEW LGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQ LYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR

CD19bbz -2A- inducible caspase-9, nucleotide sequence (SEQ ID NO: 3020)

ATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACGCCGCCAGGCCGGACATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTGGGAGACAGAGTCACCATCAGTTGCAGGGCAAGTCAGGACATTAGTAAATATTTAAATTGGTATCAGCAGAAACCAGATGGAACTGTTAAACTCCTGATCTACCATACATCAAGATTACACTCAGGAGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGAACAGATTATTCTCTCACCATTAGCAACCTGGAGCAAGAAGATATTGCCACTTACTTTTGCCAACAGGGTAATACGCTTCCGTACACGTTCGGAGGGGGGACTAAGTTGGAAATAACAGGTGGCGGTGGCTCGGGCGGTGGTGGGTCGGGTGGCGGCGGATCTGAGGTGAAACTGCAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCACAGAGCCTGTCCGTCACATGCACTGTCTCAGGGGTCTCATTACCCGACTATGGTGTAAGCTGGATTCGCCAGCCTCCACGAAAGGGTCTGGAGTGGCTGGGAGTAATATGGGGTAGTGAAACCACATACTATAATTCAGCTCTCAAATCCAGACTGACCATCATCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTGCAAACTGATGACACAGCCATTTACTACTGTGCCAAACATTATTACTACGGTGGTAGCTATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTCGGAAGCGACGGGGCTCCGGCGCAACAAATTTCTCCTTGCTGAAACAGGCAGGCGACGTTGAGGAAAATCCCGGCCCA GGGGTTCAGGTGGAGACTATCAGCCCGGGCGA CGGACGGACATTCCCAAAGCGCGGGCAGACGTGTGTGGTGCATTACACCGGGATGCTTGAGGACGGAAAGAAAGTGGACTCTTCCCGAGACCGAAATAAACCATTCAAGTTCATGTTGGGCAAGCAGGAGGTTATCAGAGGGTGGGAGGAGGGCGTCGCTCAGATGAGTGTCGGACAGAGGGCCAAGCTCACGATCTCCCCTGATTACGCCTACGGGGCAACTGGTCACCCCGGAATCATCCCCCCTCACGCAACCCTCGTGTTCGACGTCGAGCTGCTCAAACTGGAATCAGGCGGAGGCAGTGGCGGGTTTGGCGATGTCGGTGCCCTTGAAAGCTTGAGAGGAAATGCCGATCTCGCTTACATCTTGAGCATGGAGCCCTGTGGGCACTGTCTGATCATCAACAATGTTAACTTTTGCCGGGAGTCCGGCCTGCGCACACGCACAGGCTCCAACATTGACTGCGAAAAACTTCGAAGGAGGTTTAGCTCTCTGCATTTCATGGTAGAGGTGAAGGGGGATCTGACCGCCAAGAAAATGGTTCTCGCCCTTCTCGAGCTTGCGCAGCAGGACCATGGAGCGCTTGACTGTTGTGTCGTTGTGATACTGAGCCATGGCTGTCAGGCTTCCCATCTCCAGTTTCCAGGGGCCGTGTACGGAACCGATGGATGCCCTGTGTCAGTTGAAAAGATCGTAAACATCTTTAACGGAACATCTTGCCCGAGCCTCGGCGGTAAACCGAAGCTTTTTTTTATCCAGGCCTGCGGCGGTGAACAGAAAGATCATGGCTTCGAGGTTGCCAGTACCAGCCCTGAAGACGAATCCCCCGGGTCAAATCCTGAACCAGATGCGACCCCTTTCCAGGAAGGACTCCGCACTTTTGACCAGCTTGACGCCATTTCCTCCCTGCCAACACCTTCCGACATATTTGTAAGCTACTCCACCTTTCCAGGATTCGTGAGCTGGCGCGACCCAAAATCCGGCAGTTGGTATGTTGAAACCCTGGACGATATCTTCGAACAATGGGCCCACAGTGAGGACCTGCAGTCCCTTCTTCTGCGCGTAGCCAATGCCGTGTCAGTCAAAGGGATTTACAAGCAGATGCCAGGCTGCTTTAATTTCCTGCGCAAGAAACTGTTTTTTAAGACCAGTTGAGTCGACGGAGGAGGAG

CD19bbz -2A- inducible caspase-9, amino acid sequence (SEQ ID NO: 3021)

MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEW LGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQ LYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRRKRRGSGATNFSLLKQAGDVEENPGPGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLESGGGSGGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLELAQQ DHGALDCCVVVILSHGCQASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVASTSPEDESPGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSGSWYVETLDDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTS

Human anti-CD20 signal peptide - CD8 hinge - transmembrane CD8-CD137-CD247, nucleotide sequence (SEQ ID NO:3022)

CCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCGCGTCGCAGCCCCTGTCCCCTGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATTCCGGA ATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC

Human anti-CD20 signal peptide - CD8 hinge - transmembrane CD8-CD137-CD247, amino acid sequence (SEQ ID NO: 3023)

MALPVTALLLPLALLLHAARPGSDIQLTQSPSSLSASVGDRVTMTCRASSSVSYIHWFQQKPGKAPKPWIYATSNLASGVPVRFSGSGSGTDYTFTISSLQPEDIATYCQQWTSNPPTFGGGTKLEIKRGGGGSGGGGGSGGGGSQVQLQQSGAEVKKPGSSVKVSCKASGYTFTSYNMHWVK QAPGQGLEWIGAIYPGMGDTSYNQKFKGKATLTADESTNTAYMELSSLRSEDTAFYYCARSTYYGGDWYFDVWGQGTTVTVSSAS TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDSG IYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS RSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR Z

Human anti-CD20 bbz-2A- iCasp9, nucleotide sequence (SEQ ID NO: 3024)

ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCCCTGCTGCTGCATGCTGCCAGACCTGGCTCCGATATTCAACTTACACAGTCCCCTAGTTCCTTGTCCGCCTCCGTCGGCGACAGAGTTACCATGACTTGTCGAGCGTCTTCTAGCGTTTCCTACATTCATTGGTTCCAACAGAAGCCCGGAAAGGCACCAAAACCTTGGATCTACGCCACGTCCAATTTGGCTAGTGGTGTTCCGGTGCGATTTTCCGGGTCAGGTAGCGGGACGGACTATACTTTTACCATTTCAAGCCTTCAGCCTGAAGACATCGCGACGTACTATTGTCAGCAGTGGACCTCTAACCCTCCTACCTTTGGCGGTGGAACAAAGCTGGAGATCAAACGAGGCGGGGGTGGCTCTGGGGGAGGAGGTTCCGGTGGGGGAGGCTCTCAAGTACAACTGCAACAAAGTGGGGCTGAAGTGAAGAAGCCCGGTTCTTCAGTCAAAGTATCATGTAAGGCAAGTGGTTATACTTTTACGTCTTATAACATGCATTGGGTAAAGCAAGCCCCTGGTCAGGGCCTCGAGTGGATTGGTGCGATCTACCCTGGAATGGGTGATACGAGCTATAATCAGAAATTCAAGGGGAAAGCCACCTTGACTGCAGACGAATCTACGAACACGGCTTACATGGAGCTTAGCTCACTCAGATCAGAGGATACAGCCTTTTACTACTGCGCTAGATCAACTTATTACGGAGGAGACTGGTATTTTGATGTATGGGGTCAGGGGACCACAGTCACTGTTAGCTCTGCTAGCACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATTCCGGAATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCGGCTCCGGCGCAACAAATTTCTCCTTGCTGAAACAGGCAGGCGACGTTGAGGAAAATCCCGGCCCAGGGGTTCAGGTGGAGACTATCAGCCCGGGCGACGGACGGACATTCCCAAAGCGCGGGCAGACGTGTGTGGTGCATTACACCGGGATGCTTGAGGACGGAAAGAAAGTGGACTCTTCCCGAGACCGAAATAAACCATTCAAGTTCATGTTGGGCAAGCAGGAGGTTATCAGAGGGTGGGAGGAGGGCGTCGCTCAGATGAGTGTCGGACAGAGGGCCAAGCTCACGATCTCCCCTGATTACGCCTACGGGGCAACTGGTCACCCCGGAATCATCCCCCCTCACGCAACCCTCGTGTTCGACGTCGAGCTGCTCAAACTGGAATCAGGCGGAGGCAGTGGCGGGTTTGGCGATGTCGGTGCCCTTGAAAGCTTGAGAGGAAATGCCGATCTCGCTTACATCTTGAGCATGGAGCCCTGTGGGCACTGTCTGATCATCAACAATGTTAACTTTTGCCGGGAGTCCGGCCTGCGCACACGCACAGGCTCCAACATTGACTGCGAAAAACTTCGAAGGAGGTTTAGCTCTCTGCATTTCATGGTAGAGGTGAAGGGGGATCTGACCGCCAAGAAAATGGTTCTCGCCCTTCTCGAGCTTGCGCAGCAGGACCATGGAGCGCTTGACTGTTGTGTCGTTGTGATACTGAGCCATGGCTGTCAGGCTTCCCATCTCCAGTTTCCAGGGGCCGTGTACGGAACCGATGGATGCCCTGTGTCAGTTGAAAAGATCGTAAACATCTTTAACGGAACATCTTGCCCGAGCCTCGGCGGTAAACCGAAGCTTTTTTTTATCCAGGCCTGCGGCGGTGAACAGAAAGATCATGGCTTCGAGGTTGCCAGTACCAGCCCTGAAGACGAATCCCCCGGGTCAAATCCTGAACCAGATGCGACCCCTTTCCAGGAAGGACTCCGCACTTTTGACCAGCTTGACGCCATTTCCTCCCTGCCAACACCTTCCGACATATTTGTAAGCTACTCCACCTTTCCAGGATTCGTGAGCTGGCGCGACCCAAAATCCGGCAGTTGGTATGTTGAAACCCTGGACGATATCTTCGAACAATGGGCCCACAGTGAGGACCTGCAGTCCCTTCTTCTGCGCGTAGCCAATGCCGTGTCAGTCAAAGGGATTTACAAGCAGATGCCAGGCTGCTTTAATTTCCTGCGCAAGAAACTGTTTTTTAAGACCAGTTGA

Human anti-CD20 bbz-2A- iCasp9, amino acid sequence (SEQ ID NO: 3025)

MALPVTALLLPLALLLHAARPGSDIQLTQSPSSLSASVGDRVTMTCRASSSVSYIHWFQQKPGKAPKPWIYATSNLASGVPVRFSGSGSGTDYTFTISSLQPEDIATYCQQWTSNPPTFGGGTKLEIKRGGGGSGGGGGSGGGGSQVQLQQSGAEVKKPGSSVKVSCKASGYTFTSYNMHWVK QAPGQGLEWIGAIYPGMGDTSYNQKFKGKATLTADESTNTAYMELSSLRSEDTAFYYCARSTYYGGDWYFDVWGQGTTVTVSSASTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDSGIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRGSGATNFSLLKQAGDVEENPGP GVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLESGGGSGGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLELAQQ DHGALDCCVVVILSHGCQASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVASTSPEDESPGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSGSWYVETLDDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTS Z

iCasp9 -2A-human anti-CD20 bbz, nucleotide sequence (SEQ ID NO: 3026)

ATGCTCGAGGGGGTTCAGGTGGAGACTATCAGCCCGGGCGACGGACGGACATTCCCAAAGCGCGGGCAGACGTGTGTGGTGCATTACACCGGGATGCTTGAGGACGGAAAGAAAGTGGACTCTTCCCGAGACCGAAATAAACCATTCAAGTTCATGTTGGGCAAGCAGGAGGTTATCAGAGGGTGGGAGGAGGGCGTCGCTCAGATGAGTGTCGGACAGAGGGCCAAGCTCACGATCTCCCCTGATTACGCCTACGGGGCAACTGGTCACCCCGGAATCATCCCCCCTCACGCAACCCTCGTGTTCGACGTCGAGCTGCTCAAACTGGAATCAGGCGGAGGCAGTGGCGCTAGCGGGTTTGGCGATGTCGGTGCCCTTGAAAGCTTGAGAGGAAATGCCGATCTCGCTTACATCTTGAGCATGGAGCCCTGTGGGCACTGTCTGATCATCAACAATGTTAACTTTTGCCGGGAGTCCGGCCTGCGCACACGCACAGGCTCCAACATTGACTGCGAAAAACTTCGAAGGAGGTTTAGCTCTCTGCATTTCATGGTAGAGGTGAAGGGGGATCTGACCGCCAAGAAAATGGTTCTCGCCCTTCTCGAGCTTGCGCAGCAGGACCATGGAGCGCTTGACTGTTGTGTCGTTGTGATACTGAGCCATGGCTGTCAGGCTTCCCATCTCCAGTTTCCAGGGGCCGTGTACGGAACCGATGGATGCCCTGTGTCAGTTGAAAAGATCGTAAACATCTTTAACGGAACATCTTGCCCGAGCCTCGGCGGTAAACCGAAGCTTTTTTTTATCCAGGCCTGCGGCGGTGAACAGAAAGATCATGGCTTCGAGGTTGCCAGTACCAGCCCTGAAGACGAATCCCCCGGGTCAAATCCTGAACCAGATGCGACCCCTTTCCAGGAAGGACTCCGCACTTTTGACCAGCTTGACGCCATTTCCTCCCTGCCAACACCTTCCGACATATTTGTAAGCTACTCCACCTTTCCAGGATTCGTGAGCTGGCGCGACCCAAAATCCGGCAGTTGGTATGTTGAAACCCTGGACGATATTTTCGAACAATGGGCCCACAGTGAGGACCTGCAGTCCCTTCTTCTGCGCGTAGCCAATGCCGTGTCAGTCAAAGGGATTTACAAGCAGATGCCAGGCTGCTTTAATTTCCTGCGCAAGAAACTGTTTTTTAAGACCAGTGGCTCCGGCGCAACAAATTTCTCCTTGCTGAAACAGGCAGGCGACGTTGAGGAAAATCCCGGCCCAATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACGCCGCCAGGCCGGGATCCGATATTCAACTTACACAGTCCCCTAGTTCCTTGTCCGCCTCCGTCGGCGACAGAGTTACCATGACTTGTCGAGCGTCTTCTAGCGTTTCCTACATTCATTGGTTCCAACAGAAGCCCGGAAAGGCACCAAAACCTTGGATCTACGCCACGTCCAATTTGGCTAGTGGTGTTCCGGTGCGATTTTCCGGGTCAGGTAGCGGGACGGACTATACTTTTACCATTTCAAGCCTTCAGCCTGAAGACATCGCGACGTACTATTGTCAGCAGTGGACCTCTAACCCTCCTACCTTTGGCGGTGGAACAAAGCTGGAGATCAAACGAGGCGGGGGTGGCTCTGGGGGAGGAGGTTCCGGTGGGGGAGGCTCTCAAGTACAACTGCAACAAAGTGGGGCTGAAGTGAAGAAGCCCGGTTCTTCAGTCAAAGTATCATGTAAGGCAAGTGGTTATACTTTTACGTCTTATAACATGCATTGGGTAAAGCAAGCCCCTGGTCAGGGCCTCGAGTGGATTGGTGCGATCTACCCTGGAATGGGTGATACGAGCTATAATCAGAAATTCAAGGGGAAAGCCACCTTGACTGCAGACGAATCTACGAACACGGCTTACATGGAGCTTAGCTCACTCAGATCAGAGGATACAGCCTTTTACTACTGCGCTAGATCAACTTATTACGGAGGAGACTGGTATTTTGATGTATGGGGTCAGGGGACCACAGTCACTGTTAGCTCTGCTAGCACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATTCCGGAATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC

iCasp9-2A- human anti-CD20 bbz, amino acid sequence (SEQ ID NO: 3027)

MLEGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKVDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLESGGGSGASGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLEL AQQDHGALDCCVVVILSHGCQASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVASTSPEDESPGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSGSWYVETLDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTSGSG ATNFSLLKQAGDVEENPGP MALPVTALLLPLALLLHAARPGSDIQLTQSPSSLSASVGDRVTMTCRASSSVSYIHWFQQKPGKAPKPWIYATSNLASGVPVRFSGSGSGTDYTFTISSLQPEDIATYCQQWTSNPPTFGGGTKLEIKRGGGGSGGGGGSGGGGSQVQLQQSGAEVKKPGSSVKVSCKASGYTFTSYNMHWVK QAPGQGLEWIGAIYPGMGDTSYNQKFKGKATLTADESTNTAYMELSSLRSEDTAFYYCARSTYYGGDWYFDVWGQGTTVTVSSASTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDSGIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRS ADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR Z

FMC63-bbz-2A- revCasp9, nucleotide sequence (SEQ ID NO: 3028)

ATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACGCCGCCAGGCCGGGATCCGACATCCAGATGACACAGACTACATCCTCCCTGTCTGCCTCTCTGGGAGACAGAGTCACCATCAGTTGCAGGGCAAGTCAGGACATTAGTAAATATTTAAATTGGTATCAGCAGAAACCAGATGGAACTGTTAAACTCCTGATCTACCATACATCAAGATTACACTCAGGAGTCCCATCAAGGTTCAGTGGCAGTGGGTCTGGAACAGATTATTCTCTCACCATTAGCAACCTGGAGCAAGAAGATATTGCCACTTACTTTTGCCAACAGGGTAATACGCTTCCGTACACGTTCGGAGGGGGGACTAAGTTGGAAATAACAGGTGGCGGTGGCTCGGGCGGTGGTGGGTCGGGTGGCGGCGGATCTGAGGTGAAACTGCAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCACAGAGCCTGTCCGTCACATGCACTGTCTCAGGGGTCTCATTACCCGACTATGGTGTAAGCTGGATTCGCCAGCCTCCACGAAAGGGTCTGGAGTGGCTGGGAGTAATATGGGGTAGTGAAACCACATACTATAATTCAGCTCTCAAATCCAGACTGACCATCATCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTGCAAACTGATGACACAGCCATTTACTACTGTGCCAAACATTATTACTACGGTGGTAGCTATGCTATGGACTACTGGGGTCAAGGAACCTCAGTCACCGTCTCCTCAGCTAGCACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATTCCGGAATCTACATCTGGGCCCCTCTGGCCGGCACCTGTGGCGTGCTGCTGCTGTCTCTCGTGATCACCCTGTACTGCAAGCGGGGCAGAAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAGACCACCCAGGAAGAGGACGGCTGCTCCTGCAGATTCCCCGAGGAAGAAGAAGGCGGCTGCGAGCTGAGAGTGAAGTTCAGCAGAAGCGCCGACGCCCCTGCCTATCAGCAGGGCCAGAACCAGCTGTACAACGAGCTGAACCTGGGCAGACGGGAAGAGTACGACGTGCTGGACAAGCGGAGAGGCAGGGACCCTGAGATGGGCGGCAAGCCCAGAAGAAAGAACCCCCAGGAAGGCCTGTATAACGAACTGCAGAAAGACAAGATGGCCGAGGCCTACAGCGAGATCGGAATGAAGGGCGAGCGGAGAAGAGGCAAGGGCCACGATGGCCTGTACCAGGGCCTGAGCACCGCCACCAAGGACACCTATGACGCCCTGCACATGCAGGCCCTGCCTCCAAGAGGAAGCGGCGCCACCAATTTCAGCCTGCTGAAACAGGCCGGCGACGTGGAAGAGAACCCTGGCCCTAGAGGCGTGCAGGTGGAAACCATCTCTCCCGGCGACGGCAGAACCTTCCCTAAGAGGGGCCAGACCTGCGTGGTGCACTACACCGGCATGCTGGAAGATGGCAAGAAGATGGACAGCTCCCGGGACCGGAACAAGCCCTTCAAGTTCATGCTGGGCAAGCAGGAAGTGATCCGGGGCTGGGAAGAGGGCGTGGCACAGATGTCTGTGGGCCAGAGAGCCAAGCTGACCATCAGCCCCGATTACGCCTACGGCGCCACAGGCCACCCTGGCATCATTCCTCCACACGCCACACTGGTGTTCGATGTGGAACTGCTGAAGCTGGAAACCCGGGGAGTGCAGGTGGAAACAATCAGCCCTGGCGACGGCCGGACCTTTCCAAAACGGGGACAGACATGTGTGGTGCATTATACAGGGATGCTGGAAGATGGGAAAAAAATGGATAGCAGCCGCGACCGCAACAAACCTTTTAAGTTTATGCTGGGGAAACAGGAAGTGATTAGAGGCTGGGAAGAGGGGGTGGCACAGATGAGCGTGGGACAGCGGGCCAAACTGACAATCTCCCCCGACTATGCCTATGGGGCCACCGGACACCCCGGAATCATCCCACCTCATGCTACCCTGGTGTTTGACGTGGAACTGCTGAAACTGGAAACAAGCGGCGGAGGCAGCGGCGGCTTTGGAGATGTGGGAGCCCTGGAAAGCCTGCGGGGCAATGCCGATCTGGCCTACATCCTGAGCATGGAACCCTGCGGCCACTGCCTGATTATCAACAACGTGAACTTCTGCAGAGAGAGCGGCCTGCGGACCAGAACCGGCAGCAACATCGACTGCGAGAAGCTGCGGCGGAGATTCAGCAGCCTGCACTTCATGGTGGAAGTGAAGGGGGACCTGACCGCCAAGAAAATGGTGCTGGCTCTGCTGGAACTGGCCCAGCAGGATCATGGCGCCCTGGACTGTTGCGTGGTCGTGATCCTGAGCCACGGCTGCCAGGCCAGCCATCTGCAGTTTCCCGGCGCTGTGTATGGCACCGATGGCTGCCCTGTGTCCGTGGAAAAGATCGTGAATATCTTCAACGGCACCAGCTGCCCCAGCCTGGGCGGAAAGCCTAAGCTGTTCTTTATTCAAGCCTGTGGGGGCGAGCAGAAGGACCACGGATTTGAGGTGGCCAGCACCTCCCCCGAGGATGAGAGCCCTGGCAGCAACCCTGAGCCTGACGCCACCCCATTCCAGGAAGGACTGCGGACCTTCGACCAGCTGGACGCCATCTCTAGCCTGCCCACCCCCAGCGACATCTTCGTGTCCTACAGCACCTTCCCTGGCTTTGTGTCCTGGCGGGACCCCAAGTCCGGCTCTTGGTACGTGGAAACCCTGGACGACATCTTTGAGCAGTGGGCCCATAGCGAGGACCTGCAGAGCCTGCTGCTGAGGGTGGCCAATGCCGTGTCCGTGAAGGGCATCTACAAGCAGATGCCCGGCTGCTTCAACTTCCTGCGGAAGAAGCTGTTTTTCAAGACCAGC

FMC63-bbz-2A- revCasp9 amino acid sequence (SEQ ID NO:3029)

MALPVTALLLPLALLLHAARPGSDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLE WLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSASTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDSGIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQG QNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRGSGATNFSLLKQAGDVEENPGPRGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPD YAYGATGHPGIIIPPHATLVFDVELLKLETSGGGSGGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLELAQQDHGALDCCVVVILSHGCQASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVASTSPEDES PGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSGSWYVETLDDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTS

CD19bbz on-CAR, nucleotide sequence, CD19 on-CAR (SEQ ID NO: 977, also provided earlier herein)

Signal peptide - conditional aggregation domains (4 repeats) - furin site - FMC63bbz

TCAGCCCGGAACAGGCGGAAGAGA

CD19bbz on-CAR amino acid sequence (SEQ ID NO: 978, also found earlier herein)

Signal peptide - conditional aggregation domains (4 repeats) - furin site - FMC63bbz

MALPVTALLLPLALLLHAARPGSRGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWE EGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLETRGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLETRGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKMD SSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLET SARNRRKR GSDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSASTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDSGIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEY DVLDKRRGRRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRZ

Signal peptide - human anti-CD20 - CD8 hinge - transmembrane CD8-CD137-CD247 -2A- revCasp9, nucleotide sequence (SEQ ID NO: 3030)

ATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACGCCGCCAGGCCGGGATCC _ ATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC GGAAGCGGCGCCACCAATTTCAGCCTGCTGAAACAGGCCGGCGACGTGGAAGAGAACCCTGGCCCT AGAGGCGTGCAGGTGGAAACCATCTCTCCCGGCGACGGCAGAACCTTCCCTAAGAGGGGCCAGACCTGCGTGGTGCACTACACCGGCATGCTGGAAGATGGCAAGAAGATGGACAGCTCCCGGGACCGGAACAAGCCCTTCAAGTTCATGCTGGGCAAGCAGGAAGTGATCCGGGGCTGGGAAGAGGGCGTGGCACAGATGTCTGTGGGCCAGAGAGCCAAGCTGACCATCAGCCCCGATTACGCCTACGGCGCCACAGGCCACCCTGGCATCATTCCTCCACACGCCACACTGGTGTTCGATGTGGAACTGCTGAAGCTGGAAACCCGGGGAGTGCAGGTGGAAACAATCAGCCCTGGCGACGGCCGGACCTTTCCAAAACGGGGACAGACATGTGTGGTGCATTATACAGGGATGCTGGAAGATGGGAAAAAAATGGATAGCAGCCGCGACCGCAACAAACCTTTTAAGTTTATGCTGGGGAAACAGGAAGTGATTAGAGGCTGGGAAGAGGGGGTGGCACAGATGAGCGTGGGACAGCGGGCCAAACTGACAATCTCCCCCGACTATGCCTATGGGGCCACCGGACACCCCGGAATCATCCCACCTCATGCTACCCTGGTGTTTGACGTGGAACTGCTGAAACTGGAAACAAGCGGCGGAGGCAGCGGCGGCTTTGGAGATGTGGGAGCCCTGGAAAGCCTGCGGGGCAATGCCGATCTGGCCTACATCCTGAGCATGGAACCCTGCGGCCACTGCCTGATTATCAACAACGTGAACTTCTGCAGAGAGAGCGGCCTGCGGACCAGAACCGGCAGCAACATCGACTGCGAGAAGCTGCGGCGGAGATTCAGCAGCCTGCACTTCATGGTGGAAGTGAAGGGGGACCTGACCGCCAAGAAAATGGTGCTGGCTCTGCTGGAACTGGCCCAGCAGGATCATGGCGCCCTGGACTGTTGCGTGGTCGTGATCCTGAGCCACGGCTGCCAGGCCAGCCATCTGCAGTTTCCCGGCGCTGTGTATGGCACCGATGGCTGCCCTGTGTCCGTGGAAAAGATCGTGAATATCTTCAACGGCACCAGCTGCCCCAGCCTGGGCGGAAAGCCTAAGCTGTTCTTTATTCAAGCCTGTGGGGGCGAGCAGAAGGACCACGGATTTGAGGTGGCCAGCACCTCCCCCGAGGATGAGAGCCCTGGCAGCAACCCTGAGCCTGACGCCACCCCATTCCAGGAAGGACTGCGGACCTTCGACCAGCTGGACGCCATCTCTAGCCTGCCCACCCCCAGCGACATCTTCGTGTCCTACAGCACCTTCCCTGGCTTTGTGTCCTGGCGGGACCCCAAGTCCGGCTCTTGGTACGTGGAAACCCTGGACGACATCTTTGAGCAGTGGGCCCATAGCGAGGACCTGCAGAGCCTGCTGCTGAGGGTGGCCAATGCCGTGTCCGTGAAGGGCATCTACAAGCAGATGCCCGGCTGCTTCAACTTCCTGCGGAAGAAGCTGTTTTTCAAGACCAGC

Signal peptide - human anti-CD20 - CD8 hinge - transmembrane CD8-CD137-CD247 -2A- revCasp9, amino acid sequence (SEQ ID NO: 3031)

MALPVTALLLPLALLLHAARPGSDIQLTQSPSSLSASVGDRVTMTCRASSSVSYIHWFQQKPGKAPKPWIYATSNLASGVPVRFSGSGSGTDYTFTISSLQPEDIATYYCQQWTSNPPTFGGGTKLEIKRGGGGSGGGGSGGGGSQVQLQQSGAEVKKPGSSVKVSCKASGYTFTSYNMHWVKQAPGQGLEWIGAIYPG MGDTSYNQKFKGKATLTADESTNTAYMELSSLRSEDTAFYYCARSTYYGGDWYFDVWGQGTTVTVSSASTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDSG IYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRGSGATNFSLLKQAGDVEENPGP RGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPD YAYGATGHPGIIIPPHATLVFDVELLKLETSGGGSGGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTRTGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLELAQQDHGALDCCVVVILSHGCQASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVASTSPEDES PGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSGSWYVETLDDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTS

CD20bbz on-CAR, nucleotide sequence, CD20 on-CAR (SEQ ID NO: 3032)

Signal peptide - conditional aggregation domains (4 repeats) - furin site - anti-CD20bbz

ATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACGCCGCCAGGCCG TCAGCCCGGAACAGGCGGAAGAGA

CD20bbz on-CAR amino acid sequence (SEQ ID NO: 3033)

Signal peptide - conditional aggregation domains (4 repeats) - furin site - anti-CD20bbz

MALPVTALLLPLALLLHAARP GSRGVQVETISPDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTIS PDYAYGATGHPGIIIPPHATLVFDVELLKLETRGVQVETISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQEVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPHATLVFDVELLKLETRGVQVETIISPGDGRTFPKRGQTCVVHYTGMLEDGKKMDSSRDRNKPFKFMLGKQ EVIRGWEEGVAQMSVGQRAKLTISPDYAYGATGHPGIIPPPHATLVFDVELLKLET SARNRRKR GSDIQLTQSPSSLSASVGDRVTMTCRASSSVSYIHWFQQKPGKAPKPWIYATSNLASGVPVRFSGSGSGTDYTFTISSLQPEDIATYYCQQWTSNPPTFGGGTKLEIKRGGGGSGGGGSGGGGSQVQLQQSGAEVKKPGSSVKVSCKASGYTFTSYNMHWVKQAPGQGLEWIGAIYPG MGDTSYNQKFKGKATLTADESTNTAYMELSSLRSEDTAFYYCARSTYYGGDWYFDVWGQGTTVTVSSASTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDSGIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAYQQGQNQLYN ELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR

OTHER IMPLEMENTATION OPTIONS

The contents of each and all patents, patent applications and publications cited herein are incorporated herein by reference in their entirety. While this invention is disclosed with reference to specific embodiments, it is obvious that other embodiments and variations of this invention can be developed by experts in this field without deviating from the true essence and scope of the invention. The appended claims are to be construed as including all such embodiments and equivalent variations.

--->

SEQUENCE LIST

<110> NOVARTIS AG

THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

<120> COMPOSITIONS AND METHODS FOR SELECTIVE PROTEIN EXPRESSION

<130> N2067-7128WO

<140>

<141>

<150> 62/322.931

<151> 2016-04-15

<150> 62/481.094

<151> 2017-04-03

<160> 3036

<170>PatentIn version 3.5

<210> 1

<211> 1184

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1

cgtgaggctc cggtgcccgt cagtgggcag agcgcacatc gcccacagtc cccgagaagt

60

tggggggagg ggtcggcaat tgaaccggtg cctagagaag gtggcgcggg gtaaactgggg

120

aaagtgatgt cgtgtactgg ctccgccttt ttcccgaggg tgggggagaa ccgtatataa

180

gtgcagtagt cgccgtgaac gttctttttc gcaacgggtt tgccgccaga acacaggtaa

240

gtgccgtgtg tggttcccgc gggcctggcc tctttacgggg ttatggccct tgcgtgcctt

300

gaattacttc cacctggctg cagtacgtga ttcttgatcc cgagcttcgg gttggaagtg

360

ggtgggagag ttcgaggcct tgcgcttaag gagccccttc gcctcgtgct tgagttgagg

420

cctggcctgg gcgctggggc cgccgcgtgc gaatctggtg gcaccttcgc gcctgtctcg

480

ctgctttcga taagtctcta gccatttaaa atttttgatg acctgctgcg acgctttttt

540

tctggcaaga tagtcttgta aatgcgggcc aagatctgca cactggtatt tcggtttttg

600

gggccgcggg cggcgacggg gcccgtgcgt cccagcgcac atgttcggcg aggcggggcc

660

tgcgagcgcg gccaccgaga atcggacggg ggtagtctca agctggccgg cctgctctgg

720

tgcctggcct cgcgccgccg tgtatcgccc cgccctgggc ggcaaggctg gcccggtcgg

780

caccagttgc gtgagcggaa agatggccgc ttcccggccc tgctgcaggg agctcaaaat

840

ggaggacgcg gcgctcggga gagcgggcgg gtgagtcacc cacacaaagg aaaagggcct

900

ttccgtcctc agccgtcgct tcatgtgact ccacggagta ccgggcgccg tccaggcacc

960

tcgattagtt ctcgagcttt tggagtacgt cgtctttagg ttggggggag gggttttatg

1020

cgatggagtt tccccacact gagtgggtgg agactgaagt taggccagct tggcacttga

1080

tgtaattctc cttggaattt gccctttttg agtttggatc ttggttcatt ctcaagcctc

1140

agacagtggt tcaaagtttt tttcttccat ttcaggtgtc gtga

1184

<210> 2

<211> 21

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 2

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro

20

<210> 3

<211> 63

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 3

atggccctgc ctgtgacagc cctgctgctg ccctctggctc tgctgctgca tgccgctaga

60

ccc

63

<210> 4

<211> 45

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 4

Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala

1 5 10 15

Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly

20 25 30

Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp

35 40 45

<210> 5

<211> 135

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 5

accacgacgc cagcgccgcg accaccaaca ccggcgccca ccatcgcgtc gcagcccctg

60

tccctgcgcc cagaggcgtg ccggccagcg gcggggggcg cagtgcacac gagggggctg

120

gacttcgcct gtgat

135

<210> 6

<211> 230

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 6

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

1 5 10 15

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

20 25 30

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

35 40 45

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

50 55 60

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

65 70 75 80

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

85 90 95

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

100 105 110

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

115 120 125

Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

130 135 140

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

145 150 155 160

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

165 170 175

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

180 185 190

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

195 200 205

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

210 215 220

Leu Ser Leu Gly Lys Met

225 230

<210> 7

<211> 690

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 7

gagagcaagt acggccctcc ctgcccccct tgccctgccc ccgagttcct gggcggaccc

60

agcgtgttcc tgttcccccc caagcccaag gacaccctga tgatcagccg gacccccgag

120

gtgacctgtg tggtggtgga cgtgtcccag gaggaccccg aggtccagtt caactggtac

180

gtggacggcg tggaggtgca caacgccaag accaagcccc gggaggagca gttcaatagc

240

acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaggaa

300

tacaagtgta aggtgtccaa caagggcctg cccagcagca tcgagaaaac catcagcaag

360

gccaagggcc agcctcggga gccccaggtg tacaccctgc cccctagcca agaggagatg

420

accaagaacc aggtgtccct gacctgcctg gtgaagggct tctaccccag cgacatcgcc

480

gtggagtggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg

540

gacagcgacg gcagcttctt cctgtacagc cggctgaccg tggacaagag ccggtggcag

600

gagggcaacg tctttagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag

660

aagagcctga gcctgtccct gggcaagatg

690

<210> 8

<211> 282

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 8

Arg Trp Pro Glu Ser Pro Lys Ala Gln Ala Ser Ser Val Pro Thr Ala

1 5 10 15

Gln Pro Gln Ala Glu Gly Ser Leu Ala Lys Ala Thr Thr Ala Pro Ala

20 25 30

Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Lys Glu Lys

35 40 45

Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro

50 55 60

Ser His Thr Gln Pro Leu Gly Val Tyr Leu Leu Thr Pro Ala Val Gln

65 70 75 80

Asp Leu Trp Leu Arg Asp Lys Ala Thr Phe Thr Cys Phe Val Val Gly

85 90 95

Ser Asp Leu Lys Asp Ala His Leu Thr Trp Glu Val Ala Gly Lys Val

100 105 110

Pro Thr Gly Gly Val Glu Glu Gly Leu Leu Glu Arg His Ser Asn Gly

115 120 125

Ser Gln Ser Gln His Ser Arg Leu Thr Leu Pro Arg Ser Leu Trp Asn

130 135 140

Ala Gly Thr Ser Val Thr Cys Thr Leu Asn His Pro Ser Leu Pro Pro

145 150 155 160

Gln Arg Leu Met Ala Leu Arg Glu Pro Ala Ala Gln Ala Pro Val Lys

165 170 175

Leu Ser Leu Asn Leu Leu Ala Ser Ser Asp Pro Pro Glu Ala Ala Ser

180 185 190

Trp Leu Leu Cys Glu Val Ser Gly Phe Ser Pro Pro Asn Ile Leu Leu

195 200 205

Met Trp Leu Glu Asp Gln Arg Glu Val Asn Thr Ser Gly Phe Ala Pro

210 215 220

Ala Arg Pro Pro Pro Gln Pro Gly Ser Thr Thr Phe Trp Ala Trp Ser

225 230 235 240

Val Leu Arg Val Pro Ala Pro Pro Ser Pro Gln Pro Ala Thr Tyr Thr

245 250 255

Cys Val Val Ser His Glu Asp Ser Arg Thr Leu Leu Asn Ala Ser Arg

260 265 270

Ser Leu Glu Val Ser Tyr Val Thr Asp His

275 280

<210> 9

<211> 847

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 9

aggtggcccg aaagtcccaa ggcccaggca tctagtgttc ctactgcaca gccccaggca

60

gaaggcagcc tagccaaagc tactactgca cctgcacta cgcgcaatac tggccgtggc

120

ggggaggaga agaaaaagga gaaagagaaa gaagaacagg aagagaggga gaccaagacc

180

cctgaatgtc catcccatac ccagccgctg ggcgtctatc tcttgactcc cgcagtacag

240

gacttgtggc ttagagataa ggccaccttt acatgtttcg tcgtgggctc tgacctgaag

300

gatgcccatt tgacttggga ggttgccgga aaggtaccca cagggggggt tgaggaaggg

360

ttgctggagc gccattccaa tggctctcag agccagcact caagactcac ccttccgaga

420

tccctgtgga acgccgggac ctctgtcaca tgtactctaa atcatcctag cctgccccca

480

cagcgtctga tggcccttag agagccagcc gcccaggcac cagttaagct tagcctgaat

540

ctgctcgcca gtagtgatcc cccagaggcc gccagctggc tcttatgcga agtgtccggc

600

tttagcccgc ccaacatctt gctcatgtgg ctggaggacc agcgagaagt gaacaccagc

660

ggcttcgctc cagcccggcc cccaccccag ccgggttcta ccacattctg ggcctggagt

720

gtcttaaggg tcccagcacc acctagcccc cagccagcca catacacctg tgttgtgtcc

780

catgaagata gcaggaccct gctaaatgct tctaggagtc tggaggtttc ctacgtgact

840

gaccatt

847

<210> 10

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 10

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1 5 10

<210> 11

<211> 30

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 11

ggtggcggag gttctggagg tggaggttcc

thirty

<210> 12

<211> 24

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 12

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu

1 5 10 15

Ser Leu Val Ile Thr Leu Tyr Cys

20

<210> 13

<211> 72

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 13

atctacatct gggcgccctt ggccgggact tgtggggtcc ttctcctgtc actggttatc

60

acccttact gc

72

<210> 14

<211> 42

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 14

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

1 5 10 15

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

20 25 30

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

35 40

<210> 15

<211> 126

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 15

aaacggggca gaaagaaact cctgtatata ttcaaacaac catttatgag accagtacaa

60

actactcaag aggaagatgg ctgtagctgc cgatttccag aagaagaaga aggaggatgt

120

gaactg

126

<210> 16

<211> 48

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 16

Gln Arg Arg Lys Tyr Arg Ser Asn Lys Gly Glu Ser Pro Val Glu Pro

1 5 10 15

Ala Glu Pro Cys Arg Tyr Ser Cys Pro Arg Glu Glu Glu Gly Ser Thr

20 25 30

Ile Pro Ile Gln Glu Asp Tyr Arg Lys Pro Glu Pro Ala Cys Ser Pro

35 40 45

<210> 17

<211> 123

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 17

aggagtaaga ggagcaggct cctgcacagt gactacatga acatgactcc ccgccgcccc

60

gggccccaccc gcaagcatta ccagccctat gccccaccac gcgacttcgc agcctatcgc

120

tcc

123

<210> 18

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 18

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly

1 5 10 15

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

20 25 30

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

35 40 45

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

50 55 60

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

65 70 75 80

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

85 90 95

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

100 105 110

<210> 19

<211> 336

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 19

agagtgaagt tcagcaggag cgcagacgcc cccgcgtaca agcagggcca gaaccagctc

60

tataacgagc tcaatctagg acgaagagag gagtacgatg ttttggacaa gagacgtggc

120

cgggaccctg agatgggggg aaagccgaga aggaagaacc ctcaggaagg cctgtacaat

180

gaactgcaga aagataagat ggcggaggcc tacagtgaga ttgggatgaa aggcgagcgc

240

cggaggggca aggggcacga tggcctttac cagggtctca gtacagccac caaggacacc

300

tacgacgccc ttcacatgca ggccctgccc cctcgc

336

<210> 20

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 20

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

1 5 10 15

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

20 25 30

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

35 40 45

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

50 55 60

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

65 70 75 80

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

85 90 95

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

100 105 110

<210> 21

<211> 336

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 21

agagtgaagt tcagcaggag cgcagacgcc cccgcgtacc agcagggcca gaaccagctc

60

tataacgagc tcaatctagg acgaagagag gagtacgatg ttttggacaa gagacgtggc

120

cgggaccctg agatgggggg aaagccgaga aggaagaacc ctcaggaagg cctgtacaat

180

gaactgcaga aagataagat ggcggaggcc tacagtgaga ttgggatgaa aggcgagcgc

240

cggaggggca aggggcacga tggcctttac cagggtctca gtacagccac caaggacacc

300

tacgacgccc ttcacatgca ggccctgccc cctcgc

336

<210> 22

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 22

Gly Gly Gly Gly Ser

15

<210> 23

<211> 30

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 23

ggtggcggag gttctggagg tggaggttcc

thirty

<210> 24

<211> 150

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 24

Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr

1 5 10 15

Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp Asn Ala Thr Phe

20 25 30

Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr

35 40 45

Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu

50 55 60

Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg Val Thr Gln Leu

65 70 75 80

Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn

85 90 95

Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu Ala Pro Lys Ala

100 105 110

Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg

115 120 125

Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly

130 135 140

Gln Phe Gln Thr Leu Val

145 150

<210> 25

<211> 450

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 25

cccggatggt ttctggactc tccggatcgc ccgtggaatc ccccaacctt ctcaccggca

60

ctcttggttg tgactgaggg cgataatgcg accttcacgt gctcgttctc caacacctcc

120

gaatcattcg tgctgaactg gtaccgcatg agcccgtcaa accagaccga caagctcgcc

180

gcgtttccgg aagatcggtc gcaaccggga caggattgtc ggttccgcgt gactcaactg

240

ccgaatggca gagacttcca catgagcgtg gtccgcgcta ggcgaaacga ctccgggacc

300

tacctgtgcg gagccatctc gctggcgcct aaggcccaaa tcaaagagag cttgaggggcc

360

gaactgagag tgaccgagcg cagagctgag gtgccaactg cacatccatc cccatcgcct

420

cggcctgcgg ggcagtttca gaccctggtc

450

<210> 26

<211> 394

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 26

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro

20 25 30

Trp Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly

35 40 45

Asp Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe

50 55 60

Val Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu

65 70 75 80

Ala Ala Phe Pro Glu Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe

85 90 95

Arg Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val

100 105 110

Arg Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser

115 120 125

Leu Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg

130 135 140

Val Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser

145 150 155 160

Pro Arg Pro Ala Gly Gln Phe Gln Thr Leu Val Thr Thr Thr Pro Ala

165 170 175

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

180 185 190

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

195 200 205

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

210 215 220

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

225 230 235 240

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

245 250 255

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

260 265 270

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

275 280 285

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

290 295 300

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

305 310 315 320

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

325 330 335

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

340 345 350

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

355 360 365

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

370 375 380

Ala Leu His Met Gln Ala Leu Pro Pro Arg

385 390

<210> 27

<211> 1182

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 27

atggccctcc ctgtcactgc cctgcttctc cccctcgcac tcctgctcca cgccgctaga

60

ccacccggat ggttctctgga ctctccggat cgcccgtgga atcccccaac cttctcaccg

120

gcactcttgg ttgtgactga gggcgataat gcgaccttca cgtgctcgtt ctccaacacc

180

tccgaatcat tcgtgctgaa ctggtaccgc atgagcccgt caaaccagac cgacaagctc

240

gccgcgtttc cggaagatcg gtcgcaaccg ggacaggatt gtcggttccg cgtgactcaa

300

ctgccgaatg gcagagactt ccacatgagc gtggtccgcg ctaggcgaaa cgactccggg

360

acctacctgt gcggagccat ctcgctggcg cctaaggccc aaatcaaaga gagcttgagg

420

gccgaactga gagtgaccga gcgcagagct gaggtgccaa ctgcacatcc atccccatcg

480

cctcggcctg cggggcagtt tcagaccctg gtcacgacca ctccggcgcc gcgcccaccg

540

actccggccc caactatcgc gagccagccc ctgtcgctga ggccggaagc atgccgccct

600

gccgccggag gtgctgtgca tacccgggga ttggacttcg catgcgacat ctacatttgg

660

gctcctctcg ccggaacttg tggcgtgctc cttctgtccc tggtcatcac cctgtactgc

720

aagcggggtc ggaaaaagct tctgtacatt ttcaagcagc ccttcatgag gcccgtgcaa

780

accacccagg aggaggacgg ttgctcctgc cggttccccg aagaggaaga aggaggttgc

840

gagctgcgcg tgaagttctc ccggagcgcc gacgcccccg cctataagca gggccagaac

900

cagctgtaca acgaactgaa cctgggacgg cgggaagagt acgatgtgct ggacaagcgg

960

cgcggccggg accccgaaat gggcgggaag cctagaagaa agaaccctca ggaaggcctg

1020

tataacgagc tgcagaagga caagatggcc gaggcctact ccgaaattgg gatgaaggga

1080

gagcggcgga ggggaaaggg gcacgacggc ctgtaccaag gactgtccac cgccaccaag

1140

gacacatacg atgccctgca catgcaggcc cttccccctc gc

1182

<210> 28

<211> 40

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<220>

<221> OTHER_INDICATOR

<222> (1)..(40)

<223> /note="This sequence can include 1-10

repeating units ‘Gly Gly Gly Ser’"

<400> 28

Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

1 5 10 15

Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser

20 25 30

Gly Gly Gly Ser Gly Gly Gly Ser

35 40

<210> 29

<211> 20

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 29

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

1 5 10 15

Gly Gly Gly Ser

20

<210> 30

<211> 15

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 30

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1 5 10 15

<210> 31

<211> 4

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 31

Gly Gly Gly Ser

1

<210> 32

<211> 5000

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<220>

<221> OTHER_INDICATOR

<222> (1)..(5000)

<223> /note="This sequence can include 50-5000

nucleotides"

<220>

<221> source

<223> /note="See submitted application specification for details

descriptions

substitutions and preferred embodiments"

<400> 32

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

60

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

120

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

180

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

240

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

300

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

360

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

420

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

480

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

540

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

600

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

660

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

720

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

780

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

840

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

900

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

960

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1020

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1080

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1140

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1200

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1260

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1320

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1380

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1440

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1500

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1560

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1620

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1680

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1740

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1800

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1860

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1920

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1980

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2040

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2100

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2160

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2220

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2280

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2340

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2400

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2460

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2520

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2580

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2640

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2700

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2760

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2820

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2880

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2940

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3000

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3060

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3120

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3180

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3240

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3300

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3360

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3420

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3480

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3540

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3600

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3660

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3720

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3780

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3840

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3900

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3960

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4020

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4080

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4140

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4200

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4260

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4320

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4380

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4440

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4500

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4560

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4620

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4680

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4740

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4800

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4860

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4920

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4980

aaaaaaaaaaaaaaaaaaaa

5000

<210> 33

<211> 63

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 33

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccc

63

<210> 34

<211> 72

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 34

atctacattt gggcccctct ggctggtact tgcggggtcc tgctgctttc actcgtgatc

60

actcttact gt

72

<210> 35

<211> 5

<212> PROTEIN

<213> Unknown

<220>

<221> source

<223> /note="Description of unknown sequence:

granzyme sequence B"

<220>

<221> MOD_OST

<222> (5)..(5)

<223> Any amino acid

<400> 35

Ile Glu Pro Asp Xaa

15

<210> 36

<211> 5

<212> PROTEIN

<213> Unknown

<220>

<221> source

<223> /note="Description of unknown sequence:

enterokinase sequence"

<400> 36

Asp Asp Asp Asp Lys

15

<210> 37

<211> 6

<212> PROTEIN

<213> Unknown

<220>

<221> source

<223> /note="Description of unknown sequence:

genease sequence"

<400> 37

Pro Gly Ala Ala His Tyr

15

<210> 38

<211> 7

<212> PROTEIN

<213> Unknown

<220>

<221> source

<223> /note="Description of unknown sequence:

PreScission Protease Sequence"

<400> 38

Leu Glu Val Phe Glyn Gly Pro

15

<210> 39

<211> 373

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 39

Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr

1 5 10 15

Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp Asn Ala Thr Phe

20 25 30

Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr

35 40 45

Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu

50 55 60

Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg Val Thr Gln Leu

65 70 75 80

Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn

85 90 95

Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu Ala Pro Lys Ala

100 105 110

Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg

115 120 125

Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly

130 135 140

Gln Phe Gln Thr Leu Val Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

145 150 155 160

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

165 170 175

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

180 185 190

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

195 200 205

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

210 215 220

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

225 230 235 240

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

245 250 255

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

260 265 270

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

275 280 285

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

290 295 300

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

305 310 315 320

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

325 330 335

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

340 345 350

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

355 360 365

Ala Leu Pro Pro Arg

370

<210> 40

<211> 6

<212> PROTEIN

<213> Unknown

<220>

<221> source

<223> /note="Description of unknown sequence:

thrombin sequence"

<400> 40

Leu Val Pro Arg Gly Ser

15

<210> 41

<211> 7

<212> PROTEIN

<213> Unknown

<220>

<221> source

<223> /note="Description of unknown sequence:

TEV protease sequence"

<400> 41

Glu Asn Leu Tyr Phe Gln Gly

15

<210> 42

<211> 2

<212> PROTEIN

<213> Unknown

<220>

<221> source

<223> /note="Description of unknown sequence:

elastase sequence 1"

<220>

<221> OPTION

<222> (1)..(1)

<223> /replace="Gly" or "Ser" or "Val"

<220>

<221> MOD_OST

<222> (2)..(2)

<223> Any amino acid

<220>

<221> OTHER_INDICATOR

<222> (1)..(2)

<223> /note="The rest of the variant given in

sequences

are not preferred over those given in

annotations

for variant provisions"

<400> 42

Ala Xaa

1

<210> 43

<211> 22

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 43

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro

1 5 10 15

Ala Phe Leu Leu Ile Pro

20

<210> 44

<211> 20

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 44

Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu

1 5 10 15

Val Thr Asn Ser

20

<210> 45

<211> 21

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 45

Met Ala Gln Val Lys Leu Gln Glu Ser Gly Thr Glu Leu Ala Lys Pro

1 5 10 15

Gly Ala Ala Val Lys

20

<210> 46

<211> 19

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 46

Met Arg Phe Leu Ala Ala Thr Phe Leu Leu Leu Ala Leu Ser Thr Ala

1 5 10 15

Ala Gln Ala

<210> 47

<211> 4

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 47

Lys Asp Glu Leu

1

<210> 48

<211> 787

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 48

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Arg Thr Lys Arg

260 265 270

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr

275 280 285

Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu

290 295 300

Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly

305 310 315 320

Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly

325 330 335

Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu

340 345 350

Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys

355 360 365

Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys

370 375 380

Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr

385 390 395 400

Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln

405 410 415

Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly

420 425 430

Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala

435 440 445

Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala

450 455 460

Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg

465 470 475 480

Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu

485 490 495

Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp

500 505 510

Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln

515 520 525

Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr

530 535 540

Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala

545 550 555 560

Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro

565 570 575

Cys Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Asn

580 585 590

Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His

595 600 605

Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg

610 615 620

Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu

625 630 635 640

Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu

645 650 655

Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe

660 665 670

Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met

675 680 685

Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val

690 695 700

Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln

705 710 715 720

Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln

725 730 735

Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu

740 745 750

Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His

755 760 765

Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu

770 775 780

Asn Ala Ser

785

<210> 49

<211> 816

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 49

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actccgtact aaaaga

816

<210> 50

<400> 50

000

<210> 51

<400> 51

000

<210> 52

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 52

Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Arg Asn Leu Pro

1 5 10 15

Val

<210> 53

<211> 63

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 53

gtggtggcgg tggaagcggc ggtggcggaa gcggcggtgg cggcagcaga aacctccccg

60

tgg

63

<210> 54

<400> 54

000

<210> 55

<400> 55

000

<210> 56

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 56

Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro

1 5 10 15

Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp

20 25 30

Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe

35 40 45

Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Glu Gly Val Ala

50 55 60

Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr

65 70 75 80

Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr

85 90 95

Leu Val Phe Asp Val Glu Leu Leu Lys Pro Glu

100 105

<210> 57

<211> 158

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 57

Ile Ser Leu Ile Ala Ala Leu Ala Val Asp Tyr Val Ile Gly Met Glu

1 5 10 15

Asn Ala Met Pro Trp Asn Leu Pro Ala Asp Leu Ala Trp Phe Lys Arg

20 25 30

Asn Thr Leu Asn Lys Pro Val Ile Met Gly Arg His Thr Trp Glu Ser

35 40 45

Ile Gly Arg Pro Leu Pro Gly Arg Lys Asn Ile Ile Leu Ser Ser Gln

50 55 60

Pro Ser Thr Asp Asp Arg Val Thr Trp Val Lys Ser Val Asp Glu Ala

65 70 75 80

Ile Ala Ala Cys Gly Asp Val Pro Glu Ile Met Val Ile Gly Gly Gly

85 90 95

Arg Val Ile Glu Gln Phe Leu Pro Lys Ala Gln Lys Leu Tyr Leu Thr

100 105 110

His Ile Asp Ala Glu Val Glu Gly Asp Thr His Phe Pro Asp Tyr Glu

115 120 125

Pro Asp Asp Trp Glu Ser Val Phe Ser Glu Phe His Asp Ala Asp Ala

130 135 140

Gln Asn Ser His Ser Tyr Cys Phe Glu Ile Leu Glu Arg Arg

145 150 155

<210> 58

<211> 245

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 58

Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met Val Ser Ala Leu Leu

1 5 10 15

Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr Asp Pro Thr Arg Pro

20 25 30

Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr Asn Leu Ala Asp Arg

35 40 45

Glu Leu Val His Met Ile Asn Trp Ala Lys Arg Val Pro Gly Phe Val

50 55 60

Asp Leu Ala Leu His Asp Gln Val His Leu Leu Glu Cys Ala Trp Met

65 70 75 80

Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser Met Glu His Pro Gly

85 90 95

Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp Arg Asn Gln Gly Lys

100 105 110

Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met Leu Leu Ala Thr Ser

115 120 125

Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu Glu Phe Val Cys Leu

130 135 140

Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr Thr Phe Leu Ser Ser

145 150 155 160

Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile His Arg Val Leu Asp

165 170 175

Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala Lys Ala Gly Leu Thr

180 185 190

Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu Leu Leu Ile Leu Ser

195 200 205

His Ile Arg His Met Ser Ser Lys Arg Met Glu His Leu Tyr Ser Met

210 215 220

Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu Leu Leu Glu Met Leu

225 230 235 240

Asp Ala His Arg Leu

245

<210> 59

<211> 610

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 59

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp

20 25 30

Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr

35 40 45

Gly Met Leu Glu Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn

50 55 60

Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp

65 70 75 80

Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr

85 90 95

Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile

100 105 110

Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Pro Glu

115 120 125

Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Phe Pro Val Asp Arg Thr Lys

130 135 140

Arg Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro

145 150 155 160

Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys

165 170 175

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

180 185 190

Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser

195 200 205

Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln

210 215 220

Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro

225 230 235 240

Tyr Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly

245 250 255

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln

260 265 270

Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr

275 280 285

Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile

290 295 300

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly

305 310 315 320

Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile

325 330 335

Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val

340 345 350

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr

355 360 365

Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr

370 375 380

Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro

385 390 395 400

Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro

405 410 415

Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp

420 425 430

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu

435 440 445

Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu

450 455 460

Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu

465 470 475 480

Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys

485 490 495

Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys

500 505 510

Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu

515 520 525

Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly

530 535 540

Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu

545 550 555 560

Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly

565 570 575

Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser

580 585 590

Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro

595 600 605

Pro Arg

610

<210> 60

<211> 1830

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 60

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccggagtgc aggtggaaac catctcccca ggagacgggc gcaccttccc caagcgcggc

120

cagacctgtg tggtgcacta caccgggatg cttgaagatg gaaagaaagt cgattcctcc

180

cgggacagaa acaagccctt taagtttatg ctaggcaagc aggaggtgat ccgaggctgg

240

gaagaagggg ttgcccagat gagtgtgggt cagagagcca aactgactat atctccagat

300

tatgcctatg gtgccactgg gcacccaggc atcatcccac cacatgccac tctcgtcttc

360

gatgtggagc ttctaaaacc ggaataccct tatgatgttc ctgattatgc tttccccgtg

420

gatcgtacta aaagagaaat tgtgatgacc cagtcacccg ccactcttag cctttcaccc

480

ggtgagcgcg caaccctgtc ttgcagagcc tcccaagaca tctcaaaata ccttaattgg

540

tatcaacaga agcccggaca ggctcctcgc cttctgatct accacaccag ccggctccat

600

tctggaatcc ctgccaggtt cagcggtagc ggatctggga ccgactacac cctcactatc

660

agctcactgc agccagagga cttcgctgtc tatttctgtc agcaagggaa caccctgccc

720

tacacctttg gacagggcac caagctcgag attaaaggtg gaggtggcag cggaggaggt

780

gggtccggcg gtggaggaag ccaggtccaa ctccaagaaa gcggaccggg tcttgtgaag

840

ccatcagaaa ctctttcact gacttgtact gtgagcggag tgtctctccc cgattacggg

900

gtgtcttgga tcagacagcc accggggaag ggtctggaat ggattggagt gatttggggc

960

tctgagacta cttactactc ttcatccctc aagtcacgcg tcaccatctc aaaggacaac

1020

tctaagaatc aggtgtcact gaaactgtca tctgtgaccg cagccgacac cgccgtgtac

1080

tattgcgcta agcattacta ttatggcggg agctacgcaa tggattactg gggacagggt

1140

actctggtca ccgtgtccag caccactacc ccagcaccga ggccacccac cccggctcct

1200

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

1260

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

1320

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1380

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1440

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1500

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1560

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1620

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1680

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1740

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1800

gctcttcaca tgcaggccct gccgcctcgg

1830

<210> 61

<211> 610

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 61

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp

20 25 30

Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr

35 40 45

Gly Met Leu Glu Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn

50 55 60

Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp

65 70 75 80

Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr

85 90 95

Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile

100 105 110

Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Pro Glu

115 120 125

Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Phe Pro Val Asp Ala Thr Lys

130 135 140

Arg Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro

145 150 155 160

Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys

165 170 175

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

180 185 190

Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser

195 200 205

Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln

210 215 220

Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro

225 230 235 240

Tyr Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly

245 250 255

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln

260 265 270

Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr

275 280 285

Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile

290 295 300

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly

305 310 315 320

Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile

325 330 335

Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val

340 345 350

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr

355 360 365

Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr

370 375 380

Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro

385 390 395 400

Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro

405 410 415

Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp

420 425 430

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu

435 440 445

Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu

450 455 460

Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu

465 470 475 480

Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys

485 490 495

Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys

500 505 510

Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu

515 520 525

Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly

530 535 540

Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu

545 550 555 560

Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly

565 570 575

Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser

580 585 590

Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro

595 600 605

Pro Arg

610

<210> 62

<211> 1830

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 62

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccggagtgc aggtggaaac catctcccca ggagacgggc gcaccttccc caagcgcggc

120

cagacctgtg tggtgcacta caccgggatg cttgaagatg gaaagaaagt cgattcctcc

180

cgggacagaa acaagccctt taagtttatg ctaggcaagc aggaggtgat ccgaggctgg

240

gaagaagggg ttgcccagat gagtgtgggt cagagagcca aactgactat atctccagat

300

tatgcctatg gtgccactgg gcacccaggc atcatcccac cacatgccac tctcgtcttc

360

gatgtggagc ttctaaaacc ggaataccct tatgatgttc ctgattatgc tttccccgtg

420

gatgctacta aaagagaaat tgtgatgacc cagtcacccg ccactcttag cctttcaccc

480

ggtgagcgcg caaccctgtc ttgcagagcc tcccaagaca tctcaaaata ccttaattgg

540

tatcaacaga agcccggaca ggctcctcgc cttctgatct accacaccag ccggctccat

600

tctggaatcc ctgccaggtt cagcggtagc ggatctggga ccgactacac cctcactatc

660

agctcactgc agccagagga cttcgctgtc tatttctgtc agcaagggaa caccctgccc

720

tacacctttg gacagggcac caagctcgag attaaaggtg gaggtggcag cggaggaggt

780

gggtccggcg gtggaggaag ccaggtccaa ctccaagaaa gcggaccggg tcttgtgaag

840

ccatcagaaa ctctttcact gacttgtact gtgagcggag tgtctctccc cgattacggg

900

gtgtcttgga tcagacagcc accggggaag ggtctggaat ggattggagt gatttggggc

960

tctgagacta cttactactc ttcatccctc aagtcacgcg tcaccatctc aaaggacaac

1020

tctaagaatc aggtgtcact gaaactgtca tctgtgaccg cagccgacac cgccgtgtac

1080

tattgcgcta agcattacta ttatggcggg agctacgcaa tggattactg gggacagggt

1140

actctggtca ccgtgtccag caccactacc ccagcaccga ggccacccac cccggctcct

1200

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

1260

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

1320

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1380

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1440

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1500

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1560

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1620

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1680

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1740

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1800

gctcttcaca tgcaggccct gccgcctcgg

1830

<210> 63

<211> 661

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 63

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ile Ser Leu Ile Ala Ala Leu Ala Val Asp Tyr

20 25 30

Val Ile Gly Met Glu Asn Ala Met Pro Trp Asn Leu Pro Ala Asp Leu

35 40 45

Ala Trp Phe Lys Arg Asn Thr Leu Asn Lys Pro Val Ile Met Gly Arg

50 55 60

His Thr Trp Glu Ser Ile Gly Arg Pro Leu Pro Gly Arg Lys Asn Ile

65 70 75 80

Ile Leu Ser Ser Gln Pro Ser Thr Asp Asp Arg Val Thr Trp Val Lys

85 90 95

Ser Val Asp Glu Ala Ile Ala Ala Cys Gly Asp Val Pro Glu Ile Met

100 105 110

Val Ile Gly Gly Gly Arg Val Ile Glu Gln Phe Leu Pro Lys Ala Gln

115 120 125

Lys Leu Tyr Leu Thr His Ile Asp Ala Glu Val Glu Gly Asp Thr His

130 135 140

Phe Pro Asp Tyr Glu Pro Asp Asp Trp Glu Ser Val Phe Ser Glu Phe

145 150 155 160

His Asp Ala Asp Ala Gln Asn Ser His Ser Tyr Cys Phe Glu Ile Leu

165 170 175

Glu Arg Arg Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Phe Pro Val Asp

180 185 190

Arg Thr Lys Arg Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser

195 200 205

Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp

210 215 220

Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro

225 230 235 240

Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala

245 250 255

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser

260 265 270

Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn

275 280 285

Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly

290 295 300

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

305 310 315 320

Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu

325 330 335

Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val

340 345 350

Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val

355 360 365

Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg

370 375 380

Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu

385 390 395 400

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His

405 410 415

Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr

420 425 430

Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

435 440 445

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

450 455 460

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

465 470 475 480

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

485 490 495

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

500 505 510

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

515 520 525

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

530 535 540

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

545 550 555 560

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

565 570 575

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

580 585 590

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

595 600 605

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

610 615 620

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

625 630 635 640

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

645 650 655

Ala Leu Pro Pro Arg

660

<210> 64

<211> 1983

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 64

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccatctctc tgattgccgc tctggccgtg gactacgtga tcgggatgga aaacgctatg

120

ccatggaatc tgcccgccga tctggcttgg ttcaagagga acaccctgaa caagccagtg

180

atcatgggca gacacacttg ggagtccatt ggccggcccc tgcctggacg caagaacatc

240

attctgagct cccagccctc taccgacgac agggtgacat gggtgaaaag tgtggacgaa

300

gccattgccg cttgcggaga tgtgcccgag atcatggtca tcggcggagg gagagtgatc

360

gagcagttcc tgcctaaggc ccagaaactg tacctgactc acattgacgc tgaggtggaa

420

ggggacaccc attttcctga ttatgagcca gacgattggg aaagcgtgtt ctccgagttt

480

cacgacgccg atgctcagaa ctctcatagt tattgctttg agatcctgga aaggagatac

540

ccttatgatg ttcctgatta tgctttcccc gtggatcgta ctaaaagaga aattgtgatg

600

acccagtcac ccgccactct tagcctttca cccggtgagc gcgcaaccct gtcttgcaga

660

gcctcccaag acatctcaaa ataccttaat tggtatcaac agaagcccgg acaggctcct

720

cgccttctga tctaccacac cagccggctc cattctggaa tccctgccag gttcagcggt

780

agcggatctg ggaccgacta caccctcact atcagctcac tgcagccaga ggacttcgct

840

gtctatttct gtcagcaagg gaacaccctg ccctacacct ttggacaggg caccaagctc

900

gagattaaag gtggaggtgg cagcggagga ggtgggtccg gcggtggagg aagccaggtc

960

caactccaag aaagcggacc gggtcttgtg aagccatcag aaactctttc actgacttgt

1020

actgtgagcg gagtgtctct ccccgattac ggggtgtctt ggatcagaca gccaccgggg

1080

aagggtctgg aatggattgg agtgatttgg ggctctgaga ctacttacta ctcttcatcc

1140

ctcaagtcac gcgtcaccat ctcaaaggac aactctaaga atcaggtgtc actgaaactg

1200

tcatctgtga ccgcagccga caccgccgtg tactattgcg ctaagcatta ctattatggc

1260

gggagctacg caatggatta ctggggacag ggtactctgg tcaccgtgtc cagcaccact

1320

accccagcac cgaggccacc caccccggct cctaccatcg cctcccagcc tctgtccctg

1380

cgtccgggagg catgtagacc cgcagctggt ggggccgtgc atacccgggg tcttgacttc

1440

gcctgcgata tctacatttg ggcccctctg gctggtactt gcggggtcct gctgctttca

1500

ctcgtgatca ctctttactg taagcgcggt cggaagaagc tgctgtacat ctttaagcaa

1560

cccttcatga ggcctgtgca gactactcaa gaggaggacg gctgttcatg ccggttccca

1620

gaggaggagg aaggcggctg cgaactgcgc gtgaaattca gccgcagcgc agatgctcca

1680

gcctacaagc aggggcagaa ccagctctac aacgaactca atcttggtcg gagagaggag

1740

tacgacgtgc tggacaagcg gagaggacgg gacccagaaa tgggcgggaa gccgcgcaga

1800

aagaatcccc aagaggggcct gtacaacgag ctccaaaagg ataagatggc agaagcctat

1860

agcgagattg gtatgaaagg ggaacgcaga agaggcaaag gccacgacgg actgtaccag

1920

ggactcagca ccgccaccaa ggacacctat gacgctcttc acatgcaggc cctgccgcct

1980

cgg

1983

<210> 65

<211> 661

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 65

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ile Ser Leu Ile Ala Ala Leu Ala Val Asp Tyr

20 25 30

Val Ile Gly Met Glu Asn Ala Met Pro Trp Asn Leu Pro Ala Asp Leu

35 40 45

Ala Trp Phe Lys Arg Asn Thr Leu Asn Lys Pro Val Ile Met Gly Arg

50 55 60

His Thr Trp Glu Ser Ile Gly Arg Pro Leu Pro Gly Arg Lys Asn Ile

65 70 75 80

Ile Leu Ser Ser Gln Pro Ser Thr Asp Asp Arg Val Thr Trp Val Lys

85 90 95

Ser Val Asp Glu Ala Ile Ala Ala Cys Gly Asp Val Pro Glu Ile Met

100 105 110

Val Ile Gly Gly Gly Arg Val Ile Glu Gln Phe Leu Pro Lys Ala Gln

115 120 125

Lys Leu Tyr Leu Thr His Ile Asp Ala Glu Val Glu Gly Asp Thr His

130 135 140

Phe Pro Asp Tyr Glu Pro Asp Asp Trp Glu Ser Val Phe Ser Glu Phe

145 150 155 160

His Asp Ala Asp Ala Gln Asn Ser His Ser Tyr Cys Phe Glu Ile Leu

165 170 175

Glu Arg Arg Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Phe Pro Val Asp

180 185 190

Ala Thr Lys Arg Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser

195 200 205

Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp

210 215 220

Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro

225 230 235 240

Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala

245 250 255

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser

260 265 270

Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn

275 280 285

Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly

290 295 300

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

305 310 315 320

Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu

325 330 335

Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val

340 345 350

Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val

355 360 365

Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg

370 375 380

Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu

385 390 395 400

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His

405 410 415

Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr

420 425 430

Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

435 440 445

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

450 455 460

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

465 470 475 480

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

485 490 495

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

500 505 510

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

515 520 525

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

530 535 540

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

545 550 555 560

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

565 570 575

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

580 585 590

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

595 600 605

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

610 615 620

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

625 630 635 640

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

645 650 655

Ala Leu Pro Pro Arg

660

<210> 66

<211> 1983

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 66

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccatctctc tgattgccgc tctggccgtg gactacgtga tcgggatgga aaacgctatg

120

ccatggaatc tgcccgccga tctggcttgg ttcaagagga acaccctgaa caagccagtg

180

atcatgggca gacacacttg ggagtccatt ggccggcccc tgcctggacg caagaacatc

240

attctgagct cccagccctc taccgacgac agggtgacat gggtgaaaag tgtggacgaa

300

gccattgccg cttgcggaga tgtgcccgag atcatggtca tcggcggagg gagagtgatc

360

gagcagttcc tgcctaaggc ccagaaactg tacctgactc acattgacgc tgaggtggaa

420

ggggacaccc attttcctga ttatgagcca gacgattggg aaagcgtgtt ctccgagttt

480

cacgacgccg atgctcagaa ctctcatagt tattgctttg agatcctgga aaggagatac

540

ccttatgatg ttcctgatta tgctttcccc gtggatgcta ctaaaagaga aattgtgatg

600

acccagtcac ccgccactct tagcctttca cccggtgagc gcgcaaccct gtcttgcaga

660

gcctcccaag acatctcaaa ataccttaat tggtatcaac agaagcccgg acaggctcct

720

cgccttctga tctaccacac cagccggctc cattctggaa tccctgccag gttcagcggt

780

agcggatctg ggaccgacta caccctcact atcagctcac tgcagccaga ggacttcgct

840

gtctatttct gtcagcaagg gaacaccctg ccctacacct ttggacaggg caccaagctc

900

gagattaaag gtggaggtgg cagcggagga ggtgggtccg gcggtggagg aagccaggtc

960

caactccaag aaagcggacc gggtcttgtg aagccatcag aaactctttc actgacttgt

1020

actgtgagcg gagtgtctct ccccgattac ggggtgtctt ggatcagaca gccaccgggg

1080

aagggtctgg aatggattgg agtgatttgg ggctctgaga ctacttacta ctcttcatcc

1140

ctcaagtcac gcgtcaccat ctcaaaggac aactctaaga atcaggtgtc actgaaactg

1200

tcatctgtga ccgcagccga caccgccgtg tactattgcg ctaagcatta ctattatggc

1260

gggagctacg caatggatta ctggggacag ggtactctgg tcaccgtgtc cagcaccact

1320

accccagcac cgaggccacc caccccggct cctaccatcg cctcccagcc tctgtccctg

1380

cgtccgggagg catgtagacc cgcagctggt ggggccgtgc atacccgggg tcttgacttc

1440

gcctgcgata tctacatttg ggcccctctg gctggtactt gcggggtcct gctgctttca

1500

ctcgtgatca ctctttactg taagcgcggt cggaagaagc tgctgtacat ctttaagcaa

1560

cccttcatga ggcctgtgca gactactcaa gaggaggacg gctgttcatg ccggttccca

1620

gaggaggagg aaggcggctg cgaactgcgc gtgaaattca gccgcagcgc agatgctcca

1680

gcctacaagc aggggcagaa ccagctctac aacgaactca atcttggtcg gagagaggag

1740

tacgacgtgc tggacaagcg gagaggacgg gacccagaaa tgggcgggaa gccgcgcaga

1800

aagaatcccc aagaggggcct gtacaacgag ctccaaaagg ataagatggc agaagcctat

1860

agcgagattg gtatgaaagg ggaacgcaga agaggcaaag gccacgacgg actgtaccag

1920

ggactcagca ccgccaccaa ggacacctat gacgctcttc acatgcaggc cctgccgcct

1980

cgg

1983

<210> 67

<211> 750

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 67

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Tyr Pro Tyr Asp

260 265 270

Val Pro Asp Tyr Ala Phe Pro Val Asp Arg Thr Lys Arg Glu Ile Val

275 280 285

Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala

290 295 300

Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp

305 310 315 320

Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr

325 330 335

Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser

340 345 350

Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

355 360 365

Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly

370 375 380

Gly Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly

385 390 395 400

Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro

405 410 415

Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser

420 425 430

Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro

435 440 445

Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr

450 455 460

Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn

465 470 475 480

Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp

485 490 495

Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr

500 505 510

Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr

515 520 525

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

530 535 540

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

545 550 555 560

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

565 570 575

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

580 585 590

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

595 600 605

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

610 615 620

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

625 630 635 640

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn

645 650 655

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

660 665 670

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

675 680 685

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

690 695 700

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

705 710 715 720

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

725 730 735

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 68

<211> 2250

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 68

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actctaccct tatgatgttc ctgattatgc tttccccgtg

840

gatcgtacta aaagagaaat tgtgatgacc cagtcacccg ccactcttag cctttcaccc

900

ggtgagcgcg caaccctgtc ttgcagagcc tcccaagaca tctcaaaata ccttaattgg

960

tatcaacaga agcccggaca ggctcctcgc cttctgatct accacaccag ccggctccat

1020

tctggaatcc ctgccaggtt cagcggtagc ggatctggga ccgactacac cctcactatc

1080

agctcactgc agccagagga cttcgctgtc tatttctgtc agcaagggaa caccctgccc

1140

tacacctttg gacagggcac caagctcgag attaaaggtg gaggtggcag cggaggaggt

1200

gggtccggcg gtggaggaag ccaggtccaa ctccaagaaa gcggaccggg tcttgtgaag

1260

ccatcagaaa ctctttcact gacttgtact gtgagcggag tgtctctccc cgattacggg

1320

gtgtcttgga tcagacagcc accggggaag ggtctggaat ggattggagt gatttggggc

1380

tctgagacta cttactactc ttcatccctc aagtcacgcg tcaccatctc aaaggacaac

1440

tctaagaatc aggtgtcact gaaactgtca tctgtgaccg cagccgacac cgccgtgtac

1500

tattgcgcta agcattacta ttatggcggg agctacgcaa tggattactg gggacagggt

1560

actctggtca ccgtgtccag caccactacc ccagcaccga ggccacccac cccggctcct

1620

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

1680

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

1740

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1800

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1860

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1920

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1980

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

2040

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

2100

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

2160

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

2220

gctcttcaca tgcaggccct gccgcctcgg

2250

<210> 69

<211> 750

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 69

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Tyr Pro Tyr Asp

260 265 270

Val Pro Asp Tyr Ala Phe Pro Val Asp Ala Thr Lys Arg Glu Ile Val

275 280 285

Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala

290 295 300

Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp

305 310 315 320

Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr

325 330 335

Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser

340 345 350

Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

355 360 365

Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly

370 375 380

Gly Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly

385 390 395 400

Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro

405 410 415

Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser

420 425 430

Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro

435 440 445

Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr

450 455 460

Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn

465 470 475 480

Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp

485 490 495

Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr

500 505 510

Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr

515 520 525

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

530 535 540

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

545 550 555 560

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

565 570 575

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

580 585 590

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

595 600 605

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

610 615 620

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

625 630 635 640

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn

645 650 655

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

660 665 670

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

675 680 685

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

690 695 700

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

705 710 715 720

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

725 730 735

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 70

<211> 2250

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 70

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actctaccct tatgatgttc ctgattatgc tttccccgtg

840

gatgctacta aaagagaaat tgtgatgacc cagtcacccg ccactcttag cctttcaccc

900

ggtgagcgcg caaccctgtc ttgcagagcc tcccaagaca tctcaaaata ccttaattgg

960

tatcaacaga agcccggaca ggctcctcgc cttctgatct accacaccag ccggctccat

1020

tctggaatcc ctgccaggtt cagcggtagc ggatctggga ccgactacac cctcactatc

1080

agctcactgc agccagagga cttcgctgtc tatttctgtc agcaagggaa caccctgccc

1140

tacacctttg gacagggcac caagctcgag attaaaggtg gaggtggcag cggaggaggt

1200

gggtccggcg gtggaggaag ccaggtccaa ctccaagaaa gcggaccggg tcttgtgaag

1260

ccatcagaaa ctctttcact gacttgtact gtgagcggag tgtctctccc cgattacggg

1320

gtgtcttgga tcagacagcc accggggaag ggtctggaat ggattggagt gatttggggc

1380

tctgagacta cttactactc ttcatccctc aagtcacgcg tcaccatctc aaaggacaac

1440

tctaagaatc aggtgtcact gaaactgtca tctgtgaccg cagccgacac cgccgtgtac

1500

tattgcgcta agcattacta ttatggcggg agctacgcaa tggattactg gggacagggt

1560

actctggtca ccgtgtccag caccactacc ccagcaccga ggccacccac cccggctcct

1620

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

1680

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

1740

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1800

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1860

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1920

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1980

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

2040

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

2100

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

2160

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

2220

gctcttcaca tgcaggccct gccgcctcgg

2250

<210> 71

<211> 606

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 71

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp

20 25 30

Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr

35 40 45

Gly Met Leu Glu Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn

50 55 60

Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp

65 70 75 80

Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr

85 90 95

Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile

100 105 110

Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Pro Glu

115 120 125

Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Phe Pro Val Asp Glu Ile Val

130 135 140

Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala

145 150 155 160

Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp

165 170 175

Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr

180 185 190

Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser

195 200 205

Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

210 215 220

Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly

225 230 235 240

Gly Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly

245 250 255

Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro

260 265 270

Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser

275 280 285

Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro

290 295 300

Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr

305 310 315 320

Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn

325 330 335

Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp

340 345 350

Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr

355 360 365

Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr

370 375 380

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

385 390 395 400

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

405 410 415

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

420 425 430

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

435 440 445

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

450 455 460

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

465 470 475 480

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

485 490 495

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn

500 505 510

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

515 520 525

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

530 535 540

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

545 550 555 560

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

565 570 575

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

580 585 590

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

595 600 605

<210> 72

<211> 1818

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 72

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccggagtgc aggtggaaac catctcccca ggagacgggc gcaccttccc caagcgcggc

120

cagacctgtg tggtgcacta caccgggatg cttgaagatg gaaagaaagt cgattcctcc

180

cgggacagaa acaagccctt taagtttatg ctaggcaagc aggaggtgat ccgaggctgg

240

gaagaagggg ttgcccagat gagtgtgggt cagagagcca aactgactat atctccagat

300

tatgcctatg gtgccactgg gcacccaggc atcatcccac cacatgccac tctcgtcttc

360

gatgtggagc ttctaaaacc ggaataccct tatgatgttc ctgattatgc tttccccgtg

420

gatgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

480

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

540

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

600

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

660

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

720

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

780

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

840

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

900

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

960

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1020

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1080

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1140

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1200

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1260

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1320

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1380

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1440

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1500

agcgcagatg ctccagccta caagcagggg cagaaccagc tctacaacga actcaatctt

1560

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

1620

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

1680

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

1740

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

1800

caggccctgc cgcctcgg

1818

<210> 73

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 73

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Tyr Pro Tyr Asp

260 265 270

Val Pro Asp Tyr Ala Phe Pro Val Asp Glu Ile Val Met Thr Gln Ser

275 280 285

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

290 295 300

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys

305 310 315 320

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His

325 330 335

Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr

340 345 350

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe

355 360 365

Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys

370 375 380

Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

405 410 415

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu

420 425 430

Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

435 440 445

Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser

450 455 460

Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln

465 470 475 480

Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

485 490 495

Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

500 505 510

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 74

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 74

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actctaccct tatgatgttc ctgattatgc tttccccgtg

840

gatgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

900

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

960

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

1020

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

1080

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

1140

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

1200

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

1260

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

1320

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

1380

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1440

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1500

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1560

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta caagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 75

<211> 737

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 75

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Arg Thr Lys Arg

260 265 270

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

275 280 285

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

290 295 300

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

305 310 315 320

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

325 330 335

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

340 345 350

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

355 360 365

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

370 375 380

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

385 390 395 400

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

405 410 415

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

420 425 430

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

435 440 445

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

450 455 460

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

465 470 475 480

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

485 490 495

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

500 505 510

Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

515 520 525

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

530 535 540

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

545 550 555 560

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

565 570 575

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

580 585 590

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

595 600 605

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

610 615 620

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

625 630 635 640

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

645 650 655

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

660 665 670

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

675 680 685

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

690 695 700

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

705 710 715 720

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

725 730 735

Arg

<210> 76

<211> 2211

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 76

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actccgtact aaaagagaaa ttgtgatgac ccagtcaccc

840

gccactctta gcctttcacc cggtgagcgc gcaaccctgt cttgcagagc ctcccaagac

900

atctcaaaat accttaattg gtatcaacag aagcccggac aggctcctcg ccttctgatc

960

taccacacca gccggctcca ttctggaatc cctgccaggt tcagcggtag cggatctggg

1020

accgactaca ccctcactat cagctcactg cagccagagg acttcgctgt ctatttctgt

1080

cagcaaggga acaccctgcc ctacaccttt ggacagggca ccaagctcga gattaaaggt

1140

ggaggtggca gcggaggagg tgggtccggc ggtggaggaa gccaggtcca actccaagaa

1200

agcggaccgg gtcttgtgaa gccatcagaa actctttcac tgacttgtac tgtgagcgga

1260

gtgtctctcc ccgattacgg ggtgtcttgg atcagacagc caccggggaa gggtctggaa

1320

tggattggag tgatttgggg ctctgagact acttactact cttcatccct caagtcacgc

1380

gtcaccatct caaaggacaa ctctaagaat caggtgtcac tgaaactgtc atctgtgacc

1440

gcagccgaca ccgccgtgta ctattgcgct aagcattact attatggcgg gagctacgca

1500

atggattact ggggacaggg tactctggtc accgtgtcca gcaccactac cccagcaccg

1560

aggccaccca ccccggctcc taccatcgcc tcccagcctc tgtccctgcg tccgggaggca

1620

tgtagacccg cagctggtgg ggccgtgcat acccggggtc ttgacttcgc ctgcgatatc

1680

tacatttggg cccctctggc tggtacttgc ggggtcctgc tgctttcact cgtgatcact

1740

ctttactgta agcgcggtcg gaagaagctg ctgtacatct ttaagcaacc cttcatgagg

1800

cctgtgcaga ctactcaaga ggaggacggc tgttcatgcc ggttcccaga ggaggaggaa

1860

ggcggctgcg aactgcgcgt gaaattcagc cgcagcgcag atgctccagc ctacaagcag

1920

gggcagaacc agctctacaa cgaactcaat cttggtcgga gagaggagta cgacgtgctg

1980

gacaagcgga gaggacggga cccagaaatg ggcgggaagc cgcgcagaaa gaatccccaa

2040

gagggcctgt acaacgagct ccaaaaggat aagatggcag aagcctatag cgagattggt

2100

atgaaagggg aacgcagaag aggcaaaggc cacgacggac tgtaccaggg actcagcacc

2160

gccaccaagg acacctatga cgctcttcac atgcaggccc tgccgcctcg g

2211

<210> 77

<211> 733

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 77

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Glu Ile Val Met

260 265 270

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

275 280 285

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

290 295 300

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

305 310 315 320

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

325 330 335

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

340 345 350

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

355 360 365

Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly

370 375 380

Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly

385 390 395 400

Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly

405 410 415

Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly

420 425 430

Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr

435 440 445

Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser

450 455 460

Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr

465 470 475 480

Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala

485 490 495

Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr

500 505 510

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

515 520 525

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

530 535 540

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

545 550 555 560

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

565 570 575

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

580 585 590

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

595 600 605

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

610 615 620

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln

625 630 635 640

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

645 650 655

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

660 665 670

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

675 680 685

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

690 695 700

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

705 710 715 720

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

725 730

<210> 78

<211> 2199

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 78

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcgaaatt gtgatgaccc agtcacccgc cactcttagc

840

ctttcacccg gtgagcgcgc aaccctgtct tgcagagcct cccaagacat ctcaaaatac

900

cttaattggt atcaacagaa gcccggacag gctcctcgcc ttctgatcta ccacaccagc

960

cggctccatt ctggaatccc tgccaggttc agcggtagcg gatctgggac cgactacacc

1020

ctcactatca gctcactgca gccagaggac ttcgctgtct atttctgtca gcaagggaac

1080

accctgccct acacctttgg acagggcacc aagctcgaga ttaaaggtgg aggtggcagc

1140

ggaggaggtg ggtccggcgg tggaggaagc caggtccaac tccaagaaag cggaccgggt

1200

cttgtgaagc catcagaaac tctttcactg acttgtactg tgagcggagt gtctctcccc

1260

gattacgggg tgtcttggat cagacagcca ccggggaagg gtctggaatg gattggagtg

1320

atttggggct ctgagactac ttactactct tcatccctca agtcacgcgt caccatctca

1380

aaggacaact ctaagaatca ggtgtcactg aaactgtcat ctgtgaccgc agccgacacc

1440

gccgtgtact attgcgctaa gcattactat tatggcggga gctacgcaat ggattactgg

1500

ggacagggta ctctggtcac cgtgtccagc accactaccc cagcaccgag gccacccacc

1560

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1620

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1680

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1740

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1800

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1860

ctgcgcgtga aattcagccg cagcgcagat gctccagcct acaagcaggg gcagaaccag

1920

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

1980

ggacgggacc cagaaatgggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2040

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2100

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2160

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2199

<210> 79

<400> 79

000

<210> 80

<400> 80

000

<210> 81

<400> 81

000

<210> 82

<211> 5000

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<220>

<221> OTHER_INDICATOR

<222> (1)..(5000)

<223> /note="This sequence can include 100-5000

nucleotides"

<220>

<221> source

<223> /note="See submitted application specification for details

descriptions

substitutions and preferred embodiments"

<400> 82

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

60

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

120

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

180

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

240

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

300

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

360

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

420

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

480

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

540

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

600

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

660

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

720

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

780

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

840

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

900

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

960

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1020

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1080

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1140

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1200

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1260

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1320

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1380

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1440

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1500

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1560

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1620

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1680

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1740

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1800

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1860

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1920

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

1980

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2040

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2100

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2160

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2220

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2280

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2340

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2400

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2460

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2520

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2580

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2640

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2700

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2760

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2820

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2880

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2940

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3000

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3060

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3120

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3180

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3240

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3300

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3360

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3420

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3480

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3540

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3600

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3660

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3720

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3780

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3840

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3900

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

3960

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4020

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4080

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4140

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4200

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4260

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4320

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4380

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4440

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4500

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4560

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4620

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4680

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4740

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4800

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4860

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4920

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

4980

aaaaaaaaaaaaaaaaaaaa

5000

<210> 83

<400> 83

000

<210> 84

<400> 84

000

<210> 85

<400> 85

000

<210> 86

<400> 86

000

<210> 87

<400> 87

000

<210> 88

<400> 88

000

<210> 89

<400> 89

000

<210> 90

<400> 90

000

<210> 91

<400> 91

000

<210> 92

<400> 92

000

<210> 93

<400> 93

000

<210> 94

<400> 94

000

<210> 95

<400> 95

000

<210> 96

<400> 96

000

<210> 97

<400> 97

000

<210> 98

<400> 98

000

<210> 99

<400> 99

000

<210> 100

<400> 100

000

<210> 101

<400> 101

000

<210> 102

<400> 102

000

<210> 103

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 103

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Ser Leu Asn Leu

260 265 270

Thr Glu Ser His Asn Ser Arg Lys Lys Arg Glu Ile Val Met Thr Gln

275 280 285

Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

290 295 300

Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln

305 310 315 320

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu

325 330 335

His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

340 345 350

Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr

355 360 365

Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr

370 375 380

Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

405 410 415

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

420 425 430

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

435 440 445

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser

450 455 460

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

465 470 475 480

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

485 490 495

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

500 505 510

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 104

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 104

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcagtctc aatttgactg agtcacacaa ttccaggaag

840

aaaagggaaa ttgtgatgac ccagtcaccc gccactctta gcctttcacc cggtgagcgc

900

gcaaccctgt cttgcagagc ctcccaagac atctcaaaat accttaattg gtatcaacag

960

aagcccggac aggctcctcg ccttctgatc taccacacca gccggctcca ttctggaatc

1020

cctgccaggt tcagcggtag cggatctggg accgactaca ccctcactat cagctcactg

1080

cagccagagg acttcgctgt ctatttctgt cagcaaggga acaccctgcc ctacaccttt

1140

ggacagggca ccaagctcga gattaaaggt ggaggtggca gcggaggagg tgggtccggc

1200

ggtggaggaa gccaggtcca actccaagaa agcggaccgg gtcttgtgaa gccatcagaa

1260

actctttcac tgacttgtac tgtgagcgga gtgtctctcc ccgattacgg ggtgtcttgg

1320

atcagacagc caccggggaa gggtctggaa tggattggag tgatttgggg ctctgagact

1380

acttactact cttcatccct caagtcacgc gtcaccatct caaaggacaa ctctaagaat

1440

caggtgtcac tgaaactgtc atctgtgacc gcagccgaca ccgccgtgta ctattgcgct

1500

aagcattact attatggcgg gagctacgca atggattact ggggacaggg tactctggtc

1560

accgtgtcca gcaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 105

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 105

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln

275 280 285

Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

290 295 300

Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln

305 310 315 320

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu

325 330 335

His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

340 345 350

Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr

355 360 365

Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr

370 375 380

Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

405 410 415

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

420 425 430

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

435 440 445

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser

450 455 460

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

465 470 475 480

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

485 490 495

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

500 505 510

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 106

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 106

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcgggacg ggagctgagg atccacgacc cagcagaaag

840

cgacgggaaa ttgtgatgac ccagtcaccc gccactctta gcctttcacc cggtgagcgc

900

gcaaccctgt cttgcagagc ctcccaagac atctcaaaat accttaattg gtatcaacag

960

aagcccggac aggctcctcg ccttctgatc taccacacca gccggctcca ttctggaatc

1020

cctgccaggt tcagcggtag cggatctggg accgactaca ccctcactat cagctcactg

1080

cagccagagg acttcgctgt ctatttctgt cagcaaggga acaccctgcc ctacaccttt

1140

ggacagggca ccaagctcga gattaaaggt ggaggtggca gcggaggagg tgggtccggc

1200

ggtggaggaa gccaggtcca actccaagaa agcggaccgg gtcttgtgaa gccatcagaa

1260

actctttcac tgacttgtac tgtgagcgga gtgtctctcc ccgattacgg ggtgtcttgg

1320

atcagacagc caccggggaa gggtctggaa tggattggag tgatttgggg ctctgagact

1380

acttactact cttcatccct caagtcacgc gtcaccatct caaaggacaa ctctaagaat

1440

caggtgtcac tgaaactgtc atctgtgacc gcagccgaca ccgccgtgta ctattgcgct

1500

aagcattact attatggcgg gagctacgca atggattact ggggacaggg tactctggtc

1560

accgtgtcca gcaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 107

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 107

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Cys Lys Ile Asn

260 265 270

Gly Tyr Pro Lys Arg Gly Arg Lys Arg Arg Glu Ile Val Met Thr Gln

275 280 285

Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

290 295 300

Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln

305 310 315 320

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu

325 330 335

His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

340 345 350

Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr

355 360 365

Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr

370 375 380

Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

405 410 415

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

420 425 430

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

435 440 445

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser

450 455 460

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

465 470 475 480

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

485 490 495

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

500 505 510

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 108

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 108

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actctgcaag atcaacggct accctaagag gggcagaaag

840

cggcgggaaa ttgtgatgac ccagtcaccc gccactctta gcctttcacc cggtgagcgc

900

gcaaccctgt cttgcagagc ctcccaagac atctcaaaat accttaattg gtatcaacag

960

aagcccggac aggctcctcg ccttctgatc taccacacca gccggctcca ttctggaatc

1020

cctgccaggt tcagcggtag cggatctggg accgactaca ccctcactat cagctcactg

1080

cagccagagg acttcgctgt ctatttctgt cagcaaggga acaccctgcc ctacaccttt

1140

ggacagggca ccaagctcga gattaaaggt ggaggtggca gcggaggagg tgggtccggc

1200

ggtggaggaa gccaggtcca actccaagaa agcggaccgg gtcttgtgaa gccatcagaa

1260

actctttcac tgacttgtac tgtgagcgga gtgtctctcc ccgattacgg ggtgtcttgg

1320

atcagacagc caccggggaa gggtctggaa tggattggag tgatttgggg ctctgagact

1380

acttactact cttcatccct caagtcacgc gtcaccatct caaaggacaa ctctaagaat

1440

caggtgtcac tgaaactgtc atctgtgacc gcagccgaca ccgccgtgta ctattgcgct

1500

aagcattact attatggcgg gagctacgca atggattact ggggacaggg tactctggtc

1560

accgtgtcca gcaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 109

<211> 748

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 109

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Leu Gln Trp Leu

260 265 270

Glu Gln Gln Val Ala Lys Arg Arg Thr Lys Arg Glu Ile Val Met Thr

275 280 285

Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu

290 295 300

Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln

305 310 315 320

Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg

325 330 335

Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr

340 345 350

Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val

355 360 365

Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly

370 375 380

Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

385 390 395 400

Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

405 410 415

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

420 425 430

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

435 440 445

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

450 455 460

Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

465 470 475 480

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

485 490 495

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

500 505 510

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr

515 520 525

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

530 535 540

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

545 550 555 560

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

565 570 575

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

580 585 590

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

595 600 605

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

610 615 620

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

625 630 635 640

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu

645 650 655

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

660 665 670

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

675 680 685

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

690 695 700

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

705 710 715 720

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

725 730 735

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 110

<211> 2244

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 110

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcctgcaa tggctggagc agcaggtggc gaagcggaga

840

actaagcggg aaattgtgat gacccagtca cccgccactc ttagcctttc acccggtgag

900

cgcgcaaccc tgtcttgcag agcctcccaa gacatctcaa aataccttaa ttggtatcaa

960

cagaagcccg gacaggctcc tcgccttctg atctaccaca ccagccggct ccattctggga

1020

atccctgcca ggttcagcgg tagcggatct gggaccgact acaccctcac tatcagctca

1080

ctgcagccag aggacttcgc tgtctatttc tgtcagcaag ggaacaccct gccctacacc

1140

tttggacagg gcaccaagct cgagattaaa ggtggaggtg gcagcggagg aggtgggtcc

1200

ggcggtggag gaagccaggt ccaactccaa gaaagcggac cgggtcttgt gaagccatca

1260

gaaactcttt cactgacttg tactgtgagc ggagtgtctc tccccgatta cggggtgtct

1320

tggatcagac agccaccggg gaagggtctg gaatggattg gagtgatttg gggctctgag

1380

actacttact actcttcatc cctcaagtca cgcgtcacca tctcaaagga caactctaag

1440

aatcaggtgt cactgaaact gtcatctgtg accgcagccg acaccgccgt gtactattgc

1500

gctaagcatt actattatgg cgggagctac gcaatggatt actggggaca gggtactctg

1560

gtcaccgtgt ccagcaccac taccccagca ccgaggccac ccaccccggc tcctaccatc

1620

gcctcccagc ctctgtccct gcgtccggag gcatgtagac ccgcagctgg tggggccgtg

1680

catacccggg gtcttgactt cgcctgcgat atctacattt gggcccctct ggctggtact

1740

tgcggggtcc tgctgctttc actcgtgatc actctttact gtaagcgcgg tcggaagaag

1800

ctgctgtaca tctttaagca acccttcatg aggcctgtgc agactactca agaggaggac

1860

ggctgttcat gccggttccc agaggaggag gaaggcggct gcgaactgcg cgtgaaattc

1920

agccgcagcg cagatgctcc agcctacaag caggggcaga accagctcta caacgaactc

1980

aatcttggtc ggagaggagga gtacgacgtg ctggacaagc ggagaggacg ggacccagaa

2040

atgggcggga agccgcgcag aaagaatccc caagaggggcc tgtacaacga gctccaaaag

2100

gataagatgg cagaagccta tagcgagatt ggtatgaaag gggaacgcag aagaggcaaa

2160

ggccacgacg gactgtacca gggactcagc accgccacca aggacaccta tgacgctctt

2220

cacatgcagg ccctgccgcc tcgg

2244

<210> 111

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 111

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly

275 280 285

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

290 295 300

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

305 310 315 320

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

325 330 335

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

340 345 350

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

355 360 365

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

370 375 380

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

385 390 395 400

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

405 410 415

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

420 425 430

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

435 440 445

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

450 455 460

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

465 470 475 480

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

485 490 495

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

500 505 510

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

515 520 525

Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 112

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 112

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggtccc tcggagacgt gggtgaaatt gtgatgaccc agtcacccgc cactcttagc

900

ctttcacccg gtgagcgcgc aaccctgtct tgcagagcct cccaagacat ctcaaaatac

960

cttaattggt atcaacagaa gcccggacag gctcctcgcc ttctgatcta ccacaccagc

1020

cggctccatt ctggaatccc tgccaggttc agcggtagcg gatctgggac cgactacacc

1080

ctcactatca gctcactgca gccagaggac ttcgctgtct atttctgtca gcaagggaac

1140

accctgccct acacctttgg acagggcacc aagctcgaga ttaaaggtgg aggtggcagc

1200

ggaggaggtg ggtccggcgg tggaggaagc caggtccaac tccaagaaag cggaccgggt

1260

cttgtgaagc catcagaaac tctttcactg acttgtactg tgagcggagt gtctctcccc

1320

gattacgggg tgtcttggat cagacagcca ccggggaagg gtctggaatg gattggagtg

1380

atttggggct ctgagactac ttactactct tcatccctca agtcacgcgt caccatctca

1440

aaggacaact ctaagaatca ggtgtcactg aaactgtcat ctgtgaccgc agccgacacc

1500

gccgtgtact attgcgctaa gcattactat tatggcggga gctacgcaat ggattactgg

1560

ggacagggta ctctggtcac cgtgtccagc accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct acaagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 113

<211> 751

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 113

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Gly Glu Ile

275 280 285

Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg

290 295 300

Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn

305 310 315 320

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His

325 330 335

Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly

340 345 350

Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp

355 360 365

Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe

370 375 380

Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly

405 410 415

Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val

420 425 430

Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro

435 440 445

Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr

450 455 460

Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp

465 470 475 480

Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala

485 490 495

Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser

500 505 510

Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

515 520 525

Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala

530 535 540

Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly

545 550 555 560

Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile

565 570 575

Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val

580 585 590

Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe

595 600 605

Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly

610 615 620

Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg

625 630 635 640

Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln

645 650 655

Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp

660 665 670

Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro

675 680 685

Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp

690 695 700

Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg

705 710 715 720

Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr

725 730 735

Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 114

<211> 2253

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 114

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggcaca ggtgccgagg accctcggcc aagccgcaaa

840

aggaggtcac ttggcggcga aattgtgatg acccagtcac ccgccactct tagcctttca

900

cccggtgagc gcgcaaccct gtcttgcaga gcctcccaag acatctcaaa ataccttaat

960

tggtatcaac agaagcccgg acaggctcct cgccttctga tctaccacac cagccggctc

1020

cattctggaa tccctgccag gttcagcggt agcggatctg ggaccgacta caccctcact

1080

atcagctcac tgcagccaga ggacttcgct gtctatttct gtcagcaagg gaacaccctg

1140

ccctacacct ttggacaggg caccaagctc gagattaaag gtggaggtgg cagcggagga

1200

ggtgggtccg gcggtggagg aagccaggtc caactccaag aaagcggacc gggtcttgtg

1260

aagccatcag aaactctttc actgacttgt actgtgagcg gagtgtctct ccccgattac

1320

ggggtgtctt ggatcagaca gccaccgggg aagggtctgg aatggattgg agtgatttgg

1380

ggctctgaga ctacttacta ctcttcatcc ctcaagtcac gcgtcaccat ctcaaaggac

1440

aactctaaga atcaggtgtc actgaaactg tcatctgtga ccgcagccga caccgccgtg

1500

tactattgcg ctaagcatta ctattatggc gggagctacg caatggatta ctggggacag

1560

ggtactctgg tcaccgtgtc cagcaccact accccagcac cgaggccacc caccccggct

1620

cctaccatcg cctcccagcc tctgtccctg cgtccgggagg catgtagacc cgcagctggt

1680

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

1740

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1800

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1860

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1920

gtgaaattca gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac

1980

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

2040

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

2100

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

2160

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

2220

gacgctcttc acatgcaggc cctgccgcct cgg

2253

<210> 115

<211> 750

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 115

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Glu Ile Val

275 280 285

Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala

290 295 300

Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp

305 310 315 320

Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr

325 330 335

Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser

340 345 350

Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

355 360 365

Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly

370 375 380

Gly Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly

385 390 395 400

Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro

405 410 415

Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser

420 425 430

Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro

435 440 445

Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr

450 455 460

Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn

465 470 475 480

Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp

485 490 495

Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr

500 505 510

Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr

515 520 525

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

530 535 540

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

545 550 555 560

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

565 570 575

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

580 585 590

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

595 600 605

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

610 615 620

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

625 630 635 640

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn

645 650 655

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

660 665 670

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

675 680 685

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

690 695 700

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

705 710 715 720

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

725 730 735

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 116

<211> 2250

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 116

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggagcagaag atcccagacc aagccggaaa

840

aggcggtccc tgggtgaaat tgtgatgacc cagtcacccg ccactcttag cctttcaccc

900

ggtgagcgcg caaccctgtc ttgcagagcc tcccaagaca tctcaaaata ccttaattgg

960

tatcaacaga agcccggaca ggctcctcgc cttctgatct accacaccag ccggctccat

1020

tctggaatcc ctgccaggtt cagcggtagc ggatctggga ccgactacac cctcactatc

1080

agctcactgc agccagagga cttcgctgtc tatttctgtc agcaagggaa caccctgccc

1140

tacacctttg gacagggcac caagctcgag attaaaggtg gaggtggcag cggaggaggt

1200

gggtccggcg gtggaggaag ccaggtccaa ctccaagaaa gcggaccggg tcttgtgaag

1260

ccatcagaaa ctctttcact gacttgtact gtgagcggag tgtctctccc cgattacggg

1320

gtgtcttgga tcagacagcc accggggaag ggtctggaat ggattggagt gatttggggc

1380

tctgagacta cttactactc ttcatccctc aagtcacgcg tcaccatctc aaaggacaac

1440

tctaagaatc aggtgtcact gaaactgtca tctgtgaccg cagccgacac cgccgtgtac

1500

tattgcgcta agcattacta ttatggcggg agctacgcaa tggattactg gggacagggt

1560

actctggtca ccgtgtccag caccactacc ccagcaccga ggccacccac cccggctcct

1620

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

1680

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

1740

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1800

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1860

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1920

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1980

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

2040

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

2100

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

2160

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

2220

gctcttcaca tgcaggccct gccgcctcgg

2250

<210> 117

<400> 117

000

<210> 118

<211> 126

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 118

aagcgcggtc ggaagaagct gctgtacatc tttaagcaac ccttcatgag gcctgtgcag

60

actactcaag aggaggacgg ctgttcatgc cggttcccag aggaggagga aggcggctgc

120

gaactg

126

<210> 119

<211> 336

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 119

cgcgtgaaat tcagccgcag cgcagatgct ccagcctaca agcaggggca gaaccagctc

60

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

120

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

180

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

240

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

300

tatgacgctc ttcacatgca ggccctgccg cctcgg

336

<210> 120

<211> 35

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 120

Thr Lys Lys Lys Tyr Ser Ser Ser Val His Asp Pro Asn Gly Glu Tyr

1 5 10 15

Met Phe Met Arg Ala Val Asn Thr Ala Lys Lys Ser Arg Leu Thr Asp

20 25 30

Val Thr Leu

35

<210> 121

<211> 245

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 121

Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met Val Ser Ala Leu Leu

1 5 10 15

Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr Asp Pro Thr Arg Pro

20 25 30

Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr Asn Leu Ala Asp Arg

35 40 45

Glu Leu Val His Met Ile Asn Trp Ala Lys Arg Val Pro Gly Phe Val

50 55 60

Asp Leu Thr Leu His Asp Gln Val His Leu Leu Glu Cys Ala Trp Met

65 70 75 80

Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser Met Glu His Pro Gly

85 90 95

Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp Arg Asn Gln Gly Lys

100 105 110

Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met Leu Leu Ala Thr Ser

115 120 125

Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu Glu Phe Val Cys Leu

130 135 140

Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr Thr Phe Leu Ser Ser

145 150 155 160

Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile His Arg Val Leu Asp

165 170 175

Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala Lys Ala Gly Leu Thr

180 185 190

Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu Leu Leu Ile Leu Ser

195 200 205

His Ile Arg His Met Ser Asn Lys Arg Met Glu His Leu Tyr Ser Met

210 215 220

Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu Leu Leu Glu Met Leu

225 230 235 240

Asp Ala His Arg Leu

245

<210> 122

<211> 735

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 122

tcgttggcac tttccctgac tgccgaccag atggtgtccg cccttctgga cgccgagcct

60

ccaattctgt actcggagta cgatccgact cgcccgttct ccgaagccag catgatgggc

120

ctgttgacta acctggcgga ccgcgagttg gtgcacatga ttaactgggc taagcgggtg

180

ccgggcttcg tggacctgac cctgcacgac caagtgcacc tcctggaatg cgcctggatg

240

gaaatcctca tgatcggcct cgtgtggaga tccatggagc atcccggaaa gctcctgttt

300

gcacccaacc tcctgcttga tcgcaaccag ggaaaatgcg tggaaggggg tgtcgagatt

360

ttcgacatgc tgctcgccac ctcttcccgg ttccggatga tgaatctgca gggagaagag

420

ttcgtgtgtc tgaagtcaat catcctgctg aactccgggg tctatacctt cctgagctcg

480

accctcaagt cactggagga aaaagaccac atccatcgcg tgctcgataa gatcaccgac

540

acccttatcc atctcatggc gaaggctgga ctgaccctgc aacagcagca ccagaggctg

600

gcccagttgc tgctgattct gagccacatc cggcacatgt cgaacaagag gatggaacac

660

ctgtacagca tgaagtgcaa gaacgtcgtg cctctgtccg atctgctcct ggaaatgctg

720

gacgcgcaca gactc

735

<210> 123

<211> 4

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 123

Arg Thr Lys Arg

1

<210> 124

<211> 41

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 124

Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr

1 5 10 15

Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro

20 25 30

Pro Arg Asp Phe Ala Ala Tyr Arg Ser

35 40

<210> 125

<211> 20

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 125

Gly Thr Gly Ala Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu

1 5 10 15

Gly Asp Val Gly

20

<210> 126

<211> 60

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 126

ggaaccggcg cggaagaccc ccggccctcc aggaagcgaa ggtccctcgg agacgtgggt

60

<210> 127

<211> 14

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 127

Gly Thr Gly Ala Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg

1 5 10

<210> 128

<211> 42

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 128

ggaaccggcg cggaagaccc ccggccctcc aggaagcgaa gg

42

<210> 129

<211> 15

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 129

Leu Gln Trp Leu Glu Gln Gln Val Ala Lys Arg Arg Thr Lys Arg

1 5 10 15

<210> 130

<211> 45

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 130

ctgcaatggc tggagcagca ggtggcgaag cggagaacta agcgg

45

<210> 131

<211> 18

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 131

Gly Thr Gly Ala Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu

1 5 10 15

Gly Gly

<210> 132

<211> 54

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 132

ggcacaggtg ccgaggaccc tcggccaagc cgcaaaagga ggtcacttgg cggc

54

<210> 133

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 133

Gly Thr Gly Ala Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu

1 5 10 15

gly

<210> 134

<211> 51

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 134

ggaaccggag cagaagatcc cagaccaagc cggaaaaggc ggtccctgggg t

51

<210> 135

<211> 14

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 135

Ser Leu Asn Leu Thr Glu Ser His Asn Ser Arg Lys Lys Arg

1 5 10

<210> 136

<211> 42

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 136

agtctcaatt tgactgagtc acacaattcc aggaagaaaa gg

42

<210> 137

<211> 14

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 137

Cys Lys Ile Asn Gly Tyr Pro Lys Arg Gly Arg Lys Arg Arg

1 5 10

<210> 138

<211> 42

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 138

tgcaagatca acggctaccc taagaggggc agaaagcggc gg

42

<210> 139

<211> 21

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 139

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro

20

<210> 140

<211> 63

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 140

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccc

63

<210> 141

<211> 737

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 141

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Arg Thr Lys Arg

260 265 270

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

275 280 285

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

290 295 300

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

305 310 315 320

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

325 330 335

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

340 345 350

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

355 360 365

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

370 375 380

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

385 390 395 400

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

405 410 415

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

420 425 430

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

435 440 445

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

450 455 460

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

465 470 475 480

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

485 490 495

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

500 505 510

Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

515 520 525

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

530 535 540

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

545 550 555 560

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

565 570 575

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

580 585 590

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

595 600 605

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

610 615 620

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

625 630 635 640

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

645 650 655

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

660 665 670

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

675 680 685

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

690 695 700

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

705 710 715 720

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

725 730 735

Arg

<210> 142

<211> 2211

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 142

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actccgtact aaaagagaaa ttgtgatgac ccagtcaccc

840

gccactctta gcctttcacc cggtgagcgc gcaaccctgt cttgcagagc ctcccaagac

900

atctcaaaat accttaattg gtatcaacag aagcccggac aggctcctcg ccttctgatc

960

taccacacca gccggctcca ttctggaatc cctgccaggt tcagcggtag cggatctggg

1020

accgactaca ccctcactat cagctcactg cagccagagg acttcgctgt ctatttctgt

1080

cagcaaggga acaccctgcc ctacaccttt ggacagggca ccaagctcga gattaaaggt

1140

ggaggtggca gcggaggagg tgggtccggc ggtggaggaa gccaggtcca actccaagaa

1200

agcggaccgg gtcttgtgaa gccatcagaa actctttcac tgacttgtac tgtgagcgga

1260

gtgtctctcc ccgattacgg ggtgtcttgg atcagacagc caccggggaa gggtctggaa

1320

tggattggag tgatttgggg ctctgagact acttactact cttcatccct caagtcacgc

1380

gtcaccatct caaaggacaa ctctaagaat caggtgtcac tgaaactgtc atctgtgacc

1440

gcagccgaca ccgccgtgta ctattgcgct aagcattact attatggcgg gagctacgca

1500

atggattact ggggacaggg tactctggtc accgtgtcca gcaccactac cccagcaccg

1560

aggccaccca ccccggctcc taccatcgcc tcccagcctc tgtccctgcg tccgggaggca

1620

tgtagacccg cagctggtgg ggccgtgcat acccggggtc ttgacttcgc ctgcgatatc

1680

tacatttggg cccctctggc tggtacttgc ggggtcctgc tgctttcact cgtgatcact

1740

ctttactgta agcgcggtcg gaagaagctg ctgtacatct ttaagcaacc cttcatgagg

1800

cctgtgcaga ctactcaaga ggaggacggc tgttcatgcc ggttcccaga ggaggaggaa

1860

ggcggctgcg aactgcgcgt gaaattcagc cgcagcgcag atgctccagc ctacaagcag

1920

gggcagaacc agctctacaa cgaactcaat cttggtcgga gagaggagta cgacgtgctg

1980

gacaagcgga gaggacggga cccagaaatg ggcgggaagc cgcgcagaaa gaatccccaa

2040

gagggcctgt acaacgagct ccaaaaggat aagatggcag aagcctatag cgagattggt

2100

atgaaagggg aacgcagaag aggcaaaggc cacgacggac tgtaccaggg actcagcacc

2160

gccaccaagg acacctatga cgctcttcac atgcaggccc tgccgcctcg g

2211

<210> 143

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 143

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly

275 280 285

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

290 295 300

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

305 310 315 320

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

325 330 335

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

340 345 350

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

355 360 365

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

370 375 380

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

385 390 395 400

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

405 410 415

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

420 425 430

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

435 440 445

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

450 455 460

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

465 470 475 480

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

485 490 495

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

500 505 510

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

515 520 525

Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 144

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 144

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggtccc tcggagacgt gggtgaaatt gtgatgaccc agtcacccgc cactcttagc

900

ctttcacccg gtgagcgcgc aaccctgtct tgcagagcct cccaagacat ctcaaaatac

960

cttaattggt atcaacagaa gcccggacag gctcctcgcc ttctgatcta ccacaccagc

1020

cggctccatt ctggaatccc tgccaggttc agcggtagcg gatctgggac cgactacacc

1080

ctcactatca gctcactgca gccagaggac ttcgctgtct atttctgtca gcaagggaac

1140

accctgccct acacctttgg acagggcacc aagctcgaga ttaaaggtgg aggtggcagc

1200

ggaggaggtg ggtccggcgg tggaggaagc caggtccaac tccaagaaag cggaccgggt

1260

cttgtgaagc catcagaaac tctttcactg acttgtactg tgagcggagt gtctctcccc

1320

gattacgggg tgtcttggat cagacagcca ccggggaagg gtctggaatg gattggagtg

1380

atttggggct ctgagactac ttactactct tcatccctca agtcacgcgt caccatctca

1440

aaggacaact ctaagaatca ggtgtcactg aaactgtcat ctgtgaccgc agccgacacc

1500

gccgtgtact attgcgctaa gcattactat tatggcggga gctacgcaat ggattactgg

1560

ggacagggta ctctggtcac cgtgtccagc accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct acaagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 145

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 145

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly

275 280 285

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

290 295 300

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

305 310 315 320

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

325 330 335

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

340 345 350

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

355 360 365

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

370 375 380

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

385 390 395 400

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

405 410 415

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

420 425 430

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

435 440 445

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

450 455 460

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

465 470 475 480

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

485 490 495

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

500 505 510

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

515 520 525

Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 146

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 146

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggtccc tcggagacgt gggtgaaatt gtgatgaccc agtcacccgc cactcttagc

900

ctttcacccg gtgagcgcgc aaccctgtct tgcagagcct cccaagacat ctcaaaatac

960

cttaattggt atcaacagaa gcccggacag gctcctcgcc ttctgatcta ccacaccagc

1020

cggctccatt ctggaatccc tgccaggttc agcggtagcg gatctgggac cgactacacc

1080

ctcactatca gctcactgca gccagaggac ttcgctgtct atttctgtca gcaagggaac

1140

accctgccct acacctttgg acagggcacc aagctcgaga ttaaaggtgg aggtggcagc

1200

ggaggaggtg ggtccggcgg tggaggaagc caggtccaac tccaagaaag cggaccgggt

1260

cttgtgaagc catcagaaac tctttcactg acttgtactg tgagcggagt gtctctcccc

1320

gattacgggg tgtcttggat cagacagcca ccggggaagg gtctggaatg gattggagtg

1380

atttggggct ctgagactac ttactactct tcatccctca agtcacgcgt caccatctca

1440

aaggacaact ctaagaatca ggtgtcactg aaactgtcat ctgtgaccgc agccgacacc

1500

gccgtgtact attgcgctaa gcattactat tatggcggga gctacgcaat ggattactgg

1560

ggacagggta ctctggtcac cgtgtccagc accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 147

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 147

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln

275 280 285

Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

290 295 300

Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln

305 310 315 320

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu

325 330 335

His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

340 345 350

Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr

355 360 365

Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr

370 375 380

Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

405 410 415

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

420 425 430

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

435 440 445

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser

450 455 460

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

465 470 475 480

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

485 490 495

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

500 505 510

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 148

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 148

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcgggacg ggagctgaag atccacgacc cagcagaaag

840

cgacgggaaa ttgtgatgac ccagtcaccc gccactctta gcctttcacc cggtgagcgc

900

gcaaccctgt cttgcagagc ctcccaagac atctcaaaat accttaattg gtatcaacag

960

aagcccggac aggctcctcg ccttctgatc taccacacca gccggctcca ttctggaatc

1020

cctgccaggt tcagcggtag cggatctggg accgactaca ccctcactat cagctcactg

1080

cagccagagg acttcgctgt ctatttctgt cagcaaggga acaccctgcc ctacaccttt

1140

ggacagggca ccaagctcga gattaaaggt ggaggtggca gcggaggagg tgggtccggc

1200

ggtggaggaa gccaggtcca actccaagaa agcggaccgg gtcttgtgaa gccatcagaa

1260

actctttcac tgacttgtac tgtgagcgga gtgtctctcc ccgattacgg ggtgtcttgg

1320

atcagacagc caccggggaa gggtctggaa tggattggag tgatttgggg ctctgagact

1380

acttactact cttcatccct caagtcacgc gtcaccatct caaaggacaa ctctaagaat

1440

caggtgtcac tgaaactgtc atctgtgacc gcagccgaca ccgccgtgta ctattgcgct

1500

aagcattact attatggcgg gagctacgca atggattact ggggacaggg tactctggtc

1560

accgtgtcca gcaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 149

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 149

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln

275 280 285

Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

290 295 300

Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln

305 310 315 320

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu

325 330 335

His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

340 345 350

Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr

355 360 365

Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr

370 375 380

Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

405 410 415

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

420 425 430

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

435 440 445

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser

450 455 460

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

465 470 475 480

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

485 490 495

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

500 505 510

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 150

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 150

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcgggacg ggagctgaag atccacgacc cagcagaaag

840

cgacgggaaa ttgtgatgac ccagtcaccc gccactctta gcctttcacc cggtgagcgc

900

gcaaccctgt cttgcagagc ctcccaagac atctcaaaat accttaattg gtatcaacag

960

aagcccggac aggctcctcg ccttctgatc taccacacca gccggctcca ttctggaatc

1020

cctgccaggt tcagcggtag cggatctggg accgactaca ccctcactat cagctcactg

1080

cagccagagg acttcgctgt ctatttctgt cagcaaggga acaccctgcc ctacaccttt

1140

ggacagggca ccaagctcga gattaaaggt ggaggtggca gcggaggagg tgggtccggc

1200

ggtggaggaa gccaggtcca actccaagaa agcggaccgg gtcttgtgaa gccatcagaa

1260

actctttcac tgacttgtac tgtgagcgga gtgtctctcc ccgattacgg ggtgtcttgg

1320

atcagacagc caccggggaa gggtctggaa tggattggag tgatttgggg ctctgagact

1380

acttactact cttcatccct caagtcacgc gtcaccatct caaaggacaa ctctaagaat

1440

caggtgtcac tgaaactgtc atctgtgacc gcagccgaca ccgccgtgta ctattgcgct

1500

aagcattact attatggcgg gagctacgca atggattact ggggacaggg tactctggtc

1560

accgtgtcca gcaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 151

<211> 737

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 151

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Arg Thr Lys Arg

260 265 270

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

275 280 285

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

290 295 300

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

305 310 315 320

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

325 330 335

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

340 345 350

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

355 360 365

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

370 375 380

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

385 390 395 400

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

405 410 415

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

420 425 430

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

435 440 445

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

450 455 460

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

465 470 475 480

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

485 490 495

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

500 505 510

Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

515 520 525

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

530 535 540

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

545 550 555 560

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

565 570 575

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

580 585 590

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

595 600 605

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

610 615 620

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

625 630 635 640

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

645 650 655

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

660 665 670

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

675 680 685

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

690 695 700

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

705 710 715 720

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

725 730 735

Arg

<210> 152

<211> 2211

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 152

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actccgtact aaaagagaaa ttgtgatgac ccagtcaccc

840

gccactctta gcctttcacc cggtgagcgc gcaaccctgt cttgcagagc ctcccaagac

900

atctcaaaat accttaattg gtatcaacag aagcccggac aggctcctcg ccttctgatc

960

taccacacca gccggctcca ttctggaatc cctgccaggt tcagcggtag cggatctggg

1020

accgactaca ccctcactat cagctcactg cagccagagg acttcgctgt ctatttctgt

1080

cagcaaggga acaccctgcc ctacaccttt ggacagggca ccaagctcga gattaaaggt

1140

ggaggtggca gcggaggagg tgggtccggc ggtggaggaa gccaggtcca actccaagaa

1200

agcggaccgg gtcttgtgaa gccatcagaa actctttcac tgacttgtac tgtgagcgga

1260

gtgtctctcc ccgattacgg ggtgtcttgg atcagacagc caccggggaa gggtctggaa

1320

tggattggag tgatttgggg ctctgagact acttactact cttcatccct caagtcacgc

1380

gtcaccatct caaaggacaa ctctaagaat caggtgtcac tgaaactgtc atctgtgacc

1440

gcagccgaca ccgccgtgta ctattgcgct aagcattact attatggcgg gagctacgca

1500

atggattact ggggacaggg tactctggtc accgtgtcca gcaccactac cccagcaccg

1560

aggccaccca ccccggctcc taccatcgcc tcccagcctc tgtccctgcg tccgggaggca

1620

tgtagacccg cagctggtgg ggccgtgcat acccggggtc ttgacttcgc ctgcgatatc

1680

tacatttggg cccctctggc tggtacttgc ggggtcctgc tgctttcact cgtgatcact

1740

ctttactgta agcgcggtcg gaagaagctg ctgtacatct ttaagcaacc cttcatgagg

1800

cctgtgcaga ctactcaaga ggaggacggc tgttcatgcc ggttcccaga ggaggaggaa

1860

ggcggctgcg aactgcgcgt gaaattcagc cgcagcgcag atgctccagc ctacaagcag

1920

gggcagaacc agctctacaa cgaactcaat cttggtcgga gagaggagta cgacgtgctg

1980

gacaagcgga gaggacggga cccagaaatg ggcgggaagc cgcgcagaaa gaatccccaa

2040

gagggcctgt acaacgagct ccaaaaggat aagatggcag aagcctatag cgagattggt

2100

atgaaagggg aacgcagaag aggcaaaggc cacgacggac tgtaccaggg actcagcacc

2160

gccaccaagg acacctatga cgctcttcac atgcaggccc tgccgcctcg g

2211

<210> 153

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 153

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly

275 280 285

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

290 295 300

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

305 310 315 320

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

325 330 335

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

340 345 350

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

355 360 365

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

370 375 380

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

385 390 395 400

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

405 410 415

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

420 425 430

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

435 440 445

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

450 455 460

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

465 470 475 480

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

485 490 495

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

500 505 510

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

515 520 525

Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 154

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 154

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggtccc tcggagacgt gggtgaaatt gtgatgaccc agtcacccgc cactcttagc

900

ctttcacccg gtgagcgcgc aaccctgtct tgcagagcct cccaagacat ctcaaaatac

960

cttaattggt atcaacagaa gcccggacag gctcctcgcc ttctgatcta ccacaccagc

1020

cggctccatt ctggaatccc tgccaggttc agcggtagcg gatctgggac cgactacacc

1080

ctcactatca gctcactgca gccagaggac ttcgctgtct atttctgtca gcaagggaac

1140

accctgccct acacctttgg acagggcacc aagctcgaga ttaaaggtgg aggtggcagc

1200

ggaggaggtg ggtccggcgg tggaggaagc caggtccaac tccaagaaag cggaccgggt

1260

cttgtgaagc catcagaaac tctttcactg acttgtactg tgagcggagt gtctctcccc

1320

gattacgggg tgtcttggat cagacagcca ccggggaagg gtctggaatg gattggagtg

1380

atttggggct ctgagactac ttactactct tcatccctca agtcacgcgt caccatctca

1440

aaggacaact ctaagaatca ggtgtcactg aaactgtcat ctgtgaccgc agccgacacc

1500

gccgtgtact attgcgctaa gcattactat tatggcggga gctacgcaat ggattactgg

1560

ggacagggta ctctggtcac cgtgtccagc accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct acaagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 155

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 155

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly

275 280 285

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

290 295 300

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

305 310 315 320

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

325 330 335

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

340 345 350

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

355 360 365

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

370 375 380

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

385 390 395 400

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

405 410 415

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

420 425 430

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

435 440 445

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

450 455 460

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

465 470 475 480

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

485 490 495

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

500 505 510

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

515 520 525

Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 156

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 156

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggtccc tcggagacgt gggtgaaatt gtgatgaccc agtcacccgc cactcttagc

900

ctttcacccg gtgagcgcgc aaccctgtct tgcagagcct cccaagacat ctcaaaatac

960

cttaattggt atcaacagaa gcccggacag gctcctcgcc ttctgatcta ccacaccagc

1020

cggctccatt ctggaatccc tgccaggttc agcggtagcg gatctgggac cgactacacc

1080

ctcactatca gctcactgca gccagaggac ttcgctgtct atttctgtca gcaagggaac

1140

accctgccct acacctttgg acagggcacc aagctcgaga ttaaaggtgg aggtggcagc

1200

ggaggaggtg ggtccggcgg tggaggaagc caggtccaac tccaagaaag cggaccgggt

1260

cttgtgaagc catcagaaac tctttcactg acttgtactg tgagcggagt gtctctcccc

1320

gattacgggg tgtcttggat cagacagcca ccggggaagg gtctggaatg gattggagtg

1380

atttggggct ctgagactac ttactactct tcatccctca agtcacgcgt caccatctca

1440

aaggacaact ctaagaatca ggtgtcactg aaactgtcat ctgtgaccgc agccgacacc

1500

gccgtgtact attgcgctaa gcattactat tatggcggga gctacgcaat ggattactgg

1560

ggacagggta ctctggtcac cgtgtccagc accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 157

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 157

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln

275 280 285

Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

290 295 300

Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln

305 310 315 320

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu

325 330 335

His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

340 345 350

Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr

355 360 365

Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr

370 375 380

Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

405 410 415

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

420 425 430

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

435 440 445

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser

450 455 460

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

465 470 475 480

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

485 490 495

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

500 505 510

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 158

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 158

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcgggacg ggagctgaag atccacgacc cagcagaaag

840

cgacgggaaa ttgtgatgac ccagtcaccc gccactctta gcctttcacc cggtgagcgc

900

gcaaccctgt cttgcagagc ctcccaagac atctcaaaat accttaattg gtatcaacag

960

aagcccggac aggctcctcg ccttctgatc taccacacca gccggctcca ttctggaatc

1020

cctgccaggt tcagcggtag cggatctggg accgactaca ccctcactat cagctcactg

1080

cagccagagg acttcgctgt ctatttctgt cagcaaggga acaccctgcc ctacaccttt

1140

ggacagggca ccaagctcga gattaaaggt ggaggtggca gcggaggagg tgggtccggc

1200

ggtggaggaa gccaggtcca actccaagaa agcggaccgg gtcttgtgaa gccatcagaa

1260

actctttcac tgacttgtac tgtgagcgga gtgtctctcc ccgattacgg ggtgtcttgg

1320

atcagacagc caccggggaa gggtctggaa tggattggag tgatttgggg ctctgagact

1380

acttactact cttcatccct caagtcacgc gtcaccatct caaaggacaa ctctaagaat

1440

caggtgtcac tgaaactgtc atctgtgacc gcagccgaca ccgccgtgta ctattgcgct

1500

aagcattact attatggcgg gagctacgca atggattact ggggacaggg tactctggtc

1560

accgtgtcca gcaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 159

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 159

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln

275 280 285

Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

290 295 300

Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln

305 310 315 320

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu

325 330 335

His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

340 345 350

Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr

355 360 365

Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr

370 375 380

Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

405 410 415

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

420 425 430

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

435 440 445

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser

450 455 460

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

465 470 475 480

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

485 490 495

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

500 505 510

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 160

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 160

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcgggacg ggagctgaag atccacgacc cagcagaaag

840

cgacgggaaa ttgtgatgac ccagtcaccc gccactctta gcctttcacc cggtgagcgc

900

gcaaccctgt cttgcagagc ctcccaagac atctcaaaat accttaattg gtatcaacag

960

aagcccggac aggctcctcg ccttctgatc taccacacca gccggctcca ttctggaatc

1020

cctgccaggt tcagcggtag cggatctggg accgactaca ccctcactat cagctcactg

1080

cagccagagg acttcgctgt ctatttctgt cagcaaggga acaccctgcc ctacaccttt

1140

ggacagggca ccaagctcga gattaaaggt ggaggtggca gcggaggagg tgggtccggc

1200

ggtggaggaa gccaggtcca actccaagaa agcggaccgg gtcttgtgaa gccatcagaa

1260

actctttcac tgacttgtac tgtgagcgga gtgtctctcc ccgattacgg ggtgtcttgg

1320

atcagacagc caccggggaa gggtctggaa tggattggag tgatttgggg ctctgagact

1380

acttactact cttcatccct caagtcacgc gtcaccatct caaaggacaa ctctaagaat

1440

caggtgtcac tgaaactgtc atctgtgacc gcagccgaca ccgccgtgta ctattgcgct

1500

aagcattact attatggcgg gagctacgca atggattact ggggacaggg tactctggtc

1560

accgtgtcca gcaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 161

<211> 738

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 161

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Arg Thr Lys Arg

260 265 270

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

275 280 285

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

290 295 300

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

305 310 315 320

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

325 330 335

Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr

340 345 350

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

355 360 365

Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly

370 375 380

Gly Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro

405 410 415

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

420 425 430

Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

435 440 445

Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser

450 455 460

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

465 470 475 480

Leu Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

485 490 495

Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu

500 505 510

Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro

515 520 525

Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro

530 535 540

Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp

545 550 555 560

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu

565 570 575

Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu

580 585 590

Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu

595 600 605

Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys

610 615 620

Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln

625 630 635 640

Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu

645 650 655

Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly

660 665 670

Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu

675 680 685

Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly

690 695 700

Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser

705 710 715 720

Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro

725 730 735

Pro Arg

<210> 162

<211> 2214

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 162

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actccgtact aaaagacaag tgcaactcgt ccaaagcgga

840

gcggaagtca agaaacccgg agcgagcgtg aaagtgtcct gcaaagcctc cggctacacc

900

tttacgggct actacatgca ctgggtgcgc caggcaccag gacaggggtct tgaatggatg

960

ggatggatca accctaattc gggcggaact aactacgcac agaagttcca ggggagagtg

1020

actctgactc gggatacctc catctcaact gtctacatgg aactctcccg cttgcggtca

1080

gatgatacgg cagtgtacta ctgcgcccgc gacatgaata tcctggctac cgtgccgttc

1140

gacatctggg gacaggggac tatggttact gtctcatcgg gcggtggagg ttcaggagga

1200

ggcggctcgg gaggcgggagg ttcggacatt cagatgaccc agtccccatc ctctctgtcg

1260

gccagcgtcg gagatagggt gaccattacc tgtcgggcct cgcaaagcat ctcctcgtac

1320

ctcaactggt atcagcaaaa gccgggaaag gcgcctaagc tgctgatcta cgccgcttcg

1380

agcttgcaaa gcggggtgcc atccagattc tcgggatcag gctcaggaac cgacttcacc

1440

ctgaccgtga acagcctcca gccgggaggac tttgccactt actactgcca gcagggagac

1500

tccgtgccgc ttactttcgg ggggggtacc cgcctggaga tcaagaccac taccccagca

1560

ccgaggccac ccaccccggc tcctaccatc gcctcccagc ctctgtccct gcgtccggag

1620

gcatgtagac ccgcagctgg tggggccgtg catacccggg gtcttgactt cgcctgcgat

1680

atctacattt gggcccctct ggctggtact tgcggggtcc tgctgctttc actcgtgatc

1740

actctttact gtaagcgcgg tcggaagaag ctgctgtaca tctttaagca acccttcatg

1800

aggcctgtgc agactactca aggagaggac ggctgttcat gccggttccc aggagaggag

1860

gaaggcggct gcgaactgcg cgtgaaattc agccgcagcg cagatgctcc agcctaccag

1920

caggggcaga accagctcta caacgaactc aatcttggtc ggagagagga gtacgacgtg

1980

ctggacaagc ggagaggacg ggacccagaa atgggcggga agccgcgcag aaagaatccc

2040

caagagggcc tgtacaacga gctccaaaag gataagatgg cagaagccta tagcgagatt

2100

ggtatgaaag gggaacgcag aagaggcaaa ggccacgacg gactgtacca gggactcagc

2160

accgccacca aggacaccta tgacgctctt cacatgcagg ccctgccgcc tcgg

2214

<210> 163

<211> 754

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 163

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly

275 280 285

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

290 295 300

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

305 310 315 320

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

325 330 335

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

340 345 350

Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr

355 360 365

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

370 375 380

Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly

385 390 395 400

Gly Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

405 410 415

Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro

420 425 430

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

435 440 445

Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

450 455 460

Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser

465 470 475 480

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

485 490 495

Leu Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

500 505 510

Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu

515 520 525

Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro

530 535 540

Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro

545 550 555 560

Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp

565 570 575

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu

580 585 590

Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu

595 600 605

Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu

610 615 620

Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys

625 630 635 640

Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln

645 650 655

Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu

660 665 670

Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly

675 680 685

Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu

690 695 700

Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly

705 710 715 720

Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser

725 730 735

Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro

740 745 750

Pro Arg

<210> 164

<211> 2262

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 164

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggtccc tcggagacgt gggtcaagtg caactcgtcc aaagcggagc ggaagtcaag

900

aaacccggag cgagcgtgaa agtgtcctgc aaagcctccg gctacacctt tacgggctac

960

tacatgcact gggtgcgcca ggcaccagga cagggtcttg aatggatggg atggatcaac

1020

cctaattcgg gcggaactaa ctacgcacag aagttccagg ggagagtgac tctgactcgg

1080

gatacctcca tctcaactgt ctacatggaa ctctcccgct tgcggtcaga tgatacggca

1140

gtgtactact gcgcccgcga catgaatatc ctggctaccg tgccgttcga catctgggga

1200

caggggacta tggttactgt ctcatcgggc ggtggaggtt caggaggagg cggctcggga

1260

ggcgggaggtt cggacattca gatgacccag tccccatcct ctctgtcggc cagcgtcgga

1320

gatagggtga ccattacctg tcgggcctcg caaagcatct cctcgtacct caactggtat

1380

cagcaaaagc cgggaaaggc gcctaagctg ctgatctacg ccgcttcgag cttgcaaagc

1440

ggggtgccat ccagattctc gggatcaggc tcaggaaccg acttcaccct gaccgtgaac

1500

agcctccagc cggaggactt tgccacttac tactgccagc agggagactc cgtgccgctt

1560

actttcgggg ggggtacccg cctggagatc aagaccacta ccccagcacc gaggccaccc

1620

accccggctc ctaccatcgc ctcccagcct ctgtccctgc gtccgggaggc atgtagaccc

1680

gcagctggtg gggccgtgca tacccggggt cttgacttcg cctgcgatat ctacatttgg

1740

gcccctctgg ctggtacttg cggggtcctg ctgctttcac tcgtgatcac tctttactgt

1800

aagcgcggtc ggaagaagct gctgtacatc tttaagcaac ccttcatgag gcctgtgcag

1860

actactcaag aggaggacgg ctgttcatgc cggttcccag aggaggagga aggcggctgc

1920

gaactgcgcg tgaaattcag ccgcagcgca gatgctccag cctaccagca ggggcagaac

1980

cagctctaca acgaactcaa tcttggtcgg agagaggagt acgacgtgct ggacaagcgg

2040

agaggacgggg acccagaaat gggcgggaag ccgcgcagaa agaatcccca agaggggcctg

2100

tacaacgagc tccaaaagga taagatggca gaagcctata gcgagattgg tatgaaaggg

2160

gaacgcagaa gaggcaaagg ccacgacgga ctgtaccagg gactcagcac cgccaccaag

2220

gacacctatg acgctcttca catgcaggcc ctgccgcctc gg

2262

<210> 165

<211> 748

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 165

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln

275 280 285

Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys

290 295 300

Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg

305 310 315 320

Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn

325 330 335

Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu

340 345 350

Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu

355 360 365

Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile

370 375 380

Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr

385 390 395 400

Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser

420 425 430

Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser

435 440 445

Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu

450 455 460

Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe

465 470 475 480

Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu

485 490 495

Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val

500 505 510

Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr

515 520 525

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

530 535 540

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

545 550 555 560

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

565 570 575

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

580 585 590

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

595 600 605

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

610 615 620

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

625 630 635 640

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu

645 650 655

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

660 665 670

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

675 680 685

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

690 695 700

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

705 710 715 720

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

725 730 735

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 166

<211> 2244

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 166

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggcaag tgcaactcgt ccaaagcgga gcggaagtca agaaacccgg agcgagcgtg

900

aaagtgtcct gcaaagcctc cggctacacc tttacgggct actacatgca ctgggtgcgc

960

caggcaccag gacagggtct tgaatggatg ggatggatca accctaattc gggcggaact

1020

aactacgcac agaagttcca ggggagagtg actctgactc gggatacctc catctcaact

1080

gtctacatgg aactctcccg cttgcggtca gatgatacgg cagtgtacta ctgcgcccgc

1140

gacatgaata tcctggctac cgtgccgttc gacatctggg gacaggggac tatggttact

1200

gtctcatcgg gcggtggagg ttcaggagga ggcggctcgg gaggcggagg ttcggacatt

1260

cagatgaccc agtccccatc ctctctgtcg gccagcgtcg gagatagggt gaccattacc

1320

tgtcgggcct cgcaaagcat ctcctcgtac ctcaactggt atcagcaaaa gccgggaaag

1380

gcgcctaagc tgctgatcta cgccgcttcg agcttgcaaa gcggggtgcc atccagattc

1440

tcgggatcag gctcaggaac cgacttcacc ctgaccgtga acagcctcca gccggaggac

1500

tttgccactt actactgcca gcagggagac tccgtgccgc ttactttcgg ggggggtacc

1560

cgcctggaga tcaagaccac taccccagca ccgaggccac ccaccccggc tcctaccatc

1620

gcctcccagc ctctgtccct gcgtccggag gcatgtagac ccgcagctgg tggggccgtg

1680

catacccggg gtcttgactt cgcctgcgat atctacattt gggcccctct ggctggtact

1740

tgcggggtcc tgctgctttc actcgtgatc actctttact gtaagcgcgg tcggaagaag

1800

ctgctgtaca tctttaagca acccttcatg aggcctgtgc agactactca agaggaggac

1860

ggctgttcat gccggttccc agaggaggag gaaggcggct gcgaactgcg cgtgaaattc

1920

agccgcagcg cagatgctcc agcctaccag caggggcaga accagctcta caacgaactc

1980

aatcttggtc ggagaggagga gtacgacgtg ctggacaagc ggagaggacg ggacccagaa

2040

atgggcggga agccgcgcag aaagaatccc caagaggggcc tgtacaacga gctccaaaag

2100

gataagatgg cagaagccta tagcgagatt ggtatgaaag gggaacgcag aagaggcaaa

2160

ggccacgacg gactgtacca gggactcagc accgccacca aggacaccta tgacgctctt

2220

cacatgcagg ccctgccgcc tcgg

2244

<210> 167

<211> 738

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 167

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Arg Thr Lys Arg

260 265 270

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

275 280 285

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

290 295 300

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

305 310 315 320

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

325 330 335

Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr

340 345 350

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

355 360 365

Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly

370 375 380

Gly Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro

405 410 415

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

420 425 430

Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

435 440 445

Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser

450 455 460

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

465 470 475 480

Leu Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

485 490 495

Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu

500 505 510

Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro

515 520 525

Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro

530 535 540

Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp

545 550 555 560

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu

565 570 575

Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu

580 585 590

Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu

595 600 605

Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys

610 615 620

Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln

625 630 635 640

Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu

645 650 655

Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly

660 665 670

Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu

675 680 685

Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly

690 695 700

Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser

705 710 715 720

Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro

725 730 735

Pro Arg

<210> 168

<211> 2214

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 168

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actccgtact aaaagacaag tgcaactcgt ccaaagcgga

840

gcggaagtca agaaacccgg agcgagcgtg aaagtgtcct gcaaagcctc cggctacacc

900

tttacgggct actacatgca ctgggtgcgc caggcaccag gacaggggtct tgaatggatg

960

ggatggatca accctaattc gggcggaact aactacgcac agaagttcca ggggagagtg

1020

actctgactc gggatacctc catctcaact gtctacatgg aactctcccg cttgcggtca

1080

gatgatacgg cagtgtacta ctgcgcccgc gacatgaata tcctggctac cgtgccgttc

1140

gacatctggg gacaggggac tatggttact gtctcatcgg gcggtggagg ttcaggagga

1200

ggcggctcgg gaggcgggagg ttcggacatt cagatgaccc agtccccatc ctctctgtcg

1260

gccagcgtcg gagatagggt gaccattacc tgtcgggcct cgcaaagcat ctcctcgtac

1320

ctcaactggt atcagcaaaa gccgggaaag gcgcctaagc tgctgatcta cgccgcttcg

1380

agcttgcaaa gcggggtgcc atccagattc tcgggatcag gctcaggaac cgacttcacc

1440

ctgaccgtga acagcctcca gccgggaggac tttgccactt actactgcca gcagggagac

1500

tccgtgccgc ttactttcgg ggggggtacc cgcctggaga tcaagaccac taccccagca

1560

ccgaggccac ccaccccggc tcctaccatc gcctcccagc ctctgtccct gcgtccggag

1620

gcatgtagac ccgcagctgg tggggccgtg catacccggg gtcttgactt cgcctgcgat

1680

atctacattt gggcccctct ggctggtact tgcggggtcc tgctgctttc actcgtgatc

1740

actctttact gtaagcgcgg tcggaagaag ctgctgtaca tctttaagca acccttcatg

1800

aggcctgtgc agactactca aggagaggac ggctgttcat gccggttccc aggagaggag

1860

gaaggcggct gcgaactgcg cgtgaaattc agccgcagcg cagatgctcc agcctaccag

1920

caggggcaga accagctcta caacgaactc aatcttggtc ggagagagga gtacgacgtg

1980

ctggacaagc ggagaggacg ggacccagaa atgggcggga agccgcgcag aaagaatccc

2040

caagagggcc tgtacaacga gctccaaaag gataagatgg cagaagccta tagcgagatt

2100

ggtatgaaag gggaacgcag aagaggcaaa ggccacgacg gactgtacca gggactcagc

2160

accgccacca aggacaccta tgacgctctt cacatgcagg ccctgccgcc tcgg

2214

<210> 169

<211> 754

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 169

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly

275 280 285

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

290 295 300

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

305 310 315 320

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

325 330 335

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

340 345 350

Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr

355 360 365

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

370 375 380

Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly

385 390 395 400

Gly Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

405 410 415

Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro

420 425 430

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

435 440 445

Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

450 455 460

Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser

465 470 475 480

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

485 490 495

Leu Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

500 505 510

Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu

515 520 525

Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro

530 535 540

Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro

545 550 555 560

Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp

565 570 575

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu

580 585 590

Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu

595 600 605

Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu

610 615 620

Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys

625 630 635 640

Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln

645 650 655

Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu

660 665 670

Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly

675 680 685

Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu

690 695 700

Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly

705 710 715 720

Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser

725 730 735

Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro

740 745 750

Pro Arg

<210> 170

<211> 2262

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 170

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggtccc tcggagacgt gggtcaagtg caactcgtcc aaagcggagc ggaagtcaag

900

aaacccggag cgagcgtgaa agtgtcctgc aaagcctccg gctacacctt tacgggctac

960

tacatgcact gggtgcgcca ggcaccagga cagggtcttg aatggatggg atggatcaac

1020

cctaattcgg gcggaactaa ctacgcacag aagttccagg ggagagtgac tctgactcgg

1080

gatacctcca tctcaactgt ctacatggaa ctctcccgct tgcggtcaga tgatacggca

1140

gtgtactact gcgcccgcga catgaatatc ctggctaccg tgccgttcga catctgggga

1200

caggggacta tggttactgt ctcatcgggc ggtggaggtt caggaggagg cggctcggga

1260

ggcgggaggtt cggacattca gatgacccag tccccatcct ctctgtcggc cagcgtcgga

1320

gatagggtga ccattacctg tcgggcctcg caaagcatct cctcgtacct caactggtat

1380

cagcaaaagc cgggaaaggc gcctaagctg ctgatctacg ccgcttcgag cttgcaaagc

1440

ggggtgccat ccagattctc gggatcaggc tcaggaaccg acttcaccct gaccgtgaac

1500

agcctccagc cggaggactt tgccacttac tactgccagc agggagactc cgtgccgctt

1560

actttcgggg ggggtacccg cctggagatc aagaccacta ccccagcacc gaggccaccc

1620

accccggctc ctaccatcgc ctcccagcct ctgtccctgc gtccgggaggc atgtagaccc

1680

gcagctggtg gggccgtgca tacccggggt cttgacttcg cctgcgatat ctacatttgg

1740

gcccctctgg ctggtacttg cggggtcctg ctgctttcac tcgtgatcac tctttactgt

1800

aagcgcggtc ggaagaagct gctgtacatc tttaagcaac ccttcatgag gcctgtgcag

1860

actactcaag aggaggacgg ctgttcatgc cggttcccag aggaggagga aggcggctgc

1920

gaactgcgcg tgaaattcag ccgcagcgca gatgctccag cctaccagca ggggcagaac

1980

cagctctaca acgaactcaa tcttggtcgg agagaggagt acgacgtgct ggacaagcgg

2040

agaggacgggg acccagaaat gggcgggaag ccgcgcagaa agaatcccca agaggggcctg

2100

tacaacgagc tccaaaagga taagatggca gaagcctata gcgagattgg tatgaaaggg

2160

gaacgcagaa gaggcaaagg ccacgacgga ctgtaccagg gactcagcac cgccaccaag

2220

gacacctatg acgctcttca catgcaggcc ctgccgcctc gg

2262

<210> 171

<211> 748

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 171

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln

275 280 285

Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys

290 295 300

Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg

305 310 315 320

Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn

325 330 335

Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu

340 345 350

Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu

355 360 365

Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile

370 375 380

Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr

385 390 395 400

Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser

420 425 430

Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser

435 440 445

Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu

450 455 460

Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe

465 470 475 480

Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu

485 490 495

Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val

500 505 510

Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr

515 520 525

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

530 535 540

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

545 550 555 560

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

565 570 575

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

580 585 590

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

595 600 605

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

610 615 620

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

625 630 635 640

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu

645 650 655

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

660 665 670

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

675 680 685

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

690 695 700

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

705 710 715 720

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

725 730 735

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 172

<211> 2244

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 172

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcgggacg ggagctgaag atccacgacc cagcagaaag

840

cgacggcaag tgcaactcgt ccaaagcgga gcggaagtca agaaacccgg agcgagcgtg

900

aaagtgtcct gcaaagcctc cggctacacc tttacgggct actacatgca ctgggtgcgc

960

caggcaccag gacagggtct tgaatggatg ggatggatca accctaattc gggcggaact

1020

aactacgcac agaagttcca ggggagagtg actctgactc gggatacctc catctcaact

1080

gtctacatgg aactctcccg cttgcggtca gatgatacgg cagtgtacta ctgcgcccgc

1140

gacatgaata tcctggctac cgtgccgttc gacatctggg gacaggggac tatggttact

1200

gtctcatcgg gcggtggagg ttcaggagga ggcggctcgg gaggcggagg ttcggacatt

1260

cagatgaccc agtccccatc ctctctgtcg gccagcgtcg gagatagggt gaccattacc

1320

tgtcgggcct cgcaaagcat ctcctcgtac ctcaactggt atcagcaaaa gccgggaaag

1380

gcgcctaagc tgctgatcta cgccgcttcg agcttgcaaa gcggggtgcc atccagattc

1440

tcgggatcag gctcaggaac cgacttcacc ctgaccgtga acagcctcca gccggaggac

1500

tttgccactt actactgcca gcagggagac tccgtgccgc ttactttcgg ggggggtacc

1560

cgcctggaga tcaagaccac taccccagca ccgaggccac ccaccccggc tcctaccatc

1620

gcctcccagc ctctgtccct gcgtccggag gcatgtagac ccgcagctgg tggggccgtg

1680

catacccggg gtcttgactt cgcctgcgat atctacattt gggcccctct ggctggtact

1740

tgcggggtcc tgctgctttc actcgtgatc actctttact gtaagcgcgg tcggaagaag

1800

ctgctgtaca tctttaagca acccttcatg aggcctgtgc agactactca agaggaggac

1860

ggctgttcat gccggttccc agaggaggag gaaggcggct gcgaactgcg cgtgaaattc

1920

agccgcagcg cagatgctcc agcctaccag caggggcaga accagctcta caacgaactc

1980

aatcttggtc ggagaggagga gtacgacgtg ctggacaagc ggagaggacg ggacccagaa

2040

atgggcggga agccgcgcag aaagaatccc caagaggggcc tgtacaacga gctccaaaag

2100

gataagatgg cagaagccta tagcgagatt ggtatgaaag gggaacgcag aagaggcaaa

2160

ggccacgacg gactgtacca gggactcagc accgccacca aggacaccta tgacgctctt

2220

cacatgcagg ccctgccgcc tcgg

2244

<210> 173

<211> 734

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 173

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Arg Thr Lys Arg

260 265 270

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

275 280 285

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

290 295 300

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

305 310 315 320

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

325 330 335

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

340 345 350

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

355 360 365

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

370 375 380

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

385 390 395 400

Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser

405 410 415

Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser

420 425 430

Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

435 440 445

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

450 455 460

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

465 470 475 480

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr

485 490 495

Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr

500 505 510

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

515 520 525

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

530 535 540

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

545 550 555 560

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

565 570 575

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

580 585 590

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

595 600 605

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

610 615 620

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn

625 630 635 640

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

645 650 655

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

660 665 670

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

675 680 685

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

690 695 700

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

705 710 715 720

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

725 730

<210> 174

<211> 2202

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 174

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actccgtact aaaagagaag tgcaattggt ggaatcaggg

840

ggaggacttg tgcagcctgg aggatcgctg agactgtcat gtgccgtgtc cggctttgcc

900

ctgtccaacc acgggatgtc ctgggtccgc cgcgcgcctg gaaagggcct cgaatgggtg

960

tcgggtattg tgtacagcgg tagcacctac tatgccgcat ccgtgaaggg gagattcacc

1020

atcagccggg acaactccag gaacactctg tacctccaaa tgaattcgct gaggccagag

1080

gacactgcca tctactactg ctccgcgcat ggcggagagt ccgacgtctg gggacagggg

1140

acccgtga ccgtgtctag cgcgtccggc ggaggcggca gcgggggtcg ggcatcaggg

1200

ggcggcggat cggacatcca gctcacccag tccccgagct cgctgtccgc ctccgtggga

1260

gatcgggtca ccatcacgtg ccgcgccagc cagtcgattt cctcctacct gaactggtac

1320

caacagaagc ccggaaaagc cccgaagctt ctcatctacg ccgcctcgag cctgcagtca

1380

ggagtgccct cacggttctc cggctccggt tccggtactg atttcaccct gaccattttcc

1440

tccctgcaac cggaggactt cgctacttac tactgccagc agtcgtactc caccccctac

1500

actttcggac aaggcaccaa ggtcgaaatc aagacacta ccccagcacc gaggccaccc

1560

accccggctc ctaccatcgc ctcccagcct ctgtccctgc gtccgggaggc atgtagaccc

1620

gcagctggtg gggccgtgca tacccggggt cttgacttcg cctgcgatat ctacatttgg

1680

gcccctctgg ctggtacttg cggggtcctg ctgctttcac tcgtgatcac tctttactgt

1740

aagcgcggtc ggaagaagct gctgtacatc tttaagcaac ccttcatgag gcctgtgcag

1800

actactcaag aggaggacgg ctgttcatgc cggttcccag aggaggagga aggcggctgc

1860

gaactgcgcg tgaaattcag ccgcagcgca gatgctccag cctaccagca ggggcagaac

1920

cagctctaca acgaactcaa tcttggtcgg agagaggagt acgacgtgct ggacaagcgg

1980

agaggacgggg acccagaaat gggcgggaag ccgcgcagaa agaatcccca agaggggcctg

2040

tacaacgagc tccaaaagga taagatggca gaagcctata gcgagattgg tatgaaaggg

2100

gaacgcagaa gaggcaaagg ccacgacgga ctgtaccagg gactcagcac cgccaccaag

2160

gacacctatg acgctcttca catgcaggcc ctgccgcctc gg

2202

<210> 175

<211> 750

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 175

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly

275 280 285

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

290 295 300

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

305 310 315 320

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

325 330 335

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

340 345 350

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

355 360 365

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

370 375 380

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

385 390 395 400

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

405 410 415

Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser

420 425 430

Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser

435 440 445

Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

450 455 460

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

465 470 475 480

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

485 490 495

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr

500 505 510

Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr

515 520 525

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

530 535 540

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

545 550 555 560

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

565 570 575

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

580 585 590

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

595 600 605

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

610 615 620

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

625 630 635 640

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn

645 650 655

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

660 665 670

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

675 680 685

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

690 695 700

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

705 710 715 720

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

725 730 735

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 176

<211> 2250

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 176

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggtccc tcggagacgt gggtgaagtg caattggtgg aatcaggggg aggacttgtg

900

cagcctggag gatcgctgag actgtcatgt gccgtgtccg gctttgccct gtccaaccac

960

gggatgtcct gggtccgccg cgcgcctgga aagggcctcg aatgggtgtc gggtattgtg

1020

tacagcggta gcacctacta tgccgcatcc gtgaagggga gattcaccat cagccgggac

1080

aactccagga acactctgta cctccaaatg aattcgctga ggccagagga cactgccatc

1140

tactactgct ccgcgcatgg cggagagtcc gacgtctgggg gacaggggac caccgtgacc

1200

gtgtctagcg cgtccggcgg aggcggcagc gggggtcggg catcaggggg cggcggatcg

1260

gacatccagc tcacccagtc cccgagctcg ctgtccgcct ccgtgggaga tcgggtcacc

1320

atcacgtgcc gcgccagcca gtcgatttcc tcctacctga actggtacca acagaagccc

1380

ggaaaagccc cgaagcttct catctacgcc gcctcgagcc tgcagtcagg agtgccctca

1440

cggttctccg gctccggttc cggtactgat ttcaccctga ccatttcctc cctgcaaccg

1500

gaggacttcg ctacttacta ctgccagcag tcgtactcca ccccctacac tttcggacaa

1560

ggcaccaagg tcgaaatcaa gaccactacc ccagcaccga ggccacccac cccggctcct

1620

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

1680

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

1740

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1800

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1860

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1920

aaattcagcc gcagcgcaga tgctccagcc taccagcagg ggcagaacca gctctacaac

1980

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

2040

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

2100

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

2160

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

2220

gctcttcaca tgcaggccct gccgcctcgg

2250

<210> 177

<211> 744

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 177

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu

275 280 285

Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys

290 295 300

Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg

305 310 315 320

Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser

325 330 335

Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser

340 345 350

Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg

355 360 365

Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser

370 375 380

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile

405 410 415

Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg

420 425 430

Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

435 440 445

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala

450 455 460

Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly

465 470 475 480

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp

485 490 495

Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe

500 505 510

Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg

515 520 525

Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg

530 535 540

Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly

545 550 555 560

Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr

565 570 575

Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg

580 585 590

Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro

595 600 605

Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu

610 615 620

Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala

625 630 635 640

Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu

645 650 655

Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly

660 665 670

Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu

675 680 685

Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser

690 695 700

Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly

705 710 715 720

Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu

725 730 735

His Met Gln Ala Leu Pro Pro Arg

740

<210> 178

<211> 2232

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 178

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctggcc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gtccaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcgggacg ggagctgaag atccacgacc cagcagaaag

840

cgacgggaag tgcaattggt ggaatcaggg ggaggacttg tgcagcctgg aggatcgctg

900

agactgtcat gtgccgtgtc cggctttgcc ctgtccaacc acgggatgtc ctgggtccgc

960

cgcgcgcctg gaaagggcct cgaatgggtg tcgggtattg tgtacagcgg tagcacctac

1020

tatgccgcat ccgtgaaggg gagattcacc atcagccggg acaactccag gaacactctg

1080

tacctccaaa tgaattcgct gaggccagag gacactgcca tctactactg ctccgcgcat

1140

ggcggagagt ccgacgtctg gggacagggg accaccgtga ccgtgtctag cgcgtccggc

1200

ggaggcggca gcgggggtcg ggcatcaggg ggcggcggat cggacatcca gctcacccag

1260

tccccgagct cgctgtccgc ctccgtggga gatcgggtca ccatcacgtg ccgcgccagc

1320

cagtcgattt cctcctacct gaactggtac caacagaagc cgggaaaagc cccgaagctt

1380

ctcatctacg ccgcctcgag cctgcagtca ggagtgccct cacggttctc cggctccggt

1440

tccggtactg atttcaccct gaccattttcc tccctgcaac cggaggactt cgctacttac

1500

tactgccagc agtcgtactc caccccctac actttcggac aaggcaccaa ggtcgaaatc

1560

aagaccacta ccccagcacc gaggccaccc accccggctc ctaccatcgc ctcccagcct

1620

ctgtccctgc gtccgggaggc atgtagaccc gcagctggtg gggccgtgca tacccggggt

1680

cttgacttcg cctgcgatat ctacatttgg gcccctctgg ctggtacttg cggggtcctg

1740

ctgctttcac tcgtgatcac tctttactgt aagcgcggtc ggaagaagct gctgtacatc

1800

tttaagcaac ccttcatgag gcctgtgcag actactcaag aggaggacgg ctgttcatgc

1860

cggttcccag aggaggagga aggcggctgc gaactgcgcg tgaaattcag ccgcagcgca

1920

gatgctccag cctaccagca ggggcagaac cagctctaca acgaactcaa tcttggtcgg

1980

agagaggagt acgacgtgct ggacaagcgg agaggacggg acccagaaat gggcgggaag

2040

ccgcgcagaa agaatcccca agagggcctg tacaacgagc tccaaaagga taagatggca

2100

gaagcctata gcgagattgg tatgaaaggg gaacgcagaa gaggcaaagg ccacgacggga

2160

ctgtaccagg gactcagcac cgccaccaag gacacctatg acgctcttca catgcaggcc

2220

ctgccgcctc gg

2232

<210> 179

<211> 734

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 179

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Arg Thr Lys Arg

260 265 270

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

275 280 285

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

290 295 300

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

305 310 315 320

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

325 330 335

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

340 345 350

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

355 360 365

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

370 375 380

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

385 390 395 400

Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser

405 410 415

Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser

420 425 430

Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

435 440 445

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

450 455 460

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

465 470 475 480

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr

485 490 495

Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr

500 505 510

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

515 520 525

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

530 535 540

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

545 550 555 560

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

565 570 575

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

580 585 590

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

595 600 605

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

610 615 620

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn

625 630 635 640

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

645 650 655

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

660 665 670

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

675 680 685

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

690 695 700

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

705 710 715 720

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

725 730

<210> 180

<211> 2202

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 180

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actccgtact aaaagagaag tgcaattggt ggaatcaggg

840

ggaggacttg tgcagcctgg aggatcgctg agactgtcat gtgccgtgtc cggctttgcc

900

ctgtccaacc acgggatgtc ctgggtccgc cgcgcgcctg gaaagggcct cgaatgggtg

960

tcgggtattg tgtacagcgg tagcacctac tatgccgcat ccgtgaaggg gagattcacc

1020

atcagccggg acaactccag gaacactctg tacctccaaa tgaattcgct gaggccagag

1080

gacactgcca tctactactg ctccgcgcat ggcggagagt ccgacgtctg gggacagggg

1140

acccgtga ccgtgtctag cgcgtccggc ggaggcggca gcgggggtcg ggcatcaggg

1200

ggcggcggat cggacatcca gctcacccag tccccgagct cgctgtccgc ctccgtggga

1260

gatcgggtca ccatcacgtg ccgcgccagc cagtcgattt cctcctacct gaactggtac

1320

caacagaagc ccggaaaagc cccgaagctt ctcatctacg ccgcctcgag cctgcagtca

1380

ggagtgccct cacggttctc cggctccggt tccggtactg atttcaccct gaccattttcc

1440

tccctgcaac cggaggactt cgctacttac tactgccagc agtcgtactc caccccctac

1500

actttcggac aaggcaccaa ggtcgaaatc aagacacta ccccagcacc gaggccaccc

1560

accccggctc ctaccatcgc ctcccagcct ctgtccctgc gtccgggaggc atgtagaccc

1620

gcagctggtg gggccgtgca tacccggggt cttgacttcg cctgcgatat ctacatttgg

1680

gcccctctgg ctggtacttg cggggtcctg ctgctttcac tcgtgatcac tctttactgt

1740

aagcgcggtc ggaagaagct gctgtacatc tttaagcaac ccttcatgag gcctgtgcag

1800

actactcaag aggaggacgg ctgttcatgc cggttcccag aggaggagga aggcggctgc

1860

gaactgcgcg tgaaattcag ccgcagcgca gatgctccag cctaccagca ggggcagaac

1920

cagctctaca acgaactcaa tcttggtcgg agagaggagt acgacgtgct ggacaagcgg

1980

agaggacgggg acccagaaat gggcgggaag ccgcgcagaa agaatcccca agaggggcctg

2040

tacaacgagc tccaaaagga taagatggca gaagcctata gcgagattgg tatgaaaggg

2100

gaacgcagaa gaggcaaagg ccacgacgga ctgtaccagg gactcagcac cgccaccaag

2160

gacacctatg acgctcttca catgcaggcc ctgccgcctc gg

2202

<210> 181

<211> 750

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 181

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly

275 280 285

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

290 295 300

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

305 310 315 320

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

325 330 335

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

340 345 350

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

355 360 365

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

370 375 380

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

385 390 395 400

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

405 410 415

Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser

420 425 430

Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser

435 440 445

Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

450 455 460

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

465 470 475 480

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

485 490 495

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr

500 505 510

Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr

515 520 525

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

530 535 540

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

545 550 555 560

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

565 570 575

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

580 585 590

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

595 600 605

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

610 615 620

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

625 630 635 640

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn

645 650 655

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

660 665 670

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

675 680 685

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

690 695 700

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

705 710 715 720

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

725 730 735

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 182

<211> 2250

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 182

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcggaacc ggcgcggaag acccccggcc ctccaggaag

840

cgaaggtccc tcggagacgt gggtgaagtg caattggtgg aatcaggggg aggacttgtg

900

cagcctggag gatcgctgag actgtcatgt gccgtgtccg gctttgccct gtccaaccac

960

gggatgtcct gggtccgccg cgcgcctgga aagggcctcg aatgggtgtc gggtattgtg

1020

tacagcggta gcacctacta tgccgcatcc gtgaagggga gattcaccat cagccgggac

1080

aactccagga acactctgta cctccaaatg aattcgctga ggccagagga cactgccatc

1140

tactactgct ccgcgcatgg cggagagtcc gacgtctgggg gacaggggac caccgtgacc

1200

gtgtctagcg cgtccggcgg aggcggcagc gggggtcggg catcaggggg cggcggatcg

1260

gacatccagc tcacccagtc cccgagctcg ctgtccgcct ccgtgggaga tcgggtcacc

1320

atcacgtgcc gcgccagcca gtcgatttcc tcctacctga actggtacca acagaagccc

1380

ggaaaagccc cgaagcttct catctacgcc gcctcgagcc tgcagtcagg agtgccctca

1440

cggttctccg gctccggttc cggtactgat ttcaccctga ccatttcctc cctgcaaccg

1500

gaggacttcg ctacttacta ctgccagcag tcgtactcca ccccctacac tttcggacaa

1560

ggcaccaagg tcgaaatcaa gaccactacc ccagcaccga ggccacccac cccggctcct

1620

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

1680

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

1740

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1800

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1860

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1920

aaattcagcc gcagcgcaga tgctccagcc taccagcagg ggcagaacca gctctacaac

1980

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

2040

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

2100

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

2160

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

2220

gctcttcaca tgcaggccct gccgcctcgg

2250

<210> 183

<211> 744

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 183

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp

20 25 30

Gln Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser

35 40 45

Glu Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu

50 55 60

Leu Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala

65 70 75 80

Lys Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His

85 90 95

Leu Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp

100 105 110

Arg Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu

115 120 125

Leu Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe

130 135 140

Asp Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln

145 150 155 160

Gly Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly

165 170 175

Val Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp

180 185 190

His Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu

195 200 205

Met Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala

210 215 220

Gln Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg

225 230 235 240

Met Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser

245 250 255

Asp Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala

260 265 270

Glu Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu

275 280 285

Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys

290 295 300

Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg

305 310 315 320

Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser

325 330 335

Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser

340 345 350

Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg

355 360 365

Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser

370 375 380

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile

405 410 415

Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg

420 425 430

Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

435 440 445

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala

450 455 460

Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly

465 470 475 480

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp

485 490 495

Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe

500 505 510

Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg

515 520 525

Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg

530 535 540

Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly

545 550 555 560

Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr

565 570 575

Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg

580 585 590

Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro

595 600 605

Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu

610 615 620

Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala

625 630 635 640

Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu

645 650 655

Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly

660 665 670

Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu

675 680 685

Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser

690 695 700

Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly

705 710 715 720

Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu

725 730 735

His Met Gln Ala Leu Pro Pro Arg

740

<210> 184

<211> 2232

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 184

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccggtcgt cgttggcact ttccctgact gccgaccaga tggtgtccgc ccttctggac

120

gccgagcctc caattctgta ctcggagtac gatccgactc gcccgttctc cgaagccagc

180

atgatgggcc tgttgactaa cctggcggac cgcgagttgg tgcacatgat taactgggct

240

aagcgggtgc cgggcttcgt ggacctgacc ctgcacgacc aagtgcacct cctggaatgc

300

gcctggatgg aaatcctcat gatcggcctc gtgtggagat ccatggagca tccgggaaag

360

ctcctgtttg cacccaacct cctgcttgat cgcaaccagg gaaaatgcgt ggaagggggt

420

gtcgagattt tcgacatgct gctcgccacc tcttcccggt tccggatgat gaatctgcag

480

ggagaagagt tcgtgtgtct gaagtcaatc atcctgctga actccggggt ctataccttc

540

ctgagctcga ccctcaagtc actggaggaa aaagaccaca tccatcgcgt gctcgataag

600

atcaccgaca cccttatcca tctcatggcg aaggctggac tgaccctgca acagcagcac

660

cagaggctgg cccagttgct gctgattctg agccacatcc ggcacatgtc gaacaagagg

720

atggaacacc tgtacagcat gaagtgcaag aacgtcgtgc ctctgtccga tctgctcctg

780

gaaatgctgg acgcgcacag actcgggacg ggagctgaag atccacgacc cagcagaaag

840

cgacgggaag tgcaattggt ggaatcaggg ggaggacttg tgcagcctgg aggatcgctg

900

agactgtcat gtgccgtgtc cggctttgcc ctgtccaacc acgggatgtc ctgggtccgc

960

cgcgcgcctg gaaagggcct cgaatgggtg tcgggtattg tgtacagcgg tagcacctac

1020

tatgccgcat ccgtgaaggg gagattcacc atcagccggg acaactccag gaacactctg

1080

tacctccaaa tgaattcgct gaggccagag gacactgcca tctactactg ctccgcgcat

1140

ggcggagagt ccgacgtctg gggacagggg accaccgtga ccgtgtctag cgcgtccggc

1200

ggaggcggca gcgggggtcg ggcatcaggg ggcggcggat cggacatcca gctcacccag

1260

tccccgagct cgctgtccgc ctccgtggga gatcgggtca ccatcacgtg ccgcgccagc

1320

cagtcgattt cctcctacct gaactggtac caacagaagc cgggaaaagc cccgaagctt

1380

ctcatctacg ccgcctcgag cctgcagtca ggagtgccct cacggttctc cggctccggt

1440

tccggtactg atttcaccct gaccattttcc tccctgcaac cggaggactt cgctacttac

1500

tactgccagc agtcgtactc caccccctac actttcggac aaggcaccaa ggtcgaaatc

1560

aagaccacta ccccagcacc gaggccaccc accccggctc ctaccatcgc ctcccagcct

1620

ctgtccctgc gtccgggaggc atgtagaccc gcagctggtg gggccgtgca tacccggggt

1680

cttgacttcg cctgcgatat ctacatttgg gcccctctgg ctggtacttg cggggtcctg

1740

ctgctttcac tcgtgatcac tctttactgt aagcgcggtc ggaagaagct gctgtacatc

1800

tttaagcaac ccttcatgag gcctgtgcag actactcaag aggaggacgg ctgttcatgc

1860

cggttcccag aggaggagga aggcggctgc gaactgcgcg tgaaattcag ccgcagcgca

1920

gatgctccag cctaccagca ggggcagaac cagctctaca acgaactcaa tcttggtcgg

1980

agagaggagt acgacgtgct ggacaagcgg agaggacggg acccagaaat gggcgggaag

2040

ccgcgcagaa agaatcccca agagggcctg tacaacgagc tccaaaagga taagatggca

2100

gaagcctata gcgagattgg tatgaaaggg gaacgcagaa gaggcaaagg ccacgacggga

2160

ctgtaccagg gactcagcac cgccaccaag gacacctatg acgctcttca catgcaggcc

2220

ctgccgcctc gg

2232

<210> 185

<211> 521

<212> DNA

<213> Unknown

<220>

<221> source

<223> /note="Description of unknown sequence:

wild-type PGK promoter"

<400> 185

acccctctct ccagccacta agccagttgc tccctcggct gacggctgca cgcgaggcct

60

ccgaacgtct tacgccttgt ggcgcgcccg tccttgtccc gggtgtgatg gcggggtgtg

120

gggcggaggg cgtggcgggg aagggccggc gacgagagcc gcgcgggacg actcgtcggc

180

gataaccggt gtcgggtagc gccagccgcg cgacggtaac gagggaccgc gacaggcaga

240

cgctcccatg atcactctgc acgccgaagg caaatagtgc aggccgtgcg gcgcttggcg

300

ttccttggaa gggctgaatc cccgcctcgt ccttcgcagc ggccccccgg gtgttcccat

360

cgccgcttct aggcccactg cgacgcttgc ctgcacttct tacacgctct gggtcccagc

420

cgcggcgacg caaagggcct tggtgcgggt ctcgtcggcg cagggacgcg tttgggtccc

480

gacggaacct ttttccgcgtt ggggttgggg caccataagc t

521

<210> 186

<211> 118

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 186

acccctctct ccagccacta agccagttgc tccctcggct gacggctgca cgcgaggcct

60

ccgaacgtct tacgccttgt ggcgcgcccg tccttgtccc gggtgtgatg gcggggtg

118

<210> 187

<211> 221

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 187

acccctctct ccagccacta agccagttgc tccctcggct gacggctgca cgcgaggcct

60

ccgaacgtct tacgccttgt ggcgcgcccg tccttgtccc gggtgtgatg gcggggtgtg

120

gggcggaggg cgtggcgggg aagggccggc gacgagagcc gcgcgggacg actcgtcggc

180

gataaccggt gtcgggtagc gccagccgcg cgacggtaac g

221

<210> 188

<211> 324

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 188

acccctctct ccagccacta agccagttgc tccctcggct gacggctgca cgcgaggcct

60

ccgaacgtct tacgccttgt ggcgcgcccg tccttgtccc gggtgtgatg gcggggtgtg

120

gggcggaggg cgtggcgggg aagggccggc gacgagagcc gcgcgggacg actcgtcggc

180

gataaccggt gtcgggtagc gccagccgcg cgacggtaac gagggaccgc gacaggcaga

240

cgctcccatg atcactctgc acgccgaagg caaatagtgc aggccgtgcg gcgcttggcg

300

ttccttggaa gggctgaatc cccg

324

<210> 189

<211> 422

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 189

acccctctct ccagccacta agccagttgc tccctcggct gacggctgca cgcgaggcct

60

ccgaacgtct tacgccttgt ggcgcgcccg tccttgtccc gggtgtgatg gcggggtgtg

120

gggcggaggg cgtggcgggg aagggccggc gacgagagcc gcgcgggacg actcgtcggc

180

gataaccggt gtcgggtagc gccagccgcg cgacggtaac gagggaccgc gacaggcaga

240

cgctcccatg atcactctgc acgccgaagg caaatagtgc aggccgtgcg gcgcttggcg

300

ttccttggaa gggctgaatc cccgcctcgt ccttcgcagc ggccccccgg gtgttcccat

360

cgccgcttct aggcccactg cgacgcttgc ctgcacttct tacacgctct gggtcccagc

420

cg

422

<210> 190

<211> 21

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<220>

<221> OPTION

<222> (1)..(3)

<223> /replace=" "

<220>

<221> OTHER_INDICATOR

<222> (1)..(21)

<223> /note="The rest of the variant given in

sequences

are not preferred over those given in

annotations

for variant provisions"

<400> 190

Gly Ser Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu

1 5 10 15

Glu Asn Pro Gly Pro

20

<210> 191

<211> 22

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<220>

<221> OPTION

<222> (1)..(3)

<223> /replace=" "

<220>

<221> OTHER_INDICATOR

<222> (1)..(22)

<223> /note="The rest of the variant given in

sequences

are not preferred over those given in

annotations

for variant provisions"

<400> 191

Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val

1 5 10 15

Glu Glu Asn Pro Gly Pro

20

<210> 192

<211> 23

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<220>

<221> OPTION

<222> (1)..(3)

<223> /replace=" "

<220>

<221> OTHER_INDICATOR

<222> (1)..(23)

<223> /note="The rest of the variant given in

sequences

are not preferred over those given in

annotations

for variant provisions"

<400> 192

Gly Ser Gly Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp

1 5 10 15

Val Glu Ser Asn Pro Gly Pro

20

<210> 193

<211> 25

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<220>

<221> OPTION

<222> (1)..(3)

<223> /replace=" "

<220>

<221> OTHER_INDICATOR

<222> (1)..(25)

<223> /note="The rest of the variant given in

sequences

are not preferred over those given in

annotations

for variant provisions"

<400> 193

Gly Ser Gly Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala

1 5 10 15

Gly Asp Val Glu Ser Asn Pro Gly Pro

20 25

<210> 194

<400> 194

000

<210> 195

<400> 195

000

<210> 196

<400> 196

000

<210> 197

<400> 197

000

<210> 198

<400> 198

000

<210> 199

<400> 199

000

<210> 200

<400> 200

000

<210> 201

<211> 241

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 201

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Glu Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Ser Gly Trp Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr

100 105 110

Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Ser Pro Ser

130 135 140

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

145 150 155 160

Ser Gln Ser Ile Arg Tyr Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Lys Ala Pro Lys Leu Leu Ile Tyr Thr Ala Ser Ile Leu Gln Asn Gly

180 185 190

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

195 200 205

Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu

210 215 220

Gln Thr Tyr Thr Pro Asp Phe Gly Pro Gly Thr Lys Val Glu Ile

225 230 235 240

Lys

<210> 202

<211> 241

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 202

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Asn Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Ser Gly Trp Asp Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr

100 105 110

Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Asp Ile Arg Met Thr Gln Ser Pro Ser

130 135 140

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

145 150 155 160

Ser Gln Ser Ile Arg Tyr Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Lys Ala Pro Lys Leu Leu Ile Tyr Thr Ala Ser Ile Leu Gln Asn Gly

180 185 190

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

195 200 205

Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu

210 215 220

Gln Thr Tyr Thr Pro Asp Phe Gly Pro Gly Thr Lys Val Glu Ile

225 230 235 240

Lys

<210> 203

<211> 239

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 203

Gln Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Glu Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr

20 25 30

Thr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile

35 40 45

Gly Leu Ile Thr Pro Tyr Asn Gly Ala Ser Ser Tyr Asn Gln Lys Phe

50 55 60

Arg Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Asp Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys

85 90 95

Ala Arg Gly Gly Tyr Asp Gly Arg Gly Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Asp Ile Glu Leu Thr Gln Ser Pro Ala Ile

130 135 140

Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser

145 150 155 160

Ser Ser Val Ser Tyr Met His Trp Tyr Gln Gln Lys Ser Gly Thr Ser

165 170 175

Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Leu Ala Ser Gly Val Pro

180 185 190

Gly Arg Phe Ser Gly Ser Gly Ser Gly Asn Ser Tyr Ser Leu Thr Ile

195 200 205

Ser Ser Val Glu Ala Glu Asp Asp Ala Thr Tyr Tyr Cys Gln Gln Trp

210 215 220

Ser Gly Tyr Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Ile

225 230 235

<210> 204

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 204

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Arg Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Met

100 105 110

Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser

130 135 140

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Ile Ser Cys

145 150 155 160

Arg Ala Ser Gln Ser Val Ser Ser Asn Phe Ala Trp Tyr Gln Gln Arg

165 170 175

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp Ala Ser Asn Arg Ala

180 185 190

Thr Gly Ile Pro Pro Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

195 200 205

Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Ala Tyr Tyr

210 215 220

Cys His Gln Arg Ser Asn Trp Leu Tyr Thr Phe Gly Gln Gly Thr Lys

225 230 235 240

Val Asp Ile Lys

<210> 205

<211> 253

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 205

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Leu Arg Arg Thr Val Val Thr Pro Arg Ala Tyr Tyr Gly

100 105 110

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

130 135 140

Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser

145 150 155 160

Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser

165 170 175

Asn Ser Leu Asn Trp Tyr Gln Gln Lys Ala Gly Lys Ala Pro Lys Leu

180 185 190

Leu Ile Tyr Asp Ala Ser Thr Leu Glu Thr Gly Val Pro Ser Arg Phe

195 200 205

Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser Phe Thr Ile Ser Ser Leu

210 215 220

Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln His Asp Asn Leu

225 230 235 240

Pro Leu Thr Phe Gly Glyn Gly Thr Lys Val Glu Ile Lys

245 250

<210> 206

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 206

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Pro Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Glu Trp Asp Gly Ser Tyr Tyr Tyr Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Leu

130 135 140

Thr Gln Thr Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr

145 150 155 160

Ile Thr Cys Arg Ala Ser Gln Ser Ile Asn Thr Tyr Leu Asn Trp Tyr

165 170 175

Gln His Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser

180 185 190

Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

210 215 220

Thr Tyr Tyr Cys Gln Gln Ser Phe Ser Pro Leu Thr Phe Gly Gly Gly

225 230 235 240

Thr Lys Leu Glu Ile Lys

245

<210> 207

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 207

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Trp Met His Trp Val Arg Gln Val Pro Gly Lys Gly Leu Val Trp Val

35 40 45

Ser Arg Ile Asn Thr Asp Gly Ser Thr Thr Thr Tyr Ala Asp Ser Val

50 55 60

Glu Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Asp Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Gly Gly His Trp Ala Val Trp Gly Gln Gly Thr Thr Val Thr Val

100 105 110

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Thr

130 135 140

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

Gln Ser Ile Ser Asp Arg Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val

180 185 190

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr

195 200 205

Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala Val Tyr Tyr Cys Gln Gln

210 215 220

Tyr Gly His Leu Pro Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu

225 230 235 240

Ile Lys

<210> 208

<211> 252

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 208

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Ser Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Tyr Arg Leu Ile Ala Val Ala Gly Asp Tyr Tyr Tyr Tyr Gly

100 105 110

Met Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

130 135 140

Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ala Ser Val

145 150 155 160

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Val Gly Arg

165 170 175

Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Thr Ala Pro Lys Leu Leu

180 185 190

Ile Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

195 200 205

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Asn Leu Gln

210 215 220

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro

225 230 235 240

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys

245 250

<210> 209

<211> 250

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 209

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Trp Lys Val Ser Ser Ser Ser Pro Ala Phe Asp Tyr Trp Gly

100 105 110

Gly Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val

130 135 140

Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala

145 150 155 160

Ile Leu Ser Cys Arg Ala Ser Gln Ser Val Tyr Thr Lys Tyr Leu Gly

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp

180 185 190

Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Arg Leu Glu Pro Glu Asp

210 215 220

Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Gly Ser Pro Leu Ile Thr

225 230 235 240

Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

245 250

<210> 210

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 210

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Thr Ser Gly Tyr Pro Phe Thr Gly Tyr

20 25 30

Ser Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp His Tyr Gly Gly Asn Ser Leu Phe Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Leu Thr

130 135 140

Gln Ser Pro Ser Ser Ile Ser Ala Ser Val Gly Asp Thr Val Ser Ile

145 150 155 160

Thr Cys Arg Ala Ser Gln Asp Ser Gly Thr Trp Leu Ala Trp Tyr Gln

165 170 175

Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Met Tyr Asp Ala Ser Thr

180 185 190

Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly Ser Ala Ser Gly Thr

195 200 205

Glu Phe Thr Leu Thr Val Asn Arg Leu Gln Pro Glu Asp Ser Ala Thr

210 215 220

Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Pro Leu Thr Phe Gly Gly Gly

225 230 235 240

Thr Lys Val Asp Ile Lys

245

<210> 211

<211> 248

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 211

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Glu Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Gly Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val His

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gly Tyr Ser Ser Ser Ser Asp Ala Phe Asp Ile Trp Gly

100 105 110

Gly Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln

130 135 140

Met Thr Gln Ser Pro Pro Ser Leu Ser Ala Ser Val Gly Asp Arg Val

145 150 155 160

Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Ala Leu Ala Trp

165 170 175

Tyr Gln Gln Lys Pro Gly Thr Pro Pro Lys Leu Leu Ile Tyr Asp Ala

180 185 190

Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

195 200 205

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

210 215 220

Ala Thr Tyr Tyr Cys Gln Gln Phe Ser Ser Tyr Pro Leu Thr Phe Gly

225 230 235 240

Gly Gly Thr Arg Leu Glu Ile Lys

245

<210> 212

<211> 255

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 212

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Val Ala Gly Gly Ile Tyr Tyr Tyr Tyr Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Ile Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile

130 135 140

Val Met Thr Gln Thr Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg

145 150 155 160

Ala Thr Ile Ser Cys Lys Ser Ser His Ser Val Leu Tyr Asn Arg Asn

165 170 175

Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro

180 185 190

Lys Leu Leu Phe Tyr Trp Ala Ser Thr Arg Lys Ser Gly Val Pro Asp

195 200 205

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

210 215 220

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Thr Gln

225 230 235 240

Thr Phe Pro Leu Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Asn

245 250 255

<210> 213

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 213

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Thr Thr Thr Thr Ser Tyr Ala Phe Asp Ile Trp Gly Gln Gly Thr

100 105 110

Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln

130 135 140

Ser Pro Ser Thr Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr

145 150 155 160

Cys Arg Ala Ser Gln Ser Ile Ser Thr Trp Leu Ala Trp Tyr Gln Gln

165 170 175

Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile Tyr Lys Ala Ser Thr Leu

180 185 190

Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu

195 200 205

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala Thr Tyr

210 215 220

Tyr Cys Gln Gln Tyr Asn Thr Tyr Ser Pro Tyr Thr Phe Gly Gln Gly

225 230 235 240

Thr Lys Leu Glu Ile Lys

245

<210> 214

<211> 249

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 214

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Phe Ile Phe Ser Asp Tyr

20 25 30

Tyr Met Gly Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Tyr Ile Gly Arg Ser Gly Ser Ser Met Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Ala Ser Pro Val Val Ala Ala Thr Glu Asp Phe Gln His Trp Gly

100 105 110

Gly Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val

130 135 140

Met Thr Gln Thr Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala

145 150 155 160

Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Asn Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Leu Phe Gly

180 185 190

Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Arg Leu Glu Pro Glu Asp

210 215 220

Phe Ala Met Tyr Tyr Cys Gln Gln Tyr Gly Ser Ala Pro Val Thr Phe

225 230 235 240

Gly Gln Gly Thr Lys Leu Glu Ile Lys

245

<210> 215

<211> 249

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 215

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Ala Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Phe Thr Phe Arg Gly Tyr

20 25 30

Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Ser Arg Ala Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Thr Ala Ser Cys Gly Gly Asp Cys Tyr Tyr Leu Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile

130 135 140

Gln Met Thr Gln Ser Pro Pro Thr Leu Ser Ala Ser Val Gly Asp Arg

145 150 155 160

Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Val Asn Ile Trp Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Lys

180 185 190

Ser Ser Ser Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Ala Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp

210 215 220

Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Gln Ser Tyr Pro Leu Thr Phe

225 230 235 240

Gly Gly Gly Thr Lys Val Asp Ile Lys

245

<210> 216

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 216

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Asp Gly Ser Ser Ser Trp Ser Trp Gly Tyr Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Ser Glu Leu Thr Gln Asp

130 135 140

Pro Ala Val Ser Val Ala Leu Gly Gln Thr Val Arg Thr Thr Cys Gln

145 150 155 160

Gly Asp Ala Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro

165 170 175

Gly Gln Ala Pro Met Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro Ser

180 185 190

Gly Ile Pro Asp Arg Phe Ser Gly Ser Asp Ser Gly Asp Thr Ala Ser

195 200 205

Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys

210 215 220

Asn Ser Arg Asp Ser Ser Gly Tyr Pro Val Phe Gly Thr Gly Thr Lys

225 230 235 240

Val Thr Val Leu

<210> 217

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 217

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Thr Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Asp Ser Ser Ser Trp Tyr Gly Gly Gly Ser Ala Phe Asp Ile

100 105 110

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Ser Glu Leu Thr Gln

130 135 140

Glu Pro Ala Val Ser Val Ala Leu Gly Gln Thr Val Arg Ile Thr Cys

145 150 155 160

Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys

165 170 175

Pro Gly Gln Ala Pro Val Leu Val Ile Phe Gly Arg Ser Arg Arg Pro

180 185 190

Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala

195 200 205

Ser Leu Ile Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr

210 215 220

Cys Asn Ser Arg Asp Asn Thr Ala Asn His Tyr Val Phe Gly Thr Gly

225 230 235 240

Thr Lys Leu Thr Val Leu

245

<210> 218

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 218

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Thr Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Lys Asp Ser Ser Ser Trp Tyr Gly Gly Gly Ser Ala Phe Asp Ile

100 105 110

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Ser Glu Leu Thr Gln

130 135 140

Asp Pro Ala Val Ser Val Ala Leu Gly Gln Thr Val Arg Ile Thr Cys

145 150 155 160

Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys

165 170 175

Pro Gly Gln Ala Pro Val Leu Val Ile Tyr Gly Lys Asn Asn Arg Pro

180 185 190

Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala

195 200 205

Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr

210 215 220

Cys Asn Ser Arg Gly Ser Ser Gly Asn His Tyr Val Phe Gly Thr Gly

225 230 235 240

Thr Lys Val Thr Val Leu

245

<210> 219

<211> 251

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 219

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Val Trp Val

35 40 45

Ser Arg Ile Asn Ser Asp Gly Ser Ser Thr Ser Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Arg Thr Gly Trp Val Gly Ser Tyr Tyr Tyr Tyr Met Asp Val Trp

100 105 110

Gly Lys Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

130 135 140

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

145 150 155 160

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn Tyr Leu

165 170 175

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Arg Leu Leu Ile Tyr

180 185 190

Asp Val Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly Gly

195 200 205

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu

210 215 220

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro Trp

225 230 235 240

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

245 250

<210> 220

<211> 250

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 220

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Gly Tyr Ser Arg Tyr Tyr Tyr Tyr Gly Met Asp Val Trp Gly

100 105 110

Gly Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val

130 135 140

Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala

145 150 155 160

Ile Leu Ser Cys Arg Ala Ser Gln Ser Val Tyr Thr Lys Tyr Leu Gly

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp

180 185 190

Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Arg Leu Glu Pro Glu Asp

210 215 220

Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Gly Ser Pro Leu Ile Thr

225 230 235 240

Phe Gly Gln Gly Thr Lys Val Asp Ile Lys

245 250

<210> 221

<211> 249

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 221

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Arg Glu Ala Ala Ala Gly His Asp Trp Tyr Phe Asp Leu Trp

100 105 110

Gly Arg Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile

130 135 140

Arg Val Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg

145 150 155 160

Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala

180 185 190

Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp

210 215 220

Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Ile Pro Leu Thr Phe

225 230 235 240

Gly Gln Gly Thr Lys Val Glu Ile Lys

245

<210> 222

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 222

Gln Val Gln Leu Val Gln Ser Trp Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Ser Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Asn Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ser Pro Arg Val Thr Thr Gly Tyr Phe Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Leu

130 135 140

Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly Asp Arg Val Thr

145 150 155 160

Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser

180 185 190

Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala

210 215 220

Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Leu Thr Phe Gly Gly

225 230 235 240

Gly Thr Arg Leu Glu Ile Lys

245

<210> 223

<211> 253

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 223

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Arg Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Arg Ala Ser Gly Asp Thr Ser Thr Arg His

20 25 30

Tyr Ile His Trp Leu Arg Gln Ala Pro Gly Gln Gly Pro Glu Trp Met

35 40 45

Gly Val Ile Asn Pro Thr Thr Gly Pro Ala Thr Gly Ser Pro Ala Tyr

50 55 60

Ala Gln Met Leu Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr

65 70 75 80

Arg Thr Val Tyr Met Glu Leu Arg Ser Leu Arg Phe Glu Asp Thr Ala

85 90 95

Val Tyr Tyr Cys Ala Arg Ser Val Val Gly Arg Ser Ala Pro Tyr Tyr

100 105 110

Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

130 135 140

Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser

145 150 155 160

Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser

165 170 175

Asp Tyr Ser Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu

180 185 190

Leu Ile Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe

195 200 205

Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Tyr Leu

210 215 220

Gln Ser Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Tyr Ser Tyr

225 230 235 240

Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys

245 250

<210> 224

<211> 249

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 224

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Gly Tyr Thr Thr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Leu Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ile Arg Ser Cys Gly Gly Asp Cys Tyr Tyr Phe Asp Asn Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile

130 135 140

Gln Leu Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly Asp Arg

145 150 155 160

Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Val Asn Ile Trp Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Lys

180 185 190

Ser Ser Ser Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Ala Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp

210 215 220

Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Gln Ser Tyr Pro Leu Thr Phe

225 230 235 240

Gly Gly Gly Thr Lys Val Asp Ile Lys

245

<210> 225

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 225

Gln Ile Thr Leu Lys Glu Ser Gly Pro Ala Leu Val Lys Pro Thr Gln

1 5 10 15

Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser Thr Ala

20 25 30

Gly Val His Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Ala Leu Glu

35 40 45

Trp Leu Ala Leu Ile Ser Trp Ala Asp Asp Lys Arg Tyr Arg Pro Ser

50 55 60

Leu Arg Ser Arg Leu Asp Ile Thr Arg Val Thr Ser Lys Asp Gln Val

65 70 75 80

Val Leu Ser Met Thr Asn Met Gln Pro Glu Asp Thr Ala Thr Tyr Tyr

85 90 95

Cys Ala Leu Gln Gly Phe Asp Gly Tyr Glu Ala Asn Trp Gly Pro Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr

130 135 140

Gln Ser Pro Ser Ser Leu Ser Ala Ser Ala Gly Asp Arg Val Thr Ile

145 150 155 160

Thr Cys Arg Ala Ser Arg Gly Ile Ser Ser Ala Leu Ala Trp Tyr Gln

165 170 175

Gln Lys Pro Gly Lys Pro Pro Lys Leu Leu Ile Tyr Asp Ala Ser Ser

180 185 190

Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr

195 200 205

Asp Phe Thr Leu Thr Ile Asp Ser Leu Glu Pro Glu Asp Phe Ala Thr

210 215 220

Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Trp Thr Phe Gly Gln Gly

225 230 235 240

Thr Lys Val Asp Ile Lys

245

<210> 226

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 226

Gly Tyr Thr Phe Thr Asp Tyr Tyr Met His

1 5 10

<210> 227

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 227

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 228

<211> 6

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 228

Gly Trp Asp Phe Asp Tyr

15

<210> 229

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 229

Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His

1 5 10

<210> 230

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 230

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Asn Phe Gln

1 5 10 15

gly

<210> 231

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 231

Gly Tyr Ser Phe Thr Gly Tyr Thr Met Asn

1 5 10

<210> 232

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 232

Leu Ile Thr Pro Tyr Asn Gly Ala Ser Ser Tyr Asn Gln Lys Phe Arg

1 5 10 15

gly

<210> 233

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 233

Gly Gly Tyr Asp Gly Arg Gly Phe Asp Tyr

1 5 10

<210> 234

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 234

Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 235

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 235

Gly Arg Tyr Tyr Gly Met Asp Val

15

<210> 236

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 236

Asp Leu Arg Arg Thr Val Val Thr Pro Arg Ala Tyr Tyr Gly Met Asp

1 5 10 15

Val

<210> 237

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 237

Gly Glu Trp Asp Gly Ser Tyr Tyr Tyr Asp Tyr

1 5 10

<210> 238

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 238

Gly Phe Thr Phe Ser Ser Tyr Trp Met His

1 5 10

<210> 239

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 239

Arg Ile Asn Thr Asp Gly Ser Thr Thr Thr Tyr Ala Asp Ser Val Glu

1 5 10 15

gly

<210> 240

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 240

Gly His Trp Ala Val

15

<210> 241

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 241

Gly Tyr Thr Phe Thr Ser Tyr Tyr Met His

1 5 10

<210> 242

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 242

Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln

1 5 10 15

<210> 243

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 243

Tyr Arg Leu Ile Ala Val Ala Gly Asp Tyr Tyr Tyr Tyr Gly Met Asp

1 5 10 15

Val

<210> 244

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 244

Gly Phe Thr Phe Ser Ser Tyr Ala Met His

1 5 10

<210> 245

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 245

Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 246

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 246

Trp Lys Val Ser Ser Ser Ser Pro Ala Phe Asp Tyr

1 5 10

<210> 247

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 247

Gly Tyr Pro Phe Thr Gly Tyr Ser Leu His

1 5 10

<210> 248

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 248

Asp His Tyr Gly Gly Asn Ser Leu Phe Tyr

1 5 10

<210> 249

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 249

Ile Ile Asn Pro Ser Gly Gly Ser Thr Gly Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 250

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 250

Gly Gly Tyr Ser Ser Ser Ser Asp Ala Phe Asp Ile

1 5 10

<210> 251

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 251

Gly Tyr Thr Phe Thr Ser Tyr Gly Ile Ser

1 5 10

<210> 252

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 252

Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Leu Gln

1 5 10 15

<210> 253

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 253

Val Ala Gly Gly Ile Tyr Tyr Tyr Tyr Gly Met Asp Val

1 5 10

<210> 254

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 254

Thr Thr Thr Ser Tyr Ala Phe Asp Ile

15

<210> 255

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 255

Gly Phe Ile Phe Ser Asp Tyr Tyr Met Gly

1 5 10

<210> 256

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 256

Tyr Ile Gly Arg Ser Gly Ser Ser Met Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 257

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 257

Ser Pro Val Val Ala Ala Thr Glu Asp Phe Gln His

1 5 10

<210> 258

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 258

Gly Phe Thr Phe Arg Gly Tyr Tyr Ile His

1 5 10

<210> 259

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 259

Ile Ile Asn Pro Ser Gly Gly Ser Arg Ala Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 260

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 260

Thr Ala Ser Cys Gly Gly Asp Cys Tyr Tyr Leu Asp Tyr

1 5 10

<210> 261

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 261

Gly Phe Thr Phe Asp Asp Tyr Ala Met His

1 5 10

<210> 262

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 262

Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val Lys

1 5 10 15

<210> 263

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 263

Asp Gly Ser Ser Ser Trp Ser Trp Gly Tyr Phe Asp Tyr

1 5 10

<210> 264

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 264

Gly Ile Ser Trp Asn Ser Gly Ser Thr Gly Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 265

<211> 14

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 265

Asp Ser Ser Ser Trp Tyr Gly Gly Gly Ser Ala Phe Asp Ile

1 5 10

<210> 266

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 266

Arg Ile Asn Ser Asp Gly Ser Ser Thr Ser Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 267

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 267

Thr Gly Trp Val Gly Ser Tyr Tyr Tyr Tyr Met Asp Val

1 5 10

<210> 268

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 268

Gly Phe Thr Phe Ser Ser Tyr Gly Met His

1 5 10

<210> 269

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 269

Gly Tyr Ser Arg Tyr Tyr Tyr Tyr Gly Met Asp Val

1 5 10

<210> 270

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 270

Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser

1 5 10

<210> 271

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 271

Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 272

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 272

Arg Glu Ala Ala Ala Gly His Asp Trp Tyr Phe Asp Leu

1 5 10

<210> 273

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 273

Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 274

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 274

Ser Pro Arg Val Thr Thr Gly Tyr Phe Asp Tyr

1 5 10

<210> 275

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 275

Gly Asp Thr Ser Thr Arg His Tyr Ile His

1 5 10

<210> 276

<211> 21

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 276

Val Ile Asn Pro Thr Thr Gly Pro Ala Thr Gly Ser Pro Ala Tyr Ala

1 5 10 15

Gln Met Leu Gln Gly

20

<210> 277

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 277

Ser Val Val Gly Arg Ser Ala Pro Tyr Tyr Phe Asp Tyr

1 5 10

<210> 278

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 278

Gly Tyr Thr Phe Thr Asn Tyr Tyr Met His

1 5 10

<210> 279

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 279

Ile Ile Asn Pro Ser Gly Gly Tyr Thr Thr Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 280

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 280

Ile Arg Ser Cys Gly Gly Asp Cys Tyr Tyr Phe Asp Asn

1 5 10

<210> 281

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 281

Gly Phe Ser Leu Ser Thr Ala Gly Val His Val Gly

1 5 10

<210> 282

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 282

Leu Ile Ser Trp Ala Asp Asp Lys Arg Tyr Arg Pro Ser Leu Arg Ser

1 5 10 15

<210> 283

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 283

Gln Gly Phe Asp Gly Tyr Glu Ala Asn

15

<210> 284

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 284

Arg Ala Ser Gln Ser Ile Arg Tyr Tyr Leu Ser

1 5 10

<210> 285

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 285

Thr Ala Ser Ile Leu Gln Asn

15

<210> 286

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 286

Leu Gln Thr Tyr Thr Thr Pro Asp

15

<210> 287

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 287

Ser Ala Ser Ser Ser Val Ser Tyr Met His

1 5 10

<210> 288

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 288

Asp Thr Ser Lys Leu Ala Ser

15

<210> 289

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 289

Gln Gln Trp Ser Gly Tyr Pro Leu Thr

15

<210> 290

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 290

Arg Ala Ser Gln Ser Val Ser Ser Asn Phe Ala

1 5 10

<210> 291

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 291

Asp Ala Ser Asn Arg Ala Thr

15

<210> 292

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 292

His Gln Arg Ser Asn Trp Leu Tyr Thr

15

<210> 293

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 293

Gln Ala Ser Gln Asp Ile Ser Asn Ser Leu Asn

1 5 10

<210> 294

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 294

Asp Ala Ser Thr Leu Glu Thr

15

<210> 295

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 295

Gln Gln His Asp Asn Leu Pro Leu Thr

15

<210> 296

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 296

Arg Ala Ser Gln Ser Ile Asn Thr Tyr Leu Asn

1 5 10

<210> 297

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 297

Ala Ala Ser Ser Leu Gln Ser

15

<210> 298

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 298

Gln Gln Ser Phe Ser Pro Leu Thr

15

<210> 299

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 299

Arg Ala Ser Gln Ser Ile Ser Asp Arg Leu Ala

1 5 10

<210> 300

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 300

Lys Ala Ser Ser Leu Glu Ser

15

<210> 301

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 301

Gln Gln Tyr Gly His Leu Pro Met Tyr Thr

1 5 10

<210> 302

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 302

Arg Ala Ser Gln Gly Val Gly Arg Trp Leu Ala

1 5 10

<210> 303

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 303

Ala Ala Ser Thr Leu Gln Ser

15

<210> 304

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 304

Gln Gln Ala Asn Ser Phe Pro Leu Thr

15

<210> 305

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 305

Arg Ala Ser Gln Ser Val Tyr Thr Lys Tyr Leu Gly

1 5 10

<210> 306

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 306

Asp Ala Ser Thr Arg Ala Thr

15

<210> 307

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 307

Gln His Tyr Gly Gly Ser Pro Leu Ile Thr

1 5 10

<210> 308

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 308

Arg Ala Ser Gln Asp Ser Gly Thr Trp Leu Ala

1 5 10

<210> 309

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 309

Asp Ala Ser Thr Leu Glu Asp

15

<210> 310

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 310

Gln Gln Tyr Asn Ser Tyr Pro Leu Thr

15

<210> 311

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 311

Arg Ala Ser Gln Asp Ile Ser Ser Ala Leu Ala

1 5 10

<210> 312

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 312

Asp Ala Ser Ser Leu Glu Ser

15

<210> 313

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 313

Gln Gln Phe Ser Ser Tyr Pro Leu Thr

15

<210> 314

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 314

Lys Ser Ser His Ser Val Leu Tyr Asn Arg Asn Asn Lys Asn Tyr Leu

1 5 10 15

Ala

<210> 315

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 315

Trp Ala Ser Thr Arg Lys Ser

15

<210> 316

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 316

Gln Gln Thr Gln Thr Phe Pro Leu Thr

15

<210> 317

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 317

Arg Ala Ser Gln Ser Ile Ser Thr Trp Leu Ala

1 5 10

<210> 318

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 318

Lys Ala Ser Thr Leu Glu Ser

15

<210> 319

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 319

Gln Gln Tyr Asn Thr Tyr Ser Pro Tyr Thr

1 5 10

<210> 320

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 320

Arg Ala Ser Gln Ser Val Thr Ser Asn Tyr Leu Ala

1 5 10

<210> 321

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 321

Gly Ala Ser Thr Arg Ala Thr

15

<210> 322

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 322

Gln Gln Tyr Gly Ser Ala Pro Val Thr

15

<210> 323

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 323

Arg Ala Ser Glu Asn Val Asn Ile Trp Leu Ala

1 5 10

<210> 324

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 324

Lys Ser Ser Ser Leu Ala Ser

15

<210> 325

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 325

Gln Gln Tyr Gln Ser Tyr Pro Leu Thr

15

<210> 326

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 326

Gln Gly Asp Ala Leu Arg Ser Tyr Tyr Ala Ser

1 5 10

<210> 327

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 327

Gly Lys Asn Asn Arg Pro Ser

15

<210> 328

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 328

Asn Ser Arg Asp Ser Ser Gly Tyr Pro Val

1 5 10

<210> 329

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 329

Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser

1 5 10

<210> 330

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 330

Gly Arg Ser Arg Arg Pro Ser

15

<210> 331

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 331

Asn Ser Arg Asp Asn Thr Ala Asn His Tyr Val

1 5 10

<210> 332

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 332

Asn Ser Arg Gly Ser Ser Gly Asn His Tyr Val

1 5 10

<210> 333

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 333

Arg Ala Ser Gln Ser Val Ser Ser Asn Tyr Leu Ala

1 5 10

<210> 334

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 334

Asp Val Ser Thr Arg Ala Thr

15

<210> 335

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 335

Gln Gln Arg Ser Asn Trp Pro Pro Trp Thr

1 5 10

<210> 336

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 336

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

1 5 10

<210> 337

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 337

Gln Gln Ser Tyr Ser Ile Pro Leu Thr

15

<210> 338

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 338

Arg Ala Ser Gln Ser Ile Ser Ser Trp Leu Ala

1 5 10

<210> 339

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 339

Gln Gln Tyr Ser Ser Tyr Pro Leu Thr

15

<210> 340

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 340

Arg Ala Ser Gln Gly Ile Ser Asp Tyr Ser

1 5 10

<210> 341

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 341

Gln Gln Tyr Tyr Ser Tyr Pro Leu Thr

15

<210> 342

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 342

Arg Ala Ser Arg Gly Ile Ser Ser Ala Leu Ala

1 5 10

<210> 343

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 343

Gln Gln Ser Tyr Ser Thr Pro Trp Thr

15

<210> 344

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 344

Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Gly Ser Gly Phe Asn Ile Glu Asp Tyr

20 25 30

Tyr Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys Tyr Gly Pro Ile Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asn Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly Thr Thr Val Thr Val

100 105 110

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr Gln Ser Pro Asp Ser

130 135 140

Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser

145 150 155 160

Gln Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln

165 170 175

Gln Lys Pro Gly Gln Pro Pro Lys Arg Leu Ile Ser Leu Val Ser Lys

180 185 190

Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr

195 200 205

Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val

210 215 220

Tyr Tyr Cys Trp Gln Gly Thr His Phe Pro Gly Thr Phe Gly Gly Gly

225 230 235 240

Thr Lys Val Glu Ile Lys

245

<210> 345

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 345

Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser

20 25 30

Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln Gln Lys Pro Gly Gln Pro

35 40 45

Pro Lys Arg Leu Ile Ser Leu Val Ser Lys Leu Asp Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

65 70 75 80

Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Trp Gln Gly

85 90 95

Thr His Phe Pro Gly Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val Lys

130 135 140

Lys Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Gly Ser Gly Phe Asn

145 150 155 160

Ile Glu Asp Tyr Tyr Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly

165 170 175

Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys Tyr

180 185 190

Gly Pro Ile Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr

195 200 205

Asn Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

210 215 220

Val Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly Thr

225 230 235 240

Thr Val Thr Val Ser Ser

245

<210> 346

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 346

Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Phe Asn Ile Glu Asp Tyr

20 25 30

Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys Tyr Gly Pro Ile Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Thr Ser Ile Asn Thr Val Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly Thr Thr Val Thr Val

100 105 110

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr Gln Ser Pro Leu Ser

130 135 140

Leu Pro Val Thr Leu Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser

145 150 155 160

Gln Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln

165 170 175

Gln Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile Ser Leu Val Ser Lys

180 185 190

Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr

195 200 205

Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val

210 215 220

Tyr Tyr Cys Trp Gln Gly Thr His Phe Pro Gly Thr Phe Gly Gly Gly

225 230 235 240

Thr Lys Val Glu Ile Lys

245

<210> 347

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 347

Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser

20 25 30

Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Ser Leu Val Ser Lys Leu Asp Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Trp Gln Gly

85 90 95

Thr His Phe Pro Gly Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val Lys

130 135 140

Lys Pro Gly Glu Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Phe Asn

145 150 155 160

Ile Glu Asp Tyr Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys Gly

165 170 175

Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys Tyr

180 185 190

Gly Pro Ile Phe Gln Gly His Val Thr Ile Ser Ala Asp Thr Ser Ile

195 200 205

Asn Thr Val Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala

210 215 220

Met Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly Thr

225 230 235 240

Thr Val Thr Val Ser Ser

245

<210> 348

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 348

Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Gly Ser Gly Phe Asn Ile Glu Asp Tyr

20 25 30

Tyr Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys Tyr Gly Pro Ile Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asn Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly Thr Thr Val Thr Val

100 105 110

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr Gln Ser Pro Leu Ser

130 135 140

Leu Pro Val Thr Leu Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser

145 150 155 160

Gln Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln

165 170 175

Gln Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile Ser Leu Val Ser Lys

180 185 190

Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr

195 200 205

Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val

210 215 220

Tyr Tyr Cys Trp Gln Gly Thr His Phe Pro Gly Thr Phe Gly Gly Gly

225 230 235 240

Thr Lys Val Glu Ile Lys

245

<210> 349

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 349

Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Phe Asn Ile Glu Asp Tyr

20 25 30

Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys Tyr Gly Pro Ile Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Thr Ser Ile Asn Thr Val Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly Thr Thr Val Thr Val

100 105 110

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr Gln Ser Pro Asp Ser

130 135 140

Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser

145 150 155 160

Gln Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln

165 170 175

Gln Lys Pro Gly Gln Pro Pro Lys Arg Leu Ile Ser Leu Val Ser Lys

180 185 190

Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr

195 200 205

Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val

210 215 220

Tyr Tyr Cys Trp Gln Gly Thr His Phe Pro Gly Thr Phe Gly Gly Gly

225 230 235 240

Thr Lys Val Glu Ile Lys

245

<210> 350

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 350

Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser

20 25 30

Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln Gln Lys Pro Gly Gln Pro

35 40 45

Pro Lys Arg Leu Ile Ser Leu Val Ser Lys Leu Asp Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

65 70 75 80

Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Trp Gln Gly

85 90 95

Thr His Phe Pro Gly Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val Lys

130 135 140

Lys Pro Gly Glu Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Phe Asn

145 150 155 160

Ile Glu Asp Tyr Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys Gly

165 170 175

Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys Tyr

180 185 190

Gly Pro Ile Phe Gln Gly His Val Thr Ile Ser Ala Asp Thr Ser Ile

195 200 205

Asn Thr Val Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala

210 215 220

Met Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly Thr

225 230 235 240

Thr Val Thr Val Ser Ser

245

<210> 351

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 351

Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser

20 25 30

Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Ser Leu Val Ser Lys Leu Asp Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Trp Gln Gly

85 90 95

Thr His Phe Pro Gly Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val Lys

130 135 140

Lys Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Gly Ser Gly Phe Asn

145 150 155 160

Ile Glu Asp Tyr Tyr Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly

165 170 175

Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys Tyr

180 185 190

Gly Pro Ile Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr

195 200 205

Asn Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

210 215 220

Val Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly Thr

225 230 235 240

Thr Val Thr Val Ser Ser

245

<210> 352

<211> 243

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 352

Glu Ile Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Leu Ser Cys Thr Gly Ser Gly Phe Asn Ile Glu Asp Tyr

20 25 30

Tyr Ile His Trp Val Lys Gln Arg Thr Glu Gln Gly Leu Glu Trp Ile

35 40 45

Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys Tyr Gly Pro Ile Phe

50 55 60

Gln Gly Arg Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr Val Tyr

65 70 75 80

Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Phe Arg Gly Gly Val Tyr Trp Gly Pro Gly Thr Thr Leu Thr Val

100 105 110

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser His Met Asp Val Val Met Thr Gln Ser Pro Leu Thr Leu Ser Val

130 135 140

Ala Ile Gly Gln Ser Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu

145 150 155 160

Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Leu Gln Arg Pro

165 170 175

Gly Gln Ser Pro Lys Arg Leu Ile Ser Leu Val Ser Lys Leu Asp Ser

180 185 190

Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr

195 200 205

Leu Arg Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Ile Tyr Tyr Cys

210 215 220

Trp Gln Gly Thr His Phe Pro Gly Thr Phe Gly Gly Gly Thr Lys Leu

225 230 235 240

Glu Ile Lys

<210> 353

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 353

Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala

1 5 10 15

Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr

20 25 30

Thr Met Asn Trp Val Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile

35 40 45

Gly Leu Ile Asn Pro Tyr Asn Gly Gly Thr Ile Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Tyr Gly Phe Val Leu Asp Tyr Trp Gly Gln Gly Thr Thr

100 105 110

Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ile Val Leu Thr Gln Ser

130 135 140

Pro Ser Ile Met Ser Val Ser Pro Gly Glu Lys Val Thr Ile Thr Cys

145 150 155 160

Ser Ala Ser Ser Ser Val Ser Tyr Met His Trp Phe Gln Gln Lys Pro

165 170 175

Gly Thr Ser Pro Lys Leu Cys Ile Tyr Ser Thr Ser Asn Leu Ala Ser

180 185 190

Gly Val Pro Ala Arg Phe Ser Gly Arg Gly Ser Gly Thr Ser Tyr Ser

195 200 205

Leu Thr Ile Ser Arg Val Ala Ala Glu Asp Ala Ala Thr Tyr Tyr Cys

210 215 220

Gln Gln Arg Ser Asn Tyr Pro Pro Trp Thr Phe Gly Gly Gly Thr Lys

225 230 235 240

Leu Glu Ile Lys

<210> 354

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 354

Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala

1 5 10 15

Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr

20 25 30

Thr Met Asn Trp Val Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile

35 40 45

Gly Leu Ile Asn Pro Tyr Asn Gly Gly Thr Ile Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Tyr Gly Phe Val Leu Asp Tyr Trp Gly Gln Gly Thr Thr

100 105 110

Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ile Val Leu Thr Gln Ser

130 135 140

Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Ile Thr Cys

145 150 155 160

Ser Ala Ser Ser Ser Val Ser Tyr Leu His Trp Phe Gln Gln Lys Pro

165 170 175

Gly Thr Ser Pro Lys Leu Trp Val Tyr Ser Thr Ser Asn Leu Pro Ser

180 185 190

Gly Val Pro Ala Arg Phe Gly Gly Ser Gly Ser Gly Thr Ser Tyr Ser

195 200 205

Leu Thr Ile Ser Arg Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys

210 215 220

Gln Gln Arg Ser Ile Tyr Pro Pro Trp Thr Phe Gly Gly Gly Thr Lys

225 230 235 240

Leu Glu Ile Lys

<210> 355

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 355

Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala

1 5 10 15

Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr

20 25 30

Thr Met Asn Trp Val Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile

35 40 45

Gly Leu Ile Asn Pro Tyr Asn Gly Gly Thr Ile Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Tyr Gly Phe Val Leu Asp Tyr Trp Gly Gln Gly Thr Thr

100 105 110

Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ile Val Leu Thr Gln Ser

130 135 140

Pro Ser Ile Met Ser Val Ser Pro Gly Glu Lys Val Thr Ile Thr Cys

145 150 155 160

Ser Ala Ser Ser Ser Val Ser Tyr Met His Trp Phe Gln Gln Lys Pro

165 170 175

Gly Thr Ser Pro Lys Leu Gly Ile Tyr Ser Thr Ser Asn Leu Ala Ser

180 185 190

Gly Val Pro Ala Arg Phe Ser Gly Arg Gly Ser Gly Thr Ser Tyr Ser

195 200 205

Leu Thr Ile Ser Arg Val Ala Ala Glu Asp Ala Ala Thr Tyr Tyr Cys

210 215 220

Gln Gln Arg Ser Asn Tyr Pro Pro Trp Thr Phe Gly Gly Gly Thr Lys

225 230 235 240

Leu Glu Ile Lys

<210> 356

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 356

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly

1 5 10 15

Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln

65 70 75 80

Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu

115 120 125

Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys

130 135 140

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

145 150 155 160

Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser

165 170 175

Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile

180 185 190

Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln

195 200 205

Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

210 215 220

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val

225 230 235 240

Ser Ser

<210> 357

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 357

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

115 120 125

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

130 135 140

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

145 150 155 160

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

165 170 175

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

180 185 190

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

195 200 205

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

210 215 220

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

225 230 235 240

Ser Ser

<210> 358

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 358

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

115 120 125

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

130 135 140

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

145 150 155 160

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

165 170 175

Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

180 185 190

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

195 200 205

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

210 215 220

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

225 230 235 240

Ser Ser

<210> 359

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 359

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Ala

130 135 140

Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala

145 150 155 160

Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly

180 185 190

Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu

195 200 205

Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln

210 215 220

Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu

225 230 235 240

Ile Lys

<210> 360

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 360

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Ala

130 135 140

Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala

145 150 155 160

Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly

180 185 190

Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu

195 200 205

Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln

210 215 220

Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu

225 230 235 240

Ile Lys

<210> 361

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 361

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

115 120 125

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

130 135 140

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

145 150 155 160

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

165 170 175

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser

180 185 190

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

195 200 205

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

210 215 220

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

225 230 235 240

Thr Leu Val Thr Val Ser Ser

245

<210> 362

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 362

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

115 120 125

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

130 135 140

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

145 150 155 160

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

165 170 175

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys Ser

180 185 190

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

195 200 205

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

210 215 220

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

225 230 235 240

Thr Leu Val Thr Val Ser Ser

245

<210> 363

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 363

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

130 135 140

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

145 150 155 160

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

180 185 190

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

210 215 220

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

225 230 235 240

Gly Thr Lys Leu Glu Ile Lys

245

<210> 364

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 364

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

130 135 140

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

145 150 155 160

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

180 185 190

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

210 215 220

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

225 230 235 240

Gly Thr Lys Leu Glu Ile Lys

245

<210> 365

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 365

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

115 120 125

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

130 135 140

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

145 150 155 160

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

165 170 175

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys Ser

180 185 190

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

195 200 205

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

210 215 220

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

225 230 235 240

Thr Leu Val Thr Val Ser Ser

245

<210> 366

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 366

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

130 135 140

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

145 150 155 160

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

180 185 190

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

210 215 220

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

225 230 235 240

Gly Thr Lys Leu Glu Ile Lys

245

<210> 367

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 367

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

115 120 125

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

130 135 140

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

145 150 155 160

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

165 170 175

Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

180 185 190

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

195 200 205

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

210 215 220

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

225 230 235 240

Ser Ser

<210> 368

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 368

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Ala

130 135 140

Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala

145 150 155 160

Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly

180 185 190

Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu

195 200 205

Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln

210 215 220

Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu

225 230 235 240

Ile Lys

<210> 369

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 369

Gly Val Ser Leu Pro Asp Tyr Gly Val Ser

1 5 10

<210> 370

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 370

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser

1 5 10 15

<210> 371

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 371

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

1 5 10

<210> 372

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 372

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser

1 5 10 15

<210> 373

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 373

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys Ser

1 5 10 15

<210> 374

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 374

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys Ser

1 5 10 15

<210> 375

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 375

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn

1 5 10

<210> 376

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 376

His Thr Ser Arg Leu His Ser

15

<210> 377

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 377

Gln Gln Gly Asn Thr Leu Pro Tyr Thr

15

<210> 378

<211> 18

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 378

Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr

1 5 10 15

Lys Gly

<210> 379

<211> 119

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 379

Gln Val Gln Leu Leu Glu Ser Gly Ala Glu Leu Val Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ala Phe Ser Ser Tyr

20 25 30

Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Gln Ile Tyr Pro Gly Asp Gly Asp Thr Asn Tyr Asn Gly Lys Phe

50 55 60

Lys Gly Gln Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Gly Leu Thr Ser Glu Asp Ser Ala Val Tyr Ser Cys

85 90 95

Ala Arg Lys Thr Ile Ser Ser Val Val Asp Phe Tyr Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr

115

<210> 380

<211> 111

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 380

Glu Leu Val Leu Thr Gln Ser Pro Lys Phe Met Ser Thr Ser Val Gly

1 5 10 15

Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gln Asn Val Gly Thr Asn

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Pro Leu Ile

35 40 45

Tyr Ser Ala Thr Tyr Arg Asn Ser Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Thr Asn Val Gln Ser

65 70 75 80

Lys Asp Leu Ala Asp Tyr Phe Tyr Phe Cys Gln Tyr Asn Arg Tyr Pro

85 90 95

Tyr Thr Ser Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Arg Ser

100 105 110

<210> 381

<211> 248

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 381

Gln Val Gln Leu Leu Glu Ser Gly Ala Glu Leu Val Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ala Phe Ser Ser Tyr

20 25 30

Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Gln Ile Tyr Pro Gly Asp Gly Asp Thr Asn Tyr Asn Gly Lys Phe

50 55 60

Lys Gly Gln Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Gly Leu Thr Ser Glu Asp Ser Ala Val Tyr Ser Cys

85 90 95

Ala Arg Lys Thr Ile Ser Ser Val Val Asp Phe Tyr Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Gly Ser Thr Ser Gly Ser Gly Lys Pro

115 120 125

Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Leu Val Leu Thr Gln Ser

130 135 140

Pro Lys Phe Met Ser Thr Ser Val Gly Asp Arg Val Ser Val Thr Cys

145 150 155 160

Lys Ala Ser Gln Asn Val Gly Thr Asn Val Ala Trp Tyr Gln Gln Lys

165 170 175

Pro Gly Gln Ser Pro Lys Pro Leu Ile Tyr Ser Ala Thr Tyr Arg Asn

180 185 190

Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe

195 200 205

Thr Leu Thr Ile Thr Asn Val Gln Ser Lys Asp Leu Ala Asp Tyr Phe

210 215 220

Tyr Phe Cys Gln Tyr Asn Arg Tyr Pro Tyr Thr Ser Gly Gly Gly Thr

225 230 235 240

Lys Leu Glu Ile Lys Arg Arg Ser

245

<210> 382

<211> 239

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 382

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

115 120 125

Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser

130 135 140

Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser

145 150 155 160

Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

165 170 175

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

180 185 190

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

195 200 205

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr

210 215 220

Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

225 230 235

<210> 383

<211> 717

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 383

gaagtgcaat tggtggaatc agggggagga cttgtgcagc ctggaggatc gctgagactg

60

tcatgtgccg tgtccggctt tgccctgtcc aaccacggga tgtcctgggt ccgccgcgcg

120

cctggaaagg gcctcgaatg ggtgtcgggt attgtgtaca gcggtagcac ctactatgcc

180

gcatccgtga aggggagatt caccatcagc cgggacaact cggaacac tctgtacctc

240

caaatgaatt cgctgaggcc agaggacact gccatctact actgctccgc gcatggcgga

300

gagtccgacg tctggggaca ggggaccacc gtgaccgtgt ctagcgcgtc cggcgggaggc

360

ggcagcgggg gtcgggcatc agggggcggc ggatcggaca tccagctcac ccagtccccg

420

agctcgctgt ccgcctccgt gggagatcgg gtcaccatca cgtgccgcgc cagccagtcg

480

atttcctcct acctgaactg gtaccaacag aagcccggaa aagccccgaa gcttctcatc

540

tacgccgcct cgagcctgca gtcaggagtg ccctcacggt tctccggctc cggttccggt

600

actgatttca ccctgaccat ttcctccctg caaccgggagg acttcgctac ttactactgc

660

cagcagtcgt actccacccc ctacactttc ggacaaggca ccaaggtcga aatcaag

717

<210> 384

<211> 115

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 384

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser

115

<210> 385

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 385

Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 386

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 386

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Gly Trp Val

35 40 45

Ser Gly Ile Ser Arg Ser Gly Glu Asn Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Asp Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ser Pro Ala His Tyr Tyr Gly Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Val Leu Thr Gln Ser

130 135 140

Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

145 150 155 160

Arg Ala Ser Gln Ser Ile Ser Ser Ser Phe Leu Ala Trp Tyr Gln Gln

165 170 175

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Arg Arg

180 185 190

Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Ser Ala Val Tyr

210 215 220

Tyr Cys Gln Gln Tyr His Ser Ser Pro Ser Trp Thr Phe Gly Gln Gly

225 230 235 240

Thr Lys Leu Glu Ile Lys

245

<210> 387

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 387

caagtgcaac tcgtggaatc tggtggagga ctcgtgcaac ccggaagatc gcttagactg

60

tcgtgtgccg ccagcggggtt cactttctcg aactacgcga tgtcctgggt ccgccaggca

120

ccgggaaagg gactcggttg ggtgtccggc atttcccggt ccggcgaaaa tacctactac

180

gccgactccg tgaagggccg cttcaccatc tcaagggaca acagcaaaaa caccctgtac

240

ttgcaaatga actccctgcg ggatgaagat acagccgtgt actattgcgc ccggtcgcct

300

gcccattact acggcggaat ggacgtctgg ggacagggaa ccactgtgac tgtcagcagc

360

gcgtcgggtg gcggcggctc agggggtcgg gcctccgggg ggggagggtc cgacatcgtg

420

ctgacccagt ccccgggaac cctgagcctg agcccgggag agcgcgcgac cctgtcatgc

480

cgggcatccc agagcattag ctcctccttt ctcgcctggt atcagcagaa gcccggacag

540

gccccgaggc tgctgatcta cggcgctagc agaagggcta cgggaatccc agaccggttc

600

tccggctccg gttccgggac cgatttcacc cttactatct cgcgcctgga acctgaggac

660

tccgccgtct actactgcca gcagtaccac tcatccccgt cgtggacgtt cggacagggc

720

accaagctgg agattaag

738

<210> 388

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 388

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Gly Trp Val

35 40 45

Ser Gly Ile Ser Arg Ser Gly Glu Asn Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Asp Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ser Pro Ala His Tyr Tyr Gly Gly Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 389

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 389

Asp Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Ser Ser

20 25 30

Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Ser Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Ser Pro

85 90 95

Ser Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 390

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 390

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ser Val His Ser Phe Leu Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr

100 105 110

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

115 120 125

Gly Gly Gly Ser Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Pro

130 135 140

Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser

145 150 155 160

Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys

165 170 175

Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala

180 185 190

Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

195 200 205

Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr

210 215 220

Cys Met Gln Ala Leu Gln Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys

225 230 235 240

Val Glu Ile Lys

<210> 391

<211> 732

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 391

caagtgcaac tcgtcgaatc cggtggaggt ctggtccaac ctggtagaag cctgagactg

60

tcgtgtgcgg ccagcggatt cacctttgat gactatgcta tgcactgggt gcggcaggcc

120

cgggaaagg gcctggaatg ggtgtcggga attagctgga actccgggtc cattggctac

180

gccgactccg tgaagggccg cttcaccatc tcccgcgaca acgcaaagaa ctccctgtac

240

ttgcaaatga actcgctcag ggctgaggat accgcgctgt actactgctc cgtgcattcc

300

ttcctggcct actggggaca gggaactctg gtcaccgtgt cgagcgcctc cggcggcggg

360

ggctcgggtg gacgggcctc gggcggaggg gggtccgaca tcgtgatgac ccagaccccg

420

ctgagcttgc ccgtgactcc cggagagcct gcatccatct cctgccggtc atcccagtcc

480

cttctccact ccaacggata caactacctc gactggtacc tccagaagcc gggacagagc

540

cctcagcttc tgatctacct ggggtcaaat agagcctcag gagtgccgga tcggttcagc

600

ggatctggtt cgggaactga tttcactctg aagatttccc gcgtggaagc cgaggacgtg

660

ggcgtctact actgtatgca ggcgctgcag accccctata ccttcggcca agggacgaaa

720

gtggagatca ag

732

<210> 392

<211> 115

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 392

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ser Val His Ser Phe Leu Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr

100 105 110

Val Ser Ser

115

<210> 393

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 393

Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 394

<211> 243

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 394

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

115 120 125

Gly Gly Gly Ser Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser

130 135 140

Val Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser

145 150 155 160

Leu Leu Arg Asn Asp Gly Lys Thr Pro Leu Tyr Trp Tyr Leu Gln Lys

165 170 175

Ala Gly Gln Pro Pro Gln Leu Leu Ile Tyr Glu Val Ser Asn Arg Phe

180 185 190

Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

195 200 205

Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Ala Tyr Tyr

210 215 220

Cys Met Gln Asn Ile Gln Phe Pro Ser Phe Gly Gly Gly Thr Lys Leu

225 230 235 240

Glu Ile Lys

<210> 395

<211> 729

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 395

gaagtgcaat tgttggaatc tggaggagga cttgtgcagc ctggaggatc actgagactt

60

tcgtgtgcgg tgtcaggctt cgccctgagc aaccacggca tgagctgggt gcggagagcc

120

ccggggaagg gtctggaatg ggtgtccggg atcgtctact ccggttcaac ttactacgcc

180

gcaagcgtga agggtcgctt caccatttcc cgcgataact cccggaacac cctgtacctc

240

caaatgaact ccctgcggcc cgaggacacc gccatctact actgttccgc gcatggagga

300

gagtccgatg tctggggaca gggcactacc gtgaccgtgt cgagcgcctc ggggggagga

360

ggctccggcg gtcgcgcctc cggggggggt ggcagcgaca ttgtgatgac gcagactcca

420

ctctcgctgt ccgtgacccc gggacagccc gcgtccatct cgtgcaagag ctcccagagc

480

ctgctgagga acgacggaaa gactcctctg tattggtacc tccagaaggc tggacagccc

540

ccgcaactgc tcatctacga agtgtcaaat cgcttctccg gggtgccgga tcggttttcc

600

ggctcgggat cgggcaccga cttcaccctg aaaatctcca gggtcgaggc cgaggacgtg

660

ggagcctact actgcatgca aaacatccag ttcccttcct tcggcggcgg cacaaagctg

720

gagattaag

729

<210> 396

<211> 115

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 396

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser

115

<210> 397

<211> 111

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 397

Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu Arg Asn

20 25 30

Asp Gly Lys Thr Pro Leu Tyr Trp Tyr Leu Gln Lys Ala Gly Gln Pro

35 40 45

Pro Gln Leu Leu Ile Tyr Glu Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Ala Tyr Tyr Cys Met Gln Asn

85 90 95

Ile Gln Phe Pro Ser Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 398

<211> 249

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 398

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Thr Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Asp Asn Phe

20 25 30

Gly Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Lys Asn Asn Asn Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Asn Thr Ala Tyr

65 70 75 80

Met Glu Val Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Pro Tyr Tyr Tyr Gln Ser Tyr Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Thr

130 135 140

Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys

145 150 155 160

Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asn

165 170 175

Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu

180 185 190

Gly Ser Lys Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu His Ile Thr Arg Val Gly Ala Glu Asp

210 215 220

Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr Pro Tyr Thr Phe

225 230 235 240

Gly Gln Gly Thr Lys Leu Glu Ile Lys

245

<210> 399

<211> 747

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 399

caagtccaac tcgtccagtc cggcgcagaa gtcagaaaaa ccggtgctag cgtgaaagtg

60

tcctgcaagg cctccggcta cattttcgat aacttcggaa tcaactgggt cagacaggcc

120

ccggggccagg ggctggaatg gatgggatgg atcaacccca agaacaacaa caccaactac

180

gcacagaagt tccaggggccg cgtgactatc accgccgatg aatcgaccaa taccgcctac

240

atggaggtgt cctccctgcg gtcggaggac actgccgtgt attactgcgc gaggggccca

300

tactactacc aaagctacat ggacgtctgg ggacagggaa ccatggtgac cgtgtcatcc

360

gcctccggtg gtggaggctc cggggggcgg gcttcaggag gcggaggaag cgatattgtg

420

atgacccaga ctccgcttag cctgcccgtg actcctggag aaccggcctc catttcctgc

480

cggtcctcgc aatcactcct gcattccaac ggttacaact acctgaattg gtacctccag

540

aagcctggcc agtcgcccca gttgctgatc tatctgggct cgaagcgcgc ctccggggtg

600

cctgaccggt ttagcggatc tgggagcggc acggacttca ctctccacat cacccgcgtg

660

ggagcggagg acgtgggagt gtactactgt atgcaggcgc tgcagactcc gtacacattc

720

ggacagggca ccaagctggga gatcaag

747

<210> 400

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 400

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Arg Lys Thr Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Asp Asn Phe

20 25 30

Gly Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Lys Asn Asn Asn Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Asn Thr Ala Tyr

65 70 75 80

Met Glu Val Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Pro Tyr Tyr Tyr Gln Ser Tyr Met Asp Val Trp Gly Gln

100 105 110

Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 401

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 401

Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asn Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Lys Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu His Ile

65 70 75 80

Thr Arg Val Gly Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 402

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 402

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Asp

20 25 30

Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Val Ile Ser Gly Ser Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Leu Asp Ser Ser Gly Tyr Tyr Tyr Ala Arg Gly Pro Arg Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln Leu

130 135 140

Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr

145 150 155 160

Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gly Ala Ser

180 185 190

Thr Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr His Phe Thr Leu Thr Ile Asn Ser Leu Gln Ser Glu Asp Ser Ala

210 215 220

Thr Tyr Tyr Cys Gln Gln Ser Tyr Lys Arg Ala Ser Phe Gly Gln Gly

225 230 235 240

Thr Lys Val Glu Ile Lys

245

<210> 403

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 403

caagtgcaac ttcaagaatc aggcggagga ctcgtgcagc ccggaggatc attgcggctc

60

tcgtgcgccg cctcgggctt caccttctcg agcgacgcca tgacctgggt ccgccaggcc

120

ccggggaagg ggctggaatg ggtgtctgtg atttccggct ccgggggaac tacgtactac

180

gccgattccg tgaaaggtcg cttcactatc tcccgggaca acagcaagaa caccctttat

240

ctgcaaatga attccctccg cgccgaggac accgccgtgt actactgcgc caagctggac

300

tcctcgggct actactatgc ccggggtccg agatactggg gacagggaac cctcgtgacc

360

gtgtcctccg cgtccggcgg aggagggtcg ggagggcggg cctccggcgg cggcggttcg

420

gacatccagc tgacccagtc cccatcctca ctgagcgcaa gcgtgggcga cagagtcacc

480

attacatgca gggcgtccca gagcatcagc tcctacctga actggtacca acagaagcct

540

ggaaaggctc ctaagctgtt gatctacggg gcttcgaccc tggcatccgg ggtgcccgcg

600

aggtttagcg gaagcggtag cggcactcac ttcactctga ccattaacag cctccagtcc

660

gaggattcag ccacttacta ctgtcagcag tcctacaagc gggccagctt cggacagggc

720

actaaggtcg agatcaag

738

<210> 404

<211> 123

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 404

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Asp

20 25 30

Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Val Ile Ser Gly Ser Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Leu Asp Ser Ser Gly Tyr Tyr Tyr Ala Arg Gly Pro Arg Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 405

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 405

Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr His Phe Thr Leu Thr Ile Asn Ser Leu Gln Ser

65 70 75 80

Glu Asp Ser Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Lys Arg Ala Ser

85 90 95

Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 406

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 406

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Asn Tyr

20 25 30

Gly Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asn Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Pro Tyr Tyr Tyr Tyr Met Asp Val Trp Gly Lys Gly Thr

100 105 110

Met Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg

115 120 125

Ala Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Leu

130 135 140

Ser Leu Pro Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser

145 150 155 160

Ser Gln Ser Leu Leu Tyr Ser Asn Gly Tyr Asn Tyr Val Asp Trp Tyr

165 170 175

Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu Gly Ser

180 185 190

Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Phe Lys Leu Gln Ile Ser Arg Val Glu Ala Glu Asp Val Gly

210 215 220

Ile Tyr Tyr Cys Met Gln Gly Arg Gln Phe Pro Tyr Ser Phe Gly Gln

225 230 235 240

Gly Thr Lys Val Glu Ile Lys

245

<210> 407

<211> 741

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 407

caagtccaac tggtccagag cggtgcagaa gtgaagaagc ccggagcgag cgtgaaagtg

60

tcctgcaagg cttccgggta caccttctcc aactacggca tcacttgggt gcgccaggcc

120

ccgggacagg gcctggaatg gatggggtgg atttccgcgt acaacggcaa tacgaactac

180

gctcagaagt tccagggtag agtgaccatg actaggaaca cctccatttc caccgcctac

240

atggaactgt cctccctgcg gagcgaggac accgccgtgt actattgcgc ccggggacca

300

tactactact acatggatgt ctgggggaag gggactatgg tcaccgtgtc atccgcctcg

360

ggaggcggcg gatcaggagg acgcgcctct ggtggtggag gatcggagat cgtgatgacc

420

cagagccctc tctccttgcc cgtgactcct ggggagcccg catccatttc atgccggagc

480

tcccagtcac ttctctactc caacggctat aactacgtgg attggtacct ccaaaagccg

540

ggccagagcc cgcagctgct gatctacctg ggctcgaaca gggccagcgg agtgcctgac

600

cggttctccg ggtcgggaag cgggaccgac ttcaagctgc aaatctcgag agtggaggcc

660

gaggacgtgg gaatctacta ctgtatgcag ggccgccagt ttccgtactc gttcggacag

720

ggcaccaaag tggaaatcaa g

741

<210> 408

<211> 118

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 408

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Asn Tyr

20 25 30

Gly Ile Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asn Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Pro Tyr Tyr Tyr Tyr Met Asp Val Trp Gly Lys Gly Thr

100 105 110

Met Val Thr Val Ser Ser

115

<210> 409

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 409

Glu Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu Tyr Ser

20 25 30

Asn Gly Tyr Asn Tyr Val Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Lys Leu Gln Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Ile Tyr Tyr Cys Met Gln Gly

85 90 95

Arg Gln Phe Pro Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 410

<211> 238

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 410

Glu Val Gln Leu Leu Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

115 120 125

Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser

130 135 140

Val Ser Pro Gly Glu Ser Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser

145 150 155 160

Val Ser Ser Asn Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro

165 170 175

Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Ala Ser Gly Ile Pro Asp

180 185 190

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

195 200 205

Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Gly

210 215 220

Ser Ser Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

225 230 235

<210> 411

<211> 714

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 411

gaagtgcaat tgctcgaaac tggaggaggt ctggtgcaac ctggaggatc acttcgcctg

60

tcctgcgccg tgtcgggctt tgccctgtcc aaccatggaa tgagctgggt ccgccgcgcg

120

ccggggaagg gcctcgaatg ggtgtccggc atcgtctact ccggctccac ctactacgcc

180

gcgtccgtga agggccggtt cacgatttca cgggacaact cgcggaacac cctgtacctc

240

caaatgaatt cccttcggcc ggaggatact gccatctact actgctccgc ccacggtggc

300

gaatccgacg tctggggcca gggaaccacc gtgaccgtgt ccagcgcgtc cgggggagga

360

ggaagcgggg gtagagcatc gggtggaggc ggatcagaga tcgtgctgac ccagtccccc

420

gccaccttga gcgtgtcacc aggagagtcc gccaccctgt catgccgcgc cagccagtcc

480

gtgtcctcca acctggcttg gtaccagcag aagccggggc aggcccctag actcctgatc

540

tatggggcgt cgacccgggc atctggaatt cccgataggt tcagcggatc gggctcgggc

600

actgacttca ctctgaccat ctcctcgctg caagccgagg acgtggctgt gtactactgt

660

cagcagtacg gaagctccct gactttcggt ggcgggacca aagtcgagat taag

714

<210> 412

<211> 115

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 412

Glu Val Gln Leu Leu Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser

115

<210> 413

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 413

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Ser Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Ser Gly Ile Pro Asp Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

65 70 75 80

Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Leu Thr

85 90 95

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 414

<211> 239

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 414

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

115 120 125

Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser

130 135 140

Val Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser

145 150 155 160

Val Ser Ser Lys Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro

165 170 175

Arg Leu Leu Met Tyr Gly Ala Ser Ile Arg Ala Thr Gly Ile Pro Asp

180 185 190

Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser

195 200 205

Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly

210 215 220

Ser Ser Ser Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

225 230 235

<210> 415

<211> 717

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 415

gaagtgcaat tggtggaaac tggaggagga cttgtgcaac ctggaggatc attgagactg

60

agctgcgcag tgtcgggatt cgccctgagc aaccatggaa tgtcctgggt cagaagggcc

120

cctggaaaag gcctcgaatg ggtgtcaggg atcgtgtact ccggttccac ttactacgcc

180

gcctccgtga aggggcgctt cactatctca cgggataact cccgcaatac cctgtacctc

240

caaatgaaca gcctgcggcc ggaggatacc gccatctact actgttccgc ccacggtgga

300

gagtctgacg tctggggcca gggaactacc gtgaccgtgt cctccgcgtc cggcggtgga

360

gggagcggcg gccgcgccag cggcggcgga ggctccgaga tcgtgatgac ccagagcccc

420

gctactctgt cggtgtcgcc cggagaaagg gcgaccctgt cctgccgggc gtcgcagtcc

480

gtgagcagca agctggcttg gtaccagcag aagccgggcc aggcaccacg cctgcttatg

540

tacggtgcct ccattcgggc caccggaatc ccggaccggt tctcggggtc ggggtccggt

600

accgagttca cactgaccat ttcctcgctc gagcccgagg actttgccgt ctattactgc

660

cagcagtacg gctcctcctc atggacgttc ggccagggga ccaaggtcga aatcaag

717

<210> 416

<211> 115

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 416

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser

115

<210> 417

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 417

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Lys

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Met

35 40 45

Tyr Gly Ala Ser Ile Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Ser Ser Trp

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 418

<211> 241

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 418

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Val Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

115 120 125

Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser

130 135 140

Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser

145 150 155 160

Val Gly Ser Thr Asn Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala

165 170 175

Pro Arg Leu Leu Ile Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro

180 185 190

Asp Arg Phe Ser Gly Gly Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

195 200 205

Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr

210 215 220

Gly Ser Ser Pro Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

Lys

<210> 419

<211> 723

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 419

gaagtgcaat tggtggagac tggaggagga gtggtgcaac ctggaggaag cctgagactg

60

tcatgcgcgg tgtcgggctt cgccctctcc aaccacggaa tgtcctgggt ccgccggggcc

120

cctgggaaag gacttgaatg ggtgtccggc atcgtgtact cgggttccac ctactacgcg

180

gcctcagtga agggccggtt tactattagc cgcgacaact ccagaaacac actgtacctc

240

caaatgaact cgctgcggcc ggaagatacc gctatctact actgctccgc ccatggggga

300

gagtcggacg tctggggaca gggcaccact gtcactgtgt ccagcgcttc cggcggtggt

360

ggaagcgggg gacgggcctc aggaggcggt ggcagcgaga ttgtgctgac ccagtccccc

420

gggaccctga gcctgtcccc gggagaaagg gccaccctct cctgtcgggc atcccagtcc

480

gtggggtcta ctaaccttgc atggtaccag cagaagcccg gccaggcccc tcgcctgctg

540

atctacgacg cgtccaatag agccaccggc atcccggatc gcttcagcgg aggcggatcg

600

ggcaccgact tcaccctcac catttcaagg ctggaaccgg aggacttcgc cgtgtactac

660

tgccagcagt atggttcgtc cccaccctgg acgttcggcc aggggactaa ggtcgagatc

720

aag

723

<210> 420

<211> 115

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 420

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Val Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser

115

<210> 421

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 421

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Thr

20 25 30

Asn Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Gly Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 422

<211> 239

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 422

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr

20 25 30

Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Asp Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala

115 120 125

Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser

130 135 140

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

145 150 155 160

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

165 170 175

Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val

180 185 190

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

210 215 220

Ser Tyr Thr Leu Ala Phe Gly Gln Gly Thr Lys Val Asp Ile Lys

225 230 235

<210> 423

<211> 717

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 423

caagtgcaac tcgtggaatc tggtggagga ctcgtgaaac ctggaggatc attgagactg

60

tcatgcgcgg cctcgggatt cacgttctcc gattactaca tgagctggat tcgccaggct

120

ccggggaagg gactggaatg ggtgtcctac atttcctcat ccggctccac catctactac

180

gcggactccg tgaaggggag attcaccatt agccgcgata acgccaagaa cagcctgtac

240

cttcagatga actccctgcg ggctgaagat actgccgtct actactgcgc aagggagagc

300

ggagatggga tggacgtctg gggacagggt accactgtga ccgtgtcgtc ggcctccggc

360

ggagggggtt cgggtggaag ggccagcggc ggcggaggca gcgacatcca gatgacccag

420

tccccctcat cgctgtccgc ctccgtgggc gaccgcgtca ccatcacatg ccgggcctca

480

cagtcgatct cctcctacct caattggtat cagcagaagc cgggaaaggc ccctaagctt

540

ctgatctacg cagcgtcctc cctgcaatcc ggggtcccat ctcggttctc cggctcggggc

600

agcggtaccg acttcactct gaccatctcg agcctgcagc cggaggactt cgccacttac

660

tactgtcagc aaagctacac cctcgcgttt ggccagggca ccaaagtgga catcaag

717

<210> 424

<211> 117

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 424

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr

20 25 30

Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ser Gly Asp Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 425

<211> 105

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 425

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Thr Leu Ala Phe

85 90 95

Gly Gln Gly Thr Lys Val Asp Ile Lys

100 105

<210> 426

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 426

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr

20 25 30

Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Asn Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ser Thr Met Val Arg Glu Asp Tyr Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala

115 120 125

Ser Gly Gly Gly Gly Ser Asp Ile Val Leu Thr Gln Ser Pro Leu Ser

130 135 140

Leu Pro Val Thr Leu Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser

145 150 155 160

Glu Ser Leu Val His Asn Ser Gly Lys Thr Tyr Leu Asn Trp Phe His

165 170 175

Gln Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile Tyr Glu Val Ser Asn

180 185 190

Arg Asp Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr

195 200 205

Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val

210 215 220

Tyr Tyr Cys Met Gln Gly Thr His Trp Pro Gly Thr Phe Gly Gln Gly

225 230 235 240

Thr Lys Leu Glu Ile Lys

245

<210> 427

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 427

caagtgcaac tggtgcaaag cggaggagga ttggtcaaac ccggaggaag cctgagactg

60

tcatgcgcgg cctctggatt caccttctcc gattactaca tgtcatggat cagacaggcc

120

ccggggaagg gcctcgaatg ggtgtcctac atctcgtcct ccgggaacac catctactac

180

gccgacagcg tgaagggccg ctttaccatt tcccgcgaca acgcaaagaa ctcgctgtac

240

cttcagatga attccctgcg ggctgaagat accgcggtgt actattgcgc ccggtccact

300

atggtccggg aggactactg gggacagggc acactcgtga ccgtgtccag cgcgagcggg

360

ggtggaggca gcggtggacg cgcctccggc ggcggcggtt cagacatcgt gctgactcag

420

tcgcccctgt cgctgccggt caccctgggc caaccggcct caattagctg caagtcctcg

480

gagagcctgg tgcacaactc aggaaagact tacctgaact ggttccatca gcggcctgga

540

cagtccccac ggaggctcat ctatgaagtg tccaacaggg attcgggggt gcccgaccgc

600

ttcactggct ccgggtccgg caccgacttc accttgaaaa tctccagagt ggaagccgag

660

gacgtgggcg tgtactactg tatgcagggt acccactggc ctggaacctt tggacaagga

720

actaagctcg agattaag

738

<210> 428

<211> 117

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 428

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr

20 25 30

Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Asn Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ser Thr Met Val Arg Glu Asp Tyr Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser

115

<210> 429

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 429

Asp Ile Val Leu Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Glu Ser Leu Val His Asn

20 25 30

Ser Gly Lys Thr Tyr Leu Asn Trp Phe His Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Tyr Glu Val Ser Asn Arg Asp Ser Gly Val Pro

50 55 60

Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly

85 90 95

Thr His Trp Pro Gly Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 430

<211> 239

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 430

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

115 120 125

Gly Gly Gly Ser Asp Ile Arg Leu Thr Gln Ser Pro Ser Pro Leu Ser

130 135 140

Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Glu Asp

145 150 155 160

Ile Asn Lys Phe Leu Asn Trp Tyr His Gln Thr Pro Gly Lys Ala Pro

165 170 175

Lys Leu Leu Ile Tyr Asp Ala Ser Thr Leu Gln Thr Gly Val Pro Ser

180 185 190

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn

195 200 205

Ser Leu Gln Pro Glu Asp Ile Gly Thr Tyr Tyr Cys Gln Gln Tyr Glu

210 215 220

Ser Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

225 230 235

<210> 431

<211> 717

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 431

caagtgcaac tcgtggaatc tggtggagga ctcgtgcaac ccggtggaag ccttaggctg

60

tcgtgcgccg tcagcggggtt tgctctgagc aaccatggaa tgtcctgggt ccgccggggca

120

ccgggaaaag ggctggaatg ggtgtccggc atcgtgtaca gcgggtcaac ctattacgcc

180

gcgtccgtga agggcagatt cactatctca agagacaaca gccggaacac cctgtacttg

240

caaatgaatt ccctgcgccc cgaggacacc gccatctact actgctccgc ccacggagga

300

gagtcggacg tgtggggcca gggaacgact gtgactgtgt ccagcgcatc aggagggggt

360

ggttcgggcg gccgggcctc ggggggagga ggttccgaca ttcggctgac ccagtccccg

420

tccccactgt cggcctccgt cggcgaccgc gtgaccatca cttgtcaggc gtccgaggac

480

attaacaagt tcctgaactg gtaccaccag acccctggaa aggcccccaa gctgctgatc

540

tacgatgcct cgacccttca aactggagtg cctagccggt tctccggggtc cggctccggc

600

actgatttca ctctgaccat caactcattg cagccggaag atatcgggac ctactattgc

660

cagcagtacg aatccctccc gctcacattc ggcgggggaa ccaaggtcga gattaag

717

<210> 432

<211> 115

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 432

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser

115

<210> 433

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 433

Asp Ile Arg Leu Thr Gln Ser Pro Ser Pro Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Glu Asp Ile Asn Lys Phe

20 25 30

Leu Asn Trp Tyr His Gln Thr Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Thr Leu Gln Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Ser Leu Gln Pro

65 70 75 80

Glu Asp Ile Gly Thr Tyr Tyr Cys Gln Gln Tyr Glu Ser Leu Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 434

<211> 240

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 434

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

115 120 125

Gly Gly Gly Ser Glu Thr Thr Leu Thr Gln Ser Pro Ala Thr Leu Ser

130 135 140

Val Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser

145 150 155 160

Val Gly Ser Asn Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Gly Pro

165 170 175

Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala

180 185 190

Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser

195 200 205

Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asn

210 215 220

Asp Trp Leu Pro Val Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

225 230 235 240

<210> 435

<211> 720

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 435

gaagtgcaat tggtggaaac tggaggagga cttgtgcaac ctggaggatc attgcggctc

60

tcatgcgctg tctccggctt cgccctgtca aatcacggga tgtcgtgggt cagacgggcc

120

ccgggaaagg gtctggaatg ggtgtcgggg attgtgtaca gcggctccac ctactacgcc

180

gcttcggtca agggccgctt cactatttca cgggacaaca gccgcaacac cctctatctg

240

caaatgaact ctctccgccc ggaggatacc gccatctact actgctccgc acacggcggc

300

gaatccgacg tgtggggaca gggaaccact gtcaccgtgt cgtccgcatc cggtggcgga

360

ggatcgggtg gccggggcctc cggggggcggc ggcagcgaga ctaccctgac ccagtcccct

420

gccactctgt ccgtgagccc gggagagaga gccaccctta gctgccgggc cagccagagc

480

gtgggctcca acctggcctg gtaccagcag aagccaggac agggtcccag gctgctgatc

540

tacggagcct ccactcgcgc gaccggcatc cccgcgaggt tctccgggtc gggttccggg

600

accgagttca ccctgaccat ctcctccctc caaccgggagg acttcgcggt gtactactgt

660

cagcagtaca acgattggct gcccgtgaca tttggacagg ggacgaaggt ggaaatcaaa

720

<210> 436

<211> 115

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 436

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser

115

<210> 437

<211> 108

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 437

Glu Thr Thr Leu Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Asn

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Gly Pro Arg Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asn Asp Trp Leu Pro

85 90 95

Val Thr Phe Gly Glyn Gly Thr Lys Val Glu Ile Lys

100 105

<210> 438

<211> 241

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 438

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly

115 120 125

Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser

130 135 140

Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser

145 150 155 160

Ile Gly Ser Ser Ser Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala

165 170 175

Pro Arg Leu Leu Met Tyr Gly Ala Ser Ser Arg Ala Ser Gly Ile Pro

180 185 190

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

195 200 205

Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr

210 215 220

Ala Gly Ser Pro Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

225 230 235 240

Lys

<210> 439

<211> 723

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 439

gaagtgcaat tggtggaatc tggtggagga cttgtgcaac ctggaggatc actgagactg

60

tcatgcgcgg tgtccggttt tgccctgagc aatcatggga tgtcgtgggt ccggcgcgcc

120

ccgggaaagg gtctggaatg ggtgtcgggt atcgtctact ccgggagcac ttactacgcc

180

gcgagcgtga agggccgctt caccatttcc cgcgataact cccgcaacac cctgtacttg

240

caaatgaact cgctccggcc tgaggacact gccatctact actgctccgc acacggagga

300

gaatccgacg tgtggggcca gggaactacc gtgaccgtca gcagcgcctc cggcggcggg

360

ggctcaggcg gacgggctag cggcggcggt ggctccgaga tcgtgctgac ccagtcgcct

420

ggcactctct cgctgagccc cggggaaagg gcaaccctgt cctgtcgggc cagccagtcc

480

attggatcat cctccctcgc ctggtatcag cagaaaccgg gacaggctcc gcggctgctt

540

atgtatgggg ccagctcaag agcctccggc attcccgacc ggttctccgg gtccggttcc

600

ggcaccgatt tcaccctgac tatctcgagg ctggagccag aggacttcgc cgtgtactac

660

tgccagcagt acgcggggtc cccgccgttc acgttcggac agggaaccaa ggtcgagatc

720

aag

723

<210> 440

<211> 115

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 440

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His

20 25 30

Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser

85 90 95

Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105 110

Val Ser Ser

115

<210> 441

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 441

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Gly Ser Ser

20 25 30

Ser Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Met Tyr Gly Ala Ser Ser Arg Ala Ser Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Ala Gly Ser Pro

85 90 95

Pro Phe Thr Phe Gly Glyn Gly Thr Lys Val Glu Ile Lys

100 105

<210> 442

<211> 243

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 442

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser

20 25 30

Tyr Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Ala Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg His Trp Gln Glu Trp Pro Asp Ala Phe Asp Ile Trp Gly

100 105 110

Gly Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Glu Thr Thr Leu Thr Gln Ser Pro

130 135 140

Ala Phe Met Ser Ala Thr Pro Gly Asp Lys Val Ile Ile Ser Cys Lys

145 150 155 160

Ala Ser Gln Asp Ile Asp Asp Ala Met Asn Trp Tyr Gln Gln Lys Pro

165 170 175

Gly Glu Ala Pro Leu Phe Ile Ile Gln Ser Ala Thr Ser Pro Val Pro

180 185 190

Gly Ile Pro Pro Arg Phe Ser Gly Ser Gly Phe Gly Thr Asp Phe Ser

195 200 205

Leu Thr Ile Asn Asn Ile Glu Ser Glu Asp Ala Ala Tyr Tyr Phe Cys

210 215 220

Leu Gln His Asp Asn Phe Pro Leu Thr Phe Gly Gln Gly Thr Lys Leu

225 230 235 240

Glu Ile Lys

<210> 443

<211> 729

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 443

caagtgcagc ttcaggaaag cggaccgggc ctggtcaagc catccgaaac tctctccctg

60

acttgcactg tgtctggcgg ttccatctca tcgtcgtact actactgggg ctggattagg

120

cagccgcccg gaaagggact ggagtggatc ggaagcatct actattccgg ctcggcgtac

180

tacaacccta gcctcaagtc gagagtgacc atctccgtgg atacctccaa gaaccagttt

240

tccctgcgcc tgagctccgt gaccgccgct gacaccgccg tgtactactg tgctcggcat

300

tggcaggaat ggcccgatgc cttcgacatt tggggccagg gcactatggt cactgtgtca

360

tccggggggtg gaggcagcgg gggaggaggg tccgggggggg gaggttcaga gacaaccttg

420

acccagtcac ccgcattcat gtccgccact ccgggagaca aggtcatcat ctcgtgcaaa

480

gcgtcccagg atatcgacga tgccatgaat tggtaccagc agaagcctgg cgaagcgccg

540

ctgttcatta tccaatccgc aacctcgccc gtgcctggaa tcccaccgcg gttcagcggc

600

agcggtttcg gaaccgactt ttccctgacc attaacaaca ttgagtccga ggacgccgcc

660

tactacttct gcctgcaaca cgacaacttc cctctcacgt tcggccaggg aaccaagctg

720

gaaatcaag

729

<210> 444

<211> 121

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 444

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser

20 25 30

Tyr Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Ala Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg His Trp Gln Glu Trp Pro Asp Ala Phe Asp Ile Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 445

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 445

Glu Thr Thr Leu Thr Gln Ser Pro Ala Phe Met Ser Ala Thr Pro Gly

1 5 10 15

Asp Lys Val Ile Ile Ser Cys Lys Ala Ser Gln Asp Ile Asp Asp Ala

20 25 30

Met Asn Trp Tyr Gln Gln Lys Pro Gly Glu Ala Pro Leu Phe Ile Ile

35 40 45

Gln Ser Ala Thr Ser Pro Val Pro Gly Ile Pro Pro Arg Phe Ser Gly

50 55 60

Ser Gly Phe Gly Thr Asp Phe Ser Leu Thr Ile Asn Asn Ile Glu Ser

65 70 75 80

Glu Asp Ala Ala Tyr Tyr Phe Cys Leu Gln His Asp Asn Phe Pro Leu

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 446

<211> 245

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 446

Gln Val Asn Leu Arg Glu Ser Gly Pro Ala Leu Val Lys Pro Thr Gln

1 5 10 15

Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Arg Thr Ser

20 25 30

Gly Met Cys Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Ala Leu Glu

35 40 45

Trp Leu Ala Arg Ile Asp Trp Asp Glu Asp Lys Phe Tyr Ser Thr Ser

50 55 60

Leu Lys Thr Arg Leu Thr Ile Ser Lys Asp Thr Ser Asp Asn Gln Val

65 70 75 80

Val Leu Arg Met Thr Asn Met Asp Pro Ala Asp Thr Ala Thr Tyr Tyr

85 90 95

Cys Ala Arg Ser Gly Ala Gly Gly Thr Ser Ala Thr Ala Phe Asp Ile

100 105 110

Trp Gly Pro Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln

130 135 140

Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr

145 150 155 160

Cys Arg Ala Ser Gln Asp Ile Tyr Asn Asn Leu Ala Trp Phe Gln Leu

165 170 175

Lys Pro Gly Ser Ala Pro Arg Ser Leu Met Tyr Ala Ala Asn Lys Ser

180 185 190

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Ala Ser Gly Thr Asp

195 200 205

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr

210 215 220

Tyr Cys Gln His Tyr Tyr Arg Phe Pro Tyr Ser Phe Gly Gln Gly Thr

225 230 235 240

Lys Leu Glu Ile Lys

245

<210> 447

<211> 735

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 447

caagtcaatc tgcgcgaatc cggccccgcc ttggtcaagc ctacccagac cctcactctg

60

acctgtactt tctccggctt ctccctgcgg acttccggga tgtgcgtgtc ctggatcaga

120

cagcctccgg gaaaggccct ggagtggctc gctcgcattg actgggatga ggacaagttc

180

tactccacct cactcaagac caggctgacc atcagcaaag atacctctga caaccaagtg

240

gtgctccgca tgaccaacat ggacccagcc gacactgcca cttactactg cgcgaggagc

300

ggagcgggcg gaacctccgc caccgccttc gatatttggg gcccgggtac catggtcacc

360

gtgtcaagcg gaggaggggg gtccggggggc ggcggttccg ggggaggcgg atcggacatt

420

cagatgactc agtcaccatc gtccctgagc gctagcgtgg gcgacagagt gacaatcact

480

tgccgggcat cccaggacat ctataacaac cttgcgtggt tccagctgaa gcctggttcc

540

gcaccgcggt cacttatgta cgccgccaac aagagccagt cgggagtgcc gtcccggttt

600

tccggttcgg ccctcgggaac tgacttcacc ctgacgatct ccagcctgca acccgaggat

660

ttcgccacct actactgcca gcactactac cgctttccct actcgttcgg acagggaacc

720

aagctggaaa tcaag

735

<210> 448

<211> 123

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 448

Gln Val Asn Leu Arg Glu Ser Gly Pro Ala Leu Val Lys Pro Thr Gln

1 5 10 15

Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Arg Thr Ser

20 25 30

Gly Met Cys Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Ala Leu Glu

35 40 45

Trp Leu Ala Arg Ile Asp Trp Asp Glu Asp Lys Phe Tyr Ser Thr Ser

50 55 60

Leu Lys Thr Arg Leu Thr Ile Ser Lys Asp Thr Ser Asp Asn Gln Val

65 70 75 80

Val Leu Arg Met Thr Asn Met Asp Pro Ala Asp Thr Ala Thr Tyr Tyr

85 90 95

Cys Ala Arg Ser Gly Ala Gly Gly Thr Ser Ala Thr Ala Phe Asp Ile

100 105 110

Trp Gly Pro Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 449

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 449

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Tyr Asn Asn

20 25 30

Leu Ala Trp Phe Gln Leu Lys Pro Gly Ser Ala Pro Arg Ser Leu Met

35 40 45

Tyr Ala Ala Asn Lys Ser Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Ala Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His Tyr Tyr Arg Phe Pro Tyr

85 90 95

Ser Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 450

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 450

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Ser Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Thr Ile Ala Ala Val Tyr Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Leu Ser

130 135 140

Leu Pro Val Thr Pro Glu Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser

145 150 155 160

Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu

165 170 175

Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn

180 185 190

Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr

195 200 205

Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val

210 215 220

Tyr Tyr Cys Met Gln Ala Leu Gln Thr Pro Tyr Thr Phe Gly Gln Gly

225 230 235 240

Thr Lys Leu Glu Ile Lys

245

<210> 451

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 451

gaagtgcagc ttgtcgaatc cgggggggga ctggtcaagc cgggcggatc actgagactg

60

tcctgcgccg cgagcggctt cacgttctcc tcctactcca tgaactgggt ccgccaagcc

120

cccgggaagg gactggaatg ggtgtcctct atctcctcgt cgtcgtccta catctactac

180

gccgactccg tgaagggaag attcaccatt tcccgcgaca acgcaaagaa ctcactgtac

240

ttgcaaatga actcactccg ggccgaagat actgctgtgt actattgcgc caagactatt

300

gccgccgtct acgctttcga catctggggc cagggaacca ccgtgactgt gtcgtccggt

360

ggtggtggct cgggcgggagg aggaagcggc ggcggggggt ccgagattgt gctgacccag

420

tcgccactga gcctccctgt gacccccgag gaacccgcca gcatcagctg ccggtccagc

480

cagtccctgc tccactccaa cggatacaat tacctcgatt ggtaccttca gaagcctgga

540

caaagcccgc agctgctcat ctacttggga tcaaaccgcg cgtcaggagt gcctgaccgg

600

ttctccggct cgggcagcgg taccgatttc accctgaaaa tctccagggt ggaggcagag

660

gacgtgggag tgtattactg tatgcaggcg ctgcagactc cgtacacatt tgggcagggc

720

accaagctgg agatcaag

738

<210> 452

<211> 119

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 452

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Ser Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Thr Ile Ala Ala Val Tyr Ala Phe Asp Ile Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser

115

<210> 453

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 453

Glu Ile Val Leu Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Glu

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 454

<211> 240

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 454

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr

20 25 30

Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Leu Arg Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr Met

100 105 110

Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Ser Tyr Val Leu Thr Gln Ser Pro Ser Val Ser Ala

130 135 140

Ala Pro Gly Tyr Thr Ala Thr Ile Ser Cys Gly Gly Asn Asn Ile Gly

145 150 155 160

Thr Lys Ser Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Leu

165 170 175

Leu Val Ile Arg Asp Asp Ser Val Arg Pro Ser Lys Ile Pro Gly Arg

180 185 190

Phe Ser Gly Ser Asn Ser Gly Asn Met Ala Thr Leu Thr Ile Ser Gly

195 200 205

Val Gln Ala Gly Asp Glu Ala Asp Phe Tyr Cys Gln Val Trp Asp Ser

210 215 220

Asp Ser Glu His Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

225 230 235 240

<210> 455

<211> 720

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 455

gaagtccagc tcgtggagtc cggcggaggc cttgtgaagc ctggaggttc gctgagactg

60

tcctgcgccg cctccggctt caccttctcc gactactaca tgtcctggat cagacaggcc

120

ccgggaaagg gcctggaatg ggtgtcctac atctcgtcat cgggcagcac tatctactac

180

gcggactcag tgaaggggcg gttcaccatt tcccgggata acgcgaagaa ctcgctgtat

240

ctgcaaatga actcactgag ggccgaggac accgccgtgt actactgcgc ccgcgatctc

300

cgcggggcat ttgacatctg gggacaggga accatggtca cagtgtccag cggaggggga

360

ggatcgggtg gcggaggttc cggggggtgga ggctcctcct acgtgctgac tcagagccca

420

agcgtcagcg ctgcgcccgg ttacacggca accatctcct gtggcggaaa caacattggg

480

accaagtctg tgcactggta tcagcagaag ccgggccaag ctcccctgtt ggtgatccgc

540

gatgactccg tgcggcctag caaaattccg ggacggttct ccggctccaa cagcggcaat

600

atggccactc tcaccatctc gggagtgcag gccggagatg aagccgactt ctactgccaa

660

gtctgggact cagactccga gcatgtggtg ttcgggggcg gaaccaagct gactgtgctc

720

<210> 456

<211> 117

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 456

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr

20 25 30

Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Leu Arg Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr Met

100 105 110

Val Thr Val Ser Ser

115

<210> 457

<211> 108

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 457

Ser Tyr Val Leu Thr Gln Ser Pro Ser Val Ser Ala Ala Pro Gly Tyr

1 5 10 15

Thr Ala Thr Ile Ser Cys Gly Gly Asn Asn Ile Gly Thr Lys Ser Val

20 25 30

His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Leu Leu Val Ile Arg

35 40 45

Asp Asp Ser Val Arg Pro Ser Lys Ile Pro Gly Arg Phe Ser Gly Ser

50 55 60

Asn Ser Gly Asn Met Ala Thr Leu Thr Ile Ser Gly Val Gln Ala Gly

65 70 75 80

Asp Glu Ala Asp Phe Tyr Cys Gln Val Trp Asp Ser Asp Ser Glu His

85 90 95

Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 458

<211> 241

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 458

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Pro Ser Gly Tyr Thr Val Thr Ser His

20 25 30

Tyr Ile His Trp Val Arg Arg Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asn Pro Ser Gly Val Thr Ala Tyr Ser Gln Thr Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Ser Asp Thr Ser Ser Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Ser Gly Ser Gly Trp Tyr Phe Asp Phe Trp Gly Arg

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Ser Tyr Val Leu Thr Gln Pro Pro Ser

130 135 140

Val Ser Val Ser Pro Gly Gln Thr Ala Ser Ile Thr Cys Ser Gly Asp

145 150 155 160

Gly Leu Ser Lys Lys Tyr Val Ser Trp Tyr Gln Gln Lys Ala Gly Gln

165 170 175

Ser Pro Val Val Leu Ile Ser Arg Asp Lys Glu Arg Pro Ser Gly Ile

180 185 190

Pro Asp Arg Phe Ser Gly Ser Asn Ser Ala Asp Thr Ala Thr Leu Thr

195 200 205

Ile Ser Gly Thr Gln Ala Met Asp Glu Ala Asp Tyr Tyr Cys Gln Ala

210 215 220

Trp Asp Asp Thr Thr Val Val Phe Gly Gly Gly Thr Lys Leu Thr Val

225 230 235 240

Leu

<210> 459

<211> 723

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 459

caagtgcagc tggtgcagag cggggccgaa gtcaagaagc cgggagcctc cgtgaaagtg

60

tcctgcaagc cttcgggata caccgtgacc tcccactaca ttcattgggt ccgccgcgcc

120

cccggccaag gactcgagtg gatgggcatg atcaacccta gcggcggagt gaccgcgtac

180

agccagacgc tgcagggacg cgtgactatg acctcggata cctcctcctc caccgtctat

240

atggaactgt ccagcctgcg gtccgaggat accgccatgt actactgcgc ccgggaagga

300

tcaggctccg ggtggtattt cgacttctgg ggaagaggca ccctcgtgac tgtgtcatct

360

gggggagggg gttccggtgg tggcggatcg ggaggaggcg gttcatccta cgtgctgacc

420

cagccaccct ccgtgtccgt gagccccggc cagactgcat cgattacatg tagcggcgac

480

ggcctctcca agaaatacgt gtcgtggtac cagcagaagg ccggacagag cccggtggtg

540

ctgatctcaa gagataagga gcggcctagc ggaatcccgg acaggttctc gggttccaac

600

tccgcggaca ctgctactct gaccatctcg gggacccagg ctatggacga agccgattac

660

tactgccaag cctgggacga cactactgtc gtgtttggag ggggcaccaa gttgaccgtc

720

ctt

723

<210> 460

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 460

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Pro Ser Gly Tyr Thr Val Thr Ser His

20 25 30

Tyr Ile His Trp Val Arg Arg Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Met Ile Asn Pro Ser Gly Val Thr Ala Tyr Ser Gln Thr Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Ser Asp Thr Ser Ser Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Ser Gly Ser Gly Trp Tyr Phe Asp Phe Trp Gly Arg

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 461

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 461

Ser Tyr Val Leu Thr Gln Pro Ser Val Ser Val Ser Pro Gly Gln

1 5 10 15

Thr Ala Ser Ile Thr Cys Ser Gly Asp Gly Leu Ser Lys Lys Tyr Val

20 25 30

Ser Trp Tyr Gln Gln Lys Ala Gly Gln Ser Pro Val Val Leu Ile Ser

35 40 45

Arg Asp Lys Glu Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Asn Ser Ala Asp Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Gln Ala Trp Asp Asp Thr Thr Val Val

85 90 95

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105

<210> 462

<211> 245

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 462

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg Ala Gly Ile Ala Ala Arg Leu Arg Gly Ala Phe Asp Ile

100 105 110

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln

130 135 140

Ser Pro Ser Ser Val Ser Ala Ser Val Gly Asp Arg Val Ile Ile Thr

145 150 155 160

Cys Arg Ala Ser Gln Gly Ile Arg Asn Trp Leu Ala Trp Tyr Gln Gln

165 170 175

Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile Tyr Ala Ala Ser Asn Leu

180 185 190

Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Ala Asp

195 200 205

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Ala Thr Tyr

210 215 220

Tyr Cys Gln Lys Tyr Asn Ser Ala Pro Phe Thr Phe Gly Pro Gly Thr

225 230 235 240

Lys Val Asp Ile Lys

245

<210> 463

<211> 735

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 463

caagtgcagc ttcaggagag cggcccggga ctcgtgaagc cgtcccagac cctgtccctg

60

acttgcaccg tgtcgggagg aagcatctcg agcggaggct actattggtc gtggattcgg

120

cagcaccctg gaaagggcct ggaatggatc ggctacatct actactccgg ctcgacctac

180

tacaacccat cgctgaagtc cagagtgaca atctcagtgg acacgtccaa gaatcagttc

240

agcctgaagc tctcttccgt gactgcggcc gacaccgccg tgtactactg cgcacgcgct

300

ggaattgccg cccggctgag gggtgccttc gacatttggg gacaggggcac catggtcacc

360

gtgtcctccg gcggcggagg ttccgggggt ggaggctcag gaggaggggg gtccgacatc

420

gtcatgactc agtcgccctc aagcgtcagc gcgtccgtcg gggacagagt gatcatcacc

480

tgtcgggcgt cccagggaat tcgcaactgg ctggcctggt atcagcagaa gccgggaaag

540

gcccccaacc tgttgatcta cgccgcctca aacctccaat ccggggtgcc gagccgcttc

600

agcggctccg gttcgggtgc cgatttcact ctgaccatct cctccctgca acctgaagat

660

gtggctacct actactgcca aaagtacaac tccgcacctt ttactttcgg accggggacc

720

aaagtggaca ttaag

735

<210> 464

<211> 123

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 464

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg Ala Gly Ile Ala Ala Arg Leu Arg Gly Ala Phe Asp Ile

100 105 110

Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 465

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 465

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Ile Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Ala Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Val Ala Thr Tyr Tyr Cys Gln Lys Tyr Asn Ser Ala Pro Phe

85 90 95

Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 466

<211> 253

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 466

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Gly Gly Tyr Gln Leu Leu Arg Trp Asp Val Gly Leu Leu

100 105 110

Arg Ser Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser

115 120 125

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

130 135 140

Ser Tyr Val Leu Thr Gln Pro Ser Val Ser Val Ala Pro Gly Gln

145 150 155 160

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val

165 170 175

His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Leu Tyr

180 185 190

Gly Lys Asn Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser

195 200 205

Arg Ser Gly Thr Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

210 215 220

Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Arg Asp Ser Ser Gly Asp His

225 230 235 240

Leu Arg Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu

245 250

<210> 467

<211> 759

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 467

caagtgcagc tggtccagtc gggcgccgag gtcaagaagc ccgggagctc tgtgaaagtg

60

tcctgcaagg cctccggggg cacctttagc tcctacgcca tctcctgggt ccgccaagca

120

ccgggtcaag gcctggagtg gatgggggga attatcccta tcttcggcac tgccaactac

180

gcccagaagt tccagggacg cgtgaccatt accgcggacg aatccacctc caccgcttat

240

atggagctgt ccagcttgcg ctcggaagat accgccgtgt actactgcgc ccggaggggt

300

ggataccagc tgctgagatg ggacgtgggc ctcctgcggt cggcgttcga catctggggc

360

cagggcacta tggtcactgt gtccagcgga ggaggcggat cgggaggcgg cggatcaggg

420

ggaggcggtt ccagctacgt gcttactcaa cccccttcgg tgtccgtggc cccgggacag

480

accgccagaa tcacttgcgg aggaaacaac attgggtcca agagcgtgca ttggtaccag

540

cagaagccag gacaggcccc tgtgctggtg ctctacggga agaacaatcg gcccagcggga

600

gtgccggaca ggttctcggg ttcacgctcc ggtacaaccg cttcactgac tatcaccggg

660

gcccaggcag aggatgaagc ggactactac tgttcctccc gggattcatc cggcgaccac

720

ctccgggtgt tcggaaccgg aacgaaggtc accgtgctg

759

<210> 468

<211> 129

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 468

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Gly Gly Tyr Gln Leu Leu Arg Trp Asp Val Gly Leu Leu

100 105 110

Arg Ser Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser

115 120 125

Ser

<210> 469

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 469

Ser Tyr Val Leu Thr Gln Pro Ser Val Ser Val Ala Pro Gly Gln

1 5 10 15

Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile Gly Ser Lys Ser Val

20 25 30

His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Leu Tyr

35 40 45

Gly Lys Asn Asn Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser

50 55 60

Arg Ser Gly Thr Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Arg Asp Ser Ser Gly Asp His

85 90 95

Leu Arg Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu

100 105

<210> 470

<211> 248

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 470

Glu Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn

20 25 30

Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu

35 40 45

Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp Tyr Ser Phe Tyr Ala

50 55 60

Ile Ser Leu Lys Ser Arg Ile Ile Ile Asn Pro Asp Thr Ser Lys Asn

65 70 75 80

Gln Phe Ser Leu Gln Leu Lys Ser Val Thr Pro Glu Asp Thr Ala Val

85 90 95

Tyr Tyr Cys Ala Arg Ser Ser Pro Glu Gly Leu Phe Leu Tyr Trp Phe

100 105 110

Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Asp

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Ser Glu Leu

130 135 140

Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln Thr Ile Arg Ile

145 150 155 160

Thr Cys Gln Gly Asp Ser Leu Gly Asn Tyr Tyr Ala Thr Trp Tyr Gln

165 170 175

Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr Gly Thr Asn Asn

180 185 190

Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Ala Ser Ser Ser Gly Asn

195 200 205

Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala Asp

210 215 220

Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly His His Leu Leu Phe Gly

225 230 235 240

Thr Gly Thr Lys Val Thr Val Leu

245

<210> 471

<211> 744

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 471

gaagtgcagc tccaacagtc aggaccgggg ctcgtgaagc catcccagac cctgtccctg

60

acttgtgcca tctcgggaga tagcgtgtca tcgaactccg ccgcctggaa ctggattcgg

120

cagagcccgt cccgcggact ggagtggctt ggaaggacct actaccggtc caagtggtac

180

tctttctacg cgatctcgct gaagtcccgc attatcatta accctgatac ctccaagaat

240

cagttctccc tccaactgaa atccgtcacc cccgaggaca cagcagtgta ttactgcgca

300

cggagcagcc ccgaaggact gttcctgtat tggtttgacc cctggggcca ggggactctt

360

gtgaccgtgt cgagcggcgg agatgggtcc ggtggcggtg gttcgggggg cggcggatca

420

tcatccgaac tgacccagga cccggctgtg tccgtggcgc tgggacaaac catccgcatt

480

acgtgccagg gagactccct gggcaactac tacgccactt ggtaccagca gaagccggggc

540

caagcccctg tgttggtcat ctacgggacc aacaacagac cttccggcat ccccgaccgg

600

ttcagcgctt cgtcctccgg caacactgcc agcctgacca tcactggagc gcaggccgaa

660

gatgaggccg actactactg caacagcaga gactcctcgg gtcatcacct cttgttcgga

720

actggaacca aggtcaccgt gctg

744

<210> 472

<211> 125

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 472

Glu Val Gln Leu Gln Gln Ser Gly Pro Gly Leu Val Lys Pro Ser Gln

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn

20 25 30

Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu

35 40 45

Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp Tyr Ser Phe Tyr Ala

50 55 60

Ile Ser Leu Lys Ser Arg Ile Ile Ile Asn Pro Asp Thr Ser Lys Asn

65 70 75 80

Gln Phe Ser Leu Gln Leu Lys Ser Val Thr Pro Glu Asp Thr Ala Val

85 90 95

Tyr Tyr Cys Ala Arg Ser Ser Pro Glu Gly Leu Phe Leu Tyr Trp Phe

100 105 110

Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125

<210> 473

<211> 108

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 473

Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln

1 5 10 15

Thr Ile Arg Ile Thr Cys Gln Gly Asp Ser Leu Gly Asn Tyr Tyr Ala

20 25 30

Thr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr

35 40 45

Gly Thr Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Ala Ser

50 55 60

Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu

65 70 75 80

Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly His His

85 90 95

Leu Leu Phe Gly Thr Gly Thr Lys Val Thr Val Leu

100 105

<210> 474

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 474

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Val Glu Gly Ser Gly Ser Leu Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Gly Thr Leu

130 135 140

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

145 150 155 160

Ser Val Ser Ser Ala Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

165 170 175

Pro Pro Arg Leu Leu Ile Ser Gly Ala Ser Thr Arg Ala Thr Gly Ile

180 185 190

Pro Asp Arg Phe Gly Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His

210 215 220

Tyr Gly Ser Ser Phe Asn Gly Ser Ser Leu Phe Thr Phe Gly Gln Gly

225 230 235 240

Thr Arg Leu Glu Ile Lys

245

<210> 475

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 475

gaagtgcagc tcgtggagtc aggaggcggc ctggtccagc cgggagggtc ccttagactg

60

tcatgcgccg caagcggatt cactttctcc tcctatgcca tgagctgggt ccgccaagcc

120

ccgggaaagg gactggaatg ggtgtccgcc atctcggggt ctggaggctc aacttactac

180

gctgactccg tgaagggacg gttcaccatt agccgcgaca actccaagaa caccctctac

240

ctccaaatga actccctgcg ggccgaggat accgccgtct actactgcgc caaagtggaa

300

ggttcaggat cgctggacta ctggggacag ggtactctcg tgaccgtgtc atcgggcgga

360

ggaggttccg gcggtggcgg ctccggcggc ggagggtcgg agatcgtgat gacccagagc

420

cctggtactc tgagcctttc gccgggagaa agggccaccc tgtcctgccg cgcttcccaa

480

tccgtgtcct ccgcgtactt ggcgtggtac cagcagaagc cgggacagcc ccctcggctg

540

ctgatcagcg gggccagcac cggggcaacc ggaatcccag acagattcgg gggttccggc

600

agcggcacag atttcaccct gactatttcg aggttggagc ccgaggactt tgcggtgtat

660

tactgtcagc actacgggtc gtcctttaat ggctccagcc tgttcacgtt cggacagggg

720

acccgcctgg aaatcaag

738

<210> 476

<211> 118

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 476

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Val Glu Gly Ser Gly Ser Leu Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 477

<211> 113

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 477

Glu Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ala

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Arg Leu Leu

35 40 45

Ile Ser Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe Gly

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Ser Ser Phe

85 90 95

Asn Gly Ser Ser Leu Phe Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile

100 105 110

Lys

<210> 478

<211> 241

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 478

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ile Thr Phe Ser Arg Tyr

20 25 30

Pro Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Asp Ser Gly Val Ser Thr Tyr Tyr Ala Asp Ser Ala

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe

65 70 75 80

Leu Gln Met Ser Ser Leu Arg Asp Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Thr Arg Ala Gly Ser Glu Ala Ser Asp Ile Trp Gly Gln Gly Thr

100 105 110

Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu

130 135 140

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

145 150 155 160

Ser Val Ser Asn Ser Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala

165 170 175

Pro Arg Leu Leu Ile Tyr Asp Ala Ser Ser Arg Ala Thr Gly Ile Pro

180 185 190

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

195 200 205

Ser Arg Leu Glu Pro Glu Asp Phe Ala Ile Tyr Tyr Cys Gln Gln Phe

210 215 220

Gly Thr Ser Ser Gly Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile

225 230 235 240

Lys

<210> 479

<211> 723

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 479

gaagtgcaac tggtggaaac cggtggcggc ctggtgcagc ctggaggatc attgaggctg

60

tcatgcgcgg ccagcggtat taccttctcc cggtacccca tgtcctggggt cagacaggcc

120

ccggggaaag ggcttgaatg ggtgtccggg atctcggact ccggtgtcag cacttactac

180

gccgactccg ccaagggacg cttcaccatt tcccgggaca actcgaagaa caccctgttc

240

ctccaaatga gctccctccg ggacgaggat actgcagtgt actactgcgt gacccgcgcc

300

gggtccgagg cgtctgacat ttggggacag ggcactatgg tcaccgtgtc gtccggcgga

360

gggggctcgg gaggcggtgg cagcggagga ggagggtccg agatcgtgct gacccaatcc

420

ccggccaccc tctcgctgag ccctggagaa agggcaacct tgtcctgtcg cgcgagccag

480

tccgtgagca actccctggc ctggtaccag cagaagcccg gacaggctcc gagacttctg

540

atctacgacg cttcgagccg ggccactgga atccccgacc gcttttcggg gtccggctca

600

ggaaccgatt tcaccctgac aatctcacgg ctggagccag aggatttcgc catctattac

660

tgccagcagt tcggtacttc ctccggcctg actttcggag gcggcacgaa gctcgaaatc

720

aag

723

<210> 480

<211> 118

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 480

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ile Thr Phe Ser Arg Tyr

20 25 30

Pro Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Gly Ile Ser Asp Ser Gly Val Ser Thr Tyr Tyr Ala Asp Ser Ala

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe

65 70 75 80

Leu Gln Met Ser Ser Leu Arg Asp Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Thr Arg Ala Gly Ser Glu Ala Ser Asp Ile Trp Gly Gln Gly Thr

100 105 110

Met Val Thr Val Ser Ser

115

<210> 481

<211> 108

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 481

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Asn Ser

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Ile Tyr Tyr Cys Gln Gln Phe Gly Thr Ser Ser Gly

85 90 95

Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 482

<211> 248

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 482

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Ala Thr Tyr Lys Arg Glu Leu Arg Tyr Tyr Tyr Gly Met Asp

100 105 110

Val Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr

130 135 140

Gln Ser Pro Gly Thr Val Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu

145 150 155 160

Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Phe Leu Ala Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser

180 185 190

Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Ser Ala

210 215 220

Val Tyr Tyr Cys Gln Gln Tyr His Ser Ser Pro Ser Trp Thr Phe Gly

225 230 235 240

Gln Gly Thr Arg Leu Glu Ile Lys

245

<210> 483

<211> 744

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 483

caagtgcagc tcgtggaatc gggtggcgga ctggtgcagc cggggggctc acttagactg

60

tcctgcgcgg ccagcggatt cactttctcc tcctacgcca tgtcctgggt cagacaggcc

120

cctggaaagg gcctggaatg ggtgtccgca atcagcggca gcggcggctc gacctattac

180

gcggattcag tgaagggcag attcaccatt tcccgggaca acgccaagaa ctccttgtac

240

cttcaaatga actccctccg cgcggaagat accgcaatct actactgcgc tcgggccact

300

tacaagaggg aactgcgcta ctactacggg atggacgtct ggggccaggg aaccatggtc

360

accgtgtcca gcggaggagg aggatcggga ggaggcggta gcgggggtgg agggtcggag

420

atcgtgatga cccagtcccc cggcactgtg tcgctgtccc ccggcgaacg ggccaccctg

480

tcatgtcggg ccagccagtc agtgtcgtca agcttcctcg cctggtacca gcagaaaccg

540

ggacaagctc cccgcctgct gatctacgga gccagcagcc gggccaccgg tattcctgac

600

cggttctccg gttcggggtc cgggaccgac tttactctga ctatctctcg cctcgagcca

660

gaggactccg ccgtgtatta ctgccagcag taccactcct ccccgtcctg gacgttcgga

720

cagggcacaa ggctggagat taag

744

<210> 484

<211> 124

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 484

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Ala Thr Tyr Lys Arg Glu Leu Arg Tyr Tyr Tyr Gly Met Asp

100 105 110

Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 485

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 485

Glu Ile Val Met Thr Gln Ser Pro Gly Thr Val Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Ser Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Ser Pro

85 90 95

Ser Trp Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

100 105

<210> 486

<211> 248

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 486

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Thr Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Thr Tyr Lys Arg Glu Leu Arg Tyr Tyr Tyr Gly Met Asp

100 105 110

Val Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr

130 135 140

Gln Ser Pro Ser Thr Leu Ser Leu Ser Pro Gly Glu Ser Ala Thr Leu

145 150 155 160

Ser Cys Arg Ala Ser Gln Ser Val Ser Thr Thr Phe Leu Ala Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ser Ser

180 185 190

Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Phe Thr Leu Thr Ile Arg Arg Leu Glu Pro Glu Asp Phe Ala

210 215 220

Val Tyr Tyr Cys Gln Gln Tyr His Ser Ser Pro Ser Trp Thr Phe Gly

225 230 235 240

Gln Gly Thr Lys Val Glu Ile Lys

245

<210> 487

<211> 744

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 487

gaggtgcagc ttgtggaaac cggtggcgga ctggtgcagc ccggaggaag cctcaggctg

60

tcctgcgccg cgtccggctt caccttctcc tcgtacgcca tgtcctgggt ccgccaggcc

120

ccgggaaagg gcctggaatg ggtgtccgcc atctctggaa gcgggaggttc cacgtactac

180

gcggacagcg tcaagggaag gttcacaatc tcccgcgata attcgaagaa cactctgtac

240

cttcaaatga acaccctgaa ggccgaggac actgctgtgt actactgcgc acggggccacc

300

tacaagagag agctccggta ctactacgga atggacgtct ggggccaggg aactactgtg

360

accgtgtcct cgggggggg tggctccgggg gggggcggct ccggcgggagg cggttccgag

420

attgtgctga cccagtcacc ttcaactctg tcgctgtccc cgggagagag cgctactctg

480

agctgccggg ccagccagtc cgtgtccacc accttcctcg cctggtatca gcagaagccg

540

gggcaggcac cacggctctt gatctacgggg tcaagcaaca gagcgaccgg aattcctgac

600

cgcttctcgg ggagcggttc aggcaccgac ttcaccctga ctatccggcg cctggaaccc

660

gaagatttcg ccgtgtatta ctgtcaacag taccactcct cgccgtcctg gacctttggc

720

caaggaacca aagtggaaat caag

744

<210> 488

<211> 124

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 488

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Thr Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Thr Tyr Lys Arg Glu Leu Arg Tyr Tyr Tyr Gly Met Asp

100 105 110

Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 489

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 489

Glu Ile Val Leu Thr Gln Ser Pro Ser Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Ser Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Thr Thr

20 25 30

Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ser Ser Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Ser Pro

85 90 95

Ser Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 490

<211> 239

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 490

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Asp Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Val Gly Lys Ala Val Pro Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Asp Ile Val Met Thr Gln Thr Pro Ser Ser Leu Ser

130 135 140

Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser

145 150 155 160

Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

165 170 175

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

180 185 190

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

195 200 205

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr

210 215 220

Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

225 230 235

<210> 491

<211> 717

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 491

gaagtgcagc tcgtggaaac tggaggtgga ctcgtgcagc ctggacggtc gctgcggctg

60

agctgcgctg catccggctt caccttcgac gattatgcca tgcactgggt cagacaggcg

120

ccagggaagg gacttgagtg ggtgtccggt atcagctgga atagcggctc aatcggatac

180

gcggactccg tgaagggaag gttcaccatt tcccgcgaca acgccaagaa ctccctgtac

240

ttgcaaatga acagcctccg ggatgaggac actgccgtgt actactgcgc ccgcgtcgga

300

aaagctgtgc ccgacgtctg gggccaggga accactgtga ccgtgtccag cggcgggggt

360

ggatcgggcg gtggagggtc cggtggaggg ggctcagata ttgtgatgac cggaccccc

420

tcgtccctgt ccgcctcggt cggcgaccgc gtgactatca catgtagagc ctcgcagagc

480

atctccagct acctgaactg gtatcagcag aagccgggga aggccccgaa gctcctgatc

540

tacgcggcat catcactgca atcgggagtg ccgagccggt tttccgggtc cggctccggc

600

accgacttca cgctgaccat ttcttccctg caacccgagg acttcgccac ttactactgc

660

cagcagtcct actccacccc ttactccttc ggccaaggaa ccaggctgga aatcaag

717

<210> 492

<211> 117

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 492

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Glu Trp Val

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Asp Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Val Gly Lys Ala Val Pro Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 493

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 493

Asp Ile Val Met Thr Gln Thr Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr

85 90 95

Ser Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

100 105

<210> 494

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 494

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Arg Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ala Ser Ile Asn Trp Lys Gly Asn Ser Leu Ala Tyr Gly Asp Ser Val

50 55 60

Lys Gly Arg Phe Ala Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Phe

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Thr Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Ser His Gln Gly Val Ala Tyr Tyr Asn Tyr Ala Met Asp Val Trp

100 105 110

Gly Arg Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser

130 135 140

Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

145 150 155 160

Arg Ala Thr Gln Ser Ile Gly Ser Ser Phe Leu Ala Trp Tyr Gln Gln

165 170 175

Arg Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Gln Arg

180 185 190

Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Arg Gly Ser Gly Thr Asp

195 200 205

Phe Thr Leu Thr Ile Ser Arg Val Glu Pro Glu Asp Ser Ala Val Tyr

210 215 220

Tyr Cys Gln His Tyr Glu Ser Ser Pro Ser Trp Thr Phe Gly Gln Gly

225 230 235 240

Thr Lys Val Glu Ile Lys

245

<210> 495

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 495

gaagtgcagc tcgtggagag cgggggagga ttggtgcagc ccggaaggtc cctgcggctc

60

tcctgcactg cgtctggctt caccttcgac gactacgcga tgcactgggt cagacagcgc

120

ccgggaaagg gcctggaatg ggtcgcctca atcaactgga agggaaactc cctggcctat

180

ggcgacagcg tgaagggccg cttcgccatt tcgcgcgaca acgccaagaa caccgtgttt

240

ctgcaaatga attccctgcg gaccgaggat accgctgtgt actactgcgc cagccaccag

300

ggcgtggcat actataacta cgccatggac gtgtggggaa gagggacgct cgtcaccgtg

360

tcctccgggg gcggtggatc gggtggagga ggaagcggtg gcgggggcag cgaaatcgtg

420

ctgactcaga gcccgggaac tctttcactg tccccgggag aacgggccac tctctcgtgc

480

cgggccaccc agtccatcgg ctcctccttc cttgcctggt accagcagag gccaggacag

540

gcgccccgcc tgctgatcta cggtgcttcc caacgcgcca ctggcattcc tgaccggttc

600

agcggcagag ggtcgggaac cgatttcaca ctgaccattt cccgggtgga gcccgaagat

660

tcggcagtct actactgtca gcattacgag tcctcccctt catggacctt cggtcaaggg

720

accaaagtgg agatcaag

738

<210> 496

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 496

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Asp Asp Tyr

20 25 30

Ala Met His Trp Val Arg Gln Arg Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ala Ser Ile Asn Trp Lys Gly Asn Ser Leu Ala Tyr Gly Asp Ser Val

50 55 60

Lys Gly Arg Phe Ala Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Phe

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Thr Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Ser His Gln Gly Val Ala Tyr Tyr Asn Tyr Ala Met Asp Val Trp

100 105 110

Gly Arg Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 497

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 497

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Thr Gln Ser Ile Gly Ser Ser

20 25 30

Phe Leu Ala Trp Tyr Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Gln Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Arg Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Val Glu

65 70 75 80

Pro Glu Asp Ser Ala Val Tyr Tyr Cys Gln His Tyr Glu Ser Ser Pro

85 90 95

Ser Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 498

<211> 241

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 498

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Val Val Arg Asp Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser

130 135 140

Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser

145 150 155 160

Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala

165 170 175

Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro

180 185 190

Asp Arg Phe Ser Gly Asn Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

195 200 205

Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr

210 215 220

Gly Ser Pro Pro Arg Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile

225 230 235 240

Lys

<210> 499

<211> 723

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 499

gaggtgcagt tggtcgaaag cggggggcggg cttgtgcagc ctggcggatc actgcggctg

60

tcctgcgcgg catcaggctt cacgttttct tcctacgcca tgtcctggggt gcgccaggcc

120

cctggaaagg gactggaatg ggtgtccgcg atttcggggt ccggcgggag cacctactac

180

gccgattccg tgaagggccg cttcactatc tcgcgggaca actccaagaa caccctctac

240

ctccaaatga atagcctgcg ggccgaggat accgccgtct actattgcgc taaggtcgtg

300

cgcgacggaa tggacgtgtg gggacagggt accaccgtga cagtgtcctc ggggggaggc

360

ggtagcggcg gaggaggaag cggtggtgga ggttccgaga ttgtgctgac tcaatcaccc

420

gcgaccctga gcctgtcccc cggcgaaagg gccactctgt cctgtcgggc cagccaatca

480

gtctcctcct cgtacctggc ctggtaccag cagaagccag gacaggctcc gagactcctt

540

atctatggcg catcctcccg cgccaccggga atcccggata ggttctcggg aaacggatcg

600

gggaccgact tcactctcac catctcccgg ctggaaccgg aggacttcgc cgtgtactac

660

tgccagcagt acggcagccc gcctagattc actttcggcc ccggcaccaa agtggacatc

720

aag

723

<210> 500

<211> 117

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 500

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Val Val Arg Asp Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 501

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 501

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Asn Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Pro

85 90 95

Arg Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 502

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 502

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Ile Pro Gln Thr Gly Thr Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

115 120 125

Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu

130 135 140

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

145 150 155 160

Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Arg Pro Gly Gln

165 170 175

Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile

180 185 190

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

195 200 205

Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His

210 215 220

Tyr Gly Ser Ser Pro Ser Trp Thr Phe Gly Gln Gly Thr Arg Leu Glu

225 230 235 240

Ile Lys

<210> 503

<211> 726

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 503

gaagtgcagc tgctggagtc cggcggtgga ttggtgcaac cggggggatc gctcagactg

60

tcctgtgcgg cgtcaggctt caccttctcg agctacgcca tgtcatgggt cagacaggcc

120

cctggaaagg gtctggaatg ggtgtccgcc atttccggga gcgggggatc tacatactac

180

gccgatagcg tgaagggccg cttcaccatt tcccgggaca actccaagaa cactctctat

240

ctgcaaatga actccctccg cgctgaggac actgccgtgt actactgcgc caaaatccct

300

cagaccggca ccttcgacta ctggggacag gggactctgg tcaccgtcag cagcggtggc

360

ggaggttcgg ggggaggagg aagcggcggc ggagggtccg agattgtgct gacccagtca

420

cccggcactt tgtccctgtc gcctggagaa agggccaccc tttcctgccg ggcatcccaa

480

tccgtgtcct cctcgtacct ggcctggtac cagcagaggc ccggacaggc cccacggctt

540

ctgatctacg gagcaagcag ccgcgcgacc ggtatcccgg accggttttc gggctcggggc

600

tcaggaactg acttcaccct caccatctcc cgcctggaac ccgaagattt cgctgtgtat

660

tactgccagc actacggcag ctccccgtcc tggacgttcg gccagggaac tcggctggag

720

atcaag

726

<210> 504

<211> 118

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 504

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Ile Pro Gln Thr Gly Thr Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 505

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 505

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Ser Ser Pro

85 90 95

Ser Trp Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

100 105

<210> 506

<211> 248

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 506

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Met Ser Arg Glu Asn Asp Lys Asn Ser Val Phe

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr Gly Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Asn Tyr Lys Arg Glu Leu Arg Tyr Tyr Tyr Gly Met Asp

100 105 110

Val Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly

115 120 125

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr

130 135 140

Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Ser Ala Thr Leu

145 150 155 160

Ser Cys Arg Ala Ser Gln Arg Val Ala Ser Asn Tyr Leu Ala Trp Tyr

165 170 175

Gln His Lys Pro Gly Gln Ala Pro Ser Leu Leu Ile Ser Gly Ala Ser

180 185 190

Ser Arg Ala Thr Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Phe Thr Leu Ala Ile Ser Arg Leu Glu Pro Glu Asp Ser Ala

210 215 220

Val Tyr Tyr Cys Gln His Tyr Asp Ser Ser Pro Ser Trp Thr Phe Gly

225 230 235 240

Gln Gly Thr Lys Val Glu Ile Lys

245

<210> 507

<211> 744

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 507

gaagtgcaac tggtggaaac cggtggagga ctcgtgcagc ctggcggcag cctccggctg

60

agctgcgccg cttcgggatt caccttttcc tcctacgcga tgtcttgggt cagacaggcc

120

ccgggaaagg ggctggaatg ggtgtcagcc atctccggct ccggcggatc aacgtactac

180

gccgactccg tgaaaggccg gttcaccatg tcgcgcgaga atgacaagaa ctccgtgttc

240

ctgcaaatga actccctgag ggtggaggac accggagtgt actattgtgc gcgcgccaac

300

tacaagagag agctgcggta ctactacgga atggacgtct ggggacaggg aactatggtg

360

accgtgtcat ccggtggagg gggaagcggc ggtggaggca gcgggggcgg gggttcagaa

420

attgtcatga cccagtcccc gggaactctt tccctctccc ccggggaatc cgcgactttg

480

tcctgccggg ccagccagcg cgtggcctcg aactacctcg catggtacca gcataagcca

540

ggccaagccc cttccctgct gatttccggg gctagcagcc gcgccactgg cgtgccggat

600

aggttctcgg gaagcggctc gggtaccgat ttcaccctgg caatctcgcg gctggaaccg

660

gaggattcgg ccgtgtacta ctgccagcac tatgactcat ccccctcctg gacattcgga

720

cagggcacca aggtcgagat caag

744

<210> 508

<211> 124

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 508

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Met Ser Arg Glu Asn Asp Lys Asn Ser Val Phe

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr Gly Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Asn Tyr Lys Arg Glu Leu Arg Tyr Tyr Tyr Gly Met Asp

100 105 110

Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 509

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 509

Glu Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Ser Ala Thr Leu Ser Cys Arg Ala Ser Gln Arg Val Ala Ser Asn

20 25 30

Tyr Leu Ala Trp Tyr Gln His Lys Pro Gly Gln Ala Pro Ser Leu Leu

35 40 45

Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Val Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ala Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Ser Ala Val Tyr Tyr Cys Gln His Tyr Asp Ser Ser Pro

85 90 95

Ser Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 510

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 510

Glu Val Gln Leu Leu Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Ala Leu Val Gly Ala Thr Gly Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly

130 135 140

Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala

145 150 155 160

Ser Gln Ser Leu Ser Ser Asn Phe Leu Ala Trp Tyr Gln Gln Lys Pro

165 170 175

Gly Gln Ala Pro Gly Leu Leu Ile Tyr Gly Ala Ser Asn Trp Ala Thr

180 185 190

Gly Thr Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

195 200 205

Leu Thr Ile Thr Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

210 215 220

Gln Tyr Tyr Gly Thr Ser Pro Met Tyr Thr Phe Gly Gln Gly Thr Lys

225 230 235 240

Val Glu Ile Lys

<210> 511

<211> 732

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 511

gaagtgcagc tgctcgaaac cggtggaggg ctggtgcagc cagggggctc cctgaggctt

60

tcatgcgccg ctagcggatt ctccttctcc tcttacgcca tgtcgtgggt ccgccaagcc

120

cctggaaaag gcctggaatg ggtgtccgcg atttccggga gcggaggttc gacctattac

180

gccgactccg tgaagggccg ctttaccatc tcccgggata actccaagaa cactctgtac

240

ctccaaatga actcgctgag agccgaggac accgccgtgt attactgcgc gaaggcgctg

300

gtcggcgcga ctggggcatt cgacatctgg ggacagggaa ctcttgtgac cgtgtcgagc

360

ggaggcggcg gctccggcgg aggagggagc gggggcggtg gttccgaaat cgtgttgact

420

cagtccccgg gaaccctgag cttgtcaccc ggggagcggg ccactctctc ctgtcgcgcc

480

tcccaatcgc tctcatccaa tttcctggcc tggtaccagc agaagccgg acaggccccg

540

ggcctgctca tctacggcgc ttcaaactgg gcaacgggaa cccctgatcg gttcagcgga

600

agcggatcgg gtactgactt taccctgacc atcaccagac tggaaccggga ggacttcgcc

660

gtgtactact gccagtacta cggcacctcc cccatgtaca cattcggaca gggtaccaag

720

gtcgagatta ag

732

<210> 512

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 512

Glu Val Gln Leu Leu Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Ala Leu Val Gly Ala Thr Gly Ala Phe Asp Ile Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 513

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 513

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Leu Ser Ser Asn

20 25 30

Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Gly Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Asn Trp Ala Thr Gly Thr Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Thr Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Tyr Tyr Gly Thr Ser Pro

85 90 95

Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 514

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 514

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Trp Phe Gly Glu Gly Phe Asp Pro Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Asp Ile Val Leu Thr Gln Ser Pro Leu Ser Leu Pro

130 135 140

Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser

145 150 155 160

Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys

165 170 175

Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala

180 185 190

Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

195 200 205

Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr

210 215 220

Cys Met Gln Ala Leu Gln Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys

225 230 235 240

Val Asp Ile Lys

<210> 515

<211> 733

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 515

gaagtgcagc tgcttgagag cggtggaggt ctggtgcagc ccgggggatc actgcgcctg

60

tcctgtgccg cgtccggttt cactttctcc tcgtacgcca tgtcgtgggt cagacaggca

120

ccgggaaagg gactggaatg ggtgtcagcc atttcgggtt cggggggcag cacctactac

180

gctgactccg tgaagggccg gttcaccatt tcccgcgaca actccaagaa caccttgtac

240

ctccaaatga actccctgcg ggccgaagat accgccgtgt attactgcgt gctgtggttc

300

ggagagggat tcgacccgtg gggacaagga acactcgtga ctgtgtcatc cggcggaggc

360

ggcagcggtg gcggcggttc cggcggcggc ggatctgaca tcgtgttgac ccagtcccct

420

ctgagcctgc cggtcactcc tggcgaacca gccagcatct cctgccggtc gagccagtcc

480

ctcctgcact ccaatgggta caactacctc gattggtatc tgcaaaagcc gggccagagc

540

ccccagctgc tgatctacct tgggtcaaac cgcgcttccg gggtgcctga tagattctcc

600

gggtccggga gcggaaccga ctttaccctg aaaatctcga gggtggaggc cgaggacgtc

660

ggagtgtact actgcatgca ggcgctccag actccctga ccttcgggagg aggaacgaag

720

gtcgacatca aga

733

<210> 516

<211> 117

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 516

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Trp Phe Gly Glu Gly Phe Asp Pro Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser

115

<210> 517

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 517

Asp Ile Val Leu Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys

100 105 110

<210> 518

<211> 251

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 518

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Val Gly Tyr Asp Ser Ser Gly Tyr Tyr Arg Asp Tyr Tyr Gly

100 105 110

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly

115 120 125

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val

130 135 140

Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala

145 150 155 160

Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

165 170 175

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly

180 185 190

Thr Ser Ser Arg Ala Thr Gly Ile Ser Asp Arg Phe Ser Gly Ser Gly

195 200 205

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp

210 215 220

Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Asn Ser Pro Pro Lys Phe

225 230 235 240

Thr Phe Gly Pro Gly Thr Lys Leu Glu Ile Lys

245 250

<210> 519

<211> 753

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 519

caagtgcagc tcgtggagtc aggcggagga ctggtgcagc ccgggggctc cctgagactt

60

tcctgcgcgg catcgggttt taccttctcc tcctatgcta tgtcctgggt gcgccaggcc

120

ccgggaaagg gactggaatg ggtgtccgca atcagcggta gcgggggctc aacatactac

180

gccgactccg tcaagggtcg cttcactatt tcccgggaca actccaagaa taccctgtac

240

ctccaaatga acagcctcag ggccgaggat actgccgtgt actactgcgc caaagtcgga

300

tacgatagct ccggttacta ccgggactac tacggaatgg acgtgtgggg acagggcacc

360

accgtgaccg tgtcaagcgg cggaggcggt tcaggagggg gaggctccgg cggtggaggg

420

tccgaaatcg tcctgactca gtcgcctggc actctgtcgt tgtccccgggg ggagcgcgct

480

accctgtcgt gtcgggcgtc gcagtccgtg tcgagctcct acctcgcgtg gtaccagcag

540

aagcccggac aggcccctag acttctgatc tacggcactt cttcacgcgc caccgggatc

600

agcgacaggt tcagcggctc cggctccgggg accgacttca ccctgaccat tagccggctg

660

gagcctgaag atttcgccgt gtattactgc caacactacg gaaactcgcc gccaaagttc

720

acgttcggac ccggaaccaa gctggaaatc aag

753

<210> 520

<211> 126

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 520

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Val Gly Tyr Asp Ser Ser Gly Tyr Tyr Arg Asp Tyr Tyr Gly

100 105 110

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

<210> 521

<211> 110

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 521

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Thr Ser Ser Arg Ala Thr Gly Ile Ser Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Asn Ser Pro

85 90 95

Pro Lys Phe Thr Phe Gly Pro Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 522

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 522

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Met Gly Trp Ser Ser Gly Tyr Leu Gly Ala Phe Asp Ile Trp

100 105 110

Gly Glyn Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser

130 135 140

Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

145 150 155 160

Arg Ala Ser Gln Ser Val Ala Ser Ser Phe Leu Ala Trp Tyr Gln Gln

165 170 175

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Gly Arg

180 185 190

Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

195 200 205

Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr

210 215 220

Tyr Cys Gln His Tyr Gly Gly Ser Pro Arg Leu Thr Phe Gly Gly Gly

225 230 235 240

Thr Lys Val Asp Ile Lys

245

<210> 523

<211> 739

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 523

gaagtccaac tggtggagtc cgggggagggg ctcgtgcagc ccggaggcag ccttcggctg

60

tcgtgcgccg cctccggggtt cacgttctca tcctacgcga tgtcgtggggt cagacaggca

120

cgggaaagg gactggaatg ggtgtccgcc attagcggct ccggcggtag cacctactat

180

gccgactcag tgaagggaag gttcactatc tcccgcgaca acagcaagaa caccctgtac

240

ctccaaatga actctctgcg ggccgaggat accgcggtgt actattgcgc caagatgggt

300

tggtccagcg gatacttggg agccttcgac atttggggac agggcactac tgtgaccgtg

360

tcctccgggg gtggcggatc gggaggcggc ggctcgggtg gagggggttc cgaaatcgtg

420

ttgacccagt caccgggaac cctctcgctg tccccgggag aacgggctac actgtcatgt

480

agagcgtccc agtccgtggc ttcctcgttc ctggcctggt accagcagaa gccgggacag

540

gcaccccgcc tgctcatcta cggagccagc ggccgggcga ccggcatccc tgaccgcttc

600

tccggttccg gctcgggcac cgactttact ctgaccatta gcaggcttga gcccgaggat

660

tttgccgtgt actactgcca acactacggg gggagccctc gcctgacctt cggaggcggga

720

actaaggtcg atatcaaaa

739

<210> 524

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 524

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Lys Met Gly Trp Ser Ser Gly Tyr Leu Gly Ala Phe Asp Ile Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 525

<211> 109

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 525

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ala Ser Ser

20 25 30

Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Gly Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Gly Ser Pro

85 90 95

Arg Leu Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys

100 105

<210> 526

<211> 122

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 526

Gln Ile Gln Leu Val Gln Ser Gly Pro Asp Leu Lys Lys Pro Gly Glu

1 5 10 15

Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Phe

20 25 30

Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Phe Lys Trp Met

35 40 45

Ala Trp Ile Asn Thr Tyr Thr Gly Glu Ser Tyr Phe Ala Asp Asp Phe

50 55 60

Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Thr Thr Ala Tyr

65 70 75 80

Leu Gln Ile Asn Asn Leu Lys Thr Glu Asp Thr Ala Thr Tyr Phe Cys

85 90 95

Ala Arg Gly Glu Ile Tyr Tyr Gly Tyr Asp Gly Gly Phe Ala Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ala

115 120

<210> 527

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 527

Asp Val Val Met Thr Gln Ser His Arg Phe Met Ser Thr Ser Val Gly

1 5 10 15

Asp Arg Val Ser Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala

20 25 30

Val Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile

35 40 45

Phe Ser Ala Ser Tyr Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

Ser Gly Ser Gly Ala Asp Phe Thr Leu Thr Ile Ser Ser Val Gln Ala

65 70 75 80

Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Trp

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Asp Ile Lys

100 105

<210> 528

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 528

Gln Ile Gln Leu Val Gln Ser Gly Pro Asp Leu Lys Lys Pro Gly Glu

1 5 10 15

Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Phe

20 25 30

Gly Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Phe Lys Trp Met

35 40 45

Ala Trp Ile Asn Thr Tyr Thr Gly Glu Ser Tyr Phe Ala Asp Asp Phe

50 55 60

Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Thr Thr Ala Tyr

65 70 75 80

Leu Gln Ile Asn Asn Leu Lys Thr Glu Asp Thr Ala Thr Tyr Phe Cys

85 90 95

Ala Arg Gly Glu Ile Tyr Tyr Gly Tyr Asp Gly Gly Phe Ala Tyr Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr Gln Ser

130 135 140

His Arg Phe Met Ser Thr Ser Val Gly Asp Arg Val Ser Ile Thr Cys

145 150 155 160

Arg Ala Ser Gln Asp Val Asn Thr Ala Val Ser Trp Tyr Gln Gln Lys

165 170 175

Pro Gly Gln Ser Pro Lys Leu Leu Ile Phe Ser Ala Ser Tyr Arg Tyr

180 185 190

Thr Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Ala Asp Phe

195 200 205

Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr

210 215 220

Cys Gln Gln His Tyr Ser Thr Pro Trp Thr Phe Gly Gly Gly Thr Lys

225 230 235 240

Leu Asp Ile Lys

<210> 529

<211> 117

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 529

Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Ser Ile Asn Trp Val Lys Arg Ala Pro Gly Lys Gly Leu Lys Trp Met

35 40 45

Gly Trp Ile Asn Thr Glu Thr Arg Glu Pro Ala Tyr Ala Tyr Asp Phe

50 55 60

Arg Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Tyr

65 70 75 80

Leu Gln Ile Asn Asn Leu Lys Tyr Glu Asp Thr Ala Thr Tyr Phe Cys

85 90 95

Ala Leu Asp Tyr Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

100 105 110

Val Thr Val Ser Ser

115

<210> 530

<211> 111

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 530

Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Met Ser Leu Gly

1 5 10 15

Lys Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Ser Val Ile

20 25 30

Gly Ala His Leu Ile His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro

35 40 45

Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Glu Thr Gly Val Pro Ala

50 55 60

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asp

65 70 75 80

Pro Val Glu Glu Asp Asp Val Ala Ile Tyr Ser Cys Leu Gln Ser Arg

85 90 95

Ile Phe Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 531

<211> 249

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 531

Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Ser Ile Asn Trp Val Lys Arg Ala Pro Gly Lys Gly Leu Lys Trp Met

35 40 45

Gly Trp Ile Asn Thr Glu Thr Arg Glu Pro Ala Tyr Ala Tyr Asp Phe

50 55 60

Arg Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Tyr

65 70 75 80

Leu Gln Ile Asn Asn Leu Lys Tyr Glu Asp Thr Ala Thr Tyr Phe Cys

85 90 95

Ala Leu Asp Tyr Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

100 105 110

Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys

130 135 140

Lys Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr

145 150 155 160

Phe Thr Asp Tyr Ser Ile Asn Trp Val Lys Arg Ala Pro Gly Lys Gly

165 170 175

Leu Lys Trp Met Gly Trp Ile Asn Thr Glu Thr Arg Glu Pro Ala Tyr

180 185 190

Ala Tyr Asp Phe Arg Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala

195 200 205

Ser Thr Ala Tyr Leu Gln Ile Asn Asn Leu Lys Tyr Glu Asp Thr Ala

210 215 220

Thr Tyr Phe Cys Ala Leu Asp Tyr Ser Tyr Ala Met Asp Tyr Trp Gly

225 230 235 240

Gln Gly Thr Ser Val Thr Val Ser Ser

245

<210> 532

<211> 117

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 532

Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Arg His Tyr

20 25 30

Ser Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met

35 40 45

Gly Arg Ile Asn Thr Glu Ser Gly Val Pro Ile Tyr Ala Asp Asp Phe

50 55 60

Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Ser Thr Ala Tyr

65 70 75 80

Leu Val Ile Asn Asn Leu Lys Asp Glu Asp Thr Ala Ser Tyr Phe Cys

85 90 95

Ser Asn Asp Tyr Leu Tyr Ser Leu Asp Phe Trp Gly Gln Gly Thr Ala

100 105 110

Leu Thr Val Ser Ser

115

<210> 533

<211> 111

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 533

Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala Met Ser Leu Gly

1 5 10 15

Lys Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Thr Ile Leu

20 25 30

Gly Ser His Leu Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro

35 40 45

Thr Leu Leu Ile Gln Leu Ala Ser Asn Val Gln Thr Gly Val Pro Ala

50 55 60

Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asp

65 70 75 80

Pro Val Glu Glu Asp Asp Val Ala Val Tyr Tyr Cys Leu Gln Ser Arg

85 90 95

Thr Ile Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 534

<211> 243

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 534

Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Arg His Tyr

20 25 30

Ser Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met

35 40 45

Gly Arg Ile Asn Thr Glu Ser Gly Val Pro Ile Tyr Ala Asp Asp Phe

50 55 60

Lys Gly Arg Phe Ala Phe Ser Val Glu Thr Ser Ala Ser Thr Ala Tyr

65 70 75 80

Leu Val Ile Asn Asn Leu Lys Asp Glu Asp Thr Ala Ser Tyr Phe Cys

85 90 95

Ser Asn Asp Tyr Leu Tyr Ser Leu Asp Phe Trp Gly Gln Gly Thr Ala

100 105 110

Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala

130 135 140

Met Ser Leu Gly Lys Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser

145 150 155 160

Val Thr Ile Leu Gly Ser His Leu Ile Tyr Trp Tyr Gln Gln Lys Pro

165 170 175

Gly Gln Pro Pro Thr Leu Leu Ile Gln Leu Ala Ser Asn Val Gln Thr

180 185 190

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr

195 200 205

Leu Thr Ile Asp Pro Val Glu Glu Asp Asp Val Ala Val Tyr Tyr Cys

210 215 220

Leu Gln Ser Arg Thr Ile Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu

225 230 235 240

Glu Ile Lys

<210> 535

<211> 117

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 535

Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr

20 25 30

Ser Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met

35 40 45

Gly Arg Ile Asn Thr Glu Thr Gly Glu Pro Leu Tyr Ala Asp Asp Phe

50 55 60

Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Tyr

65 70 75 80

Leu Val Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Phe Phe Cys

85 90 95

Ser Asn Asp Tyr Leu Tyr Ser Cys Asp Tyr Trp Gly Gln Gly Thr Thr

100 105 110

Leu Thr Val Ser Ser

115

<210> 536

<211> 111

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 536

Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala Met Ser Leu Gly

1 5 10 15

Lys Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Thr Ile Leu

20 25 30

Gly Ser His Leu Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro

35 40 45

Thr Leu Leu Ile Gln Leu Ala Ser Asn Val Gln Thr Gly Val Pro Ala

50 55 60

Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr Leu Thr Ile Asp

65 70 75 80

Pro Val Glu Glu Asp Asp Val Ala Val Tyr Tyr Cys Leu Gln Ser Arg

85 90 95

Thr Ile Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 537

<211> 243

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 537

Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu

1 5 10 15

Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr His Tyr

20 25 30

Ser Met Asn Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Lys Trp Met

35 40 45

Gly Arg Ile Asn Thr Glu Thr Gly Glu Pro Leu Tyr Ala Asp Asp Phe

50 55 60

Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Tyr

65 70 75 80

Leu Val Ile Asn Asn Leu Lys Asn Glu Asp Thr Ala Thr Phe Phe Cys

85 90 95

Ser Asn Asp Tyr Leu Tyr Ser Cys Asp Tyr Trp Gly Gln Gly Thr Thr

100 105 110

Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

Gly Gly Gly Ser Asp Ile Val Leu Thr Gln Ser Pro Pro Ser Leu Ala

130 135 140

Met Ser Leu Gly Lys Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser

145 150 155 160

Val Thr Ile Leu Gly Ser His Leu Ile Tyr Trp Tyr Gln Gln Lys Pro

165 170 175

Gly Gln Pro Pro Thr Leu Leu Ile Gln Leu Ala Ser Asn Val Gln Thr

180 185 190

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Arg Thr Asp Phe Thr

195 200 205

Leu Thr Ile Asp Pro Val Glu Glu Asp Asp Val Ala Val Tyr Tyr Cys

210 215 220

Leu Gln Ser Arg Thr Ile Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu

225 230 235 240

Glu Ile Lys

<210> 538

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 538

Asn His Gly Met Ser

15

<210> 539

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 539

Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly

1 5 10 15

<210> 540

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 540

His Gly Gly Glu Ser Asp Val

15

<210> 541

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 541

Asn Tyr Ala Met Ser

15

<210> 542

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 542

Gly Ile Ser Arg Ser Gly Glu Asn Thr Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 543

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 543

Ser Pro Ala His Tyr Tyr Gly Gly Met Asp Val

1 5 10

<210> 544

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 544

Asp Tyr Ala Met His

15

<210> 545

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 545

Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 546

<211> 6

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 546

His Ser Phe Leu Ala Tyr

15

<210> 547

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 547

Asn Phe Gly Ile Asn

15

<210> 548

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 548

Trp Ile Asn Pro Lys Asn Asn Asn Thr Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 549

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 549

Gly Pro Tyr Tyr Tyr Gln Ser Tyr Met Asp Val

1 5 10

<210> 550

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 550

Ser Asp Ala Met Thr

15

<210> 551

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 551

Val Ile Ser Gly Ser Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 552

<211> 14

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 552

Leu Asp Ser Ser Gly Tyr Tyr Tyr Ala Arg Gly Pro Arg Tyr

1 5 10

<210> 553

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 553

Asn Tyr Gly Ile Thr

15

<210> 554

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 554

Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 555

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 555

Gly Pro Tyr Tyr Tyr Tyr Met Asp Val

15

<210> 556

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 556

Asp Tyr Tyr Met Ser

15

<210> 557

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 557

Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 558

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 558

Glu Ser Gly Asp Gly Met Asp Val

15

<210> 559

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 559

Tyr Ile Ser Ser Ser Gly Asn Thr Ile Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 560

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 560

Ser Thr Met Val Arg Glu Asp Tyr

15

<210> 561

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 561

Ser Ser Tyr Tyr Tyr Trp Gly

15

<210> 562

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 562

Ser Ile Tyr Tyr Ser Gly Ser Ala Tyr Tyr Asn Pro Ser Leu Lys Ser

1 5 10 15

<210> 563

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 563

His Trp Gln Glu Trp Pro Asp Ala Phe Asp Ile

1 5 10

<210> 564

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 564

Thr Ser Gly Met Cys Val Ser

15

<210> 565

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 565

Arg Ile Asp Trp Asp Glu Asp Lys Phe Tyr Ser Thr Ser Leu Lys Thr

1 5 10 15

<210> 566

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 566

Ser Gly Ala Gly Gly Thr Ser Ala Thr Ala Phe Asp Ile

1 5 10

<210> 567

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 567

Ser Tyr Ser Met Asn

15

<210> 568

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 568

Ser Ile Ser Ser Ser Ser Ser Ser Tyr Ile Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 569

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 569

Thr Ile Ala Ala Val Tyr Ala Phe Asp Ile

1 5 10

<210> 570

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 570

Asp Leu Arg Gly Ala Phe Asp Ile

15

<210> 571

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 571

Ser His Tyr Ile His

15

<210> 572

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 572

Met Ile Asn Pro Ser Gly Gly Val Thr Ala Tyr Ser Gln Thr Leu Gln

1 5 10 15

gly

<210> 573

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 573

Glu Gly Ser Gly Ser Gly Trp Tyr Phe Asp Phe

1 5 10

<210> 574

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 574

Ser Gly Gly Tyr Tyr Trp Ser

15

<210> 575

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 575

Tyr Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser

1 5 10 15

<210> 576

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 576

Ala Gly Ile Ala Ala Arg Leu Arg Gly Ala Phe Asp Ile

1 5 10

<210> 577

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 577

Ser Tyr Ala Ile Ser

15

<210> 578

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 578

Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 579

<211> 20

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 579

Arg Gly Gly Tyr Gln Leu Leu Arg Trp Asp Val Gly Leu Leu Arg Ser

1 5 10 15

Ala Phe Asp Ile

20

<210> 580

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 580

Ser Asn Ser Ala Ala Trp Asn

15

<210> 581

<211> 18

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 581

Arg Thr Tyr Tyr Arg Ser Lys Trp Tyr Ser Phe Tyr Ala Ile Ser Leu

1 5 10 15

Lys Ser

<210> 582

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 582

Ser Ser Pro Glu Gly Leu Phe Leu Tyr Trp Phe Asp Pro

1 5 10

<210> 583

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 583

Ser Tyr Ala Met Ser

15

<210> 584

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 584

Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 585

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 585

Val Glu Gly Ser Gly Ser Leu Asp Tyr

15

<210> 586

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 586

Arg Tyr Pro Met Ser

15

<210> 587

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 587

Gly Ile Ser Asp Ser Gly Val Ser Thr Tyr Tyr Ala Asp Ser Ala Lys

1 5 10 15

gly

<210> 588

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 588

Arg Ala Gly Ser Glu Ala Ser Asp Ile

15

<210> 589

<211> 15

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 589

Ala Thr Tyr Lys Arg Glu Leu Arg Tyr Tyr Tyr Gly Met Asp Val

1 5 10 15

<210> 590

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 590

Val Gly Lys Ala Val Pro Asp Val

15

<210> 591

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 591

Ser Ile Asn Trp Lys Gly Asn Ser Leu Ala Tyr Gly Asp Ser Val Lys

1 5 10 15

gly

<210> 592

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 592

His Gln Gly Val Ala Tyr Tyr Asn Tyr Ala Met Asp Val

1 5 10

<210> 593

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 593

Val Val Arg Asp Gly Met Asp Val

15

<210> 594

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 594

Ile Pro Gln Thr Gly Thr Phe Asp Tyr

15

<210> 595

<211> 15

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 595

Ala Asn Tyr Lys Arg Glu Leu Arg Tyr Tyr Tyr Gly Met Asp Val

1 5 10 15

<210> 596

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 596

Ala Leu Val Gly Ala Thr Gly Ala Phe Asp Ile

1 5 10

<210> 597

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 597

Trp Phe Gly Glu Gly Phe Asp Pro

15

<210> 598

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 598

Val Gly Tyr Asp Ser Ser Gly Tyr Tyr Arg Asp Tyr Tyr Gly Met Asp

1 5 10 15

Val

<210> 599

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 599

Met Gly Trp Ser Ser Gly Tyr Leu Gly Ala Phe Asp Ile

1 5 10

<210> 600

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 600

Asn Phe Gly Met Asn

15

<210> 601

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 601

Trp Ile Asn Thr Tyr Thr Gly Glu Ser Tyr Phe Ala Asp Asp Phe Lys

1 5 10 15

gly

<210> 602

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 602

Gly Glu Ile Tyr Tyr Gly Tyr Asp Gly Gly Phe Ala Tyr

1 5 10

<210> 603

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 603

Asp Tyr Ser Ile Asn

15

<210> 604

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 604

Trp Ile Asn Thr Glu Thr Arg Glu Pro Ala Tyr Ala Tyr Asp Phe Arg

1 5 10 15

gly

<210> 605

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 605

Asp Tyr Ser Tyr Ala Met Asp Tyr

15

<210> 606

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 606

His Tyr Ser Met Asn

15

<210> 607

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 607

Arg Ile Asn Thr Glu Ser Gly Val Pro Ile Tyr Ala Asp Asp Phe Lys

1 5 10 15

gly

<210> 608

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 608

Asp Tyr Leu Tyr Ser Leu Asp Phe

15

<210> 609

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 609

Arg Ile Asn Thr Glu Thr Gly Glu Pro Leu Tyr Ala Asp Asp Phe Lys

1 5 10 15

gly

<210> 610

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 610

Asp Tyr Leu Tyr Ser Cys Asp Tyr

15

<210> 611

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 611

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

1 5 10

<210> 612

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 612

Ala Ala Ser Ser Leu Gln Ser

15

<210> 613

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 613

Gln Gln Ser Tyr Ser Thr Pro Tyr Thr

15

<210> 614

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 614

Arg Ala Ser Gln Ser Ile Ser Ser Ser Phe Leu Ala

1 5 10

<210> 615

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 615

Gly Ala Ser Arg Arg Ala Thr

15

<210> 616

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 616

Gln Gln Tyr His Ser Ser Pro Ser Trp Thr

1 5 10

<210> 617

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 617

Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp

1 5 10 15

<210> 618

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 618

Leu Gly Ser Asn Arg Ala Ser

15

<210> 619

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 619

Met Gln Ala Leu Gln Thr Pro Tyr Thr

15

<210> 620

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 620

Lys Ser Ser Gln Ser Leu Leu Arg Asn Asp Gly Lys Thr Pro Leu Tyr

1 5 10 15

<210> 621

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 621

Glu Val Ser Asn Arg Phe Ser

15

<210> 622

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 622

Met Gln Asn Ile Gln Phe Pro Ser

15

<210> 623

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 623

Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asn

1 5 10 15

<210> 624

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 624

Leu Gly Ser Lys Arg Ala Ser

15

<210> 625

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 625

Gly Ala Ser Thr Leu Ala Ser

15

<210> 626

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 626

Gln Gln Ser Tyr Lys Arg Ala Ser

15

<210> 627

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 627

Arg Ser Ser Gln Ser Leu Leu Tyr Ser Asn Gly Tyr Asn Tyr Val Asp

1 5 10 15

<210> 628

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 628

Met Gln Gly Arg Gln Phe Pro Tyr Ser

15

<210> 629

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 629

Arg Ala Ser Gln Ser Val Ser Ser Asn Leu Ala

1 5 10

<210> 630

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 630

Gly Ala Ser Thr Arg Ala Ser

15

<210> 631

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 631

Gln Gln Tyr Gly Ser Ser Leu Thr

15

<210> 632

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 632

Arg Ala Ser Gln Ser Val Ser Ser Lys Leu Ala

1 5 10

<210> 633

<400> 633

000

<210> 634

<400> 634

000

<210> 635

<400> 635

000

<210> 636

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 636

Gly Ala Ser Ile Arg Ala Thr

15

<210> 637

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 637

Gln Gln Tyr Gly Ser Ser Ser Trp Thr

15

<210> 638

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 638

Arg Ala Ser Gln Ser Val Gly Ser Thr Asn Leu Ala

1 5 10

<210> 639

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 639

Asp Ala Ser Asn Arg Ala Thr

15

<210> 640

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 640

Gln Gln Tyr Gly Ser Ser Pro Pro Trp Thr

1 5 10

<210> 641

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 641

Gln Gln Ser Tyr Thr Leu Ala

15

<210> 642

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 642

Lys Ser Ser Glu Ser Leu Val His Asn Ser Gly Lys Thr Tyr Leu Asn

1 5 10 15

<210> 643

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 643

Glu Val Ser Asn Arg Asp Ser

15

<210> 644

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 644

Met Gln Gly Thr His Trp Pro Gly Thr

15

<210> 645

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 645

Gln Ala Ser Glu Asp Ile Asn Lys Phe Leu Asn

1 5 10

<210> 646

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 646

Asp Ala Ser Thr Leu Gln Thr

15

<210> 647

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 647

Gln Gln Tyr Glu Ser Leu Pro Leu Thr

15

<210> 648

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 648

Arg Ala Ser Gln Ser Val Gly Ser Asn Leu Ala

1 5 10

<210> 649

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 649

Gly Ala Ser Thr Arg Ala Thr

15

<210> 650

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 650

Gln Gln Tyr Asn Asp Trp Leu Pro Val Thr

1 5 10

<210> 651

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 651

Arg Ala Ser Gln Ser Ile Gly Ser Ser Ser Leu Ala

1 5 10

<210> 652

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 652

Gly Ala Ser Ser Arg Ala Ser

15

<210> 653

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 653

Gln Gln Tyr Ala Gly Ser Pro Pro Phe Thr

1 5 10

<210> 654

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 654

Lys Ala Ser Gln Asp Ile Asp Asp Ala Met Asn

1 5 10

<210> 655

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 655

Ser Ala Thr Ser Pro Val Pro

15

<210> 656

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 656

Leu Gln His Asp Asn Phe Pro Leu Thr

15

<210> 657

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 657

Arg Ala Ser Gln Asp Ile Tyr Asn Asn Leu Ala

1 5 10

<210> 658

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 658

Ala Ala Asn Lys Ser Gln Ser

15

<210> 659

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 659

Gln His Tyr Tyr Arg Phe Pro Tyr Ser

15

<210> 660

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 660

Gly Gly Asn Asn Ile Gly Thr Lys Ser Val His

1 5 10

<210> 661

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 661

Asp Asp Ser Val Arg Pro Ser

15

<210> 662

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 662

Gln Val Trp Asp Ser Asp Ser Glu His Val Val

1 5 10

<210> 663

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 663

Ser Gly Asp Gly Leu Ser Lys Lys Tyr Val Ser

1 5 10

<210> 664

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 664

Arg Asp Lys Glu Arg Pro Ser

15

<210> 665

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 665

Gln Ala Trp Asp Asp Thr Thr Val Val

15

<210> 666

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 666

Arg Ala Ser Gln Gly Ile Arg Asn Trp Leu Ala

1 5 10

<210> 667

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 667

Ala Ala Ser Asn Leu Gln Ser

15

<210> 668

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 668

Gln Lys Tyr Asn Ser Ala Pro Phe Thr

15

<210> 669

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 669

Gly Gly Asn Asn Ile Gly Ser Lys Ser Val His

1 5 10

<210> 670

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 670

Gly Lys Asn Asn Arg Pro Ser

15

<210> 671

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 671

Ser Ser Arg Asp Ser Ser Gly Asp His Leu Arg Val

1 5 10

<210> 672

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 672

Gln Gly Asp Ser Leu Gly Asn Tyr Tyr Ala Thr

1 5 10

<210> 673

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 673

Gly Thr Asn Asn Arg Pro Ser

15

<210> 674

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 674

Asn Ser Arg Asp Ser Ser Gly His His Leu Leu

1 5 10

<210> 675

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 675

Arg Ala Ser Gln Ser Val Ser Ser Ala Tyr Leu Ala

1 5 10

<210> 676

<211> 14

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 676

Gln His Tyr Gly Ser Ser Phe Asn Gly Ser Ser Leu Phe Thr

1 5 10

<210> 677

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 677

Arg Ala Ser Gln Ser Val Ser Asn Ser Leu Ala

1 5 10

<210> 678

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 678

Asp Ala Ser Ser Arg Ala Thr

15

<210> 679

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 679

Gln Gln Phe Gly Thr Ser Ser Gly Leu Thr

1 5 10

<210> 680

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 680

Arg Ala Ser Gln Ser Val Ser Ser Ser Phe Leu Ala

1 5 10

<210> 681

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 681

Gly Ala Ser Ser Arg Ala Thr

15

<210> 682

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 682

Arg Ala Ser Gln Ser Val Ser Thr Thr Phe Leu Ala

1 5 10

<210> 683

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 683

Gly Ser Ser Asn Arg Ala Thr

15

<210> 684

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 684

Gln Gln Ser Tyr Ser Thr Pro Tyr Ser

15

<210> 685

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 685

Arg Ala Thr Gln Ser Ile Gly Ser Ser Phe Leu Ala

1 5 10

<210> 686

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 686

Gly Ala Ser Gln Arg Ala Thr

15

<210> 687

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 687

Gln His Tyr Glu Ser Ser Pro Ser Trp Thr

1 5 10

<210> 688

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 688

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala

1 5 10

<210> 689

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 689

Gln Gln Tyr Gly Ser Pro Arg Phe Thr

1 5 10

<210> 690

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 690

Gln His Tyr Gly Ser Ser Pro Ser Trp Thr

1 5 10

<210> 691

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 691

Arg Ala Ser Gln Arg Val Ala Ser Asn Tyr Leu Ala

1 5 10

<210> 692

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 692

Gln His Tyr Asp Ser Ser Pro Ser Trp Thr

1 5 10

<210> 693

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 693

Arg Ala Ser Gln Ser Leu Ser Ser Asn Phe Leu Ala

1 5 10

<210> 694

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 694

Gly Ala Ser Asn Trp Ala Thr

15

<210> 695

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 695

Gln Tyr Tyr Gly Thr Ser Pro Met Tyr Thr

1 5 10

<210> 696

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 696

Met Gln Ala Leu Gln Thr Pro Leu Thr

15

<210> 697

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 697

Gly Thr Ser Ser Arg Ala Thr

15

<210> 698

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 698

Gln His Tyr Gly Asn Ser Pro Pro Lys Phe Thr

1 5 10

<210> 699

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 699

Arg Ala Ser Gln Ser Val Ala Ser Ser Phe Leu Ala

1 5 10

<210> 700

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 700

Gly Ala Ser Gly Arg Ala Thr

15

<210> 701

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 701

Gln His Tyr Gly Gly Ser Pro Arg Leu Thr

1 5 10

<210> 702

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 702

Arg Ala Ser Gln Asp Val Asn Thr Ala Val Ser

1 5 10

<210> 703

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 703

Ser Ala Ser Tyr Arg Tyr Thr

15

<210> 704

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 704

Gln Gln His Tyr Ser Thr Pro Trp Thr

15

<210> 705

<211> 15

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 705

Arg Ala Ser Glu Ser Val Ser Val Ile Gly Ala His Leu Ile His

1 5 10 15

<210> 706

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 706

Leu Ala Ser Asn Leu Glu Thr

15

<210> 707

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 707

Leu Gln Ser Arg Ile Phe Pro Arg Thr

15

<210> 708

<211> 15

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 708

Arg Ala Ser Glu Ser Val Thr Ile Leu Gly Ser His Leu Ile Tyr

1 5 10 15

<210> 709

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 709

Leu Ala Ser Asn Val Gln Thr

15

<210> 710

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 710

Leu Gln Ser Arg Thr Ile Pro Arg Thr

15

<210> 711

<400> 711

000

<210> 712

<400> 712

000

<210> 713

<400> 713

000

<210> 714

<400> 714

000

<210> 715

<400> 715

000

<210> 716

<400> 716

000

<210> 717

<400> 717

000

<210> 718

<400> 718

000

<210> 719

<400> 719

000

<210> 720

<400> 720

000

<210> 721

<400> 721

000

<210> 722

<400> 722

000

<210> 723

<400> 723

000

<210> 724

<211> 485

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 724

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Glu Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Asp Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Ser Gly Trp Asp Phe Asp Tyr Trp Gly Gln

115 120 125

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met

145 150 155 160

Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr

165 170 175

Ile Thr Cys Arg Ala Ser Gln Ser Ile Arg Tyr Tyr Leu Ser Trp Tyr

180 185 190

Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Thr Ala Ser

195 200 205

Ile Leu Gln Asn Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly

210 215 220

Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

225 230 235 240

Thr Tyr Tyr Cys Leu Gln Thr Tyr Thr Thr Pro Asp Phe Gly Pro Gly

245 250 255

Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

260 265 270

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

275 280 285

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

290 295 300

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

305 310 315 320

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

325 330 335

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

340 345 350

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

355 360 365

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

370 375 380

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

385 390 395 400

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

405 410 415

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

420 425 430

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

435 440 445

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

450 455 460

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

465 470 475 480

Ala Leu Pro Pro Arg

485

<210> 725

<211> 485

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 725

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Asn Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Arg Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Ser Gly Trp Asp Phe Asp Tyr Trp Gly Gln

115 120 125

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Arg Met

145 150 155 160

Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr

165 170 175

Ile Thr Cys Arg Ala Ser Gln Ser Ile Arg Tyr Tyr Leu Ser Trp Tyr

180 185 190

Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Thr Ala Ser

195 200 205

Ile Leu Gln Asn Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly

210 215 220

Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

225 230 235 240

Thr Tyr Tyr Cys Leu Gln Thr Tyr Thr Thr Pro Asp Phe Gly Pro Gly

245 250 255

Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

260 265 270

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

275 280 285

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

290 295 300

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

305 310 315 320

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

325 330 335

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

340 345 350

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

355 360 365

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

370 375 380

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

385 390 395 400

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

405 410 415

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

420 425 430

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

435 440 445

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

450 455 460

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

465 470 475 480

Ala Leu Pro Pro Arg

485

<210> 726

<211> 383

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 726

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Ser Gly Pro Glu Leu

20 25 30

Glu Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Ser Phe Thr Gly Tyr Thr Met Asn Trp Val Lys Gln Ser His Gly Lys

50 55 60

Ser Leu Glu Trp Ile Gly Leu Ile Thr Pro Tyr Asn Gly Ala Ser Ser

65 70 75 80

Tyr Asn Gln Lys Phe Arg Gly Lys Ala Thr Leu Thr Val Asp Lys Ser

85 90 95

Ser Ser Thr Ala Tyr Met Asp Leu Leu Ser Leu Thr Ser Glu Asp Ser

100 105 110

Ala Val Tyr Phe Cys Ala Arg Gly Gly Tyr Asp Gly Arg Gly Phe Asp

115 120 125

Tyr Trp Gly Glyn Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Glu Leu Thr

145 150 155 160

Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met

165 170 175

Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met His Trp Tyr Gln Gln

180 185 190

Lys Ser Gly Thr Ser Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Leu

195 200 205

Ala Ser Gly Val Pro Gly Arg Phe Ser Gly Ser Gly Ser Gly Asn Ser

210 215 220

Tyr Ser Leu Thr Ile Ser Val Glu Ala Glu Asp Asp Ala Thr Tyr

225 230 235 240

Tyr Cys Gln Gln Trp Ser Gly Tyr Pro Leu Thr Phe Gly Ala Gly Thr

245 250 255

Lys Leu Glu Ile Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala

260 265 270

Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg

275 280 285

Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys

290 295 300

Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu

305 310 315 320

Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu

325 330 335

Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln

340 345 350

Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly

355 360 365

Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala

370 375 380

<210> 727

<211> 488

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 727

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Gly Arg Tyr Tyr Gly Met Asp Val Trp

115 120 125

Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Ile Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn Phe Ala

180 185 190

Trp Tyr Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp

195 200 205

Ala Ser Asn Arg Ala Thr Gly Ile Pro Arg Phe Ser Gly Ser Gly

210 215 220

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp

225 230 235 240

Phe Ala Ala Tyr Tyr Cys His Gln Arg Ser Asn Trp Leu Tyr Thr Phe

245 250 255

Gly Gln Gly Thr Lys Val Asp Ile Lys Thr Thr Thr Pro Ala Pro Arg

260 265 270

Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg

275 280 285

Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly

290 295 300

Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr

305 310 315 320

Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg

325 330 335

Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro

340 345 350

Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu

355 360 365

Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala

370 375 380

Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu

385 390 395 400

Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly

405 410 415

Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu

420 425 430

Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser

435 440 445

Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly

450 455 460

Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu

465 470 475 480

His Met Gln Ala Leu Pro Pro Arg

485

<210> 728

<211> 497

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 728

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Leu Arg Arg Thr Val Val Thr Pro

115 120 125

Arg Ala Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr

130 135 140

Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

145 150 155 160

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser

165 170 175

Thr Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala

180 185 190

Ser Gln Asp Ile Ser Asn Ser Leu Asn Trp Tyr Gln Gln Lys Ala Gly

195 200 205

Lys Ala Pro Lys Leu Leu Ile Tyr Asp Ala Ser Thr Leu Glu Thr Gly

210 215 220

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser Phe

225 230 235 240

Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln

245 250 255

Gln His Asp Asn Leu Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu

260 265 270

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

275 280 285

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

290 295 300

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

305 310 315 320

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

325 330 335

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

340 345 350

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

355 360 365

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

370 375 380

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

385 390 395 400

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

405 410 415

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

420 425 430

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

435 440 445

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

450 455 460

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

465 470 475 480

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

485 490 495

Arg

<210> 729

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 729

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Pro Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Gly Glu Trp Asp Gly Ser Tyr Tyr Tyr

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

145 150 155 160

Ser Asp Ile Val Leu Thr Gln Thr Pro Ser Ser Leu Ser Ala Ser Val

165 170 175

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Asn Thr

180 185 190

Tyr Leu Asn Trp Tyr Gln His Lys Pro Gly Lys Ala Pro Lys Leu Leu

195 200 205

Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln

225 230 235 240

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Phe Ser Pro Leu

245 250 255

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 730

<211> 486

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 730

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Trp Met His Trp Val Arg Gln Val Pro Gly Lys

50 55 60

Gly Leu Val Trp Val Ser Arg Ile Asn Thr Asp Gly Ser Thr Thr Thr

65 70 75 80

Tyr Ala Asp Ser Val Glu Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Asp Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Val Gly Gly His Trp Ala Val Trp Gly Gln Gly

115 120 125

Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr

145 150 155 160

Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile

165 170 175

Thr Cys Arg Ala Ser Gln Ser Ile Ser Asp Arg Leu Ala Trp Tyr Gln

180 185 190

Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Ser

195 200 205

Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr

210 215 220

Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala Val

225 230 235 240

Tyr Tyr Cys Gln Gln Tyr Gly His Leu Pro Met Tyr Thr Phe Gly Gln

245 250 255

Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg

485

<210> 731

<211> 497

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 731

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Ser Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Tyr Arg Leu Ile Ala Val Ala Gly Asp

115 120 125

Tyr Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Met Val Thr

130 135 140

Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

145 150 155 160

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

165 170 175

Ser Val Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

180 185 190

Ser Gln Gly Val Gly Arg Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly

195 200 205

Thr Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Thr Leu Gln Ser Gly

210 215 220

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

225 230 235 240

Thr Ile Asn Asn Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

245 250 255

Gln Ala Asn Ser Phe Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu

260 265 270

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

275 280 285

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

290 295 300

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

305 310 315 320

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

325 330 335

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

340 345 350

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

355 360 365

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

370 375 380

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

385 390 395 400

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

405 410 415

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

420 425 430

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

435 440 445

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

450 455 460

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

465 470 475 480

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

485 490 495

Arg

<210> 732

<211> 494

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 732

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Gly Gly Val

20 25 30

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Trp Lys Val Ser Ser Ser Ser Pro Ala

115 120 125

Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

145 150 155 160

Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser

165 170 175

Pro Gly Glu Arg Ala Ile Leu Ser Cys Arg Ala Ser Gln Ser Val Tyr

180 185 190

Thr Lys Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg

195 200 205

Leu Leu Ile Tyr Asp Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Arg

225 230 235 240

Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Gly

245 250 255

Ser Pro Leu Ile Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Thr

260 265 270

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

275 280 285

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

290 295 300

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

305 310 315 320

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

325 330 335

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

340 345 350

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

355 360 365

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

370 375 380

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn

385 390 395 400

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

405 410 415

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

420 425 430

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

435 440 445

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

450 455 460

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

465 470 475 480

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 733

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 733

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Thr Ser Gly Tyr

35 40 45

Pro Phe Thr Gly Tyr Ser Leu His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp His Tyr Gly Gly Asn Ser Leu Phe

115 120 125

Tyr Trp Gly Glyn Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Ile Ser Ala Ser Val Gly

165 170 175

Asp Thr Val Ser Ile Thr Cys Arg Ala Ser Gln Asp Ser Gly Thr Trp

180 185 190

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Met

195 200 205

Tyr Asp Ala Ser Thr Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly

210 215 220

Ser Ala Ser Gly Thr Glu Phe Thr Leu Thr Val Asn Arg Leu Gln Pro

225 230 235 240

Glu Asp Ser Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Pro Leu

245 250 255

Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 734

<211> 492

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 734

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Glu Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Ser Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Gly

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Thr Ser Thr Val His Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Gly Gly Tyr Ser Ser Ser Ser Ser Asp Ala

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

145 150 155 160

Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Pro Ser Leu Ser Ala Ser

165 170 175

Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser

180 185 190

Ser Ala Leu Ala Trp Tyr Gln Gln Lys Pro Gly Thr Pro Pro Lys Leu

195 200 205

Leu Ile Tyr Asp Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe

210 215 220

Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu

225 230 235 240

Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Phe Ser Ser Tyr

245 250 255

Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr

260 265 270

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

275 280 285

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

290 295 300

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

305 310 315 320

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

325 330 335

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

340 345 350

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

355 360 365

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

370 375 380

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu

385 390 395 400

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

405 410 415

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

420 425 430

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

435 440 445

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

450 455 460

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

465 470 475 480

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 735

<211> 499

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 735

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Ser Tyr Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn

65 70 75 80

Tyr Ala Gln Lys Leu Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser

85 90 95

Thr Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Val Ala Gly Gly Ile Tyr Tyr Tyr Tyr

115 120 125

Gly Met Asp Val Trp Gly Gln Gly Thr Thr Ile Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

145 150 155 160

Gly Gly Ser Asp Ile Val Met Thr Gln Thr Pro Asp Ser Leu Ala Val

165 170 175

Ser Leu Gly Glu Arg Ala Thr Ile Ser Cys Lys Ser Ser His Ser Val

180 185 190

Leu Tyr Asn Arg Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys

195 200 205

Pro Gly Gln Pro Pro Lys Leu Leu Phe Tyr Trp Ala Ser Thr Arg Lys

210 215 220

Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

225 230 235 240

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe

245 250 255

Cys Gln Gln Thr Gln Thr Phe Pro Leu Thr Phe Gly Gln Gly Thr Arg

260 265 270

Leu Glu Ile Asn Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala

275 280 285

Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg

290 295 300

Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys

305 310 315 320

Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu

325 330 335

Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu

340 345 350

Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln

355 360 365

Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly

370 375 380

Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr

385 390 395 400

Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg

405 410 415

Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met

420 425 430

Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu

435 440 445

Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys

450 455 460

Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu

465 470 475 480

Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu

485 490 495

Pro Pro Arg

<210> 736

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 736

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Arg Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser

85 90 95

Thr Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Thr Thr Thr Ser Tyr Ala Phe Asp Ile

115 120 125

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp

145 150 155 160

Ile Gln Leu Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly Asp

165 170 175

Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Thr Trp Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile Tyr

195 200 205

Lys Ala Ser Thr Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp

225 230 235 240

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Thr Tyr Ser Pro Tyr

245 250 255

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 737

<211> 493

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 737

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu

20 25 30

Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Phe

35 40 45

Ile Phe Ser Asp Tyr Tyr Met Gly Trp Ile Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Tyr Ile Gly Arg Ser Gly Ser Ser Met Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Phe Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Ala Ser Pro Val Val Ala Ala Thr Glu Asp

115 120 125

Phe Gln His Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

145 150 155 160

Gly Ser Asp Ile Val Met Thr Gln Thr Pro Ala Thr Leu Ser Leu Ser

165 170 175

Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Thr

180 185 190

Ser Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg

195 200 205

Leu Leu Leu Phe Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Arg

225 230 235 240

Leu Glu Pro Glu Asp Phe Ala Met Tyr Tyr Cys Gln Gln Tyr Gly Ser

245 250 255

Ala Pro Val Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr

260 265 270

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

275 280 285

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

290 295 300

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

305 310 315 320

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

325 330 335

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

340 345 350

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

355 360 365

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

370 375 380

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln

385 390 395 400

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

405 410 415

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

420 425 430

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

435 440 445

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

450 455 460

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

465 470 475 480

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 738

<211> 493

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 738

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Arg Ala Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Phe

35 40 45

Thr Phe Arg Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Ile Ile Asn Pro Ser Gly Gly Ser Arg Ala

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Asp Asp Thr

100 105 110

Ala Met Tyr Tyr Cys Ala Arg Thr Ala Ser Cys Gly Gly Asp Cys Tyr

115 120 125

Tyr Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

145 150 155 160

Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Pro Thr Leu Ser Ala

165 170 175

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Val

180 185 190

Asn Ile Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

195 200 205

Leu Leu Ile Tyr Lys Ser Ser Ser Leu Ala Ser Gly Val Pro Ser Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Ala Glu Phe Thr Leu Thr Ile Ser Ser

225 230 235 240

Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Gln Ser

245 250 255

Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys Thr Thr

260 265 270

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

275 280 285

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

290 295 300

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

305 310 315 320

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

325 330 335

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

340 345 350

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

355 360 365

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

370 375 380

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln

385 390 395 400

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

405 410 415

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

420 425 430

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

435 440 445

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

450 455 460

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

465 470 475 480

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 739

<211> 488

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 739

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Asp Asp Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Asp Gly Ser Ser Ser Trp Ser Trp Gly

115 120 125

Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Ser

145 150 155 160

Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln Thr Val

165 170 175

Arg Thr Thr Cys Gln Gly Asp Ala Leu Arg Ser Tyr Tyr Ala Ser Trp

180 185 190

Tyr Gln Gln Lys Pro Gly Gln Ala Pro Met Leu Val Ile Tyr Gly Lys

195 200 205

Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Asp Ser

210 215 220

Gly Asp Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu

225 230 235 240

Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly Tyr Pro Val Phe

245 250 255

Gly Thr Gly Thr Lys Val Thr Val Leu Thr Thr Thr Pro Ala Pro Arg

260 265 270

Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg

275 280 285

Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly

290 295 300

Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr

305 310 315 320

Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg

325 330 335

Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro

340 345 350

Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu

355 360 365

Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala

370 375 380

Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu

385 390 395 400

Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly

405 410 415

Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu

420 425 430

Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser

435 440 445

Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly

450 455 460

Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu

465 470 475 480

His Met Gln Ala Leu Pro Pro Arg

485

<210> 740

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 740

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Asp Asp Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Thr Gly

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Leu Tyr Tyr Cys Ala Lys Asp Ser Ser Ser Trp Tyr Gly Gly Gly

115 120 125

Ser Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser

145 150 155 160

Ser Glu Leu Thr Gln Glu Pro Ala Val Ser Val Ala Leu Gly Gln Thr

165 170 175

Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser

180 185 190

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Phe Gly

195 200 205

Arg Ser Arg Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser

210 215 220

Ser Gly Asn Thr Ala Ser Leu Ile Ile Thr Gly Ala Gln Ala Glu Asp

225 230 235 240

Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Asn Thr Ala Asn His Tyr

245 250 255

Val Phe Gly Thr Gly Thr Lys Leu Thr Val Leu Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 741

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 741

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Asp Asp Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Thr Gly

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Leu Tyr Tyr Cys Ala Lys Asp Ser Ser Ser Trp Tyr Gly Gly Gly

115 120 125

Ser Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser

145 150 155 160

Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln Thr

165 170 175

Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser

180 185 190

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr Gly

195 200 205

Lys Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser

210 215 220

Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp

225 230 235 240

Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Gly Ser Ser Gly Asn His Tyr

245 250 255

Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 742

<211> 495

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 742

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Val Trp Val Ser Arg Ile Asn Ser Asp Gly Ser Ser Thr Ser

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Val Arg Thr Gly Trp Val Gly Ser Tyr Tyr Tyr

115 120 125

Tyr Met Asp Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

145 150 155 160

Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu

165 170 175

Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val

180 185 190

Ser Ser Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro

195 200 205

Arg Leu Leu Ile Tyr Asp Val Ser Thr Arg Ala Thr Gly Ile Pro Ala

210 215 220

Arg Phe Ser Gly Gly Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

225 230 235 240

Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser

245 250 255

Asn Trp Pro Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

260 265 270

Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala

275 280 285

Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly

290 295 300

Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile

305 310 315 320

Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val

325 330 335

Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe

340 345 350

Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly

355 360 365

Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg

370 375 380

Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln

385 390 395 400

Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp

405 410 415

Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro

420 425 430

Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp

435 440 445

Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg

450 455 460

Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr

465 470 475 480

Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490 495

<210> 743

<211> 494

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 743

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Gly Gly Val

20 25 30

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Gly Tyr Ser Arg Tyr Tyr Tyr Tyr Gly

115 120 125

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

145 150 155 160

Gly Ser Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser

165 170 175

Pro Gly Glu Arg Ala Ile Leu Ser Cys Arg Ala Ser Gln Ser Val Tyr

180 185 190

Thr Lys Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg

195 200 205

Leu Leu Ile Tyr Asp Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Arg

225 230 235 240

Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Gly

245 250 255

Ser Pro Leu Ile Thr Phe Gly Gln Gly Thr Lys Val Asp Ile Lys Thr

260 265 270

Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser

275 280 285

Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly

290 295 300

Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp

305 310 315 320

Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile

325 330 335

Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys

340 345 350

Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys

355 360 365

Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val

370 375 380

Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn

385 390 395 400

Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val

405 410 415

Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg

420 425 430

Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys

435 440 445

Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg

450 455 460

Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys

465 470 475 480

Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 744

<211> 493

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 744

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Arg Glu Ala Ala Ala Gly His Asp Trp

115 120 125

Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

145 150 155 160

Gly Gly Ser Asp Ile Arg Val Thr Gln Ser Pro Ser Ser Leu Ser Ala

165 170 175

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile

180 185 190

Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

195 200 205

Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

225 230 235 240

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser

245 250 255

Ile Pro Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr

260 265 270

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

275 280 285

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

290 295 300

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

305 310 315 320

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

325 330 335

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

340 345 350

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

355 360 365

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

370 375 380

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln

385 390 395 400

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

405 410 415

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

420 425 430

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

435 440 445

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

450 455 460

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

465 470 475 480

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 745

<211> 491

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 745

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Trp Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Ser Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Thr Ser Thr Val Tyr Met Glu Leu Ser Asn Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Ser Pro Arg Val Thr Thr Gly Tyr Phe

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

145 150 155 160

Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val

165 170 175

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

180 185 190

Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

195 200 205

Ile Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln

225 230 235 240

Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro

245 250 255

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

305 310 315 320

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

325 330 335

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

340 345 350

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

355 360 365

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

370 375 380

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

385 390 395 400

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

405 410 415

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

420 425 430

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

435 440 445

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

450 455 460

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

465 470 475 480

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 746

<211> 497

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 746

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Arg Arg Pro Gly Ala Ser Val Lys Ile Ser Cys Arg Ala Ser Gly Asp

35 40 45

Thr Ser Thr Arg His Tyr Ile His Trp Leu Arg Gln Ala Pro Gly Gln

50 55 60

Gly Pro Glu Trp Met Gly Val Ile Asn Pro Thr Thr Gly Pro Ala Thr

65 70 75 80

Gly Ser Pro Ala Tyr Ala Gln Met Leu Gln Gly Arg Val Thr Met Thr

85 90 95

Arg Asp Thr Ser Thr Arg Thr Val Tyr Met Glu Leu Arg Ser Leu Arg

100 105 110

Phe Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Val Val Gly Arg

115 120 125

Ser Ala Pro Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr

130 135 140

Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

145 150 155 160

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

165 170 175

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

180 185 190

Ser Gln Gly Ile Ser Asp Tyr Ser Ala Trp Tyr Gln Gln Lys Pro Gly

195 200 205

Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Thr Leu Gln Ser Gly

210 215 220

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

225 230 235 240

Thr Ile Ser Tyr Leu Gln Ser Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

245 250 255

Gln Tyr Tyr Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp

260 265 270

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

275 280 285

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

290 295 300

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

305 310 315 320

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

325 330 335

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

340 345 350

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

355 360 365

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

370 375 380

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

385 390 395 400

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

405 410 415

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

420 425 430

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

435 440 445

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

450 455 460

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

465 470 475 480

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

485 490 495

Arg

<210> 747

<211> 493

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 747

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Asn Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Ile Ile Asn Pro Ser Gly Gly Tyr Thr Thr

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Leu Thr Met Thr Arg Asp Thr Ser

85 90 95

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Ile Arg Ser Cys Gly Gly Asp Cys Tyr

115 120 125

Tyr Phe Asp Asn Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

145 150 155 160

Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Thr Leu Ser Ala

165 170 175

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Val

180 185 190

Asn Ile Trp Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

195 200 205

Leu Leu Ile Tyr Lys Ser Ser Ser Leu Ala Ser Gly Val Pro Ser Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Ala Glu Phe Thr Leu Thr Ile Ser Ser

225 230 235 240

Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Gln Ser

245 250 255

Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys Thr Thr

260 265 270

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

275 280 285

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

290 295 300

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

305 310 315 320

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

325 330 335

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

340 345 350

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

355 360 365

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

370 375 380

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln

385 390 395 400

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

405 410 415

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

420 425 430

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

435 440 445

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

450 455 460

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

465 470 475 480

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 748

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 748

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ile Thr Leu Lys Glu Ser Gly Pro Ala Leu

20 25 30

Val Lys Pro Thr Gln Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe

35 40 45

Ser Leu Ser Thr Ala Gly Val His Val Gly Trp Ile Arg Gln Pro Pro

50 55 60

Gly Lys Ala Leu Glu Trp Leu Ala Leu Ile Ser Trp Ala Asp Asp Lys

65 70 75 80

Arg Tyr Arg Pro Ser Leu Arg Ser Arg Leu Asp Ile Thr Arg Val Thr

85 90 95

Ser Lys Asp Gln Val Val Leu Ser Met Thr Asn Met Gln Pro Glu Asp

100 105 110

Thr Ala Thr Tyr Tyr Cys Ala Leu Gln Gly Phe Asp Gly Tyr Glu Ala

115 120 125

Asn Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Ala Gly

165 170 175

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Arg Gly Ile Ser Ser Ala

180 185 190

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Lys Leu Leu Ile

195 200 205

Tyr Asp Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly

210 215 220

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asp Ser Leu Glu Pro

225 230 235 240

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Trp

245 250 255

Thr Phe Gly Gln Gly Thr Lys Val Asp Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 749

<211> 1461

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 749

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc aactcgtcca aagcggagcg gaagtcaaga aacccggagc gagcgtgaaa

120

gtgtcctgca aagcctccgg ctacaccttt acgggctact acatgcactg ggtgcgccag

180

gcaccaggac agggtcttga atggatggga tggatcaacc ctaattcggg cggaactaac

240

tacgcacaga agttccaggg gagagtgact ctgactcggg atacctccat ctcaactgtc

300

tacatggaac tctcccgctt gcggtcagat gatacggcag tgtactactg cgcccgcgac

360

atgaatatcc tggctaccgt gccgttcgac atctggggac aggggactat ggttactgtc

420

tcatcgggcg gtggaggttc aggaggaggc ggctcgggag gcggaggttc ggacattcag

480

atgacccagt ccccatcctc tctgtcggcc agcgtcggag atagggtgac cattacctgt

540

cgggcctcgc aaagcatctc ctcgtacctc aactggtatc agcaaaagcc gggaaaggcg

600

cctaagctgc tgatctacgc cgcttcgagc ttgcaaagcg gggtgccatc cagattctcg

660

ggatcaggct caggaaccga cttcaccctg accgtgaaca gcctccagcc ggaggacttt

720

gccacttact actgccagca gggagactcc gtgccgctta ctttcggggg gggtacccgc

780

ctggagatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

840

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

900

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

960

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1020

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1080

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1140

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1200

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

1260

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

1320

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

1380

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

1440

atgcaggccc tgccgcctcg g

1461

<210> 750

<211> 487

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 750

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln

145 150 155 160

Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

165 170 175

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

180 185 190

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

195 200 205

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

210 215 220

Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln Pro Glu Asp Phe

225 230 235 240

Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly

245 250 255

Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

260 265 270

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

275 280 285

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

290 295 300

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

305 310 315 320

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

325 330 335

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

340 345 350

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

355 360 365

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

370 375 380

Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

385 390 395 400

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

405 410 415

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

420 425 430

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

435 440 445

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

450 455 460

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

465 470 475 480

Met Gln Ala Leu Pro Pro Arg

485

<210> 751

<211> 264

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 751

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln

145 150 155 160

Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

165 170 175

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

180 185 190

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

195 200 205

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

210 215 220

Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln Pro Glu Asp Phe

225 230 235 240

Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly

245 250 255

Gly Gly Thr Arg Leu Glu Ile Lys

260

<210> 752

<211> 121

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 752

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 753

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 753

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys

100 105

<210> 754

<211> 1461

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 754

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtcc aactcgttca atccggcgca gaagtcaaga agccaggagc atcagtgaaa

120

gtgtcctgca aagcctcagg ctacatcttc acgggatact acatccactg ggtgcgccag

180

gctccgggcc agggccttga gtggatgggc tggatcaacc ctaactctgg gggaaccaac

240

tacgctcaga agttccaggg gagggtcact atgactcgcg atacctccat ctccactgcg

300

tacatggaac tctcgggact gagatccgac gatcctgccg tgtactactg cgcccgggac

360

atgaacatct tggcgaccgt gccgtttgac atttggggac agggcaccct cgtcactgtg

420

tcgagcggtg gaggaggctc ggggggtggc ggatcaggag ggggaggaag cgacatccag

480

ctgactcaga gcccatcgtc gttgtccgcg tcggtggggg atagagtgac cattacttgc

540

cgcgccagcc agagcatctc atcatatctg aattggtacc agcagaagcc cggaaaggcc

600

ccaaaactgc tgatctacgc tgcaagcagc ctccaatcgg gagtgccgtc acggttctcc

660

gggtccggtt cgggaactga ctttaccctg accgtgaatt cgctgcaacc ggaggatttc

720

gccacgtact actgtcagca aggagactcc gtgccgctga ccttcggtgg aggcaccaag

780

gtcgaaatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

840

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

900

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

960

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1020

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1080

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1140

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1200

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

1260

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

1320

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

1380

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

1440

atgcaggccc tgccgcctcg g

1461

<210> 755

<211> 487

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 755

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Ile Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Gly Leu Arg Ser Asp Asp Pro

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln

145 150 155 160

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

165 170 175

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

180 185 190

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

195 200 205

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

210 215 220

Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln Pro Glu Asp Phe

225 230 235 240

Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly

245 250 255

Gly Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

260 265 270

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

275 280 285

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

290 295 300

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

305 310 315 320

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

325 330 335

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

340 345 350

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

355 360 365

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

370 375 380

Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

385 390 395 400

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

405 410 415

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

420 425 430

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

435 440 445

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

450 455 460

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

465 470 475 480

Met Gln Ala Leu Pro Pro Arg

485

<210> 756

<211> 264

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 756

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Ile Phe Thr Gly Tyr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Gly Leu Arg Ser Asp Asp Pro

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln

145 150 155 160

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

165 170 175

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

180 185 190

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

195 200 205

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

210 215 220

Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln Pro Glu Asp Phe

225 230 235 240

Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly

245 250 255

Gly Gly Thr Lys Val Glu Ile Lys

260

<210> 757

<211> 121

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 757

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Gly Tyr

20 25 30

Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Gly Leu Arg Ser Asp Asp Pro Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 758

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 758

Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 759

<211> 1467

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 759

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtcc aactccaaca gtcaggcgca gaagtgaaaa agagcggtgc atcggtgaaa

120

gtgtcatgca aagcctcggg ctacaccttc actgactact atatgcactg gctgcggcag

180

gcaccgggac agggacttga gtggatggga tggatcaacc cgaattcagg ggacactaac

240

tacgcgcaga agttccaggg gagagtgacc ctgacgaggg acacctcaat ttcgaccgtc

300

tacatggaat tgtcgcgcct gagatcggac gatactgctg tgtactactg tgcccgcgac

360

atgaacatcc tcgcgactgt gccttttgat atctggggac aggggactat ggtcaccgtt

420

tcctccgctt ccggtggcgg aggctcggga ggccgggcct ccggtggagg aggcagcgac

480

atccagatga ctcagagccc ttcctcgctg agcgcctcag tgggagatcg cgtgaccatc

540

acttgccggg ccagccagtc catttcgtcc tacctcaatt ggtaccagca gaagccggga

600

aaggcgccca agctcttgat ctacgctgcg agctccctgc aaagcggggt gccgagccga

660

ttctcgggtt ccggctcggg aaccgacttc actctgacca tctcatccct gcaaccagag

720

gactttgcca cctactactg ccaacaagga gattctgtcc cactgacgtt cggcggagga

780

accaaggtcg aaatcaagac cactacccca gcaccgaggc cacccacccc ggctcctacc

840

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

900

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

960

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1020

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1080

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1140

ttcagccgca gcgcagatgc tccagcctac aagcaggggc agaaccagct ctacaacgaa

1200

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

1260

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

1320

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

1380

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

1440

cttcacatgc aggccctgcc gcctcgg

1467

<210> 760

<211> 336

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 760

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Ser Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Asp Tyr Tyr Met His Trp Leu Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Asp Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp

145 150 155 160

Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp

165 170 175

Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu

180 185 190

Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr

195 200 205

Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

225 230 235 240

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu Thr

245 250 255

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro

260 265 270

Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu

275 280 285

Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg

290 295 300

Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly

305 310 315 320

Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys

325 330 335

<210> 761

<211> 266

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 761

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Ser Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Asp Tyr Tyr Met His Trp Leu Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Asp Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp

145 150 155 160

Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp

165 170 175

Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu

180 185 190

Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr

195 200 205

Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

225 230 235 240

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu Thr

245 250 255

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

260 265

<210> 762

<211> 121

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 762

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Ser Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Tyr Met His Trp Leu Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Asp Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 763

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 763

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 764

<211> 1461

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 764

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtcc aactcgtcca gtcaggagcg gaagtcaaga agcccggagc gtcagtcaaa

120

gtgtcatgca aagcctcggg ctacactttc actgggtact acatgcactg ggtgcgccag

180

gctccaggac agggactgga atggatggga tggatcaacc cgaactccgg tggcaccaat

240

tacgcccaga agttccaggg gagggtgacc atgactcgcg acacgtcgat cagcaccgca

300

tacatggagc tgtcaagact ccggtccgac gatactgccg tgtactactg cgcacgggac

360

atgaacattc tggccaccgt gccttttgac atctggggtc agggaactat ggttaccgtg

420

tcctctggtg gaggcggctc cggcgggggg ggaagcggag gcggtggaag cgacattcag

480

atgacccagt cgccttcatc cctttcggcg agcgtgggag atcgcgtcac tatcacttgt

540

cgggcctcgc agtccatctc cacctacctc aattggtacc agcagaagcc aggaaaagca

600

ccgaatctgc tgatctacgc cgcgttttcc ttgcaatcgg gagtgccaag cagattcagc

660

ggatcgggat caggcactga tttcaccctc accatcaact cgctgcaacc ggaggatttc

720

gctacgtact attgccaaca aggagacagc gtgccgctca ccttcggcgg agggactaag

780

ctggaaatca agaccactac ccgcaccg aggccaccca ccccggctcc taccatcgcc

840

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

900

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

960

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1020

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1080

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1140

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1200

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

1260

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

1320

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

1380

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

1440

atgcaggccc tgccgcctcg g

1461

<210> 765

<211> 487

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 765

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln

145 150 155 160

Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

165 170 175

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Thr Tyr Leu Asn Trp

180 185 190

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile Tyr Ala Ala

195 200 205

Phe Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

210 215 220

Gly Thr Asp Phe Thr Leu Thr Ile Asn Ser Leu Gln Pro Glu Asp Phe

225 230 235 240

Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly

245 250 255

Gly Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

260 265 270

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

275 280 285

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

290 295 300

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

305 310 315 320

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

325 330 335

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

340 345 350

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

355 360 365

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

370 375 380

Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

385 390 395 400

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

405 410 415

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

420 425 430

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

435 440 445

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

450 455 460

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

465 470 475 480

Met Gln Ala Leu Pro Pro Arg

485

<210> 766

<211> 264

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 766

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln

145 150 155 160

Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

165 170 175

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Thr Tyr Leu Asn Trp

180 185 190

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile Tyr Ala Ala

195 200 205

Phe Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

210 215 220

Gly Thr Asp Phe Thr Leu Thr Ile Asn Ser Leu Gln Pro Glu Asp Phe

225 230 235 240

Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu Thr Phe Gly

245 250 255

Gly Gly Thr Lys Leu Glu Ile Lys

260

<210> 767

<211> 121

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 767

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly

100 105 110

Gln Gly Thr Met Val Thr Val Ser Ser

115 120

<210> 768

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 768

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Thr Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile

35 40 45

Tyr Ala Ala Phe Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 769

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 769

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagatcc agctggtgca gtcgggagct gaagtcaaaa agcctggcgc aaccgtcaag

120

atctcgtgca aggatcagg gttcaacatc gaggactact acatccattg ggtgcaacag

180

gcaccgggaa aaggcctgga gtggatgggg aggattgacc cagaaaatga cgaaaccaag

240

tacggaccga tcttccaagg acgggtgacc atcacggctg acacttccac taacaccgtc

300

tacatggaac tctcgagcct tcgctcggaa gataccgcgg tgtactactg cgcctttaga

360

ggtggagtct actggggaca agggactacc gtcaccgtgt cgtcaggtgg cggaggatca

420

ggcgggaggcg gctccggtgg aggaggaagc ggaggaggtg gctccgacgt ggtgatgacg

480

cagtcaccgg actccttggc ggtgagcctg ggtgaacgcg ccactatcaa ctgcaagagc

540

tcccagagct tgctggactc cgatggaaag acttatctca attggctgca acagaagcct

600

ggccagccgc caaagagact catctcactg gtgagcaagc tggatagcgg agtgccagat

660

cggttttcgg gatcgggctc aggcaccgac ttcaccctga ctatttcctc cctccaagcc

720

gaggatgtgg ccgtctacta ctgttggcag gggactcact tcccggggac cttcggtgga

780

ggcactaagg tggagatcaa aaccactacc cggcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 770

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 770

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Gly Ser Gly Phe

35 40 45

Asn Ile Glu Asp Tyr Tyr Ile His Trp Val Gln Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys

65 70 75 80

Tyr Gly Pro Ile Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser

85 90 95

Thr Asn Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly

115 120 125

Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr

145 150 155 160

Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile

165 170 175

Asn Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr

180 185 190

Leu Asn Trp Leu Gln Gln Lys Pro Gly Gln Pro Pro Lys Arg Leu Ile

195 200 205

Ser Leu Val Ser Lys Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly

210 215 220

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

225 230 235 240

Glu Asp Val Ala Val Tyr Tyr Cys Trp Gln Gly Thr His Phe Pro Gly

245 250 255

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 771

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 771

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgacgtgg tcatgactca aagcccagat tccttggctg tctcccttgg agaaagagca

120

acgatcaatt gcaaaagctc gcagtccctg ttggactccg atggaaaaac ctacctcaac

180

tggctgcagc agaagccggg acaaccacca aagcggctga tttccctcgt gtccaagctg

240

gacagcggcg tgccggatcg cttctcgggc agcggctcgg gaaccgattt tactctcact

300

atttcgtcac tgcaagcgga ggacgtggcg gtgtattact gctggcaggg cactcacttc

360

ccgggtactt ttggtggagg taccaaagtc gaaatcaagg gtggaggcgg gagcggagga

420

ggcgggtcgg gaggaggagg atcgggtggc ggaggctcag aaatccagct ggtgcagtca

480

ggtgccgaag tgaagaagcc tggggccacg gtgaagatct cgtgcaaggg gagcggattc

540

aacatcgagg attactacat ccattggggtg caacaggccc ctggcaaagg gctggaatgg

600

atgggaagga tcgaccccga gaatgacgag actaagtacg gcccgatctt ccaaggacgg

660

gtgaccatca ctgcagacac ttcaaccaac accgtctaca tggaactctc ctcgctgcgc

720

tccgaggaca ccgccgtgta ctactgtgct ttcagaggag gagtctactg gggacaggga

780

acgaccgtga ccgtcagctc aaccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 772

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 772

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu

20 25 30

Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln

35 40 45

Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln Gln

50 55 60

Lys Pro Gly Gln Pro Pro Lys Arg Leu Ile Ser Leu Val Ser Lys Leu

65 70 75 80

Asp Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

85 90 95

Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr

100 105 110

Tyr Cys Trp Gly Thr His Phe Pro Gly Thr Phe Gly Gly Gly Thr

115 120 125

Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Gln Leu Val Gln Ser

145 150 155 160

Gly Ala Glu Val Lys Lys Pro Gly Ala Thr Val Lys Ile Ser Cys Lys

165 170 175

Gly Ser Gly Phe Asn Ile Glu Asp Tyr Tyr Ile His Trp Val Gln Gln

180 185 190

Ala Pro Gly Lys Gly Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn

195 200 205

Asp Glu Thr Lys Tyr Gly Pro Ile Phe Gln Gly Arg Val Thr Ile Thr

210 215 220

Ala Asp Thr Ser Thr Asn Thr Val Tyr Met Glu Leu Ser Ser Leu Arg

225 230 235 240

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr

245 250 255

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 773

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 773

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaatcc agctggtgca aagcggagcc gaggtgaaga agcccggaga atccctgcgc

120

atctcgtgta agggttccgg ctttaacatc gaggattact acatccactg ggtgagacag

180

atgccgggca aaggtctgga atggatgggc cgcatcgacc cggagaacga cgaaaccaaa

240

tacggaccaa tcttccaagg acatgtgact atttccgcgg atacctccat caacactgtc

300

tacttgcagt ggagctcgct caaggcgtcg gataccgcca tgtactactg cgcattcaga

360

ggaggtgtgt actggggcca gggcactacg gtcaccgtgt cctcgggagg tggagggtca

420

ggaggcggag gctcgggcgg tggaggatca ggcggaggag gaagcgatgt ggtcatgact

480

caatccccac tgtcactgcc tgtcactctg gggcaaccgg cttccatctc atgcaagtca

540

agccaatcgc tgctcgactc cgacggaaaa acctacctca attggcttca gcagcgccca

600

ggccagtcgc ctcgggaggct gatctcactc gtgtcgaagc ttgactccgg ggtgccggat

660

cggtttagcg gaagcggatc ggggaccgac ttcacgttga agattagccg ggtggaagcc

720

gaggacgtgg gagtctatta ctgctggcag gggacccact tcccggggac tttcggagga

780

ggcaccaaag tcgagattaa gaccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 774

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 774

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Glu Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Phe

35 40 45

Asn Ile Glu Asp Tyr Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys

50 55 60

Gly Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys

65 70 75 80

Tyr Gly Pro Ile Phe Gln Gly His Val Thr Ile Ser Ala Asp Thr Ser

85 90 95

Ile Asn Thr Val Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr

100 105 110

Ala Met Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly

115 120 125

Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr

145 150 155 160

Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly Gln Pro Ala Ser Ile

165 170 175

Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr

180 185 190

Leu Asn Trp Leu Gln Gln Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile

195 200 205

Ser Leu Val Ser Lys Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly

210 215 220

Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala

225 230 235 240

Glu Asp Val Gly Val Tyr Tyr Cys Trp Gln Gly Thr His Phe Pro Gly

245 250 255

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 775

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 775

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgacgtcg tcatgaccca atcccctctc tccctgccgg tcaccctggg tcagccggcg

120

tcgatctcat gcaaaagctc acagtccctg ctggattcgg acggaaaaac ctacttgaac

180

tggctccaac agaggccggg tcagtcccct cgcagactga tctcgctggt gagcaagctc

240

gactcgggtg tgccggatcg gttctccggg tcaggatcgg gcaccgactt tacgctcaag

300

atttcgagag tggaggccga ggatgtggga gtgtactatt gctggcaggg cacgcatttc

360

cccgggacct ttggaggcgg gactaaggtg gaaatcaagg gaggtggcgg atcaggcggga

420

ggaggcagcg gcggaggtgg atcaggaggc ggagggtcag agatccagct ggtccaaagc

480

ggagcagagg tgaagaagcc aggcgagtcc cttcgcattt cgtgcaaagg gagcggcttc

540

aacattgaag attactacat ccactgggtg cggcaaatgc caggaaaggg tctggaatgg

600

atgggacgga tcgacccaga aaatgatgaa actaagtacg gaccgatctt ccaaggacac

660

gtcactatct ccgcggacac ttcgatcaac accgtgtacc tccagtggag cagcttgaaa

720

gcctccgaca ccgctatgta ctactgtgcc ttccgcggag gagtctactg gggacagggg

780

actactgtga ccgtgtcgtc caccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 776

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 776

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu

20 25 30

Pro Val Thr Leu Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln

35 40 45

Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln Gln

50 55 60

Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile Ser Leu Val Ser Lys Leu

65 70 75 80

Asp Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

85 90 95

Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr

100 105 110

Tyr Cys Trp Gly Thr His Phe Pro Gly Thr Phe Gly Gly Gly Thr

115 120 125

Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Gln Leu Val Gln Ser

145 150 155 160

Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Arg Ile Ser Cys Lys

165 170 175

Gly Ser Gly Phe Asn Ile Glu Asp Tyr Tyr Ile His Trp Val Arg Gln

180 185 190

Met Pro Gly Lys Gly Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn

195 200 205

Asp Glu Thr Lys Tyr Gly Pro Ile Phe Gln Gly His Val Thr Ile Ser

210 215 220

Ala Asp Thr Ser Ile Asn Thr Val Tyr Leu Gln Trp Ser Ser Leu Lys

225 230 235 240

Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr

245 250 255

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 777

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 777

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaatcc agctcgtgca gagcggagcc gaggtcaaga aaccgggtgc taccgtgaag

120

atttcatgca agggatcggg cttcaacatc gaggattact acatccactg ggtgcagcag

180

gcaccaggaa aaggacttga atggatgggc cggatcgacc cggaaaatga cgagactaag

240

tacggcccta tcttccaagg acgggtgacg atcaccgcag acactagcac caacaccgtc

300

tatatggaac tctcgtccct gaggtccgaa gatactgccg tgtactactg tgcgtttcgc

360

ggaggtgtgt actggggaca gggtaccacc gtcaccgtgt catcgggcgg tggaggctcc

420

ggtggaggag ggtcaggagg cggtggaagc ggaggaggcg gcagcgacgt ggtcatgact

480

caatcgccgc tgtcgctgcc cgtcactctg ggacaacccg cgtccatcag ctgcaaatcc

540

tcgcagtcac tgcttgactc cgatggaaag acctacctca actggctgca gcaacgccca

600

ggccaatccc caagacgcct gatctcgttg gtgtcaaagc tggactcagg ggtgccggac

660

cggttctccg ggagcgggtc gggcacggat ttcactctca agatctccag agtggaagcc

720

gaggatgtgg gagtctacta ctgctggcag ggaacccatt tccctggaac ttttggcgga

780

ggaactaagg tcgagattaa aaccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 778

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 778

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Thr Val Lys Ile Ser Cys Lys Gly Ser Gly Phe

35 40 45

Asn Ile Glu Asp Tyr Tyr Ile His Trp Val Gln Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys

65 70 75 80

Tyr Gly Pro Ile Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser

85 90 95

Thr Asn Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly

115 120 125

Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr

145 150 155 160

Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly Gln Pro Ala Ser Ile

165 170 175

Ser Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr

180 185 190

Leu Asn Trp Leu Gln Gln Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile

195 200 205

Ser Leu Val Ser Lys Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly

210 215 220

Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala

225 230 235 240

Glu Asp Val Gly Val Tyr Tyr Cys Trp Gln Gly Thr His Phe Pro Gly

245 250 255

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 779

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 779

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagattc agctcgtgca atcgggagcg gaagtcaaga agccaggaga gtccttgcgg

120

atctcatgca agggtagcgg ctttaacatc gaggattact acatccactg ggtgaggcag

180

atgccgggga agggactcga atggatggga cggatcgacc cagaaaacga cgaaactaag

240

tacggtccga tcttccaagg ccatgtgact attagcgccg atacttcaat caataccgtg

300

tatctgcaat ggtcctcatt gaaagcctca gataccgcga tgtactactg tgctttcaga

360

ggaggggtct actggggaca gggaactacc gtgactgtct cgtccggcgg aggcgggtca

420

ggaggtggcg gcagcggagg aggagggtcc ggcggaggtg ggtccgacgt cgtgatgacc

480

cagagccctg acagcctggc agtgagcctg ggcgaaagag ctaccattaa ctgcaaatcg

540

tcgcagagcc tgctggactc ggacggaaaa acgtacctca attggctgca gcaaaagcct

600

ggccagccac cgaagcgcct tatctcactg gtgtcgaagc tggattcggg agtgcccgat

660

cgcttctccg gctcgggatc gggtactgac ttcaccctca ctatctcctc gcttcaagca

720

gaggacgtgg ccgtctacta ctgctggcag ggaacccact ttccgggaac cttcggcgga

780

gggacgaaag tggagatcaa gacactacc cggcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 780

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 780

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Glu Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Phe

35 40 45

Asn Ile Glu Asp Tyr Tyr Ile His Trp Val Arg Gln Met Pro Gly Lys

50 55 60

Gly Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys

65 70 75 80

Tyr Gly Pro Ile Phe Gln Gly His Val Thr Ile Ser Ala Asp Thr Ser

85 90 95

Ile Asn Thr Val Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr

100 105 110

Ala Met Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr Trp Gly Gln Gly

115 120 125

Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr

145 150 155 160

Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile

165 170 175

Asn Cys Lys Ser Ser Gln Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr

180 185 190

Leu Asn Trp Leu Gln Gln Lys Pro Gly Gln Pro Pro Lys Arg Leu Ile

195 200 205

Ser Leu Val Ser Lys Leu Asp Ser Gly Val Pro Asp Arg Phe Ser Gly

210 215 220

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala

225 230 235 240

Glu Asp Val Ala Val Tyr Tyr Cys Trp Gln Gly Thr His Phe Pro Gly

245 250 255

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 781

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 781

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgacgtgg tgatgactca gtcgcctgac tcgctggctg tgtcccttgg agagcgggcc

120

actatcaatt gcaagtcatc ccagtcgctg ctggattccg acgggaaaac ctacctcaat

180

tggctgcagc aaaaaccggg acagcctcca aagcggctca tcagcctggt gtccaagttg

240

gacagcggcg tgccagaccg cttctccggt tcgggaagcg gtactgatt cacgctgacc

300

atctcatccc tccaagcgga ggatgtggca gtctactact gttggcaggg cacgcatttt

360

ccgggcactt ttggaggagg gaccaaggtc gaaatcaagg gaggaggtgg ctcgggcggga

420

ggaggctcgg gaggaggagg atcaggaggc ggtggaagcg agattcaact ggtccagagc

480

ggcgcagaag tcaagaagcc gggtgaatcg ctcagaatct cgtgcaaagg atcgggattc

540

aacatcgagg actactacat tcactgggtc agacaaatgc cgggcaaagg gctggaatgg

600

atggggagga tcgaccccga aaacgatgaa accaagtacg gaccaatctt ccaagggcac

660

gtgaccattt cggcggacac ctcaatcaac actgtgtacc tccagtggag ctcacttaag

720

gccagcgata ccgccatgta ctattgcgct ttccgcggag gggtgtactg gggacagggc

780

actactgtga ccgtgtcatc caccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 782

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 782

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Val Val Met Thr Gln Ser Pro Asp Ser Leu

20 25 30

Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln

35 40 45

Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln Gln

50 55 60

Lys Pro Gly Gln Pro Pro Lys Arg Leu Ile Ser Leu Val Ser Lys Leu

65 70 75 80

Asp Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

85 90 95

Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr

100 105 110

Tyr Cys Trp Gly Thr His Phe Pro Gly Thr Phe Gly Gly Gly Thr

115 120 125

Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Gln Leu Val Gln Ser

145 150 155 160

Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Arg Ile Ser Cys Lys

165 170 175

Gly Ser Gly Phe Asn Ile Glu Asp Tyr Tyr Ile His Trp Val Arg Gln

180 185 190

Met Pro Gly Lys Gly Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn

195 200 205

Asp Glu Thr Lys Tyr Gly Pro Ile Phe Gln Gly His Val Thr Ile Ser

210 215 220

Ala Asp Thr Ser Ile Asn Thr Val Tyr Leu Gln Trp Ser Ser Leu Lys

225 230 235 240

Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr

245 250 255

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 783

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 783

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgatgtgg tcatgacgca gtcaccactg tccctccccg tgacccttgg acagccagcg

120

tcgattagct gcaagtcatc ccaatccctg ctcgattcgg atggaaagac ctatctcaac

180

tggctgcagc aaagacccgg tcagagccct aggagactca tctcgttggt gtcaaagctg

240

gacagcggag tgccggaccg gttttccggt tcgggatcgg ggacggactt cactctgaag

300

atttcacggg tggaagctga ggatgtggga gtgtactact gctggcaggg aacccatttc

360

cctggcactt ttggcgggagg aactaaggtc gaaatcaagg gaggaggtgg ctcgggagga

420

ggcggatcgg gcggaggcgg gagcggcggga ggagggtccg aaatccaact tgtccagtca

480

ggagccgaag tgaagaaacc gggagccacc gtcaaaatca gctgtaaggg atcgggattc

540

aatatcgagg actactacat ccactggggtg cagcaagctc cgggcaaagg actggagtgg

600

atggggcgca tcgacccaga gaacgacgaa accaaatacg gcccgatctt ccaagggcgg

660

gtgaccatca ccgcggacac ctcaactaac actgtgtaca tggagctgag ctccctgcgc

720

tccgaagata ctgcagtcta ctactgcgcc ttccgcggtg gtgtgtactg gggacagggc

780

accactgtga ctgtcagctc gaccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 784

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 784

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu

20 25 30

Pro Val Thr Leu Gly Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln

35 40 45

Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp Leu Gln Gln

50 55 60

Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile Ser Leu Val Ser Lys Leu

65 70 75 80

Asp Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

85 90 95

Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr

100 105 110

Tyr Cys Trp Gly Thr His Phe Pro Gly Thr Phe Gly Gly Gly Thr

115 120 125

Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Gln Leu Val Gln Ser

145 150 155 160

Gly Ala Glu Val Lys Lys Pro Gly Ala Thr Val Lys Ile Ser Cys Lys

165 170 175

Gly Ser Gly Phe Asn Ile Glu Asp Tyr Tyr Ile His Trp Val Gln Gln

180 185 190

Ala Pro Gly Lys Gly Leu Glu Trp Met Gly Arg Ile Asp Pro Glu Asn

195 200 205

Asp Glu Thr Lys Tyr Gly Pro Ile Phe Gln Gly Arg Val Thr Ile Thr

210 215 220

Ala Asp Thr Ser Thr Asn Thr Val Tyr Met Glu Leu Ser Ser Leu Arg

225 230 235 240

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr

245 250 255

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 785

<211> 1461

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 785

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccggagatcc agctccaaca gagcggagcc gaactggtca aaccgggagc gtcggtgaag

120

ttgtcatgca ctggatcggg cttcaacatc gaggattact acatccactg ggtcaagcaa

180

cgcaccgagc aggggctgga atggatcgga cggatcgacc ccgaaaacga tgaaaccaag

240

tacggggccta tcttccaagg acgggccacc attacggctg acacgtcaag caataccgtc

300

tacctccagc tttccagcct gacctccgag gacactgccg tgtactactg cgccttcaga

360

ggaggcgtgt actggggacc aggaaccact ttgaccgtgt ccagcggagg cggtggatca

420

ggaggaggag gctcaggcgg tggcggctcg cacatggacg tggtcatgac tcagtccccg

480

ctgaccctgt cggtggcaat tggacagagc gcatccatct cgtgcaagag ctcacagtcg

540

ctgctggatt ccgacggaaa gacttatctg aactggctgc tccaaagacc agggcaatca

600

ccgaaacgcc ttatctccct ggtgtcgaaa ctcgactcgg gtgtgccgga tcggtttacc

660

ggtagcgggt ccggcacgga cttcactctc cgcatttcga gggtggaagc ggaggatctc

720

gggatctact actgttggca gggaacccac ttccctggga cttttggagg cggaactaag

780

ctggaaatca agaccactac ccgcaccg aggccaccca ccccggctcc taccatcgcc

840

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

900

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

960

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1020

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1080

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1140

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1200

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

1260

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

1320

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

1380

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

1440

atgcaggccc tgccgcctcg g

1461

<210> 786

<211> 487

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 786

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Gln Leu Gln Gln Ser Gly Ala Glu Leu

20 25 30

Val Lys Pro Gly Ala Ser Val Lys Leu Ser Cys Thr Gly Ser Gly Phe

35 40 45

Asn Ile Glu Asp Tyr Tyr Ile His Trp Val Lys Gln Arg Thr Glu Gln

50 55 60

Gly Leu Glu Trp Ile Gly Arg Ile Asp Pro Glu Asn Asp Glu Thr Lys

65 70 75 80

Tyr Gly Pro Ile Phe Gln Gly Arg Ala Thr Ile Thr Ala Asp Thr Ser

85 90 95

Ser Asn Thr Val Tyr Leu Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Phe Arg Gly Gly Val Tyr Trp Gly Pro Gly

115 120 125

Thr Thr Leu Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser His Met Asp Val Val Met Thr Gln Ser Pro

145 150 155 160

Leu Thr Leu Ser Val Ala Ile Gly Gln Ser Ala Ser Ile Ser Cys Lys

165 170 175

Ser Ser Gln Ser Leu Leu Asp Ser Asp Gly Lys Thr Tyr Leu Asn Trp

180 185 190

Leu Leu Gln Arg Pro Gly Gln Ser Pro Lys Arg Leu Ile Ser Leu Val

195 200 205

Ser Lys Leu Asp Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser

210 215 220

Gly Thr Asp Phe Thr Leu Arg Ile Ser Arg Val Glu Ala Glu Asp Leu

225 230 235 240

Gly Ile Tyr Tyr Cys Trp Gly Thr His Phe Pro Gly Thr Phe Gly

245 250 255

Gly Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

260 265 270

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

275 280 285

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

290 295 300

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

305 310 315 320

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

325 330 335

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

340 345 350

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

355 360 365

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

370 375 380

Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

385 390 395 400

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

405 410 415

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

420 425 430

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

435 440 445

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

450 455 460

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

465 470 475 480

Met Gln Ala Leu Pro Pro Arg

485

<210> 787

<211> 1452

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 787

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgatatcc aaatgactca gagcccttca tccctgagcg ccagcgtcgg agacagggtg

120

accatcacgt gccgggcatc ccaaggcatt agaaataact tggcgtggta tcagcaaaaa

180

cgggaaagg ccccgaagcg cctgatctac gcggcctcca accttcagtc aggagtgccc

240

tcgcgcttca ccgggagcgg tagcggaact gagtttaccc ttatcgtgtc gtccctgcag

300

ccagaggact tcgcgaccta ctactgcctc cagcatcact cgtacccgtt gacttcggga

360

ggcggaacca aggtcgaaat caaacgcact ggctcgacgt cagggtccgg taaaccggga

420

tcgggagaag gatcggaagt ccaagtgctg gagagcggag gcggactcgt gcaacctggc

480

gggtcgctgc ggctcagctg tgccgcgtcg ggttttactt tcagctcgta cgctatgtca

540

tgggtgcggc aggctccggg aaaggggctg gaatgggtgt ccgctatttc cggctcgggt

600

ggaagcacca attacgccga ctccgtgaag ggacgcttca ccatctcacg ggataactcc

660

aagaatactc tgtacctcca gatgaactcg ctgagagccg aggacaccgc agtgtactac

720

tgcgcagggt caagcggctg gtccgaatac tggggacagg gcaccctcgt cactgtcagc

780

tccacacta ccccagcacc gaggccaccc accccggctc ctaccatcgc ctcccagcct

840

ctgtccctgc gtccgggaggc atgtagaccc gcagctggtg gggccgtgca tacccggggt

900

cttgacttcg cctgcgatat ctacatttgg gcccctctgg ctggtacttg cggggtcctg

960

ctgctttcac tcgtgatcac tctttactgt aagcgcggtc ggaagaagct gctgtacatc

1020

tttaagcaac ccttcatgag gcctgtgcag actactcaag aggaggacgg ctgttcatgc

1080

cggttcccag aggaggagga aggcggctgc gaactgcgcg tgaaattcag ccgcagcgca

1140

gatgctccag cctacaagca ggggcagaac cagctctaca acgaactcaa tcttggtcgg

1200

agagaggagt acgacgtgct ggacaagcgg agaggacggg acccagaaat gggcgggaag

1260

ccgcgcagaa agaatcccca agagggcctg tacaacgagc tccaaaagga taagatggca

1320

gaagcctata gcgagattgg tatgaaaggg gaacgcagaa gaggcaaagg ccacgacggga

1380

ctgtaccagg gactcagcac cgccaccaag gacacctatg acgctcttca catgcaggcc

1440

ctgccgcctc gg

1452

<210> 788

<211> 484

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 788

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu

20 25 30

Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln

35 40 45

Gly Ile Arg Asn Asn Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala

50 55 60

Pro Lys Arg Leu Ile Tyr Ala Ala Ser Asn Leu Gln Ser Gly Val Pro

65 70 75 80

Ser Arg Phe Thr Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Ile Val

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln His

100 105 110

His Ser Tyr Pro Leu Thr Ser Gly Gly Gly Thr Lys Val Glu Ile Lys

115 120 125

Arg Thr Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly

130 135 140

Ser Glu Val Gln Val Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly

145 150 155 160

Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser

165 170 175

Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp

180 185 190

Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Asn Tyr Ala Asp Ser

195 200 205

Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu

210 215 220

Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr

225 230 235 240

Cys Ala Gly Ser Ser Gly Trp Ser Glu Tyr Trp Gly Gln Gly Thr Leu

245 250 255

Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro

260 265 270

Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys

275 280 285

Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala

290 295 300

Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu

305 310 315 320

Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys

325 330 335

Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr

340 345 350

Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly

355 360 365

Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala

370 375 380

Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg

385 390 395 400

Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu

405 410 415

Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn

420 425 430

Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met

435 440 445

Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly

450 455 460

Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala

465 470 475 480

Leu Pro Pro Arg

<210> 789

<211> 483

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 789

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe

35 40 45

Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr

65 70 75 80

Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg

85 90 95

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala

100 105 110

Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln

115 120 125

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser

145 150 155 160

Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys

165 170 175

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys

180 185 190

Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln

195 200 205

Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

210 215 220

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr

225 230 235 240

Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys

245 250 255

Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala

260 265 270

Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg

275 280 285

Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys

290 295 300

Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu

305 310 315 320

Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu

325 330 335

Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln

340 345 350

Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly

355 360 365

Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr

370 375 380

Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg

385 390 395 400

Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met

405 410 415

Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu

420 425 430

Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys

435 440 445

Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu

450 455 460

Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu

465 470 475 480

Pro Pro Arg

<210> 790

<211> 1449

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 790

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc aattggtgga atcaggggga ggacttgtgc agcctggagg atcgctgaga

120

ctgtcatgtg ccgtgtccgg ctttgccctg tccaaccacg ggatgtcctg ggtccgccgc

180

gcgcctggaa agggcctcga atgggtgtcg ggtattgtgt acagcggtag cacctactat

240

gccgcatccg tgaaggggag attcaccatc agccgggaca actccaggaa cactctgtac

300

ctccaaatga attcgctgag gccagaggac actgccatct actactgctc cgcgcatggc

360

ggagagtccg acgtctgggg acaggggacc accgtgaccg tgtctagcgc gtccggcgga

420

ggcggcagcg ggggtcgggc atcaggggggc ggcggatcgg acatccagct cacccagtcc

480

ccgagctcgc tgtccgcctc cgtgggagat cgggtcacca tcacgtgccg cgccagccag

540

tcgatttcct cctacctgaa ctggtaccaa cagaagcccg gaaaagcccc gaagcttctc

600

atctacgccg cctcgagcct gcagtcagga gtgccctcac ggttctccgg ctccggttcc

660

ggtactgatt tcaccctgac catttcctcc ctgcaaccgg aggacttcgc tacttactac

720

tgccagcagt cgtactccac cccctacact ttcggacaag gcaccaaggt cgaaatcaag

780

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

840

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

900

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

960

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1020

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1080

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1140

gctccagcct acaagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1200

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

1260

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

1320

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

1380

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

1440

ccgcctcgg

1449

<210> 791

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 791

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Asn Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Gly Trp Val Ser Gly Ile Ser Arg Ser Gly Glu Asn Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Asp Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Ser Pro Ala His Tyr Tyr Gly Gly Met

115 120 125

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Ser Ser Ser Phe Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

195 200 205

Gly Ala Ser Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

225 230 235 240

Asp Ser Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Ser Pro Ser Trp

245 250 255

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 792

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 792

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc aactcgtgga atctggtgga ggactcgtgc aacccggaag atcgcttaga

120

ctgtcgtgtg ccgccagcgg gttcactttc tcgaactacg cgatgtcctg ggtccgccag

180

gcaccgggaa agggactcgg ttgggtgtcc ggcatttccc ggtccggcga aaatacctac

240

tacgccgact ccgtgaaggg ccgcttcacc atctcaaggg acaacagcaa aaacaccctg

300

tacttgcaaa tgaactccct gcgggatgaa gatacagccg tgtactattg cgcccggtcg

360

cctgcccatt actacggcgg aatggacgtc tggggacagg gaaccactgt gactgtcagc

420

agcgcgtcgg gtggcggcgg ctcaggggggt cgggcctccg gggggggagg gtccgacatc

480

gtgctgaccc agtccccggg aaccctgagc ctgagcccgg gagagcgcgc gaccctgtca

540

tgccgggcat ccgagcat tagctcctcc tttctcgcct ggtatcagca gaagccggga

600

caggccccga ggctgctgat ctacggcgct agcagaaggg ctaccggaat cccagaccgg

660

ttctccggct ccggttccgg gaccgatttc acccttacta tctcgcgcct ggaacctgag

720

gactccgccg tctactactg ccagcagtac cactcatccc cgtcgtggac gttcggacag

780

ggcaccaagc tggagattaa gaccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 793

<211> 488

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 793

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Asp Asp Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Leu Tyr Tyr Cys Ser Val His Ser Phe Leu Ala Tyr Trp Gly Gln

115 120 125

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Thr

145 150 155 160

Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys

165 170 175

Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp

180 185 190

Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu

195 200 205

Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

210 215 220

Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp

225 230 235 240

Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr Pro Tyr Thr Phe

245 250 255

Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg

260 265 270

Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg

275 280 285

Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly

290 295 300

Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr

305 310 315 320

Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg

325 330 335

Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro

340 345 350

Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu

355 360 365

Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala

370 375 380

Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu

385 390 395 400

Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly

405 410 415

Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu

420 425 430

Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser

435 440 445

Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly

450 455 460

Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu

465 470 475 480

His Met Gln Ala Leu Pro Pro Arg

485

<210> 794

<211> 1464

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 794

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc aactcgtcga atccggtgga ggtctggtcc aacctggtag aagcctgaga

120

ctgtcgtgtg cggccagcgg attcaccttt gatgactatg ctatgcactg ggtgcggcag

180

gccccaggaa agggcctgga atgggtgtcg ggaattagct ggaactccgg gtccattggc

240

tacgccgact ccgtgaaggg ccgcttcacc atctcccgcg acaacgcaaa gaactccctg

300

tacttgcaaa tgaactcgct cagggctgag gataccgcgc tgtactactg ctccgtgcat

360

tccttcctgg cctactgggg acagggaact ctggtcaccg tgtcgagcgc ctccggcggc

420

gggggctcgg gtggacgggc ctcgggcggga ggggggtccg acatcgtgat gacccagacc

480

ccgctgagct tgcccgtgac tcccggagag cctgcatcca tctcctgccg gtcatcccag

540

tcccttctcc actccaacgg atacaactac ctcgactggt acctccagaa gccgggacag

600

agccctcagc ttctgatcta cctggggtca aatagagcct caggagtgcc ggatcggttc

660

agcggatctg gttcgggaac tgatttcact ctgaagattt cccgcgtgga agccgaggac

720

gtgggcgtct actactgtat gcaggcgctg cagaccccct ataccttcgg ccaagggacg

780

aaagtggaga tcaagaccac taccccagca ccgaggccac ccaccccggc tcctaccatc

840

gcctcccagc ctctgtccct gcgtccggag gcatgtagac ccgcagctgg tggggccgtg

900

catacccggg gtcttgactt cgcctgcgat atctacattt gggcccctct ggctggtact

960

tgcggggtcc tgctgctttc actcgtgatc actctttact gtaagcgcgg tcggaagaag

1020

ctgctgtaca tctttaagca acccttcatg aggcctgtgc agactactca agaggaggac

1080

ggctgttcat gccggttccc agaggaggag gaaggcggct gcgaactgcg cgtgaaattc

1140

agccgcagcg cagatgctcc agcctacaag caggggcaga accagctcta caacgaactc

1200

aatcttggtc ggagaggagga gtacgacgtg ctggacaagc ggagaggacg ggacccagaa

1260

atgggcggga agccgcgcag aaagaatccc caagaggggcc tgtacaacga gctccaaaag

1320

gataagatgg cagaagccta tagcgagatt ggtatgaaag gggaacgcag aagaggcaaa

1380

ggccacgacg gactgtacca gggactcagc accgccacca aggacaccta tgacgctctt

1440

cacatgcagg ccctgccgcc tcgg

1464

<210> 795

<211> 487

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 795

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe

35 40 45

Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr

65 70 75 80

Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg

85 90 95

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala

100 105 110

Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln

115 120 125

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Thr

145 150 155 160

Pro Leu Ser Leu Ser Val Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys

165 170 175

Lys Ser Ser Gln Ser Leu Leu Arg Asn Asp Gly Lys Thr Pro Leu Tyr

180 185 190

Trp Tyr Leu Gln Lys Ala Gly Gln Pro Pro Gln Leu Leu Ile Tyr Glu

195 200 205

Val Ser Asn Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

210 215 220

Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp

225 230 235 240

Val Gly Ala Tyr Tyr Cys Met Gln Asn Ile Gln Phe Pro Ser Phe Gly

245 250 255

Gly Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

260 265 270

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

275 280 285

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

290 295 300

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

305 310 315 320

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

325 330 335

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

340 345 350

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

355 360 365

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

370 375 380

Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

385 390 395 400

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

405 410 415

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

420 425 430

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

435 440 445

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

450 455 460

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

465 470 475 480

Met Gln Ala Leu Pro Pro Arg

485

<210> 796

<211> 1461

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 796

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc aattgttgga atctggagga ggacttgtgc agcctggagg atcactgaga

120

ctttcgtgtg cggtgtcagg cttcgccctg agcaaccacg gcatgagctg ggtgcggaga

180

gccccgggga agggtctgga atgggtgtcc gggatcgtct actccggttc aacttactac

240

gccgcaagcg tgaagggtcg cttcaccatt tcccgcgata actcccggaa caccctgtac

300

ctccaaatga actccctgcg gcccgaggac accgccatct actactgttc cgcgcatgga

360

ggagagtccg atgtctgggg acagggcact accgtgaccg tgtcgagcgc ctcgggggga

420

ggaggctccg gcggtcgcgc ctccgggggg ggtggcagcg acattgtgat gacgcagact

480

ccactctcgc tgtccgtgac cccgggacag cccgcgtcca tctcgtgcaa gagctcccag

540

agcctgctga ggaacgacgg aaagactcct ctgtattggt acctccagaa ggctggacag

600

cccccgcaac tgctcatcta cgaagtgtca aatcgcttct ccggggtgcc ggatcggttt

660

tccggctcgg gatcgggcac cgacttcacc ctgaaaatct ccagggtcga ggccgaggac

720

gtgggagcct actactgcat gcaaaacatc cagttccctt ccttcggcgg cggcacaaag

780

ctggagatta agaccactac ccgcaccg aggccaccca ccccggctcc taccatcgcc

840

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

900

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

960

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1020

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1080

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1140

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1200

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

1260

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

1320

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

1380

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

1440

atgcaggccc tgccgcctcg g

1461

<210> 797

<211> 493

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 797

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Arg Lys Thr Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Ile Phe Asp Asn Phe Gly Ile Asn Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Lys Asn Asn Asn Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser

85 90 95

Thr Asn Thr Ala Tyr Met Glu Val Ser Ser Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Gly Pro Tyr Tyr Tyr Gln Ser Tyr Met

115 120 125

Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile

145 150 155 160

Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro

165 170 175

Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly

180 185 190

Tyr Asn Tyr Leu Asn Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln

195 200 205

Leu Leu Ile Tyr Leu Gly Ser Lys Arg Ala Ser Gly Val Pro Asp Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu His Ile Thr Arg

225 230 235 240

Val Gly Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln

245 250 255

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr

260 265 270

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

275 280 285

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

290 295 300

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

305 310 315 320

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

325 330 335

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

340 345 350

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

355 360 365

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

370 375 380

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln

385 390 395 400

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

405 410 415

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

420 425 430

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

435 440 445

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

450 455 460

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

465 470 475 480

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 798

<211> 1479

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 798

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtcc aactcgtcca gtccggcgca gaagtcagaa aaaccggtgc tagcgtgaaa

120

gtgtcctgca aggcctccgg ctacattttc gataacttcg gaatcaactg ggtcagacag

180

gccccggggcc aggggctgga atggatggga tggatcaacc ccaagaacaa caacaccaac

240

tacgcacaga agttccaggg ccgcgtgact atcaccgccg atgaatcgac caataccgcc

300

tacatggagg tgtcctccct gcggtcggag gacactgccg tgtattactg cgcgaggggc

360

ccatactact accaaagcta catggacgtc tggggacagg gaaccatggt gaccgtgtca

420

tccgcctccg gtggtggagg ctccgggggg cgggcttcag gaggcggagg aagcgatatt

480

gtgatgaccc agactccgct tagcctgccc gtgactcctg gagaaccggc ctccatttcc

540

tgccggtcct cgcaatcact cctgcattcc aacggttaca actacctgaa ttggtacctc

600

cagaagcctg gccagtcgcc ccagttgctg atctatctgg gctcgaagcg cgcctccggg

660

gtgcctgacc ggtttagcgg atctgggagc ggcacggact tcactctcca catcacccgc

720

gtgggagcgg aggacgtggg agtgtactac tgtatgcagg cgctgcagac tccgtacaca

780

ttcggacagg gcaccaagct ggagatcaag accactaccc cagcaccgag gccacccacc

840

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

900

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

960

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1020

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1080

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1140

ctgcgcgtga aattcagccg cagcgcagat gctccagcct acaagcaggg gcagaaccag

1200

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

1260

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

1320

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

1380

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

1440

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

1479

<210> 799

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 799

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Asp Ala Met Thr Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Val Ile Ser Gly Ser Gly Gly Thr Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Leu Asp Ser Ser Gly Tyr Tyr Tyr Ala

115 120 125

Arg Gly Pro Arg Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

130 135 140

Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly

145 150 155 160

Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val

165 170 175

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

180 185 190

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

195 200 205

Ile Tyr Gly Ala Ser Thr Leu Ala Ser Gly Val Pro Ala Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr His Phe Thr Leu Thr Ile Asn Ser Leu Gln

225 230 235 240

Ser Glu Asp Ser Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Lys Arg Ala

245 250 255

Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 800

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 800

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc aacttcaaga atcaggcgga ggactcgtgc agcccgggagg atcattgcgg

120

ctctcgtgcg ccgcctcggg cttcaccttc tcgagcgacg ccatgacctg ggtccgccag

180

gccccgggga aggggctgga atgggtgtct gtgatttccg gctccggggg aactacgtac

240

tacgccgatt ccgtgaaagg tcgcttcact atctcccggg acaacagcaa gaacaccctt

300

tatctgcaaa tgaattccct ccgcgccgag gacaccgccg tgtactactg cgccaagctg

360

gactcctcgg gctactacta tgcccggggt ccgagatact ggggacaggg aaccctcgtg

420

accgtgtcct ccgcgtccgg cggaggaggg tcgggaggggc gggcctccgg cggcggcggt

480

tcggacatcc agctgaccca gtccccatcc tcactgagcg caagcgtggg cgacagagtc

540

accattacat gcagggcgtc ccagagcatc agctcctacc tgaactggta ccaacagaag

600

ccctggaaagg ctcctaagct gttgatctac ggggcttcga ccctggcatc cggggtgccc

660

gcgaggttta gcggaagcgg tagcggcact cacttcactc tgaccattaa cagcctccag

720

tccgaggatt cagccactta ctactgtcag cagtcctaca agcgggccag cttcggacag

780

ggcactaagg tcgagatcaa gaccactacc cgcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 801

<211> 491

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 801

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr

35 40 45

Thr Phe Ser Asn Tyr Gly Ile Thr Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Trp Ile Ser Ala Tyr Asn Gly Asn Thr Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asn Thr Ser

85 90 95

Ile Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Gly Pro Tyr Tyr Tyr Tyr Met Asp Val

115 120 125

Trp Gly Lys Gly Thr Met Val Thr Val Ser Ser Ala Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Glu Ile Val Met

145 150 155 160

Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro Ala Ser

165 170 175

Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu Tyr Ser Asn Gly Tyr Asn

180 185 190

Tyr Val Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu

195 200 205

Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Phe Lys Leu Gln Ile Ser Arg Val Glu

225 230 235 240

Ala Glu Asp Val Gly Ile Tyr Tyr Cys Met Gln Gly Arg Gln Phe Pro

245 250 255

Tyr Ser Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

305 310 315 320

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

325 330 335

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

340 345 350

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

355 360 365

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

370 375 380

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

385 390 395 400

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

405 410 415

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

420 425 430

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

435 440 445

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

450 455 460

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

465 470 475 480

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 802

<211> 1473

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 802

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtcc aactggtcca gagcggtgca gaagtgaaga agcccggagc gagcgtgaaa

120

gtgtcctgca aggcttccgg gtacaccttc tccaactacg gcatcacttg ggtgcgccag

180

gccccgggac agggcctgga atggatgggg tggatttccg cgtacaacgg caatacgaac

240

tacgctcaga agttccaggg tagagtgacc atgactagga acacctccat ttccaccgcc

300

tacatggaac tgtcctccct gcggagcgag gacaccgccg tgtactattg cgcccggggga

360

ccatactact actacatgga tgtctggggg aaggggacta tggtcaccgt gtcatccgcc

420

tcgggaggcg gcggatcagg aggacgcgcc tctggtggtg gaggatcgga gatcgtgatg

480

acccagagcc ctctctcctt gcccgtgact cctggggagc ccgcatccat ttcatgccgg

540

agctcccagt cacttctcta ctccaacggc tataactacg tggattggta cctccaaaag

600

ccggggccaga gcccgcagct gctgatctac ctgggctcga acagggccag cggagtgcct

660

gaccggttct ccgggtcggg aagcgggacc gacttcaagc tgcaaatctc gagagtggag

720

gccgaggacg tgggaatcta ctactgtatg cagggccgcc agtttccgta ctcgttcgga

780

cagggcacca aagtggaaat caagaccact accccagcac cgaggccacc caccccggct

840

cctaccatcg cctcccagcc tctgtccctg cgtccgggagg catgtagacc cgcagctggt

900

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

960

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1020

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1080

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1140

gtgaaattca gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac

1200

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

1260

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

1320

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

1380

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

1440

gacgctcttc acatgcaggc cctgccgcct cgg

1473

<210> 803

<211> 482

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 803

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Leu Glu Thr Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe

35 40 45

Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr

65 70 75 80

Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg

85 90 95

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala

100 105 110

Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln

115 120 125

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Arg Ala Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser

145 150 155 160

Pro Ala Thr Leu Ser Val Ser Pro Gly Glu Ser Ala Thr Leu Ser Cys

165 170 175

Arg Ala Ser Gln Ser Val Ser Ser Asn Leu Ala Trp Tyr Gln Gln Lys

180 185 190

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Ala

195 200 205

Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

210 215 220

Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr

225 230 235 240

Cys Gln Gln Tyr Gly Ser Ser Leu Thr Phe Gly Gly Gly Thr Lys Val

245 250 255

Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro

260 265 270

Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro

275 280 285

Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp

290 295 300

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu

305 310 315 320

Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu

325 330 335

Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu

340 345 350

Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys

355 360 365

Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys

370 375 380

Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu

385 390 395 400

Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly

405 410 415

Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu

420 425 430

Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly

435 440 445

Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser

450 455 460

Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro

465 470 475 480

Pro Arg

<210> 804

<211> 1446

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 804

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc aattgctcga aactggagga ggtctggtgc aacctggagg atcacttcgc

120

ctgtcctgcg ccgtgtcggg ctttgccctg tccaaccatg gaatgagctg ggtccgccgc

180

gcgccgggga agggcctcga atgggtgtcc ggcatcgtct actccggctc cacctactac

240

gccgcgtccg tgaagggccg gttcacgatt tcacgggaca actcgcggaa caccctgtac

300

ctccaaatga attcccttcg gccggaggat actgccatct actactgctc cgcccacggt

360

ggcgaatccg acgtctgggg ccagggaacc accgtgaccg tgtccagcgc gtccggggga

420

ggaggaagcg ggggtagagc atcgggtgga ggcggatcag agatcgtgct gacccagtcc

480

cccgccacct tgagcgtgtc accaggagag tccgccaccc tgtcatgccg cgccagccag

540

tccgtgtcct ccaacctggc ttggtaccag cagaagccgg ggcaggcccc tagactcctg

600

atctatgggg cgtcgacccg ggcatctgga attcccgata ggttcagcgg atcgggctcg

660

ggcactgact tcactctgac catctcctcg ctgcaagccg aggacgtggc tgtgtactac

720

tgtcagcagt acggaagctc cctgactttc ggtggcggga ccaaagtcga gattaagacc

780

actaccccag caccgaggcc acccaccccg gctcctacca tcgcctccca gcctctgtcc

840

ctgcgtccgg aggcatgtag acccgcagct ggtggggccg tgcatacccg gggtcttgac

900

ttcgcctgcg atatctacat ttgggcccct ctggctggta cttgcggggt cctgctgctt

960

tcactcgtga tcactcttta ctgtaagcgc ggtcggaaga agctgctgta catctttaag

1020

caacccttca tgaggcctgt gcagactact caagggagg acggctgttc atgccggttc

1080

ccagaggagg aggaaggcgg ctgcgaactg cgcgtgaaat tcagccgcag cgcagatgct

1140

ccagcctaca agcaggggca gaaccagctc tacaacgaac tcaatcttgg tcggagagag

1200

gagtacgacg tgctggacaa gcggagagga cgggacccag aaatgggcgg gaagccgcgc

1260

agaaagaatc cccaagggg cctgtacaac gagctccaaa aggataagat ggcagaagcc

1320

tatagcgaga ttggtatgaa aggggaacgc agaagaggca aaggccacga cggactgtac

1380

cagggactca gcaccgccac caaggacacc tatgacgctc ttcacatgca ggccctgccg

1440

ccctcgg

1446

<210> 805

<211> 483

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 805

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe

35 40 45

Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr

65 70 75 80

Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg

85 90 95

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala

100 105 110

Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln

115 120 125

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Arg Ala Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser

145 150 155 160

Pro Ala Thr Leu Ser Val Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

165 170 175

Arg Ala Ser Gln Ser Val Ser Ser Lys Leu Ala Trp Tyr Gln Gln Lys

180 185 190

Pro Gly Gln Ala Pro Arg Leu Leu Met Tyr Gly Ala Ser Ile Arg Ala

195 200 205

Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe

210 215 220

Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr

225 230 235 240

Cys Gln Gln Tyr Gly Ser Ser Ser Trp Thr Phe Gly Gln Gly Thr Lys

245 250 255

Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala

260 265 270

Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg

275 280 285

Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys

290 295 300

Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu

305 310 315 320

Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu

325 330 335

Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln

340 345 350

Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly

355 360 365

Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr

370 375 380

Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg

385 390 395 400

Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met

405 410 415

Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu

420 425 430

Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys

435 440 445

Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu

450 455 460

Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu

465 470 475 480

Pro Pro Arg

<210> 806

<211> 1449

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 806

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc aattggtgga aactggagga ggacttgtgc aacctggagg atcattgaga

120

ctgagctgcg cagtgtcggg attcgccctg agcaaccatg gaatgtcctg ggtcagaagg

180

gcccctggaa aaggcctcga atgggtgtca gggatcgtgt actccggttc cacttactac

240

gccgcctccg tgaaggggcg cttcactatc tcacgggata actcccgcaa taccctgtac

300

ctccaaatga acagcctgcg gccggaggat accgccatct actactgttc cgcccacggt

360

ggagagtctg acgtctgggg ccagggaact accgtgaccg tgtcctccgc gtccggcggt

420

ggagggagcg gcggccgcgc cagcggcggc ggaggctccg agatcgtgat gacccagagc

480

cccgctactc tgtcggtgtc gcccggagaa agggcgaccc tgtcctgccg ggcgtcgcag

540

tccgtgagca gcaagctggc ttggtaccag cagaagccgg gccaggcacc acgcctgctt

600

atgtacggtg cctccattcg ggccaccgga atcccggacc ggttctcggg gtcggggtcc

660

ggtaccgagt tcacactgac catttcctcg ctcgagcccg aggactttgc cgtctattac

720

tgccagcagt acggctcctc ctcatggacg ttcggccagg ggaccaaggt cgaaatcaag

780

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

840

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

900

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

960

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1020

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1080

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1140

gctccagcct acaagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1200

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

1260

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

1320

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

1380

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

1440

ccgcctcgg

1449

<210> 807

<211> 485

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 807

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Thr Gly Gly Gly Val

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe

35 40 45

Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr

65 70 75 80

Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg

85 90 95

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala

100 105 110

Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln

115 120 125

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Arg Ala Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser

145 150 155 160

Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

165 170 175

Arg Ala Ser Gln Ser Val Gly Ser Thr Asn Leu Ala Trp Tyr Gln Gln

180 185 190

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp Ala Ser Asn Arg

195 200 205

Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Gly Gly Ser Gly Thr Asp

210 215 220

Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr

225 230 235 240

Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Pro Trp Thr Phe Gly Gln Gly

245 250 255

Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

260 265 270

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

275 280 285

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

290 295 300

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

305 310 315 320

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

325 330 335

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

340 345 350

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

355 360 365

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

370 375 380

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

385 390 395 400

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

405 410 415

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

420 425 430

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

435 440 445

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

450 455 460

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

465 470 475 480

Ala Leu Pro Pro Arg

485

<210> 808

<211> 1455

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 808

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc aattggtgga gactggagga ggagtggtgc aacctggagg aagcctgaga

120

ctgtcatgcg cggtgtcggg cttcgccctc tccaaccacg gaatgtcctg ggtccgccgg

180

gcccctggga aaggacttga atgggtgtcc ggcatcgtgt actcgggttc cacctactac

240

gcggcctcag tgaagggccg gtttactatt agccgcgaca actccagaaa cacactgtac

300

ctccaaatga actcgctgcg gccggaagat accgctatct actactgctc cgcccatggg

360

ggagagtcgg acgtctgggg acagggcacc actgtcactg tgtccagcgc ttccggcggt

420

ggtggaagcg ggggacgggc ctcaggaggc ggtggcagcg agattgtgct gacccagtcc

480

cccgggaccc tgagcctgtc cccgggagaa agggccaccc tctcctgtcg ggcatcccag

540

tccgtggggt ctactaacct tgcatggtac cagcagaagc ccggccaggc ccctcgcctg

600

ctgatctacg acgcgtccaa tagagccacc ggcatcccgg atcgcttcag cggaggcgga

660

tcgggcaccg acttcaccct caccattttca aggctggaac cggaggactt cgccgtgtac

720

tactgccagc agtatggttc gtccccaccc tggacgttcg gccaggggac taaggtcgag

780

atcaagacca ctaccccagc accgaggcca cccaccccgg ctcctaccat cgcctcccag

840

cctctgtccc tgcgtccgga ggcatgtaga cccgcagctg gtggggccgt gcatacccgg

900

ggtcttgact tcgcctgcga tatctacatt tgggcccctc tggctggtac ttgcggggtc

960

ctgctgcttt cactcgtgat cactctttac tgtaagcgcg gtcggaagaa gctgctgtac

1020

atctttaagc aacccttcat gaggcctgtg cagactactc aagaggagga cggctgttca

1080

tgccggttcc cagaggagga ggaaggcggc tgcgaactgc gcgtgaaatt cagccgcagc

1140

gcagatgctc cagcctacaa gcaggggcag aaccagctct acaacgaact caatcttggt

1200

cggagagagg agtacgacgt gctggacaag cggagaggac gggacccaga aatgggcggg

1260

aagccgcgca gaaagaatcc ccaagagggc ctgtacaacg agctccaaaa ggataagatg

1320

gcagaagcct atagcgagat tggtatgaaa ggggaacgca gaagaggcaa aggccacgac

1380

ggactgtacc agggactcag caccgccacc aaggacacct atgacgctct tcacatgcag

1440

gccctgccgc ctcgg

1455

<210> 809

<211> 483

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 809

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Asp Tyr Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Glu Ser Gly Asp Gly Met Asp Val Trp

115 120 125

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr

145 150 155 160

Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile

165 170 175

Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln

180 185 190

Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser

195 200 205

Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr

210 215 220

Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr

225 230 235 240

Tyr Tyr Cys Gln Gln Ser Tyr Thr Leu Ala Phe Gly Gln Gly Thr Lys

245 250 255

Val Asp Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala

260 265 270

Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg

275 280 285

Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys

290 295 300

Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu

305 310 315 320

Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu

325 330 335

Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln

340 345 350

Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly

355 360 365

Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr

370 375 380

Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg

385 390 395 400

Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met

405 410 415

Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu

420 425 430

Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys

435 440 445

Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu

450 455 460

Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu

465 470 475 480

Pro Pro Arg

<210> 810

<211> 1449

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 810

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc aactcgtgga atctggtgga ggactcgtga aacctggagg atcattgaga

120

ctgtcatgcg cggcctcggg attcacgttc tccgattact acatgagctg gattcgccag

180

gctccgggga agggactgga atgggtgtcc tacatttcct catccggctc caccatctac

240

tacgcggact ccgtgaaggg gagattcacc attagccgcg ataacgccaa gaacagcctg

300

taccttcaga tgaactccct gcgggctgaa gatactgccg tctactactg cgcaagggag

360

agcggagatg ggatggacgt ctggggacag ggtaccactg tgaccgtgtc gtcggcctcc

420

ggcgggagggg gttcgggtgg aagggccagc ggcggcggag gcagcgacat ccagatgacc

480

cagtccccct catcgctgtc cgcctccgtg ggcgaccgcg tcaccatcac atgccggggcc

540

tcacagtcga tctcctccta cctcaattgg tatcagcaga agcccggaaa ggcccctaag

600

cttctgatct acgcagcgtc ctccctgcaa tccggggtcc catctcggtt ctccggctcg

660

ggcagcggta ccgacttcac tctgaccatc tcgagcctgc agccggagga cttcgccact

720

tactactgtc agcaaagcta caccctcgcg tttggccagg gcaccaaagt ggacatcaag

780

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

840

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

900

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

960

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1020

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1080

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1140

gctccagcct acaagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1200

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

1260

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

1320

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

1380

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

1440

ccgcctcgg

1449

<210> 811

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 811

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu

20 25 30

Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Asp Tyr Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Tyr Ile Ser Ser Ser Gly Asn Thr Ile Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Ser Thr Met Val Arg Glu Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Val Leu Thr

145 150 155 160

Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly Gln Pro Ala Ser Ile

165 170 175

Ser Cys Lys Ser Ser Glu Ser Leu Val His Asn Ser Gly Lys Thr Tyr

180 185 190

Leu Asn Trp Phe His Gln Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile

195 200 205

Tyr Glu Val Ser Asn Arg Asp Ser Gly Val Pro Asp Arg Phe Thr Gly

210 215 220

Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala

225 230 235 240

Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly Thr His Trp Pro Gly

245 250 255

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 812

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 812

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc aactggtgca aagcggagga ggattggtca aacccgggagg aagcctgaga

120

ctgtcatgcg cggcctctgg attcaccttc tccgattact acatgtcatg gatcagacag

180

gccccgggga agggcctcga atgggtgtcc tacatctcgt cctccgggaa caccatctac

240

tacgccgaca gcgtgaaggg ccgctttacc atttcccgcg acaacgcaaa gaactcgctg

300

taccttcaga tgaattccct gcgggctgaa gataccgcgg tgtactattg cgcccggtcc

360

actatggtcc gggaggacta ctggggacag ggcacactcg tgaccgtgtc cagcgcgagc

420

gggggtggag gcagcggtgg acgcgcctcc ggcggcggcg gttcagacat cgtgctgact

480

cagtcgcccc tgtcgctgcc ggtcaccctg ggccaaccgg cctcaattag ctgcaagtcc

540

tcggagagcc tggtgcacaa ctcaggaaag acttacctga actggttcca tcagcggcct

600

ggacagtccc cacggaggct catctatgaa gtgtccaaca gggattcggg ggtgcccgac

660

cgcttcactg gctccgggtc cggcaccgac ttcaccttga aaatctccag agtggaagcc

720

gaggacgtgg gcgtgtacta ctgtatgcag ggtacccact ggcctggaac ctttggacaa

780

ggaactaagc tcgagattaa gaccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 813

<211> 483

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 813

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe

35 40 45

Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr

65 70 75 80

Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg

85 90 95

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala

100 105 110

Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln

115 120 125

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Arg Leu Thr Gln Ser

145 150 155 160

Pro Ser Pro Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys

165 170 175

Gln Ala Ser Glu Asp Ile Asn Lys Phe Leu Asn Trp Tyr His Gln Thr

180 185 190

Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Asp Ala Ser Thr Leu Gln

195 200 205

Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

210 215 220

Thr Leu Thr Ile Asn Ser Leu Gln Pro Glu Asp Ile Gly Thr Tyr Tyr

225 230 235 240

Cys Gln Gln Tyr Glu Ser Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys

245 250 255

Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala

260 265 270

Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg

275 280 285

Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys

290 295 300

Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu

305 310 315 320

Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu

325 330 335

Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln

340 345 350

Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly

355 360 365

Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr

370 375 380

Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg

385 390 395 400

Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met

405 410 415

Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu

420 425 430

Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys

435 440 445

Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu

450 455 460

Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu

465 470 475 480

Pro Pro Arg

<210> 814

<211> 1449

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 814

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc aactcgtgga atctggtgga ggactcgtgc aacccggtgg aagccttagg

120

ctgtcgtgcg ccgtcagcgg gtttgctctg agcaaccatg gaatgtcctg ggtccgccgg

180

gcaccgggaa aagggctgga atgggtgtcc ggcatcgtgt acagcgggtc aacctattac

240

gccgcgtccg tgaagggcag attcactatc tcaagagaca acagccggaa caccctgtac

300

ttgcaaatga attccctgcg ccccgaggac accgccatct actactgctc cgcccacgga

360

ggagagtcgg acgtgtgggg ccagggaacg actgtgactg tgtccagcgc atcaggaggg

420

ggtggttcgg gcggccgggc ctcggggggga ggaggttccg acattcggct gacccagtcc

480

ccgtccccac tgtcggcctc cgtcggcgac cgcgtgacca tcacttgtca ggcgtccgag

540

gacattaaca agttcctgaa ctggtaccac cagacccctg gaaaggcccc caagctgctg

600

atctacgatg cctcgaccct tcaaactgga gtgcctagcc ggttctccgg gtccggctcc

660

ggcactgatt tcactctgac catcaactca ttgcagccgg aagatatcgg gacctactat

720

tgccagcagt acgaatccct cccgctcaca ttcggcgggg gaaccaaggt cgagattaag

780

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

840

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

900

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

960

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1020

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1080

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1140

gctccagcct acaagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1200

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

1260

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

1320

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

1380

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

1440

ccgcctcgg

1449

<210> 815

<211> 484

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 815

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe

35 40 45

Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr

65 70 75 80

Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg

85 90 95

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala

100 105 110

Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln

115 120 125

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Arg Ala Ser Gly Gly Gly Gly Ser Glu Thr Thr Leu Thr Gln Ser

145 150 155 160

Pro Ala Thr Leu Ser Val Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

165 170 175

Arg Ala Ser Gln Ser Val Gly Ser Asn Leu Ala Trp Tyr Gln Gln Lys

180 185 190

Pro Gly Gln Gly Pro Arg Leu Leu Ile Tyr Gly Ala Ser Thr Arg Ala

195 200 205

Thr Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe

210 215 220

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Tyr

225 230 235 240

Cys Gln Gln Tyr Asn Asp Trp Leu Pro Val Thr Phe Gly Gln Gly Thr

245 250 255

Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro

260 265 270

Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys

275 280 285

Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala

290 295 300

Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu

305 310 315 320

Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys

325 330 335

Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr

340 345 350

Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly

355 360 365

Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala

370 375 380

Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg

385 390 395 400

Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu

405 410 415

Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn

420 425 430

Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met

435 440 445

Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly

450 455 460

Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala

465 470 475 480

Leu Pro Pro Arg

<210> 816

<211> 1452

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 816

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc aattggtgga aactggagga ggacttgtgc aacctggagg atcattgcgg

120

ctctcatgcg ctgtctccgg cttcgccctg tcaaatcacg ggatgtcgtg ggtcagacgg

180

gccccgggaa agggtctgga atgggtgtcg gggattgtgt acagcggctc cacctactac

240

gccgcttcgg tcaagggccg cttcactatt tcacgggaca acagccgcaa caccctctat

300

ctgcaaatga actctctccg cccggaggat accgccatct actactgctc cgcacacggc

360

ggcgaatccg acgtgtgggg acagggaacc actgtcaccg tgtcgtccgc atccggtggc

420

ggaggatcgg gtggccgggc ctccgggggc ggcggcagcg agactaccct gacccagtcc

480

cctgccactc tgtccgtgag cccgggagag agagccaccc ttagctgccg ggccagccag

540

agcgtgggct ccaacctggc ctggtaccag cagaagccag gacagggtcc caggctgctg

600

atctacggag cctccactcg cgcgaccggc atccccgcga ggttctccgg gtcgggttcc

660

gggaccgagt tcaccctgac catctcctcc ctccaaccgg aggacttcgc ggtgtactac

720

tgtcagcagt acaacgattg gctgcccgtg acatttggac aggggacgaa ggtggaaatc

780

aaaaccacta ccccagcacc gaggccaccc accccggctc ctaccatcgc ctcccagcct

840

ctgtccctgc gtccgggaggc atgtagaccc gcagctggtg gggccgtgca tacccggggt

900

cttgacttcg cctgcgatat ctacatttgg gcccctctgg ctggtacttg cggggtcctg

960

ctgctttcac tcgtgatcac tctttactgt aagcgcggtc ggaagaagct gctgtacatc

1020

tttaagcaac ccttcatgag gcctgtgcag actactcaag aggaggacgg ctgttcatgc

1080

cggttcccag aggaggagga aggcggctgc gaactgcgcg tgaaattcag ccgcagcgca

1140

gatgctccag cctacaagca ggggcagaac cagctctaca acgaactcaa tcttggtcgg

1200

agagaggagt acgacgtgct ggacaagcgg agaggacggg acccagaaat gggcgggaag

1260

ccgcgcagaa agaatcccca agagggcctg tacaacgagc tccaaaagga taagatggca

1320

gaagcctata gcgagattgg tatgaaaggg gaacgcagaa gaggcaaagg ccacgacggga

1380

ctgtaccagg gactcagcac cgccaccaag gacacctatg acgctcttca catgcaggcc

1440

ctgccgcctc gg

1452

<210> 817

<211> 485

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 817

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe

35 40 45

Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr

65 70 75 80

Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg

85 90 95

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala

100 105 110

Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val Trp Gly Gln

115 120 125

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Arg Ala Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser

145 150 155 160

Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

165 170 175

Arg Ala Ser Gln Ser Ile Gly Ser Ser Ser Leu Ala Trp Tyr Gln Gln

180 185 190

Lys Pro Gly Gln Ala Pro Arg Leu Leu Met Tyr Gly Ala Ser Ser Arg

195 200 205

Ala Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

210 215 220

Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr

225 230 235 240

Tyr Cys Gln Gln Tyr Ala Gly Ser Pro Pro Phe Thr Phe Gly Gln Gly

245 250 255

Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

260 265 270

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

275 280 285

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

290 295 300

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

305 310 315 320

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

325 330 335

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

340 345 350

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

355 360 365

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

370 375 380

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

385 390 395 400

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

405 410 415

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

420 425 430

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

435 440 445

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

450 455 460

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

465 470 475 480

Ala Leu Pro Pro Arg

485

<210> 818

<211> 1455

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 818

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc aattggtgga atctggtgga ggacttgtgc aacctggagg atcactgaga

120

ctgtcatgcg cggtgtccgg ttttgccctg agcaatcatg ggatgtcgtg ggtccggcgc

180

gccccgggaa agggtctgga atgggtgtcg ggtatcgtct actccgggag cacttactac

240

gccgcgagcg tgaagggccg cttcaccatt tcccgcgata actcccgcaa caccctgtac

300

ttgcaaatga actcgctccg gcctgaggac actgccatct actactgctc cgcacacgga

360

ggagaatccg acgtgtgggg ccagggaact accgtgaccg tcagcagcgc ctccggcggc

420

gggggctcag gcggacgggc tagcggcggc ggtggctccg agatcgtgct gacccagtcg

480

cctggcactc tctcgctgag ccccggggaa agggcaaccc tgtcctgtcg ggccagccag

540

tccattggat catcctccct cgcctggtat cagcagaaac cgggacaggc tccgcggctg

600

cttatgtatg gggccagctc aagagcctcc ggcattcccg accggttctc cgggtccggt

660

tccggcaccg atttcaccct gactatctcg aggctggagc cagaggactt cgccgtgtac

720

tactgccagc agtacgcggg gtccccgccg ttcacgttcg gacagggaac caaggtcgag

780

atcaagacca ctaccccagc accgaggcca cccaccccgg ctcctaccat cgcctcccag

840

cctctgtccc tgcgtccgga ggcatgtaga cccgcagctg gtggggccgt gcatacccgg

900

ggtcttgact tcgcctgcga tatctacatt tgggcccctc tggctggtac ttgcggggtc

960

ctgctgcttt cactcgtgat cactctttac tgtaagcgcg gtcggaagaa gctgctgtac

1020

atctttaagc aacccttcat gaggcctgtg cagactactc aagaggagga cggctgttca

1080

tgccggttcc cagaggagga ggaaggcggc tgcgaactgc gcgtgaaatt cagccgcagc

1140

gcagatgctc cagcctacaa gcaggggcag aaccagctct acaacgaact caatcttggt

1200

cggagagagg agtacgacgt gctggacaag cggagaggac gggacccaga aatgggcggg

1260

aagccgcgca gaaagaatcc ccaagagggc ctgtacaacg agctccaaaa ggataagatg

1320

gcagaagcct atagcgagat tggtatgaaa ggggaacgca gaagaggcaa aggccacgac

1380

ggactgtacc agggactcag caccgccacc aaggacacct atgacgctct tcacatgcag

1440

gccctgccgc ctcgg

1455

<210> 819

<211> 487

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 819

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly

35 40 45

Ser Ile Ser Ser Ser Tyr Tyr Tyr Trp Gly Trp Ile Arg Gln Pro Pro

50 55 60

Gly Lys Gly Leu Glu Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Ala

65 70 75 80

Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr

85 90 95

Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp

100 105 110

Thr Ala Val Tyr Tyr Cys Ala Arg His Trp Gln Glu Trp Pro Asp Ala

115 120 125

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly

130 135 140

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Thr

145 150 155 160

Leu Thr Gln Ser Pro Ala Phe Met Ser Ala Thr Pro Gly Asp Lys Val

165 170 175

Ile Ile Ser Cys Lys Ala Ser Gln Asp Ile Asp Asp Ala Met Asn Trp

180 185 190

Tyr Gln Gln Lys Pro Gly Glu Ala Pro Leu Phe Ile Ile Gln Ser Ala

195 200 205

Thr Ser Pro Val Pro Gly Ile Pro Pro Arg Phe Ser Gly Ser Gly Phe

210 215 220

Gly Thr Asp Phe Ser Leu Thr Ile Asn Asn Ile Glu Ser Glu Asp Ala

225 230 235 240

Ala Tyr Tyr Phe Cys Leu Gln His Asp Asn Phe Pro Leu Thr Phe Gly

245 250 255

Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

260 265 270

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

275 280 285

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

290 295 300

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

305 310 315 320

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

325 330 335

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

340 345 350

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

355 360 365

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

370 375 380

Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

385 390 395 400

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

405 410 415

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

420 425 430

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

435 440 445

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

450 455 460

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

465 470 475 480

Met Gln Ala Leu Pro Pro Arg

485

<210> 820

<211> 1461

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 820

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc agcttcagga aagcggaccg ggcctggtca agccatccga aactctctcc

120

ctgacttgca ctgtgtctgg cggttccatc tcatcgtcgt actactactg gggctggatt

180

aggcagccgc ccggaaaggg actggagtgg atcggaagca tctactattc cggctcggcg

240

tactacacc ctagcctcaa gtcgagagtg accatctccg tggatacctc caagaaccag

300

ttttccctgc gcctgagctc cgtgaccgcc gctgacaccg ccgtgtacta ctgtgctcgg

360

cattggcagg aatggcccga tgccttcgac atttggggcc agggcactat ggtcactgtg

420

tcatccgggg gtggaggcag cgggggagga gggtccgggg ggggaggttc agagacaacc

480

ttgacccagt cacccgcatt catgtccgcc actccgggag acaaggtcat catctcgtgc

540

aaagcgtccc aggatatcga cgatgccatg aattggtacc agcagaagcc tggcgaagcg

600

ccgctgttca ttatccaatc cgcaacctcg cccgtgcctg gaatcccacc gcggttcagc

660

ggcagcggtt tcggaaccga ctttttccctg accattaaca acattgagtc cgaggacgcc

720

gcctactact tctgcctgca acacgacaac ttccctctca cgttcggcca gggaaccaag

780

ctggaaatca agaccactac ccgcaccg aggccaccca ccccggctcc taccatcgcc

840

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

900

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

960

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1020

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1080

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1140

cgcagcgcag atgctccagc ctacaagcag gggcagaacc agctctacaa cgaactcaat

1200

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

1260

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

1320

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

1380

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

1440

atgcaggccc tgccgcctcg g

1461

<210> 821

<211> 489

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 821

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Asn Leu Arg Glu Ser Gly Pro Ala Leu

20 25 30

Val Lys Pro Thr Gln Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe

35 40 45

Ser Leu Arg Thr Ser Gly Met Cys Val Ser Trp Ile Arg Gln Pro Pro

50 55 60

Gly Lys Ala Leu Glu Trp Leu Ala Arg Ile Asp Trp Asp Glu Asp Lys

65 70 75 80

Phe Tyr Ser Thr Ser Leu Lys Thr Arg Leu Thr Ile Ser Lys Asp Thr

85 90 95

Ser Asp Asn Gln Val Val Leu Arg Met Thr Asn Met Asp Pro Ala Asp

100 105 110

Thr Ala Thr Tyr Tyr Cys Ala Arg Ser Gly Ala Gly Gly Thr Ser Ala

115 120 125

Thr Ala Phe Asp Ile Trp Gly Pro Gly Thr Met Val Thr Val Ser Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp

145 150 155 160

Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp

165 170 175

Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Tyr Asn Asn Leu

180 185 190

Ala Trp Phe Gln Leu Lys Pro Gly Ser Ala Pro Arg Ser Leu Met Tyr

195 200 205

Ala Ala Asn Lys Ser Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser

210 215 220

Ala Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

225 230 235 240

Asp Phe Ala Thr Tyr Tyr Cys Gln His Tyr Tyr Arg Phe Pro Tyr Ser

245 250 255

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro

260 265 270

Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu

275 280 285

Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg

290 295 300

Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly

305 310 315 320

Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys

325 330 335

Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg

340 345 350

Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro

355 360 365

Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser

370 375 380

Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu

385 390 395 400

Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg

405 410 415

Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln

420 425 430

Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr

435 440 445

Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp

450 455 460

Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala

465 470 475 480

Leu His Met Gln Ala Leu Pro Pro Arg

485

<210> 822

<211> 1467

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 822

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtca atctgcgcga atccggcccc gccttggtca agcctaccca gaccctcact

120

ctgacctgta ctttctccgg cttctccctg cggacttccg ggatgtgcgt gtcctggatc

180

agacagcctc cgggaaaggc cctggagtgg ctcgctcgca ttgactggga tgaggacaag

240

ttctactcca cctcactcaa gaccaggctg accatcagca aagatacctc tgacaaccaa

300

gtggtgctcc gcatgaccaa catggaccca gccgacactg ccacttacta ctgcgcgagg

360

agcggagcgg gcggaacctc cgccaccgcc ttcgatattt ggggcccgggg taccatggtc

420

accgtgtcaa gcggaggagg ggggtccggg ggcggcggtt ccgggggagg cggatcggac

480

attcagatga ctcagtcacc atcgtccctg agcgctagcg tgggcgacag agtgacaatc

540

acttgccggg catccgga catctataac aaccttgcgt ggttccagct gaagcctggt

600

tccgcaccgc ggtcacttat gtacgccgcc aacaagagcc agtcgggagt gccgtcccgg

660

ttttccggtt cggcctcggg aactgacttc accctgacga tctccagcct gcaacccgag

720

gatttcgcca cctactactg ccagcactac taccgctttc cctactcgtt cggacaggga

780

accaagctgg aaatcaagac cactaccca gcaccgaggc cacccacccc ggctcctacc

840

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

900

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

960

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1020

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1080

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1140

ttcagccgca gcgcagatgc tccagcctac aagcaggggc agaaccagct ctacaacgaa

1200

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

1260

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

1320

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

1380

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

1440

cttcacatgc aggccctgcc gcctcgg

1467

<210> 823

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 823

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ser Met Asn Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ser Ile Ser Ser Ser Ser Ser Tyr Ile Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Thr Ile Ala Ala Val Tyr Ala Phe Asp

115 120 125

Ile Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr

145 150 155 160

Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Glu Glu Pro Ala Ser Ile

165 170 175

Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr

180 185 190

Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile

195 200 205

Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly

210 215 220

Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala

225 230 235 240

Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr Pro Tyr

245 250 255

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 824

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 824

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc agcttgtcga atccgggggg ggactggtca agccggggcgg atcactgaga

120

ctgtcctgcg ccgcgagcgg cttcacgttc tcctcctact ccatgaactg ggtccgccaa

180

gcccccggga agggactgga atgggtgtcc tctatctcct cgtcgtcgtc ctacatctac

240

tacgccgact ccgtgaaggg aagattcacc atttcccgcg acaacgcaaa gaactcactg

300

tacttgcaaa tgaactcact ccgggccgaa gatactgctg tgtactattg cgccaagact

360

attgccgccg tctacgcttt cgacatctgg ggccagggaa ccaccgtgac tgtgtcgtcc

420

ggtggtggtg gctcgggcgg aggaggaagc ggcggcgggg ggtccgagat tgtgctgacc

480

cagtcgccac tgagcctccc tgtgaccccc gaggaacccg ccagcatcag ctgccggtcc

540

agccagtccc tgctccactc caacggatac aattacctcg attggtacct tcagaagcct

600

ggacaaagcc cgcagctgct catctacttg ggatcaaacc gcgcgtcagg agtgcctgac

660

cggttctccg gctcgggcag cggtaccgat ttcaccctga aaatctccag ggtggaggca

720

gaggacgtgg gagtgtatta ctgtatgcag gcgctgcaga ctccgtacac atttgggcag

780

ggcaccaagc tggagatcaa gaccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 825

<211> 484

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 825

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Lys Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Asp Tyr Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Asp Leu Arg Gly Ala Phe Asp Ile Trp

115 120 125

Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Tyr Val Leu Thr Gln Ser

145 150 155 160

Pro Ser Val Ser Ala Ala Pro Gly Tyr Thr Ala Thr Ile Ser Cys Gly

165 170 175

Gly Asn Asn Ile Gly Thr Lys Ser Val His Trp Tyr Gln Gln Lys Pro

180 185 190

Gly Gln Ala Pro Leu Leu Val Ile Arg Asp Asp Ser Val Arg Pro Ser

195 200 205

Lys Ile Pro Gly Arg Phe Ser Gly Ser Asn Ser Gly Asn Met Ala Thr

210 215 220

Leu Thr Ile Ser Gly Val Gln Ala Gly Asp Glu Ala Asp Phe Tyr Cys

225 230 235 240

Gln Val Trp Asp Ser Asp Ser Glu His Val Val Phe Gly Gly Gly Thr

245 250 255

Lys Leu Thr Val Leu Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro

260 265 270

Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys

275 280 285

Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala

290 295 300

Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu

305 310 315 320

Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys

325 330 335

Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr

340 345 350

Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly

355 360 365

Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala

370 375 380

Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg

385 390 395 400

Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu

405 410 415

Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn

420 425 430

Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met

435 440 445

Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly

450 455 460

Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala

465 470 475 480

Leu Pro Pro Arg

<210> 826

<211> 1452

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 826

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtcc agctcgtgga gtccggcgga ggccttgtga agcctggagg ttcgctgaga

120

ctgtcctgcg ccgcctccgg cttcaccttc tccgactact acatgtcctg gatcagacag

180

gccccgggaa agggcctgga atgggtgtcc tacatctcgt catcggggcag cactatctac

240

tacgcggact cagtgaaggg gcggttcacc atttcccggg ataacgcgaa gaactcgctg

300

tatctgcaaa tgaactcact gagggccgag gacaccgccg tgtactactg cgcccgcgat

360

ctccgcgggg catttgacat ctggggacag ggaaccatgg tcacagtgtc cagcggaggg

420

ggaggatcgg gtggcggagg ttccgggggt ggaggctcct cctacgtgct gactcagagc

480

ccaagcgtca gcgctgcgcc cggttacacg gcaaccatct cctgtggcgg aaacaacatt

540

gggaccaagt ctgtgcactg gtatcagcag aagccgggcc aagctcccct gttggtgatc

600

cgcgatgact ccgtgcggcc tagcaaaatt ccgggacggt tctccggctc caacagcggc

660

aatatggcca ctctcaccat ctcgggagtg caggccggag atgaagccga cttctactgc

720

caagtctggg actcagactc cgagcatgtg gtgttcgggg gcggaaccaa gctgactgtg

780

ctcaccacta ccccagcacc gaggccaccc accccggctc ctaccatcgc ctcccagcct

840

ctgtccctgc gtccgggaggc atgtagaccc gcagctggtg gggccgtgca tacccggggt

900

cttgacttcg cctgcgatat ctacatttgg gcccctctgg ctggtacttg cggggtcctg

960

ctgctttcac tcgtgatcac tctttactgt aagcgcggtc ggaagaagct gctgtacatc

1020

tttaagcaac ccttcatgag gcctgtgcag actactcaag aggaggacgg ctgttcatgc

1080

cggttcccag aggaggagga aggcggctgc gaactgcgcg tgaaattcag ccgcagcgca

1140

gatgctccag cctacaagca ggggcagaac cagctctaca acgaactcaa tcttggtcgg

1200

agagaggagt acgacgtgct ggacaagcgg agaggacggg acccagaaat gggcgggaag

1260

ccgcgcagaa agaatcccca agagggcctg tacaacgagc tccaaaagga taagatggca

1320

gaagcctata gcgagattgg tatgaaaggg gaacgcagaa gaggcaaagg ccacgacggga

1380

ctgtaccagg gactcagcac cgccaccaag gacacctatg acgctcttca catgcaggcc

1440

ctgccgcctc gg

1452

<210> 827

<211> 485

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 827

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Pro Ser Gly Tyr

35 40 45

Thr Val Thr Ser His Tyr Ile His Trp Val Arg Arg Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Met Ile Asn Pro Ser Gly Gly Val Thr Ala

65 70 75 80

Tyr Ser Gln Thr Leu Gln Gly Arg Val Thr Met Thr Ser Asp Thr Ser

85 90 95

Ser Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

100 105 110

Ala Met Tyr Tyr Cys Ala Arg Glu Gly Ser Gly Ser Gly Trp Tyr Phe

115 120 125

Asp Phe Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Tyr Val Leu

145 150 155 160

Thr Gln Pro Pro Ser Val Ser Val Ser Pro Gly Gln Thr Ala Ser Ile

165 170 175

Thr Cys Ser Gly Asp Gly Leu Ser Lys Lys Tyr Val Ser Trp Tyr Gln

180 185 190

Gln Lys Ala Gly Gln Ser Pro Val Val Leu Ile Ser Arg Asp Lys Glu

195 200 205

Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Asn Ser Ala Asp

210 215 220

Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Met Asp Glu Ala Asp

225 230 235 240

Tyr Tyr Cys Gln Ala Trp Asp Asp Thr Thr Val Val Phe Gly Gly Gly

245 250 255

Thr Lys Leu Thr Val Leu Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

260 265 270

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

275 280 285

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

290 295 300

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

305 310 315 320

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

325 330 335

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

340 345 350

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

355 360 365

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

370 375 380

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

385 390 395 400

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

405 410 415

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

420 425 430

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

435 440 445

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

450 455 460

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

465 470 475 480

Ala Leu Pro Pro Arg

485

<210> 828

<211> 1455

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 828

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc agctggtgca gagcggggcc gaagtcaaga agccgggagc ctccgtgaaa

120

gtgtcctgca agccttcggg atacaccgtg acctcccact acattcattg ggtccgccgc

180

gcccccggcc aaggactcga gtggatgggc atgatcaacc ctagcggcgg agtgaccgcg

240

tacagccaga cgctgcaggg acgcgtgact atgacctcgg atacctcctc ctccaccgtc

300

tatatggaac tgtccagcct gcggtccgag gataccgcca tgtactactg cgcccgggaa

360

ggatcaggct ccgggtggta tttcgacttc tggggaagag gcaccctcgt gactgtgtca

420

tctgggggag ggggttccgg tggtggcgga tcgggaggag gcggttcatc ctacgtgctg

480

acccagccac cctccgtgtc cgtgagcccc ggccagactg catcgattac atgtagcggc

540

gacggcctct ccaagaaata cgtgtcgtgg taccagcaga aggccggaca gagcccggtg

600

gtgctgatct caagagataa ggagcggcct agcggaatcc cggacaggtt ctcgggttcc

660

aactccgcgg acactgctac tctgaccatc tcggggaccc aggctatgga cgaagccgat

720

tactactgcc aagcctggga cgacactact gtcgtgtttg gagggggcac caagttgacc

780

gtccttacca ctaccccagc accgaggcca cccaccccgg ctcctaccat cgcctcccag

840

cctctgtccc tgcgtccgga ggcatgtaga cccgcagctg gtggggccgt gcatacccgg

900

ggtcttgact tcgcctgcga tatctacatt tgggcccctc tggctggtac ttgcggggtc

960

ctgctgcttt cactcgtgat cactctttac tgtaagcgcg gtcggaagaa gctgctgtac

1020

atctttaagc aacccttcat gaggcctgtg cagactactc aagaggagga cggctgttca

1080

tgccggttcc cagaggagga ggaaggcggc tgcgaactgc gcgtgaaatt cagccgcagc

1140

gcagatgctc cagcctacaa gcaggggcag aaccagctct acaacgaact caatcttggt

1200

cggagagagg agtacgacgt gctggacaag cggagaggac gggacccaga aatgggcggg

1260

aagccgcgca gaaagaatcc ccaagagggc ctgtacaacg agctccaaaa ggataagatg

1320

gcagaagcct atagcgagat tggtatgaaa ggggaacgca gaagaggcaa aggccacgac

1380

ggactgtacc agggactcag caccgccacc aaggacacct atgacgctct tcacatgcag

1440

gccctgccgc ctcgg

1455

<210> 829

<211> 489

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 829

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly

35 40 45

Ser Ile Ser Ser Gly Gly Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro

50 55 60

Gly Lys Gly Leu Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr

65 70 75 80

Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr

85 90 95

Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp

100 105 110

Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly Ile Ala Ala Arg Leu Arg

115 120 125

Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp

145 150 155 160

Ile Val Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly Asp

165 170 175

Arg Val Ile Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Trp Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Asn Leu Leu Ile Tyr

195 200 205

Ala Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Ala Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

225 230 235 240

Asp Val Ala Thr Tyr Tyr Cys Gln Lys Tyr Asn Ser Ala Pro Phe Thr

245 250 255

Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Thr Thr Thr Pro Ala Pro

260 265 270

Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu

275 280 285

Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg

290 295 300

Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly

305 310 315 320

Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys

325 330 335

Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg

340 345 350

Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro

355 360 365

Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser

370 375 380

Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu

385 390 395 400

Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg

405 410 415

Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln

420 425 430

Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr

435 440 445

Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp

450 455 460

Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala

465 470 475 480

Leu His Met Gln Ala Leu Pro Pro Arg

485

<210> 830

<211> 1467

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 830

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc agcttcagga gagcggcccg ggactcgtga agccgtccca gaccctgtcc

120

ctgacttgca ccgtgtcggg aggaagcatc tcgagcggag gctactattg gtcgtggatt

180

cggcagcacc ctggaaaggg cctggaatgg atcggctaca tctactactc cggctcgacc

240

tactacacc catcgctgaa gtccagagtg acaatctcag tggacacgtc caagaatcag

300

ttcagcctga agctctcttc cgtgactgcg gccgacaccg ccgtgtacta ctgcgcacgc

360

gctggaattg ccgcccggct gaggggtgcc ttcgacattt ggggacaggg caccatggtc

420

accgtgtcct ccggcggcgg aggttccggg ggtggaggct caggaggagg ggggtccgac

480

atcgtcatga ctcagtcgcc ctcaagcgtc agcgcgtccg tcggggacag agtgatcatc

540

acctgtcggg cgtcccaggg aattcgcaac tggctggcct ggtatcagca gaagccggga

600

aaggccccca acctgttgat ctacgccgcc tcaaacctcc aatccggggt gccgagccgc

660

ttcagcggct ccggttcggg tgccgatttc actctgacca tctcctccct gcaacctgaa

720

gatgtggcta cctactactg ccaaaagtac aactccgcac cttttacttt cggaccgggg

780

accaaagtgg acattaagac cactaccca gcaccgaggc cacccacccc ggctcctacc

840

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

900

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

960

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1020

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1080

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1140

ttcagccgca gcgcagatgc tccagcctac aagcaggggc agaaccagct ctacaacgaa

1200

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

1260

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

1320

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

1380

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

1440

cttcacatgc aggccctgcc gcctcgg

1467

<210> 831

<211> 497

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 831

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

20 25 30

Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly

35 40 45

Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln

50 55 60

Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn

65 70 75 80

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser

85 90 95

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Arg Gly Gly Tyr Gln Leu Leu Arg Trp

115 120 125

Asp Val Gly Leu Leu Arg Ser Ala Phe Asp Ile Trp Gly Gln Gly Thr

130 135 140

Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Gly Gly Gly Gly Ser Ser Tyr Val Leu Thr Gln Pro Pro Ser Val Ser

165 170 175

Val Ala Pro Gly Gln Thr Ala Arg Ile Thr Cys Gly Gly Asn Asn Ile

180 185 190

Gly Ser Lys Ser Val His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro

195 200 205

Val Leu Val Leu Tyr Gly Lys Asn Asn Arg Pro Ser Gly Val Pro Asp

210 215 220

Arg Phe Ser Gly Ser Arg Ser Gly Thr Thr Ala Ser Leu Thr Ile Thr

225 230 235 240

Gly Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Arg Asp

245 250 255

Ser Ser Gly Asp His Leu Arg Val Phe Gly Thr Gly Thr Lys Val Thr

260 265 270

Val Leu Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

275 280 285

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

290 295 300

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

305 310 315 320

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

325 330 335

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

340 345 350

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

355 360 365

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

370 375 380

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

385 390 395 400

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

405 410 415

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

420 425 430

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

435 440 445

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

450 455 460

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

465 470 475 480

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

485 490 495

Arg

<210> 832

<211> 1491

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 832

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc agctggtcca gtcgggcgcc gaggtcaaga agcccgggag ctctgtgaaa

120

gtgtcctgca aggcctccgg gggcaccttt agctcctacg ccatctcctg ggtccgccaa

180

gcaccgggtc aaggcctgga gtggatgggg ggaattatcc ctatcttcgg cactgccaac

240

tacgcccaga agttccaggg acgcgtgacc attaccgcgg acgaatccac ctccaccgct

300

tatatggagc tgtccagctt gcgctcggaa gataccgccg tgtactactg cgcccgggagg

360

ggtggatacc agctgctgag atgggacgtg ggcctcctgc ggtcggcgtt cgacatctgg

420

ggccagggca ctatggtcac tgtgtccagc ggaggaggcg gatcgggagg cggcggatca

480

gggggaggcg gttccagcta cgtgcttact caaccccctt cggtgtccgt ggccccggga

540

cagaccgcca gaatcacttg cggaggaaac aacattgggt ccaagagcgt gcattggtac

600

cagcagaagc caggacaggc ccctgtgctg gtgctctacg ggaagaacaa tcggcccagc

660

ggagtgccgg acaggttctc gggttcacgc tccggtacaa ccgcttcact gactatcacc

720

ggggcccagg cagaggatga agcggactac tactgttcct cccgggattc atccggcgac

780

cacctccggg tgttcggaac cggaacgaag gtcaccgtgc tgaccactac cccagcaccg

840

aggccaccca ccccggctcc taccatcgcc tcccagcctc tgtccctgcg tccgggaggca

900

tgtagacccg cagctggtgg ggccgtgcat acccggggtc ttgacttcgc ctgcgatatc

960

tacatttggg cccctctggc tggtacttgc ggggtcctgc tgctttcact cgtgatcact

1020

ctttactgta agcgcggtcg gaagaagctg ctgtacatct ttaagcaacc cttcatgagg

1080

cctgtgcaga ctactcaaga ggaggacggc tgttcatgcc ggttcccaga ggaggaggaa

1140

ggcggctgcg aactgcgcgt gaaattcagc cgcagcgcag atgctccagc ctacaagcag

1200

gggcagaacc agctctacaa cgaactcaat cttggtcgga gagaggagta cgacgtgctg

1260

gacaagcgga gaggacggga cccagaaatg ggcgggaagc cgcgcagaaa gaatccccaa

1320

gagggcctgt acaacgagct ccaaaaggat aagatggcag aagcctatag cgagattggt

1380

atgaaagggg aacgcagaag aggcaaaggc cacgacggac tgtaccaggg actcagcacc

1440

gccaccaagg acacctatga cgctcttcac atgcaggccc tgccgcctcg g

1491

<210> 833

<211> 492

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 833

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Gln Gln Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp

35 40 45

Ser Val Ser Ser Asn Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro

50 55 60

Ser Arg Gly Leu Glu Trp Leu Gly Arg Thr Tyr Tyr Arg Ser Lys Trp

65 70 75 80

Tyr Ser Phe Tyr Ala Ile Ser Leu Lys Ser Arg Ile Ile Ile Asn Pro

85 90 95

Asp Thr Ser Lys Asn Gln Phe Ser Leu Gln Leu Lys Ser Val Thr Pro

100 105 110

Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Ser Pro Glu Gly Leu

115 120 125

Phe Leu Tyr Trp Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val

130 135 140

Ser Ser Gly Gly Asp Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

145 150 155 160

Ser Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly

165 170 175

Gln Thr Ile Arg Ile Thr Cys Gln Gly Asp Ser Leu Gly Asn Tyr Tyr

180 185 190

Ala Thr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile

195 200 205

Tyr Gly Thr Asn Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Ala

210 215 220

Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala

225 230 235 240

Glu Asp Glu Ala Asp Tyr Tyr Cys Asn Ser Arg Asp Ser Ser Gly His

245 250 255

His Leu Leu Phe Gly Thr Gly Thr Lys Val Thr Val Leu Thr Thr Thr

260 265 270

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

275 280 285

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

290 295 300

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

305 310 315 320

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

325 330 335

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

340 345 350

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

355 360 365

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

370 375 380

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu

385 390 395 400

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

405 410 415

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

420 425 430

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

435 440 445

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

450 455 460

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

465 470 475 480

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 834

<211> 1476

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 834

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc agctccaaca gtcaggaccg gggctcgtga agccatccca gaccctgtcc

120

ctgacttgtg ccatctcggg agatagcgtg tcatcgaact ccgccgcctg gaactggatt

180

cggcagagcc cgtcccgcgg actggagtgg cttggaagga cctactaccg gtccaagtgg

240

tactctttct acgcgatctc gctgaagtcc cgcattatca ttaaccctga tacctccaag

300

aatcagttct ccctccaact gaaatccgtc acccccgagg acacagcagt gtattactgc

360

gcacggagca gccccgaagg actgttcctg tattggtttg acccctgggg ccaggggact

420

cttgtgaccg tgtcgagcgg cggagatggg tccggtggcg gtggttcggg gggcggcggga

480

tcatcatccg aactgaccca ggacccggct gtgtccgtgg cgctgggaca aaccatccgc

540

attacgtgcc agggagactc cctgggcaac tactacgcca cttggtacca gcagaagccg

600

ggccaagccc ctgtgttggt catctacggg accaacaaca gaccttccgg catccccgac

660

cggttcagcg cttcgtcctc cggcaacact gccagcctga ccatcactgg agcgcaggcc

720

gaagatgagg ccgactacta ctgcaacagc agagactcct cgggtcatca cctcttgttc

780

ggaactggaa ccaaggtcac cgtgctgacc actaccccag caccgaggcc acccaccccg

840

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

900

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

960

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1020

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1080

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1140

cgcgtgaaat tcagccgcag cgcagatgct ccagcctaca agcaggggca gaaccagctc

1200

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

1260

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

1320

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

1380

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

1440

tatgacgctc ttcacatgca ggccctgccg cctcgg

1476

<210> 835

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 835

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Val Glu Gly Ser Gly Ser Leu Asp Tyr

115 120 125

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln

145 150 155 160

Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

165 170 175

Cys Arg Ala Ser Gln Ser Val Ser Ser Ala Tyr Leu Ala Trp Tyr Gln

180 185 190

Gln Lys Pro Gly Gln Pro Pro Arg Leu Leu Ile Ser Gly Ala Ser Thr

195 200 205

Arg Ala Thr Gly Ile Pro Asp Arg Phe Gly Gly Ser Gly Ser Gly Thr

210 215 220

Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val

225 230 235 240

Tyr Tyr Cys Gln His Tyr Gly Ser Ser Phe Asn Gly Ser Ser Leu Phe

245 250 255

Thr Phe Gly Glyn Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 836

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 836

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc agctcgtgga gtcaggaggc ggcctggtcc agccgggagg gtcccttaga

120

ctgtcatgcg ccgcaagcgg attcactttc tcctcctatg ccatgagctg ggtccgccaa

180

gccccgggaa agggactgga atgggtgtcc gccatctcgg ggtctggagg ctcaacttac

240

tacgctgact ccgtgaaggg acggttcacc attagccgcg acaactccaa gaacaccctc

300

tacctccaaa tgaactccct gcgggccgag gataccgccg tctactactg cgccaaagtg

360

gaaggttcag gatcgctgga ctactgggga cagggtactc tcgtgaccgt gtcatcgggc

420

ggaggaggtt ccggcggtgg cggctccggc ggcggagggt cggagatcgt gatgacccag

480

agccctggta ctctgagcct ttcgccggga gaaagggcca ccctgtcctg ccgcgcttcc

540

caatccgtgt cctccgcgta cttggcgtgg taccagcaga agccgggaca gccccctcgg

600

ctgctgatca gcggggccag cacccgggca accggaatcc cagacagatt cgggggttcc

660

ggcagcggca cagatttcac cctgactatt tcgaggttgg agcccgagga ctttgcggtg

720

tattactgtc agcactacgg gtcgtccttt aatggctcca gcctgttcac gttcggacag

780

gggacccgcc tggaaatcaa gaccactacc cggcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 837

<211> 485

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 837

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ile

35 40 45

Thr Phe Ser Arg Tyr Pro Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Ser Asp Ser Gly Val Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Phe Leu Gln Met Ser Ser Leu Arg Asp Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Val Thr Arg Ala Gly Ser Glu Ala Ser Asp Ile

115 120 125

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln

145 150 155 160

Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

165 170 175

Cys Arg Ala Ser Gln Ser Val Ser Asn Ser Leu Ala Trp Tyr Gln Gln

180 185 190

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Asp Ala Ser Ser Arg

195 200 205

Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

210 215 220

Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Ile Tyr

225 230 235 240

Tyr Cys Gln Gln Phe Gly Thr Ser Ser Gly Leu Thr Phe Gly Gly Gly

245 250 255

Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

260 265 270

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

275 280 285

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

290 295 300

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

305 310 315 320

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

325 330 335

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

340 345 350

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

355 360 365

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

370 375 380

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

385 390 395 400

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

405 410 415

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

420 425 430

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

435 440 445

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

450 455 460

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

465 470 475 480

Ala Leu Pro Pro Arg

485

<210> 838

<211> 1455

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 838

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc aactggtgga aaccggtggc ggcctggtgc agcctggagg atcattgagg

120

ctgtcatgcg cggccagcgg tattaccttc tcccggtacc ccatgtcctg ggtcagacag

180

gccccgggga aagggcttga atgggtgtcc gggatctcgg actccggtgt cagcacttac

240

tacgccgact ccgccaaggg acgcttcacc atttcccggg acaactcgaa gaacaccctg

300

ttcctccaaa tgagctccct ccgggacgag gatactgcag tgtactactg cgtgacccgc

360

gccgggtccg aggcgtctga catttgggga cagggcacta tggtcaccgt gtcgtccggc

420

ggagggggct cgggaggcgg tggcagcgga ggaggagggt ccgagatcgt gctgacccaa

480

tccccggcca ccctctcgct gagccctgga gaaagggcaa ccttgtcctg tcgcgcgagc

540

cagtccgtga gcaactccct ggcctggtac cagcagaagc ccggacaggc tccgagactt

600

ctgatctacg acgcttcgag ccgggccact ggaatccccg accgcttttc ggggtccggc

660

tcaggaaccg atttcaccct gacaatctca cggctggagc cagaggattt cgccatctat

720

tactgccagc agttcggtac ttcctccggc ctgactttcg gaggcggcac gaagctcgaa

780

atcaagacca ctaccccagc accgaggcca cccaccccgg ctcctaccat cgcctcccag

840

cctctgtccc tgcgtccgga ggcatgtaga cccgcagctg gtggggccgt gcatacccgg

900

ggtcttgact tcgcctgcga tatctacatt tgggcccctc tggctggtac ttgcggggtc

960

ctgctgcttt cactcgtgat cactctttac tgtaagcgcg gtcggaagaa gctgctgtac

1020

atctttaagc aacccttcat gaggcctgtg cagactactc aagaggagga cggctgttca

1080

tgccggttcc cagaggagga ggaaggcggc tgcgaactgc gcgtgaaatt cagccgcagc

1140

gcagatgctc cagcctacaa gcaggggcag aaccagctct acaacgaact caatcttggt

1200

cggagagagg agtacgacgt gctggacaag cggagaggac gggacccaga aatgggcggg

1260

aagccgcgca gaaagaatcc ccaagagggc ctgtacaacg agctccaaaa ggataagatg

1320

gcagaagcct atagcgagat tggtatgaaa ggggaacgca gaagaggcaa aggccacgac

1380

ggactgtacc agggactcag caccgccacc aaggacacct atgacgctct tcacatgcag

1440

gccctgccgc ctcgg

1455

<210> 839

<211> 492

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 839

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Ile Tyr Tyr Cys Ala Arg Ala Thr Tyr Lys Arg Glu Leu Arg Tyr

115 120 125

Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Glu Ile Val Met Thr Gln Ser Pro Gly Thr Val Ser Leu Ser Pro Gly

165 170 175

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

180 185 190

Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

195 200 205

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

225 230 235 240

Pro Glu Asp Ser Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Ser Pro

245 250 255

Ser Trp Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr

260 265 270

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

275 280 285

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

290 295 300

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

305 310 315 320

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

325 330 335

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

340 345 350

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

355 360 365

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

370 375 380

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu

385 390 395 400

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

405 410 415

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

420 425 430

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

435 440 445

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

450 455 460

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

465 470 475 480

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 840

<211> 1476

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 840

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc agctcgtgga atcgggtggc ggactggtgc agccgggggg ctcacttaga

120

ctgtcctgcg cggccagcgg attcactttc tcctcctacg ccatgtcctg ggtcagacag

180

gcccctggaa agggcctgga atgggtgtcc gcaatcagcg gcagcggcgg ctcgacctat

240

tacgcggatt cagtgaaggg cagattcacc atttcccggg acaacgccaa gaactccttg

300

taccttcaaa tgaactccct ccgcgcggaa gataccgcaa tctactactg cgctcgggcc

360

acttacaaga gggaactgcg ctactactac gggatggacg tctggggcca gggaaccatg

420

gtcaccgtgt ccagcgggagg aggaggatcg ggaggaggcg gtagcggggg tggagggtcg

480

gagatcgtga tgacccagtc ccccggcact gtgtcgctgt cccccggcga acgggccacc

540

ctgtcatgtc gggccagcca gtcagtgtcg tcaagcttcc tcgcctggta ccagcagaaa

600

ccgggacaag ctccccgcct gctgatctac ggagccagca gccgggccac cggtattcct

660

gaccggttct ccggttcggg gtccgggacc gactttactc tgactatctc tcgcctcgag

720

ccagaggact ccgccgtgta ttactgccag cagtaccact cctccccgtc ctggacgttc

780

ggacagggca caaggctgga gattaagacc actaccccag caccgaggcc acccaccccg

840

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

900

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

960

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1020

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1080

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1140

cgcgtgaaat tcagccgcag cgcagatgct ccagcctaca agcaggggca gaaccagctc

1200

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

1260

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

1320

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

1380

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

1440

tatgacgctc ttcacatgca ggccctgccg cctcgg

1476

<210> 841

<211> 492

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 841

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Thr Leu Lys Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Ala Thr Tyr Lys Arg Glu Leu Arg Tyr

115 120 125

Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Glu Ile Val Leu Thr Gln Ser Pro Ser Thr Leu Ser Leu Ser Pro Gly

165 170 175

Glu Ser Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Thr Thr

180 185 190

Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

195 200 205

Ile Tyr Gly Ser Ser Asn Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Arg Arg Leu Glu

225 230 235 240

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr His Ser Ser Pro

245 250 255

Ser Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr

260 265 270

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

275 280 285

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

290 295 300

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

305 310 315 320

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

325 330 335

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

340 345 350

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

355 360 365

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

370 375 380

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu

385 390 395 400

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

405 410 415

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

420 425 430

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

435 440 445

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

450 455 460

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

465 470 475 480

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 842

<211> 1476

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 842

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaggtgc agcttgtgga aaccggtggc ggactggtgc agcccgggagg aagcctcagg

120

ctgtcctgcg ccgcgtccgg cttcaccttc tcctcgtacg ccatgtcctg ggtccgccag

180

gccccgggaa agggcctgga atgggtgtcc gccatctctg gaagcgggagg ttccacgtac

240

tacgcggaca gcgtcaaggg aaggttcaca atctcccgcg ataattcgaa gaacactctg

300

taccttcaaa tgaacaccct gaaggccgag gacactgctg tgtactactg cgcacggggcc

360

acctacaaga gagagctccg gtactactac ggaatggacg tctggggcca gggaactact

420

gtgaccgtgt cctcgggagg gggtggctcc ggggggggcg gctccggcgg aggcggttcc

480

gagattgtgc tgacccagtc accttcaact ctgtcgctgt ccccgggaga gagcgctact

540

ctgagctgcc gggccagcca gtccgtgtcc accaccttcc tcgcctggta tcagcagaag

600

ccggggcagg caccacggct cttgatctac gggtcaagca acagagcgac cggaattcct

660

gaccgcttct cggggagcgg ttcaggcacc gacttcaccc tgactatccg gcgcctggaa

720

cccgaagatt tcgccgtgta ttactgtcaa cagtaccact cctcgccgtc ctggaccttt

780

ggccaaggaa ccaaagtgga aatcaagacc actaccccag caccgaggcc acccaccccg

840

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

900

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

960

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1020

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1080

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1140

cgcgtgaaat tcagccgcag cgcagatgct ccagcctaca agcaggggca gaaccagctc

1200

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

1260

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

1320

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

1380

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

1440

tatgacgctc ttcacatgca ggccctgccg cctcgg

1476

<210> 843

<211> 483

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 843

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Asp Asp Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Asp Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Arg Val Gly Lys Ala Val Pro Asp Val Trp

115 120 125

Gly Glyn Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Met Thr Gln Thr

145 150 155 160

Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys

165 170 175

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys

180 185 190

Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln

195 200 205

Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

210 215 220

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr

225 230 235 240

Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Ser Phe Gly Gln Gly Thr Arg

245 250 255

Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala

260 265 270

Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg

275 280 285

Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys

290 295 300

Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu

305 310 315 320

Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu

325 330 335

Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln

340 345 350

Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly

355 360 365

Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr

370 375 380

Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg

385 390 395 400

Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met

405 410 415

Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu

420 425 430

Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys

435 440 445

Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu

450 455 460

Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu

465 470 475 480

Pro Pro Arg

<210> 844

<211> 1449

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 844

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc agctcgtgga aactggaggt ggactcgtgc agcctggacg gtcgctgcgg

120

ctgagctgcg ctgcatccgg cttcaccttc gacgattatg ccatgcactg ggtcagacag

180

gcgccaggga agggacttga gtgggtgtcc ggtatcagct ggaatagcgg ctcaatcgga

240

tacgcggact ccgtgaaggg aaggttcacc atttcccgcg acaacgccaa gaactccctg

300

tacttgcaaa tgaacagcct ccgggatgag gacactgccg tgtactactg cgcccgcgtc

360

ggaaaagctg tgcccgacgt ctggggccag ggaaccactg tgaccgtgtc cagcggcggg

420

ggtggatcgg gcggtggagg gtccggtgga gggggctcag atattgtgat gacccagacc

480

ccctcgtccc tgtccgcctc ggtcggcgac cgcgtgacta tcacatgtag agcctcgcag

540

agcatctcca gctacctgaa ctggtatcag cagaagccgg ggaaggcccc gaagctcctg

600

atctacgcgg catcatcact gcaatcggga gtgccgagcc ggttttccgg gtccggctcc

660

ggcaccgact tcacgctgac catttcttcc ctgcaacccg aggacttcgc cacttactac

720

tgccagcagt cctactccac cccttactcc ttcggccaag gaaccaggct ggaaatcaag

780

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

840

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

900

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

960

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1020

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1080

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1140

gctccagcct acaagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1200

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

1260

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

1320

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

1380

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

1440

ccgcctcgg

1449

<210> 845

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 845

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe

35 40 45

Thr Phe Asp Asp Tyr Ala Met His Trp Val Arg Gln Arg Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ala Ser Ile Asn Trp Lys Gly Asn Ser Leu Ala

65 70 75 80

Tyr Gly Asp Ser Val Lys Gly Arg Phe Ala Ile Ser Arg Asp Asn Ala

85 90 95

Lys Asn Thr Val Phe Leu Gln Met Asn Ser Leu Arg Thr Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Ser His Gln Gly Val Ala Tyr Tyr Asn Tyr

115 120 125

Ala Met Asp Val Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Leu Ser Cys Arg Ala Thr Gln Ser Ile Gly Ser Ser Phe Leu

180 185 190

Ala Trp Tyr Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

195 200 205

Gly Ala Ser Gln Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Arg

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Val Glu Pro Glu

225 230 235 240

Asp Ser Ala Val Tyr Tyr Cys Gln His Tyr Glu Ser Ser Pro Ser Trp

245 250 255

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 846

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 846

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc agctcgtgga gagcggggga ggattggtgc agcccggaag gtccctgcgg

120

ctctcctgca ctgcgtctgg cttcaccttc gacgactacg cgatgcactg ggtcagacag

180

cgcccgggaa agggcctgga atgggtcgcc tcaatcaact ggaagggaaa ctccctggcc

240

tatggcgaca gcgtgaaggg ccgcttcgcc atttcgcgcg acaacgccaa gaacaccgtg

300

tttctgcaaa tgaattccct gcggaccgag gataccgctg tgtactactg cgccagccac

360

cagggcgtgg catactataa ctacgccatg gacgtgtggg gaagagggac gctcgtcacc

420

gtgtcctccg ggggcggtgg atcgggtgga ggaggaagcg gtggcggggg cagcgaaatc

480

gtgctgactc agagcccggg aactctttca ctgtccccgg gagaacggggc cactctctcg

540

tgccgggcca cccagtccat cggctcctcc ttccttgcct ggtaccagca gaggccagga

600

caggcgcccc gcctgctgat ctacggtgct tcccaacgcg ccactggcat tcctgaccgg

660

ttcagcggca gagggtcggg aaccgatttc acactgacca tttcccgggt ggagcccgaa

720

gattcggcag tctactactg tcagcattac gagtcctccc cttcatggac cttcggtcaa

780

gggaccaaag tggagatcaa gaccactacc ccagcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 847

<211> 485

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 847

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Val Val Arg Asp Gly Met Asp Val Trp

115 120 125

Gly Glyn Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser

145 150 155 160

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

165 170 175

Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln

180 185 190

Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg

195 200 205

Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Asn Gly Ser Gly Thr Asp

210 215 220

Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr

225 230 235 240

Tyr Cys Gln Gln Tyr Gly Ser Pro Arg Phe Thr Phe Gly Pro Gly

245 250 255

Thr Lys Val Asp Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr

260 265 270

Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala

275 280 285

Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe

290 295 300

Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val

305 310 315 320

Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys

325 330 335

Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr

340 345 350

Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu

355 360 365

Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro

370 375 380

Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly

385 390 395 400

Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro

405 410 415

Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr

420 425 430

Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly

435 440 445

Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln

450 455 460

Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln

465 470 475 480

Ala Leu Pro Pro Arg

485

<210> 848

<211> 1455

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 848

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaggtgc agttggtcga aagcggggggc gggcttgtgc agcctggcgg atcactgcgg

120

ctgtcctgcg cggcatcagg cttcacgttt tcttcctacg ccatgtcctg ggtgcgccag

180

gcccctggaa agggactgga atgggtgtcc gcgatttcgg ggtccggcgg gagcacctac

240

tacgccgatt ccgtgaaggg ccgcttcact atctcgcggg acaactccaa gaacaccctc

300

tacctccaaa tgaatagcct gcgggccgag gataccgccg tctactattg cgctaaggtc

360

gtgcgcgacg gaatggacgt gtggggacag ggtaccaccg tgacagtgtc ctcgggggga

420

ggcggtagcg gcggaggagg aagcggtggt ggaggttccg agattgtgct gactcaatca

480

cccgcgaccc tgagcctgtc ccccggcgaa agggccactc tgtcctgtcg ggccagccaa

540

tcagtctcct cctcgtacct ggcctggtac cagcagaagc caggacaggc tccgagactc

600

cttatctatg gcgcatcctc ccgcgccacc ggaatcccgg ataggttctc gggaaacgga

660

tcggggaccg acttcactct caccatctcc cggctggaac cggaggactt cgccgtgtac

720

tactgccagc agtacggcag cccgcctaga ttcactttcg gccccggcac caaagtggac

780

atcaagacca ctaccccagc accgaggcca cccaccccgg ctcctaccat cgcctcccag

840

cctctgtccc tgcgtccgga ggcatgtaga cccgcagctg gtggggccgt gcatacccgg

900

ggtcttgact tcgcctgcga tatctacatt tgggcccctc tggctggtac ttgcggggtc

960

ctgctgcttt cactcgtgat cactctttac tgtaagcgcg gtcggaagaa gctgctgtac

1020

atctttaagc aacccttcat gaggcctgtg cagactactc aagaggagga cggctgttca

1080

tgccggttcc cagaggagga ggaaggcggc tgcgaactgc gcgtgaaatt cagccgcagc

1140

gcagatgctc cagcctacaa gcaggggcag aaccagctct acaacgaact caatcttggt

1200

cggagagagg agtacgacgt gctggacaag cggagaggac gggacccaga aatgggcggg

1260

aagccgcgca gaaagaatcc ccaagagggc ctgtacaacg agctccaaaa ggataagatg

1320

gcagaagcct atagcgagat tggtatgaaa ggggaacgca gaagaggcaa aggccacgac

1380

ggactgtacc agggactcag caccgccacc aaggacacct atgacgctct tcacatgcag

1440

gccctgccgc ctcgg

1455

<210> 849

<211> 486

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 849

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Ile Pro Gln Thr Gly Thr Phe Asp Tyr

115 120 125

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser

130 135 140

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln

145 150 155 160

Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser

165 170 175

Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln

180 185 190

Gln Arg Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser

195 200 205

Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr

210 215 220

Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val

225 230 235 240

Tyr Tyr Cys Gln His Tyr Gly Ser Ser Pro Ser Trp Thr Phe Gly Gln

245 250 255

Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg

485

<210> 850

<211> 1458

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 850

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc agctgctgga gtccggcggt ggattggtgc aaccgggggg atcgctcaga

120

ctgtcctgtg cggcgtcagg cttcaccttc tcgagctacg ccatgtcatg ggtcagacag

180

gcccctggaa agggtctgga atgggtgtcc gccatttccg ggagcggggg atctacatac

240

tacgccgata gcgtgaaggg ccgcttcacc atttcccggg acaactccaa gaacactctc

300

tatctgcaaa tgaactccct ccgcgctgag gacactgccg tgtactactg cgccaaaatc

360

cctcagaccg gcaccttcga ctactgggga caggggactc tggtcaccgt cagcagcggt

420

ggcgggaggtt cgggggggagg aggaagcggc ggcggagggt ccgagattgt gctgacccag

480

tcacccggca ctttgtccct gtcgcctgga gaaagggcca ccctttcctg ccgggcatcc

540

caatccgtgt ccctcctcgta cctggcctgg taccagcaga ggcccggaca ggccccacgg

600

cttctgatct acggagcaag cagccgcgcg accggtatcc cggaccggtt ttcgggctcg

660

ggctcaggaa ctgacttcac cctcaccatc tcccgcctgg aacccgaaga tttcgctgtg

720

tattactgcc agcactacgg cagctccccg tcctggacgt tcggccaggg aactcggctg

780

gagatcaaga ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

840

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

900

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

960

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1020

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1080

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1140

agcgcagatg ctccagccta caagcagggg cagaaccagc tctacaacga actcaatctt

1200

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

1260

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

1320

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

1380

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

1440

caggccctgc cgcctcgg

1458

<210> 851

<211> 492

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 851

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Met Ser Arg Glu Asn Asp

85 90 95

Lys Asn Ser Val Phe Leu Gln Met Asn Ser Leu Arg Val Glu Asp Thr

100 105 110

Gly Val Tyr Tyr Cys Ala Arg Ala Asn Tyr Lys Arg Glu Leu Arg Tyr

115 120 125

Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Met Val Thr Val Ser

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Glu Ile Val Met Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

165 170 175

Glu Ser Ala Thr Leu Ser Cys Arg Ala Ser Gln Arg Val Ala Ser Asn

180 185 190

Tyr Leu Ala Trp Tyr Gln His Lys Pro Gly Gln Ala Pro Ser Leu Leu

195 200 205

Ile Ser Gly Ala Ser Ser Arg Ala Thr Gly Val Pro Asp Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ala Ile Ser Arg Leu Glu

225 230 235 240

Pro Glu Asp Ser Ala Val Tyr Tyr Cys Gln His Tyr Asp Ser Ser Pro

245 250 255

Ser Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr

260 265 270

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

275 280 285

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

290 295 300

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

305 310 315 320

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

325 330 335

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

340 345 350

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

355 360 365

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

370 375 380

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu

385 390 395 400

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

405 410 415

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

420 425 430

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

435 440 445

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

450 455 460

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

465 470 475 480

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 852

<211> 1476

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 852

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc aactggtgga aaccggtgga ggactcgtgc agcctggcgg cagcctccgg

120

ctgagctgcg ccgcttcggg attcaccttt tcctcctacg cgatgtcttg ggtcagacag

180

gccccgggaa aggggctgga atgggtgtca gccatctccg gctccggcgg atcaacgtac

240

tacgccgact ccgtgaaagg ccggttcacc atgtcgcgcg agaatgacaa gaactccgtg

300

ttcctgcaaa tgaactccct gagggtggag gacaccggag tgtactattg tgcgcgcgcc

360

aactacaaga gagagctgcg gtactactac ggaatggacg tctggggaca gggaactatg

420

gtgaccgtgt catccggtgg agggggaagc ggcggtggag gcagcggggg cgggggttca

480

gaaattgtca tgacccagtc cccgggaact ctttccctct cccccgggga atccgcgact

540

ttgtcctgcc gggccagcca gcgcgtggcc tcgaactacc tcgcatggta cgcataag

600

ccaggccaag ccccttccct gctgatttcc ggggctagca gccgcgccac tggcgtgccg

660

gataggttct cgggaagcgg ctcgggtacc gatttcaccc tggcaatctc gcggctggaa

720

ccggaggatt cggccgtgta ctactgccag cactatgact catccccctc ctggacattc

780

ggacagggca ccaaggtcga gatcaagacc actaccccag caccgaggcc acccaccccg

840

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

900

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

960

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1020

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1080

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1140

cgcgtgaaat tcagccgcag cgcagatgct ccagcctaca agcaggggca gaaccagctc

1200

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

1260

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

1320

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

1380

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

1440

tatgacgctc ttcacatgca ggccctgccg cctcgg

1476

<210> 853

<211> 488

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 853

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Leu Glu Thr Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Ser Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Ala Leu Val Gly Ala Thr Gly Ala Phe

115 120 125

Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu

145 150 155 160

Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

165 170 175

Leu Ser Cys Arg Ala Ser Gln Ser Leu Ser Ser Asn Phe Leu Ala Trp

180 185 190

Tyr Gln Gln Lys Pro Gly Gln Ala Pro Gly Leu Leu Ile Tyr Gly Ala

195 200 205

Ser Asn Trp Ala Thr Gly Thr Pro Asp Arg Phe Ser Gly Ser Gly Ser

210 215 220

Gly Thr Asp Phe Thr Leu Thr Ile Thr Arg Leu Glu Pro Glu Asp Phe

225 230 235 240

Ala Val Tyr Tyr Cys Gln Tyr Tyr Gly Thr Ser Pro Met Tyr Thr Phe

245 250 255

Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg

260 265 270

Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg

275 280 285

Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly

290 295 300

Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr

305 310 315 320

Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg

325 330 335

Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro

340 345 350

Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu

355 360 365

Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala

370 375 380

Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu

385 390 395 400

Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly

405 410 415

Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu

420 425 430

Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser

435 440 445

Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly

450 455 460

Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu

465 470 475 480

His Met Gln Ala Leu Pro Pro Arg

485

<210> 854

<211> 1464

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 854

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc agctgctcga aaccggtgga gggctggtgc agccaggggg ctccctgagg

120

ctttcatgcg ccgctagcgg attctccttc tcctcttacg ccatgtcgtg ggtccgccaa

180

gcccctggaa aaggcctgga atgggtgtcc gcgatttccg ggagcggagg ttcgacctat

240

tacgccgact ccgtgaaggg ccgctttacc atctcccggg ataactccaa gaacactctg

300

tacctccaaa tgaactcgct gagagccgag gacaccgccg tgtattactg cgcgaaggcg

360

ctggtcggcg cgactggggc attcgacatc tggggacagg gaactcttgt gaccgtgtcg

420

agcgggaggcg gcggctccgg cggaggaggg agcgggggcg gtggttccga aatcgtgttg

480

actcagtccc cgggaaccct gagcttgtca cccggggagc gggccactct ctcctgtcgc

540

gcctcccaat cgctctcatc caatttcctg gcctggtacc agcagaagcc cggacaggcc

600

ccggggcctgc tcatctacgg cgcttcaaac tgggcaacgg gaacccctga tcggttcagc

660

ggaagcggat cgggtactga ctttaccctg accatcacca gactggaacc ggaggacttc

720

gccgtgtact actgccagta ctacggcacc tcccccatgt acacattcgg acagggtacc

780

aaggtcgaga ttaagaccac taccccagca ccgaggccac ccaccccggc tcctaccatc

840

gcctcccagc ctctgtccct gcgtccggag gcatgtagac ccgcagctgg tggggccgtg

900

catacccggg gtcttgactt cgcctgcgat atctacattt gggcccctct ggctggtact

960

tgcggggtcc tgctgctttc actcgtgatc actctttact gtaagcgcgg tcggaagaag

1020

ctgctgtaca tctttaagca acccttcatg aggcctgtgc agactactca agaggaggac

1080

ggctgttcat gccggttccc agaggaggag gaaggcggct gcgaactgcg cgtgaaattc

1140

agccgcagcg cagatgctcc agcctacaag caggggcaga accagctcta caacgaactc

1200

aatcttggtc ggagaggagga gtacgacgtg ctggacaagc ggagaggacg ggacccagaa

1260

atgggcggga agccgcgcag aaagaatccc caagaggggcc tgtacaacga gctccaaaag

1320

gataagatgg cagaagccta tagcgagatt ggtatgaaag gggaacgcag aagaggcaaa

1380

ggccacgacg gactgtacca gggactcagc accgccacca aggacaccta tgacgctctt

1440

cacatgcagg ccctgccgcc tcgg

1464

<210> 855

<211> 488

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 855

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Val Leu Trp Phe Gly Glu Gly Phe Asp Pro Trp

115 120 125

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Leu Thr Gln Ser

145 150 155 160

Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys

165 170 175

Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp

180 185 190

Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu

195 200 205

Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly

210 215 220

Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp

225 230 235 240

Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr Pro Leu Thr Phe

245 250 255

Gly Gly Gly Thr Lys Val Asp Ile Lys Thr Thr Thr Pro Ala Pro Arg

260 265 270

Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg

275 280 285

Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly

290 295 300

Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr

305 310 315 320

Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg

325 330 335

Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro

340 345 350

Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu

355 360 365

Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala

370 375 380

Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu

385 390 395 400

Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly

405 410 415

Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu

420 425 430

Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser

435 440 445

Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly

450 455 460

Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu

465 470 475 480

His Met Gln Ala Leu Pro Pro Arg

485

<210> 856

<211> 1464

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 856

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtgc agctgcttga gagcggtgga ggtctggtgc agcccggggg atcactgcgc

120

ctgtcctgtg ccgcgtccgg tttcactttc tcctcgtacg ccatgtcgtg ggtcagacag

180

gcaccgggaa agggactgga atgggtgtca gccatttcgg gttcgggggg cagcacctac

240

tacgctgact ccgtgaaggg ccggttcacc atttcccgcg acaactccaa gaacaccttg

300

tacctccaaa tgaactccct gcgggccgaa gataccgccg tgtattactg cgtgctgtgg

360

ttcggagagg gattcgaccc gtggggacaa ggaacactcg tgactgtgtc atccggcgga

420

ggcggcagcg gtggcggcgg ttccggcggc ggcggatctg acatcgtgtt gacccagtcc

480

cctctgagcc tgccggtcac tcctggcgaa ccagccagca tctcctgccg gtcgagccag

540

tccctcctgc actccaatgg gtacaactac ctcgattggt atctgcaaaa gccgggccag

600

agcccccagc tgctgatcta ccttgggtca aaccgcgctt ccggggtgcc tgatagattc

660

tccgggtccg ggagcggaac cgactttacc ctgaaaatct cgagggtgga ggccgaggac

720

gtcggagtgt actactgcat gcaggcgctc cagactcccc tgaccttcgg aggaggaacg

780

aaggtcgaca tcaagaccac taccccagca ccgaggccac ccaccccggc tcctaccatc

840

gcctcccagc ctctgtccct gcgtccggag gcatgtagac ccgcagctgg tggggccgtg

900

catacccggg gtcttgactt cgcctgcgat atctacattt gggcccctct ggctggtact

960

tgcggggtcc tgctgctttc actcgtgatc actctttact gtaagcgcgg tcggaagaag

1020

ctgctgtaca tctttaagca acccttcatg aggcctgtgc agactactca agaggaggac

1080

ggctgttcat gccggttccc agaggaggag gaaggcggct gcgaactgcg cgtgaaattc

1140

agccgcagcg cagatgctcc agcctacaag caggggcaga accagctcta caacgaactc

1200

aatcttggtc ggagaggagga gtacgacgtg ctggacaagc ggagaggacg ggacccagaa

1260

atgggcggga agccgcgcag aaagaatccc caagaggggcc tgtacaacga gctccaaaag

1320

gataagatgg cagaagccta tagcgagatt ggtatgaaag gggaacgcag aagaggcaaa

1380

ggccacgacg gactgtacca gggactcagc accgccacca aggacaccta tgacgctctt

1440

cacatgcagg ccctgccgcc tcgg

1464

<210> 857

<211> 495

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 857

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Val Gly Tyr Asp Ser Ser Gly Tyr Tyr

115 120 125

Arg Asp Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr

130 135 140

Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

145 150 155 160

Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser

165 170 175

Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser

180 185 190

Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg

195 200 205

Leu Leu Ile Tyr Gly Thr Ser Ser Arg Ala Thr Gly Ile Ser Asp Arg

210 215 220

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg

225 230 235 240

Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Asn

245 250 255

Ser Pro Pro Lys Phe Thr Phe Gly Pro Gly Thr Lys Leu Glu Ile Lys

260 265 270

Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala

275 280 285

Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly

290 295 300

Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile

305 310 315 320

Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val

325 330 335

Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe

340 345 350

Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly

355 360 365

Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg

370 375 380

Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln

385 390 395 400

Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp

405 410 415

Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro

420 425 430

Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp

435 440 445

Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg

450 455 460

Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr

465 470 475 480

Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490 495

<210> 858

<211> 1485

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 858

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccaagtgc agctcgtgga gtcaggcgga ggactggtgc agcccgggggg ctccctgaga

120

ctttcctgcg cggcatcggg ttttaccttc tcctcctatg ctatgtcctg ggtgcgccag

180

gccccgggaa agggactgga atgggtgtcc gcaatcagcg gtagcgggggg ctcaacatac

240

tacgccgact ccgtcaaggg tcgcttcact atttcccggg acaactccaa gaataccctg

300

tacctccaaa tgaacagcct cagggccgag gatactgccg tgtactactg cgccaaagtc

360

ggatacgata gctccggtta ctaccgggac tactacggaa tggacgtgtg gggacagggc

420

acccgtga ccgtgtcaag cggcgggaggc ggttcaggag ggggaggctc cggcggtgga

480

gggtccgaaa tcgtcctgac tcagtcgcct ggcactctgt cgttgtcccc gggggagcgc

540

gctaccctgt cgtgtcgggc gtcgcagtcc gtgtcgagct cctacctcgc gtggtaccag

600

cagaagcccg gacaggcccc tagacttctg atctacggca cttcttcacg cgccaccgggg

660

atcagcgaca ggttcagcgg ctccggctcc gggaccgact tcaccctgac cattagccgg

720

ctggagcctg aagatttcgc cgtgtattac tgccaacact acggaaactc gccgccaaag

780

ttcacgttcg gaccgggaac caagctggaa atcaagacca ctaccccagc accgaggcca

840

cccaccccgg ctcctaccat cgcctcccag cctctgtccc tgcgtccgga ggcatgtaga

900

cccgcagctg gtggggccgt gcatacccgg ggtcttgact tcgcctgcga tatctacatt

960

tgggcccctc tggctggtac ttgcggggtc ctgctgcttt cactcgtgat cactctttac

1020

tgtaagcgcg gtcggaagaa gctgctgtac atctttaagc aacccttcat gaggcctgtg

1080

cagactactc aagaggagga cggctgttca tgccggttcc cagaggagga ggaaggcggc

1140

tgcgaactgc gcgtgaaatt cagccgcagc gcagatgctc cagcctacaa gcaggggcag

1200

aaccagctct acaacgaact caatcttggt cggagagagg agtacgacgt gctggacaag

1260

cggagaggac gggacccaga aatgggcggg aagccgcgca gaaagaatcc ccaaggggc

1320

ctgtacaacg agctccaaaa ggataagatg gcagaagcct atagcgagat tggtatgaaa

1380

ggggaacgca gaagaggcaa aggccacgac ggactgtacc agggactcag caccgccacc

1440

aaggacacct atgacgctct tcacatgcag gccctgccgc ctcgg

1485

<210> 859

<211> 490

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 859

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu

20 25 30

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

35 40 45

Thr Phe Ser Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys

50 55 60

Gly Leu Glu Trp Val Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr

65 70 75 80

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

85 90 95

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

100 105 110

Ala Val Tyr Tyr Cys Ala Lys Met Gly Trp Ser Ser Gly Tyr Leu Gly

115 120 125

Ala Phe Asp Ile Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly

130 135 140

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile

145 150 155 160

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

165 170 175

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ala Ser Ser Phe Leu

180 185 190

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

195 200 205

Gly Ala Ser Gly Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

210 215 220

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

225 230 235 240

Asp Phe Ala Val Tyr Tyr Cys Gln His Tyr Gly Gly Ser Pro Arg Leu

245 250 255

Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

305 310 315 320

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

325 330 335

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

340 345 350

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

355 360 365

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

370 375 380

Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn

385 390 395 400

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

405 410 415

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

420 425 430

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

435 440 445

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

450 455 460

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

465 470 475 480

Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 860

<211> 1470

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 860

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaagtcc aactggtgga gtccggggga gggctcgtgc agcccgggagg cagccttcgg

120

ctgtcgtgcg ccgcctccgg gttcacgttc tcatcctacg cgatgtcgtg ggtcagacag

180

gcaccaggaa agggactgga atgggtgtcc gccattagcg gctccggcgg tagcacctac

240

tatgccgact cagtgaaggg aaggttcact atctcccgcg acaacagcaa gaacaccctg

300

tacctccaaa tgaactctct gcggggccgag gataccgcgg tgtactattg cgccaagatg

360

ggttggtcca gcggatactt gggagccttc gacatttggg gacagggcac tactgtgacc

420

gtgtcctccg ggggtggcgg atcgggaggc ggcggctcgg gtggaggggg ttccgaaatc

480

gtgttgaccc agtcaccggg aaccctctcg ctgtccccgg gagaacgggc tacactgtca

540

tgtagagcgt cccagtccgt ggcttcctcg ttcctggcct ggtaccagca gaagccggga

600

caggcacccc gcctgctcat ctacggagcc agcggccggg cgaccggcat ccctgaccgc

660

ttctccggtt ccggctcgggg caccgacttt actctgacca ttagcaggct tgagcccgag

720

gattttgccg tgtactactg ccaacactac ggggggagcc ctcgcctgac cttcggaggc

780

ggaactaagg tcgatatcaa aaccactacc cggcaccga ggccacccac cccggctcct

840

accatcgcct cccagcctct gtccctgcgt cgggaggcat gtagacccgc agctggtggg

900

gccgtgcata cccggggtct tgacttcgcc tgcgatatct acatttgggc ccctctggct

960

ggtacttgcg gggtcctgct gctttcactc gtgatcactc tttactgtaa gcgcggtcgg

1020

aagaagctgc tgtacatctt taagcaaccc ttcatgaggc ctgtgcagac tactcaagag

1080

gaggacggct gttcatgccg gttcccagag gaggaggaag gcggctgcga actgcgcgtg

1140

aaattcagcc gcagcgcaga tgctccagcc tacaagcagg ggcagaacca gctctacaac

1200

gaactcaatc ttggtcggag agaggagtac gacgtgctgg acaagcggag aggacgggac

1260

ccagaaatgg gcgggaagcc gcgcagaaag aatccccaag agggcctgta caacgagctc

1320

caaaaggata agatggcaga agcctatagc gagattggta tgaaagggga acgcagaaga

1380

ggcaaaggcc acgacggact gtaccaggga ctcagcaccg ccaccaagga cacctatgac

1440

gctcttcaca tgcaggccct gccgcctcgg

1470

<210> 861

<400> 861

000

<210> 862

<400> 862

000

<210> 863

<400> 863

000

<210> 864

<400> 864

000

<210> 865

<400> 865

000

<210> 866

<400> 866

000

<210> 867

<400> 867

000

<210> 868

<400> 868

000

<210> 869

<400> 869

000

<210> 870

<400> 870

000

<210> 871

<400> 871

000

<210> 872

<400> 872

000

<210> 873

<400> 873

000

<210> 874

<400> 874

000

<210> 875

<400> 875

000

<210> 876

<400> 876

000

<210> 877

<400> 877

000

<210> 878

<400> 878

000

<210> 879

<400> 879

000

<210> 880

<400> 880

000

<210> 881

<400> 881

000

<210> 882

<400> 882

000

<210> 883

<400> 883

000

<210> 884

<400> 884

000

<210> 885

<400> 885

000

<210> 886

<400> 886

000

<210> 887

<400> 887

000

<210> 888

<400> 888

000

<210> 889

<400> 889

000

<210> 890

<400> 890

000

<210> 891

<211> 486

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 891

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu

20 25 30

Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr

50 55 60

Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro

65 70 75 80

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile

85 90 95

Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu

130 135 140

Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser

145 150 155 160

Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser

195 200 205

Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys

210 215 220

Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Ser Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg

485

<210> 892

<211> 465

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 892

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly

1 5 10 15

Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln

65 70 75 80

Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu

115 120 125

Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys

130 135 140

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

145 150 155 160

Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser

165 170 175

Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile

180 185 190

Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln

195 200 205

Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

210 215 220

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val

225 230 235 240

Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

245 250 255

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

260 265 270

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

275 280 285

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

290 295 300

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

305 310 315 320

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

325 330 335

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

340 345 350

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln

355 360 365

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

370 375 380

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

385 390 395 400

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

405 410 415

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

420 425 430

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

435 440 445

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

450 455 460

Arg

465

<210> 893

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 893

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

115 120 125

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

130 135 140

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

145 150 155 160

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

165 170 175

Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

180 185 190

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

195 200 205

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

210 215 220

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

225 230 235 240

Ser Ser

<210> 894

<211> 813

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 894

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

480

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

540

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

600

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

660

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

720

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

780

gtgtccagcc accaccatca tcaccatcac cat

813

<210> 895

<211> 271

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 895

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

130 135 140

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

145 150 155 160

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser

195 200 205

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

210 215 220

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Leu Val Thr Val Ser Ser His His His His His His His His

260 265 270

<210> 896

<211> 1458

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 896

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

480

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

540

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

600

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

660

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

720

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

780

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

840

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

900

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

960

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1020

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1080

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1140

agcgcagatg ctccagccta caagcagggg cagaaccagc tctacaacga actcaatctt

1200

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

1260

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

1320

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

1380

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

1440

caggccctgc cgcctcgg

1458

<210> 897

<211> 486

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 897

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

130 135 140

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

145 150 155 160

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser

195 200 205

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

210 215 220

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg

485

<210> 898

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 898

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

115 120 125

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

130 135 140

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

145 150 155 160

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

165 170 175

Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

180 185 190

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

195 200 205

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

210 215 220

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

225 230 235 240

Ser Ser

<210> 899

<211> 813

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 899

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

480

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

540

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

600

tactaccaat catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

660

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

720

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

780

gtgtccagcc accaccatca tcaccatcac cat

813

<210> 900

<211> 271

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 900

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

130 135 140

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

145 150 155 160

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys Ser

195 200 205

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

210 215 220

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Leu Val Thr Val Ser Ser His His His His His His His His

260 265 270

<210> 901

<211> 1458

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 901

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

480

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

540

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

600

tactaccaat catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

660

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

720

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

780

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

840

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

900

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

960

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1020

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1080

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1140

agcgcagatg ctccagccta caagcagggg cagaaccagc tctacaacga actcaatctt

1200

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

1260

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

1320

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

1380

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

1440

caggccctgc cgcctcgg

1458

<210> 902

<211> 486

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 902

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

130 135 140

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

145 150 155 160

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys Ser

195 200 205

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

210 215 220

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg

485

<210> 903

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 903

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Ala

130 135 140

Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala

145 150 155 160

Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly

180 185 190

Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu

195 200 205

Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln

210 215 220

Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu

225 230 235 240

Ile Lys

<210> 904

<211> 813

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 904

atggctctgc ccgtgaccgc actcctcctg ccactggctc tgctgcttca cgccgctcgc

60

ccacaagtcc agcttcaaga atcagggcct ggtctggtga agccatctga gactctgtcc

120

ctcacttgca ccgtgagcgg agtgtccctc ccagactacg gagtgagctg gattagacag

180

cctccgggaa agggactgga gtggatcgga gtgatttggg gtagcgaaac cacttactat

240

tcatcttccc tgaagtcacg ggtcaccatt tcaaaggata actcaaagaa tcaagtgagc

300

ctcaagctct catcagtcac cgccgctgac accgccgtgt attactgtgc caagcattac

360

tactatggag ggtcctacgc catggactac tggggccagg gaactctggt cactgtgtca

420

tctggtggag gaggtagcgg aggaggcggg agcggtggag gtggctccga aatcgtgatg

480

acccagagcc ctgcaaccct gtccctttct cccggggaac gggctaccct ttcttgtcgg

540

gcatcacaag atatctcaaa atacctcaat tggtatcaac agaagccggg acaggcccct

600

aggcttctta tctaccacac ctctcgcctg catagcggga ttcccgcacg ctttagcggg

660

tctggaagcg ggaccgacta cactctgacc atctcatctc tccagcccga ggacttcgcc

720

gtctacttct gccagcaggg taacaccctg ccgtacacct tcggccaggg caccaagctt

780

gagatcaaac atcaccacca tcatcaccat cac

813

<210> 905

<211> 271

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 905

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

145 150 155 160

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

165 170 175

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

180 185 190

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

195 200 205

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

210 215 220

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

225 230 235 240

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

245 250 255

Gly Thr Lys Leu Glu Ile Lys His His His His His His His His His

260 265 270

<210> 906

<211> 1458

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 906

atggctctgc ccgtgaccgc actcctcctg ccactggctc tgctgcttca cgccgctcgc

60

ccacaagtcc agcttcaaga atcagggcct ggtctggtga agccatctga gactctgtcc

120

ctcacttgca ccgtgagcgg agtgtccctc ccagactacg gagtgagctg gattagacag

180

cctccgggaa agggactgga gtggatcgga gtgatttggg gtagcgaaac cacttactat

240

tcatcttccc tgaagtcacg ggtcaccatt tcaaaggata actcaaagaa tcaagtgagc

300

ctcaagctct catcagtcac cgccgctgac accgccgtgt attactgtgc caagcattac

360

tactatggag ggtcctacgc catggactac tggggccagg gaactctggt cactgtgtca

420

tctggtggag gaggtagcgg aggaggcggg agcggtggag gtggctccga aatcgtgatg

480

acccagagcc ctgcaaccct gtccctttct cccggggaac gggctaccct ttcttgtcgg

540

gcatcacaag atatctcaaa atacctcaat tggtatcaac agaagccggg acaggcccct

600

aggcttctta tctaccacac ctctcgcctg catagcggga ttcccgcacg ctttagcggg

660

tctggaagcg ggaccgacta cactctgacc atctcatctc tccagcccga ggacttcgcc

720

gtctacttct gccagcaggg taacaccctg ccgtacacct tcggccaggg caccaagctt

780

gagatcaaaa ccactactcc cgctccaagg ccacccaccc ctgccccgac catcgcctct

840

cagccgcttt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

900

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

960

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1020

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1080

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1140

agcgcagatg ctccagccta caagcagggg cagaaccagc tctacaacga actcaatctt

1200

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

1260

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

1320

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

1380

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

1440

caggccctgc cgcctcgg

1458

<210> 907

<211> 486

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 907

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

145 150 155 160

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

165 170 175

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

180 185 190

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

195 200 205

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

210 215 220

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

225 230 235 240

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

245 250 255

Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg

485

<210> 908

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 908

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Ala

130 135 140

Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala

145 150 155 160

Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly

180 185 190

Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu

195 200 205

Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln

210 215 220

Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu

225 230 235 240

Ile Lys

<210> 909

<211> 813

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 909

atggctctgc ccgtgaccgc actcctcctg ccactggctc tgctgcttca cgccgctcgc

60

ccacaagtcc agcttcaaga atcagggcct ggtctggtga agccatctga gactctgtcc

120

ctcacttgca ccgtgagcgg agtgtccctc ccagactacg gagtgagctg gattagacag

180

cctccgggaa agggactgga gtggatcgga gtgatttggg gtagcgaaac cacttactat

240

caatcttccc tgaagtcacg ggtcaccatt tcaaaggata actcaaagaa tcaagtgagc

300

ctcaagctct catcagtcac cgccgctgac accgccgtgt attactgtgc caagcattac

360

tactatggag ggtcctacgc catggactac tggggccagg gaactctggt cactgtgtca

420

tctggtggag gaggtagcgg aggaggcggg agcggtggag gtggctccga aatcgtgatg

480

acccagagcc ctgcaaccct gtccctttct cccggggaac gggctaccct ttcttgtcgg

540

gcatcacaag atatctcaaa atacctcaat tggtatcaac agaagccggg acaggcccct

600

aggcttctta tctaccacac ctctcgcctg catagcggga ttcccgcacg ctttagcggg

660

tctggaagcg ggaccgacta cactctgacc atctcatctc tccagcccga ggacttcgcc

720

gtctacttct gccagcaggg taacaccctg ccgtacacct tcggccaggg caccaagctt

780

gagatcaaac atcaccacca tcatcaccat cac

813

<210> 910

<211> 271

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 910

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Gln Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

145 150 155 160

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

165 170 175

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

180 185 190

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

195 200 205

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

210 215 220

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

225 230 235 240

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

245 250 255

Gly Thr Lys Leu Glu Ile Lys His His His His His His His His His

260 265 270

<210> 911

<211> 1458

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 911

atggctctgc ccgtgaccgc actcctcctg ccactggctc tgctgcttca cgccgctcgc

60

ccacaagtcc agcttcaaga atcagggcct ggtctggtga agccatctga gactctgtcc

120

ctcacttgca ccgtgagcgg agtgtccctc ccagactacg gagtgagctg gattagacag

180

cctccgggaa agggactgga gtggatcgga gtgatttggg gtagcgaaac cacttactat

240

caatcttccc tgaagtcacg ggtcaccatt tcaaaggata actcaaagaa tcaagtgagc

300

ctcaagctct catcagtcac cgccgctgac accgccgtgt attactgtgc caagcattac

360

tactatggag ggtcctacgc catggactac tggggccagg gaactctggt cactgtgtca

420

tctggtggag gaggtagcgg aggaggcggg agcggtggag gtggctccga aatcgtgatg

480

acccagagcc ctgcaaccct gtccctttct cccggggaac gggctaccct ttcttgtcgg

540

gcatcacaag atatctcaaa atacctcaat tggtatcaac agaagccggg acaggcccct

600

aggcttctta tctaccacac ctctcgcctg catagcggga ttcccgcacg ctttagcggg

660

tctggaagcg ggaccgacta cactctgacc atctcatctc tccagcccga ggacttcgcc

720

gtctacttct gccagcaggg taacaccctg ccgtacacct tcggccaggg caccaagctt

780

gagatcaaaa ccactactcc cgctccaagg ccacccaccc ctgccccgac catcgcctct

840

cagccgcttt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

900

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

960

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1020

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1080

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1140

agcgcagatg ctccagccta caagcagggg cagaaccagc tctacaacga actcaatctt

1200

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

1260

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

1320

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

1380

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

1440

caggccctgc cgcctcgg

1458

<210> 912

<211> 486

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 912

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Gln Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

145 150 155 160

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

165 170 175

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

180 185 190

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

195 200 205

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

210 215 220

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

225 230 235 240

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

245 250 255

Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg

485

<210> 913

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 913

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

115 120 125

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

130 135 140

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

145 150 155 160

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

165 170 175

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser

180 185 190

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

195 200 205

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

210 215 220

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

225 230 235 240

Thr Leu Val Thr Val Ser Ser

245

<210> 914

<211> 828

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 914

atggccctcc cagtgaccgc tctgctgctg cctctcgcac ttcttctcca tgccgctcgg

60

cctgagatcg tcatgaccca aagccccgct accctgtccc tgtcacccgg cgagagggca

120

accctttcat gcagggccag cgggacatt tctaagtacc tcaactggta tcagcagaag

180

ccagggcagg ctcctcgcct gctgatctac cacaccagcc gcctccacag cggtatcccc

240

gccagatttt ccgggagcgg gtctggaacc gactacaccc tcaccatctc ttctctgcag

300

cccgaggatt tcgccgtcta tttctgccag caggggaata ctctgccgta caccttcggt

360

caaggtacca agctggaaat caagggaggc ggaggatcag gcggtggcgg aagcggagga

420

ggtggctccg gaggaggagg ttcccaagtg cagcttcaag aatcaggacc cggacttgtg

480

aagccatcag aaaccctctc cctgacttgt accgtgtccg gtgtgagcct ccccgactac

540

ggagtctctt ggattcgcca gcctccgggg aagggtcttg aatggattgg ggtgatttgg

600

ggatcagaga ctacttacta ctcttcatca cttaagtcac gggtcaccat cagcaaagat

660

aatagcaaga accaagtgtc acttaagctg tcatctgtga ccgccgctga caccgccgtg

720

tactattgtg ccaaacatta ctattacgga gggtcttatg ctatggacta ctggggacag

780

gggaccctgg tgactgtctc tagccatcac catcaccacc atcatcac

828

<210> 915

<211> 276

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 915

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

145 150 155 160

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

165 170 175

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

180 185 190

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser

195 200 205

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

210 215 220

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

225 230 235 240

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

245 250 255

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser His His His His

260 265 270

His His His His

275

<210> 916

<211> 1473

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 916

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcg gcggaggcgg gagccaggtc caactccaag aaagcggacc gggtcttgtg

480

aagccatcag aaactctttc actgacttgt actgtgagcg gagtgtctct ccccgattac

540

ggggtgtctt ggatcagaca gccaccgggg aagggtctgg aatggattgg agtgatttgg

600

ggctctgaga ctacttacta ctcttcatcc ctcaagtcac gcgtcaccat ctcaaaggac

660

aactctaaga atcaggtgtc actgaaactg tcatctgtga ccgcagccga caccgccgtg

720

tactattgcg ctaagcatta ctattatggc gggagctacg caatggatta ctggggacag

780

ggtactctgg tcaccgtgtc cagcaccact accccagcac cgaggccacc caccccggct

840

cctaccatcg cctcccagcc tctgtccctg cgtccgggagg catgtagacc cgcagctggt

900

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

960

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1020

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1080

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1140

gtgaaattca gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac

1200

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

1260

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

1320

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

1380

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

1440

gacgctcttc acatgcaggc cctgccgcct cgg

1473

<210> 917

<211> 491

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 917

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

145 150 155 160

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

165 170 175

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

180 185 190

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser

195 200 205

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

210 215 220

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

225 230 235 240

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

245 250 255

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

305 310 315 320

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

325 330 335

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

340 345 350

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

355 360 365

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

370 375 380

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

385 390 395 400

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

405 410 415

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

420 425 430

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

435 440 445

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

450 455 460

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

465 470 475 480

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 918

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 918

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

115 120 125

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

130 135 140

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

145 150 155 160

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

165 170 175

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys Ser

180 185 190

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

195 200 205

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

210 215 220

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

225 230 235 240

Thr Leu Val Thr Val Ser Ser

245

<210> 919

<211> 828

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 919

atggccctcc cagtgaccgc tctgctgctg cctctcgcac ttcttctcca tgccgctcgg

60

cctgagatcg tcatgaccca aagccccgct accctgtccc tgtcacccgg cgagagggca

120

accctttcat gcagggccag cgggacatt tctaagtacc tcaactggta tcagcagaag

180

ccagggcagg ctcctcgcct gctgatctac cacaccagcc gcctccacag cggtatcccc

240

gccagatttt ccgggagcgg gtctggaacc gactacaccc tcaccatctc ttctctgcag

300

cccgaggatt tcgccgtcta tttctgccag caggggaata ctctgccgta caccttcggt

360

caaggtacca agctggaaat caagggaggc ggaggatcag gcggtggcgg aagcggagga

420

ggtggctccg gaggaggagg ttcccaagtg cagcttcaag aatcaggacc cggacttgtg

480

aagccatcag aaaccctctc cctgacttgt accgtgtccg gtgtgagcct ccccgactac

540

ggagtctctt ggattcgcca gcctccgggg aagggtcttg aatggattgg ggtgatttgg

600

ggatcagaga ctacttacta ccagtcatca cttaagtcac gggtcaccat cagcaaagat

660

aatagcaaga accaagtgtc acttaagctg tcatctgtga ccgccgctga caccgccgtg

720

tactattgtg ccaaacatta ctattacgga gggtcttatg ctatggacta ctggggacag

780

gggaccctgg tgactgtctc tagccatcac catcaccacc atcatcac

828

<210> 920

<211> 276

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 920

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

145 150 155 160

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

165 170 175

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

180 185 190

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln

195 200 205

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

210 215 220

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

225 230 235 240

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

245 250 255

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser His His His His

260 265 270

His His His His

275

<210> 921

<211> 1473

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 921

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcg gaggcggagg gagccaggtc caactccaag aaagcggacc gggtcttgtg

480

aagccatcag aaactctttc actgacttgt actgtgagcg gagtgtctct ccccgattac

540

ggggtgtctt ggatcagaca gccaccgggg aagggtctgg aatggattgg agtgatttgg

600

ggctctgaga ctacttacta ccaatcatcc ctcaagtcac gcgtcaccat ctcaaaggac

660

aactctaaga atcaggtgtc actgaaactg tcatctgtga ccgcagccga caccgccgtg

720

tactattgcg ctaagcatta ctattatggc gggagctacg caatggatta ctggggacag

780

ggtactctgg tcaccgtgtc cagcaccact accccagcac cgaggccacc caccccggct

840

cctaccatcg cctcccagcc tctgtccctg cgtccgggagg catgtagacc cgcagctggt

900

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

960

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1020

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1080

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1140

gtgaaattca gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac

1200

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

1260

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

1320

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

1380

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

1440

gacgctcttc acatgcaggc cctgccgcct cgg

1473

<210> 922

<211> 491

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 922

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

145 150 155 160

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

165 170 175

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

180 185 190

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln

195 200 205

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

210 215 220

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

225 230 235 240

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

245 250 255

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

305 310 315 320

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

325 330 335

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

340 345 350

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

355 360 365

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

370 375 380

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

385 390 395 400

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

405 410 415

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

420 425 430

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

435 440 445

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

450 455 460

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

465 470 475 480

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 923

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 923

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

130 135 140

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

145 150 155 160

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

180 185 190

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

210 215 220

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

225 230 235 240

Gly Thr Lys Leu Glu Ile Lys

245

<210> 924

<211> 828

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 924

atggcactgc ctgtcactgc cctcctgctg ccctctggccc tccttctgca tgccgccagg

60

ccccaagtcc agctgcaaga gtcaggaccc ggactggtga agccgtctga gactctctca

120

ctgacttgta ccgtcagcgg cgtgtccctc cccgactacg gagtgtcatg gatccgccaa

180

cctcccggga aagggcttga atggattggt gtcatctggg gttctgaaac cacctactac

240

tcatcttccc tgaagtccag ggtgaccatc agcaaggata attccaagaa ccaggtcagc

300

cttaagctgt catctgtgac cgctgctgac accgccgtgt attactgcgc caagcactac

360

tattacggag gaagctacgc tatggactat tggggacagg gcactctcgt gactgtgagc

420

agcggcggtg gagggtctgg aggtggagga tccggtggtg gtgggtcagg cggaggaggg

480

agcgagattg tgatgactca gtcaccagcc accctttctc tttcacccgg cgagagagca

540

accctgagct gtagagccag ccaggacatt tctaagtacc tcaactggta tcagcaaaaa

600

ccggggcagg cccctcgcct cctgatctac catacctcac gccttcactc tggtatcccc

660

gctcggttta gcggatcagg atctggtacc gactacactc tgaccatttc cagcctgcag

720

ccagaagatt tcgcagtgta tttctgccag cagggcaata cccttcctta caccttcggt

780

cagggaacca agctcgaaat caagcaccat caccatcatc accaccat

828

<210> 925

<211> 276

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 925

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

145 150 155 160

Ser Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro

165 170 175

Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys

180 185 190

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

195 200 205

Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln

225 230 235 240

Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro

245 250 255

Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys His His His His

260 265 270

His His His His

275

<210> 926

<211> 1473

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 926

atggctctgc ccgtgaccgc actcctcctg ccactggctc tgctgcttca cgccgctcgc

60

ccacaagtcc agcttcaaga atcagggcct ggtctggtga agccatctga gactctgtcc

120

ctcacttgca ccgtgagcgg agtgtccctc ccagactacg gagtgagctg gattagacag

180

cctccgggaa agggactgga gtggatcgga gtgatttggg gtagcgaaac cacttactat

240

tcatcttccc tgaagtcacg ggtcaccatt tcaaaggata actcaaagaa tcaagtgagc

300

ctcaagctct catcagtcac cgccgctgac accgccgtgt attactgtgc caagcattac

360

tactatggag ggtcctacgc catggactac tggggccagg gaactctggt cactgtgtca

420

tctggtggag gaggtagcgg aggaggcggg agcggtggag gtggctccgg aggtggcgga

480

agcgaaatcg tgatgaccca gagccctgca accctgtccc tttctcccgg ggaacggggct

540

accctttctt gtcgggcatc acaagatatc tcaaaatacc tcaattggta tcaacagaag

600

ccgggacagg cccctaggct tcttatctac cacacctctc gcctgcatag cgggattccc

660

gcacgcttta gcgggtctgg aagcgggacc gactacactc tgaccatctc atctctccag

720

cccgaggact tcgccgtcta cttctgccag cagggtaaca ccctgccgta caccttcggc

780

cagggcacca agcttgagat caaaaccact actcccgctc caaggccacc cacccctgcc

840

ccgaccatcg cctctcagcc gctttccctg cgtccgggagg catgtagacc cgcagctggt

900

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

960

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1020

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1080

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1140

gtgaaattca gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac

1200

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

1260

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

1320

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

1380

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

1440

gacgctcttc acatgcaggc cctgccgcct cgg

1473

<210> 927

<211> 491

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 927

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

145 150 155 160

Ser Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro

165 170 175

Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys

180 185 190

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

195 200 205

Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln

225 230 235 240

Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro

245 250 255

Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

305 310 315 320

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

325 330 335

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

340 345 350

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

355 360 365

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

370 375 380

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

385 390 395 400

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

405 410 415

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

420 425 430

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

435 440 445

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

450 455 460

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

465 470 475 480

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 928

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 928

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

130 135 140

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

145 150 155 160

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

180 185 190

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

210 215 220

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

225 230 235 240

Gly Thr Lys Leu Glu Ile Lys

245

<210> 929

<211> 828

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 929

atggcactgc ctgtcactgc cctcctgctg ccctctggccc tccttctgca tgccgccagg

60

ccccaagtcc agctgcaaga gtcaggaccc ggactggtga agccgtctga gactctctca

120

ctgacttgta ccgtcagcgg cgtgtccctc cccgactacg gagtgtcatg gatccgccaa

180

cctcccggga aagggcttga atggattggt gtcatctggg gttctgaaac cacctactac

240

cagtcttccc tgaagtccag ggtgaccatc agcaaggata attccaagaa ccaggtcagc

300

cttaagctgt catctgtgac cgctgctgac accgccgtgt attactgcgc caagcactac

360

tattacggag gaagctacgc tatggactat tggggacagg gcactctcgt gactgtgagc

420

agcggcggtg gagggtctgg aggtggagga tccggtggtg gtgggtcagg cggaggaggg

480

agcgagattg tgatgactca gtcaccagcc accctttctc tttcacccgg cgagagagca

540

accctgagct gtagagccag ccaggacatt tctaagtacc tcaactggta tcagcaaaaa

600

ccggggcagg cccctcgcct cctgatctac catacctcac gccttcactc tggtatcccc

660

gctcggttta gcggatcagg atctggtacc gactacactc tgaccatttc cagcctgcag

720

ccagaagatt tcgcagtgta tttctgccag cagggcaata cccttcctta caccttcggt

780

cagggaacca agctcgaaat caagcaccat caccatcatc atcaccac

828

<210> 930

<211> 276

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 930

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Gln Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

145 150 155 160

Ser Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro

165 170 175

Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys

180 185 190

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

195 200 205

Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln

225 230 235 240

Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro

245 250 255

Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys His His His His

260 265 270

His His His His

275

<210> 931

<211> 1473

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 931

atggctctgc ccgtgaccgc actcctcctg ccactggctc tgctgcttca cgccgctcgc

60

ccacaagtcc agcttcaaga atcagggcct ggtctggtga agccatctga gactctgtcc

120

ctcacttgca ccgtgagcgg agtgtccctc ccagactacg gagtgagctg gattagacag

180

cctccgggaa agggactgga gtggatcgga gtgatttggg gtagcgaaac cacttactat

240

caatcttccc tgaagtcacg ggtcaccatt tcaaaggata actcaaagaa tcaagtgagc

300

ctcaagctct catcagtcac cgccgctgac accgccgtgt attactgtgc caagcattac

360

tactatggag ggtcctacgc catggactac tggggccagg gaactctggt cactgtgtca

420

tctggtggag gaggtagcgg aggaggcggg agcggtggag gtggctccgg aggcggtgggg

480

tcagaaatcg tgatgaccca gagccctgca accctgtccc tttctcccgg ggaacggggct

540

accctttctt gtcgggcatc acaagatatc tcaaaatacc tcaattggta tcaacagaag

600

ccgggacagg cccctaggct tcttatctac cacacctctc gcctgcatag cgggattccc

660

gcacgcttta gcgggtctgg aagcgggacc gactacactc tgaccatctc atctctccag

720

cccgaggact tcgccgtcta cttctgccag cagggtaaca ccctgccgta caccttcggc

780

cagggcacca agcttgagat caaaaccact actcccgctc caaggccacc cacccctgcc

840

ccgaccatcg cctctcagcc gctttccctg cgtccgggagg catgtagacc cgcagctggt

900

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

960

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1020

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1080

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1140

gtgaaattca gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac

1200

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

1260

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

1320

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

1380

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

1440

gacgctcttc acatgcaggc cctgccgcct cgg

1473

<210> 932

<211> 491

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 932

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Gln Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

145 150 155 160

Ser Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro

165 170 175

Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys

180 185 190

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

195 200 205

Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln

225 230 235 240

Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro

245 250 255

Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

305 310 315 320

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

325 330 335

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

340 345 350

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

355 360 365

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

370 375 380

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

385 390 395 400

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

405 410 415

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

420 425 430

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

435 440 445

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

450 455 460

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

465 470 475 480

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 933

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 933

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

115 120 125

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

130 135 140

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

145 150 155 160

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

165 170 175

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys Ser

180 185 190

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

195 200 205

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

210 215 220

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

225 230 235 240

Thr Leu Val Thr Val Ser Ser

245

<210> 934

<211> 828

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 934

atggccctcc cagtgaccgc tctgctgctg cctctcgcac ttcttctcca tgccgctcgg

60

cctgagatcg tcatgaccca aagccccgct accctgtccc tgtcacccgg cgagagggca

120

accctttcat gcagggccag cgggacatt tctaagtacc tcaactggta tcagcagaag

180

ccagggcagg ctcctcgcct gctgatctac cacaccagcc gcctccacag cggtatcccc

240

gccagatttt ccgggagcgg gtctggaacc gactacaccc tcaccatctc ttctctgcag

300

cccgaggatt tcgccgtcta tttctgccag caggggaata ctctgccgta caccttcggt

360

caaggtacca agctggaaat caagggaggc ggaggatcag gcggtggcgg aagcggagga

420

ggtggctccg gaggaggagg ttcccaagtg cagcttcaag aatcaggacc cggacttgtg

480

aagccatcag aaaccctctc cctgacttgt accgtgtccg gtgtgagcct ccccgactac

540

ggagtctctt ggattcgcca gcctccgggg aagggtcttg aatggattgg ggtgatttgg

600

ggatcagaga ctacttacta caattcatca cttaagtcac gggtcaccat cagcaaagat

660

aatagcaaga accaagtgtc acttaagctg tcatctgtga ccgccgctga caccgccgtg

720

tactattgtg ccaaacatta ctattacgga gggtcttatg ctatggacta ctggggacag

780

gggaccctgg tgactgtctc tagccatcac catcaccacc atcatcac

828

<210> 935

<211> 276

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 935

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

145 150 155 160

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

165 170 175

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

180 185 190

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn

195 200 205

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

210 215 220

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

225 230 235 240

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

245 250 255

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser His His His His

260 265 270

His His His His

275

<210> 936

<211> 1473

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 936

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcg gaggcggtgg gagccaggtc caactccaag aaagcggacc gggtcttgtg

480

aagccatcag aaactctttc actgacttgt actgtgagcg gagtgtctct ccccgattac

540

ggggtgtctt ggatcagaca gccaccgggg aagggtctgg aatggattgg agtgatttgg

600

ggctctgaga ctacttacta caactcatcc ctcaagtcac gcgtcaccat ctcaaaggac

660

aactctaaga atcaggtgtc actgaaactg tcatctgtga ccgcagccga caccgccgtg

720

tactattgcg ctaagcatta ctattatggc gggagctacg caatggatta ctggggacag

780

ggtactctgg tcaccgtgtc cagcaccact accccagcac cgaggccacc caccccggct

840

cctaccatcg cctcccagcc tctgtccctg cgtccgggagg catgtagacc cgcagctggt

900

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

960

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1020

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1080

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1140

gtgaaattca gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac

1200

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

1260

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

1320

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

1380

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

1440

gacgctcttc acatgcaggc cctgccgcct cgg

1473

<210> 937

<211> 491

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 937

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

145 150 155 160

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

165 170 175

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

180 185 190

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn

195 200 205

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

210 215 220

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

225 230 235 240

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

245 250 255

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

305 310 315 320

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

325 330 335

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

340 345 350

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

355 360 365

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

370 375 380

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

385 390 395 400

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

405 410 415

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

420 425 430

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

435 440 445

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

450 455 460

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

465 470 475 480

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 938

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 938

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

130 135 140

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

145 150 155 160

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

165 170 175

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

180 185 190

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

195 200 205

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

210 215 220

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

225 230 235 240

Gly Thr Lys Leu Glu Ile Lys

245

<210> 939

<211> 828

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 939

atggcactgc ctgtcactgc cctcctgctg ccctctggccc tccttctgca tgccgccagg

60

ccccaagtcc agctgcaaga gtcaggaccc ggactggtga agccgtctga gactctctca

120

ctgacttgta ccgtcagcgg cgtgtccctc cccgactacg gagtgtcatg gatccgccaa

180

cctcccggga aagggcttga atggattggt gtcatctggg gttctgaaac cacctactac

240

aactcttccc tgaagtccag ggtgaccatc agcaaggata attccaagaa ccaggtcagc

300

cttaagctgt catctgtgac cgctgctgac accgccgtgt attactgcgc caagcactac

360

tattacggag gaagctacgc tatggactat tggggacagg gcactctcgt gactgtgagc

420

agcggcggtg gagggtctgg aggtggagga tccggtggtg gtgggtcagg cggaggaggg

480

agcgagattg tgatgactca gtcaccagcc accctttctc tttcacccgg cgagagagca

540

accctgagct gtagagccag ccaggacatt tctaagtacc tcaactggta tcagcaaaaa

600

ccggggcagg cccctcgcct cctgatctac catacctcac gccttcactc tggtatcccc

660

gctcggttta gcggatcagg atctggtacc gactacactc tgaccatttc cagcctgcag

720

ccagaagatt tcgcagtgta tttctgccag cagggcaata cccttcctta caccttcggt

780

cagggaacca agctcgaaat caagcaccat caccatcatc accaccat

828

<210> 940

<211> 276

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 940

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Asn Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

145 150 155 160

Ser Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro

165 170 175

Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys

180 185 190

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

195 200 205

Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln

225 230 235 240

Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro

245 250 255

Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys His His His His

260 265 270

His His His His

275

<210> 941

<211> 1473

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 941

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcg gaggcggtgg gagccaggtc caactccaag aaagcggacc gggtcttgtg

480

aagccatcag aaactctttc actgacttgt actgtgagcg gagtgtctct ccccgattac

540

ggggtgtctt ggatcagaca gccaccgggg aagggtctgg aatggattgg agtgatttgg

600

ggctctgaga ctacttacta caactcatcc ctcaagtcac gcgtcaccat ctcaaaggac

660

aactctaaga atcaggtgtc actgaaactg tcatctgtga ccgcagccga caccgccgtg

720

tactattgcg ctaagcatta ctattatggc gggagctacg caatggatta ctggggacag

780

ggtactctgg tcaccgtgtc cagcaccact accccagcac cgaggccacc caccccggct

840

cctaccatcg cctcccagcc tctgtccctg cgtccgggagg catgtagacc cgcagctggt

900

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

960

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1020

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1080

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1140

gtgaaattca gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac

1200

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

1260

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

1320

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

1380

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

1440

gacgctcttc acatgcaggc cctgccgcct cgg

1473

<210> 942

<211> 491

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 942

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

130 135 140

Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val

145 150 155 160

Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser

165 170 175

Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly

180 185 190

Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn

195 200 205

Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn

210 215 220

Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

225 230 235 240

Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp

245 250 255

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

305 310 315 320

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

325 330 335

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

340 345 350

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

355 360 365

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

370 375 380

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

385 390 395 400

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

405 410 415

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

420 425 430

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

435 440 445

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

450 455 460

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

465 470 475 480

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 943

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 943

Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Glyn Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

115 120 125

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

130 135 140

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

145 150 155 160

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser

165 170 175

Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys Ser Arg Val Thr Ile Ser

180 185 190

Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr

195 200 205

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

210 215 220

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

225 230 235 240

Ser Ser

<210> 944

<211> 813

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 944

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

480

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

540

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

600

tactacaatt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

660

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

720

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

780

gtgtccagcc accaccatca tcaccatcac cat

813

<210> 945

<211> 271

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 945

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

130 135 140

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

145 150 155 160

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys Ser

195 200 205

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

210 215 220

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Leu Val Thr Val Ser Ser His His His His His His His His

260 265 270

<210> 946

<211> 1473

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 946

atggctctgc ccgtgaccgc actcctcctg ccactggctc tgctgcttca cgccgctcgc

60

ccacaagtcc agcttcaaga atcagggcct ggtctggtga agccatctga gactctgtcc

120

ctcacttgca ccgtgagcgg agtgtccctc ccagactacg gagtgagctg gattagacag

180

cctccgggaa agggactgga gtggatcgga gtgatttggg gtagcgaaac cacttactat

240

aactcttccc tgaagtcacg ggtcaccatt tcaaaggata actcaaagaa tcaagtgagc

300

ctcaagctct catcagtcac cgccgctgac accgccgtgt attactgtgc caagcattac

360

tactatggag ggtcctacgc catggactac tggggccagg gaactctggt cactgtgtca

420

tctggtggag gaggtagcgg aggaggcggg agcggtggag gtggctccgg aggtggcgga

480

agcgaaatcg tgatgaccca gagccctgca accctgtccc tttctcccgg ggaacggggct

540

accctttctt gtcgggcatc acaagatatc tcaaaatacc tcaattggta tcaacagaag

600

ccgggacagg cccctaggct tcttatctac cacacctctc gcctgcatag cgggattccc

660

gcacgcttta gcgggtctgg aagcgggacc gactacactc tgaccatctc atctctccag

720

cccgaggact tcgccgtcta cttctgccag cagggtaaca ccctgccgta caccttcggc

780

cagggcacca agcttgagat caaaaccact actcccgctc caaggccacc cacccctgcc

840

ccgaccatcg cctctcagcc gctttccctg cgtccgggagg catgtagacc cgcagctggt

900

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

960

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1020

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1080

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1140

gtgaaattca gccgcagcgc agatgctcca gcctacaagc aggggcagaa ccagctctac

1200

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

1260

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

1320

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

1380

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

1440

gacgctcttc acatgcaggc cctgccgcct cgg

1473

<210> 947

<211> 491

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 947

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Asn Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

145 150 155 160

Ser Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro

165 170 175

Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys

180 185 190

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

195 200 205

Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser

210 215 220

Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln

225 230 235 240

Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro

245 250 255

Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Thr Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

305 310 315 320

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

325 330 335

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

340 345 350

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

355 360 365

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

370 375 380

Arg Ser Ala Asp Ala Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr

385 390 395 400

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

405 410 415

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

420 425 430

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

435 440 445

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

450 455 460

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

465 470 475 480

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

485 490

<210> 948

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 948

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr

20 25 30

Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys

50 55 60

Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu

65 70 75 80

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met Thr Gln Ser Pro Ala

130 135 140

Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala

145 150 155 160

Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly

180 185 190

Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu

195 200 205

Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln

210 215 220

Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu

225 230 235 240

Ile Lys

<210> 949

<211> 813

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 949

atggctctgc ccgtgaccgc actcctcctg ccactggctc tgctgcttca cgccgctcgc

60

ccacaagtcc agcttcaaga atcagggcct ggtctggtga agccatctga gactctgtcc

120

ctcacttgca ccgtgagcgg agtgtccctc ccagactacg gagtgagctg gattagacag

180

cctccgggaa agggactgga gtggatcgga gtgatttggg gtagcgaaac cacttactat

240

aactcttccc tgaagtcacg ggtcaccatt tcaaaggata actcaaagaa tcaagtgagc

300

ctcaagctct catcagtcac cgccgctgac accgccgtgt attactgtgc caagcattac

360

tactatggag ggtcctacgc catggactac tggggccagg gaactctggt cactgtgtca

420

tctggtggag gaggtagcgg aggaggcggg agcggtggag gtggctccga aatcgtgatg

480

acccagagcc ctgcaaccct gtccctttct cccggggaac gggctaccct ttcttgtcgg

540

gcatcacaag atatctcaaa atacctcaat tggtatcaac agaagccggg acaggcccct

600

aggcttctta tctaccacac ctctcgcctg catagcggga ttcccgcacg ctttagcggg

660

tctggaagcg ggaccgacta cactctgacc atctcatctc tccagcccga ggacttcgcc

720

gtctacttct gccagcaggg taacaccctg ccgtacacct tcggccaggg caccaagctt

780

gagatcaaac atcaccacca tcatcaccat cac

813

<210> 950

<211> 271

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 950

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu

20 25 30

Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val

35 40 45

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys

50 55 60

Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

65 70 75 80

Asn Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys

85 90 95

Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala

100 105 110

Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

115 120 125

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Met

145 150 155 160

Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr

165 170 175

Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr

180 185 190

Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser

195 200 205

Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly

210 215 220

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

225 230 235 240

Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln

245 250 255

Gly Thr Lys Leu Glu Ile Lys His His His His His His His His His

260 265 270

<210> 951

<211> 1458

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 951

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

120

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

180

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

240

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

300

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

360

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

420

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

480

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

540

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

600

tactacaact catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

660

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

720

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

780

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

840

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

900

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

960

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1020

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1080

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1140

agcgcagatg ctccagccta caagcagggg cagaaccagc tctacaacga actcaatctt

1200

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

1260

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

1320

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

1380

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

1440

caggccctgc cgcctcgg

1458

<210> 952

<211> 486

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 952

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu

20 25 30

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala

50 55 60

Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Ile Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile

85 90 95

Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

130 135 140

Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr

145 150 155 160

Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys Ser

195 200 205

Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val Ser Leu Lys

210 215 220

Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg

485

<210> 953

<211> 813

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 953

atggccctgc ccgtcaccgc tctgctgctg ccccttgctc tgcttcttca tgcagcaagg

60

ccggacatcc agatgaccca aaccacctca tccctctctg cctctcttgg agacaggggtg

120

accatttctt gtcgcgccag ccaggacatc agcaagtatc tgaactggta tcagcagaag

180

ccggacggaa ccgtgaagct cctgatctac catacctctc gcctgcatag cggcgtgccc

240

tcacgcttct ctggaagcgg atcaggaacc gattattctc tcactatttc aaatcttgag

300

caggaagata ttgccaccta tttctgccag cagggtaata ccctgcccta caccttcgga

360

ggagggacca agctcgaaat caccggtgga ggaggcagcg gcggtggagg gtctggtgga

420

ggtggttctg aggtgaagct gcaagaatca ggccctggac ttgtggcccc ttcacagtcc

480

ctgagcgtga cttgcaccgt gtccggagtc tccctgcccg actacggagt gtcatggatc

540

agacaacctc cacggaaagg actggaatgg ctcggtgtca tctggggtag cgaaactact

600

tactacaatt cagccctcaa aagcaggctg actattatca aggacaacag caagtcccaa

660

gtctttctta agatgaactc actccagact gacgacaccg caatctacta ttgtgctaag

720

cactactact acggaggatc ctacgctatg gattactggg gacaaggtac ttccgtcact

780

gtctcttcac accatcatca ccatcaccat cac

813

<210> 954

<211> 271

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 954

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu

20 25 30

Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr

50 55 60

Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro

65 70 75 80

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile

85 90 95

Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu

130 135 140

Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser

145 150 155 160

Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser

195 200 205

Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys

210 215 220

Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Ser Val Thr Val Ser Ser His His His His His His His His His

260 265 270

<210> 955

<211> 1458

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 955

atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg

60

ccggacatcc agatgacaca gactacatcc tccctgtctg cctctctggg agacagagtc

120

accatcagtt gcagggcaag tcaggacatt agtaaatatt taaattggta tcagcagaaa

180

ccagatggaa ctgttaaact cctgatctac catacatcaa gattacactc aggagtccca

240

tcaaggttca gtggcagtgg gtctggaaca gattattctc tcaccattag caacctggag

300

caagaagata ttgccactta cttttgccaa cagggtaata cgcttccgta cacgttcgga

360

ggggggacca agctggagat cacaggtggc ggtggctcgg gcggtggtgg gtcgggtggc

420

ggcggatctg aggtgaaact gcaggagtca ggacctggcc tggtggcgcc ctcacagagc

480

ctgtccgtca catgcactgt ctcaggggtc tcattacccg actatggtgt aagctggatt

540

cgccagcctc cacgaaaggg tctggagtgg ctgggagtaa tatggggtag tgaaaccaca

600

tactataatt cagctctcaa atccagactg accatcatca aggacaactc caagagccaa

660

gttttcttaa aaatgaacag tctgcaaact gatgacacag ccatttacta ctgtgccaaa

720

cattattact acggtggtag ctatgctatg gactactggg gccaaggaac ctcagtcacc

780

gtctcctcaa ccacgacgcc agcgccgcga ccaccaacac cggcgcccac catcgcgtcg

840

cagcccctgt ccctgcgccc agaggcgtgc cggccagcgg cggggggcgc agtgcacacg

900

agggggctgg acttcgcctg tgatatctac atctgggcgc ccttggccgg gacttgtggg

960

gtccttctcc tgtcactggt tatcaccctt tactgcaaac ggggcagaaa gaaactcctg

1020

tatatattca aacaaccatt tatgagacca gtacaaacta ctcaagagga agatggctgt

1080

agctgccgat ttccagaaga agaagaagga ggatgtgaac tgagagtgaa gttcagcagg

1140

agcgcagacg cccccgcgta caagcagggc cagaaccagc tctataacga gctcaatcta

1200

ggacgaagag aggagtacga tgttttggac aagagacgtg gccgggaccc tgagatgggg

1260

ggaaagccga gaaggaagaa ccctcaggaa ggcctgtaca atgaactgca gaaagataag

1320

atggcgggagg cctacagtga gattgggatg aaaggcgagc gccgggagggg caaggggcac

1380

gatggccttt accagggtct cagtacagcc accaggaca cctacgacgc ccttcacatg

1440

caggccctgc cccctcgc

1458

<210> 956

<211> 486

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 956

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu

20 25 30

Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr

50 55 60

Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro

65 70 75 80

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile

85 90 95

Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu

130 135 140

Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser

145 150 155 160

Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser

195 200 205

Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys

210 215 220

Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Ser Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Lys Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg

485

<210> 957

<211> 242

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 957

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly

1 5 10 15

Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln

65 70 75 80

Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu

115 120 125

Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys

130 135 140

Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg

145 150 155 160

Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser

165 170 175

Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile

180 185 190

Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln

195 200 205

Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly

210 215 220

Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val

225 230 235 240

Ser Ser

<210> 958

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 958

Asp Tyr Gly Val Ser

15

<210> 959

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 959

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser

1 5 10 15

<210> 960

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 960

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

1 5 10

<210> 961

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 961

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser

1 5 10 15

<210> 962

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 962

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Gln Ser Ser Leu Lys Ser

1 5 10 15

<210> 963

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 963

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ser Leu Lys Ser

1 5 10 15

<210> 964

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 964

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn

1 5 10

<210> 965

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 965

His Thr Ser Arg Leu His Ser

15

<210> 966

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 966

Gln Gln Gly Asn Thr Leu Pro Tyr Thr

15

<210> 967

<211> 30

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<220>

<221> OTHER_INDICATOR

<222> (1)..(30)

<223> /note="This sequence can include 1-6

repeating units 'Gly Gly Gly Gly Ser'"

<400> 967

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

1 5 10 15

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

20 25 30

<210> 968

<211> 100

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 968

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

60

tttttttttt tttttttttt tttttttttt tttttttttt

100

<210> 969

<211> 400

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<220>

<221> OTHER_INDICATOR

<222> (1)..(400)

<223> /note="This sequence can include 100-400

nucleotides"

<220>

<221> source

<223> /note="See submitted application specification for details

descriptions

substitutions and preferred embodiments"

<400> 969

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

60

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

120

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

180

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

240

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

300

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

360

aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

400

<210> 970

<211> 245

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 970

Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met Val Ser Ala Leu Leu

1 5 10 15

Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr Asp Pro Thr Arg Pro

20 25 30

Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr Asn Leu Ala Asp Arg

35 40 45

Glu Leu Val His Met Ile Asn Trp Ala Lys Arg Val Pro Gly Phe Val

50 55 60

Asp Leu Thr Leu His Asp Gln Val His Leu Leu Glu Cys Ala Trp Leu

65 70 75 80

Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser Met Glu His Pro Gly

85 90 95

Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp Arg Asn Gln Gly Lys

100 105 110

Cys Val Glu Gly Met Val Glu Ile Phe Asp Met Leu Leu Ala Thr Ser

115 120 125

Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu Glu Phe Val Cys Leu

130 135 140

Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr Thr Phe Leu Ser Ser

145 150 155 160

Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile His Arg Val Leu Asp

165 170 175

Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala Lys Ala Gly Leu Thr

180 185 190

Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu Leu Leu Ile Leu Ser

195 200 205

His Ile Arg His Met Ser Asn Lys Gly Met Glu His Leu Tyr Ser Met

210 215 220

Lys Cys Lys Asn Val Val Pro Leu Tyr Asp Leu Leu Leu Glu Met Leu

225 230 235 240

Asp Ala His Arg Leu

245

<210> 971

<211> 735

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 971

tcgttggcac tttccctgac tgccgaccag atggtgtccg cccttctgga cgccgagcct

60

ccaattctgt actcggagta cgatccgact cgcccgttct ccgaagccag catgatgggc

120

ctgttgacta acctggcgga ccgcgagttg gtgcacatga ttaactgggc taagcgggtg

180

ccgggcttcg tggacctgac tctgcacgac caagtgcacc tcctggaatg cgcctggctg

240

gaaatcctca tgatcggcct cgtgtggaga tccatggagc atcccggaaa gctcctgttt

300

gcacccaacc tcctgcttga tcgcaaccag ggaaaatgcg tggaagggat ggtcgagatt

360

ttcgacatgc tgctcgccac ctcttcccgg ttccggatga tgaatctgca gggagaagag

420

ttcgtgtgtc tgaagtcaat catcctgctg aactccgggg tctatacctt cctgagctcg

480

accctcaagt cactggagga aaaagaccac atccatcgcg tgctcgataa gatcaccgac

540

acccttatcc atctcatggc gaaggctgga ctgaccctgc aacagcagca ccagaggctg

600

gcccagttgc tgctgattct gagccacatc cggcacatgt cgaacaaggg gatggaacac

660

ctgtacagca tgaagtgcaa gaacgtcgtg cctctgtacg atctgctcct ggaaatgctg

720

gacgcgcaca gactc

735

<210> 972

<211> 69

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 972

Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala

1 5 10 15

Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly

20 25 30

Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Phe Trp Leu

35 40 45

Pro Ile Gly Cys Ala Ala Phe Val Val Val Cys Ile Leu Gly Cys Ile

50 55 60

Leu Ile Cys Trp Leu

65

<210> 973

<211> 207

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 973

accacgacgc cagcgccgcg accaccaaca ccggcgccca ccatcgcgtc gcagcccctg

60

tccctgcgcc cagaggcgtg ccggccagcg gcggggggcg cagtgcacac gagggggctg

120

gacttcgcct gtgatttctg gttacccata ggatgtgcag cctttgttgt agtctgcatt

180

ttgggatgca tacttatttg ttggctt

207

<210> 974

<211> 5000

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<220>

<221> OTHER_INDICATOR

<222> (1)..(5000)

<223> /note="This sequence can include 50-5000

nucleotides"

<220>

<221> source

<223> /note="See submitted application specification for details

descriptions

substitutions and preferred embodiments"

<400> 974

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

60

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

120

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

180

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

240

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

300

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

360

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

420

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

480

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

540

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

600

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

660

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

720

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

780

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

840

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

900

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

960

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1020

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1080

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1140

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1200

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1260

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1320

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1380

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1440

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1500

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1560

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1620

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1680

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1740

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1800

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1860

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1920

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

1980

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2040

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2100

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2160

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2220

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2280

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2340

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2400

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2460

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2520

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2580

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2640

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2700

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2760

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2820

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2880

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

2940

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3000

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3060

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3120

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3180

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3240

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3300

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3360

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3420

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3480

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3540

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3600

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3660

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3720

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3780

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3840

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3900

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

3960

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4020

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4080

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4140

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4200

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4260

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4320

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4380

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4440

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4500

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4560

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4620

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4680

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4740

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4800

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4860

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4920

tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt tttttttttt

4980

tttttttttt tttttttttt

5000

<210> 975

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 975

Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro

1 5 10 15

Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp

20 25 30

Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe

35 40 45

Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Glu Gly Val Ala

50 55 60

Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr

65 70 75 80

Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr

85 90 95

Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu

100 105

<210> 976

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 976

Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro

1 5 10 15

Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp

20 25 30

Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe

35 40 45

Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Glu Gly Val Ala

50 55 60

Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr

65 70 75 80

Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr

85 90 95

Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu

100 105

<210> 977

<211> 2817

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 977

atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg

60

ccgggatccc ggggcgtgca ggttgagaca atttccccag gagatgggcg aacgttcccc

120

aagcgcggac agacatgcgt tgtgcactac acaggaatgt tggaggacgg aaagaaaatg

180

gacagttcaa gagatcggaa caaaccattc aaattcatgt tgggaaaaca ggaagtgata

240

cggggctggg aaggggtgt agcgcaaatg tccgttggtc aacgagcaaa actcacgata

300

agtcccgatt atgcttacgg cgcaaccggt cacccggggca tcataccgcc tcatgcgact

360

ttggtctttg atgtggagct gttgaaactt gaaactcgcg gagtacaggt tgaaacaata

420

tcacccgggg acgggcggac ttttccgaag agaggtcaga cctgcgtcgt ccattatacc

480

ggtatgctgg aggacggaaa gaaaatggac agctcacgggg accgaaataa accattcaaa

540

tttatgttgg ggaaacaaga ggttatcagg ggctgggagg agggtgtggc ccagatgtct

600

gtcggtcagc gcgcgaaact cacaatctct ccggattatg cgtatggggc gacagggcat

660

ccgggaatta tccctcccca cgctaccttg gttttcgatg ttgagcttct gaagttggag

720

accagaggag ttcaagtgga gacaatatct cctggggatg gacggacgtt ccccaagcgc

780

ggccagacct gtgtagtcca ctacacaggg atgcttgaag acggaaaaaa gatggatagc

840

agtagagatc gcaacaaacc atttaagttc atgctgggga agcaggaagt aatacgcggc

900

tgggaggaag gcgtggcaca gatgagtgtt ggtcaacggg ccaaacttac tatttctccc

960

gattatgcgt atggagccac cgggcaccct ggcattatcc caccccatgc cacattggtt

1020

tttgacgttg aattgcttaa attggagacc aggggagtcc aagtggaaac aatatcaccg

1080

ggggatggtc ggacttttcc taaaaggggc caaacctgtg tagtccatta taccggaatg

1140

ctcgaagacg gaaagaaaat ggactcttct agagaccgca ataagccctt caagttcatg

1200

ttgggtaagc aagaggtgat ccggggctgg gaagaggggg tcgctcaaat gtccgtcggt

1260

cagcgagcta aactgactat ttccccagac tacgcatatg gagcgactgg ccaccccggt

1320

attattcctc cccatgcgac tctcgtgttc gacgtagaac tcttgaaatt ggaaacgtca

1380

gcccggaaca ggcggaagag aggatccgac atccagatga cacagactac atcctccctg

1440

tctgcctctc tgggagacag agtcaccatc agttgcaggg caagtcagga cattagtaaa

1500

tatttaaatt ggtatcagca gaaaccagat ggaactgtta aactcctgat ctaccataca

1560

tcaagattac actcaggagt cccatcaagg ttcagtggca gtgggtctgg aacagattat

1620

tctctcacca ttagcaacct ggagcaagaa gatattgcca cttacttttg ccaacagggt

1680

aatacgcttc cgtacacgtt cggagggggg actaagttgg aaataacagg tggcggtggc

1740

tcgggcggtg gtgggtcggg tggcggcgga tctgaggtga aactgcagga gtcaggacct

1800

ggcctggtgg cgccctcaca gagcctgtcc gtcacatgca ctgtctcagg ggtctcatta

1860

cccgactatg gtgtaagctg gattcgccag cctccacgaa agggtctgga gtggctggga

1920

gtaatatggg gtagtgaaac cacatactat aattcagctc tcaaatccag actgaccatc

1980

atcaaggaca actccaagag ccaagttttc ttaaaaatga acagtctgca aactgatgac

2040

acagccattt actactgtgc caaacattat tactacggtg gtagctatgc tatggactac

2100

tggggtcaag gaacctcagt caccgtctcc tcagctagca ccacgacgcc agcgccgcga

2160

ccaccaacac cggcgcccac catcgcgtcg cagcccctgt ccctgcgccc agaggcgtgc

2220

cggccagcgg cggggggcgc agtgcacacg agggggctgg acttcgcctg tgattccgga

2280

atctacatct gggcgccctt ggccgggact tgtggggtcc ttctcctgtc actggttatc

2340

accctttact gcaaacgggg cagaaagaaa ctcctgtata tattcaaaca accatttatg

2400

agaccagtac aaactactca agaggaagat ggctgtagct gccgatttcc agaagaagaa

2460

gaaggaggat gtgaactgag agtgaagttc agcaggagcg cagacgcccc cgcgtaccag

2520

cagggccaga accagctcta taacgagctc aatctaggac gaagagagga gtacgatgtt

2580

ttggacaaga gacgtggccg ggaccctgag atggggggaa agccgagaag gaagaaccct

2640

caggaaggcc tgtacaatga actgcagaaa gataagatgg cggaggccta cagtgagatt

2700

gggatgaaag gcgagcgccg gaggggcaag gggcacgatg gcctttacca gggtctcagt

2760

acagccacca aggacaccta cgacgccctt cacatgcagg ccctgccccc tcgctaa

2817

<210> 978

<211> 939

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 978

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Ser Arg Gly Val Gln Val Glu Thr Ile Ser

20 25 30

Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val

35 40 45

His Tyr Thr Gly Met Leu Glu Asp Gly Lys Lys Met Asp Ser Ser Arg

50 55 60

Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile

65 70 75 80

Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala

85 90 95

Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro

100 105 110

Gly Ile Ile Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu

115 120 125

Lys Leu Glu Thr Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp

130 135 140

Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr

145 150 155 160

Gly Met Leu Glu Asp Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn

165 170 175

Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp

180 185 190

Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr

195 200 205

Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile

210 215 220

Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu

225 230 235 240

Thr Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr

245 250 255

Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu

260 265 270

Glu Asp Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe

275 280 285

Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly

290 295 300

Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro

305 310 315 320

Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His

325 330 335

Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Arg Gly

340 345 350

Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys

355 360 365

Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp Gly

370 375 380

Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met

385 390 395 400

Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Glu Gly Val Ala Gln

405 410 415

Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr Ala

420 425 430

Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr Leu

435 440 445

Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Ser Ala Arg Asn Arg

450 455 460

Arg Lys Arg Gly Ser Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu

465 470 475 480

Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln

485 490 495

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr

500 505 510

Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro

515 520 525

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile

530 535 540

Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly

545 550 555 560

Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr

565 570 575

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu

580 585 590

Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser

595 600 605

Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

610 615 620

Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly

625 630 635 640

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser

645 650 655

Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys

660 665 670

Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys

675 680 685

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

690 695 700

Thr Ser Val Thr Val Ser Ser Ala Ser Thr Thr Thr Pro Ala Pro Arg

705 710 715 720

Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg

725 730 735

Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly

740 745 750

Leu Asp Phe Ala Cys Asp Ser Gly Ile Tyr Ile Trp Ala Pro Leu Ala

755 760 765

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

770 775 780

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

785 790 795 800

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

805 810 815

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

820 825 830

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

835 840 845

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

850 855 860

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

865 870 875 880

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

885 890 895

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

900 905 910

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

915 920 925

Ala Leu His Met Gln Ala Leu Pro Pro Arg Glx

930 935

<210> 979

<211> 436

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 979

Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe

1 5 10 15

Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu

20 25 30

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys

35 40 45

Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val

50 55 60

Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp

65 70 75 80

Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala

85 90 95

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Arg Gly Val

100 105 110

Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg

115 120 125

Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp Gly Lys

130 135 140

Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met Leu

145 150 155 160

Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val Ala Gln Met

165 170 175

Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr

180 185 190

Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr Leu Val

195 200 205

Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Arg Gly Val Gln Val Glu

210 215 220

Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr

225 230 235 240

Cys Val Val His Tyr Thr Gly Met Leu Glu Asp Gly Lys Lys Met Asp

245 250 255

Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln

260 265 270

Glu Val Ile Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly

275 280 285

Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr

290 295 300

Gly His Pro Gly Ile Ile Pro His Ala Thr Leu Val Phe Asp Val

305 310 315 320

Glu Leu Leu Lys Leu Glu Thr Arg Gly Val Gln Val Glu Thr Ile Ser

325 330 335

Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val

340 345 350

His Tyr Thr Gly Met Leu Glu Asp Gly Lys Lys Met Asp Ser Ser Arg

355 360 365

Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile

370 375 380

Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala

385 390 395 400

Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro

405 410 415

Gly Ile Ile Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu

420 425 430

Lys Leu Glu Thr

435

<210> 980

<211> 436

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 980

Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe

1 5 10 15

Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu

20 25 30

Asp Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys

35 40 45

Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val

50 55 60

Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp

65 70 75 80

Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala

85 90 95

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Arg Gly Val

100 105 110

Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg

115 120 125

Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp Gly Lys

130 135 140

Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met Leu

145 150 155 160

Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val Ala Gln Met

165 170 175

Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr

180 185 190

Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr Leu Val

195 200 205

Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Arg Gly Val Gln Val Glu

210 215 220

Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr

225 230 235 240

Cys Val Val His Tyr Thr Gly Met Leu Glu Asp Gly Lys Lys Met Asp

245 250 255

Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln

260 265 270

Glu Val Ile Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly

275 280 285

Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr

290 295 300

Gly His Pro Gly Ile Ile Pro His Ala Thr Leu Val Phe Asp Val

305 310 315 320

Glu Leu Leu Lys Leu Glu Thr Arg Gly Val Gln Val Glu Thr Ile Ser

325 330 335

Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val

340 345 350

His Tyr Thr Gly Met Leu Glu Asp Gly Lys Lys Met Asp Ser Ser Arg

355 360 365

Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile

370 375 380

Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala

385 390 395 400

Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro

405 410 415

Gly Ile Ile Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu

420 425 430

Lys Leu Glu Thr

435

<210> 981

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 981

Ser Ala Arg Asn Arg Gln Lys Arg

15

<210> 982

<211> 4

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 982

Arg Gly Asp Ser

1

<210> 983

<211> 244

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 983

Gln Val Gln Leu Leu Glu Ser Gly Ala Glu Leu Val Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ala Phe Ser Ser Tyr

20 25 30

Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Gln Ile Tyr Pro Gly Asp Gly Asp Thr Asn Tyr Asn Gly Lys Phe

50 55 60

Lys Gly Gln Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Gly Leu Thr Ser Glu Asp Ser Ala Val Tyr Ser Cys

85 90 95

Ala Arg Lys Thr Ile Ser Ser Val Val Asp Phe Tyr Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Gly Gly Gly Ser Gly Gly Gly Ser Gly

115 120 125

Gly Gly Ser Gly Gly Gly Ser Glu Leu Val Leu Thr Gln Ser Pro Lys

130 135 140

Phe Met Ser Thr Ser Val Gly Asp Arg Val Ser Val Thr Cys Lys Ala

145 150 155 160

Ser Gln Asn Val Gly Thr Asn Val Ala Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Gln Ser Pro Lys Pro Leu Ile Tyr Ser Ala Thr Tyr Arg Asn Ser Gly

180 185 190

Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

195 200 205

Thr Ile Thr Asn Val Gln Ser Lys Asp Leu Ala Asp Tyr Phe Cys Gln

210 215 220

Tyr Asn Arg Tyr Pro Tyr Thr Ser Phe Phe Phe Thr Lys Leu Glu Ile

225 230 235 240

Lys Arg Arg Ser

<210> 984

<211> 464

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 984

Gln Val Gln Leu Leu Glu Ser Gly Ala Glu Leu Val Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ala Phe Ser Ser Tyr

20 25 30

Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Gln Ile Tyr Pro Gly Asp Gly Asp Thr Asn Tyr Asn Gly Lys Phe

50 55 60

Lys Gly Gln Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Gly Leu Thr Ser Glu Asp Ser Ala Val Tyr Ser Cys

85 90 95

Ala Arg Lys Thr Ile Ser Ser Val Val Asp Phe Tyr Phe Asp Tyr Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Gly Gly Gly Ser Gly Gly Gly Ser Gly

115 120 125

Gly Gly Ser Gly Gly Gly Ser Glu Leu Val Leu Thr Gln Ser Pro Lys

130 135 140

Phe Met Ser Thr Ser Val Gly Asp Arg Val Ser Val Thr Cys Lys Ala

145 150 155 160

Ser Gln Asn Val Gly Thr Asn Val Ala Trp Tyr Gln Gln Lys Pro Gly

165 170 175

Gln Ser Pro Lys Pro Leu Ile Tyr Ser Ala Thr Tyr Arg Asn Ser Gly

180 185 190

Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

195 200 205

Thr Ile Thr Asn Val Gln Ser Lys Asp Leu Ala Asp Tyr Phe Cys Gln

210 215 220

Tyr Asn Arg Tyr Pro Tyr Thr Ser Phe Phe Phe Thr Lys Leu Glu Ile

225 230 235 240

Lys Arg Arg Ser Lys Ile Glu Val Met Tyr Pro Pro Pro Tyr Leu Asp

245 250 255

Asn Glu Lys Ser Asn Gly Thr Ile Ile His Val Lys Gly Lys His Leu

260 265 270

Cys Pro Ser Pro Leu Phe Pro Gly Pro Ser Lys Pro Phe Trp Val Leu

275 280 285

Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val

290 295 300

Ala Phe Ile Ile Phe Trp Val Arg Ser Lys Arg Ser Arg Leu Leu His

305 310 315 320

Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro Gly Pro Thr Arg Lys

325 330 335

His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala Ala Tyr Arg Ser

340 345 350

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

355 360 365

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

370 375 380

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

385 390 395 400

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

405 410 415

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

420 425 430

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

435 440 445

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

450 455 460

<210> 985

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 985

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly

1 5 10 15

Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln

65 70 75 80

Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly

100 105 110

Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys

115 120 125

Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser

130 135 140

Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser

145 150 155 160

Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile

165 170 175

Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu

180 185 190

Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn

195 200 205

Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr

210 215 220

Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

225 230 235 240

Val Thr Val Ser Ser Glu

245

<210> 986

<211> 439

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 986

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly

1 5 10 15

Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln

65 70 75 80

Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly

100 105 110

Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys

115 120 125

Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser

130 135 140

Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser

145 150 155 160

Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile

165 170 175

Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu

180 185 190

Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn

195 200 205

Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr

210 215 220

Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

225 230 235 240

Val Thr Val Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys

245 250 255

Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr

260 265 270

Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly

275 280 285

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

290 295 300

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Glu Glu Glu

305 310 315 320

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

325 330 335

Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

340 345 350

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

355 360 365

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

370 375 380

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

385 390 395 400

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

405 410 415

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

420 425 430

Gln Ala Leu Pro Pro Arg Leu

435

<210> 987

<211> 819

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 987

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly

1 5 10 15

Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln

65 70 75 80

Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly

100 105 110

Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys

115 120 125

Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser

130 135 140

Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser

145 150 155 160

Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile

165 170 175

Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu

180 185 190

Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn

195 200 205

Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr

210 215 220

Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

225 230 235 240

Val Thr Val Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys

245 250 255

Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr

260 265 270

Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Lys Arg Gly

275 280 285

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

290 295 300

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Glu Glu Glu

305 310 315 320

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

325 330 335

Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

340 345 350

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

355 360 365

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

370 375 380

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

385 390 395 400

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

405 410 415

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

420 425 430

Gln Ala Leu Pro Pro Arg Leu Glu Gly Gly Gly Glu Gly Arg Gly Ser

435 440 445

Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro Gly Pro Arg Met Leu

450 455 460

Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro Ala Phe

465 470 475 480

Leu Leu Ile Pro Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe

485 490 495

Lys Asp Ser Leu Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn

500 505 510

Cys Thr Ser Ile Ser Gly Asp Leu His Ile Leu Pro Val Ala Phe Arg

515 520 525

Gly Asp Ser Phe Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp

530 535 540

Ile Leu Lys Thr Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala

545 550 555 560

Trp Pro Glu Asn Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile

565 570 575

Ile Arg Gly Arg Thr Lys Gln His Gly Gln Phe Ser Leu Ala Val Val

580 585 590

Ser Leu Asn Ile Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser

595 600 605

Asp Gly Asp Val Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn

610 615 620

Thr Ile Asn Trp Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys

625 630 635 640

Ile Ile Ser Asn Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val

645 650 655

Cys His Ala Leu Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg

660 665 670

Asp Cys Val Ser Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp

675 680 685

Lys Cys Asn Leu Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser

690 695 700

Glu Cys Ile Gln Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile

705 710 715 720

Thr Cys Thr Gly Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr

725 730 735

Ile Asp Gly Pro His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly

740 745 750

Glu Asn Asn Thr Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys

755 760 765

His Leu Cys His Pro Asn Cys Thr Tyr Gly Cys Thr Gly Pro Gly Leu

770 775 780

Glu Gly Cys Pro Thr Asn Gly Pro Lys Ile Pro Ser Ile Ala Thr Gly

785 790 795 800

Met Val Gly Ala Leu Leu Leu Leu Leu Val Val Ala Leu Gly Ile Gly

805 810 815

Leu Phe Met

<210> 988

<211> 245

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 988

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly

1 5 10 15

Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln

65 70 75 80

Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly

100 105 110

Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys

115 120 125

Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser

130 135 140

Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser

145 150 155 160

Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile

165 170 175

Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu

180 185 190

Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn

195 200 205

Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr

210 215 220

Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

225 230 235 240

Val Thr Val Ser Ser

245

<210> 989

<211> 467

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 989

Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly

1 5 10 15

Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile

35 40 45

Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln

65 70 75 80

Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly

100 105 110

Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys

115 120 125

Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser

130 135 140

Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser

145 150 155 160

Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile

165 170 175

Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu

180 185 190

Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn

195 200 205

Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr

210 215 220

Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

225 230 235 240

Val Thr Val Ser Ser Ala Ala Ala Ile Glu Val Met Tyr Pro Pro Pro

245 250 255

Tyr Leu Asp Asn Glu Lys Ser Asn Gly Thr Ile Ile His Val Lys Gly

260 265 270

Lys His Leu Cys Pro Ser Pro Leu Phe Pro Gly Pro Ser Lys Pro Phe

275 280 285

Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu Leu

290 295 300

Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg Ser Lys Arg Ser Arg

305 310 315 320

Leu Leu His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg Pro Gly Pro

325 330 335

Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp Phe Ala Ala

340 345 350

Tyr Arg Ser Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr

355 360 365

Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg

370 375 380

Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met

385 390 395 400

Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu

405 410 415

Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys

420 425 430

Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu

435 440 445

Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu

450 455 460

Pro Pro Arg

465

<210> 990

<211> 751

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 990

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu Ile

275 280 285

Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg

290 295 300

Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn

305 310 315 320

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His

325 330 335

Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly

340 345 350

Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp

355 360 365

Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe

370 375 380

Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly

405 410 415

Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val

420 425 430

Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro

435 440 445

Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr

450 455 460

Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp

465 470 475 480

Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala

485 490 495

Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser

500 505 510

Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

515 520 525

Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala

530 535 540

Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly

545 550 555 560

Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile

565 570 575

Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val

580 585 590

Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe

595 600 605

Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly

610 615 620

Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg

625 630 635 640

Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln

645 650 655

Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp

660 665 670

Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro

675 680 685

Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp

690 695 700

Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg

705 710 715 720

Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr

725 730 735

Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 991

<211> 751

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 991

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu Ile

275 280 285

Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg

290 295 300

Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn

305 310 315 320

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His

325 330 335

Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly

340 345 350

Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp

355 360 365

Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe

370 375 380

Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly

405 410 415

Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val

420 425 430

Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro

435 440 445

Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr

450 455 460

Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp

465 470 475 480

Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala

485 490 495

Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser

500 505 510

Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

515 520 525

Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala

530 535 540

Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly

545 550 555 560

Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile

565 570 575

Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val

580 585 590

Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe

595 600 605

Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly

610 615 620

Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg

625 630 635 640

Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln

645 650 655

Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp

660 665 670

Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro

675 680 685

Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp

690 695 700

Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg

705 710 715 720

Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr

725 730 735

Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 992

<211> 745

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 992

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser Pro

275 280 285

Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg

290 295 300

Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

305 310 315 320

Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser

325 330 335

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

340 345 350

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys

355 360 365

Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu

370 375 380

Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

385 390 395 400

Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro

405 410 415

Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro

420 425 430

Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

435 440 445

Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser

450 455 460

Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val

465 470 475 480

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

485 490 495

Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp

500 505 510

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro

515 520 525

Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu

530 535 540

Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg

545 550 555 560

Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly

565 570 575

Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys

580 585 590

Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg

595 600 605

Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro

610 615 620

Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser

625 630 635 640

Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu

645 650 655

Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg

660 665 670

Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln

675 680 685

Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr

690 695 700

Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp

705 710 715 720

Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala

725 730 735

Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 993

<211> 745

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 993

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser Pro

275 280 285

Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg

290 295 300

Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro

305 310 315 320

Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser

325 330 335

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

340 345 350

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe Cys

355 360 365

Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu

370 375 380

Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

385 390 395 400

Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro

405 410 415

Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu Pro

420 425 430

Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

435 440 445

Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser Ser

450 455 460

Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln Val

465 470 475 480

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

485 490 495

Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp

500 505 510

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro

515 520 525

Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu

530 535 540

Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg

545 550 555 560

Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly

565 570 575

Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys

580 585 590

Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg

595 600 605

Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro

610 615 620

Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser

625 630 635 640

Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu

645 650 655

Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg

660 665 670

Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln

675 680 685

Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr

690 695 700

Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp

705 710 715 720

Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala

725 730 735

Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 994

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 994

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln Val

275 280 285

Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val

290 295 300

Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met

305 310 315 320

His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp

325 330 335

Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly

340 345 350

Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu

355 360 365

Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

370 375 380

Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly

385 390 395 400

Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser

420 425 430

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

435 440 445

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

450 455 460

Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val

465 470 475 480

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

485 490 495

Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

500 505 510

Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile

515 520 525

Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 995

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 995

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln Val

275 280 285

Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val

290 295 300

Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met

305 310 315 320

His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp

325 330 335

Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly

340 345 350

Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu

355 360 365

Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

370 375 380

Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly

385 390 395 400

Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser

420 425 430

Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser

435 440 445

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

450 455 460

Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val

465 470 475 480

Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

485 490 495

Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln

500 505 510

Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile

515 520 525

Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 996

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 996

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser Gly

275 280 285

Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala

290 295 300

Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala

305 310 315 320

Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly

325 330 335

Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg

340 345 350

Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg Ser

355 360 365

Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala

370 375 380

Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser

385 390 395 400

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

405 410 415

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

420 425 430

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

435 440 445

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

450 455 460

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

465 470 475 480

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln Pro

485 490 495

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu

500 505 510

Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 997

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 997

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser Gly

275 280 285

Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala

290 295 300

Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln Ala

305 310 315 320

Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser Gly

325 330 335

Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg

340 345 350

Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg Ser

355 360 365

Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu Ala

370 375 380

Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser

385 390 395 400

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

405 410 415

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

420 425 430

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

435 440 445

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

450 455 460

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

465 470 475 480

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln Pro

485 490 495

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro Leu

500 505 510

Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 998

<211> 748

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 998

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu Val

275 280 285

Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu

290 295 300

Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly Met

305 310 315 320

Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly

325 330 335

Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg

340 345 350

Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met

355 360 365

Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His

370 375 380

Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser

385 390 395 400

Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly

405 410 415

Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser

420 425 430

Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser

435 440 445

Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu

450 455 460

Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe

465 470 475 480

Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu

485 490 495

Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr

500 505 510

Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr

515 520 525

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

530 535 540

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

545 550 555 560

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

565 570 575

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

580 585 590

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

595 600 605

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

610 615 620

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

625 630 635 640

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu

645 650 655

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

660 665 670

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

675 680 685

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

690 695 700

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

705 710 715 720

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

725 730 735

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 999

<211> 748

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 999

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu Val

275 280 285

Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu

290 295 300

Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly Met

305 310 315 320

Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly

325 330 335

Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg

340 345 350

Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met

355 360 365

Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His

370 375 380

Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser

385 390 395 400

Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly

405 410 415

Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser

420 425 430

Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser

435 440 445

Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu

450 455 460

Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe

465 470 475 480

Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu

485 490 495

Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr

500 505 510

Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr

515 520 525

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

530 535 540

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

545 550 555 560

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

565 570 575

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

580 585 590

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

595 600 605

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

610 615 620

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

625 630 635 640

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu

645 650 655

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

660 665 670

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

675 680 685

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

690 695 700

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

705 710 715 720

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

725 730 735

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1000

<211> 742

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1000

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser Gly

275 280 285

Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val

290 295 300

Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala

305 310 315 320

Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser

325 330 335

Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp

340 345 350

Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu

355 360 365

Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val

370 375 380

Trp Gly Glyn Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly

385 390 395 400

Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln Leu

405 410 415

Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr

420 425 430

Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr

435 440 445

Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser

450 455 460

Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly

465 470 475 480

Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

485 490 495

Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly Gln

500 505 510

Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro

515 520 525

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

530 535 540

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

545 550 555 560

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

565 570 575

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

580 585 590

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

595 600 605

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

610 615 620

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

625 630 635 640

Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

645 650 655

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

660 665 670

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

675 680 685

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

690 695 700

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

705 710 715 720

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

725 730 735

Gln Ala Leu Pro Pro Arg

740

<210> 1001

<211> 742

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1001

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met

20 25 30

Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr

35 40 45

Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr

50 55 60

Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg

65 70 75 80

Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu Leu

85 90 95

Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser

100 105 110

Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp

115 120 125

Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met

130 135 140

Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu

145 150 155 160

Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr

165 170 175

Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile

180 185 190

His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala

195 200 205

Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu

210 215 220

Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met Glu

225 230 235 240

His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu

245 250 255

Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu Asp

260 265 270

Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser Gly

275 280 285

Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Val

290 295 300

Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg Ala

305 310 315 320

Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly Ser

325 330 335

Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp

340 345 350

Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu

355 360 365

Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp Val

370 375 380

Trp Gly Glyn Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly Gly

385 390 395 400

Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln Leu

405 410 415

Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr

420 425 430

Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr

435 440 445

Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser

450 455 460

Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly

465 470 475 480

Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

485 490 495

Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly Gln

500 505 510

Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro

515 520 525

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

530 535 540

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

545 550 555 560

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

565 570 575

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

580 585 590

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

595 600 605

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

610 615 620

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

625 630 635 640

Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

645 650 655

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

660 665 670

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

675 680 685

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

690 695 700

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

705 710 715 720

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

725 730 735

Gln Ala Leu Pro Pro Arg

740

<210> 1002

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1002

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu

290 295 300

Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu

305 310 315 320

Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

325 330 335

His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser

340 345 350

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

355 360 365

Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr

370 375 380

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser

405 410 415

Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr

420 425 430

Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln

435 440 445

Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu

450 455 460

Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys

465 470 475 480

Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala

485 490 495

Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly

500 505 510

Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser

515 520 525

Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 1003

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1003

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu

290 295 300

Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu

305 310 315 320

Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

325 330 335

His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser

340 345 350

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

355 360 365

Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr

370 375 380

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser

405 410 415

Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr

420 425 430

Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln

435 440 445

Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu

450 455 460

Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys

465 470 475 480

Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala

485 490 495

Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly

500 505 510

Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser

515 520 525

Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 1004

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1004

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser

275 280 285

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

290 295 300

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys

305 310 315 320

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His

325 330 335

Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr

340 345 350

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe

355 360 365

Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys

370 375 380

Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

405 410 415

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu

420 425 430

Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

435 440 445

Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser

450 455 460

Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln

465 470 475 480

Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

485 490 495

Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

500 505 510

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1005

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1005

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser

275 280 285

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

290 295 300

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys

305 310 315 320

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His

325 330 335

Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr

340 345 350

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe

355 360 365

Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys

370 375 380

Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

405 410 415

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu

420 425 430

Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

435 440 445

Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser

450 455 460

Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln

465 470 475 480

Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

485 490 495

Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

500 505 510

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1006

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1006

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln

275 280 285

Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser

290 295 300

Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr

305 310 315 320

Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly

325 330 335

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

340 345 350

Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met

355 360 365

Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala

370 375 380

Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln

385 390 395 400

Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

420 425 430

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

435 440 445

Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

450 455 460

Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly

465 470 475 480

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

485 490 495

Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

500 505 510

Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu

515 520 525

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 1007

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1007

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln

275 280 285

Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser

290 295 300

Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr

305 310 315 320

Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly

325 330 335

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

340 345 350

Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met

355 360 365

Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala

370 375 380

Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln

385 390 395 400

Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

420 425 430

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

435 440 445

Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

450 455 460

Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly

465 470 475 480

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

485 490 495

Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

500 505 510

Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu

515 520 525

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 1008

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1008

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser

275 280 285

Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys

290 295 300

Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln

305 310 315 320

Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser

325 330 335

Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr

340 345 350

Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg

355 360 365

Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu

370 375 380

Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val

385 390 395 400

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val

420 425 430

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

435 440 445

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

450 455 460

Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

465 470 475 480

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln

485 490 495

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro

500 505 510

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1009

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1009

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser

275 280 285

Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys

290 295 300

Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln

305 310 315 320

Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser

325 330 335

Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr

340 345 350

Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg

355 360 365

Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu

370 375 380

Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val

385 390 395 400

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val

420 425 430

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

435 440 445

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

450 455 460

Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

465 470 475 480

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln

485 490 495

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro

500 505 510

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1010

<211> 749

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1010

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser

290 295 300

Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly

305 310 315 320

Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser

325 330 335

Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly

340 345 350

Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln

355 360 365

Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala

370 375 380

His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

385 390 395 400

Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly

405 410 415

Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala

420 425 430

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile

435 440 445

Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

450 455 460

Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg

465 470 475 480

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

485 490 495

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser

500 505 510

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr

515 520 525

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

530 535 540

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

545 550 555 560

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

565 570 575

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

580 585 590

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

595 600 605

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

610 615 620

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

625 630 635 640

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

645 650 655

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

660 665 670

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

675 680 685

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

690 695 700

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

705 710 715 720

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

725 730 735

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1011

<211> 749

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1011

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser

290 295 300

Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly

305 310 315 320

Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser

325 330 335

Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly

340 345 350

Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln

355 360 365

Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala

370 375 380

His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

385 390 395 400

Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly

405 410 415

Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala

420 425 430

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile

435 440 445

Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

450 455 460

Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg

465 470 475 480

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

485 490 495

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser

500 505 510

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr

515 520 525

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

530 535 540

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

545 550 555 560

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

565 570 575

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

580 585 590

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

595 600 605

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

610 615 620

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

625 630 635 640

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

645 650 655

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

660 665 670

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

675 680 685

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

690 695 700

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

705 710 715 720

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

725 730 735

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1012

<211> 743

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1012

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser

275 280 285

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala

290 295 300

Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg

305 310 315 320

Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly

325 330 335

Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

340 345 350

Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro

355 360 365

Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp

370 375 380

Val Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln

405 410 415

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

420 425 430

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

435 440 445

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

450 455 460

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

465 470 475 480

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

485 490 495

Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly

500 505 510

Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

515 520 525

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

530 535 540

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

545 550 555 560

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

565 570 575

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

580 585 590

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

595 600 605

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

610 615 620

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

625 630 635 640

Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

645 650 655

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

660 665 670

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

675 680 685

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

690 695 700

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

705 710 715 720

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

725 730 735

Met Gln Ala Leu Pro Pro Arg

740

<210> 1013

<211> 743

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1013

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser

275 280 285

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala

290 295 300

Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg

305 310 315 320

Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly

325 330 335

Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

340 345 350

Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro

355 360 365

Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp

370 375 380

Val Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln

405 410 415

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

420 425 430

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

435 440 445

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

450 455 460

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

465 470 475 480

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

485 490 495

Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly

500 505 510

Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

515 520 525

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

530 535 540

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

545 550 555 560

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

565 570 575

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

580 585 590

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

595 600 605

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

610 615 620

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

625 630 635 640

Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

645 650 655

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

660 665 670

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

675 680 685

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

690 695 700

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

705 710 715 720

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

725 730 735

Met Gln Ala Leu Pro Pro Arg

740

<210> 1014

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1014

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu

290 295 300

Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu

305 310 315 320

Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

325 330 335

His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser

340 345 350

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

355 360 365

Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr

370 375 380

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser

405 410 415

Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr

420 425 430

Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln

435 440 445

Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu

450 455 460

Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys

465 470 475 480

Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala

485 490 495

Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly

500 505 510

Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser

515 520 525

Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 1015

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1015

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu

290 295 300

Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu

305 310 315 320

Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

325 330 335

His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser

340 345 350

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

355 360 365

Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr

370 375 380

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser

405 410 415

Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr

420 425 430

Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln

435 440 445

Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu

450 455 460

Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys

465 470 475 480

Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala

485 490 495

Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly

500 505 510

Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser

515 520 525

Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 1016

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1016

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser

275 280 285

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

290 295 300

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys

305 310 315 320

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His

325 330 335

Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr

340 345 350

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe

355 360 365

Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys

370 375 380

Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

405 410 415

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu

420 425 430

Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

435 440 445

Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser

450 455 460

Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln

465 470 475 480

Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

485 490 495

Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

500 505 510

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1017

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1017

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser

275 280 285

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

290 295 300

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys

305 310 315 320

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His

325 330 335

Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr

340 345 350

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe

355 360 365

Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys

370 375 380

Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

405 410 415

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu

420 425 430

Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

435 440 445

Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser

450 455 460

Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln

465 470 475 480

Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

485 490 495

Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

500 505 510

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1018

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1018

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln

275 280 285

Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser

290 295 300

Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr

305 310 315 320

Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly

325 330 335

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

340 345 350

Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met

355 360 365

Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala

370 375 380

Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln

385 390 395 400

Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

420 425 430

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

435 440 445

Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

450 455 460

Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly

465 470 475 480

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

485 490 495

Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

500 505 510

Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu

515 520 525

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 1019

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1019

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln

275 280 285

Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser

290 295 300

Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr

305 310 315 320

Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly

325 330 335

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

340 345 350

Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met

355 360 365

Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala

370 375 380

Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln

385 390 395 400

Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

420 425 430

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

435 440 445

Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

450 455 460

Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly

465 470 475 480

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

485 490 495

Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

500 505 510

Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu

515 520 525

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 1020

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1020

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser

275 280 285

Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys

290 295 300

Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln

305 310 315 320

Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser

325 330 335

Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr

340 345 350

Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg

355 360 365

Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu

370 375 380

Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val

385 390 395 400

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val

420 425 430

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

435 440 445

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

450 455 460

Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

465 470 475 480

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln

485 490 495

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro

500 505 510

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1021

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1021

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser

275 280 285

Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys

290 295 300

Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln

305 310 315 320

Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser

325 330 335

Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr

340 345 350

Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg

355 360 365

Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu

370 375 380

Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val

385 390 395 400

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val

420 425 430

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

435 440 445

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

450 455 460

Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

465 470 475 480

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln

485 490 495

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro

500 505 510

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1022

<211> 749

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1022

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser

290 295 300

Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly

305 310 315 320

Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser

325 330 335

Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly

340 345 350

Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln

355 360 365

Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala

370 375 380

His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

385 390 395 400

Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly

405 410 415

Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala

420 425 430

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile

435 440 445

Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

450 455 460

Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg

465 470 475 480

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

485 490 495

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser

500 505 510

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr

515 520 525

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

530 535 540

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

545 550 555 560

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

565 570 575

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

580 585 590

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

595 600 605

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

610 615 620

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

625 630 635 640

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

645 650 655

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

660 665 670

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

675 680 685

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

690 695 700

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

705 710 715 720

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

725 730 735

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1023

<211> 749

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1023

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser

290 295 300

Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly

305 310 315 320

Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser

325 330 335

Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly

340 345 350

Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln

355 360 365

Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala

370 375 380

His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

385 390 395 400

Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly

405 410 415

Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala

420 425 430

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile

435 440 445

Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

450 455 460

Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg

465 470 475 480

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

485 490 495

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser

500 505 510

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr

515 520 525

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

530 535 540

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

545 550 555 560

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

565 570 575

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

580 585 590

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

595 600 605

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

610 615 620

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

625 630 635 640

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

645 650 655

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

660 665 670

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

675 680 685

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

690 695 700

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

705 710 715 720

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

725 730 735

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1024

<211> 743

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1024

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser

275 280 285

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala

290 295 300

Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg

305 310 315 320

Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly

325 330 335

Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

340 345 350

Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro

355 360 365

Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp

370 375 380

Val Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln

405 410 415

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

420 425 430

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

435 440 445

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

450 455 460

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

465 470 475 480

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

485 490 495

Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly

500 505 510

Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

515 520 525

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

530 535 540

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

545 550 555 560

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

565 570 575

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

580 585 590

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

595 600 605

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

610 615 620

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

625 630 635 640

Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

645 650 655

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

660 665 670

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

675 680 685

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

690 695 700

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

705 710 715 720

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

725 730 735

Met Gln Ala Leu Pro Pro Arg

740

<210> 1025

<211> 743

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1025

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asn Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser

275 280 285

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala

290 295 300

Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg

305 310 315 320

Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly

325 330 335

Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

340 345 350

Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro

355 360 365

Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp

370 375 380

Val Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln

405 410 415

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

420 425 430

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

435 440 445

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

450 455 460

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

465 470 475 480

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

485 490 495

Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly

500 505 510

Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

515 520 525

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

530 535 540

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

545 550 555 560

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

565 570 575

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

580 585 590

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

595 600 605

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

610 615 620

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

625 630 635 640

Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

645 650 655

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

660 665 670

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

675 680 685

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

690 695 700

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

705 710 715 720

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

725 730 735

Met Gln Ala Leu Pro Pro Arg

740

<210> 1026

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1026

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu

290 295 300

Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu

305 310 315 320

Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

325 330 335

His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser

340 345 350

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

355 360 365

Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr

370 375 380

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser

405 410 415

Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr

420 425 430

Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln

435 440 445

Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu

450 455 460

Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys

465 470 475 480

Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala

485 490 495

Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly

500 505 510

Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser

515 520 525

Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 1027

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1027

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu

290 295 300

Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu

305 310 315 320

Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

325 330 335

His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser

340 345 350

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

355 360 365

Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr

370 375 380

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser

405 410 415

Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr

420 425 430

Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln

435 440 445

Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu

450 455 460

Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys

465 470 475 480

Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala

485 490 495

Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly

500 505 510

Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser

515 520 525

Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 1028

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1028

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser

275 280 285

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

290 295 300

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys

305 310 315 320

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His

325 330 335

Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr

340 345 350

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe

355 360 365

Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys

370 375 380

Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

405 410 415

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu

420 425 430

Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

435 440 445

Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser

450 455 460

Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln

465 470 475 480

Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

485 490 495

Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

500 505 510

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1029

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1029

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser

275 280 285

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

290 295 300

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys

305 310 315 320

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His

325 330 335

Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr

340 345 350

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe

355 360 365

Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys

370 375 380

Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

405 410 415

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu

420 425 430

Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

435 440 445

Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser

450 455 460

Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln

465 470 475 480

Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

485 490 495

Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

500 505 510

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1030

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1030

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln

275 280 285

Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser

290 295 300

Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr

305 310 315 320

Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly

325 330 335

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

340 345 350

Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met

355 360 365

Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala

370 375 380

Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln

385 390 395 400

Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

420 425 430

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

435 440 445

Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

450 455 460

Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly

465 470 475 480

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

485 490 495

Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

500 505 510

Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu

515 520 525

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 1031

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1031

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln

275 280 285

Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser

290 295 300

Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr

305 310 315 320

Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly

325 330 335

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

340 345 350

Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met

355 360 365

Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala

370 375 380

Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln

385 390 395 400

Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

420 425 430

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

435 440 445

Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

450 455 460

Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly

465 470 475 480

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

485 490 495

Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

500 505 510

Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu

515 520 525

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 1032

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1032

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser

275 280 285

Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys

290 295 300

Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln

305 310 315 320

Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser

325 330 335

Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr

340 345 350

Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg

355 360 365

Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu

370 375 380

Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val

385 390 395 400

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val

420 425 430

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

435 440 445

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

450 455 460

Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

465 470 475 480

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln

485 490 495

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro

500 505 510

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1033

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1033

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser

275 280 285

Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys

290 295 300

Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln

305 310 315 320

Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser

325 330 335

Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr

340 345 350

Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg

355 360 365

Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu

370 375 380

Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val

385 390 395 400

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val

420 425 430

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

435 440 445

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

450 455 460

Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

465 470 475 480

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln

485 490 495

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro

500 505 510

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1034

<211> 749

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1034

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser

290 295 300

Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly

305 310 315 320

Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser

325 330 335

Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly

340 345 350

Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln

355 360 365

Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala

370 375 380

His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

385 390 395 400

Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly

405 410 415

Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala

420 425 430

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile

435 440 445

Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

450 455 460

Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg

465 470 475 480

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

485 490 495

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser

500 505 510

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr

515 520 525

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

530 535 540

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

545 550 555 560

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

565 570 575

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

580 585 590

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

595 600 605

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

610 615 620

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

625 630 635 640

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

645 650 655

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

660 665 670

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

675 680 685

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

690 695 700

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

705 710 715 720

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

725 730 735

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1035

<211> 749

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1035

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser

290 295 300

Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly

305 310 315 320

Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser

325 330 335

Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly

340 345 350

Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln

355 360 365

Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala

370 375 380

His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

385 390 395 400

Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly

405 410 415

Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala

420 425 430

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile

435 440 445

Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

450 455 460

Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg

465 470 475 480

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

485 490 495

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser

500 505 510

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr

515 520 525

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

530 535 540

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

545 550 555 560

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

565 570 575

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

580 585 590

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

595 600 605

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

610 615 620

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

625 630 635 640

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

645 650 655

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

660 665 670

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

675 680 685

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

690 695 700

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

705 710 715 720

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

725 730 735

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1036

<211> 743

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1036

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser

275 280 285

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala

290 295 300

Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg

305 310 315 320

Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly

325 330 335

Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

340 345 350

Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro

355 360 365

Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp

370 375 380

Val Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln

405 410 415

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

420 425 430

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

435 440 445

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

450 455 460

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

465 470 475 480

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

485 490 495

Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly

500 505 510

Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

515 520 525

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

530 535 540

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

545 550 555 560

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

565 570 575

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

580 585 590

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

595 600 605

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

610 615 620

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

625 630 635 640

Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

645 650 655

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

660 665 670

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

675 680 685

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

690 695 700

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

705 710 715 720

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

725 730 735

Met Gln Ala Leu Pro Pro Arg

740

<210> 1037

<211> 743

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1037

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Glu Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser

275 280 285

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala

290 295 300

Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg

305 310 315 320

Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly

325 330 335

Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

340 345 350

Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro

355 360 365

Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp

370 375 380

Val Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln

405 410 415

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

420 425 430

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

435 440 445

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

450 455 460

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

465 470 475 480

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

485 490 495

Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly

500 505 510

Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

515 520 525

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

530 535 540

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

545 550 555 560

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

565 570 575

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

580 585 590

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

595 600 605

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

610 615 620

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

625 630 635 640

Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

645 650 655

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

660 665 670

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

675 680 685

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

690 695 700

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

705 710 715 720

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

725 730 735

Met Gln Ala Leu Pro Pro Arg

740

<210> 1038

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1038

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu

290 295 300

Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu

305 310 315 320

Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

325 330 335

His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser

340 345 350

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

355 360 365

Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr

370 375 380

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser

405 410 415

Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr

420 425 430

Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln

435 440 445

Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu

450 455 460

Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys

465 470 475 480

Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala

485 490 495

Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly

500 505 510

Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser

515 520 525

Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 1039

<211> 752

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1039

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu

290 295 300

Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu

305 310 315 320

Asn Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

325 330 335

His Thr Ser Arg Leu His Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser

340 345 350

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu

355 360 365

Asp Phe Ala Val Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr

370 375 380

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly

385 390 395 400

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser

405 410 415

Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr

420 425 430

Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln

435 440 445

Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Val Ile Trp Gly Ser Glu

450 455 460

Thr Thr Tyr Tyr Ser Ser Ser Leu Lys Ser Arg Val Thr Ile Ser Lys

465 470 475 480

Asp Asn Ser Lys Asn Gln Val Ser Leu Lys Leu Ser Ser Val Thr Ala

485 490 495

Ala Asp Thr Ala Val Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly

500 505 510

Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser

515 520 525

Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile

530 535 540

Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala

545 550 555 560

Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr

565 570 575

Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu

580 585 590

Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile

595 600 605

Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp

610 615 620

Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

625 630 635 640

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

645 650 655

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

660 665 670

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

675 680 685

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

690 695 700

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

705 710 715 720

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

725 730 735

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745 750

<210> 1040

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1040

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser

275 280 285

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

290 295 300

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys

305 310 315 320

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His

325 330 335

Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr

340 345 350

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe

355 360 365

Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys

370 375 380

Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

405 410 415

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu

420 425 430

Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

435 440 445

Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser

450 455 460

Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln

465 470 475 480

Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

485 490 495

Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

500 505 510

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1041

<211> 746

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1041

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Ile Val Met Thr Gln Ser

275 280 285

Pro Ala Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys

290 295 300

Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys

305 310 315 320

Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr His Thr Ser Arg Leu His

325 330 335

Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr

340 345 350

Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Val Tyr Phe

355 360 365

Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys

370 375 380

Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

385 390 395 400

Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys

405 410 415

Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Val Ser Leu

420 425 430

Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu

435 440 445

Glu Trp Ile Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Ser Ser

450 455 460

Ser Leu Lys Ser Arg Val Thr Ile Ser Lys Asp Asn Ser Lys Asn Gln

465 470 475 480

Val Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr

485 490 495

Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr

500 505 510

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Thr Thr Thr Pro Ala

515 520 525

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

530 535 540

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

545 550 555 560

Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala

565 570 575

Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys

580 585 590

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

595 600 605

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

610 615 620

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg

625 630 635 640

Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn

645 650 655

Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg

660 665 670

Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro

675 680 685

Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala

690 695 700

Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His

705 710 715 720

Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp

725 730 735

Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1042

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1042

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln

275 280 285

Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser

290 295 300

Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr

305 310 315 320

Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly

325 330 335

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

340 345 350

Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met

355 360 365

Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala

370 375 380

Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln

385 390 395 400

Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

420 425 430

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

435 440 445

Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

450 455 460

Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly

465 470 475 480

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

485 490 495

Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

500 505 510

Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu

515 520 525

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 1043

<211> 753

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1043

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Gln

275 280 285

Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser

290 295 300

Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr

305 310 315 320

Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly

325 330 335

Trp Ile Asn Pro Asn Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln

340 345 350

Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Val Tyr Met

355 360 365

Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala

370 375 380

Arg Asp Met Asn Ile Leu Ala Thr Val Pro Phe Asp Ile Trp Gly Gln

385 390 395 400

Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser

420 425 430

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala

435 440 445

Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly

450 455 460

Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly

465 470 475 480

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

485 490 495

Thr Val Asn Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

500 505 510

Gln Gly Asp Ser Val Pro Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu

515 520 525

Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

530 535 540

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

545 550 555 560

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile

565 570 575

Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser

580 585 590

Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr

595 600 605

Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu

610 615 620

Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu

625 630 635 640

Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln

645 650 655

Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu

660 665 670

Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly

675 680 685

Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

690 695 700

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

705 710 715 720

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

725 730 735

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

740 745 750

Arg

<210> 1044

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1044

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser

275 280 285

Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys

290 295 300

Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln

305 310 315 320

Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser

325 330 335

Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr

340 345 350

Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg

355 360 365

Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu

370 375 380

Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val

385 390 395 400

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val

420 425 430

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

435 440 445

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

450 455 460

Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

465 470 475 480

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln

485 490 495

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro

500 505 510

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1045

<211> 747

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1045

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Gln Val Gln Leu Val Gln Ser

275 280 285

Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys

290 295 300

Ala Ser Gly Tyr Thr Phe Thr Gly Tyr Tyr Met His Trp Val Arg Gln

305 310 315 320

Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Asn Pro Asn Ser

325 330 335

Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr

340 345 350

Arg Asp Thr Ser Ile Ser Thr Val Tyr Met Glu Leu Ser Arg Leu Arg

355 360 365

Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Met Asn Ile Leu

370 375 380

Ala Thr Val Pro Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val

385 390 395 400

Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

405 410 415

Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val

420 425 430

Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser

435 440 445

Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu

450 455 460

Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser

465 470 475 480

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Val Asn Ser Leu Gln

485 490 495

Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Asp Ser Val Pro

500 505 510

Leu Thr Phe Gly Gly Gly Thr Arg Leu Glu Ile Lys Thr Thr Thr Pro

515 520 525

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

530 535 540

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

545 550 555 560

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu

565 570 575

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

580 585 590

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

595 600 605

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

610 615 620

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

625 630 635 640

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

645 650 655

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

660 665 670

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

675 680 685

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

690 695 700

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

705 710 715 720

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

725 730 735

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1046

<211> 749

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1046

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser

290 295 300

Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly

305 310 315 320

Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser

325 330 335

Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly

340 345 350

Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln

355 360 365

Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala

370 375 380

His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

385 390 395 400

Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly

405 410 415

Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala

420 425 430

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile

435 440 445

Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

450 455 460

Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg

465 470 475 480

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

485 490 495

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser

500 505 510

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr

515 520 525

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

530 535 540

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

545 550 555 560

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

565 570 575

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

580 585 590

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

595 600 605

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

610 615 620

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

625 630 635 640

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

645 650 655

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

660 665 670

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

675 680 685

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

690 695 700

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

705 710 715 720

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

725 730 735

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1047

<211> 749

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1047

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Ser Leu Gly Asp Val Gly Glu

275 280 285

Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser

290 295 300

Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Ala Leu Ser Asn His Gly

305 310 315 320

Met Ser Trp Val Arg Arg Ala Pro Gly Lys Gly Leu Glu Trp Val Ser

325 330 335

Gly Ile Val Tyr Ser Gly Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly

340 345 350

Arg Phe Thr Ile Ser Arg Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln

355 360 365

Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala

370 375 380

His Gly Gly Glu Ser Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

385 390 395 400

Ser Ser Ala Ser Gly Gly Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly

405 410 415

Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala

420 425 430

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile

435 440 445

Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

450 455 460

Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg

465 470 475 480

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

485 490 495

Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser

500 505 510

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Thr

515 520 525

Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln

530 535 540

Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala

545 550 555 560

Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala

565 570 575

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

580 585 590

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

595 600 605

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

610 615 620

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

625 630 635 640

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

645 650 655

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

660 665 670

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

675 680 685

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

690 695 700

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

705 710 715 720

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

725 730 735

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

740 745

<210> 1048

<211> 743

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1048

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Ser Ser Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser

275 280 285

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala

290 295 300

Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg

305 310 315 320

Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly

325 330 335

Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

340 345 350

Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro

355 360 365

Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp

370 375 380

Val Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln

405 410 415

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

420 425 430

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

435 440 445

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

450 455 460

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

465 470 475 480

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

485 490 495

Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly

500 505 510

Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

515 520 525

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

530 535 540

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

545 550 555 560

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

565 570 575

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

580 585 590

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

595 600 605

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

610 615 620

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

625 630 635 640

Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

645 650 655

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

660 665 670

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

675 680 685

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

690 695 700

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

705 710 715 720

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

725 730 735

Met Gln Ala Leu Pro Pro Arg

740

<210> 1049

<211> 743

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1049

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gln Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln

20 25 30

Met Val Ser Ala Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu

35 40 45

Tyr Asp Pro Thr Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu

50 55 60

Thr Asn Leu Ala Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys

65 70 75 80

Arg Val Pro Gly Phe Val Asp Leu Thr Leu His Asp Gln Val His Leu

85 90 95

Leu Glu Cys Ala Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg

100 105 110

Ser Met Glu His Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu

115 120 125

Asp Arg Asn Gln Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp

130 135 140

Met Leu Leu Ala Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly

145 150 155 160

Glu Glu Phe Val Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val

165 170 175

Tyr Thr Phe Leu Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His

180 185 190

Ile His Arg Val Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met

195 200 205

Ala Lys Ala Gly Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln

210 215 220

Leu Leu Leu Ile Leu Ser His Ile Arg His Met Ser Asn Lys Arg Met

225 230 235 240

Glu His Leu Tyr Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp

245 250 255

Leu Leu Leu Glu Met Leu Asp Ala His Arg Leu Gly Thr Gly Ala Glu

260 265 270

Asp Pro Arg Pro Ser Arg Lys Arg Arg Glu Val Gln Leu Val Glu Ser

275 280 285

Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala

290 295 300

Val Ser Gly Phe Ala Leu Ser Asn His Gly Met Ser Trp Val Arg Arg

305 310 315 320

Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Gly Ile Val Tyr Ser Gly

325 330 335

Ser Thr Tyr Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

340 345 350

Asp Asn Ser Arg Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro

355 360 365

Glu Asp Thr Ala Ile Tyr Tyr Cys Ser Ala His Gly Gly Glu Ser Asp

370 375 380

Val Trp Gly Gly Gly Thr Thr Val Thr Val Ser Ser Ala Ser Gly Gly

385 390 395 400

Gly Gly Ser Gly Gly Arg Ala Ser Gly Gly Gly Gly Ser Asp Ile Gln

405 410 415

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

420 425 430

Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp

435 440 445

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala

450 455 460

Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser

465 470 475 480

Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe

485 490 495

Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly

500 505 510

Gln Gly Thr Lys Val Glu Ile Lys Thr Thr Thr Pro Ala Pro Arg Pro

515 520 525

Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro

530 535 540

Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu

545 550 555 560

Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys

565 570 575

Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly

580 585 590

Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val

595 600 605

Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu

610 615 620

Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp

625 630 635 640

Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn

645 650 655

Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg

660 665 670

Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly

675 680 685

Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu

690 695 700

Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu

705 710 715 720

Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His

725 730 735

Met Gln Ala Leu Pro Pro Arg

740

<210> 1050

<211> 2253

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1050

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct ggccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgtccaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg aaccggcgcg gaagaccccc ggccctccag gaagcgaagg

840

tccctcggag acgtgggtga aattgtgatg acccagtcac ccgccactct tagcctttca

900

cccggtgagc gcgcaaccct gtcttgcaga gcctcccaag acatctcaaa ataccttaat

960

tggtatcaac agaagcccgg acaggctcct cgccttctga tctaccacac cagccggctc

1020

cattctggaa tccctgccag gttcagcggt agcggatctg ggaccgacta caccctcact

1080

atcagctcac tgcagccaga ggacttcgct gtctatttct gtcagcaagg gaacaccctg

1140

ccctacacct ttggacaggg caccaagctc gagattaaag gtggaggtgg cagcggagga

1200

ggtgggtccg gcggtggagg aagccaggtc caactccaag aaagcggacc gggtcttgtg

1260

aagccatcag aaactctttc actgacttgt actgtgagcg gagtgtctct ccccgattac

1320

ggggtgtctt ggatcagaca gccaccgggg aagggtctgg aatggattgg agtgatttgg

1380

ggctctgaga ctacttacta ctcttcatcc ctcaagtcac gcgtcaccat ctcaaaggac

1440

aactctaaga atcaggtgtc actgaaactg tcatctgtga ccgcagccga caccgccgtg

1500

tactattgcg ctaagcatta ctattatggc gggagctacg caatggatta ctggggacag

1560

ggtactctgg tcaccgtgtc cagcaccact accccagcac cgaggccacc caccccggct

1620

cctaccatcg cctcccagcc tctgtccctg cgtccgggagg catgtagacc cgcagctggt

1680

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

1740

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1800

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1860

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1920

gtgaaattca gccgcagcgc agatgctcca gcctaccagc aggggcagaa ccagctctac

1980

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

2040

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

2100

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

2160

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

2220

gacgctcttc acatgcaggc cctgccgcct cgg

2253

<210> 1051

<211> 2253

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1051

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct gaccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgaacaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg aaccggcgcg gaagaccccc ggccctccag gaagcgaagg

840

tccctcggag acgtgggtga aattgtgatg acccagtcac ccgccactct tagcctttca

900

cccggtgagc gcgcaaccct gtcttgcaga gcctcccaag acatctcaaa ataccttaat

960

tggtatcaac agaagcccgg acaggctcct cgccttctga tctaccacac cagccggctc

1020

cattctggaa tccctgccag gttcagcggt agcggatctg ggaccgacta caccctcact

1080

atcagctcac tgcagccaga ggacttcgct gtctatttct gtcagcaagg gaacaccctg

1140

ccctacacct ttggacaggg caccaagctc gagattaaag gtggaggtgg cagcggagga

1200

ggtgggtccg gcggtggagg aagccaggtc caactccaag aaagcggacc gggtcttgtg

1260

aagccatcag aaactctttc actgacttgt actgtgagcg gagtgtctct ccccgattac

1320

ggggtgtctt ggatcagaca gccaccgggg aagggtctgg aatggattgg agtgatttgg

1380

ggctctgaga ctacttacta ctcttcatcc ctcaagtcac gcgtcaccat ctcaaaggac

1440

aactctaaga atcaggtgtc actgaaactg tcatctgtga ccgcagccga caccgccgtg

1500

tactattgcg ctaagcatta ctattatggc gggagctacg caatggatta ctggggacag

1560

ggtactctgg tcaccgtgtc cagcaccact accccagcac cgaggccacc caccccggct

1620

cctaccatcg cctcccagcc tctgtccctg cgtccgggagg catgtagacc cgcagctggt

1680

ggggccgtgc atacccgggg tcttgacttc gcctgcgata tctacatttg ggcccctctg

1740

gctggtactt gcggggtcct gctgctttca ctcgtgatca ctctttactg taagcgcggt

1800

cggaagaagc tgctgtacat ctttaagcaa cccttcatga ggcctgtgca gactactcaa

1860

gaggaggagg gctgttcatg ccggttccca gaggaggagg aaggcggctg cgaactgcgc

1920

gtgaaattca gccgcagcgc agatgctcca gcctaccagc aggggcagaa ccagctctac

1980

aacgaactca atcttggtcg gagagaggag tacgacgtgc tggacaagcg gagaggacgg

2040

gacccagaaa tgggcgggaa gccgcgcaga aagaatcccc aaggggcct gtacaacgag

2100

ctccaaaagg ataagatggc agaagcctat agcgagattg gtatgaaagg ggaacgcaga

2160

agaggcaaag gccacgacgg actgtaccag ggactcagca ccgccaccaa ggacacctat

2220

gacgctcttc acatgcaggc cctgccgcct cgg

2253

<210> 1052

<211> 2235

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1052

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct ggccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgtccaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg gacgggagct gaagatccac gacccagcag aaagcgacgg

840

gaaattgtga tgacccagtc acccgccact cttagccttt cacccggtga gcgcgcaacc

900

ctgtcttgca gagcctccca agacatctca aaatacctta attggtatca acagaagccc

960

ggacaggctc ctcgccttct gatctaccac accagccggc tccattctgg aatccctgcc

1020

aggttcagcg gtagcggatc tgggaccgac tacaccctca ctatcagctc actgcagcca

1080

gaggacttcg ctgtctattt ctgtcagcaa gggaacaccc tgccctacac ctttggacag

1140

ggcaccaagc tcgagattaa aggtggaggt ggcagcggag gaggtgggtc cggcggtgga

1200

ggaagccagg tccaactcca agaaagcggga ccgggtcttg tgaagccatc agaaactctt

1260

tcactgactt gtactgtgag cggagtgtct ctccccgatt acggggtgtc ttggatcaga

1320

cagccaccgg ggaagggtct ggaatggatt ggagtgattt ggggctctga gactacttac

1380

tactcttcat ccctcaagtc acgcgtcacc atctcaaagg acaactctaa gaatcaggtg

1440

tcactgaaac tgtcatctgt gaccgcagcc gacaccgccg tgtactattg cgctaagcat

1500

tactattatg gcgggagcta cgcaatggat tactggggac agggtactct ggtcaccgtg

1560

tccagcacca ctaccccagc accgaggcca cccaccccgg ctcctaccat cgcctcccag

1620

cctctgtccc tgcgtccgga ggcatgtaga cccgcagctg gtggggccgt gcatacccgg

1680

ggtcttgact tcgcctgcga tatctacatt tgggcccctc tggctggtac ttgcggggtc

1740

ctgctgcttt cactcgtgat cactctttac tgtaagcgcg gtcggaagaa gctgctgtac

1800

atctttaagc aacccttcat gaggcctgtg cagactactc aagaggagga cggctgttca

1860

tgccggttcc cagaggagga ggaaggcggc tgcgaactgc gcgtgaaatt cagccgcagc

1920

gcagatgctc cagcctacca gcaggggcag aaccagctct acaacgaact caatcttggt

1980

cggagagagg agtacgacgt gctggacaag cggagaggac gggacccaga aatgggcggg

2040

aagccgcgca gaaagaatcc ccaagagggc ctgtacaacg agctccaaaa ggataagatg

2100

gcagaagcct atagcgagat tggtatgaaa ggggaacgca gaagaggcaa aggccacgac

2160

ggactgtacc agggactcag caccgccacc aaggacacct atgacgctct tcacatgcag

2220

gccctgccgc ctcgg

2235

<210> 1053

<211> 2235

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1053

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct gaccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgaacaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg gacgggagct gaagatccac gacccagcag aaagcgacgg

840

gaaattgtga tgacccagtc acccgccact cttagccttt cacccggtga gcgcgcaacc

900

ctgtcttgca gagcctccca agacatctca aaatacctta attggtatca acagaagccc

960

ggacaggctc ctcgccttct gatctaccac accagccggc tccattctgg aatccctgcc

1020

aggttcagcg gtagcggatc tgggaccgac tacaccctca ctatcagctc actgcagcca

1080

gaggacttcg ctgtctattt ctgtcagcaa gggaacaccc tgccctacac ctttggacag

1140

ggcaccaagc tcgagattaa aggtggaggt ggcagcggag gaggtgggtc cggcggtgga

1200

ggaagccagg tccaactcca agaaagcggga ccgggtcttg tgaagccatc agaaactctt

1260

tcactgactt gtactgtgag cggagtgtct ctccccgatt acggggtgtc ttggatcaga

1320

cagccaccgg ggaagggtct ggaatggatt ggagtgattt ggggctctga gactacttac

1380

tactcttcat ccctcaagtc acgcgtcacc atctcaaagg acaactctaa gaatcaggtg

1440

tcactgaaac tgtcatctgt gaccgcagcc gacaccgccg tgtactattg cgctaagcat

1500

tactattatg gcgggagcta cgcaatggat tactggggac agggtactct ggtcaccgtg

1560

tccagcacca ctaccccagc accgaggcca cccaccccgg ctcctaccat cgcctcccag

1620

cctctgtccc tgcgtccgga ggcatgtaga cccgcagctg gtggggccgt gcatacccgg

1680

ggtcttgact tcgcctgcga tatctacatt tgggcccctc tggctggtac ttgcggggtc

1740

ctgctgcttt cactcgtgat cactctttac tgtaagcgcg gtcggaagaa gctgctgtac

1800

atctttaagc aacccttcat gaggcctgtg cagactactc aagaggagga cggctgttca

1860

tgccggttcc cagaggagga ggaaggcggc tgcgaactgc gcgtgaaatt cagccgcagc

1920

gcagatgctc cagcctacca gcaggggcag aaccagctct acaacgaact caatcttggt

1980

cggagagagg agtacgacgt gctggacaag cggagaggac gggacccaga aatgggcggg

2040

aagccgcgca gaaagaatcc ccaagagggc ctgtacaacg agctccaaaa ggataagatg

2100

gcagaagcct atagcgagat tggtatgaaa ggggaacgca gaagaggcaa aggccacgac

2160

ggactgtacc agggactcag caccgccacc aaggacacct atgacgctct tcacatgcag

2220

gccctgccgc ctcgg

2235

<210> 1054

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1054

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct ggccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgtccaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg aaccggcgcg gaagaccccc ggccctccag gaagcgaagg

840

tccctcggag acgtgggtca agtgcaactc gtccaaagcg gagcggaagt caagaaaccc

900

ggagcgagcg tgaaagtgtc ctgcaaagcc tccggctaca cctttacgggg ctactacatg

960

cactgggtgc gccaggcacc aggacagggt cttgaatgga tgggatggat caaccctaat

1020

tcgggcggaa ctaactacgc acagaagttc caggggagag tgactctgac tcgggatacc

1080

tccatctcaa ctgtctacat ggaactctcc cgcttgcggt cagatgatac ggcagtgtac

1140

tactgcgccc gcgacatgaa tatcctggct accgtgccgt tcgacatctg gggacagggg

1200

actatggtta ctgtctcatc gggcggtgga ggttcaggag gaggcggctc gggaggcgga

1260

ggttcggaca ttcagatgac ccagtcccca tcctctctgt cggccagcgt cggagatagg

1320

gtgaccatta cctgtcgggc ctcgcaaagc atctcctcgt acctcaactg gtatcagcaa

1380

aagccgggaa aggcgcctaa gctgctgatc tacgccgctt cgagcttgca aagcggggtg

1440

ccatccagat tctcgggatc aggctcagga accgacttca ccctgaccgt gaacagcctc

1500

cagccggagg actttgccac ttactactgc cagcagggag actccgtgcc gcttactttc

1560

ggggggggta cccgcctgga gatcaagacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1055

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1055

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct gaccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgaacaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg aaccggcgcg gaagaccccc ggccctccag gaagcgaagg

840

tccctcggag acgtgggtca agtgcaactc gtccaaagcg gagcggaagt caagaaaccc

900

ggagcgagcg tgaaagtgtc ctgcaaagcc tccggctaca cctttacgggg ctactacatg

960

cactgggtgc gccaggcacc aggacagggt cttgaatgga tgggatggat caaccctaat

1020

tcgggcggaa ctaactacgc acagaagttc caggggagag tgactctgac tcgggatacc

1080

tccatctcaa ctgtctacat ggaactctcc cgcttgcggt cagatgatac ggcagtgtac

1140

tactgcgccc gcgacatgaa tatcctggct accgtgccgt tcgacatctg gggacagggg

1200

actatggtta ctgtctcatc gggcggtgga ggttcaggag gaggcggctc gggaggcgga

1260

ggttcggaca ttcagatgac ccagtcccca tcctctctgt cggccagcgt cggagatagg

1320

gtgaccatta cctgtcgggc ctcgcaaagc atctcctcgt acctcaactg gtatcagcaa

1380

aagccgggaa aggcgcctaa gctgctgatc tacgccgctt cgagcttgca aagcggggtg

1440

ccatccagat tctcgggatc aggctcagga accgacttca ccctgaccgt gaacagcctc

1500

cagccggagg actttgccac ttactactgc cagcagggag actccgtgcc gcttactttc

1560

ggggggggta cccgcctgga gatcaagacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1056

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1056

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct ggccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgtccaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg aaccggcgcg gaagaccccc ggccctccag gaagcgaagg

840

caagtgcaac tcgtccaaag cggagcggaa gtcaagaaac ccggagcgag cgtgaaagtg

900

tcctgcaaag cctccggcta cacctttacg ggctactaca tgcactgggt gcgccaggca

960

cggacagg gtcttgaatg gatgggatgg atcaacccta attcgggcgg aactaactac

1020

gcacagaagt tccaggggag agtgactctg actcgggata cctccatctc aactgtctac

1080

atggaactct cccgcttgcg gtcagatgat acggcagtgt actactgcgc ccgcgacatg

1140

aatatcctgg ctaccgtgcc gttcgacatc tggggacagg ggactatggt tactgtctca

1200

tcgggcggtg gaggttcagg aggaggcggc tcgggaggcg gaggttcggga cattcagatg

1260

acccagtccc catcctctct gtcggccagc gtcggagata gggtgaccat tacctgtcgg

1320

gcctcgcaaa gcatctcctc gtacctcaac tggtatcagc aaaagccggg aaaggcgcct

1380

aagctgctga tctacgccgc ttcgagcttg caaagcgggg tgccatccag attctcggga

1440

tcaggctcag gaaccgactt caccctgacc gtgaacagcc tccagccgga ggactttgcc

1500

acttactact gccagcaggg agactccgtg ccgcttactt tcgggggggg tacccgcctg

1560

gagatcaaga ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1057

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1057

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct gaccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgaacaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg gacgggagct gaagatccac gacccagcag aaagcgacgg

840

caagtgcaac tcgtccaaag cggagcggaa gtcaagaaac ccggagcgag cgtgaaagtg

900

tcctgcaaag cctccggcta cacctttacg ggctactaca tgcactgggt gcgccaggca

960

cggacagg gtcttgaatg gatgggatgg atcaacccta attcgggcgg aactaactac

1020

gcacagaagt tccaggggag agtgactctg actcgggata cctccatctc aactgtctac

1080

atggaactct cccgcttgcg gtcagatgat acggcagtgt actactgcgc ccgcgacatg

1140

aatatcctgg ctaccgtgcc gttcgacatc tggggacagg ggactatggt tactgtctca

1200

tcgggcggtg gaggttcagg aggaggcggc tcgggaggcg gaggttcggga cattcagatg

1260

acccagtccc catcctctct gtcggccagc gtcggagata gggtgaccat tacctgtcgg

1320

gcctcgcaaa gcatctcctc gtacctcaac tggtatcagc aaaagccggg aaaggcgcct

1380

aagctgctga tctacgccgc ttcgagcttg caaagcgggg tgccatccag attctcggga

1440

tcaggctcag gaaccgactt caccctgacc gtgaacagcc tccagccgga ggactttgcc

1500

acttactact gccagcaggg agactccgtg ccgcttactt tcgggggggg tacccgcctg

1560

gagatcaaga ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1058

<211> 2244

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1058

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct ggccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgtccaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg aaccggcgcg gaagaccccc ggccctccag gaagcgaagg

840

tccctcggag acgtgggtga agtgcaattg gtggaatcag ggggaggact tgtgcagcct

900

ggaggatcgc tgagactgtc atgtgccgtg tccggctttg ccctgtccaa ccacgggatg

960

tcctgggtcc gccgcgcgcc tggaaagggc ctcgaatggg tgtcgggtat tgtgtacagc

1020

ggtagcacct actatgccgc atccgtgaag gggagattca ccatcagccg ggacaactcc

1080

aggaacactc tgtacctcca aatgaattcg ctgaggccag aggacactgc catctactac

1140

tgctccgcgc atggcggaga gtccgacgtc tggggacagg ggaccaccgt gaccgtgtct

1200

agcgcgtccg gcggaggcgg cagcgggggt cgggcatcag ggggcggcgg atcggacatc

1260

cagctcaccc agtccccgag ctcgctgtcc gcctccgtgg gagatcgggt caccatcacg

1320

tgccgcgcca gccagtcgat ttcctcctac ctgaactggt accaacagaa gccgggaaaa

1380

gccccgaagc ttctcatcta cgccgcctcg agcctgcagt caggagtgcc ctcacggttc

1440

tccggctccg gttccggtac tgatttcacc ctgaccattt cctccctgca accggaggac

1500

ttcgctactt actactgcca gcagtcgtac tccaccccct acactttcgg acaaggcacc

1560

aaggtcgaaa tcaagaccac taccccagca ccgaggccac ccaccccggc tcctaccatc

1620

gcctcccagc ctctgtccct gcgtccggag gcatgtagac ccgcagctgg tggggccgtg

1680

catacccggg gtcttgactt cgcctgcgat atctacattt gggcccctct ggctggtact

1740

tgcggggtcc tgctgctttc actcgtgatc actctttact gtaagcgcgg tcggaagaag

1800

ctgctgtaca tctttaagca acccttcatg aggcctgtgc agactactca agaggaggac

1860

ggctgttcat gccggttccc agaggaggag gaaggcggct gcgaactgcg cgtgaaattc

1920

agccgcagcg cagatgctcc agcctaccag caggggcaga accagctcta caacgaactc

1980

aatcttggtc ggagaggagga gtacgacgtg ctggacaagc ggagaggacg ggacccagaa

2040

atgggcggga agccgcgcag aaagaatccc caagaggggcc tgtacaacga gctccaaaag

2100

gataagatgg cagaagccta tagcgagatt ggtatgaaag gggaacgcag aagaggcaaa

2160

ggccacgacg gactgtacca gggactcagc accgccacca aggacaccta tgacgctctt

2220

cacatgcagg ccctgccgcc tcgg

2244

<210> 1059

<211> 2244

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1059

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct gaccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgaacaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg aaccggcgcg gaagaccccc ggccctccag gaagcgaagg

840

tccctcggag acgtgggtga agtgcaattg gtggaatcag ggggaggact tgtgcagcct

900

ggaggatcgc tgagactgtc atgtgccgtg tccggctttg ccctgtccaa ccacgggatg

960

tcctgggtcc gccgcgcgcc tggaaagggc ctcgaatggg tgtcgggtat tgtgtacagc

1020

ggtagcacct actatgccgc atccgtgaag gggagattca ccatcagccg ggacaactcc

1080

aggaacactc tgtacctcca aatgaattcg ctgaggccag aggacactgc catctactac

1140

tgctccgcgc atggcggaga gtccgacgtc tggggacagg ggaccaccgt gaccgtgtct

1200

agcgcgtccg gcggaggcgg cagcggggggt cgggcatcag ggggcggcgg atcggacatc

1260

cagctcaccc agtccccgag ctcgctgtcc gcctccgtgg gagatcgggt caccatcacg

1320

tgccgcgcca gccagtcgat ttcctcctac ctgaactggt accaacagaa gccgggaaaa

1380

gccccgaagc ttctcatcta cgccgcctcg agcctgcagt caggagtgcc ctcacggttc

1440

tccggctccg gttccggtac tgatttcacc ctgaccattt cctccctgca accggaggac

1500

ttcgctactt actactgcca gcagtcgtac tccaccccct acactttcgg acaaggcacc

1560

aaggtcgaaa tcaagaccac taccccagca ccgaggccac ccaccccggc tcctaccatc

1620

gcctcccagc ctctgtccct gcgtccggag gcatgtagac ccgcagctgg tggggccgtg

1680

catacccggg gtcttgactt cgcctgcgat atctacattt gggcccctct ggctggtact

1740

tgcggggtcc tgctgctttc actcgtgatc actctttact gtaagcgcgg tcggaagaag

1800

ctgctgtaca tctttaagca acccttcatg aggcctgtgc agactactca agaggaggac

1860

ggctgttcat gccggttccc agaggaggag gaaggcggct gcgaactgcg cgtgaaattc

1920

agccgcagcg cagatgctcc agcctaccag caggggcaga accagctcta caacgaactc

1980

aatcttggtc ggagaggagga gtacgacgtg ctggacaagc ggagaggacg ggacccagaa

2040

atgggcggga agccgcgcag aaagaatccc caagaggggcc tgtacaacga gctccaaaag

2100

gataagatgg cagaagccta tagcgagatt ggtatgaaag gggaacgcag aagaggcaaa

2160

ggccacgacg gactgtacca gggactcagc accgccacca aggacaccta tgacgctctt

2220

cacatgcagg ccctgccgcc tcgg

2244

<210> 1060

<211> 2226

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1060

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct ggccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgtccaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg gacgggagct gaagatccac gacccagcag aaagcgacgg

840

gaagtgcaat tggtggaatc agggggagga cttgtgcagc ctggaggatc gctgagactg

900

tcatgtgccg tgtccggctt tgccctgtcc aaccacggga tgtcctgggt ccgccgcgcg

960

cctggaaagg gcctcgaatg ggtgtcgggt attgtgtaca gcggtagcac ctactatgcc

1020

gcatccgtga aggggagatt caccatcagc cgggacaact cggaacac tctgtacctc

1080

caaatgaatt cgctgaggcc agaggacact gccatctact actgctccgc gcatggcgga

1140

gagtccgacg tctggggaca ggggaccacc gtgaccgtgt ctagcgcgtc cggcgggaggc

1200

ggcagcgggg gtcgggcatc agggggcggc ggatcggaca tccagctcac ccagtccccg

1260

agctcgctgt ccgcctccgt gggagatcgg gtcaccatca cgtgccgcgc cagccagtcg

1320

atttcctcct acctgaactg gtaccaacag aagcccggaa aagccccgaa gcttctcatc

1380

tacgccgcct cgagcctgca gtcaggagtg ccctcacggt tctccggctc cggttccggt

1440

actgatttca ccctgaccat ttcctccctg caaccgggagg acttcgctac ttactactgc

1500

cagcagtcgt actccacccc ctacactttc ggacaaggca ccaaggtcga aatcaagacc

1560

actaccccag caccgaggcc acccaccccg gctcctacca tcgcctccca gcctctgtcc

1620

ctgcgtccgg aggcatgtag acccgcagct ggtggggccg tgcatacccg gggtcttgac

1680

ttcgcctgcg atatctacat ttgggcccct ctggctggta cttgcggggt cctgctgctt

1740

tcactcgtga tcactcttta ctgtaagcgc ggtcggaaga agctgctgta catctttaag

1800

caacccttca tgaggcctgt gcagactact caagggagg acggctgttc atgccggttc

1860

ccagaggagg aggaaggcgg ctgcgaactg cgcgtgaaat tcagccgcag cgcagatgct

1920

ccagcctacc agcaggggca gaaccagctc tacaacgaac tcaatcttgg tcggagagag

1980

gagtacgacg tgctggacaa gcggagagga cgggacccag aaatgggcgg gaagccgcgc

2040

agaaagaatc cccaagggg cctgtacaac gagctccaaa aggataagat ggcagaagcc

2100

tatagcgaga ttggtatgaa aggggaacgc agaagaggca aaggccacga cggactgtac

2160

cagggactca gcaccgccac caaggacacc tatgacgctc ttcacatgca ggccctgccg

2220

ccctcgg

2226

<210> 1061

<211> 2226

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1061

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccctcgttgg cactttccct gactgccgac cagatggtgt ccgcccttct ggacgccgag

120

cctccaattc tgtactcgga gtacgatccg actcgcccgt tctccgaagc cagcatgatg

180

ggcctgttga ctaacctggc ggaccgcgag ttggtgcaca tgattaactg ggctaagcgg

240

gtgccgggct tcgtggacct gaccctgcac gaccaagtgc acctcctgga atgcgcctgg

300

atggaaatcc tcatgatcgg cctcgtgtgg agatccatgg agcatcccgg aaagctcctg

360

tttgcaccca acctcctgct tgatcgcaac cagggaaaat gcgtggaagg gggtgtcgag

420

attttcgaca tgctgctcgc cacctcttcc cggttccgga tgatgaatct gcagggagaa

480

gagttcgtgt gtctgaagtc aatcatcctg ctgaactccg gggtctatac cttcctgagc

540

tcgaccctca agtcactgga ggaaaaagac cacatccatc gcgtgctcga taagatcacc

600

gacaccctta tccatctcat ggcgaaggct ggactgaccc tgcaacagca gcaccagagg

660

ctggcccagt tgctgctgat tctgagccac atccggcaca tgtcgaacaa gaggatggaa

720

cacctgtaca gcatgaagtg caagaacgtc gtgcctctgt ccgatctgct cctggaaatg

780

ctggacgcgc acagactcgg gacgggagct gaagatccac gacccagcag aaagcgacgg

840

gaagtgcaat tggtggaatc agggggagga cttgtgcagc ctggaggatc gctgagactg

900

tcatgtgccg tgtccggctt tgccctgtcc aaccacggga tgtcctgggt ccgccgcgcg

960

cctggaaagg gcctcgaatg ggtgtcgggt attgtgtaca gcggtagcac ctactatgcc

1020

gcatccgtga aggggagatt caccatcagc cgggacaact cggaacac tctgtacctc

1080

caaatgaatt cgctgaggcc agaggacact gccatctact actgctccgc gcatggcgga

1140

gagtccgacg tctggggaca ggggaccacc gtgaccgtgt ctagcgcgtc cggcgggaggc

1200

ggcagcgggg gtcgggcatc agggggcggc ggatcggaca tccagctcac ccagtccccg

1260

agctcgctgt ccgcctccgt gggagatcgg gtcaccatca cgtgccgcgc cagccagtcg

1320

atttcctcct acctgaactg gtaccaacag aagcccggaa aagccccgaa gcttctcatc

1380

tacgccgcct cgagcctgca gtcaggagtg ccctcacggt tctccggctc cggttccggt

1440

actgatttca ccctgaccat ttcctccctg caaccgggagg acttcgctac ttactactgc

1500

cagcagtcgt actccacccc ctacactttc ggacaaggca ccaaggtcga aatcaagacc

1560

actaccccag caccgaggcc acccaccccg gctcctacca tcgcctccca gcctctgtcc

1620

ctgcgtccgg aggcatgtag acccgcagct ggtggggccg tgcatacccg gggtcttgac

1680

ttcgcctgcg atatctacat ttgggcccct ctggctggta cttgcggggt cctgctgctt

1740

tcactcgtga tcactcttta ctgtaagcgc ggtcggaaga agctgctgta catctttaag

1800

caacccttca tgaggcctgt gcagactact caagggagg acggctgttc atgccggttc

1860

ccagaggagg aggaaggcgg ctgcgaactg cgcgtgaaat tcagccgcag cgcagatgct

1920

ccagcctacc agcaggggca gaaccagctc tacaacgaac tcaatcttgg tcggagagag

1980

gagtacgacg tgctggacaa gcggagagga cgggacccag aaatgggcgg gaagccgcgc

2040

agaaagaatc cccaagggg cctgtacaac gagctccaaa aggataagat ggcagaagcc

2100

tatagcgaga ttggtatgaa aggggaacgc agaagaggca aaggccacga cggactgtac

2160

cagggactca gcaccgccac caaggacacc tatgacgctc ttcacatgca ggccctgccg

2220

ccctcgg

2226

<210> 1062

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1062

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaaattgtg atgacccagt cacccgccac tcttagcctt

900

tcacccggtg agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt

960

aattggtatc aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg

1020

ctccattctg gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc

1080

actatcagct cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc

1140

ctgccctaca cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga

1200

ggaggtgggt ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt

1260

gtgaagccat cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat

1320

tacggggtgt cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt

1380

tggggctctg agactactta ctactcttca tccctcaagt cacgcgtcac catctcaaag

1440

gacaactcta agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc

1500

gtgtactatt gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga

1560

cagggtactc tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1063

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1063

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaaattgtg atgacccagt cacccgccac tcttagcctt

900

tcacccggtg agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt

960

aattggtatc aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg

1020

ctccattctg gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc

1080

actatcagct cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc

1140

ctgccctaca cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga

1200

ggaggtgggt ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt

1260

gtgaagccat cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat

1320

tacggggtgt cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt

1380

tggggctctg agactactta ctactcttca tccctcaagt cacgcgtcac catctcaaag

1440

gacaactcta agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc

1500

gtgtactatt gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga

1560

cagggtactc tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1064

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1064

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

900

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

960

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

1020

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

1080

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

1140

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

1200

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

1260

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

1320

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

1380

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1440

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1500

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1560

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1065

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1065

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

900

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

960

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

1020

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

1080

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

1140

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

1200

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

1260

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

1320

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

1380

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1440

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1500

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1560

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1066

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1066

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tcaagtgcaa ctcgtccaaa gcggagcggga agtcaagaaa

900

cccggagcga gcgtgaaagt gtcctgcaaa gcctccggct acacctttac gggctactac

960

atgcactggg tgcgccaggc accaggacag ggtcttgaat ggatgggatg gatcaaccct

1020

aattcgggcg gaactaacta cgcacagaag ttccagggga gagtgactct gactcgggat

1080

acctccatct caactgtcta catggaactc tcccgcttgc ggtcagatga tacggcagtg

1140

tactactgcg cccgcgacat gaatatcctg gctaccgtgc cgttcgacat ctggggacag

1200

gggactatgg ttactgtctc atcgggcggt ggaggttcag gaggaggcgg ctcgggaggc

1260

ggaggttcgg acattcagat gacccagtcc ccatcctctc tgtcggccag cgtcggagat

1320

agggtgacca ttacctgtcg ggcctcgcaa agcatctcct cgtacctcaa ctggtatcag

1380

caaaagccgg gaaaggcgcc taagctgctg atctacgccg cttcgagctt gcaaagcggg

1440

gtgccatcca gattctcggg atcaggctca ggaaccgact tcaccctgac cgtgaacagc

1500

ctccagccgg aggactttgc cacttactac tgccagcagg gagactccgt gccgcttact

1560

ttcgggggggg gtacccgcct ggagatcaag accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 1067

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1067

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tcaagtgcaa ctcgtccaaa gcggagcggga agtcaagaaa

900

cccggagcga gcgtgaaagt gtcctgcaaa gcctccggct acacctttac gggctactac

960

atgcactggg tgcgccaggc accaggacag ggtcttgaat ggatgggatg gatcaaccct

1020

aattcgggcg gaactaacta cgcacagaag ttccagggga gagtgactct gactcgggat

1080

acctccatct caactgtcta catggaactc tcccgcttgc ggtcagatga tacggcagtg

1140

tactactgcg cccgcgacat gaatatcctg gctaccgtgc cgttcgacat ctggggacag

1200

gggactatgg ttactgtctc atcgggcggt ggaggttcag gaggaggcgg ctcgggaggc

1260

ggaggttcgg acattcagat gacccagtcc ccatcctctc tgtcggccag cgtcggagat

1320

agggtgacca ttacctgtcg ggcctcgcaa agcatctcct cgtacctcaa ctggtatcag

1380

caaaagccgg gaaaggcgcc taagctgctg atctacgccg cttcgagctt gcaaagcggg

1440

gtgccatcca gattctcggg atcaggctca ggaaccgact tcaccctgac cgtgaacagc

1500

ctccagccgg aggactttgc cacttactac tgccagcagg gagactccgt gccgcttact

1560

ttcgggggggg gtacccgcct ggagatcaag accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 1068

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1068

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggcaagtgc aactcgtcca aagcggagcg gaagtcaaga aacccggagc gagcgtgaaa

900

gtgtcctgca aagcctccgg ctacaccttt acgggctact acatgcactg ggtgcgccag

960

gcaccaggac agggtcttga atggatggga tggatcaacc ctaattcggg cggaactaac

1020

tacgcacaga agttccaggg gagagtgact ctgactcggg atacctccat ctcaactgtc

1080

tacatggaac tctcccgctt gcggtcagat gatacggcag tgtactactg cgcccgcgac

1140

atgaatatcc tggctaccgt gccgttcgac atctggggac aggggactat ggttactgtc

1200

tcatcgggcg gtggaggttc aggaggaggc ggctcgggag gcggaggttc ggacattcag

1260

atgacccagt ccccatcctc tctgtcggcc agcgtcggag atagggtgac cattacctgt

1320

cgggcctcgc aaagcatctc ctcgtacctc aactggtatc agcaaaagcc gggaaaggcg

1380

cctaagctgc tgatctacgc cgcttcgagc ttgcaaagcg gggtgccatc cagattctcg

1440

ggatcaggct caggaaccga cttcaccctg accgtgaaca gcctccagcc ggaggacttt

1500

gccacttact actgccagca gggagactcc gtgccgctta ctttcggggg gggtacccgc

1560

ctggagatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 1069

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1069

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cggcaagtgc aactcgtcca aagcggagcg gaagtcaaga aacccggagc gagcgtgaaa

900

gtgtcctgca aagcctccgg ctacaccttt acgggctact acatgcactg ggtgcgccag

960

gcaccaggac agggtcttga atggatggga tggatcaacc ctaattcggg cggaactaac

1020

tacgcacaga agttccaggg gagagtgact ctgactcggg atacctccat ctcaactgtc

1080

tacatggaac tctcccgctt gcggtcagat gatacggcag tgtactactg cgcccgcgac

1140

atgaatatcc tggctaccgt gccgttcgac atctggggac aggggactat ggttactgtc

1200

tcatcgggcg gtggaggttc aggaggaggc ggctcgggag gcggaggttc ggacattcag

1260

atgacccagt ccccatcctc tctgtcggcc agcgtcggag atagggtgac cattacctgt

1320

cgggcctcgc aaagcatctc ctcgtacctc aactggtatc agcaaaagcc gggaaaggcg

1380

cctaagctgc tgatctacgc cgcttcgagc ttgcaaagcg gggtgccatc cagattctcg

1440

ggatcaggct caggaaccga cttcaccctg accgtgaaca gcctccagcc ggaggacttt

1500

gccacttact actgccagca gggagactcc gtgccgctta ctttcggggg gggtacccgc

1560

ctggagatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 1070

<211> 2247

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1070

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaagtgcaa ttggtggaat cagggggagg acttgtgcag

900

cctggaggat cgctgagact gtcatgtgcc gtgtccggct ttgccctgtc caaccacggg

960

atgtcctggg tccgccgcgc gcctggaaag ggcctcgaat gggtgtcggg tattgtgtac

1020

agcggtagca cctactatgc cgcatccgtg aaggggagat tcaccatcag ccgggacaac

1080

tcggaaca ctctgtacct ccaaatgaat tcgctgaggc cagaggacac tgccatctac

1140

tactgctccg cgcatggcgg agagtccgac gtctggggac aggggaccac cgtgaccgtg

1200

tctagcgcgt ccggcggagg cggcagcggg ggtcgggcat cagggggcgg cggatcggac

1260

atccagctca cccagtcccc gagctcgctg tccgcctccg tgggagatcg ggtcaccatc

1320

acgtgccgcg ccagccagtc gatttcctcc tacctgaact ggtaccaaca gaagccggga

1380

aaagccccga agcttctcat ctacgccgcc tcgagcctgc agtcaggagt gccctcacgg

1440

ttctccggct ccggttccgg tactgatttc accctgacca ttttcctccct gcaaccggag

1500

gacttcgcta cttactactg ccagcagtcg tactccaccc cctacacttt cggacaaggc

1560

accaaggtcg aaatcaagac cactacccca gcaccgaggc cacccacccc ggctcctacc

1620

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

1680

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

1740

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1800

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1860

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1920

ttcagccgca gcgcagatgc tccagcctac cagcaggggc agaaccagct ctacaacgaa

1980

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

2040

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

2100

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

2160

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

2220

cttcacatgc aggccctgcc gcctcgg

2247

<210> 1071

<211> 2247

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1071

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaagtgcaa ttggtggaat cagggggagg acttgtgcag

900

cctggaggat cgctgagact gtcatgtgcc gtgtccggct ttgccctgtc caaccacggg

960

atgtcctggg tccgccgcgc gcctggaaag ggcctcgaat gggtgtcggg tattgtgtac

1020

agcggtagca cctactatgc cgcatccgtg aaggggagat tcaccatcag ccgggacaac

1080

tcggaaca ctctgtacct ccaaatgaat tcgctgaggc cagaggacac tgccatctac

1140

tactgctccg cgcatggcgg agagtccgac gtctggggac aggggaccac cgtgaccgtg

1200

tctagcgcgt ccggcggagg cggcagcggg ggtcgggcat cagggggcgg cggatcggac

1260

atccagctca cccagtcccc gagctcgctg tccgcctccg tgggagatcg ggtcaccatc

1320

acgtgccgcg ccagccagtc gatttcctcc tacctgaact ggtaccaaca gaagccggga

1380

aaagccccga agcttctcat ctacgccgcc tcgagcctgc agtcaggagt gccctcacgg

1440

ttctccggct ccggttccgg tactgatttc accctgacca ttttcctccct gcaaccggag

1500

gacttcgcta cttactactg ccagcagtcg tactccaccc cctacacttt cggacaaggc

1560

accaaggtcg aaatcaagac cactacccca gcaccgaggc cacccacccc ggctcctacc

1620

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

1680

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

1740

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1800

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1860

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1920

ttcagccgca gcgcagatgc tccagcctac cagcaggggc agaaccagct ctacaacgaa

1980

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

2040

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

2100

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

2160

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

2220

cttcacatgc aggccctgcc gcctcgg

2247

<210> 1072

<211> 2229

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1072

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaagtgc aattggtgga atcaggggga ggacttgtgc agcctggagg atcgctgaga

900

ctgtcatgtg ccgtgtccgg ctttgccctg tccaaccacg ggatgtcctg ggtccgccgc

960

gcgcctggaa agggcctcga atgggtgtcg ggtattgtgt acagcggtag cacctactat

1020

gccgcatccg tgaaggggag attcaccatc agccgggaca actccaggaa cactctgtac

1080

ctccaaatga attcgctgag gccagaggac actgccatct actactgctc cgcgcatggc

1140

ggagagtccg acgtctgggg acaggggacc accgtgaccg tgtctagcgc gtccggcgga

1200

ggcggcagcg ggggtcgggc atcaggggggc ggcggatcgg acatccagct cacccagtcc

1260

ccgagctcgc tgtccgcctc cgtgggagat cgggtcacca tcacgtgccg cgccagccag

1320

tcgatttcct cctacctgaa ctggtaccaa cagaagcccg gaaaagcccc gaagcttctc

1380

atctacgccg cctcgagcct gcagtcagga gtgccctcac ggttctccgg ctccggttcc

1440

ggtactgatt tcaccctgac catttcctcc ctgcaaccgg aggacttcgc tacttactac

1500

tgccagcagt cgtactccac cccctacact ttcggacaag gcaccaaggt cgaaatcaag

1560

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

1620

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

1680

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

1740

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1800

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1860

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1920

gctccagcct accagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1980

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

2040

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

2100

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

2160

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

2220

ccgcctcgg

2229

<210> 1073

<211> 2229

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1073

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgattcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaagtgc aattggtgga atcaggggga ggacttgtgc agcctggagg atcgctgaga

900

ctgtcatgtg ccgtgtccgg ctttgccctg tccaaccacg ggatgtcctg ggtccgccgc

960

gcgcctggaa agggcctcga atgggtgtcg ggtattgtgt acagcggtag cacctactat

1020

gccgcatccg tgaaggggag attcaccatc agccgggaca actccaggaa cactctgtac

1080

ctccaaatga attcgctgag gccagaggac actgccatct actactgctc cgcgcatggc

1140

ggagagtccg acgtctgggg acaggggacc accgtgaccg tgtctagcgc gtccggcgga

1200

ggcggcagcg ggggtcgggc atcaggggggc ggcggatcgg acatccagct cacccagtcc

1260

ccgagctcgc tgtccgcctc cgtgggagat cgggtcacca tcacgtgccg cgccagccag

1320

tcgatttcct cctacctgaa ctggtaccaa cagaagcccg gaaaagcccc gaagcttctc

1380

atctacgccg cctcgagcct gcagtcagga gtgccctcac ggttctccgg ctccggttcc

1440

ggtactgatt tcaccctgac catttcctcc ctgcaaccgg aggacttcgc tacttactac

1500

tgccagcagt cgtactccac cccctacact ttcggacaag gcaccaaggt cgaaatcaag

1560

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

1620

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

1680

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

1740

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1800

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1860

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1920

gctccagcct accagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1980

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

2040

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

2100

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

2160

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

2220

ccgcctcgg

2229

<210> 1074

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1074

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaaattgtg atgacccagt cacccgccac tcttagcctt

900

tcacccggtg agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt

960

aattggtatc aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg

1020

ctccattctg gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc

1080

actatcagct cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc

1140

ctgccctaca cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga

1200

ggaggtgggt ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt

1260

gtgaagccat cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat

1320

tacggggtgt cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt

1380

tggggctctg agactactta ctactcttca tccctcaagt cacgcgtcac catctcaaag

1440

gacaactcta agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc

1500

gtgtactatt gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga

1560

cagggtactc tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1075

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1075

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaaattgtg atgacccagt cacccgccac tcttagcctt

900

tcacccggtg agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt

960

aattggtatc aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg

1020

ctccattctg gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc

1080

actatcagct cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc

1140

ctgccctaca cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga

1200

ggaggtgggt ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt

1260

gtgaagccat cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat

1320

tacggggtgt cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt

1380

tggggctctg agactactta ctactcttca tccctcaagt cacgcgtcac catctcaaag

1440

gacaactcta agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc

1500

gtgtactatt gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga

1560

cagggtactc tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1076

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1076

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

900

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

960

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

1020

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

1080

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

1140

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

1200

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

1260

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

1320

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

1380

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1440

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1500

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1560

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1077

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1077

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

900

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

960

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

1020

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

1080

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

1140

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

1200

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

1260

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

1320

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

1380

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1440

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1500

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1560

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1078

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1078

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tcaagtgcaa ctcgtccaaa gcggagcggga agtcaagaaa

900

cccggagcga gcgtgaaagt gtcctgcaaa gcctccggct acacctttac gggctactac

960

atgcactggg tgcgccaggc accaggacag ggtcttgaat ggatgggatg gatcaaccct

1020

aattcgggcg gaactaacta cgcacagaag ttccagggga gagtgactct gactcgggat

1080

acctccatct caactgtcta catggaactc tcccgcttgc ggtcagatga tacggcagtg

1140

tactactgcg cccgcgacat gaatatcctg gctaccgtgc cgttcgacat ctggggacag

1200

gggactatgg ttactgtctc atcgggcggt ggaggttcag gaggaggcgg ctcgggaggc

1260

ggaggttcgg acattcagat gacccagtcc ccatcctctc tgtcggccag cgtcggagat

1320

agggtgacca ttacctgtcg ggcctcgcaa agcatctcct cgtacctcaa ctggtatcag

1380

caaaagccgg gaaaggcgcc taagctgctg atctacgccg cttcgagctt gcaaagcggg

1440

gtgccatcca gattctcggg atcaggctca ggaaccgact tcaccctgac cgtgaacagc

1500

ctccagccgg aggactttgc cacttactac tgccagcagg gagactccgt gccgcttact

1560

ttcgggggggg gtacccgcct ggagatcaag accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 1079

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1079

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tcaagtgcaa ctcgtccaaa gcggagcggga agtcaagaaa

900

cccggagcga gcgtgaaagt gtcctgcaaa gcctccggct acacctttac gggctactac

960

atgcactggg tgcgccaggc accaggacag ggtcttgaat ggatgggatg gatcaaccct

1020

aattcgggcg gaactaacta cgcacagaag ttccagggga gagtgactct gactcgggat

1080

acctccatct caactgtcta catggaactc tcccgcttgc ggtcagatga tacggcagtg

1140

tactactgcg cccgcgacat gaatatcctg gctaccgtgc cgttcgacat ctggggacag

1200

gggactatgg ttactgtctc atcgggcggt ggaggttcag gaggaggcgg ctcgggaggc

1260

ggaggttcgg acattcagat gacccagtcc ccatcctctc tgtcggccag cgtcggagat

1320

agggtgacca ttacctgtcg ggcctcgcaa agcatctcct cgtacctcaa ctggtatcag

1380

caaaagccgg gaaaggcgcc taagctgctg atctacgccg cttcgagctt gcaaagcggg

1440

gtgccatcca gattctcggg atcaggctca ggaaccgact tcaccctgac cgtgaacagc

1500

ctccagccgg aggactttgc cacttactac tgccagcagg gagactccgt gccgcttact

1560

ttcgggggggg gtacccgcct ggagatcaag accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 1080

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1080

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggcaagtgc aactcgtcca aagcggagcg gaagtcaaga aacccggagc gagcgtgaaa

900

gtgtcctgca aagcctccgg ctacaccttt acgggctact acatgcactg ggtgcgccag

960

gcaccaggac agggtcttga atggatggga tggatcaacc ctaattcggg cggaactaac

1020

tacgcacaga agttccaggg gagagtgact ctgactcggg atacctccat ctcaactgtc

1080

tacatggaac tctcccgctt gcggtcagat gatacggcag tgtactactg cgcccgcgac

1140

atgaatatcc tggctaccgt gccgttcgac atctggggac aggggactat ggttactgtc

1200

tcatcgggcg gtggaggttc aggaggaggc ggctcgggag gcggaggttc ggacattcag

1260

atgacccagt ccccatcctc tctgtcggcc agcgtcggag atagggtgac cattacctgt

1320

cgggcctcgc aaagcatctc ctcgtacctc aactggtatc agcaaaagcc gggaaaggcg

1380

cctaagctgc tgatctacgc cgcttcgagc ttgcaaagcg gggtgccatc cagattctcg

1440

ggatcaggct caggaaccga cttcaccctg accgtgaaca gcctccagcc ggaggacttt

1500

gccacttact actgccagca gggagactcc gtgccgctta ctttcggggg gggtacccgc

1560

ctggagatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 1081

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1081

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cggcaagtgc aactcgtcca aagcggagcg gaagtcaaga aacccggagc gagcgtgaaa

900

gtgtcctgca aagcctccgg ctacaccttt acgggctact acatgcactg ggtgcgccag

960

gcaccaggac agggtcttga atggatggga tggatcaacc ctaattcggg cggaactaac

1020

tacgcacaga agttccaggg gagagtgact ctgactcggg atacctccat ctcaactgtc

1080

tacatggaac tctcccgctt gcggtcagat gatacggcag tgtactactg cgcccgcgac

1140

atgaatatcc tggctaccgt gccgttcgac atctggggac aggggactat ggttactgtc

1200

tcatcgggcg gtggaggttc aggaggaggc ggctcgggag gcggaggttc ggacattcag

1260

atgacccagt ccccatcctc tctgtcggcc agcgtcggag atagggtgac cattacctgt

1320

cgggcctcgc aaagcatctc ctcgtacctc aactggtatc agcaaaagcc gggaaaggcg

1380

cctaagctgc tgatctacgc cgcttcgagc ttgcaaagcg gggtgccatc cagattctcg

1440

ggatcaggct caggaaccga cttcaccctg accgtgaaca gcctccagcc ggaggacttt

1500

gccacttact actgccagca gggagactcc gtgccgctta ctttcggggg gggtacccgc

1560

ctggagatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 1082

<211> 2247

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1082

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaagtgcaa ttggtggaat cagggggagg acttgtgcag

900

cctggaggat cgctgagact gtcatgtgcc gtgtccggct ttgccctgtc caaccacggg

960

atgtcctggg tccgccgcgc gcctggaaag ggcctcgaat gggtgtcggg tattgtgtac

1020

agcggtagca cctactatgc cgcatccgtg aaggggagat tcaccatcag ccgggacaac

1080

tcggaaca ctctgtacct ccaaatgaat tcgctgaggc cagaggacac tgccatctac

1140

tactgctccg cgcatggcgg agagtccgac gtctggggac aggggaccac cgtgaccgtg

1200

tctagcgcgt ccggcggagg cggcagcggg ggtcgggcat cagggggcgg cggatcggac

1260

atccagctca cccagtcccc gagctcgctg tccgcctccg tgggagatcg ggtcaccatc

1320

acgtgccgcg ccagccagtc gatttcctcc tacctgaact ggtaccaaca gaagccggga

1380

aaagccccga agcttctcat ctacgccgcc tcgagcctgc agtcaggagt gccctcacgg

1440

ttctccggct ccggttccgg tactgatttc accctgacca ttttcctccct gcaaccggag

1500

gacttcgcta cttactactg ccagcagtcg tactccaccc cctacacttt cggacaaggc

1560

accaaggtcg aaatcaagac cactacccca gcaccgaggc cacccacccc ggctcctacc

1620

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

1680

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

1740

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1800

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1860

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1920

ttcagccgca gcgcagatgc tccagcctac cagcaggggc agaaccagct ctacaacgaa

1980

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

2040

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

2100

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

2160

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

2220

cttcacatgc aggccctgcc gcctcgg

2247

<210> 1083

<211> 2247

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1083

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaagtgcaa ttggtggaat cagggggagg acttgtgcag

900

cctggaggat cgctgagact gtcatgtgcc gtgtccggct ttgccctgtc caaccacggg

960

atgtcctggg tccgccgcgc gcctggaaag ggcctcgaat gggtgtcggg tattgtgtac

1020

agcggtagca cctactatgc cgcatccgtg aaggggagat tcaccatcag ccgggacaac

1080

tcggaaca ctctgtacct ccaaatgaat tcgctgaggc cagaggacac tgccatctac

1140

tactgctccg cgcatggcgg agagtccgac gtctggggac aggggaccac cgtgaccgtg

1200

tctagcgcgt ccggcggagg cggcagcggg ggtcgggcat cagggggcgg cggatcggac

1260

atccagctca cccagtcccc gagctcgctg tccgcctccg tgggagatcg ggtcaccatc

1320

acgtgccgcg ccagccagtc gatttcctcc tacctgaact ggtaccaaca gaagccggga

1380

aaagccccga agcttctcat ctacgccgcc tcgagcctgc agtcaggagt gccctcacgg

1440

ttctccggct ccggttccgg tactgatttc accctgacca ttttcctccct gcaaccggag

1500

gacttcgcta cttactactg ccagcagtcg tactccaccc cctacacttt cggacaaggc

1560

accaaggtcg aaatcaagac cactacccca gcaccgaggc cacccacccc ggctcctacc

1620

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

1680

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

1740

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1800

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1860

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1920

ttcagccgca gcgcagatgc tccagcctac cagcaggggc agaaccagct ctacaacgaa

1980

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

2040

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

2100

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

2160

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

2220

cttcacatgc aggccctgcc gcctcgg

2247

<210> 1084

<211> 2229

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1084

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaagtgc aattggtgga atcaggggga ggacttgtgc agcctggagg atcgctgaga

900

ctgtcatgtg ccgtgtccgg ctttgccctg tccaaccacg ggatgtcctg ggtccgccgc

960

gcgcctggaa agggcctcga atgggtgtcg ggtattgtgt acagcggtag cacctactat

1020

gccgcatccg tgaaggggag attcaccatc agccgggaca actccaggaa cactctgtac

1080

ctccaaatga attcgctgag gccagaggac actgccatct actactgctc cgcgcatggc

1140

ggagagtccg acgtctgggg acaggggacc accgtgaccg tgtctagcgc gtccggcgga

1200

ggcggcagcg ggggtcgggc atcaggggggc ggcggatcgg acatccagct cacccagtcc

1260

ccgagctcgc tgtccgcctc cgtgggagat cgggtcacca tcacgtgccg cgccagccag

1320

tcgatttcct cctacctgaa ctggtaccaa cagaagcccg gaaaagcccc gaagcttctc

1380

atctacgccg cctcgagcct gcagtcagga gtgccctcac ggttctccgg ctccggttcc

1440

ggtactgatt tcaccctgac catttcctcc ctgcaaccgg aggacttcgc tacttactac

1500

tgccagcagt cgtactccac cccctacact ttcggacaag gcaccaaggt cgaaatcaag

1560

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

1620

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

1680

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

1740

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1800

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1860

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1920

gctccagcct accagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1980

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

2040

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

2100

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

2160

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

2220

ccgcctcgg

2229

<210> 1085

<211> 2229

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1085

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccaactcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaagtgc aattggtgga atcaggggga ggacttgtgc agcctggagg atcgctgaga

900

ctgtcatgtg ccgtgtccgg ctttgccctg tccaaccacg ggatgtcctg ggtccgccgc

960

gcgcctggaa agggcctcga atgggtgtcg ggtattgtgt acagcggtag cacctactat

1020

gccgcatccg tgaaggggag attcaccatc agccgggaca actccaggaa cactctgtac

1080

ctccaaatga attcgctgag gccagaggac actgccatct actactgctc cgcgcatggc

1140

ggagagtccg acgtctgggg acaggggacc accgtgaccg tgtctagcgc gtccggcgga

1200

ggcggcagcg ggggtcgggc atcaggggggc ggcggatcgg acatccagct cacccagtcc

1260

ccgagctcgc tgtccgcctc cgtgggagat cgggtcacca tcacgtgccg cgccagccag

1320

tcgatttcct cctacctgaa ctggtaccaa cagaagcccg gaaaagcccc gaagcttctc

1380

atctacgccg cctcgagcct gcagtcagga gtgccctcac ggttctccgg ctccggttcc

1440

ggtactgatt tcaccctgac catttcctcc ctgcaaccgg aggacttcgc tacttactac

1500

tgccagcagt cgtactccac cccctacact ttcggacaag gcaccaaggt cgaaatcaag

1560

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

1620

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

1680

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

1740

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1800

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1860

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1920

gctccagcct accagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1980

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

2040

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

2100

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

2160

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

2220

ccgcctcgg

2229

<210> 1086

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1086

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaaattgtg atgacccagt cacccgccac tcttagcctt

900

tcacccggtg agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt

960

aattggtatc aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg

1020

ctccattctg gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc

1080

actatcagct cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc

1140

ctgccctaca cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga

1200

ggaggtgggt ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt

1260

gtgaagccat cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat

1320

tacggggtgt cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt

1380

tggggctctg agactactta ctactcttca tccctcaagt cacgcgtcac catctcaaag

1440

gacaactcta agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc

1500

gtgtactatt gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga

1560

cagggtactc tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1087

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1087

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaaattgtg atgacccagt cacccgccac tcttagcctt

900

tcacccggtg agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt

960

aattggtatc aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg

1020

ctccattctg gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc

1080

actatcagct cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc

1140

ctgccctaca cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga

1200

ggaggtgggt ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt

1260

gtgaagccat cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat

1320

tacggggtgt cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt

1380

tggggctctg agactactta ctactcttca tccctcaagt cacgcgtcac catctcaaag

1440

gacaactcta agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc

1500

gtgtactatt gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga

1560

cagggtactc tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1088

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1088

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

900

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

960

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

1020

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

1080

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

1140

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

1200

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

1260

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

1320

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

1380

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1440

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1500

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1560

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1089

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1089

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

900

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

960

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

1020

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

1080

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

1140

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

1200

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

1260

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

1320

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

1380

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1440

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1500

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1560

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1090

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1090

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tcaagtgcaa ctcgtccaaa gcggagcggga agtcaagaaa

900

cccggagcga gcgtgaaagt gtcctgcaaa gcctccggct acacctttac gggctactac

960

atgcactggg tgcgccaggc accaggacag ggtcttgaat ggatgggatg gatcaaccct

1020

aattcgggcg gaactaacta cgcacagaag ttccagggga gagtgactct gactcgggat

1080

acctccatct caactgtcta catggaactc tcccgcttgc ggtcagatga tacggcagtg

1140

tactactgcg cccgcgacat gaatatcctg gctaccgtgc cgttcgacat ctggggacag

1200

gggactatgg ttactgtctc atcgggcggt ggaggttcag gaggaggcgg ctcgggaggc

1260

ggaggttcgg acattcagat gacccagtcc ccatcctctc tgtcggccag cgtcggagat

1320

agggtgacca ttacctgtcg ggcctcgcaa agcatctcct cgtacctcaa ctggtatcag

1380

caaaagccgg gaaaggcgcc taagctgctg atctacgccg cttcgagctt gcaaagcggg

1440

gtgccatcca gattctcggg atcaggctca ggaaccgact tcaccctgac cgtgaacagc

1500

ctccagccgg aggactttgc cacttactac tgccagcagg gagactccgt gccgcttact

1560

ttcgggggggg gtacccgcct ggagatcaag accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 1091

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1091

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tcaagtgcaa ctcgtccaaa gcggagcggga agtcaagaaa

900

cccggagcga gcgtgaaagt gtcctgcaaa gcctccggct acacctttac gggctactac

960

atgcactggg tgcgccaggc accaggacag ggtcttgaat ggatgggatg gatcaaccct

1020

aattcgggcg gaactaacta cgcacagaag ttccagggga gagtgactct gactcgggat

1080

acctccatct caactgtcta catggaactc tcccgcttgc ggtcagatga tacggcagtg

1140

tactactgcg cccgcgacat gaatatcctg gctaccgtgc cgttcgacat ctggggacag

1200

gggactatgg ttactgtctc atcgggcggt ggaggttcag gaggaggcgg ctcgggaggc

1260

ggaggttcgg acattcagat gacccagtcc ccatcctctc tgtcggccag cgtcggagat

1320

agggtgacca ttacctgtcg ggcctcgcaa agcatctcct cgtacctcaa ctggtatcag

1380

caaaagccgg gaaaggcgcc taagctgctg atctacgccg cttcgagctt gcaaagcggg

1440

gtgccatcca gattctcggg atcaggctca ggaaccgact tcaccctgac cgtgaacagc

1500

ctccagccgg aggactttgc cacttactac tgccagcagg gagactccgt gccgcttact

1560

ttcgggggggg gtacccgcct ggagatcaag accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 1092

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1092

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggcaagtgc aactcgtcca aagcggagcg gaagtcaaga aacccggagc gagcgtgaaa

900

gtgtcctgca aagcctccgg ctacaccttt acgggctact acatgcactg ggtgcgccag

960

gcaccaggac agggtcttga atggatggga tggatcaacc ctaattcggg cggaactaac

1020

tacgcacaga agttccaggg gagagtgact ctgactcggg atacctccat ctcaactgtc

1080

tacatggaac tctcccgctt gcggtcagat gatacggcag tgtactactg cgcccgcgac

1140

atgaatatcc tggctaccgt gccgttcgac atctggggac aggggactat ggttactgtc

1200

tcatcgggcg gtggaggttc aggaggaggc ggctcgggag gcggaggttc ggacattcag

1260

atgacccagt ccccatcctc tctgtcggcc agcgtcggag atagggtgac cattacctgt

1320

cgggcctcgc aaagcatctc ctcgtacctc aactggtatc agcaaaagcc gggaaaggcg

1380

cctaagctgc tgatctacgc cgcttcgagc ttgcaaagcg gggtgccatc cagattctcg

1440

ggatcaggct caggaaccga cttcaccctg accgtgaaca gcctccagcc ggaggacttt

1500

gccacttact actgccagca gggagactcc gtgccgctta ctttcggggg gggtacccgc

1560

ctggagatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 1093

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1093

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cggcaagtgc aactcgtcca aagcggagcg gaagtcaaga aacccggagc gagcgtgaaa

900

gtgtcctgca aagcctccgg ctacaccttt acgggctact acatgcactg ggtgcgccag

960

gcaccaggac agggtcttga atggatggga tggatcaacc ctaattcggg cggaactaac

1020

tacgcacaga agttccaggg gagagtgact ctgactcggg atacctccat ctcaactgtc

1080

tacatggaac tctcccgctt gcggtcagat gatacggcag tgtactactg cgcccgcgac

1140

atgaatatcc tggctaccgt gccgttcgac atctggggac aggggactat ggttactgtc

1200

tcatcgggcg gtggaggttc aggaggaggc ggctcgggag gcggaggttc ggacattcag

1260

atgacccagt ccccatcctc tctgtcggcc agcgtcggag atagggtgac cattacctgt

1320

cgggcctcgc aaagcatctc ctcgtacctc aactggtatc agcaaaagcc gggaaaggcg

1380

cctaagctgc tgatctacgc cgcttcgagc ttgcaaagcg gggtgccatc cagattctcg

1440

ggatcaggct caggaaccga cttcaccctg accgtgaaca gcctccagcc ggaggacttt

1500

gccacttact actgccagca gggagactcc gtgccgctta ctttcggggg gggtacccgc

1560

ctggagatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 1094

<211> 2247

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1094

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaagtgcaa ttggtggaat cagggggagg acttgtgcag

900

cctggaggat cgctgagact gtcatgtgcc gtgtccggct ttgccctgtc caaccacggg

960

atgtcctggg tccgccgcgc gcctggaaag ggcctcgaat gggtgtcggg tattgtgtac

1020

agcggtagca cctactatgc cgcatccgtg aaggggagat tcaccatcag ccgggacaac

1080

tcggaaca ctctgtacct ccaaatgaat tcgctgaggc cagaggacac tgccatctac

1140

tactgctccg cgcatggcgg agagtccgac gtctggggac aggggaccac cgtgaccgtg

1200

tctagcgcgt ccggcggagg cggcagcggg ggtcgggcat cagggggcgg cggatcggac

1260

atccagctca cccagtcccc gagctcgctg tccgcctccg tgggagatcg ggtcaccatc

1320

acgtgccgcg ccagccagtc gatttcctcc tacctgaact ggtaccaaca gaagccggga

1380

aaagccccga agcttctcat ctacgccgcc tcgagcctgc agtcaggagt gccctcacgg

1440

ttctccggct ccggttccgg tactgatttc accctgacca ttttcctccct gcaaccggag

1500

gacttcgcta cttactactg ccagcagtcg tactccaccc cctacacttt cggacaaggc

1560

accaaggtcg aaatcaagac cactacccca gcaccgaggc cacccacccc ggctcctacc

1620

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

1680

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

1740

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1800

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1860

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1920

ttcagccgca gcgcagatgc tccagcctac cagcaggggc agaaccagct ctacaacgaa

1980

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

2040

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

2100

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

2160

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

2220

cttcacatgc aggccctgcc gcctcgg

2247

<210> 1095

<211> 2247

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1095

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaagtgcaa ttggtggaat cagggggagg acttgtgcag

900

cctggaggat cgctgagact gtcatgtgcc gtgtccggct ttgccctgtc caaccacggg

960

atgtcctggg tccgccgcgc gcctggaaag ggcctcgaat gggtgtcggg tattgtgtac

1020

agcggtagca cctactatgc cgcatccgtg aaggggagat tcaccatcag ccgggacaac

1080

tcggaaca ctctgtacct ccaaatgaat tcgctgaggc cagaggacac tgccatctac

1140

tactgctccg cgcatggcgg agagtccgac gtctggggac aggggaccac cgtgaccgtg

1200

tctagcgcgt ccggcggagg cggcagcggg ggtcgggcat cagggggcgg cggatcggac

1260

atccagctca cccagtcccc gagctcgctg tccgcctccg tgggagatcg ggtcaccatc

1320

acgtgccgcg ccagccagtc gatttcctcc tacctgaact ggtaccaaca gaagccggga

1380

aaagccccga agcttctcat ctacgccgcc tcgagcctgc agtcaggagt gccctcacgg

1440

ttctccggct ccggttccgg tactgatttc accctgacca ttttcctccct gcaaccggag

1500

gacttcgcta cttactactg ccagcagtcg tactccaccc cctacacttt cggacaaggc

1560

accaaggtcg aaatcaagac cactacccca gcaccgaggc cacccacccc ggctcctacc

1620

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

1680

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

1740

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1800

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1860

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1920

ttcagccgca gcgcagatgc tccagcctac cagcaggggc agaaccagct ctacaacgaa

1980

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

2040

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

2100

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

2160

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

2220

cttcacatgc aggccctgcc gcctcgg

2247

<210> 1096

<211> 2229

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1096

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaagtgc aattggtgga atcaggggga ggacttgtgc agcctggagg atcgctgaga

900

ctgtcatgtg ccgtgtccgg ctttgccctg tccaaccacg ggatgtcctg ggtccgccgc

960

gcgcctggaa agggcctcga atgggtgtcg ggtattgtgt acagcggtag cacctactat

1020

gccgcatccg tgaaggggag attcaccatc agccgggaca actccaggaa cactctgtac

1080

ctccaaatga attcgctgag gccagaggac actgccatct actactgctc cgcgcatggc

1140

ggagagtccg acgtctgggg acaggggacc accgtgaccg tgtctagcgc gtccggcgga

1200

ggcggcagcg ggggtcgggc atcaggggggc ggcggatcgg acatccagct cacccagtcc

1260

ccgagctcgc tgtccgcctc cgtgggagat cgggtcacca tcacgtgccg cgccagccag

1320

tcgatttcct cctacctgaa ctggtaccaa cagaagcccg gaaaagcccc gaagcttctc

1380

atctacgccg cctcgagcct gcagtcagga gtgccctcac ggttctccgg ctccggttcc

1440

ggtactgatt tcaccctgac catttcctcc ctgcaaccgg aggacttcgc tacttactac

1500

tgccagcagt cgtactccac cccctacact ttcggacaag gcaccaaggt cgaaatcaag

1560

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

1620

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

1680

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

1740

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1800

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1860

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1920

gctccagcct accagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1980

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

2040

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

2100

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

2160

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

2220

ccgcctcgg

2229

<210> 1097

<211> 2229

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1097

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

cccgagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaagtgc aattggtgga atcaggggga ggacttgtgc agcctggagg atcgctgaga

900

ctgtcatgtg ccgtgtccgg ctttgccctg tccaaccacg ggatgtcctg ggtccgccgc

960

gcgcctggaa agggcctcga atgggtgtcg ggtattgtgt acagcggtag cacctactat

1020

gccgcatccg tgaaggggag attcaccatc agccgggaca actccaggaa cactctgtac

1080

ctccaaatga attcgctgag gccagaggac actgccatct actactgctc cgcgcatggc

1140

ggagagtccg acgtctgggg acaggggacc accgtgaccg tgtctagcgc gtccggcgga

1200

ggcggcagcg ggggtcgggc atcaggggggc ggcggatcgg acatccagct cacccagtcc

1260

ccgagctcgc tgtccgcctc cgtgggagat cgggtcacca tcacgtgccg cgccagccag

1320

tcgatttcct cctacctgaa ctggtaccaa cagaagcccg gaaaagcccc gaagcttctc

1380

atctacgccg cctcgagcct gcagtcagga gtgccctcac ggttctccgg ctccggttcc

1440

ggtactgatt tcaccctgac catttcctcc ctgcaaccgg aggacttcgc tacttactac

1500

tgccagcagt cgtactccac cccctacact ttcggacaag gcaccaaggt cgaaatcaag

1560

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

1620

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

1680

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

1740

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1800

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1860

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1920

gctccagcct accagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1980

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

2040

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

2100

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

2160

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

2220

ccgcctcgg

2229

<210> 1098

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1098

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaaattgtg atgacccagt cacccgccac tcttagcctt

900

tcacccggtg agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt

960

aattggtatc aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg

1020

ctccattctg gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc

1080

actatcagct cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc

1140

ctgccctaca cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga

1200

ggaggtgggt ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt

1260

gtgaagccat cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat

1320

tacggggtgt cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt

1380

tggggctctg agactactta ctactcttca tccctcaagt cacgcgtcac catctcaaag

1440

gacaactcta agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc

1500

gtgtactatt gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga

1560

cagggtactc tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1099

<211> 2256

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1099

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaaattgtg atgacccagt cacccgccac tcttagcctt

900

tcacccggtg agcgcgcaac cctgtcttgc agagcctccc aagacatctc aaaatacctt

960

aattggtatc aacagaagcc cggacaggct cctcgccttc tgatctacca caccagccgg

1020

ctccattctg gaatccctgc caggttcagc ggtagcggat ctgggaccga ctacaccctc

1080

actatcagct cactgcagcc agaggacttc gctgtctatt tctgtcagca agggaacacc

1140

ctgccctaca cctttggaca gggcaccaag ctcgagatta aaggtggagg tggcagcgga

1200

ggaggtgggt ccggcggtgg aggaagccag gtccaactcc aagaaagcgg accgggtctt

1260

gtgaagccat cagaaactct ttcactgact tgtactgtga gcggagtgtc tctccccgat

1320

tacggggtgt cttggatcag acagccaccg gggaagggtc tggaatggat tggagtgatt

1380

tggggctctg agactactta ctactcttca tccctcaagt cacgcgtcac catctcaaag

1440

gacaactcta agaatcaggt gtcactgaaa ctgtcatctg tgaccgcagc cgacaccgcc

1500

gtgtactatt gcgctaagca ttactattat ggcgggagct acgcaatgga ttactgggga

1560

cagggtactc tggtcaccgt gtccagcacc actaccccag caccgaggcc acccaccccg

1620

gctcctacca tcgcctccca gcctctgtcc ctgcgtccgg aggcatgtag acccgcagct

1680

ggtggggccg tgcatacccg gggtcttgac ttcgcctgcg atatctacat ttgggcccct

1740

ctggctggta cttgcggggt cctgctgctt tcactcgtga tcactcttta ctgtaagcgc

1800

ggtcggaaga agctgctgta catctttaag caacccttca tgaggcctgt gcagactact

1860

caagaggagg acggctgttc atgccggttc ccagaggagg aggaaggcgg ctgcgaactg

1920

cgcgtgaaat tcagccgcag cgcagatgct ccagcctacc agcaggggca gaaccagctc

1980

tacaacgaac tcaatcttgg tcggagagag gagtacgacg tgctggacaa gcggagagga

2040

cgggacccag aaatgggcgg gaagccgcgc agaaagaatc cccaagaggg cctgtacaac

2100

gagctccaaa aggataagat ggcagaagcc tatagcgaga ttggtatgaa aggggaacgc

2160

agaagaggca aaggccacga cggactgtac cagggactca gcaccgccac caaggacacc

2220

tatgacgctc ttcacatgca ggccctgccg cctcgg

2256

<210> 1100

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1100

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

900

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

960

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

1020

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

1080

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

1140

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

1200

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

1260

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

1320

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

1380

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1440

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1500

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1560

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1101

<211> 2238

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1101

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaaattg tgatgaccca gtcacccgcc actcttagcc tttcacccgg tgagcgcgca

900

accctgtctt gcagagcctc ccaagacatc tcaaaatacc ttaattggta tcaacagaag

960

ccgggacagg ctcctcgcct tctgatctac cacaccagcc ggctccattc tggaatccct

1020

gccaggttca gcggtagcgg atctgggacc gactacaccc tcactatcag ctcactgcag

1080

ccagaggact tcgctgtcta tttctgtcag caagggaaca ccctgcccta caccttttgga

1140

cagggcacca agctcgagat taaaggtgga ggtggcagcg gaggaggtgg gtccggcggt

1200

ggaggaagcc aggtccaact ccaagaaagc ggaccgggtc ttgtgaagcc atcagaaact

1260

ctttcactga cttgtactgt gagcggagtg tctctccccg attacggggt gtcttggatc

1320

agacagccac cggggaaggg tctggaatgg attggagtga tttggggctc tgagactact

1380

tactactctt catccctcaa gtcacgcgtc accatctcaa aggacaactc taagaatcag

1440

gtgtcactga aactgtcatc tgtgaccgca gccgacaccg ccgtgtacta ttgcgctaag

1500

cattactatt atggcgggag ctacgcaatg gattactggg gacagggtac tctggtcacc

1560

gtgtccagca ccactacccc agcaccgagg ccacccaccc cggctcctac catcgcctcc

1620

cagcctctgt ccctgcgtcc ggaggcatgt agacccgcag ctggtggggc cgtgcatacc

1680

cggggtcttg acttcgcctg cgatatctac atttgggccc ctctggctgg tacttgcggg

1740

gtcctgctgc tttcactcgt gatcactctt tactgtaagc gcggtcggaa gaagctgctg

1800

tacatcttta agcaaccctt catgaggcct gtgcagacta ctcaagagga ggacggctgt

1860

tcatgccggt tcccagagga ggaggaaggc ggctgcgaac tgcgcgtgaa attcagccgc

1920

agcgcagatg ctccagccta ccagcagggg cagaaccagc tctacaacga actcaatctt

1980

ggtcggagag aggagtacga cgtgctggac aagcggagag gacgggaccc agaaatgggc

2040

gggaagccgc gcagaaagaa tccccaagag ggcctgtaca acgagctcca aaaggataag

2100

atggcagaag cctatagcga gattggtatg aaaggggaac gcagaagagg caaaggccac

2160

gacggactgt accagggact cagcaccgcc acccaaggaca cctatgacgc tcttcacatg

2220

caggccctgc cgcctcgg

2238

<210> 1102

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1102

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tcaagtgcaa ctcgtccaaa gcggagcggga agtcaagaaa

900

cccggagcga gcgtgaaagt gtcctgcaaa gcctccggct acacctttac gggctactac

960

atgcactggg tgcgccaggc accaggacag ggtcttgaat ggatgggatg gatcaaccct

1020

aattcgggcg gaactaacta cgcacagaag ttccagggga gagtgactct gactcgggat

1080

acctccatct caactgtcta catggaactc tcccgcttgc ggtcagatga tacggcagtg

1140

tactactgcg cccgcgacat gaatatcctg gctaccgtgc cgttcgacat ctggggacag

1200

gggactatgg ttactgtctc atcgggcggt ggaggttcag gaggaggcgg ctcgggaggc

1260

ggaggttcgg acattcagat gacccagtcc ccatcctctc tgtcggccag cgtcggagat

1320

agggtgacca ttacctgtcg ggcctcgcaa agcatctcct cgtacctcaa ctggtatcag

1380

caaaagccgg gaaaggcgcc taagctgctg atctacgccg cttcgagctt gcaaagcggg

1440

gtgccatcca gattctcggg atcaggctca ggaaccgact tcaccctgac cgtgaacagc

1500

ctccagccgg aggactttgc cacttactac tgccagcagg gagactccgt gccgcttact

1560

ttcgggggggg gtacccgcct ggagatcaag accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatgggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 1103

<211> 2259

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1103

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tcaagtgcaa ctcgtccaaa gcggagcggga agtcaagaaa

900

cccggagcga gcgtgaaagt gtcctgcaaa gcctccggct acacctttac gggctactac

960

atgcactggg tgcgccaggc accaggacag ggtcttgaat ggatgggatg gatcaaccct

1020

aattcgggcg gaactaacta cgcacagaag ttccagggga gagtgactct gactcgggat

1080

acctccatct caactgtcta catggaactc tcccgcttgc ggtcagatga tacggcagtg

1140

tactactgcg cccgcgacat gaatatcctg gctaccgtgc cgttcgacat ctggggacag

1200

gggactatgg ttactgtctc atcgggcggt ggaggttcag gaggaggcgg ctcgggaggc

1260

ggaggttcgg acattcagat gacccagtcc ccatcctctc tgtcggccag cgtcggagat

1320

agggtgacca ttacctgtcg ggcctcgcaa agcatctcct cgtacctcaa ctggtatcag

1380

caaaagccgg gaaaggcgcc taagctgctg atctacgccg cttcgagctt gcaaagcggg

1440

gtgccatcca gattctcggg atcaggctca ggaaccgact tcaccctgac cgtgaacagc

1500

ctccagccgg aggactttgc cacttactac tgccagcagg gagactccgt gccgcttact

1560

ttcgggggggg gtacccgcct ggagatcaag accactaccc cagcaccgag gccacccacc

1620

ccggctccta ccatcgcctc ccagcctctg tccctgcgtc cggaggcatg tagacccgca

1680

gctggtgggg ccgtgcatac ccggggtctt gacttcgcct gcgatatcta catttgggcc

1740

cctctggctg gtacttgcgg ggtcctgctg ctttcactcg tgatcactct ttactgtaag

1800

cgcggtcgga agaagctgct gtacatcttt aagcaaccct tcatgaggcc tgtgcagact

1860

actcaagagg aggacggctg ttcatgccgg ttcccagagg aggaggaagg cggctgcgaa

1920

ctgcgcgtga aattcagccg cagcgcagat gctccagcct accagcaggg gcagaaccag

1980

ctctacaacg aactcaatct tggtcggaga gaggagtacg acgtgctgga caagcggaga

2040

ggacgggacc cagaaatggg cgggaagccg cgcagaaaga atccccaaga gggcctgtac

2100

aacgagctcc aaaaggataa gatggcagaa gcctatagcg agattggtat gaaaggggaa

2160

cgcagaagag gcaaaggcca cgacggactg taccagggac tcagcaccgc caccaaggac

2220

acctatgacg ctcttcacat gcaggccctg ccgcctcgg

2259

<210> 1104

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1104

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggcaagtgc aactcgtcca aagcggagcg gaagtcaaga aacccggagc gagcgtgaaa

900

gtgtcctgca aagcctccgg ctacaccttt acgggctact acatgcactg ggtgcgccag

960

gcaccaggac agggtcttga atggatggga tggatcaacc ctaattcggg cggaactaac

1020

tacgcacaga agttccaggg gagagtgact ctgactcggg atacctccat ctcaactgtc

1080

tacatggaac tctcccgctt gcggtcagat gatacggcag tgtactactg cgcccgcgac

1140

atgaatatcc tggctaccgt gccgttcgac atctggggac aggggactat ggttactgtc

1200

tcatcgggcg gtggaggttc aggaggaggc ggctcgggag gcggaggttc ggacattcag

1260

atgacccagt ccccatcctc tctgtcggcc agcgtcggag atagggtgac cattacctgt

1320

cgggcctcgc aaagcatctc ctcgtacctc aactggtatc agcaaaagcc gggaaaggcg

1380

cctaagctgc tgatctacgc cgcttcgagc ttgcaaagcg gggtgccatc cagattctcg

1440

ggatcaggct caggaaccga cttcaccctg accgtgaaca gcctccagcc ggaggacttt

1500

gccacttact actgccagca gggagactcc gtgccgctta ctttcggggg gggtacccgc

1560

ctggagatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 1105

<211> 2241

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1105

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cggcaagtgc aactcgtcca aagcggagcg gaagtcaaga aacccggagc gagcgtgaaa

900

gtgtcctgca aagcctccgg ctacaccttt acgggctact acatgcactg ggtgcgccag

960

gcaccaggac agggtcttga atggatggga tggatcaacc ctaattcggg cggaactaac

1020

tacgcacaga agttccaggg gagagtgact ctgactcggg atacctccat ctcaactgtc

1080

tacatggaac tctcccgctt gcggtcagat gatacggcag tgtactactg cgcccgcgac

1140

atgaatatcc tggctaccgt gccgttcgac atctggggac aggggactat ggttactgtc

1200

tcatcgggcg gtggaggttc aggaggaggc ggctcgggag gcggaggttc ggacattcag

1260

atgacccagt ccccatcctc tctgtcggcc agcgtcggag atagggtgac cattacctgt

1320

cgggcctcgc aaagcatctc ctcgtacctc aactggtatc agcaaaagcc gggaaaggcg

1380

cctaagctgc tgatctacgc cgcttcgagc ttgcaaagcg gggtgccatc cagattctcg

1440

ggatcaggct caggaaccga cttcaccctg accgtgaaca gcctccagcc ggaggacttt

1500

gccacttact actgccagca gggagactcc gtgccgctta ctttcggggg gggtacccgc

1560

ctggagatca agaccactac cccagcaccg aggccaccca ccccggctcc taccatcgcc

1620

tcccagcctc tgtccctgcg tcgggaggca tgtagacccg cagctggtgg ggccgtgcat

1680

acccggggtc ttgacttcgc ctgcgatatc tacatttggg cccctctggc tggtacttgc

1740

ggggtcctgc tgctttcact cgtgatcact ctttactgta agcgcggtcg gaagaagctg

1800

ctgtacatct ttaagcaacc cttcatgagg cctgtgcaga ctactcaaga ggaggacggc

1860

tgttcatgcc ggttcccaga ggaggaggaa ggcggctgcg aactgcgcgt gaaattcagc

1920

cgcagcgcag atgctccagc ctaccagcag gggcagaacc agctctacaa cgaactcaat

1980

cttggtcgga gagaggagta cgacgtgctg gacaagcggga gaggacggga cccagaaatg

2040

ggcgggaagc cgcgcagaaa gaatccccaa gagggcctgt acaacgagct ccaaaaggat

2100

aagatggcag aagcctatag cgagattggt atgaaagggg aacgcagaag aggcaaaggc

2160

cacgacggac tgtaccaggg actcagcacc gccaccaagg acacctatga cgctcttcac

2220

atgcaggccc tgccgcctcg g

2241

<210> 1106

<211> 2247

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1106

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaagtgcaa ttggtggaat cagggggagg acttgtgcag

900

cctggaggat cgctgagact gtcatgtgcc gtgtccggct ttgccctgtc caaccacggg

960

atgtcctggg tccgccgcgc gcctggaaag ggcctcgaat gggtgtcggg tattgtgtac

1020

agcggtagca cctactatgc cgcatccgtg aaggggagat tcaccatcag ccgggacaac

1080

tcggaaca ctctgtacct ccaaatgaat tcgctgaggc cagaggacac tgccatctac

1140

tactgctccg cgcatggcgg agagtccgac gtctggggac aggggaccac cgtgaccgtg

1200

tctagcgcgt ccggcggagg cggcagcggg ggtcgggcat cagggggcgg cggatcggac

1260

atccagctca cccagtcccc gagctcgctg tccgcctccg tgggagatcg ggtcaccatc

1320

acgtgccgcg ccagccagtc gatttcctcc tacctgaact ggtaccaaca gaagccggga

1380

aaagccccga agcttctcat ctacgccgcc tcgagcctgc agtcaggagt gccctcacgg

1440

ttctccggct ccggttccgg tactgatttc accctgacca ttttcctccct gcaaccggag

1500

gacttcgcta cttactactg ccagcagtcg tactccaccc cctacacttt cggacaaggc

1560

accaaggtcg aaatcaagac cactacccca gcaccgaggc cacccacccc ggctcctacc

1620

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

1680

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

1740

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1800

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1860

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1920

ttcagccgca gcgcagatgc tccagcctac cagcaggggc agaaccagct ctacaacgaa

1980

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

2040

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

2100

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

2160

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

2220

cttcacatgc aggccctgcc gcctcgg

2247

<210> 1107

<211> 2247

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1107

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cggaaccggc gcggaagacc cccggccctc caggaagcga

840

aggtccctcg gagacgtggg tgaagtgcaa ttggtggaat cagggggagg acttgtgcag

900

cctggaggat cgctgagact gtcatgtgcc gtgtccggct ttgccctgtc caaccacggg

960

atgtcctggg tccgccgcgc gcctggaaag ggcctcgaat gggtgtcggg tattgtgtac

1020

agcggtagca cctactatgc cgcatccgtg aaggggagat tcaccatcag ccgggacaac

1080

tcggaaca ctctgtacct ccaaatgaat tcgctgaggc cagaggacac tgccatctac

1140

tactgctccg cgcatggcgg agagtccgac gtctggggac aggggaccac cgtgaccgtg

1200

tctagcgcgt ccggcggagg cggcagcggg ggtcgggcat cagggggcgg cggatcggac

1260

atccagctca cccagtcccc gagctcgctg tccgcctccg tgggagatcg ggtcaccatc

1320

acgtgccgcg ccagccagtc gatttcctcc tacctgaact ggtaccaaca gaagccggga

1380

aaagccccga agcttctcat ctacgccgcc tcgagcctgc agtcaggagt gccctcacgg

1440

ttctccggct ccggttccgg tactgatttc accctgacca ttttcctccct gcaaccggag

1500

gacttcgcta cttactactg ccagcagtcg tactccaccc cctacacttt cggacaaggc

1560

accaaggtcg aaatcaagac cactacccca gcaccgaggc cacccacccc ggctcctacc

1620

atcgcctccc agcctctgtc cctgcgtccg gaggcatgta gacccgcagc tggtggggcc

1680

gtgcataccc ggggtcttga cttcgcctgc gatatctaca tttgggcccc tctggctggt

1740

acttgcgggg tcctgctgct ttcactcgtg atcactcttt actgtaagcg cggtcggaag

1800

aagctgctgt acatctttaa gcaacccttc atgaggcctg tgcagactac tcaagaggag

1860

gacggctgtt catgccggtt cccagaggag gaggaaggcg gctgcgaact gcgcgtgaaa

1920

ttcagccgca gcgcagatgc tccagcctac cagcaggggc agaaccagct ctacaacgaa

1980

ctcaatcttg gtcggagaga ggagtacgac gtgctggaca agcggagagg acgggaccca

2040

gaaatgggcg ggaagccgcg cagaaagaat ccccaagagg gcctgtacaa cgagctccaa

2100

aaggataaga tggcagaagc ctatagcgag attggtatga aaggggaacg cagaagaggc

2160

aaaggccacg acggactgta ccagggactc agcaccgcca ccaaggacac ctatgacgct

2220

cttcacatgc aggccctgcc gcctcgg

2247

<210> 1108

<211> 2229

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1108

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctggccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgtc caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaagtgc aattggtgga atcaggggga ggacttgtgc agcctggagg atcgctgaga

900

ctgtcatgtg ccgtgtccgg ctttgccctg tccaaccacg ggatgtcctg ggtccgccgc

960

gcgcctggaa agggcctcga atgggtgtcg ggtattgtgt acagcggtag cacctactat

1020

gccgcatccg tgaaggggag attcaccatc agccgggaca actccaggaa cactctgtac

1080

ctccaaatga attcgctgag gccagaggac actgccatct actactgctc cgcgcatggc

1140

ggagagtccg acgtctgggg acaggggacc accgtgaccg tgtctagcgc gtccggcgga

1200

ggcggcagcg ggggtcgggc atcaggggggc ggcggatcgg acatccagct cacccagtcc

1260

ccgagctcgc tgtccgcctc cgtgggagat cgggtcacca tcacgtgccg cgccagccag

1320

tcgatttcct cctacctgaa ctggtaccaa cagaagcccg gaaaagcccc gaagcttctc

1380

atctacgccg cctcgagcct gcagtcagga gtgccctcac ggttctccgg ctccggttcc

1440

ggtactgatt tcaccctgac catttcctcc ctgcaaccgg aggacttcgc tacttactac

1500

tgccagcagt cgtactccac cccctacact ttcggacaag gcaccaaggt cgaaatcaag

1560

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

1620

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

1680

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

1740

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1800

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1860

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1920

gctccagcct accagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1980

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

2040

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

2100

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

2160

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

2220

ccgcctcgg

2229

<210> 1109

<211> 2229

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1109

atggccctcc ctgtcaccgc cctgctgctt ccgctggctc ttctgctcca cgccgctcgg

60

ccccagtcgt tggcactttc cctgactgcc gaccagatgg tgtccgccct tctggacgcc

120

gagcctccaa ttctgtactc ggagtacgat ccgactcgcc cgttctccga agccagcatg

180

atgggcctgt tgactaacct ggcggaccgc gagttggtgc acatgattaa ctgggctaag

240

cgggtgccgg gcttcgtgga cctgaccctg cacgaccaag tgcacctcct ggaatgcgcc

300

tggatggaaa tcctcatgat cggcctcgtg tggagatcca tggagcatcc cggaaagctc

360

ctgtttgcac ccaacctcct gcttgatcgc aaccagggaa aatgcgtgga agggggtgtc

420

gagattttcg acatgctgct cgccacctct tcccggttcc ggatgatgaa tctgcaggga

480

gaagagttcg tgtgtctgaa gtcaatcatc ctgctgaact ccggggtcta taccttcctg

540

agctcgaccc tcaagtcact ggaggaaaaa gaccacatcc atcgcgtgct cgataagatc

600

accgacaccc ttatccatct catggcgaag gctggactga ccctgcaaca gcagcaccag

660

aggctggccc agttgctgct gattctgagc cacatccggc acatgtcgaa caagaggatg

720

gaacacctgt acagcatgaa gtgcaagaac gtcgtgcctc tgtccgatct gctcctggaa

780

atgctggacg cgcacagact cgggacggga gctgaagatc cacgacccag cagaaagcga

840

cgggaagtgc aattggtgga atcaggggga ggacttgtgc agcctggagg atcgctgaga

900

ctgtcatgtg ccgtgtccgg ctttgccctg tccaaccacg ggatgtcctg ggtccgccgc

960

gcgcctggaa agggcctcga atgggtgtcg ggtattgtgt acagcggtag cacctactat

1020

gccgcatccg tgaaggggag attcaccatc agccgggaca actccaggaa cactctgtac

1080

ctccaaatga attcgctgag gccagaggac actgccatct actactgctc cgcgcatggc

1140

ggagagtccg acgtctgggg acaggggacc accgtgaccg tgtctagcgc gtccggcgga

1200

ggcggcagcg ggggtcgggc atcaggggggc ggcggatcgg acatccagct cacccagtcc

1260

ccgagctcgc tgtccgcctc cgtgggagat cgggtcacca tcacgtgccg cgccagccag

1320

tcgatttcct cctacctgaa ctggtaccaa cagaagcccg gaaaagcccc gaagcttctc

1380

atctacgccg cctcgagcct gcagtcagga gtgccctcac ggttctccgg ctccggttcc

1440

ggtactgatt tcaccctgac catttcctcc ctgcaaccgg aggacttcgc tacttactac

1500

tgccagcagt cgtactccac cccctacact ttcggacaag gcaccaaggt cgaaatcaag

1560

accactaccc cagcaccgag gccacccacc ccggctccta ccatcgcctc ccagcctctg

1620

tccctgcgtc cggaggcatg tagacccgca gctggtgggg ccgtgcatac ccggggtctt

1680

gacttcgcct gcgatatcta catttgggcc cctctggctg gtacttgcgg ggtcctgctg

1740

ctttcactcg tgatcactct ttactgtaag cgcggtcgga agaagctgct gtacatcttt

1800

aagcaaccct tcatgaggcc tgtgcagact actcaagagg aggacggctg ttcatgccgg

1860

ttcccagagg aggaggaagg cggctgcgaa ctgcgcgtga aattcagccg cagcgcagat

1920

gctccagcct accagcaggg gcagaaccag ctctacaacg aactcaatct tggtcggaga

1980

gaggagtacg acgtgctgga caagcggaga ggacgggacc cagaaatgggg cgggaagccg

2040

cgcagaaaga atccccaaga gggcctgtac aacgagctcc aaaaggataa gatggcagaa

2100

gcctatagcg agattggtat gaaaggggaa cgcagaagag gcaaaggcca cgacggactg

2160

taccagggac tcagcaccgc caccaaggac acctatgacg ctcttcacat gcaggccctg

2220

ccgcctcgg

2229

<210> 1110

<211> 735

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1110

tcgttggcac tttccctgac tgccgaccag atggtgtccg cccttctgga cgccgagcct

60

ccaattctgt actcggagta cgatccgact cgcccgttct ccgaagccag catgatgggc

120

ctgttgacta acctggcgga ccgcgagttg gtgcacatga ttaactgggc taagcgggtg

180

ccgggcttcg tggacctggc cctgcacgac caagtgcacc tcctggaatg cgcctggatg

240

gaaatcctca tgatcggcct cgtgtggaga tccatggagc atcccggaaa gctcctgttt

300

gcacccaacc tcctgcttga tcgcaaccag ggaaaatgcg tggaaggggg tgtcgagatt

360

ttcgacatgc tgctcgccac ctcttcccgg ttccggatga tgaatctgca gggagaagag

420

ttcgtgtgtc tgaagtcaat catcctgctg aactccgggg tctatacctt cctgagctcg

480

accctcaagt cactggagga aaaagaccac atccatcgcg tgctcgataa gatcaccgac

540

acccttatcc atctcatggc gaaggctgga ctgaccctgc aacagcagca ccagaggctg

600

gcccagttgc tgctgattct gagccacatc cggcacatgt cgtccaagag gatggaacac

660

ctgtacagca tgaagtgcaa gaacgtcgtg cctctgtccg atctgctcct ggaaatgctg

720

gacgcgcaca gactc

735

<210> 1111

<211> 105

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1111

acaaaaaaga agtattcatc cagtgtgcac gaccctaacg gtgaatacat gttcatgaga

60

gcagtgaaca cagccaaaaa atccagactc acagatgtga cccta

105

<210> 1112

<211> 12

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 1112

cgtactaaaa ga

12

<210> 1113

<211> 123

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 1113

aggagtaaga ggagcaggct cctgcacagt gactacatga acatgactcc ccgccgcccc

60

gggccccaccc gcaagcatta ccagccctat gccccaccac gcgacttcgc agcctatcgc

120

tcc

123

<210> 1114

<211> 21

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 1114

Met Gly Leu Leu Gln Leu Leu Ala Phe Ser Phe Leu Ala Leu Cys Arg

1 5 10 15

Ala Arg Val Arg Ala

20

<210> 1115

<211> 21

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 1115

Met Leu Leu Ala Trp Val Gln Ala Phe Leu Val Ser Asn Met Leu Leu

1 5 10 15

Ala Glu Ala Tyr Gly

20

<210> 1116

<211> 21

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 1116

Met Lys Phe Gln Gly Pro Leu Ala Cys Leu Leu Leu Ala Leu Cys Leu

1 5 10 15

Gly Ser Gly Glu Ala

20

<210> 1117

<211> 22

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 1117

Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly

1 5 10 15

Ala Val Phe Val Ser Pro

20

<210> 1118

<211> 35

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1118

Met Gly Thr Val Ser Ser Arg Arg Ser Trp Trp Pro Leu Pro Leu Leu

1 5 10 15

Leu Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ala Arg Ala Gln Glu

20 25 30

Asp Glu Asp

35

<210> 1119

<211> 247

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 1119

Arg Ser Ser Leu Ala Leu Ser Leu Thr Ala Asp Gln Met Val Ser Ala

1 5 10 15

Leu Leu Asp Ala Glu Pro Pro Ile Leu Tyr Ser Glu Tyr Asp Pro Thr

20 25 30

Arg Pro Phe Ser Glu Ala Ser Met Met Gly Leu Leu Thr Asn Leu Ala

35 40 45

Asp Arg Glu Leu Val His Met Ile Asn Trp Ala Lys Arg Val Pro Gly

50 55 60

Phe Val Asp Leu Ala Leu His Asp Gln Val His Leu Leu Glu Cys Ala

65 70 75 80

Trp Met Glu Ile Leu Met Ile Gly Leu Val Trp Arg Ser Met Glu His

85 90 95

Pro Gly Lys Leu Leu Phe Ala Pro Asn Leu Leu Leu Asp Arg Asn Gln

100 105 110

Gly Lys Cys Val Glu Gly Gly Val Glu Ile Phe Asp Met Leu Leu Ala

115 120 125

Thr Ser Ser Arg Phe Arg Met Met Asn Leu Gln Gly Glu Glu Phe Val

130 135 140

Cys Leu Lys Ser Ile Ile Leu Leu Asn Ser Gly Val Tyr Thr Phe Leu

145 150 155 160

Ser Ser Thr Leu Lys Ser Leu Glu Glu Lys Asp His Ile His Arg Val

165 170 175

Leu Asp Lys Ile Thr Asp Thr Leu Ile His Leu Met Ala Lys Ala Gly

180 185 190

Leu Thr Leu Gln Gln Gln His Gln Arg Leu Ala Gln Leu Leu Leu Ile

195 200 205

Leu Ser His Ile Arg His Met Ser Ser Lys Arg Met Glu His Leu Tyr

210 215 220

Ser Met Lys Cys Lys Asn Val Val Pro Leu Ser Asp Leu Leu Leu Glu

225 230 235 240

Met Leu Asp Ala His Arg Leu

245

<210> 1120

<400> 1120

000

<210> 1121

<400> 1121

000

<210> 1122

<400> 1122

000

<210> 1123

<400> 1123

000

<210> 1124

<400> 1124

000

<210> 1125

<400> 1125

000

<210> 1126

<400> 1126

000

<210> 1127

<400> 1127

000

<210> 1128

<400> 1128

000

<210> 1129

<400> 1129

000

<210> 1130

<400> 1130

000

<210> 1131

<400> 1131

000

<210> 1132

<400> 1132

000

<210> 1133

<400> 1133

000

<210> 1134

<400> 1134

000

<210> 1135

<400> 1135

000

<210> 1136

<400> 1136

000

<210> 1137

<400> 1137

000

<210> 1138

<400> 1138

000

<210> 1139

<400> 1139

000

<210> 1140

<400> 1140

000

<210> 1141

<400> 1141

000

<210> 1142

<400> 1142

000

<210> 1143

<400> 1143

000

<210> 1144

<400> 1144

000

<210> 1145

<400> 1145

000

<210> 1146

<400> 1146

000

<210> 1147

<400> 1147

000

<210> 1148

<400> 1148

000

<210> 1149

<400> 1149

000

<210> 1150

<400> 1150

000

<210> 1151

<400> 1151

000

<210> 1152

<400> 1152

000

<210> 1153

<400> 1153

000

<210> 1154

<400> 1154

000

<210> 1155

<400> 1155

000

<210> 1156

<400> 1156

000

<210> 1157

<400> 1157

000

<210> 1158

<400> 1158

000

<210> 1159

<400> 1159

000

<210> 1160

<400> 1160

000

<210> 1161

<400> 1161

000

<210> 1162

<400> 1162

000

<210> 1163

<400> 1163

000

<210> 1164

<400> 1164

000

<210> 1165

<400> 1165

000

<210> 1166

<400> 1166

000

<210> 1167

<400> 1167

000

<210> 1168

<400> 1168

000

<210> 1169

<400> 1169

000

<210> 1170

<400> 1170

000

<210> 1171

<400> 1171

000

<210> 1172

<400> 1172

000

<210> 1173

<400> 1173

000

<210> 1174

<400> 1174

000

<210> 1175

<400> 1175

000

<210> 1176

<400> 1176

000

<210> 1177

<400> 1177

000

<210> 1178

<400> 1178

000

<210> 1179

<400> 1179

000

<210> 1180

<400> 1180

000

<210> 1181

<400> 1181

000

<210> 1182

<400> 1182

000

<210> 1183

<400> 1183

000

<210> 1184

<400> 1184

000

<210> 1185

<400> 1185

000

<210> 1186

<400> 1186

000

<210> 1187

<400> 1187

000

<210> 1188

<400> 1188

000

<210> 1189

<400> 1189

000

<210> 1190

<400> 1190

000

<210> 1191

<400> 1191

000

<210> 1192

<400> 1192

000

<210> 1193

<400> 1193

000

<210> 1194

<400> 1194

000

<210> 1195

<400> 1195

000

<210> 1196

<400> 1196

000

<210> 1197

<400> 1197

000

<210> 1198

<400> 1198

000

<210> 1199

<400> 1199

000

<210> 1200

<400> 1200

000

<210> 1201

<400> 1201

000

<210> 1202

<400> 1202

000

<210> 1203

<400> 1203

000

<210> 1204

<400> 1204

000

<210> 1205

<400> 1205

000

<210> 1206

<400> 1206

000

<210> 1207

<400> 1207

000

<210> 1208

<400> 1208

000

<210> 1209

<400> 1209

000

<210> 1210

<400> 1210

000

<210> 1211

<400> 1211

000

<210> 1212

<400> 1212

000

<210> 1213

<400> 1213

000

<210> 1214

<400> 1214

000

<210> 1215

<400> 1215

000

<210> 1216

<400> 1216

000

<210> 1217

<400> 1217

000

<210> 1218

<400> 1218

000

<210> 1219

<400> 1219

000

<210> 1220

<400> 1220

000

<210> 1221

<400> 1221

000

<210> 1222

<400> 1222

000

<210> 1223

<400> 1223

000

<210> 1224

<400> 1224

000

<210> 1225

<400> 1225

000

<210> 1226

<400> 1226

000

<210> 1227

<400> 1227

000

<210> 1228

<400> 1228

000

<210> 1229

<400> 1229

000

<210> 1230

<400> 1230

000

<210> 1231

<400> 1231

000

<210> 1232

<400> 1232

000

<210> 1233

<400> 1233

000

<210> 1234

<400> 1234

000

<210> 1235

<400> 1235

000

<210> 1236

<400> 1236

000

<210> 1237

<400> 1237

000

<210> 1238

<400> 1238

000

<210> 1239

<400> 1239

000

<210> 1240

<400> 1240

000

<210> 1241

<400> 1241

000

<210> 1242

<400> 1242

000

<210> 1243

<400> 1243

000

<210> 1244

<400> 1244

000

<210> 1245

<400> 1245

000

<210> 1246

<400> 1246

000

<210> 1247

<400> 1247

000

<210> 1248

<400> 1248

000

<210> 1249

<400> 1249

000

<210> 1250

<400> 1250

000

<210> 1251

<400> 1251

000

<210> 1252

<400> 1252

000

<210> 1253

<400> 1253

000

<210> 1254

<400> 1254

000

<210> 1255

<400> 1255

000

<210> 1256

<400> 1256

000

<210> 1257

<400> 1257

000

<210> 1258

<400> 1258

000

<210> 1259

<400> 1259

000

<210> 1260

<400> 1260

000

<210> 1261

<400> 1261

000

<210> 1262

<400> 1262

000

<210> 1263

<400> 1263

000

<210> 1264

<400> 1264

000

<210> 1265

<400> 1265

000

<210> 1266

<400> 1266

000

<210> 1267

<400> 1267

000

<210> 1268

<400> 1268

000

<210> 1269

<400> 1269

000

<210> 1270

<400> 1270

000

<210> 1271

<400> 1271

000

<210> 1272

<400> 1272

000

<210> 1273

<400> 1273

000

<210> 1274

<400> 1274

000

<210> 1275

<400> 1275

000

<210> 1276

<400> 1276

000

<210> 1277

<400> 1277

000

<210> 1278

<400> 1278

000

<210> 1279

<400> 1279

000

<210> 1280

<400> 1280

000

<210> 1281

<400> 1281

000

<210> 1282

<400> 1282

000

<210> 1283

<400> 1283

000

<210> 1284

<400> 1284

000

<210> 1285

<400> 1285

000

<210> 1286

<400> 1286

000

<210> 1287

<400> 1287

000

<210> 1288

<400> 1288

000

<210> 1289

<400> 1289

000

<210> 1290

<400> 1290

000

<210> 1291

<400> 1291

000

<210> 1292

<400> 1292

000

<210> 1293

<400> 1293

000

<210> 1294

<400> 1294

000

<210> 1295

<400> 1295

000

<210> 1296

<400> 1296

000

<210> 1297

<400> 1297

000

<210> 1298

<400> 1298

000

<210> 1299

<400> 1299

000

<210> 1300

<400> 1300

000

<210> 1301

<400> 1301

000

<210> 1302

<400> 1302

000

<210> 1303

<400> 1303

000

<210> 1304

<400> 1304

000

<210> 1305

<400> 1305

000

<210> 1306

<400> 1306

000

<210> 1307

<400> 1307

000

<210> 1308

<400> 1308

000

<210> 1309

<400> 1309

000

<210> 1310

<400> 1310

000

<210> 1311

<400> 1311

000

<210> 1312

<400> 1312

000

<210> 1313

<400> 1313

000

<210> 1314

<400> 1314

000

<210> 1315

<400> 1315

000

<210> 1316

<400> 1316

000

<210> 1317

<400> 1317

000

<210> 1318

<400> 1318

000

<210> 1319

<400> 1319

000

<210> 1320

<400> 1320

000

<210> 1321

<400> 1321

000

<210> 1322

<400> 1322

000

<210> 1323

<400> 1323

000

<210> 1324

<400> 1324

000

<210> 1325

<400> 1325

000

<210> 1326

<400> 1326

000

<210> 1327

<400> 1327

000

<210> 1328

<400> 1328

000

<210> 1329

<400> 1329

000

<210> 1330

<400> 1330

000

<210> 1331

<400> 1331

000

<210> 1332

<400> 1332

000

<210> 1333

<400> 1333

000

<210> 1334

<400> 1334

000

<210> 1335

<400> 1335

000

<210> 1336

<400> 1336

000

<210> 1337

<400> 1337

000

<210> 1338

<400> 1338

000

<210> 1339

<400> 1339

000

<210> 1340

<400> 1340

000

<210> 1341

<400> 1341

000

<210> 1342

<400> 1342

000

<210> 1343

<400> 1343

000

<210> 1344

<400> 1344

000

<210> 1345

<400> 1345

000

<210> 1346

<400> 1346

000

<210> 1347

<400> 1347

000

<210> 1348

<400> 1348

000

<210> 1349

<400> 1349

000

<210> 1350

<400> 1350

000

<210> 1351

<400> 1351

000

<210> 1352

<400> 1352

000

<210> 1353

<400> 1353

000

<210> 1354

<400> 1354

000

<210> 1355

<400> 1355

000

<210> 1356

<400> 1356

000

<210> 1357

<400> 1357

000

<210> 1358

<400> 1358

000

<210> 1359

<400> 1359

000

<210> 1360

<400> 1360

000

<210> 1361

<400> 1361

000

<210> 1362

<400> 1362

000

<210> 1363

<400> 1363

000

<210> 1364

<400> 1364

000

<210> 1365

<400> 1365

000

<210> 1366

<400> 1366

000

<210> 1367

<400> 1367

000

<210> 1368

<400> 1368

000

<210> 1369

<400> 1369

000

<210> 1370

<400> 1370

000

<210> 1371

<400> 1371

000

<210> 1372

<400> 1372

000

<210> 1373

<400> 1373

000

<210> 1374

<400> 1374

000

<210> 1375

<400> 1375

000

<210> 1376

<400> 1376

000

<210> 1377

<400> 1377

000

<210> 1378

<400> 1378

000

<210> 1379

<400> 1379

000

<210> 1380

<400> 1380

000

<210> 1381

<400> 1381

000

<210> 1382

<400> 1382

000

<210> 1383

<400> 1383

000

<210> 1384

<400> 1384

000

<210> 1385

<400> 1385

000

<210> 1386

<400> 1386

000

<210> 1387

<400> 1387

000

<210> 1388

<400> 1388

000

<210> 1389

<400> 1389

000

<210> 1390

<400> 1390

000

<210> 1391

<400> 1391

000

<210> 1392

<400> 1392

000

<210> 1393

<400> 1393

000

<210> 1394

<400> 1394

000

<210> 1395

<400> 1395

000

<210> 1396

<400> 1396

000

<210> 1397

<400> 1397

000

<210> 1398

<400> 1398

000

<210> 1399

<400> 1399

000

<210> 1400

<400> 1400

000

<210> 1401

<400> 1401

000

<210> 1402

<400> 1402

000

<210> 1403

<400> 1403

000

<210> 1404

<400> 1404

000

<210> 1405

<400> 1405

000

<210> 1406

<400> 1406

000

<210> 1407

<400> 1407

000

<210> 1408

<400> 1408

000

<210> 1409

<400> 1409

000

<210> 1410

<400> 1410

000

<210> 1411

<400> 1411

000

<210> 1412

<400> 1412

000

<210> 1413

<400> 1413

000

<210> 1414

<400> 1414

000

<210> 1415

<400> 1415

000

<210> 1416

<400> 1416

000

<210> 1417

<400> 1417

000

<210> 1418

<400> 1418

000

<210> 1419

<400> 1419

000

<210> 1420

<400> 1420

000

<210> 1421

<400> 1421

000

<210> 1422

<400> 1422

000

<210> 1423

<400> 1423

000

<210> 1424

<400> 1424

000

<210> 1425

<400> 1425

000

<210> 1426

<400> 1426

000

<210> 1427

<400> 1427

000

<210> 1428

<400> 1428

000

<210> 1429

<400> 1429

000

<210> 1430

<400> 1430

000

<210> 1431

<400> 1431

000

<210> 1432

<400> 1432

000

<210> 1433

<400> 1433

000

<210> 1434

<400> 1434

000

<210> 1435

<400> 1435

000

<210> 1436

<400> 1436

000

<210> 1437

<400> 1437

000

<210> 1438

<400> 1438

000

<210> 1439

<400> 1439

000

<210> 1440

<400> 1440

000

<210> 1441

<400> 1441

000

<210> 1442

<400> 1442

000

<210> 1443

<400> 1443

000

<210> 1444

<400> 1444

000

<210> 1445

<400> 1445

000

<210> 1446

<400> 1446

000

<210> 1447

<400> 1447

000

<210> 1448

<400> 1448

000

<210> 1449

<400> 1449

000

<210> 1450

<400> 1450

000

<210> 1451

<400> 1451

000

<210> 1452

<400> 1452

000

<210> 1453

<400> 1453

000

<210> 1454

<400> 1454

000

<210> 1455

<400> 1455

000

<210> 1456

<400> 1456

000

<210> 1457

<400> 1457

000

<210> 1458

<400> 1458

000

<210> 1459

<400> 1459

000

<210> 1460

<400> 1460

000

<210> 1461

<400> 1461

000

<210> 1462

<400> 1462

000

<210> 1463

<400> 1463

000

<210> 1464

<400> 1464

000

<210> 1465

<400> 1465

000

<210> 1466

<400> 1466

000

<210> 1467

<400> 1467

000

<210> 1468

<400> 1468

000

<210> 1469

<400> 1469

000

<210> 1470

<400> 1470

000

<210> 1471

<400> 1471

000

<210> 1472

<400> 1472

000

<210> 1473

<400> 1473

000

<210> 1474

<400> 1474

000

<210> 1475

<400> 1475

000

<210> 1476

<400> 1476

000

<210> 1477

<400> 1477

000

<210> 1478

<400> 1478

000

<210> 1479

<400> 1479

000

<210> 1480

<400> 1480

000

<210> 1481

<400> 1481

000

<210> 1482

<400> 1482

000

<210> 1483

<400> 1483

000

<210> 1484

<400> 1484

000

<210> 1485

<400> 1485

000

<210> 1486

<400> 1486

000

<210> 1487

<400> 1487

000

<210> 1488

<400> 1488

000

<210> 1489

<400> 1489

000

<210> 1490

<400> 1490

000

<210> 1491

<400> 1491

000

<210> 1492

<400> 1492

000

<210> 1493

<400> 1493

000

<210> 1494

<400> 1494

000

<210> 1495

<400> 1495

000

<210> 1496

<400> 1496

000

<210> 1497

<400> 1497

000

<210> 1498

<400> 1498

000

<210> 1499

<400> 1499

000

<210> 1500

<400> 1500

000

<210> 1501

<400> 1501

000

<210> 1502

<400> 1502

000

<210> 1503

<400> 1503

000

<210> 1504

<400> 1504

000

<210> 1505

<400> 1505

000

<210> 1506

<400> 1506

000

<210> 1507

<400> 1507

000

<210> 1508

<400> 1508

000

<210> 1509

<400> 1509

000

<210> 1510

<400> 1510

000

<210> 1511

<400> 1511

000

<210> 1512

<400> 1512

000

<210> 1513

<400> 1513

000

<210> 1514

<400> 1514

000

<210> 1515

<400> 1515

000

<210> 1516

<400> 1516

000

<210> 1517

<400> 1517

000

<210> 1518

<400> 1518

000

<210> 1519

<400> 1519

000

<210> 1520

<400> 1520

000

<210> 1521

<400> 1521

000

<210> 1522

<400> 1522

000

<210> 1523

<400> 1523

000

<210> 1524

<400> 1524

000

<210> 1525

<400> 1525

000

<210> 1526

<400> 1526

000

<210> 1527

<400> 1527

000

<210> 1528

<400> 1528

000

<210> 1529

<400> 1529

000

<210> 1530

<400> 1530

000

<210> 1531

<400> 1531

000

<210> 1532

<400> 1532

000

<210> 1533

<400> 1533

000

<210> 1534

<400> 1534

000

<210> 1535

<400> 1535

000

<210> 1536

<400> 1536

000

<210> 1537

<400> 1537

000

<210> 1538

<400> 1538

000

<210> 1539

<400> 1539

000

<210> 1540

<400> 1540

000

<210> 1541

<400> 1541

000

<210> 1542

<400> 1542

000

<210> 1543

<400> 1543

000

<210> 1544

<400> 1544

000

<210> 1545

<400> 1545

000

<210> 1546

<400> 1546

000

<210> 1547

<400> 1547

000

<210> 1548

<400> 1548

000

<210> 1549

<400> 1549

000

<210> 1550

<400> 1550

000

<210> 1551

<400> 1551

000

<210> 1552

<400> 1552

000

<210> 1553

<400> 1553

000

<210> 1554

<400> 1554

000

<210> 1555

<400> 1555

000

<210> 1556

<400> 1556

000

<210> 1557

<400> 1557

000

<210> 1558

<400> 1558

000

<210> 1559

<400> 1559

000

<210> 1560

<400> 1560

000

<210> 1561

<400> 1561

000

<210> 1562

<400> 1562

000

<210> 1563

<400> 1563

000

<210> 1564

<400> 1564

000

<210> 1565

<400> 1565

000

<210> 1566

<400> 1566

000

<210> 1567

<400> 1567

000

<210> 1568

<400> 1568

000

<210> 1569

<400> 1569

000

<210> 1570

<400> 1570

000

<210> 1571

<400> 1571

000

<210> 1572

<400> 1572

000

<210> 1573

<400> 1573

000

<210> 1574

<400> 1574

000

<210> 1575

<400> 1575

000

<210> 1576

<400> 1576

000

<210> 1577

<400> 1577

000

<210> 1578

<400> 1578

000

<210> 1579

<400> 1579

000

<210> 1580

<400> 1580

000

<210> 1581

<400> 1581

000

<210> 1582

<400> 1582

000

<210> 1583

<400> 1583

000

<210> 1584

<400> 1584

000

<210> 1585

<400> 1585

000

<210> 1586

<400> 1586

000

<210> 1587

<400> 1587

000

<210> 1588

<400> 1588

000

<210> 1589

<400> 1589

000

<210> 1590

<400> 1590

000

<210> 1591

<400> 1591

000

<210> 1592

<400> 1592

000

<210> 1593

<400> 1593

000

<210> 1594

<400> 1594

000

<210> 1595

<400> 1595

000

<210> 1596

<400> 1596

000

<210> 1597

<400> 1597

000

<210> 1598

<400> 1598

000

<210> 1599

<400> 1599

000

<210> 1600

<400> 1600

000

<210> 1601

<400> 1601

000

<210> 1602

<400> 1602

000

<210> 1603

<400> 1603

000

<210> 1604

<400> 1604

000

<210> 1605

<400> 1605

000

<210> 1606

<400> 1606

000

<210> 1607

<400> 1607

000

<210> 1608

<400> 1608

000

<210> 1609

<400> 1609

000

<210> 1610

<400> 1610

000

<210> 1611

<400> 1611

000

<210> 1612

<400> 1612

000

<210> 1613

<400> 1613

000

<210> 1614

<400> 1614

000

<210> 1615

<400> 1615

000

<210> 1616

<400> 1616

000

<210> 1617

<400> 1617

000

<210> 1618

<400> 1618

000

<210> 1619

<400> 1619

000

<210> 1620

<400> 1620

000

<210> 1621

<400> 1621

000

<210> 1622

<400> 1622

000

<210> 1623

<400> 1623

000

<210> 1624

<400> 1624

000

<210> 1625

<400> 1625

000

<210> 1626

<400> 1626

000

<210> 1627

<400> 1627

000

<210> 1628

<400> 1628

000

<210> 1629

<400> 1629

000

<210> 1630

<400> 1630

000

<210> 1631

<400> 1631

000

<210> 1632

<400> 1632

000

<210> 1633

<400> 1633

000

<210> 1634

<400> 1634

000

<210> 1635

<400> 1635

000

<210> 1636

<400> 1636

000

<210> 1637

<400> 1637

000

<210> 1638

<400> 1638

000

<210> 1639

<400> 1639

000

<210> 1640

<400> 1640

000

<210> 1641

<400> 1641

000

<210> 1642

<400> 1642

000

<210> 1643

<400> 1643

000

<210> 1644

<400> 1644

000

<210> 1645

<400> 1645

000

<210> 1646

<400> 1646

000

<210> 1647

<400> 1647

000

<210> 1648

<400> 1648

000

<210> 1649

<400> 1649

000

<210> 1650

<400> 1650

000

<210> 1651

<400> 1651

000

<210> 1652

<400> 1652

000

<210> 1653

<400> 1653

000

<210> 1654

<400> 1654

000

<210> 1655

<400> 1655

000

<210> 1656

<400> 1656

000

<210> 1657

<400> 1657

000

<210> 1658

<400> 1658

000

<210> 1659

<400> 1659

000

<210> 1660

<400> 1660

000

<210> 1661

<400> 1661

000

<210> 1662

<400> 1662

000

<210> 1663

<400> 1663

000

<210> 1664

<400> 1664

000

<210> 1665

<400> 1665

000

<210> 1666

<400> 1666

000

<210> 1667

<400> 1667

000

<210> 1668

<400> 1668

000

<210> 1669

<400> 1669

000

<210> 1670

<400> 1670

000

<210> 1671

<400> 1671

000

<210> 1672

<400> 1672

000

<210> 1673

<400> 1673

000

<210> 1674

<400> 1674

000

<210> 1675

<400> 1675

000

<210> 1676

<400> 1676

000

<210> 1677

<400> 1677

000

<210> 1678

<400> 1678

000

<210> 1679

<400> 1679

000

<210> 1680

<400> 1680

000

<210> 1681

<400> 1681

000

<210> 1682

<400> 1682

000

<210> 1683

<400> 1683

000

<210> 1684

<400> 1684

000

<210> 1685

<400> 1685

000

<210> 1686

<400> 1686

000

<210> 1687

<400> 1687

000

<210> 1688

<400> 1688

000

<210> 1689

<400> 1689

000

<210> 1690

<400> 1690

000

<210> 1691

<400> 1691

000

<210> 1692

<400> 1692

000

<210> 1693

<400> 1693

000

<210> 1694

<400> 1694

000

<210> 1695

<400> 1695

000

<210> 1696

<400> 1696

000

<210> 1697

<400> 1697

000

<210> 1698

<400> 1698

000

<210> 1699

<400> 1699

000

<210> 1700

<400> 1700

000

<210> 1701

<400> 1701

000

<210> 1702

<400> 1702

000

<210> 1703

<400> 1703

000

<210> 1704

<400> 1704

000

<210> 1705

<400> 1705

000

<210> 1706

<400> 1706

000

<210> 1707

<400> 1707

000

<210> 1708

<400> 1708

000

<210> 1709

<400> 1709

000

<210> 1710

<400> 1710

000

<210> 1711

<400> 1711

000

<210> 1712

<400> 1712

000

<210> 1713

<400> 1713

000

<210> 1714

<400> 1714

000

<210> 1715

<400> 1715

000

<210> 1716

<400> 1716

000

<210> 1717

<400> 1717

000

<210> 1718

<400> 1718

000

<210> 1719

<400> 1719

000

<210> 1720

<400> 1720

000

<210> 1721

<400> 1721

000

<210> 1722

<400> 1722

000

<210> 1723

<400> 1723

000

<210> 1724

<400> 1724

000

<210> 1725

<400> 1725

000

<210> 1726

<400> 1726

000

<210> 1727

<400> 1727

000

<210> 1728

<400> 1728

000

<210> 1729

<400> 1729

000

<210> 1730

<400> 1730

000

<210> 1731

<400> 1731

000

<210> 1732

<400> 1732

000

<210> 1733

<400> 1733

000

<210> 1734

<400> 1734

000

<210> 1735

<400> 1735

000

<210> 1736

<400> 1736

000

<210> 1737

<400> 1737

000

<210> 1738

<400> 1738

000

<210> 1739

<400> 1739

000

<210> 1740

<400> 1740

000

<210> 1741

<400> 1741

000

<210> 1742

<400> 1742

000

<210> 1743

<400> 1743

000

<210> 1744

<400> 1744

000

<210> 1745

<400> 1745

000

<210> 1746

<400> 1746

000

<210> 1747

<400> 1747

000

<210> 1748

<400> 1748

000

<210> 1749

<400> 1749

000

<210> 1750

<400> 1750

000

<210> 1751

<400> 1751

000

<210> 1752

<400> 1752

000

<210> 1753

<400> 1753

000

<210> 1754

<400> 1754

000

<210> 1755

<400> 1755

000

<210> 1756

<400> 1756

000

<210> 1757

<400> 1757

000

<210> 1758

<400> 1758

000

<210> 1759

<400> 1759

000

<210> 1760

<400> 1760

000

<210> 1761

<400> 1761

000

<210> 1762

<400> 1762

000

<210> 1763

<400> 1763

000

<210> 1764

<400> 1764

000

<210> 1765

<400> 1765

000

<210> 1766

<400> 1766

000

<210> 1767

<400> 1767

000

<210> 1768

<400> 1768

000

<210> 1769

<400> 1769

000

<210> 1770

<400> 1770

000

<210> 1771

<400> 1771

000

<210> 1772

<400> 1772

000

<210> 1773

<400> 1773

000

<210> 1774

<400> 1774

000

<210> 1775

<400> 1775

000

<210> 1776

<400> 1776

000

<210> 1777

<400> 1777

000

<210> 1778

<400> 1778

000

<210> 1779

<400> 1779

000

<210> 1780

<400> 1780

000

<210> 1781

<400> 1781

000

<210> 1782

<400> 1782

000

<210> 1783

<400> 1783

000

<210> 1784

<400> 1784

000

<210> 1785

<400> 1785

000

<210> 1786

<400> 1786

000

<210> 1787

<400> 1787

000

<210> 1788

<400> 1788

000

<210> 1789

<400> 1789

000

<210> 1790

<400> 1790

000

<210> 1791

<400> 1791

000

<210> 1792

<400> 1792

000

<210> 1793

<400> 1793

000

<210> 1794

<400> 1794

000

<210> 1795

<400> 1795

000

<210> 1796

<400> 1796

000

<210> 1797

<400> 1797

000

<210> 1798

<400> 1798

000

<210> 1799

<400> 1799

000

<210> 1800

<400> 1800

000

<210> 1801

<400> 1801

000

<210> 1802

<400> 1802

000

<210> 1803

<400> 1803

000

<210> 1804

<400> 1804

000

<210> 1805

<400> 1805

000

<210> 1806

<400> 1806

000

<210> 1807

<400> 1807

000

<210> 1808

<400> 1808

000

<210> 1809

<400> 1809

000

<210> 1810

<400> 1810

000

<210> 1811

<400> 1811

000

<210> 1812

<400> 1812

000

<210> 1813

<400> 1813

000

<210> 1814

<400> 1814

000

<210> 1815

<400> 1815

000

<210> 1816

<400> 1816

000

<210> 1817

<400> 1817

000

<210> 1818

<400> 1818

000

<210> 1819

<400> 1819

000

<210> 1820

<400> 1820

000

<210> 1821

<400> 1821

000

<210> 1822

<400> 1822

000

<210> 1823

<400> 1823

000

<210> 1824

<400> 1824

000

<210> 1825

<400> 1825

000

<210> 1826

<400> 1826

000

<210> 1827

<400> 1827

000

<210> 1828

<400> 1828

000

<210> 1829

<400> 1829

000

<210> 1830

<400> 1830

000

<210> 1831

<400> 1831

000

<210> 1832

<400> 1832

000

<210> 1833

<400> 1833

000

<210> 1834

<400> 1834

000

<210> 1835

<400> 1835

000

<210> 1836

<400> 1836

000

<210> 1837

<400> 1837

000

<210> 1838

<400> 1838

000

<210> 1839

<400> 1839

000

<210> 1840

<400> 1840

000

<210> 1841

<400> 1841

000

<210> 1842

<400> 1842

000

<210> 1843

<400> 1843

000

<210> 1844

<400> 1844

000

<210> 1845

<400> 1845

000

<210> 1846

<400> 1846

000

<210> 1847

<400> 1847

000

<210> 1848

<400> 1848

000

<210> 1849

<400> 1849

000

<210> 1850

<400> 1850

000

<210> 1851

<400> 1851

000

<210> 1852

<400> 1852

000

<210> 1853

<400> 1853

000

<210> 1854

<400> 1854

000

<210> 1855

<400> 1855

000

<210> 1856

<400> 1856

000

<210> 1857

<400> 1857

000

<210> 1858

<400> 1858

000

<210> 1859

<400> 1859

000

<210> 1860

<400> 1860

000

<210> 1861

<400> 1861

000

<210> 1862

<400> 1862

000

<210> 1863

<400> 1863

000

<210> 1864

<400> 1864

000

<210> 1865

<400> 1865

000

<210> 1866

<400> 1866

000

<210> 1867

<400> 1867

000

<210> 1868

<400> 1868

000

<210> 1869

<400> 1869

000

<210> 1870

<400> 1870

000

<210> 1871

<400> 1871

000

<210> 1872

<400> 1872

000

<210> 1873

<400> 1873

000

<210> 1874

<400> 1874

000

<210> 1875

<400> 1875

000

<210> 1876

<400> 1876

000

<210> 1877

<400> 1877

000

<210> 1878

<400> 1878

000

<210> 1879

<400> 1879

000

<210> 1880

<400> 1880

000

<210> 1881

<400> 1881

000

<210> 1882

<400> 1882

000

<210> 1883

<400> 1883

000

<210> 1884

<400> 1884

000

<210> 1885

<400> 1885

000

<210> 1886

<400> 1886

000

<210> 1887

<400> 1887

000

<210> 1888

<400> 1888

000

<210> 1889

<400> 1889

000

<210> 1890

<400> 1890

000

<210> 1891

<400> 1891

000

<210> 1892

<400> 1892

000

<210> 1893

<400> 1893

000

<210> 1894

<400> 1894

000

<210> 1895

<400> 1895

000

<210> 1896

<400> 1896

000

<210> 1897

<400> 1897

000

<210> 1898

<400> 1898

000

<210> 1899

<400> 1899

000

<210> 1900

<400> 1900

000

<210> 1901

<400> 1901

000

<210> 1902

<400> 1902

000

<210> 1903

<400> 1903

000

<210> 1904

<400> 1904

000

<210> 1905

<400> 1905

000

<210> 1906

<400> 1906

000

<210> 1907

<400> 1907

000

<210> 1908

<400> 1908

000

<210> 1909

<400> 1909

000

<210> 1910

<400> 1910

000

<210> 1911

<400> 1911

000

<210> 1912

<400> 1912

000

<210> 1913

<400> 1913

000

<210> 1914

<400> 1914

000

<210> 1915

<400> 1915

000

<210> 1916

<400> 1916

000

<210> 1917

<400> 1917

000

<210> 1918

<400> 1918

000

<210> 1919

<400> 1919

000

<210> 1920

<400> 1920

000

<210> 1921

<400> 1921

000

<210> 1922

<400> 1922

000

<210> 1923

<400> 1923

000

<210> 1924

<400> 1924

000

<210> 1925

<400> 1925

000

<210> 1926

<400> 1926

000

<210> 1927

<400> 1927

000

<210> 1928

<400> 1928

000

<210> 1929

<400> 1929

000

<210> 1930

<400> 1930

000

<210> 1931

<400> 1931

000

<210> 1932

<400> 1932

000

<210> 1933

<400> 1933

000

<210> 1934

<400> 1934

000

<210> 1935

<400> 1935

000

<210> 1936

<400> 1936

000

<210> 1937

<400> 1937

000

<210> 1938

<400> 1938

000

<210> 1939

<400> 1939

000

<210> 1940

<400> 1940

000

<210> 1941

<400> 1941

000

<210> 1942

<400> 1942

000

<210> 1943

<400> 1943

000

<210> 1944

<400> 1944

000

<210> 1945

<400> 1945

000

<210> 1946

<400> 1946

000

<210> 1947

<400> 1947

000

<210> 1948

<400> 1948

000

<210> 1949

<400> 1949

000

<210> 1950

<400> 1950

000

<210> 1951

<400> 1951

000

<210> 1952

<400> 1952

000

<210> 1953

<400> 1953

000

<210> 1954

<400> 1954

000

<210> 1955

<400> 1955

000

<210> 1956

<400> 1956

000

<210> 1957

<400> 1957

000

<210> 1958

<400> 1958

000

<210> 1959

<400> 1959

000

<210> 1960

<400> 1960

000

<210> 1961

<400> 1961

000

<210> 1962

<400> 1962

000

<210> 1963

<400> 1963

000

<210> 1964

<400> 1964

000

<210> 1965

<400> 1965

000

<210> 1966

<400> 1966

000

<210> 1967

<400> 1967

000

<210> 1968

<400> 1968

000

<210> 1969

<400> 1969

000

<210> 1970

<400> 1970

000

<210> 1971

<400> 1971

000

<210> 1972

<400> 1972

000

<210> 1973

<400> 1973

000

<210> 1974

<400> 1974

000

<210> 1975

<400> 1975

000

<210> 1976

<400> 1976

000

<210> 1977

<400> 1977

000

<210> 1978

<400> 1978

000

<210> 1979

<400> 1979

000

<210> 1980

<400> 1980

000

<210> 1981

<400> 1981

000

<210> 1982

<400> 1982

000

<210> 1983

<400> 1983

000

<210> 1984

<400> 1984

000

<210> 1985

<400> 1985

000

<210> 1986

<400> 1986

000

<210> 1987

<400> 1987

000

<210> 1988

<400> 1988

000

<210> 1989

<400> 1989

000

<210> 1990

<400> 1990

000

<210> 1991

<400> 1991

000

<210> 1992

<400> 1992

000

<210> 1993

<400> 1993

000

<210> 1994

<400> 1994

000

<210> 1995

<400> 1995

000

<210> 1996

<400> 1996

000

<210> 1997

<400> 1997

000

<210> 1998

<400> 1998

000

<210> 1999

<400> 1999

000

<210> 2000

<400> 2000

000

<210> 2001

<400> 2001

000

<210> 2002

<400> 2002

000

<210> 2003

<400> 2003

000

<210> 2004

<400> 2004

000

<210> 2005

<400> 2005

000

<210> 2006

<400> 2006

000

<210> 2007

<400> 2007

000

<210> 2008

<400> 2008

000

<210> 2009

<400> 2009

000

<210> 2010

<400> 2010

000

<210> 2011

<400> 2011

000

<210> 2012

<400> 2012

000

<210> 2013

<400> 2013

000

<210> 2014

<400> 2014

000

<210> 2015

<400> 2015

000

<210> 2016

<400> 2016

000

<210> 2017

<400> 2017

000

<210> 2018

<400> 2018

000

<210> 2019

<400> 2019

000

<210> 2020

<400> 2020

000

<210> 2021

<400> 2021

000

<210> 2022

<400> 2022

000

<210> 2023

<400> 2023

000

<210> 2024

<400> 2024

000

<210> 2025

<400> 2025

000

<210> 2026

<400> 2026

000

<210> 2027

<400> 2027

000

<210> 2028

<400> 2028

000

<210> 2029

<400> 2029

000

<210> 2030

<400> 2030

000

<210> 2031

<400> 2031

000

<210> 2032

<400> 2032

000

<210> 2033

<400> 2033

000

<210> 2034

<400> 2034

000

<210> 2035

<400> 2035

000

<210> 2036

<400> 2036

000

<210> 2037

<400> 2037

000

<210> 2038

<400> 2038

000

<210> 2039

<400> 2039

000

<210> 2040

<400> 2040

000

<210> 2041

<400> 2041

000

<210> 2042

<400> 2042

000

<210> 2043

<400> 2043

000

<210> 2044

<400> 2044

000

<210> 2045

<400> 2045

000

<210> 2046

<400> 2046

000

<210> 2047

<400> 2047

000

<210> 2048

<400> 2048

000

<210> 2049

<400> 2049

000

<210> 2050

<400> 2050

000

<210> 2051

<400> 2051

000

<210> 2052

<400> 2052

000

<210> 2053

<400> 2053

000

<210> 2054

<400> 2054

000

<210> 2055

<400> 2055

000

<210> 2056

<400> 2056

000

<210> 2057

<400> 2057

000

<210> 2058

<400> 2058

000

<210> 2059

<400> 2059

000

<210> 2060

<400> 2060

000

<210> 2061

<400> 2061

000

<210> 2062

<400> 2062

000

<210> 2063

<400> 2063

000

<210> 2064

<400> 2064

000

<210> 2065

<400> 2065

000

<210> 2066

<400> 2066

000

<210> 2067

<400> 2067

000

<210> 2068

<400> 2068

000

<210> 2069

<400> 2069

000

<210> 2070

<400> 2070

000

<210> 2071

<400> 2071

000

<210> 2072

<400> 2072

000

<210> 2073

<400> 2073

000

<210> 2074

<400> 2074

000

<210> 2075

<400> 2075

000

<210> 2076

<400> 2076

000

<210> 2077

<400> 2077

000

<210> 2078

<400> 2078

000

<210> 2079

<400> 2079

000

<210> 2080

<400> 2080

000

<210> 2081

<400> 2081

000

<210> 2082

<400> 2082

000

<210> 2083

<400> 2083

000

<210> 2084

<400> 2084

000

<210> 2085

<400> 2085

000

<210> 2086

<400> 2086

000

<210> 2087

<400> 2087

000

<210> 2088

<400> 2088

000

<210> 2089

<400> 2089

000

<210> 2090

<400> 2090

000

<210> 2091

<400> 2091

000

<210> 2092

<400> 2092

000

<210> 2093

<400> 2093

000

<210> 2094

<400> 2094

000

<210> 2095

<400> 2095

000

<210> 2096

<400> 2096

000

<210> 2097

<400> 2097

000

<210> 2098

<400> 2098

000

<210> 2099

<400> 2099

000

<210> 2100

<400> 2100

000

<210> 2101

<400> 2101

000

<210> 2102

<400> 2102

000

<210> 2103

<400> 2103

000

<210> 2104

<400> 2104

000

<210> 2105

<400> 2105

000

<210> 2106

<400> 2106

000

<210> 2107

<400> 2107

000

<210> 2108

<400> 2108

000

<210> 2109

<400> 2109

000

<210> 2110

<400> 2110

000

<210> 2111

<400> 2111

000

<210> 2112

<400> 2112

000

<210> 2113

<400> 2113

000

<210> 2114

<400> 2114

000

<210> 2115

<400> 2115

000

<210> 2116

<400> 2116

000

<210> 2117

<400> 2117

000

<210> 2118

<400> 2118

000

<210> 2119

<400> 2119

000

<210> 2120

<400> 2120

000

<210> 2121

<400> 2121

000

<210> 2122

<400> 2122

000

<210> 2123

<400> 2123

000

<210> 2124

<400> 2124

000

<210> 2125

<400> 2125

000

<210> 2126

<400> 2126

000

<210> 2127

<400> 2127

000

<210> 2128

<400> 2128

000

<210> 2129

<400> 2129

000

<210> 2130

<400> 2130

000

<210> 2131

<400> 2131

000

<210> 2132

<400> 2132

000

<210> 2133

<400> 2133

000

<210> 2134

<400> 2134

000

<210> 2135

<400> 2135

000

<210> 2136

<400> 2136

000

<210> 2137

<400> 2137

000

<210> 2138

<400> 2138

000

<210> 2139

<400> 2139

000

<210> 2140

<400> 2140

000

<210> 2141

<400> 2141

000

<210> 2142

<400> 2142

000

<210> 2143

<400> 2143

000

<210> 2144

<400> 2144

000

<210> 2145

<400> 2145

000

<210> 2146

<400> 2146

000

<210> 2147

<400> 2147

000

<210> 2148

<400> 2148

000

<210> 2149

<400> 2149

000

<210> 2150

<400> 2150

000

<210> 2151

<400> 2151

000

<210> 2152

<400> 2152

000

<210> 2153

<400> 2153

000

<210> 2154

<400> 2154

000

<210> 2155

<400> 2155

000

<210> 2156

<400> 2156

000

<210> 2157

<400> 2157

000

<210> 2158

<400> 2158

000

<210> 2159

<400> 2159

000

<210> 2160

<400> 2160

000

<210> 2161

<400> 2161

000

<210> 2162

<400> 2162

000

<210> 2163

<400> 2163

000

<210> 2164

<400> 2164

000

<210> 2165

<400> 2165

000

<210> 2166

<400> 2166

000

<210> 2167

<400> 2167

000

<210> 2168

<400> 2168

000

<210> 2169

<400> 2169

000

<210> 2170

<400> 2170

000

<210> 2171

<400> 2171

000

<210> 2172

<400> 2172

000

<210> 2173

<400> 2173

000

<210> 2174

<400> 2174

000

<210> 2175

<400> 2175

000

<210> 2176

<400> 2176

000

<210> 2177

<400> 2177

000

<210> 2178

<400> 2178

000

<210> 2179

<400> 2179

000

<210> 2180

<400> 2180

000

<210> 2181

<400> 2181

000

<210> 2182

<400> 2182

000

<210> 2183

<400> 2183

000

<210> 2184

<400> 2184

000

<210> 2185

<400> 2185

000

<210> 2186

<400> 2186

000

<210> 2187

<400> 2187

000

<210> 2188

<400> 2188

000

<210> 2189

<400> 2189

000

<210> 2190

<400> 2190

000

<210> 2191

<400> 2191

000

<210> 2192

<400> 2192

000

<210> 2193

<400> 2193

000

<210> 2194

<400> 2194

000

<210> 2195

<400> 2195

000

<210> 2196

<400> 2196

000

<210> 2197

<400> 2197

000

<210> 2198

<400> 2198

000

<210> 2199

<400> 2199

000

<210> 2200

<400> 2200

000

<210> 2201

<400> 2201

000

<210> 2202

<400> 2202

000

<210> 2203

<400> 2203

000

<210> 2204

<400> 2204

000

<210> 2205

<400> 2205

000

<210> 2206

<400> 2206

000

<210> 2207

<400> 2207

000

<210> 2208

<400> 2208

000

<210> 2209

<400> 2209

000

<210> 2210

<400> 2210

000

<210> 2211

<400> 2211

000

<210> 2212

<400> 2212

000

<210> 2213

<400> 2213

000

<210> 2214

<400> 2214

000

<210> 2215

<400> 2215

000

<210> 2216

<400> 2216

000

<210> 2217

<400> 2217

000

<210> 2218

<400> 2218

000

<210> 2219

<400> 2219

000

<210> 2220

<400> 2220

000

<210> 2221

<400> 2221

000

<210> 2222

<400> 2222

000

<210> 2223

<400> 2223

000

<210> 2224

<400> 2224

000

<210> 2225

<400> 2225

000

<210> 2226

<400> 2226

000

<210> 2227

<400> 2227

000

<210> 2228

<400> 2228

000

<210> 2229

<400> 2229

000

<210> 2230

<400> 2230

000

<210> 2231

<400> 2231

000

<210> 2232

<400> 2232

000

<210> 2233

<400> 2233

000

<210> 2234

<400> 2234

000

<210> 2235

<400> 2235

000

<210> 2236

<400> 2236

000

<210> 2237

<400> 2237

000

<210> 2238

<400> 2238

000

<210> 2239

<400> 2239

000

<210> 2240

<400> 2240

000

<210> 2241

<400> 2241

000

<210> 2242

<400> 2242

000

<210> 2243

<400> 2243

000

<210> 2244

<400> 2244

000

<210> 2245

<400> 2245

000

<210> 2246

<400> 2246

000

<210> 2247

<400> 2247

000

<210> 2248

<400> 2248

000

<210> 2249

<400> 2249

000

<210> 2250

<400> 2250

000

<210> 2251

<400> 2251

000

<210> 2252

<400> 2252

000

<210> 2253

<400> 2253

000

<210> 2254

<400> 2254

000

<210> 2255

<400> 2255

000

<210> 2256

<400> 2256

000

<210> 2257

<400> 2257

000

<210> 2258

<400> 2258

000

<210> 2259

<400> 2259

000

<210> 2260

<400> 2260

000

<210> 2261

<400> 2261

000

<210> 2262

<400> 2262

000

<210> 2263

<400> 2263

000

<210> 2264

<400> 2264

000

<210> 2265

<400> 2265

000

<210> 2266

<400> 2266

000

<210> 2267

<400> 2267

000

<210> 2268

<400> 2268

000

<210> 2269

<400> 2269

000

<210> 2270

<400> 2270

000

<210> 2271

<400> 2271

000

<210> 2272

<400> 2272

000

<210> 2273

<400> 2273

000

<210> 2274

<400> 2274

000

<210> 2275

<400> 2275

000

<210> 2276

<400> 2276

000

<210> 2277

<400> 2277

000

<210> 2278

<400> 2278

000

<210> 2279

<400> 2279

000

<210> 2280

<400> 2280

000

<210> 2281

<400> 2281

000

<210> 2282

<400> 2282

000

<210> 2283

<400> 2283

000

<210> 2284

<400> 2284

000

<210> 2285

<400> 2285

000

<210> 2286

<400> 2286

000

<210> 2287

<400> 2287

000

<210> 2288

<400> 2288

000

<210> 2289

<400> 2289

000

<210> 2290

<400> 2290

000

<210> 2291

<400> 2291

000

<210> 2292

<400> 2292

000

<210> 2293

<400> 2293

000

<210> 2294

<400> 2294

000

<210> 2295

<400> 2295

000

<210> 2296

<400> 2296

000

<210> 2297

<400> 2297

000

<210> 2298

<400> 2298

000

<210> 2299

<400> 2299

000

<210> 2300

<400> 2300

000

<210> 2301

<400> 2301

000

<210> 2302

<400> 2302

000

<210> 2303

<400> 2303

000

<210> 2304

<400> 2304

000

<210> 2305

<400> 2305

000

<210> 2306

<400> 2306

000

<210> 2307

<400> 2307

000

<210> 2308

<400> 2308

000

<210> 2309

<400> 2309

000

<210> 2310

<400> 2310

000

<210> 2311

<400> 2311

000

<210> 2312

<400> 2312

000

<210> 2313

<400> 2313

000

<210> 2314

<400> 2314

000

<210> 2315

<400> 2315

000

<210> 2316

<400> 2316

000

<210> 2317

<400> 2317

000

<210> 2318

<400> 2318

000

<210> 2319

<400> 2319

000

<210> 2320

<400> 2320

000

<210> 2321

<400> 2321

000

<210> 2322

<400> 2322

000

<210> 2323

<400> 2323

000

<210> 2324

<400> 2324

000

<210> 2325

<400> 2325

000

<210> 2326

<400> 2326

000

<210> 2327

<400> 2327

000

<210> 2328

<400> 2328

000

<210> 2329

<400> 2329

000

<210> 2330

<400> 2330

000

<210> 2331

<400> 2331

000

<210> 2332

<400> 2332

000

<210> 2333

<400> 2333

000

<210> 2334

<400> 2334

000

<210> 2335

<400> 2335

000

<210> 2336

<400> 2336

000

<210> 2337

<400> 2337

000

<210> 2338

<400> 2338

000

<210> 2339

<400> 2339

000

<210> 2340

<400> 2340

000

<210> 2341

<400> 2341

000

<210> 2342

<400> 2342

000

<210> 2343

<400> 2343

000

<210> 2344

<400> 2344

000

<210> 2345

<400> 2345

000

<210> 2346

<400> 2346

000

<210> 2347

<400> 2347

000

<210> 2348

<400> 2348

000

<210> 2349

<400> 2349

000

<210> 2350

<400> 2350

000

<210> 2351

<400> 2351

000

<210> 2352

<400> 2352

000

<210> 2353

<400> 2353

000

<210> 2354

<400> 2354

000

<210> 2355

<400> 2355

000

<210> 2356

<400> 2356

000

<210> 2357

<400> 2357

000

<210> 2358

<400> 2358

000

<210> 2359

<400> 2359

000

<210> 2360

<400> 2360

000

<210> 2361

<400> 2361

000

<210> 2362

<400> 2362

000

<210> 2363

<400> 2363

000

<210> 2364

<400> 2364

000

<210> 2365

<400> 2365

000

<210> 2366

<400> 2366

000

<210> 2367

<400> 2367

000

<210> 2368

<400> 2368

000

<210> 2369

<400> 2369

000

<210> 2370

<400> 2370

000

<210> 2371

<400> 2371

000

<210> 2372

<400> 2372

000

<210> 2373

<400> 2373

000

<210> 2374

<400> 2374

000

<210> 2375

<400> 2375

000

<210> 2376

<400> 2376

000

<210> 2377

<400> 2377

000

<210> 2378

<400> 2378

000

<210> 2379

<400> 2379

000

<210> 2380

<400> 2380

000

<210> 2381

<400> 2381

000

<210> 2382

<400> 2382

000

<210> 2383

<400> 2383

000

<210> 2384

<400> 2384

000

<210> 2385

<400> 2385

000

<210> 2386

<400> 2386

000

<210> 2387

<400> 2387

000

<210> 2388

<400> 2388

000

<210> 2389

<400> 2389

000

<210> 2390

<400> 2390

000

<210> 2391

<400> 2391

000

<210> 2392

<400> 2392

000

<210> 2393

<400> 2393

000

<210> 2394

<400> 2394

000

<210> 2395

<400> 2395

000

<210> 2396

<400> 2396

000

<210> 2397

<400> 2397

000

<210> 2398

<400> 2398

000

<210> 2399

<400> 2399

000

<210> 2400

<400> 2400

000

<210> 2401

<400> 2401

000

<210> 2402

<400> 2402

000

<210> 2403

<400> 2403

000

<210> 2404

<400> 2404

000

<210> 2405

<400> 2405

000

<210> 2406

<400> 2406

000

<210> 2407

<400> 2407

000

<210> 2408

<400> 2408

000

<210> 2409

<400> 2409

000

<210> 2410

<400> 2410

000

<210> 2411

<400> 2411

000

<210> 2412

<400> 2412

000

<210> 2413

<400> 2413

000

<210> 2414

<400> 2414

000

<210> 2415

<400> 2415

000

<210> 2416

<400> 2416

000

<210> 2417

<400> 2417

000

<210> 2418

<400> 2418

000

<210> 2419

<400> 2419

000

<210> 2420

<400> 2420

000

<210> 2421

<400> 2421

000

<210> 2422

<400> 2422

000

<210> 2423

<400> 2423

000

<210> 2424

<400> 2424

000

<210> 2425

<400> 2425

000

<210> 2426

<400> 2426

000

<210> 2427

<400> 2427

000

<210> 2428

<400> 2428

000

<210> 2429

<400> 2429

000

<210> 2430

<400> 2430

000

<210> 2431

<400> 2431

000

<210> 2432

<400> 2432

000

<210> 2433

<400> 2433

000

<210> 2434

<400> 2434

000

<210> 2435

<400> 2435

000

<210> 2436

<400> 2436

000

<210> 2437

<400> 2437

000

<210> 2438

<400> 2438

000

<210> 2439

<400> 2439

000

<210> 2440

<400> 2440

000

<210> 2441

<400> 2441

000

<210> 2442

<400> 2442

000

<210> 2443

<400> 2443

000

<210> 2444

<400> 2444

000

<210> 2445

<400> 2445

000

<210> 2446

<400> 2446

000

<210> 2447

<400> 2447

000

<210> 2448

<400> 2448

000

<210> 2449

<400> 2449

000

<210> 2450

<400> 2450

000

<210> 2451

<400> 2451

000

<210> 2452

<400> 2452

000

<210> 2453

<400> 2453

000

<210> 2454

<400> 2454

000

<210> 2455

<400> 2455

000

<210> 2456

<400> 2456

000

<210> 2457

<400> 2457

000

<210> 2458

<400> 2458

000

<210> 2459

<400> 2459

000

<210> 2460

<400> 2460

000

<210> 2461

<400> 2461

000

<210> 2462

<400> 2462

000

<210> 2463

<400> 2463

000

<210> 2464

<400> 2464

000

<210> 2465

<400> 2465

000

<210> 2466

<400> 2466

000

<210> 2467

<400> 2467

000

<210> 2468

<400> 2468

000

<210> 2469

<400> 2469

000

<210> 2470

<400> 2470

000

<210> 2471

<400> 2471

000

<210> 2472

<400> 2472

000

<210> 2473

<400> 2473

000

<210> 2474

<400> 2474

000

<210> 2475

<400> 2475

000

<210> 2476

<400> 2476

000

<210> 2477

<400> 2477

000

<210> 2478

<400> 2478

000

<210> 2479

<400> 2479

000

<210> 2480

<400> 2480

000

<210> 2481

<400> 2481

000

<210> 2482

<400> 2482

000

<210> 2483

<400> 2483

000

<210> 2484

<400> 2484

000

<210> 2485

<400> 2485

000

<210> 2486

<400> 2486

000

<210> 2487

<400> 2487

000

<210> 2488

<400> 2488

000

<210> 2489

<400> 2489

000

<210> 2490

<400> 2490

000

<210> 2491

<400> 2491

000

<210> 2492

<400> 2492

000

<210> 2493

<400> 2493

000

<210> 2494

<400> 2494

000

<210> 2495

<400> 2495

000

<210> 2496

<400> 2496

000

<210> 2497

<400> 2497

000

<210> 2498

<400> 2498

000

<210> 2499

<400> 2499

000

<210> 2500

<400> 2500

000

<210> 2501

<400> 2501

000

<210> 2502

<400> 2502

000

<210> 2503

<400> 2503

000

<210> 2504

<400> 2504

000

<210> 2505

<400> 2505

000

<210> 2506

<400> 2506

000

<210> 2507

<400> 2507

000

<210> 2508

<400> 2508

000

<210> 2509

<400> 2509

000

<210> 2510

<400> 2510

000

<210> 2511

<400> 2511

000

<210> 2512

<400> 2512

000

<210> 2513

<400> 2513

000

<210> 2514

<400> 2514

000

<210> 2515

<400> 2515

000

<210> 2516

<400> 2516

000

<210> 2517

<400> 2517

000

<210> 2518

<400> 2518

000

<210> 2519

<400> 2519

000

<210> 2520

<400> 2520

000

<210> 2521

<400> 2521

000

<210> 2522

<400> 2522

000

<210> 2523

<400> 2523

000

<210> 2524

<400> 2524

000

<210> 2525

<400> 2525

000

<210> 2526

<400> 2526

000

<210> 2527

<400> 2527

000

<210> 2528

<400> 2528

000

<210> 2529

<400> 2529

000

<210> 2530

<400> 2530

000

<210> 2531

<400> 2531

000

<210> 2532

<400> 2532

000

<210> 2533

<400> 2533

000

<210> 2534

<400> 2534

000

<210> 2535

<400> 2535

000

<210> 2536

<400> 2536

000

<210> 2537

<400> 2537

000

<210> 2538

<400> 2538

000

<210> 2539

<400> 2539

000

<210> 2540

<400> 2540

000

<210> 2541

<400> 2541

000

<210> 2542

<400> 2542

000

<210> 2543

<400> 2543

000

<210> 2544

<400> 2544

000

<210> 2545

<400> 2545

000

<210> 2546

<400> 2546

000

<210> 2547

<400> 2547

000

<210> 2548

<400> 2548

000

<210> 2549

<400> 2549

000

<210> 2550

<400> 2550

000

<210> 2551

<400> 2551

000

<210> 2552

<400> 2552

000

<210> 2553

<400> 2553

000

<210> 2554

<400> 2554

000

<210> 2555

<400> 2555

000

<210> 2556

<400> 2556

000

<210> 2557

<400> 2557

000

<210> 2558

<400> 2558

000

<210> 2559

<400> 2559

000

<210> 2560

<400> 2560

000

<210> 2561

<400> 2561

000

<210> 2562

<400> 2562

000

<210> 2563

<400> 2563

000

<210> 2564

<400> 2564

000

<210> 2565

<400> 2565

000

<210> 2566

<400> 2566

000

<210> 2567

<400> 2567

000

<210> 2568

<400> 2568

000

<210> 2569

<400> 2569

000

<210> 2570

<400> 2570

000

<210> 2571

<400> 2571

000

<210> 2572

<400> 2572

000

<210> 2573

<400> 2573

000

<210> 2574

<400> 2574

000

<210> 2575

<400> 2575

000

<210> 2576

<400> 2576

000

<210> 2577

<400> 2577

000

<210> 2578

<400> 2578

000

<210> 2579

<400> 2579

000

<210> 2580

<400> 2580

000

<210> 2581

<400> 2581

000

<210> 2582

<400> 2582

000

<210> 2583

<400> 2583

000

<210> 2584

<400> 2584

000

<210> 2585

<400> 2585

000

<210> 2586

<400> 2586

000

<210> 2587

<400> 2587

000

<210> 2588

<400> 2588

000

<210> 2589

<400> 2589

000

<210> 2590

<400> 2590

000

<210> 2591

<400> 2591

000

<210> 2592

<400> 2592

000

<210> 2593

<400> 2593

000

<210> 2594

<400> 2594

000

<210> 2595

<400> 2595

000

<210> 2596

<400> 2596

000

<210> 2597

<400> 2597

000

<210> 2598

<400> 2598

000

<210> 2599

<400> 2599

000

<210> 2600

<400> 2600

000

<210> 2601

<400> 2601

000

<210> 2602

<400> 2602

000

<210> 2603

<400> 2603

000

<210> 2604

<400> 2604

000

<210> 2605

<400> 2605

000

<210> 2606

<400> 2606

000

<210> 2607

<400> 2607

000

<210> 2608

<400> 2608

000

<210> 2609

<400> 2609

000

<210> 2610

<400> 2610

000

<210> 2611

<400> 2611

000

<210> 2612

<400> 2612

000

<210> 2613

<400> 2613

000

<210> 2614

<400> 2614

000

<210> 2615

<400> 2615

000

<210> 2616

<400> 2616

000

<210> 2617

<400> 2617

000

<210> 2618

<400> 2618

000

<210> 2619

<400> 2619

000

<210> 2620

<400> 2620

000

<210> 2621

<400> 2621

000

<210> 2622

<400> 2622

000

<210> 2623

<400> 2623

000

<210> 2624

<400> 2624

000

<210> 2625

<400> 2625

000

<210> 2626

<400> 2626

000

<210> 2627

<400> 2627

000

<210> 2628

<400> 2628

000

<210> 2629

<400> 2629

000

<210> 2630

<400> 2630

000

<210> 2631

<400> 2631

000

<210> 2632

<400> 2632

000

<210> 2633

<400> 2633

000

<210> 2634

<400> 2634

000

<210> 2635

<400> 2635

000

<210> 2636

<400> 2636

000

<210> 2637

<400> 2637

000

<210> 2638

<400> 2638

000

<210> 2639

<400> 2639

000

<210> 2640

<400> 2640

000

<210> 2641

<400> 2641

000

<210> 2642

<400> 2642

000

<210> 2643

<400> 2643

000

<210> 2644

<400> 2644

000

<210> 2645

<400> 2645

000

<210> 2646

<400> 2646

000

<210> 2647

<400> 2647

000

<210> 2648

<400> 2648

000

<210> 2649

<400> 2649

000

<210> 2650

<400> 2650

000

<210> 2651

<400> 2651

000

<210> 2652

<400> 2652

000

<210> 2653

<400> 2653

000

<210> 2654

<400> 2654

000

<210> 2655

<400> 2655

000

<210> 2656

<400> 2656

000

<210> 2657

<400> 2657

000

<210> 2658

<400> 2658

000

<210> 2659

<400> 2659

000

<210> 2660

<400> 2660

000

<210> 2661

<400> 2661

000

<210> 2662

<400> 2662

000

<210> 2663

<400> 2663

000

<210> 2664

<400> 2664

000

<210> 2665

<400> 2665

000

<210> 2666

<400> 2666

000

<210> 2667

<400> 2667

000

<210> 2668

<400> 2668

000

<210> 2669

<400> 2669

000

<210> 2670

<400> 2670

000

<210> 2671

<400> 2671

000

<210> 2672

<400> 2672

000

<210> 2673

<400> 2673

000

<210> 2674

<400> 2674

000

<210> 2675

<400> 2675

000

<210> 2676

<400> 2676

000

<210> 2677

<400> 2677

000

<210> 2678

<400> 2678

000

<210> 2679

<400> 2679

000

<210> 2680

<400> 2680

000

<210> 2681

<400> 2681

000

<210> 2682

<400> 2682

000

<210> 2683

<400> 2683

000

<210> 2684

<400> 2684

000

<210> 2685

<400> 2685

000

<210> 2686

<400> 2686

000

<210> 2687

<400> 2687

000

<210> 2688

<400> 2688

000

<210> 2689

<400> 2689

000

<210> 2690

<400> 2690

000

<210> 2691

<400> 2691

000

<210> 2692

<400> 2692

000

<210> 2693

<400> 2693

000

<210> 2694

<400> 2694

000

<210> 2695

<400> 2695

000

<210> 2696

<400> 2696

000

<210> 2697

<400> 2697

000

<210> 2698

<400> 2698

000

<210> 2699

<400> 2699

000

<210> 2700

<400> 2700

000

<210> 2701

<400> 2701

000

<210> 2702

<400> 2702

000

<210> 2703

<400> 2703

000

<210> 2704

<400> 2704

000

<210> 2705

<400> 2705

000

<210> 2706

<400> 2706

000

<210> 2707

<400> 2707

000

<210> 2708

<400> 2708

000

<210> 2709

<400> 2709

000

<210> 2710

<400> 2710

000

<210> 2711

<400> 2711

000

<210> 2712

<400> 2712

000

<210> 2713

<400> 2713

000

<210> 2714

<400> 2714

000

<210> 2715

<400> 2715

000

<210> 2716

<400> 2716

000

<210> 2717

<400> 2717

000

<210> 2718

<400> 2718

000

<210> 2719

<400> 2719

000

<210> 2720

<400> 2720

000

<210> 2721

<400> 2721

000

<210> 2722

<400> 2722

000

<210> 2723

<400> 2723

000

<210> 2724

<400> 2724

000

<210> 2725

<400> 2725

000

<210> 2726

<400> 2726

000

<210> 2727

<400> 2727

000

<210> 2728

<400> 2728

000

<210> 2729

<400> 2729

000

<210> 2730

<400> 2730

000

<210> 2731

<400> 2731

000

<210> 2732

<400> 2732

000

<210> 2733

<400> 2733

000

<210> 2734

<400> 2734

000

<210> 2735

<400> 2735

000

<210> 2736

<400> 2736

000

<210> 2737

<400> 2737

000

<210> 2738

<400> 2738

000

<210> 2739

<400> 2739

000

<210> 2740

<400> 2740

000

<210> 2741

<400> 2741

000

<210> 2742

<400> 2742

000

<210> 2743

<400> 2743

000

<210> 2744

<400> 2744

000

<210> 2745

<400> 2745

000

<210> 2746

<400> 2746

000

<210> 2747

<400> 2747

000

<210> 2748

<400> 2748

000

<210> 2749

<400> 2749

000

<210> 2750

<400> 2750

000

<210> 2751

<400> 2751

000

<210> 2752

<400> 2752

000

<210> 2753

<400> 2753

000

<210> 2754

<400> 2754

000

<210> 2755

<400> 2755

000

<210> 2756

<400> 2756

000

<210> 2757

<400> 2757

000

<210> 2758

<400> 2758

000

<210> 2759

<400> 2759

000

<210> 2760

<400> 2760

000

<210> 2761

<400> 2761

000

<210> 2762

<400> 2762

000

<210> 2763

<400> 2763

000

<210> 2764

<400> 2764

000

<210> 2765

<400> 2765

000

<210> 2766

<400> 2766

000

<210> 2767

<400> 2767

000

<210> 2768

<400> 2768

000

<210> 2769

<400> 2769

000

<210> 2770

<400> 2770

000

<210> 2771

<400> 2771

000

<210> 2772

<400> 2772

000

<210> 2773

<400> 2773

000

<210> 2774

<400> 2774

000

<210> 2775

<400> 2775

000

<210> 2776

<400> 2776

000

<210> 2777

<400> 2777

000

<210> 2778

<400> 2778

000

<210> 2779

<400> 2779

000

<210> 2780

<400> 2780

000

<210> 2781

<400> 2781

000

<210> 2782

<400> 2782

000

<210> 2783

<400> 2783

000

<210> 2784

<400> 2784

000

<210> 2785

<400> 2785

000

<210> 2786

<400> 2786

000

<210> 2787

<400> 2787

000

<210> 2788

<400> 2788

000

<210> 2789

<400> 2789

000

<210> 2790

<400> 2790

000

<210> 2791

<400> 2791

000

<210> 2792

<400> 2792

000

<210> 2793

<400> 2793

000

<210> 2794

<400> 2794

000

<210> 2795

<400> 2795

000

<210> 2796

<400> 2796

000

<210> 2797

<400> 2797

000

<210> 2798

<400> 2798

000

<210> 2799

<400> 2799

000

<210> 2800

<400> 2800

000

<210> 2801

<400> 2801

000

<210> 2802

<400> 2802

000

<210> 2803

<400> 2803

000

<210> 2804

<400> 2804

000

<210> 2805

<400> 2805

000

<210> 2806

<400> 2806

000

<210> 2807

<400> 2807

000

<210> 2808

<400> 2808

000

<210> 2809

<400> 2809

000

<210> 2810

<400> 2810

000

<210> 2811

<400> 2811

000

<210> 2812

<400> 2812

000

<210> 2813

<400> 2813

000

<210> 2814

<400> 2814

000

<210> 2815

<400> 2815

000

<210> 2816

<400> 2816

000

<210> 2817

<400> 2817

000

<210> 2818

<400> 2818

000

<210> 2819

<400> 2819

000

<210> 2820

<400> 2820

000

<210> 2821

<400> 2821

000

<210> 2822

<400> 2822

000

<210> 2823

<400> 2823

000

<210> 2824

<400> 2824

000

<210> 2825

<400> 2825

000

<210> 2826

<400> 2826

000

<210> 2827

<400> 2827

000

<210> 2828

<400> 2828

000

<210> 2829

<400> 2829

000

<210> 2830

<400> 2830

000

<210> 2831

<400> 2831

000

<210> 2832

<400> 2832

000

<210> 2833

<400> 2833

000

<210> 2834

<400> 2834

000

<210> 2835

<400> 2835

000

<210> 2836

<400> 2836

000

<210> 2837

<400> 2837

000

<210> 2838

<400> 2838

000

<210> 2839

<400> 2839

000

<210> 2840

<400> 2840

000

<210> 2841

<400> 2841

000

<210> 2842

<400> 2842

000

<210> 2843

<400> 2843

000

<210> 2844

<400> 2844

000

<210> 2845

<400> 2845

000

<210> 2846

<400> 2846

000

<210> 2847

<400> 2847

000

<210> 2848

<400> 2848

000

<210> 2849

<400> 2849

000

<210> 2850

<400> 2850

000

<210> 2851

<400> 2851

000

<210> 2852

<400> 2852

000

<210> 2853

<400> 2853

000

<210> 2854

<400> 2854

000

<210> 2855

<400> 2855

000

<210> 2856

<400> 2856

000

<210> 2857

<400> 2857

000

<210> 2858

<400> 2858

000

<210> 2859

<400> 2859

000

<210> 2860

<400> 2860

000

<210> 2861

<400> 2861

000

<210> 2862

<400> 2862

000

<210> 2863

<400> 2863

000

<210> 2864

<400> 2864

000

<210> 2865

<400> 2865

000

<210> 2866

<400> 2866

000

<210> 2867

<400> 2867

000

<210> 2868

<400> 2868

000

<210> 2869

<400> 2869

000

<210> 2870

<400> 2870

000

<210> 2871

<400> 2871

000

<210> 2872

<400> 2872

000

<210> 2873

<400> 2873

000

<210> 2874

<400> 2874

000

<210> 2875

<400> 2875

000

<210> 2876

<400> 2876

000

<210> 2877

<400> 2877

000

<210> 2878

<400> 2878

000

<210> 2879

<400> 2879

000

<210> 2880

<400> 2880

000

<210> 2881

<400> 2881

000

<210> 2882

<400> 2882

000

<210> 2883

<400> 2883

000

<210> 2884

<400> 2884

000

<210> 2885

<400> 2885

000

<210> 2886

<400> 2886

000

<210> 2887

<400> 2887

000

<210> 2888

<400> 2888

000

<210> 2889

<400> 2889

000

<210> 2890

<400> 2890

000

<210> 2891

<400> 2891

000

<210> 2892

<400> 2892

000

<210> 2893

<400> 2893

000

<210> 2894

<400> 2894

000

<210> 2895

<400> 2895

000

<210> 2896

<400> 2896

000

<210> 2897

<400> 2897

000

<210> 2898

<400> 2898

000

<210> 2899

<400> 2899

000

<210> 2900

<400> 2900

000

<210> 2901

<400> 2901

000

<210> 2902

<400> 2902

000

<210> 2903

<400> 2903

000

<210> 2904

<400> 2904

000

<210> 2905

<400> 2905

000

<210> 2906

<400> 2906

000

<210> 2907

<400> 2907

000

<210> 2908

<400> 2908

000

<210> 2909

<400> 2909

000

<210> 2910

<400> 2910

000

<210> 2911

<400> 2911

000

<210> 2912

<400> 2912

000

<210> 2913

<400> 2913

000

<210> 2914

<400> 2914

000

<210> 2915

<400> 2915

000

<210> 2916

<400> 2916

000

<210> 2917

<400> 2917

000

<210> 2918

<400> 2918

000

<210> 2919

<400> 2919

000

<210> 2920

<400> 2920

000

<210> 2921

<400> 2921

000

<210> 2922

<400> 2922

000

<210> 2923

<400> 2923

000

<210> 2924

<400> 2924

000

<210> 2925

<400> 2925

000

<210> 2926

<400> 2926

000

<210> 2927

<400> 2927

000

<210> 2928

<400> 2928

000

<210> 2929

<400> 2929

000

<210> 2930

<400> 2930

000

<210> 2931

<400> 2931

000

<210> 2932

<400> 2932

000

<210> 2933

<400> 2933

000

<210> 2934

<400> 2934

000

<210> 2935

<400> 2935

000

<210> 2936

<400> 2936

000

<210> 2937

<400> 2937

000

<210> 2938

<400> 2938

000

<210> 2939

<400> 2939

000

<210> 2940

<400> 2940

000

<210> 2941

<400> 2941

000

<210> 2942

<400> 2942

000

<210> 2943

<400> 2943

000

<210> 2944

<400> 2944

000

<210> 2945

<400> 2945

000

<210> 2946

<400> 2946

000

<210> 2947

<400> 2947

000

<210> 2948

<400> 2948

000

<210> 2949

<400> 2949

000

<210> 2950

<400> 2950

000

<210> 2951

<400> 2951

000

<210> 2952

<400> 2952

000

<210> 2953

<400> 2953

000

<210> 2954

<400> 2954

000

<210> 2955

<400> 2955

000

<210> 2956

<400> 2956

000

<210> 2957

<400> 2957

000

<210> 2958

<400> 2958

000

<210> 2959

<400> 2959

000

<210> 2960

<400> 2960

000

<210> 2961

<400> 2961

000

<210> 2962

<400> 2962

000

<210> 2963

<400> 2963

000

<210> 2964

<400> 2964

000

<210> 2965

<400> 2965

000

<210> 2966

<400> 2966

000

<210> 2967

<400> 2967

000

<210> 2968

<400> 2968

000

<210> 2969

<400> 2969

000

<210> 2970

<400> 2970

000

<210> 2971

<400> 2971

000

<210> 2972

<400> 2972

000

<210> 2973

<400> 2973

000

<210> 2974

<400> 2974

000

<210> 2975

<400> 2975

000

<210> 2976

<400> 2976

000

<210> 2977

<400> 2977

000

<210> 2978

<400> 2978

000

<210> 2979

<400> 2979

000

<210> 2980

<400> 2980

000

<210> 2981

<400> 2981

000

<210> 2982

<400> 2982

000

<210> 2983

<400> 2983

000

<210> 2984

<400> 2984

000

<210> 2985

<400> 2985

000

<210> 2986

<400> 2986

000

<210> 2987

<400> 2987

000

<210> 2988

<400> 2988

000

<210> 2989

<400> 2989

000

<210> 2990

<400> 2990

000

<210> 2991

<400> 2991

000

<210> 2992

<400> 2992

000

<210> 2993

<400> 2993

000

<210> 2994

<400> 2994

000

<210> 2995

<400> 2995

000

<210> 2996

<400> 2996

000

<210> 2997

<400> 2997

000

<210> 2998

<400> 2998

000

<210> 2999

<400> 2999

000

<210> 3000

<400> 3000

000

<210> 3001

<211> 1200

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3001

atgctcgagg gggttcaggt ggagactatc agcccgggcg acggacggac attcccaaag

60

cgcgggcaga cgtgtgtggt gcattacacc gggatgcttg aggacggaaa gaaagtggac

120

tcttcccgag accgaaataa accattcaag ttcatgttgg gcaagcagga ggttatcaga

180

gggtgggagg agggcgtcgc tcagatgagt gtcggacaga gggccaagct cacgatctcc

240

cctgattacg cctacggggc aactggtcac cccggaatca tcccccctca cgcaaccctc

300

gtgttcgacg tcgagctgct caaactggaa tcaggcggag gcagtggcgc tagcgggttt

360

ggcgatgtcg gtgcccttga aagcttgaga ggaaatgccg atctcgctta catcttgagc

420

atggagccct gtgggcactg tctgatcatc aacaatgtta acttttgccg ggagtccggc

480

ctgcgcacac gcacaggctc caacattgac tgcgaaaaac ttcgaaggag gtttagctct

540

ctgcatttca tggtagaggt gaagggggat ctgaccgcca agaaaatggt tctcgccctt

600

ctcgagcttg cgcagcagga ccatggagcg cttgactgtt gtgtcgttgt gatactgagc

660

catggctgtc aggcttccca tctccagttt ccaggggccg tgtacggaac cgatggatgc

720

cctgtgtcag ttgaaaagat cgtaaacatc tttaacggaa catcttgccc gagcctcggc

780

ggtaaaccga agcttttttt tatccaggcc tgcggcggtg aacagaaaga tcatggcttc

840

gaggttgcca gtaccagccc tgaagacgaa tcccccgggt caaatcctga accagatgcg

900

acccctttcc aggaaggact ccgcactttt gaccagcttg acgccatttc ctccctgcca

960

acaccttccg acatatttgt aagctactcc acctttccag gattcgtgag ctggcgcgac

1020

ccaaaatccg gcagttggta tgttgaaacc ctggacgata ttttcgaaca atgggcccac

1080

agtgaggacc tgcagtccct tcttctgcgc gtagccaatg ccgtgtcagt caaagggatt

1140

tacaagcaga tgccaggctg ctttaatttc ctgcgcaaga aactgttttt taagaccagt

1200

<210> 3002

<211> 1172

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3002

cggacggaca ttcccaaagc gcgggcagac gtgtgtggtg cattacaccg ggatgcttga

60

ggacggaaag aaagtggact cttcccgaga ccgaaataaa ccattcaagt tcatgttgggg

120

caagcaggag gttatcagag ggtgggagga gggcgtcgct cagatgagtg tcggacagag

180

ggccaagctc acgatctccc ctgattacgc ctacggggca actggtcacc ccggaatcat

240

cccccctcac gcaaccctcg tgttcgacgt cgagctgctc aaactggaat caggcgggagg

300

cagtggcggg tttggcgatg tcggtgccct tgaaagcttg agaggaaatg ccgatctcgc

360

ttacatcttg agcatggagc ctgtgggca ctgtctgatc atcaacaatg ttaacttttg

420

ccgggagtcc ggcctgcgca cacgcacagg ctccaacatt gactgcgaaa aacttcgaag

480

gaggtttagc tctctgcatt tcatggtaga ggtgaagggg gatctgaccg ccaagaaaat

540

ggttctcgcc cttctcgagc ttgcgcagca ggaccatgga gcgcttgact gttgtgtcgt

600

tgtgatactg agccatggct gtcaggcttc ccatctccag tttccagggg ccgtgtacgg

660

aaccgatgga tgccctgtgt cagttgaaaa gatcgtaaac atctttaacg gaacatcttg

720

cccgagcctc ggcggtaaac cgaagctttt ttttatccag gcctgcggcg gtgaacagaa

780

agatcatggc ttcgaggttg ccagtaccag ccctgaagac gaatcccccg ggtcaaatcc

840

tgaaccagat gcgacccctt tccaggaagg actccgcact tttgaccagc ttgacgccat

900

ttcctccctg ccaacacctt ccgacatatt tgtaagctac tccacctttc caggattcgt

960

gagctggcgc gacccaaaat ccggcagttg gtatgttgaa accctggacg atatcttcga

1020

acaatgggcc cacagtgagg acctgcagtc ccttcttctg cgcgtagcca atgccgtgtc

1080

agtcaaaggg attacaagc agatgccagg ctgctttaat ttcctgcgca agaaactgtt

1140

ttttaagacc agttgagtcg acggaggagg ag

1172

<210> 3003

<211> 1188

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3003

ggggttcagg tggagactat cagcccgggc gacggacgga cattcccaaa gcgcgggcag

60

acgtgtgtgg tgcattacac cgggatgctt gaggacggaa agaaagtgga ctcttcccga

120

gaccgaaata aaccattcaa gttcatgttg ggcaagcagg aggttatcag agggtgggag

180

gagggcgtcg ctcagatgag tgtcggacag agggccaagc tcacgatctc ccctgattac

240

gcctacgggg caactggtca ccccggaatc atcccccctc acgcaaccct cgtgttcgac

300

gtcgagctgc tcaaactgga atcaggcgga ggcagtggcg ggtttggcga tgtcggtgcc

360

cttgaaagct tgaggaaa tgccgatctc gcttacatct tgagcatgga gccctgtggg

420

cactgtctga tcatcaacaa tgttaacttt tgccgggagt ccggcctgcg cacacgcaca

480

ggctccaaca ttgactgcga aaaacttcga aggaggttta gctctctgca tttcatggta

540

gaggtgaagg gggatctgac cgccaagaaa atggttctcg cccttctcga gcttgcgcag

600

caggaccatg gagcgcttga ctgttgtgtc gttgtgatac tgagccatgg ctgtcaggct

660

tcccatctcc agtttccagg ggccgtgtac ggaaccgatg gatgccctgt gtcagttgaa

720

aagatcgtaa acatctttaa cggaacatct tgcccgagcc tcggcggtaa accgaagctt

780

ttttttatcc aggcctgcgg cggtgaacag aaagatcatg gcttcgaggt tgccagtacc

840

agccctgaag acgaatcccc cgggtcaaat cctgaaccag atgcgacccc tttccaggaa

900

ggactccgca cttttgacca gcttgacgcc atttcctccc tgccaacacc ttccgacata

960

tttgtaagct actccacctt tccaggattc gtgagctggc gcgacccaaa atccggcagt

1020

tggtatgttg aaaccctgga cgatatcttc gaacaatggg cccacagtga ggacctgcag

1080

tcccttcttc tgcgcgtagc caatgccgtg tcagtcaaag ggatttacaa gcagatgcca

1140

ggctgcttta atttcctgcg caagaaactg ttttttaaga ccagttga

1188

<210> 3004

<211> 1518

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3004

agaggcgtgc aggtggaaac catctctccc ggcgacggca gaaccttccc taagaggggc

60

cagacctgcg tggtgcacta caccggcatg ctggaagatg gcaagaagat ggacagctcc

120

cgggaccgga acaagccctt caagttcatg ctgggcaagc aggaagtgat ccggggctgg

180

gaagagggcg tggcacagat gtctgtgggc cagagagcca agctgaccat cagccccgat

240

tacgcctacg gcgccacagg ccaccctggc atcattcctc cacacgccac actggtgttc

300

gatgtggaac tgctgaagct ggaaacccgg ggagtgcagg tggaaacaat cagccctggc

360

gacggccgga cctttccaaa acggggacag acatgtgtgg tgcattatac agggatgctg

420

gaagatggga aaaaaatgga tagcagccgc gaccgcaaca aaccttttaa gtttatgctg

480

gggaaacagg aagtgattag aggctgggaa gagggggtgg cacagatgag cgtgggacag

540

cgggccaaac tgacaatctc ccccgactat gcctatgggg ccaccggaca ccccggaatc

600

atcccacctc atgctaccct ggtgtttgac gtggaactgc tgaaactgga aacaagcggc

660

ggaggcagcg gcggctttgg agatgtggga gccctggaaa gcctgcgggg caatgccgat

720

ctggcctaca tcctgagcat ggaaccctgc ggccactgcc tgattatcaa caacgtgaac

780

ttctgcagag agagcggcct gcggaccaga accggcagca acatcgactg cgagaagctg

840

cggcggagat tcagcagcct gcacttcatg gtggaagtga agggggacct gaccgccaag

900

aaaatggtgc tggctctgct ggaactggcc cagcaggatc atggcgccct ggactgttgc

960

gtggtcgtga tcctgagcca cggctgccag gccagccatc tgcagtttcc cggcgctgtg

1020

tatggcaccg atggctgccc tgtgtccgtg gaaaagatcg tgaatatctt caacggcacc

1080

agctgcccca gcctggggcgg aaagcctaag ctgttcttta ttcaagcctg tgggggcgag

1140

cagaaggacc acggatttga ggtggccagc acctcccccg aggatgagag ccctggcagc

1200

aaccctgagc ctgacgccac cccattccag gaaggactgc ggaccttcga ccagctggac

1260

gccatctcta gcctgcccac ccccagcgac atcttcgtgt cctacagcac cttccctggc

1320

tttgtgtcct ggcgggaccc caagtccggc tcttggtacg tggaaaccct ggacgacatc

1380

tttgagcagt gggcccatag cgaggacctg cagagcctgc tgctgagggt ggccaatgcc

1440

gtgtccgtga agggcatcta caagcagatg cccggctgct tcaacttcct gcggaagaag

1500

ctgtttttca agaccagc

1518

<210> 3005

<211> 400

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3005

Met Leu Glu Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg

1 5 10 15

Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met

20 25 30

Leu Glu Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro

35 40 45

Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu

50 55 60

Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser

65 70 75 80

Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro

85 90 95

His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Ser Gly

100 105 110

Gly Gly Ser Gly Ala Ser Gly Phe Gly Asp Val Gly Ala Leu Glu Ser

115 120 125

Leu Arg Gly Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys

130 135 140

Gly His Cys Leu Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly

145 150 155 160

Leu Arg Thr Arg Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg

165 170 175

Arg Phe Ser Ser Leu His Phe Met Val Glu Val Lys Gly Asp Leu Thr

180 185 190

Ala Lys Lys Met Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His

195 200 205

Gly Ala Leu Asp Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln

210 215 220

Ala Ser His Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys

225 230 235 240

Pro Val Ser Val Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys

245 250 255

Pro Ser Leu Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly

260 265 270

Gly Glu Gln Lys Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu

275 280 285

Asp Glu Ser Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln

290 295 300

Glu Gly Leu Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro

305 310 315 320

Thr Pro Ser Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val

325 330 335

Ser Trp Arg Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp

340 345 350

Asp Ile Phe Glu Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu

355 360 365

Leu Arg Val Ala Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met

370 375 380

Pro Gly Cys Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser

385 390 395 400

<210> 3006

<211> 395

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3006

Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro

1 5 10 15

Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp

20 25 30

Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe

35 40 45

Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Glu Gly Val Ala

50 55 60

Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr

65 70 75 80

Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr

85 90 95

Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Ser Gly Gly Gly Ser

100 105 110

Gly Gly Phe Gly Asp Val Gly Ala Leu Glu Ser Leu Arg Gly Asn Ala

115 120 125

Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys Gly His Cys Leu Ile

130 135 140

Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly Leu Arg Thr Arg Thr

145 150 155 160

Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg Arg Phe Ser Ser Leu

165 170 175

His Phe Met Val Glu Val Lys Gly Asp Leu Thr Ala Lys Lys Met Val

180 185 190

Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His Gly Ala Leu Asp Cys

195 200 205

Cys Val Val Val Ile Leu Ser His Gly Cys Gln Ala Ser His Leu Gln

210 215 220

Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys Pro Val Ser Val Glu

225 230 235 240

Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys Pro Ser Leu Gly Gly

245 250 255

Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly Gly Glu Gln Lys Asp

260 265 270

His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu Asp Glu Ser Pro Gly

275 280 285

Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln Glu Gly Leu Arg Thr

290 295 300

Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro Thr Pro Ser Asp Ile

305 310 315 320

Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val Ser Trp Arg Asp Pro

325 330 335

Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp Asp Ile Phe Glu Gln

340 345 350

Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu Leu Arg Val Ala Asn

355 360 365

Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met Pro Gly Cys Phe Asn

370 375 380

Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser

385 390 395

<210> 3007

<211> 506

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3007

Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe

1 5 10 15

Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu

20 25 30

Asp Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys

35 40 45

Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val

50 55 60

Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp

65 70 75 80

Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala

85 90 95

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Arg Gly Val

100 105 110

Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg

115 120 125

Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp Gly Lys

130 135 140

Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met Leu

145 150 155 160

Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val Ala Gln Met

165 170 175

Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr

180 185 190

Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr Leu Val

195 200 205

Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Ser Gly Gly Gly Ser Gly

210 215 220

Gly Phe Gly Asp Val Gly Ala Leu Glu Ser Leu Arg Gly Asn Ala Asp

225 230 235 240

Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys Gly His Cys Leu Ile Ile

245 250 255

Asn Asn Val Asn Phe Cys Arg Glu Ser Gly Leu Arg Thr Arg Thr Gly

260 265 270

Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg Arg Phe Ser Ser Ser Leu His

275 280 285

Phe Met Val Glu Val Lys Gly Asp Leu Thr Ala Lys Lys Met Val Leu

290 295 300

Ala Leu Leu Glu Leu Ala Gln Gln Asp His Gly Ala Leu Asp Cys Cys

305 310 315 320

Val Val Val Ile Leu Ser His Gly Cys Gln Ala Ser His Leu Gln Phe

325 330 335

Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys Pro Val Ser Val Glu Lys

340 345 350

Ile Val Asn Ile Phe Asn Gly Thr Ser Cys Pro Ser Leu Gly Gly Lys

355 360 365

Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly Gly Glu Gln Lys Asp His

370 375 380

Gly Phe Glu Val Ala Ser Thr Ser Pro Glu Asp Glu Ser Pro Gly Ser

385 390 395 400

Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln Glu Gly Leu Arg Thr Phe

405 410 415

Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro Thr Pro Ser Asp Ile Phe

420 425 430

Val Ser Tyr Ser Thr Phe Pro Gly Phe Val Ser Trp Arg Asp Pro Lys

435 440 445

Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp Asp Ile Phe Glu Gln Trp

450 455 460

Ala His Ser Glu Asp Leu Gln Ser Leu Leu Leu Arg Val Ala Asn Ala

465 470 475 480

Val Ser Val Lys Gly Ile Tyr Lys Gln Met Pro Gly Cys Phe Asn Phe

485 490 495

Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser

500 505

<210> 3008

<211> 66

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 3008

ggaagcggcg ccaccaattt cagcctgctg aaacaggccg gcgacgtgga agagaaccct

60

ggccct

66

<210> 3009

<211> 69

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 3009

agtggctccg gcgcaacaaa tttctccttg ctgaaacagg caggcgacgt tgaggaaaat

60

cccggccca

69

<210> 3010

<211> 66

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 3010

ggctccggcg caacaaattt ctccttgctg aaacaggcag gcgacgttga ggaaaatccc

60

ggcca

66

<210> 3011

<211> 32

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 3011

ggggttcagg tggagactat cagcccggggc ga

32

<210> 3012

<211> 66

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 3012

ggctccggcg caacaaattt ctccttgctg aaacaggcag gcgacgttga ggaaaatccc

60

ggcca

66

<210> 3013

<211> 22

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 3013

Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val

1 5 10 15

Glu Glu Asn Pro Gly Pro

20

<210> 3014

<211> 26

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 3014

Arg Lys Arg Arg Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln

1 5 10 15

Ala Gly Asp Val Glu Glu Asn Pro Gly Pro

20 25

<210> 3015

<211> 1308

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3015

cggggcgtgc aggttgagac aatttcccca ggagatgggc gaacgttccc caagcgcgga

60

cagacatgcg ttgtgcacta cacaggaatg ttggaggacg gaaagaaaat ggacagttca

120

agagatcgga acaaaccatt caaattcatg ttgggaaaac aggaagtgat acggggctgg

180

gaagagggtg tagcgcaaat gtccgttggt caacgagcaa aactcacgat aagtcccgat

240

tatgcttacg gcgcaaccgg tcacccgggc atcataccgc ctcatgcgac tttggtcttt

300

gatgtggagc tgttgaaact tgaaactcgc ggagtacagg ttgaaacaat atcacccggg

360

gacgggcgga cttttccgaa gagaggtcag acctgcgtcg tccattatac cggtatgctg

420

gaggacggaa agaaaatgga cagctcacgg gaccgaaata aaccattcaa atttatgttg

480

gggaaacaag aggttatcag gggctgggag gagggtgtgg cccagatgtc tgtcggtcag

540

cgcgcgaaac tcacaatctc tccggattat gcgtatgggg cgacagggca tccgggaatt

600

atccctcccc acgctacctt ggttttcgat gttgagcttc tgaagttgga gaccagagga

660

gttcaagtgg agacaatatc tcctggggat ggacggacgt tccccaagcg cggccagacc

720

tgtgtagtcc actacacagg gatgcttgaa gacggaaaaa agatggatag cagtagagat

780

cgcaacaaac catttaagtt catgctgggg aagcaggaag taatacgcgg ctgggaggaa

840

ggcgtggcac agatgagtgt tggtcaacgg gccaaactta ctatttctcc cgattatgcg

900

tatggagcca ccgggcaccc tggcattatc ccaccccatg ccacattggt ttttgacgtt

960

gaattgctta aattggagac caggggagtc caagtggaaa caatatcacc gggggatggt

1020

cggacttttc ctaaaagggg ccaaacctgt gtagtccatt ataccggaat gctcgaagac

1080

ggaaagaaaa tggactcttc tagagaccgc aataagccct tcaagttcat gttgggtaag

1140

caagaggtga tccggggctg ggaagagggg gtcgctcaaa tgtccgtcgg tcagcgagct

1200

aaactgacta tttccccaga ctacgcatat ggagcgactg gccaccccgg tattattcct

1260

ccccatgcga ctctcgtgtt cgacgtagaa ctcttgaaat tggaaacg

1308

<210> 3016

<211> 24

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 3016

tcagcccgga acaggcggaa gaga

24

<210> 3017

<211> 8

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 3017

Ser Ala Arg Asn Arg Arg Lys Arg

15

<210> 3018

<211> 2727

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3018

atgctcgagg gggttcaggt ggagactatc agcccgggcg acggacggac attcccaaag

60

cgcgggcaga cgtgtgtggt gcattacacc gggatgcttg aggacggaaa gaaagtggac

120

tcttcccgag accgaaataa accattcaag ttcatgttgg gcaagcagga ggttatcaga

180

gggtgggagg agggcgtcgc tcagatgagt gtcggacaga gggccaagct cacgatctcc

240

cctgattacg cctacggggc aactggtcac cccggaatca tcccccctca cgcaaccctc

300

gtgttcgacg tcgagctgct caaactggaa tcaggcggag gcagtggcgc tagcgggttt

360

ggcgatgtcg gtgcccttga aagcttgaga ggaaatgccg atctcgctta catcttgagc

420

atggagccct gtgggcactg tctgatcatc aacaatgtta acttttgccg ggagtccggc

480

ctgcgcacac gcacaggctc caacattgac tgcgaaaaac ttcgaaggag gtttagctct

540

ctgcatttca tggtagaggt gaagggggat ctgaccgcca agaaaatggt tctcgccctt

600

ctcgagcttg cgcagcagga ccatggagcg cttgactgtt gtgtcgttgt gatactgagc

660

catggctgtc aggcttccca tctccagttt ccaggggccg tgtacggaac cgatggatgc

720

cctgtgtcag ttgaaaagat cgtaaacatc tttaacggaa catcttgccc gagcctcggc

780

ggtaaaccga agcttttttt tatccaggcc tgcggcggtg aacagaaaga tcatggcttc

840

gaggttgcca gtaccagccc tgaagacgaa tcccccgggt caaatcctga accagatgcg

900

acccctttcc aggaaggact ccgcactttt gaccagcttg acgccatttc ctccctgcca

960

acaccttccg acatatttgt aagctactcc acctttccag gattcgtgag ctggcgcgac

1020

ccaaaatccg gcagttggta tgttgaaacc ctggacgata ttttcgaaca atgggcccac

1080

agtgaggacc tgcagtccct tcttctgcgc gtagccaatg ccgtgtcagt caaagggatt

1140

tacaagcaga tgccaggctg ctttaatttc ctgcgcaaga aactgttttt taagaccagt

1200

ggctccggcg caacaaattt ctccttgctg aaacaggcag gcgacgttga ggaaaatccc

1260

ggcccaatgg ccttaccagt gaccgccttg ctcctgccgc tggccttgct gctccacgcc

1320

gccaggccgg acatccagat gacacagact acatcctccc tgtctgcctc tctgggagac

1380

agagtcacca tcagttgcag ggcaagtcag gacattagta aatatttaaa ttggtatcag

1440

cagaaaccag atggaactgt taaactcctg atctaccata catcaagatt acactcagga

1500

gtcccatcaa ggttcagtgg cagtgggtct ggaacagatt attctctcac cattagcaac

1560

ctggagcaag aagatattgc cacttacttt tgccaacagg gtaatacgct tccgtacacg

1620

ttcggagggg ggactaagtt ggaaataaca ggtggcggtg gctcgggcgg tggtgggtcg

1680

ggtggcggcg gatctgaggt gaaactgcag gagtcaggac ctggcctggt ggcgccctca

1740

cagagcctgt ccgtcacatg cactgtctca ggggtctcat tacccgacta tggtgtaagc

1800

tggattcgcc agcctccacg aaagggtctg gagtggctgg gagtaatatg gggtagtgaa

1860

accacatact ataattcagc tctcaaatcc agactgacca tcatcaagga caactccaag

1920

agccaagttt tcttaaaaat gaacagtctg caaactgatg acacagccat ttactactgt

1980

gccaaacatt attactacgg tggtagctat gctatggact actggggtca aggaacctca

2040

gtcaccgtct cctcaaccac gacgccagcg ccgcgaccac caacaccggc gcccaccatc

2100

gcgtcgcagc ccctgtccct gcgccgag gcgtgccggc cagcggcggg gggcgcagtg

2160

cacacgaggg ggctggactt cgcctgtgat atctacatct gggcgccctt ggccgggact

2220

tgtggggtcc ttctcctgtc actggttatc accctttact gcaaacgggg cagaaagaaa

2280

ctcctgtata tattcaaaca accatttatg agaccagtac aaactactca agaggaagat

2340

ggctgtagct gccgatttcc agaagaagaa gaaggaggat gtgaactgag agtgaagttc

2400

agcaggagcg cagacgcccc cgcgtaccag cagggccaga accagctcta taacgagctc

2460

aatctaggac gaagagagga gtacgatgtt ttggacaaga gacgtggccg ggaccctgag

2520

atggggggaa agccgagaag gaagaaccct caggaaggcc tgtacaatga actgcagaaa

2580

gataagatgg cggaggccta cagtgagatt gggatgaaag gcgagcgccg gaggggcaag

2640

gggcacgatg gcctttacca gggtctcagt acagccacca aggacaccta cgacgccctt

2700

cacatgcagg ccctgccccc tcgctaa

2727

<210> 3019

<211> 908

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3019

Met Leu Glu Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg

1 5 10 15

Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met

20 25 30

Leu Glu Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro

35 40 45

Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu

50 55 60

Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser

65 70 75 80

Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro

85 90 95

His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Ser Gly

100 105 110

Gly Gly Ser Gly Ala Ser Gly Phe Gly Asp Val Gly Ala Leu Glu Ser

115 120 125

Leu Arg Gly Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys

130 135 140

Gly His Cys Leu Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly

145 150 155 160

Leu Arg Thr Arg Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg

165 170 175

Arg Phe Ser Ser Leu His Phe Met Val Glu Val Lys Gly Asp Leu Thr

180 185 190

Ala Lys Lys Met Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His

195 200 205

Gly Ala Leu Asp Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln

210 215 220

Ala Ser His Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys

225 230 235 240

Pro Val Ser Val Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys

245 250 255

Pro Ser Leu Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly

260 265 270

Gly Glu Gln Lys Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu

275 280 285

Asp Glu Ser Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln

290 295 300

Glu Gly Leu Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro

305 310 315 320

Thr Pro Ser Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val

325 330 335

Ser Trp Arg Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp

340 345 350

Asp Ile Phe Glu Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu

355 360 365

Leu Arg Val Ala Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met

370 375 380

Pro Gly Cys Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser

385 390 395 400

Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val

405 410 415

Glu Glu Asn Pro Gly Pro Met Ala Leu Pro Val Thr Ala Leu Leu Leu

420 425 430

Pro Leu Ala Leu Leu Leu His Ala Ala Arg Pro Asp Ile Gln Met Thr

435 440 445

Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile

450 455 460

Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln

465 470 475 480

Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg

485 490 495

Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr

500 505 510

Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr

515 520 525

Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly

530 535 540

Thr Lys Leu Glu Ile Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

545 550 555 560

Gly Gly Gly Gly Ser Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu

565 570 575

Val Ala Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val

580 585 590

Ser Leu Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys

595 600 605

Gly Leu Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr

610 615 620

Asn Ser Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys

625 630 635 640

Ser Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala

645 650 655

Ile Tyr Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met

660 665 670

Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Thr Thr Thr

675 680 685

Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro

690 695 700

Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val

705 710 715 720

His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro

725 730 735

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

740 745 750

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

755 760 765

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

770 775 780

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

785 790 795 800

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu

805 810 815

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

820 825 830

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

835 840 845

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

850 855 860

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

865 870 875 880

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

885 890 895

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

900 905

<210> 3020

<211> 2741

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3020

atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg

60

ccggacatcc agatgacaca gactacatcc tccctgtctg cctctctggg agacagagtc

120

accatcagtt gcagggcaag tcaggacatt agtaaatatt taaattggta tcagcagaaa

180

ccagatggaa ctgttaaact cctgatctac catacatcaa gattacactc aggagtccca

240

tcaaggttca gtggcagtgg gtctggaaca gattattctc tcaccattag caacctggag

300

caagaagata ttgccactta cttttgccaa cagggtaata cgcttccgta cacgttcgga

360

ggggggacta agttggaaat aacaggtggc ggtggctcgg gcggtggtgg gtcgggtggc

420

ggcggatctg aggtgaaact gcaggagtca ggacctggcc tggtggcgcc ctcacagagc

480

ctgtccgtca catgcactgt ctcaggggtc tcattacccg actatggtgt aagctggatt

540

cgccagcctc cacgaaaggg tctggagtgg ctgggagtaa tatggggtag tgaaaccaca

600

tactataatt cagctctcaa atccagactg accatcatca aggacaactc caagagccaa

660

gttttcttaa aaatgaacag tctgcaaact gatgacacag ccatttacta ctgtgccaaa

720

cattattact acggtggtag ctatgctatg gactactggg gtcaaggaac ctcagtcacc

780

gtctcctcaa ccacgacgcc agcgccgcga ccaccaacac cggcgcccac catcgcgtcg

840

cagcccctgt ccctgcgccc agaggcgtgc cggccagcgg cggggggcgc agtgcacacg

900

agggggctgg acttcgcctg tgatatctac atctgggcgc ccttggccgg gacttgtggg

960

gtccttctcc tgtcactggt tatcaccctt tactgcaaac ggggcagaaa gaaactcctg

1020

tatatattca aacaaccatt tatgagacca gtacaaacta ctcaagagga agatggctgt

1080

agctgccgat ttccagaaga agaagaagga ggatgtgaac tgagagtgaa gttcagcagg

1140

agcgcagacg cccccgcgta ccagcagggc cagaaccagc tctataacga gctcaatcta

1200

ggacgaagag aggagtacga tgttttggac aagagacgtg gccgggaccc tgagatgggg

1260

ggaaagccga gaaggaagaa ccctcaggaa ggcctgtaca atgaactgca gaaagataag

1320

atggcgggagg cctacagtga gattgggatg aaaggcgagc gccgggagggg caaggggcac

1380

gatggccttt accagggtct cagtacagcc accaggaca cctacgacgc ccttcacatg

1440

caggccctgc cccctcgctc ggaagcgacg gggctccggc gcaacaaatt tctccttgct

1500

gaaacaggca ggcgacgttg aggaaaatcc cggcccaggg gttcaggtgg agactatcag

1560

cccgggcgac ggacggacat tcccaaagcg cgggcagacg tgtgtggtgc attacaccgg

1620

gatgcttgag gacggaaaga aagtggactc ttcccgagac cgaaataaac cattcaagtt

1680

catgttgggc aagcaggagg ttatcagagg gtgggaggag ggcgtcgctc agatgagtgt

1740

cggacagagg gccaagctca cgatctcccc tgattacgcc tacggggcaa ctggtcaccc

1800

cggaatcatc ccccctcacg caaccctcgt gttcgacgtc gagctgctca aactggaatc

1860

aggcgggaggc agtggcgggt ttggcgatgt cggtgccctt gaaagcttga gaggaaatgc

1920

cgatctcgct tacatcttga gcatggagcc ctgtgggcac tgtctgatca tcaacaatgt

1980

taacttttgc cgggagtccg gcctgcgcac acgcacaggc tccaacattg actgcgaaaa

2040

acttcgaagg aggtttagct ctctgcattt catggtagag gtgaaggggg atctgaccgc

2100

caagaaaatg gttctcgccc ttctcgagct tgcgcagcag gaccatggag cgcttgactg

2160

ttgtgtcgtt gtgatactga gccatggctg tcaggcttcc catctccagt ttccaggggc

2220

cgtgtacgga accgatggat gccctgtgtc agttgaaaag atcgtaaaca tctttaacgg

2280

aacatcttgc cggagcctcg gcggtaaacc gaagcttttt tttatccagg cctgcggcgg

2340

tgaacagaaa gatcatggct tcgaggttgc cagtaccagc cctgaagacg aatcccccgg

2400

gtcaaatcct gaaccagatg cgaccccttt cggaagga ctccgcactt ttgaccagct

2460

tgacgccatt tcctccctgc caacaccttc cgacatattt gtaagctact ccacctttcc

2520

aggattcgtg agctggcgcg acccaaaatc cggcagttgg tatgttgaaa ccctggacga

2580

tatcttcgaa caatgggccc acagtgagga cctgcagtcc cttcttctgc gcgtagccaa

2640

tgccgtgtca gtcaaaggga tttacaagca gatgccaggc tgctttaatt tcctgcgcaa

2700

gaaactgttt tttaagacca gttgagtcga cggagggagga g

2741

<210> 3021

<211> 907

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3021

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu

20 25 30

Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln

35 40 45

Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr

50 55 60

Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val Pro

65 70 75 80

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile

85 90 95

Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly

100 105 110

Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr

115 120 125

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu

130 135 140

Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser

145 150 155 160

Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly

165 170 175

Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly

180 185 190

Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser

195 200 205

Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys

210 215 220

Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys

225 230 235 240

His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly

245 250 255

Thr Ser Val Thr Val Ser Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro

260 265 270

Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu

275 280 285

Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp

290 295 300

Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly

305 310 315 320

Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg

325 330 335

Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln

340 345 350

Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu

355 360 365

Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala

370 375 380

Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu

385 390 395 400

Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp

405 410 415

Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu

420 425 430

Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile

435 440 445

Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr

450 455 460

Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met

465 470 475 480

Gln Ala Leu Pro Pro Arg Arg Lys Arg Arg Gly Ser Gly Ala Thr Asn

485 490 495

Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro

500 505 510

Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro

515 520 525

Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp

530 535 540

Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe

545 550 555 560

Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Glu Gly Val Ala

565 570 575

Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr

580 585 590

Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr

595 600 605

Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Ser Gly Gly Gly Ser

610 615 620

Gly Gly Phe Gly Asp Val Gly Ala Leu Glu Ser Leu Arg Gly Asn Ala

625 630 635 640

Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys Gly His Cys Leu Ile

645 650 655

Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly Leu Arg Thr Arg Thr

660 665 670

Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg Arg Phe Ser Ser Leu

675 680 685

His Phe Met Val Glu Val Lys Gly Asp Leu Thr Ala Lys Lys Met Val

690 695 700

Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His Gly Ala Leu Asp Cys

705 710 715 720

Cys Val Val Val Ile Leu Ser His Gly Cys Gln Ala Ser His Leu Gln

725 730 735

Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys Pro Val Ser Val Glu

740 745 750

Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys Pro Ser Leu Gly Gly

755 760 765

Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly Gly Glu Gln Lys Asp

770 775 780

His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu Asp Glu Ser Pro Gly

785 790 795 800

Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln Glu Gly Leu Arg Thr

805 810 815

Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro Thr Pro Ser Asp Ile

820 825 830

Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val Ser Trp Arg Asp Pro

835 840 845

Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp Asp Ile Phe Glu Gln

850 855 860

Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu Leu Arg Val Ala Asn

865 870 875 880

Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met Pro Gly Cys Phe Asn

885 890 895

Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser

900 905

<210> 3022

<211> 1479

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3022

atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg

60

ccgggatccg atattcaact tacacagtcc cctagttcct tgtccgcctc cgtcggcgac

120

agagttacca tgacttgtcg agcgtcttct agcgtttcct acattcattg gttccaacag

180

aagcccggaa aggcaccaaa accttggatc tacgccacgt ccaatttggc tagtggtgtt

240

ccggtgcgat tttccgggtc aggtagcggg acggactata cttttaccat ttcaagcctt

300

cagcctgaag acatcgcgac gtactattgt cagcagtgga cctctaaccc tcctaccttt

360

ggcggtggaa caaagctgga gatcaaacga ggcggggggtg gctctggggg aggaggttcc

420

ggtgggggag gctctcaagt acaactgcaa caaagtgggg ctgaagtgaa gaagcccggt

480

tcttcagtca aagtatcatg taaggcaagt ggttatactt ttacgtctta taacatgcat

540

tgggtaaagc aagcccctgg tcagggcctc gagtggattg gtgcgatcta ccctggaatg

600

ggtgatacga gctataatca gaaattcaag gggaaagcca ccttgactgc agacgaatct

660

acgaacacgg cttacatgga gcttagctca ctcagatcag aggatacagc cttttactac

720

tgcgctagat caacttatta cggaggagac tggtattttg atgtatgggg tcaggggacc

780

acagtcactg ttagctctgc tagcaccacg acgccagcgc cgcgaccacc aacaccggcg

840

cccaccatcg cgtcgcagcc cctgtccctg cgcccagagg cgtgccggcc agcggcgggg

900

ggcgcagtgc acacgagggg gctggacttc gcctgtgatt ccggaatcta catctgggcg

960

cccttggccg ggacttgtgg ggtccttctc ctgtcactgg ttatcaccct ttactgcaaa

1020

cggggcagaa agaaactcct gtatatattc aaacaaccat ttatgagacc agtacaaact

1080

actcaagagg aagatggctg tagctgccga tttccagaag aagaagaagg aggatgtgaa

1140

ctgagagtga agttcagcag gagcgcagac gcccccgcgt accagcaggg ccagaaccag

1200

ctctataacg agctcaatct aggacgaaga gaggagtacg atgttttgga caagagacgt

1260

ggccgggacc ctgagatgggg gggaaagccg agaaggaaga accctcagga aggcctgtac

1320

aatgaactgc agaaagataa gatggcggag gcctacagtg agattgggat gaaaggcgag

1380

cgccggaggg gcaaggggca cgatggcctt taccagggtc tcagtacagc caccaaggac

1440

acctacgacg cccttcacat gcaggccctg ccccctcgc

1479

<210> 3023

<211> 494

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3023

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser

20 25 30

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Met Thr Cys Arg Ala

35 40 45

Ser Ser Ser Val Ser Tyr Ile His Trp Phe Gln Gln Lys Pro Gly Lys

50 55 60

Ala Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val

65 70 75 80

Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr

85 90 95

Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln

100 105 110

Trp Thr Ser Asn Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile

115 120 125

Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly

145 150 155 160

Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser

165 170 175

Tyr Asn Met His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp

180 185 190

Ile Gly Ala Ile Tyr Pro Gly Met Gly Asp Thr Ser Tyr Asn Gln Lys

195 200 205

Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Glu Ser Thr Asn Thr Ala

210 215 220

Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Phe Tyr Tyr

225 230 235 240

Cys Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asp Val Trp

245 250 255

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ser Gly Ile Tyr Ile Trp Ala

305 310 315 320

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

325 330 335

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

340 345 350

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

355 360 365

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

370 375 380

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

385 390 395 400

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

405 410 415

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

420 425 430

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

435 440 445

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

450 455 460

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

465 470 475 480

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg Glx

485 490

<210> 3024

<211> 2733

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3024

atggctctgc ctgtgacagc tctgctgctg cctctggccc tgctgctgca tgctgccaga

60

cctggctccg atattcaact tacacagtcc cctagttcct tgtccgcctc cgtcggcgac

120

agagttacca tgacttgtcg agcgtcttct agcgtttcct acattcattg gttccaacag

180

aagcccggaa aggcaccaaa accttggatc tacgccacgt ccaatttggc tagtggtgtt

240

ccggtgcgat tttccgggtc aggtagcggg acggactata cttttaccat ttcaagcctt

300

cagcctgaag acatcgcgac gtactattgt cagcagtgga cctctaaccc tcctaccttt

360

ggcggtggaa caaagctgga gatcaaacga ggcggggggtg gctctggggg aggaggttcc

420

ggtgggggag gctctcaagt acaactgcaa caaagtgggg ctgaagtgaa gaagcccggt

480

tcttcagtca aagtatcatg taaggcaagt ggttatactt ttacgtctta taacatgcat

540

tgggtaaagc aagcccctgg tcagggcctc gagtggattg gtgcgatcta ccctggaatg

600

ggtgatacga gctataatca gaaattcaag gggaaagcca ccttgactgc agacgaatct

660

acgaacacgg cttacatgga gcttagctca ctcagatcag aggatacagc cttttactac

720

tgcgctagat caacttatta cggaggagac tggtattttg atgtatgggg tcaggggacc

780

acagtcactg ttagctctgc tagcaccacg acgccagcgc cgcgaccacc aacaccggcg

840

cccaccatcg cgtcgcagcc cctgtccctg cgcccagagg cgtgccggcc agcggcgggg

900

ggcgcagtgc acacgagggg gctggacttc gcctgtgatt ccggaatcta catctgggcg

960

cccttggccg ggacttgtgg ggtccttctc ctgtcactgg ttatcaccct ttactgcaaa

1020

cggggcagaa agaaactcct gtatatattc aaacaaccat ttatgagacc agtacaaact

1080

actcaagagg aagatggctg tagctgccga tttccagaag aagaagaagg aggatgtgaa

1140

ctgagagtga agttcagcag gagcgcagac gcccccgcgt accagcaggg ccagaaccag

1200

ctctataacg agctcaatct aggacgaaga gaggagtacg atgttttgga caagagacgt

1260

ggccgggacc ctgagatgggg gggaaagccg agaaggaaga accctcagga aggcctgtac

1320

aatgaactgc agaaagataa gatggcggag gcctacagtg agattgggat gaaaggcgag

1380

cgccggaggg gcaaggggca cgatggcctt taccagggtc tcagtacagc caccaaggac

1440

acctacgacg cccttcacat gcaggccctg ccccctcgcg gctccggcgc aacaaatttc

1500

tccttgctga aacaggcagg cgacgttgag gaaaatcccg gcccaggggt tcaggtggag

1560

actatcagcc cgggcgacgg acggacattc ccaaagcgcg ggcagacgtg tgtggtgcat

1620

tacaccggga tgcttgagga cggaaagaaa gtggactctt cccgagaccg aaataaacca

1680

ttcaagttca tgttgggcaa gcaggaggtt atcagaggggt gggaggaggg cgtcgctcag

1740

atgagtgtcg gacagagggc caagctcacg atctcccctg attacgccta cggggcaact

1800

ggtcaccccg gaatcatccc ccctcacgca accctcgtgt tcgacgtcga gctgctcaaa

1860

ctggaatcag gcggaggcag tggcgggttt ggcgatgtcg gtgcccttga aagcttgaga

1920

ggaaatgccg atctcgctta catcttgagc atggagccct gtgggcactg tctgatcatc

1980

aacaatgtta acttttgccg ggagtccggc ctgcgcacac gcacaggctc caacattgac

2040

tgcgaaaaac ttcgaaggag gtttagctct ctgcatttca tggtagaggt gaagggggat

2100

ctgaccgcca agaaaatggt tctcgccctt ctcgagcttg cgcagcagga ccatggagcg

2160

cttgactgtt gtgtcgttgt gatactgagc catggctgtc aggcttccca tctccagttt

2220

ccaggggccg tgtacggaac cgatggatgc cctgtgtcag ttgaaaagat cgtaaacatc

2280

tttaacggaa catcttgccc gagcctcggc ggtaaaccga agcttttttt tatccaggcc

2340

tgcggcggtg aacagaaaga tcatggcttc gaggttgcca gtaccagccc tgaagacgaa

2400

tcccccgggt caaatcctga accagatgcg acccctttcc aggaaggact ccgcactttt

2460

gaccagcttg acgccatttc ctccctgcca acaccttccg acatatttgt aagctactcc

2520

acctttccag gattcgtgag ctggcgcgac ccaaaatccg gcagttggta tgttgaaacc

2580

ctggacgata tcttcgaaca atgggcccac agtgaggacc tgcagtccct tcttctgcgc

2640

gtagccaatg ccgtgtcagt caaagggatt tacaagcaga tgccaggctg ctttaatttc

2700

ctgcgcaaga aactgttttt taagaccagt tga

2733

<210> 3025

<211> 911

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3025

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser

20 25 30

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Met Thr Cys Arg Ala

35 40 45

Ser Ser Ser Val Ser Tyr Ile His Trp Phe Gln Gln Lys Pro Gly Lys

50 55 60

Ala Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val

65 70 75 80

Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr

85 90 95

Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln

100 105 110

Trp Thr Ser Asn Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile

115 120 125

Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly

145 150 155 160

Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser

165 170 175

Tyr Asn Met His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp

180 185 190

Ile Gly Ala Ile Tyr Pro Gly Met Gly Asp Thr Ser Tyr Asn Gln Lys

195 200 205

Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Glu Ser Thr Asn Thr Ala

210 215 220

Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Phe Tyr Tyr

225 230 235 240

Cys Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asp Val Trp

245 250 255

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ser Gly Ile Tyr Ile Trp Ala

305 310 315 320

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

325 330 335

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

340 345 350

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

355 360 365

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

370 375 380

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

385 390 395 400

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

405 410 415

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

420 425 430

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

435 440 445

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

450 455 460

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

465 470 475 480

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg Gly Ser Gly

485 490 495

Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn

500 505 510

Pro Gly Pro Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg

515 520 525

Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met

530 535 540

Leu Glu Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro

545 550 555 560

Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu

565 570 575

Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser

580 585 590

Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro

595 600 605

His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Ser Gly

610 615 620

Gly Gly Ser Gly Gly Phe Gly Asp Val Gly Ala Leu Glu Ser Leu Arg

625 630 635 640

Gly Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys Gly His

645 650 655

Cys Leu Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly Leu Arg

660 665 670

Thr Arg Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg Arg Phe

675 680 685

Ser Ser Leu His Phe Met Val Glu Val Lys Gly Asp Leu Thr Ala Lys

690 695 700

Lys Met Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His Gly Ala

705 710 715 720

Leu Asp Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln Ala Ser

725 730 735

His Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys Pro Val

740 745 750

Ser Val Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys Pro Ser

755 760 765

Leu Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly Gly Glu

770 775 780

Gln Lys Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu Asp Glu

785 790 795 800

Ser Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln Glu Gly

805 810 815

Leu Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro Thr Pro

820 825 830

Ser Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val Ser Trp

835 840 845

Arg Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp Asp Ile

850 855 860

Phe Glu Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu Leu Arg

865 870 875 880

Val Ala Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met Pro Gly

885 890 895

Cys Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser Glx

900 905 910

<210> 3026

<211> 2745

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3026

atgctcgagg gggttcaggt ggagactatc agcccgggcg acggacggac attcccaaag

60

cgcgggcaga cgtgtgtggt gcattacacc gggatgcttg aggacggaaa gaaagtggac

120

tcttcccgag accgaaataa accattcaag ttcatgttgg gcaagcagga ggttatcaga

180

gggtgggagg agggcgtcgc tcagatgagt gtcggacaga gggccaagct cacgatctcc

240

cctgattacg cctacggggc aactggtcac cccggaatca tcccccctca cgcaaccctc

300

gtgttcgacg tcgagctgct caaactggaa tcaggcggag gcagtggcgc tagcgggttt

360

ggcgatgtcg gtgcccttga aagcttgaga ggaaatgccg atctcgctta catcttgagc

420

atggagccct gtgggcactg tctgatcatc aacaatgtta acttttgccg ggagtccggc

480

ctgcgcacac gcacaggctc caacattgac tgcgaaaaac ttcgaaggag gtttagctct

540

ctgcatttca tggtagaggt gaagggggat ctgaccgcca agaaaatggt tctcgccctt

600

ctcgagcttg cgcagcagga ccatggagcg cttgactgtt gtgtcgttgt gatactgagc

660

catggctgtc aggcttccca tctccagttt ccaggggccg tgtacggaac cgatggatgc

720

cctgtgtcag ttgaaaagat cgtaaacatc tttaacggaa catcttgccc gagcctcggc

780

ggtaaaccga agcttttttt tatccaggcc tgcggcggtg aacagaaaga tcatggcttc

840

gaggttgcca gtaccagccc tgaagacgaa tcccccgggt caaatcctga accagatgcg

900

acccctttcc aggaaggact ccgcactttt gaccagcttg acgccatttc ctccctgcca

960

acaccttccg acatatttgt aagctactcc acctttccag gattcgtgag ctggcgcgac

1020

ccaaaatccg gcagttggta tgttgaaacc ctggacgata ttttcgaaca atgggcccac

1080

agtgaggacc tgcagtccct tcttctgcgc gtagccaatg ccgtgtcagt caaagggatt

1140

tacaagcaga tgccaggctg ctttaatttc ctgcgcaaga aactgttttt taagaccagt

1200

ggctccggcg caacaaattt ctccttgctg aaacaggcag gcgacgttga ggaaaatccc

1260

ggcccaatgg ccttaccagt gaccgccttg ctcctgccgc tggccttgct gctccacgcc

1320

gccaggccgg gatccgatat tcaacttaca cagtccccta gttccttgtc cgcctccgtc

1380

ggcgacagag ttaccatgac ttgtcgagcg tcttctagcg tttcctacat tcattggttc

1440

caacagaagc ccggaaaggc accaaaacct tggatctacg ccacgtccaa tttggctagt

1500

ggtgttccgg tgcgattttc cgggtcaggt agcgggacgg actatacttt taccattttca

1560

agccttcagc ctgaagacat cgcgacgtac tattgtcagc agtggacctc taaccctcct

1620

acctttggcg gtggaacaaa gctggagatc aaacgaggcg ggggtggctc tgggggagga

1680

ggttccggtg ggggaggctc tcaagtacaa ctgcaacaaa gtggggctga agtgaagaag

1740

cccggttctt cagtcaaagt atcatgtaag gcaagtggtt atacttttac gtcttataac

1800

atgcattggg taaagcaagc ccctggtcag ggcctcgagt ggattggtgc gatctaccct

1860

ggaatgggtg atacgagcta taatcagaaa ttcaagggga aagccacctt gactgcagac

1920

gaatctacga acacggctta catggagctt agctcactca gatcagagga tacagccttt

1980

tactactgcg ctagatcaac ttattacgga ggagactggt attttgatgt atggggtcag

2040

gggaccacag tcactgttag ctctgctagc accacgacgc cagcgccgcg accaccaaca

2100

ccggcgccca ccatcgcgtc gcagcccctg tccctgcgcc cagaggcgtg ccggccagcg

2160

gcggggggcg cagtgcacac gagggggctg gacttcgcct gtgattccgg aatctacatc

2220

tgggcgccct tggccgggac ttgtggggtc cttctcctgt cactggttat caccctttac

2280

tgcaaacggg gcagaaagaa actcctgtat atattcaaac aaccatttat gagaccagta

2340

caaactactc aagaggaaga tggctgtagc tgccgatttc cagaagaaga agaaggagga

2400

tgtgaactga gagtgaagtt cagcaggagc gcagacgccc ccgcgtacca gcagggccag

2460

aaccagctct ataacgagct caatctagga cgaagagagg agtacgatgt tttggacaag

2520

agacgtggcc gggaccctga gatgggggga aagccgagaa ggaagaaccc tcaggaaggc

2580

ctgtacaatg aactgcagaa agataagatg gcggaggcct acagtgagat tgggatgaaa

2640

ggcgagcgcc ggaggggcaa ggggcacgat ggcctttacc agggtctcag tacagccacc

2700

aaggacacct acgacgccct tcacatgcag gccctgcccc ctcgc

2745

<210> 3027

<211> 916

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3027

Met Leu Glu Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg

1 5 10 15

Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met

20 25 30

Leu Glu Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro

35 40 45

Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu

50 55 60

Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser

65 70 75 80

Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro

85 90 95

His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Ser Gly

100 105 110

Gly Gly Ser Gly Ala Ser Gly Phe Gly Asp Val Gly Ala Leu Glu Ser

115 120 125

Leu Arg Gly Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys

130 135 140

Gly His Cys Leu Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly

145 150 155 160

Leu Arg Thr Arg Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg

165 170 175

Arg Phe Ser Ser Leu His Phe Met Val Glu Val Lys Gly Asp Leu Thr

180 185 190

Ala Lys Lys Met Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His

195 200 205

Gly Ala Leu Asp Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln

210 215 220

Ala Ser His Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys

225 230 235 240

Pro Val Ser Val Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys

245 250 255

Pro Ser Leu Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly

260 265 270

Gly Glu Gln Lys Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu

275 280 285

Asp Glu Ser Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln

290 295 300

Glu Gly Leu Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro

305 310 315 320

Thr Pro Ser Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val

325 330 335

Ser Trp Arg Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp

340 345 350

Asp Ile Phe Glu Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu

355 360 365

Leu Arg Val Ala Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met

370 375 380

Pro Gly Cys Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser

385 390 395 400

Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val

405 410 415

Glu Glu Asn Pro Gly Pro Met Ala Leu Pro Val Thr Ala Leu Leu Leu

420 425 430

Pro Leu Ala Leu Leu Leu His Ala Ala Arg Pro Gly Ser Asp Ile Gln

435 440 445

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

450 455 460

Thr Met Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile His Trp Phe

465 470 475 480

Gln Gln Lys Pro Gly Lys Ala Pro Lys Pro Trp Ile Tyr Ala Thr Ser

485 490 495

Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser Gly Ser Gly

500 505 510

Thr Asp Tyr Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala

515 520 525

Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr Phe Gly Gly

530 535 540

Gly Thr Lys Leu Glu Ile Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly

545 550 555 560

Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Gln Ser Gly Ala

565 570 575

Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser

580 585 590

Gly Tyr Thr Phe Thr Ser Tyr Asn Met His Trp Val Lys Gln Ala Pro

595 600 605

Gly Gln Gly Leu Glu Trp Ile Gly Ala Ile Tyr Pro Gly Met Gly Asp

610 615 620

Thr Ser Tyr Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp

625 630 635 640

Glu Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu

645 650 655

Asp Thr Ala Phe Tyr Tyr Cys Ala Arg Ser Thr Tyr Tyr Gly Gly Asp

660 665 670

Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

675 680 685

Ala Ser Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr

690 695 700

Ile Ala Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala

705 710 715 720

Ala Gly Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp Ser

725 730 735

Gly Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu

740 745 750

Leu Ser Leu Val Ile Thr Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu

755 760 765

Leu Tyr Ile Phe Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln

770 775 780

Glu Glu Asp Gly Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly

785 790 795 800

Cys Glu Leu Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr

805 810 815

Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg

820 825 830

Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met

835 840 845

Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu

850 855 860

Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys

865 870 875 880

Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu

885 890 895

Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu

900 905 910

Pro Pro Arg Glx

915

<210> 3028

<211> 3060

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3028

atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg

60

ccgggatccg acatccagat gacacagact acatcctccc tgtctgcctc tctgggagac

120

agagtcacca tcagttgcag ggcaagtcag gacattagta aatatttaaa ttggtatcag

180

cagaaaccag atggaactgt taaactcctg atctaccata catcaagatt acactcagga

240

gtcccatcaa ggttcagtgg cagtgggtct ggaacagatt attctctcac cattagcaac

300

ctggagcaag aagatattgc cacttacttt tgccaacagg gtaatacgct tccgtacacg

360

ttcggagggg ggactaagtt ggaaataaca ggtggcggtg gctcgggcgg tggtgggtcg

420

ggtggcggcg gatctgaggt gaaactgcag gagtcaggac ctggcctggt ggcgccctca

480

cagagcctgt ccgtcacatg cactgtctca ggggtctcat tacccgacta tggtgtaagc

540

tggattcgcc agcctccacg aaagggtctg gagtggctgg gagtaatatg gggtagtgaa

600

accacatact ataattcagc tctcaaatcc agactgacca tcatcaagga caactccaag

660

agccaagttt tcttaaaaat gaacagtctg caaactgatg acacagccat ttactactgt

720

gccaaacatt attactacgg tggtagctat gctatggact actggggtca aggaacctca

780

gtcaccgtct cctcagctag caccacgacg ccagcgccgc gaccaccaac accggcgccc

840

accatcgcgt cgcagcccct gtccctgcgc ccagaggcgt gccggccagc ggcggggggc

900

gcagtgcaca cgaggggggct ggacttcgcc tgtgattccg gaatctacat ctgggcccct

960

ctggccggca cctgtggcgt gctgctgctg tctctcgtga tcaccctgta ctgcaagcgg

1020

ggcagaaaga agctgctgta catcttcaag cagcccttca tgcggcccgt gcagaccacc

1080

caggaagagg acggctgctc ctgcagattc cccgaggaag aagaaggcgg ctgcgagctg

1140

agagtgaagt tcagcagaag cgccgacgcc cctgcctatc agcaggggcca gaaccagctg

1200

tacaacgagc tgaacctgggg cagacgggaa gagtacgacg tgctggacaa gcggagaggc

1260

agggacctg agatgggcgg caagcccaga agaaagaacc ccggaagg cctgtataac

1320

gaactgcaga aagacaagat ggccgaggcc tacagcgaga tcggaatgaa gggcgagcgg

1380

agaagaggca agggccacga tggcctgtac cagggcctga gcaccgccac caaggacacc

1440

tatgacgccc tgcacatgca ggccctgcct ccaaggaa gcggcgccac caatttcagc

1500

ctgctgaaac aggccggcga cgtggaagag aaccctggcc ctagaggcgt gcaggtggaa

1560

accatctctc ccggcgacgg cagaaccttc cctaagaggg gccagacctg cgtggtgcac

1620

tacaccggca tgctggaaga tggcaagaag atggacagct cccgggaccg gaacaagccc

1680

ttcaagttca tgctgggcaa gcaggaagtg atccggggct gggaagaggg cgtggcacag

1740

atgtctgtgg gccagagagc caagctgacc atcagccccg attacgccta cggcgccaca

1800

ggccaccctg gcatcattcc tccacacgcc acactggtgt tcgatgtgga actgctgaag

1860

ctggaaaccc ggggagtgca ggtggaaaca atcagccctg gcgacggccg gacctttcca

1920

aaacggggac agacatgtgt ggtgcattat acagggatgc tggaagatgg gaaaaaaatg

1980

gatagcagcc gcgaccgcaa caaacctttt aagtttatgc tggggaaaca ggaagtgatt

2040

agaggctggg aagagggggt ggcacagatg agcgtgggac agcgggccaa actgacaatc

2100

tcccccgact atgcctatgg ggccaccgga caccccggaa tcatcccacc tcatgctacc

2160

ctggtgtttg acgtggaact gctgaaactg gaaacaagcg gcggaggcag cggcggcttt

2220

ggagatgtgg gagccctgga aagcctgcgg ggcaatgccg atctggccta catcctgagc

2280

atggaaccct gcggccactg cctgattatc aacaacgtga acttctgcag agagagcggc

2340

ctgcggacca gaaccggcag caacatcgac tgcgagaagc tgcggcggag attcagcagc

2400

ctgcacttca tggtggaagt gaagggggac ctgaccgcca agaaaatggt gctggctctg

2460

ctggaactgg cccagcagga tcatggcgcc ctggactgtt gcgtggtcgt gatcctgagc

2520

cacggctgcc aggccagcca tctgcagttt cccggcgctg tgtatggcac cgatggctgc

2580

cctgtgtccg tggaaaagat cgtgaatatc ttcaacggca ccagctgccc cagcctgggc

2640

ggaaagccta agctgttctt tattcaagcc tgtgggggcg agcagaagga ccacggattt

2700

gaggtggcca gcacctcccc cgaggatgag agccctggca gcaaccctga gcctgacgcc

2760

accccattcc aggaaggact gcggaccttc gaccagctgg acgccatctc tagcctgccc

2820

acccccagcg acatcttcgt gtcctacagc accttccctg gctttgtgtc ctggcgggac

2880

cccaagtccg gctcttggta cgtggaaacc ctggacgaca tctttgagca gtgggcccat

2940

agcgaggacc tgcagagcct gctgctgagg gtggccaatg ccgtgtccgt gaagggcatc

3000

tacaagcaga tgcccggctg cttcaacttc ctgcggaaga agctgttttt caagaccagc

3060

<210> 3029

<211> 1020

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3029

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Ser Asp Ile Gln Met Thr Gln Thr Thr Ser

20 25 30

Ser Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala

35 40 45

Ser Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp

50 55 60

Gly Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly

65 70 75 80

Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu

85 90 95

Thr Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln

100 105 110

Gln Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu

115 120 125

Ile Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser

145 150 155 160

Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp

165 170 175

Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp

180 185 190

Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu

195 200 205

Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe

210 215 220

Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys

225 230 235 240

Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly

245 250 255

Gln Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Thr Thr Pro Ala

260 265 270

Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser

275 280 285

Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr

290 295 300

Arg Gly Leu Asp Phe Ala Cys Asp Ser Gly Ile Tyr Ile Trp Ala Pro

305 310 315 320

Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu

325 330 335

Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro

340 345 350

Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys

355 360 365

Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe

370 375 380

Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu

385 390 395 400

Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp

405 410 415

Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys

420 425 430

Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala

435 440 445

Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys

450 455 460

Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr

465 470 475 480

Tyr Asp Ala Leu His Met Gln Ala Leu Pro Arg Gly Ser Gly Ala

485 490 495

Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro

500 505 510

Gly Pro Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg

515 520 525

Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met

530 535 540

Leu Glu Asp Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro

545 550 555 560

Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu

565 570 575

Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser

580 585 590

Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro

595 600 605

His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Arg

610 615 620

Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro

625 630 635 640

Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp

645 650 655

Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe

660 665 670

Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Glu Gly Val Ala

675 680 685

Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr

690 695 700

Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr

705 710 715 720

Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Ser Gly Gly Gly

725 730 735

Ser Gly Gly Phe Gly Asp Val Gly Ala Leu Glu Ser Leu Arg Gly Asn

740 745 750

Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys Gly His Cys Leu

755 760 765

Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly Leu Arg Thr Arg

770 775 780

Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg Arg Phe Ser Ser

785 790 795 800

Leu His Phe Met Val Glu Val Lys Gly Asp Leu Thr Ala Lys Lys Met

805 810 815

Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His Gly Ala Leu Asp

820 825 830

Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln Ala Ser His Leu

835 840 845

Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys Pro Val Ser Val

850 855 860

Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys Pro Ser Leu Gly

865 870 875 880

Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly Gly Glu Glu Gln Lys

885 890 895

Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu Asp Glu Ser Pro

900 905 910

Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln Glu Gly Leu Arg

915 920 925

Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro Thr Pro Ser Asp

930 935 940

Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val Ser Trp Arg Asp

945 950 955 960

Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp Asp Ile Phe Glu

965 970 975

Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu Leu Arg Val Ala

980 985 990

Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met Pro Gly Cys Phe

995 1000 1005

Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser

1010 1015 1020

<210> 3030

<211> 3063

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3030

atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg

60

ccgggatccg atattcaact tacacagtcc cctagttcct tgtccgcctc cgtcggcgac

120

agagttacca tgacttgtcg agcgtcttct agcgtttcct acattcattg gttccaacag

180

aagcccggaa aggcaccaaa accttggatc tacgccacgt ccaatttggc tagtggtgtt

240

ccggtgcgat tttccgggtc aggtagcggg acggactata cttttaccat ttcaagcctt

300

cagcctgaag acatcgcgac gtactattgt cagcagtgga cctctaaccc tcctaccttt

360

ggcggtggaa caaagctgga gatcaaacga ggcggggggtg gctctggggg aggaggttcc

420

ggtgggggag gctctcaagt acaactgcaa caaagtgggg ctgaagtgaa gaagcccggt

480

tcttcagtca aagtatcatg taaggcaagt ggttatactt ttacgtctta taacatgcat

540

tgggtaaagc aagcccctgg tcagggcctc gagtggattg gtgcgatcta ccctggaatg

600

ggtgatacga gctataatca gaaattcaag gggaaagcca ccttgactgc agacgaatct

660

acgaacacgg cttacatgga gcttagctca ctcagatcag aggatacagc cttttactac

720

tgcgctagat caacttatta cggaggagac tggtattttg atgtatgggg tcaggggacc

780

acagtcactg ttagctctgc tagcaccacg acgccagcgc cgcgaccacc aacaccggcg

840

cccaccatcg cgtcgcagcc cctgtccctg cgcccagagg cgtgccggcc agcggcgggg

900

ggcgcagtgc acacgagggg gctggacttc gcctgtgatt ccggaatcta catctgggcg

960

cccttggccg ggacttgtgg ggtccttctc ctgtcactgg ttatcaccct ttactgcaaa

1020

cggggcagaa agaaactcct gtatatattc aaacaaccat ttatgagacc agtacaaact

1080

actcaagagg aagatggctg tagctgccga tttccagaag aagaagaagg aggatgtgaa

1140

ctgagagtga agttcagcag gagcgcagac gcccccgcgt accagcaggg ccagaaccag

1200

ctctataacg agctcaatct aggacgaaga gaggagtacg atgttttgga caagagacgt

1260

ggccgggacc ctgagatgggg gggaaagccg agaaggaaga accctcagga aggcctgtac

1320

aatgaactgc agaaagataa gatggcggag gcctacagtg agattgggat gaaaggcgag

1380

cgccggaggg gcaaggggca cgatggcctt taccagggtc tcagtacagc caccaaggac

1440

acctacgacg cccttcacat gcaggccctg ccccctcgcg gaagcggcgc caccaatttc

1500

agcctgctga aacaggccgg cgacgtggaa gagaaccctg gccctagagg cgtgcaggtg

1560

gaaaccatct ctcccggcga cggcagaacc ttccctaaga ggggccagac ctgcgtggtg

1620

cactacaccg gcatgctgga agatggcaag aagatggaca gctcccggga cgggaacaag

1680

cccttcaagt tcatgctggg caagcaggaa gtgatccggg gctgggaaga gggcgtggca

1740

cagatgtctg tgggccagag agccaagctg accatcagcc ccgattacgc ctacggcgcc

1800

acaggccacc ctggcatcat tcctccacac gccacactgg tgttcgatgt ggaactgctg

1860

aagctggaaa cccggggagt gcaggtggaa acaatcagcc ctggcgacgg ccggaccttt

1920

ccaaaacggg gacagacatg tgtggtgcat tatacaggga tgctggaaga tgggaaaaaa

1980

atggatagca gccgcgaccg caacaaacct tttaagttta tgctggggaa acaggaagtg

2040

attagaggct gggaagggg ggtggcacag atgagcgtgg gacagcgggc caaactgaca

2100

atctcccccg actatgccta tggggccacc ggacacccg gaatcatccc acctcatgct

2160

accctggtgt ttgacgtgga actgctgaaa ctggaaacaa gcggcggagg cagcggcggc

2220

tttggagatg tgggagccct ggaaagcctg cggggcaatg ccgatctggc ctacatcctg

2280

agcatggaac cctgcggcca ctgcctgatt atcaacaacg tgaacttctg cagagagagc

2340

ggcctgcgga ccagaaccgg cagcaacatc gactgcgaga agctgcggcg gagattcagc

2400

agcctgcact tcatggtgga agtgaagggg gacctgaccg ccaagaaaat ggtgctggct

2460

ctgctggaac tggcccagca ggatcatggc gccctggact gttgcgtggt cgtgatcctg

2520

agccacggct gccaggccag ccatctgcag tttcccggcg ctgtgtatgg caccgatggc

2580

tgccctgtgt ccgtggaaaa gatcgtgaat atcttcaacg gcaccagctg ccccagcctg

2640

ggcggaaagc ctaagctgtt ctttattcaa gcctgtgggg gcgagcagaa ggaccacggga

2700

tttgaggtgg ccagcacctc ccccgaggat gagagccctg gcagcaaccc tgagcctgac

2760

gccaccccat tcggaagg actgcggacc ttcgaccagc tggacgccat ctctagcctg

2820

cccaccccca gcgacatctt cgtgtcctac agcaccttcc ctggctttgt gtcctggcgg

2880

gaccccaagt ccggctcttg gtacgtggaa accctggacg acatctttga gcagtgggcc

2940

catagcgagg acctgcagag cctgctgctg agggtggcca atgccgtgtc cgtgaagggc

3000

atctacaagc agatgcccgg ctgcttcaac ttcctgcgga agaagctgtt tttcaagacc

3060

agc

3063

<210> 3031

<211> 1021

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3031

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser

20 25 30

Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Met Thr Cys Arg Ala

35 40 45

Ser Ser Ser Val Ser Tyr Ile His Trp Phe Gln Gln Lys Pro Gly Lys

50 55 60

Ala Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val

65 70 75 80

Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr

85 90 95

Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln

100 105 110

Trp Thr Ser Asn Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile

115 120 125

Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly

145 150 155 160

Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser

165 170 175

Tyr Asn Met His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp

180 185 190

Ile Gly Ala Ile Tyr Pro Gly Met Gly Asp Thr Ser Tyr Asn Gln Lys

195 200 205

Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Glu Ser Thr Asn Thr Ala

210 215 220

Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Phe Tyr Tyr

225 230 235 240

Cys Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asp Val Trp

245 250 255

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Thr Thr Pro

260 265 270

Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu

275 280 285

Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His

290 295 300

Thr Arg Gly Leu Asp Phe Ala Cys Asp Ser Gly Ile Tyr Ile Trp Ala

305 310 315 320

Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr

325 330 335

Leu Tyr Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln

340 345 350

Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser

355 360 365

Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys

370 375 380

Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln

385 390 395 400

Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu

405 410 415

Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg

420 425 430

Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met

435 440 445

Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly

450 455 460

Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp

465 470 475 480

Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg Gly Ser Gly

485 490 495

Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn

500 505 510

Pro Gly Pro Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly

515 520 525

Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly

530 535 540

Met Leu Glu Asp Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys

545 550 555 560

Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu

565 570 575

Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile

580 585 590

Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro

595 600 605

Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr

610 615 620

Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe

625 630 635 640

Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu

645 650 655

Asp Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys

660 665 670

Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val

675 680 685

Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp

690 695 700

Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala

705 710 715 720

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Ser Gly Gly

725 730 735

Gly Ser Gly Gly Phe Gly Asp Val Gly Ala Leu Glu Ser Leu Arg Gly

740 745 750

Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys Gly His Cys

755 760 765

Leu Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly Leu Arg Thr

770 775 780

Arg Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg Arg Phe Ser

785 790 795 800

Ser Leu His Phe Met Val Glu Val Lys Gly Asp Leu Thr Ala Lys Lys

805 810 815

Met Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His Gly Ala Leu

820 825 830

Asp Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln Ala Ser His

835 840 845

Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys Pro Val Ser

850 855 860

Val Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys Pro Ser Leu

865 870 875 880

Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly Gly Glu Gln

885 890 895

Lys Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu Asp Glu Ser

900 905 910

Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln Glu Gly Leu

915 920 925

Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro Thr Pro Ser

930 935 940

Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val Ser Trp Arg

945 950 955 960

Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp Asp Ile Phe

965 970 975

Glu Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu Leu Arg Val

980 985 990

Ala Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met Pro Gly Cys

995 1000 1005

Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser

1010 1015 1020

<210> 3032

<211> 2811

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polynucleotide"

<400> 3032

atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg

60

ccgggatccc ggggcgtgca ggttgagaca atttccccag gagatgggcg aacgttcccc

120

aagcgcggac agacatgcgt tgtgcactac acaggaatgt tggaggacgg aaagaaaatg

180

gacagttcaa gagatcggaa caaaccattc aaattcatgt tgggaaaaca ggaagtgata

240

cggggctggg aaggggtgt agcgcaaatg tccgttggtc aacgagcaaa actcacgata

300

agtcccgatt atgcttacgg cgcaaccggt cacccggggca tcataccgcc tcatgcgact

360

ttggtctttg atgtggagct gttgaaactt gaaactcgcg gagtacaggt tgaaacaata

420

tcacccgggg acgggcggac ttttccgaag agaggtcaga cctgcgtcgt ccattatacc

480

ggtatgctgg aggacggaaa gaaaatggac agctcacgggg accgaaataa accattcaaa

540

tttatgttgg ggaaacaaga ggttatcagg ggctgggagg agggtgtggc ccagatgtct

600

gtcggtcagc gcgcgaaact cacaatctct ccggattatg cgtatggggc gacagggcat

660

ccgggaatta tccctcccca cgctaccttg gttttcgatg ttgagcttct gaagttggag

720

accagaggag ttcaagtgga gacaatatct cctggggatg gacggacgtt ccccaagcgc

780

ggccagacct gtgtagtcca ctacacaggg atgcttgaag acggaaaaaa gatggatagc

840

agtagagatc gcaacaaacc atttaagttc atgctgggga agcaggaagt aatacgcggc

900

tgggaggaag gcgtggcaca gatgagtgtt ggtcaacggg ccaaacttac tatttctccc

960

gattatgcgt atggagccac cgggcaccct ggcattatcc caccccatgc cacattggtt

1020

tttgacgttg aattgcttaa attggagacc aggggagtcc aagtggaaac aatatcaccg

1080

ggggatggtc ggacttttcc taaaaggggc caaacctgtg tagtccatta taccggaatg

1140

ctcgaagacg gaaagaaaat ggactcttct agagaccgca ataagccctt caagttcatg

1200

ttgggtaagc aagaggtgat ccggggctgg gaagaggggg tcgctcaaat gtccgtcggt

1260

cagcgagcta aactgactat ttccccagac tacgcatatg gagcgactgg ccaccccggt

1320

attattcctc cccatgcgac tctcgtgttc gacgtagaac tcttgaaatt ggaaacgtca

1380

gcccggaaca ggcggaagag agatattcaa cttacacagt cccctagttc cttgtccgcc

1440

tccgtcggcg acagagttac catgacttgt cgagcgtctt ctagcgtttc ctacattcat

1500

tggttccaac agaagcccgg aaaggcacca aaaccttgga tctacgccaac gtccaatttg

1560

gctagtggtg ttccggtgcg attttccggg tcaggtagcg ggacggacta tacttttacc

1620

atttcaagcc ttcagcctga agacatcgcg acgtactatt gtcagcagtg gacctctaac

1680

cctcctacct ttggcggtgg aacaaagctg gagatcaaac gaggcggggg tggctctgggg

1740

ggaggaggtt ccggtggggg aggctctcaa gtacaactgc aacaaagtgg ggctgaagtg

1800

aagaagcccg gttcttcagt caaagtatca tgtaaggcaa gtggttatac ttttacgtct

1860

tataacatgc attgggtaaa gcaagcccct ggtcagggcc tcgagtggat tggtgcgatc

1920

taccctggaa tgggtgatac gagctataat cagaaattca agggggaaagc caccttgact

1980

gcagacgaat ctacgaacac ggcttacatg gagcttagct cactcagatc agaggataca

2040

gccttttact actgcgctag atcaacttat tacggaggag actggtattt tgatgtatgg

2100

ggtcagggga ccacagtcac tgttagctct gctagcacca cgacgccagc gccgcgacca

2160

ccaacaccgg cgcccaccat cgcgtcgcag cccctgtccc tgcgcccaga ggcgtgccgg

2220

ccagcggcgg ggggcgcagt gcacacgagg gggctggact tcgcctgtga ttcgggaatc

2280

tacatctggg cgcccttggc cgggacttgt ggggtccttc tcctgtcact ggttatcacc

2340

ctttactgca aacggggcag aaagaaactc ctgtatatat tcaaacaacc atttatgaga

2400

ccagtacaaa ctactcaaga ggaagatggc tgtagctgcc gatttccaga agaagaagaa

2460

ggaggatgtg aactgagagt gaagttcagc aggagcgcag acgcccccgc gtaccagcag

2520

ggccagaacc agctctataa cgagctcaat ctaggacgaa gagaggagta cgatgttttg

2580

gacaagagac gtggccggga ccctgagatg gggggaaagc cgagaaggaa gaaccctcag

2640

gaaggcctgt acaatgaact gcagaaagat aagatggcgg aggcctacag tgagattgggg

2700

atgaaaggcg agcgccggag gggcaagggg cacgatggcc tttaccaggg tctcagtaca

2760

gccaccaagg acacctacga cgcccttcac atgcaggccc tgccccctcg c

2811

<210> 3033

<211> 939

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

polypeptide"

<400> 3033

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro Gly Ser Arg Gly Val Gln Val Glu Thr Ile Ser

20 25 30

Pro Gly Asp Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val

35 40 45

His Tyr Thr Gly Met Leu Glu Asp Gly Lys Lys Met Asp Ser Ser Arg

50 55 60

Asp Arg Asn Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile

65 70 75 80

Arg Gly Trp Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala

85 90 95

Lys Leu Thr Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro

100 105 110

Gly Ile Ile Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu

115 120 125

Lys Leu Glu Thr Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp

130 135 140

Gly Arg Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr

145 150 155 160

Gly Met Leu Glu Asp Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn

165 170 175

Lys Pro Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp

180 185 190

Glu Glu Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr

195 200 205

Ile Ser Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile

210 215 220

Pro Pro His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu

225 230 235 240

Thr Arg Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr

245 250 255

Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu

260 265 270

Glu Asp Gly Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe

275 280 285

Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly

290 295 300

Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro

305 310 315 320

Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His

325 330 335

Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Arg Gly

340 345 350

Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe Pro Lys

355 360 365

Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu Asp Gly

370 375 380

Lys Lys Met Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys Phe Met

385 390 395 400

Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Glu Gly Val Ala Gln

405 410 415

Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp Tyr Ala

420 425 430

Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala Thr Leu

435 440 445

Val Phe Asp Val Glu Leu Leu Lys Leu Glu Thr Ser Ala Arg Asn Arg

450 455 460

Arg Lys Arg Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu

465 470 475 480

Ser Ala Ser Val Gly Asp Arg Val Thr Met Thr Cys Arg Ala Ser Ser

485 490 495

Ser Val Ser Tyr Ile His Trp Phe Gln Gln Lys Pro Gly Lys Ala Pro

500 505 510

Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val

515 520 525

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr Ile Ser

530 535 540

Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Trp Thr

545 550 555 560

Ser Asn Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg

565 570 575

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

580 585 590

Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser

595 600 605

Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Asn

610 615 620

Met His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly

625 630 635 640

Ala Ile Tyr Pro Gly Met Gly Asp Thr Ser Tyr Asn Gln Lys Phe Lys

645 650 655

Gly Lys Ala Thr Leu Thr Ala Asp Glu Ser Thr Asn Thr Ala Tyr Met

660 665 670

Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Phe Tyr Tyr Cys Ala

675 680 685

Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly Gln

690 695 700

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Thr Thr Pro Ala Pro

705 710 715 720

Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser Leu

725 730 735

Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr Arg

740 745 750

Gly Leu Asp Phe Ala Cys Asp Ser Gly Ile Tyr Ile Trp Ala Pro Leu

755 760 765

Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr

770 775 780

Cys Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe

785 790 795 800

Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg

805 810 815

Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg Val Lys Phe Ser

820 825 830

Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr

835 840 845

Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys

850 855 860

Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn

865 870 875 880

Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu

885 890 895

Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly

900 905 910

His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr

915 920 925

Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

930 935

<210> 3034

<211> 63

<212> DNA

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

oligonucleotide"

<400> 3034

atggccttac cagtgaccgc cttgctcctg ccgctggcct tgctgctcca cgccgccagg

60

ccg

63

<210> 3035

<211> 21

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 3035

Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu

1 5 10 15

His Ala Ala Arg Pro

20

<210> 3036

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

Synthetic

peptide"

<400> 3036

Ser Gly Gly Gly Ser

15

<---

Claims (74)

1. Fusion protein for use in the treatment of a subject having cancer associated with the expression of a tumor antigen, in the presence of a stabilizing compound, containing two protein domains separated by a furin cleavage site, where the first of these protein domains is a degradation domain for regulated expression of the specified fusion protein and the second of these protein domains is a chimeric antigen receptor (CAR), where: (i) the degradation domain is an estrogen receptor (ER) domain; And (ii) said CAR contains an antigen-binding domain that specifically binds said tumor antigen, a transmembrane domain, and one or more intracellular signaling domains. 2. A fusion protein for use in the treatment of a subject having cancer associated with the expression of a tumor antigen in the presence of a stabilizing compound, containing two protein domains separated by a furin cleavage site, where the first of said protein domains is a degradation domain for regulated expression of said fusion protein and the second of these protein domains is a chimeric antigen receptor (CAR), where: (i) the degradation domain is a FKB protein domain (FKBP); And (ii) said CAR contains an antigen-binding domain that specifically binds said tumor antigen, a transmembrane domain, and one or more intracellular signaling domains. 3. The fusion protein of claim 1, wherein the degradation domain contains an amino acid sequence that is at least 90%, 95%, 97%, 98%, 99%, or 100% identical to any of SEQ ID NOs: 58 or 121. 4. The fusion protein of claim 2, wherein the degradation domain contains an amino acid sequence that is at least 90%, 95%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 56. 5. Fusion protein according to any one of paragraphs. 1-4, where the degradation domain has a first state associated with a first level of surface expression and/or extracellular expression of the fusion protein, and a second state associated with a second level of surface expression and/or extracellular expression of the fusion protein, where the second level is increased, for example, at least 2, 3, 4, 5, 10, 20 or 30 times the first level, in the presence of a stabilizing compound. 6. The fusion protein of claim 1 wherein said stabilizing compound is selected from bazedoxifene and 4-hydroxy tamoxifen (4-OHT). 7. The fusion protein of claim 2, wherein said stabilizing compound is Shield-1. 8. Fusion protein according to any one of paragraphs. 1-7, wherein said furin cleavage site contains a polypeptide having the RX(K/R)R consensus motif. 9. Fusion protein according to any one of paragraphs. 1-8, wherein said furin cleavage site is selected from RTKR (SEQ ID NO: 123); GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125); GTGAEDPRPSRKRR (SEQ ID NO: 127); LQWLEQQVAKRRTKR (SEQ ID NO: 129); GTGAEDPRPSRKRRSLGG (SEQ ID NO: 131); GTGAEDPRPSRKRRSLG (SEQ ID NO: 133); SLNLTESHNSRKKR (SEQ ID NO: 135) or CKINGYPKRGRKRR (SEQ ID NO: 137). 10. The fusion protein of claim 9 wherein said furin cleavage site is GTGAEDPRPSRKRRSLGDVG (SEQ ID NO: 125). 11. The fusion protein of claim 1, wherein said intracellular signaling domain contains one or more major signaling domains. 12. The fusion protein of claim 1, wherein said intracellular signaling domain contains one or more costimulatory signaling domains. 13. The fusion protein of claim 1, wherein said intracellular signaling domain comprises one or more basic signaling domains and one or more co-stimulatory signaling domains. 14. The fusion protein of claim 11 or 13, wherein one of said one or more major signaling domains comprises a CD3 zeta stimulatory domain. 15. A fusion protein according to claim 12 or 13, wherein said one or more of said costimulatory signaling domains is an intracellular domain from a costimulatory protein selected from the group consisting of CD27, CD28, 4-1BB (CD137), OX40, GITR, CD30, CD40, ICOS, BAFFR, HVEM, ICAM-1, lymphocyte function-associated antigen 1 (LFA-1), CD2, CDS, CD7, CD287, LIGHT, NKG2C, NKG2D, SLAMF7, NKp80, NKp30, NKp44, NKp46 , CD160, B7-H3, or a ligand that specifically binds CD83. 16. The fusion protein of claim 15, wherein said one or more of said co-stimulatory signaling domains comprises a 4-1BB co-stimulatory domain. 17. The fusion protein of claim 15, wherein said one or more of said costimulatory domains comprises a CD28 costimulatory domain. 18. The fusion protein of claim 1, wherein said antigen-binding domain is scFv. 19. Fusion protein according to claim 1, where the specified antigennegative domain binds an antigen selected from the group consisting of CD19; CD123; CD22; CD30; CD171; CS-1; lectin-like C-type molecule 1, CD33; epidermal growth factor variant III receptor (EGFRvIII); ganglioside G2 (GD2); ganglioside GD3; a member of the TNF receptor family, B cell maturation antigen (BCMA); Tn antigen ((Tn Ag) or (GalNAcα-Ser/Thr)); prostate specific membrane antigen (PSMA); tyrosine kinase-like orphan receptor 1 (ROR1); Fms-like tyrosine kinase 3 (FLT3); tumor-associated glycoprotein 72 (TAG72); CD38; CD44v6; carcinoembryonic antigen (CEA); epithelial cell adhesion molecules (EPCAM); B7H3 (CD276); KIT (CD117); alpha-2 subunits of the interleukin-13 receptor; mesothelin; interleukin-11 receptor alpha subunits (IL-11Ra); prostatic stem cell antigen (PSCA); serine protease 21; vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; platelet growth factor receptor beta (PDGFR-beta); stage-specific embryonic antigen-4 (SSEA-4); CD20; folate receptor alpha; receptor tyrosine-specific protein kinase ERBB2 (Her2/neu); mucin 1 associated with the cell surface (MUC1); epidermal growth factor receptor (EGFR); neuronal adhesion molecules (NCAM); prostases; prostatic acid phosphatase (PAP); mutant elongation factor 2 (ELF2M); aphrine B2; fibroblast activation protein alpha (FAP); insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAIX); proteasome subunits (prosoma, macropain), type beta, 9 (LMP2); glycoprotein 100 (gp100); an oncogenic fusion protein comprising a rearrangement initiation site (BCR) localization region and Abelson murine leukemia viral oncogene homologue 1 (Abl) (bcr-abl); tyrosinase; aphrin A2 receptor (EphA2); fucosyl GM1; sialyl-Lewis adhesion molecules (sLe); ganglioside GM3; transglutaminase 5 (TGS5); high molecular weight melanoma-associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); folate receptor beta; tumor endothelial marker 1 (TEM1/CD248); antigen related to tumor endothelial marker 7 (TEM7R); claudin-6 (CLDN6); thyroid stimulating hormone receptor (TSHR); G protein-coupled receptor class C, group 5, member D (GPRC5D); X chromosome open reading frame 61 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); polysialic acid; placenta-specific protein 1 (PLAC1); the hexasaccharide portion of glycoceramide globoH (GloboH); breast differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); hepatitis A virus cell receptor 1 (HAVCR1); adrenoreceptor beta-3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); complex of lymphocytic antigen 6, locus K9 (LY6K); olfactory receptor 51E2 (OR51E2); protein TCR-gamma with an alternative reading frame (TARP); Wilms tumor protein (WT1); testicular cancer antigen 1 (NY-ESO-1); testicular cancer antigen 2 (LAGE-1a); melanoma-associated antigen 1 (MAGE-A1); translocation variant 6 of the ETS gene located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); family X antigens, representative 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); testicular melanoma antigen 1 (MAD-CT-1); testicular melanoma antigen 2 (MAD-CT-2); Fos-related antigen 1; tumor protein p53 (p53); p53 mutant; protein; survivin; telomerase; prostate carcinoma tumor antigen 1, melanoma antigen 1 recognized by T-cells; a protein mutant of the rat sarcoma virus (Ras); human telomerase reverse transcriptase (hTERT); break points during translocation in the case of sarcoma; an inhibitor of apoptosis from melanoma cells (ML-IAP); ERG (transmembrane serine protease 2 (TMPRSS2) and ETS fusion gene); N-acetylglucosamine transferase V (NA17); paired box protein Pax-3 (PAX3); androgen receptor; cyclin B1; a neuroblastoma-derived homologue of the v-myc oncogene of avian myelocytomatosis virus (MYCN); a member of the C family of Ras homologues (RhoC); tyrosinase-related protein 2 (TRP-2); cytochrome P450 1B1 (CYP1B1); a CCCTC-binding factor-like protein (zinc finger protein) recognized by T-cells of squamous cell carcinoma antigen 3 (SART3); paired box protein Pax-5 (PAX5); proacrosin-binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); anchor protein 4 A-kinase (AKAP-4); breakpoints 2 in X in synovial sarcoma (SSX2); receptor for advanced glycosylation end products (RAGE-1); renal ubiquitous protein 1 (RU1); renal ubiquitous protein 2 (RU2); legumain; human papillomavirus E6 protein (HPV E6); human papillomavirus E7 protein (HPV E7); intestinal carboxylesterase; mutant heat shock protein 70-2 (mut hsp70-2); CD79a; CD79b; CD72; leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Fc fragment of the IgA receptor (FCAR or CD89); leukocyte immunoglobulin-like receptors, subfamily A, member 2 (LILRA2); a family of proteins similar to the CD300 molecule, representative f (CD300LF); a family of 12 C-type domain lectins, representative A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); protein 2, like the EGF-like domain-containing mucin-like hormone receptor (EMR2); lymphocyte antigen 75 (LY75); glypican-3 (GPC3); Fc receptor-like protein 5 (FCRL5) or lambda chain-like immunoglobulin polypeptide 1 (IGLL1). 20. The fusion protein of claim 19, wherein said antigen is CD19. 21. A fusion protein according to claim 20, containing an antigen-binding domain containing an amino acid sequence selected from any of SEQ ID NOs: 356-368 or 381. 22. A fusion protein according to claim 20, containing a chimeric antigen receptor containing an amino acid sequence selected from any of SEQ ID NOs: 897, 902, 907, 912, 917, 922, 927, 932, 937, 942, 947, 952, or 956. 23. The fusion protein of claim 19, wherein said antigen is CD123. 24. A fusion protein according to claim 23, containing an antigen-binding domain containing an amino acid sequence selected from any of SEQ ID NOs: 751, 756, 761, or 766. 25. A fusion protein according to claim 23 containing a chimeric antigen receptor containing an amino acid sequence selected from any of SEQ ID NOs: 750, 755, 760, or 765. 26. The fusion protein of claim 19, wherein said antigen is BCMA. 27. A fusion protein according to claim 26, containing an antigen-binding domain containing an amino acid sequence selected from any of SEQ ID NOs: 382, 386, 390, 394, 398, 402, 406, 410, 414, 418, 422, 426, 430 , 434, 438, 442, 446, 450, 454, 458, 462, 466, 470, 474, 478, 482, 486, 490, 494, 498, 502, 506, 510, 514, 518, 522, 528, 531 , 534 or 537. 28. A fusion protein according to claim 26, containing a chimeric antigen receptor containing an amino acid sequence selected from any of SEQ ID NOs: 789, 791, 793, 795, 797, 799, 801, 803, 805, 807, 809, 811, 813, 815, 817, 819, 821, 823, 825, 827, 829, 831, 833, 835, 837, 839, 841, 843, 845, 847, 849, 851, 853, 855, 857 or 859. 29. The fusion protein of claim 19, wherein said antigen is CD20. 30. A fusion protein according to claim 29, containing an antigen-binding domain containing an amino acid sequence occupying positions 470-712 or 470-939 in SEQ ID NO: 3033. 31. A fusion protein according to claim 29 containing a chimeric antigen receptor containing the amino acid sequence of SEQ ID NO: 3033. 32. The fusion protein according to claim 1, where the degradation domain is located in: a) N-terminal direction relative to the specified second protein domain; or b) C-terminal direction relative to the specified second protein domain. 33. A fusion protein according to claim 1, additionally containing a signal peptide. 34. The fusion protein of claim 33, wherein said signal peptide is located N-terminally relative to said degradation domain. 35. The fusion protein of claim 33, further comprising a linker located between the signal peptide and another domain of the fusion protein. 36. The fusion protein of claim 35, wherein said linker is located between said signal peptide and said degradation domain. 37. A fusion protein according to claim 1, containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 67, 69, 75, 103, 105, 107, 109, 111, 113, 115, 141, 143, 145, 147 , 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183 and 990-1049. 38. A fusion protein according to claim 2, containing an amino acid sequence selected from the group consisting of SEQ ID NO: 59 or 61. 39. Nucleic acid encoding a fusion protein according to claim 37 or 38. 40. An expression vector containing the nucleic acid according to claim 39. 41. The expression vector according to claim 40, which is a viral vector. 42. The expression vector according to claim 40, which is a lentiviral vector. 43. Lentiviral particle to obtain a fusion protein containing an expression vector according to any one of paragraphs. 40-42. 44. A mammalian immune effector cell for controlled expression of a fusion protein, comprising an expression vector according to any one of paragraphs. 40-42. 45. The mammalian cell of claim 44, wherein said human effector cell is a human T cell or a human NK cell. 46. A mammalian cell according to claim 44, wherein said cell further comprises furin. 47. The mammalian cell of claim 44 wherein, in the absence of said stabilizing compound, the fusion protein is degraded in cellular degradation pathways. 48. The mammalian cell of claim 47 wherein at least 50%, 60%, 70%, 80%, 90% or more of the fusion protein is degraded. 49. The mammalian cell of claim 44, wherein in the presence of said stabilizing compound, the degradation domain assumes a conformation that is more resistant to degradation in the cell in the presence of the stabilizing compound, compared to a conformation in the absence of the stabilizing compound. 50. The mammalian cell of claim 44, wherein in the presence of said stabilizing compound, the conformation of the fusion protein is more susceptible to cleavage at the furin cleavage site in the presence of the stabilizing compound, compared to the conformation in the absence of the stabilizing compound. 51. The mammalian cell of claim 44, wherein in the presence of said stabilizing compound, the level of cell surface expression or extracellular expression of the fusion protein is increased by at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, or 30 times the level of cell surface expression or extracellular expression of the fusion protein in a cell not containing a stabilizing compound. 52. A method of treating a subject having cancer associated with the expression of a tumor antigen, comprising administering to the subject an effective amount of a mammalian cell according to claim 44 and said stabilizing compound, wherein said CAR contains, in the direction from the N-terminus to the C-terminus, an antigen-binding domain, a transmembrane domain and one or more intracellular signaling domains, and said antigen-binding domain specifically binds said tumor antigen. 53. A mammalian cell according to claim 44 for use in the treatment of cancer associated with the expression of a tumor antigen in a subject. 54. The method of claim 52, wherein said mammalian cell is autologous for said subject. 55. The method of claim 52, wherein said mammalian cell is allogeneic to said subject. 56. The method of claim 52 wherein said stabilizing compound is selected from bazedoxifene or 4-hydroxy tamoxifen (4-OHT) if the fusion protein contains a degradation domain derived from the estrogen receptor. 57. The method of claim 52, wherein said stabilizing compound is Shield-1 if the fusion protein contains a degradation domain derived from the FKB protein. 58. The method of claim 52, wherein the cancer is mesothelioma, lung cancer, pancreatic cancer, esophageal adenocarcinoma, ovarian cancer, breast cancer, colorectal cancer, bladder cancer, or any combination thereof. 59. The method of claim 58 wherein the mesothelioma is malignant pleural mesothelioma. 60. The method of claim 58, wherein the lung cancer is non-small cell lung cancer, small cell lung cancer, squamous cell lung cancer, or large cell lung cancer. 61. The method of claim 58 wherein the pancreatic cancer is pancreatic ductal adenocarcinoma or pancreatic metastatic ductal adenocarcinoma (PDA). 62. The method of claim 58 wherein the ovarian cancer is serous epithelial ovarian cancer. 63. The method of claim 52, wherein the disease associated with the expression of the tumor antigen is hematological cancer. 64. The method of claim 63 wherein the hematologic cancer is selected from leukemia and lymphoma. 65. The method of claim 63, wherein the hematologic cancer is selected from: chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), multiple myeloma, acute lymphoblastic leukemia (ALL), Hodgkin's lymphoma, B-cell acute lymphoblastic leukemia ( BALL), T-cell acute lymphoblastic leukemia (TALL), small cell lymphocytic lymphoma (SLL), B-cell prolymphocytic leukemia, blast plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B-cell lymphoma (DLBCL), DLBCL associated with chronic inflammation, chronic myeloid leukemia, myeloproliferative neoplasms, follicular lymphoma, follicular lymphoma in children, hairy cell leukemia, small cell or large cell follicular lymphoma, malignant lymphoproliferative conditions, MALT-type lymphoma (extranodal marginal zone lymphoma arising from mucosal associated lymphoid tissue ), marginal zone lymphoma, myelodysplasia, myelodysplastic syndrome, non-Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, spleen cell lymphoma/leukemia, diffuse small B-cell lymphoma of the red pulp of the spleen, hairy cell leukemia - variant, lymphoplasmic lymphoma, heavy chain disease, plasma cell myeloma, solitary bone plasmacytoma, extraosseous plasmacytoma, nodal marginal zone lymphoma, nodal marginal zone lymphoma in children, primary cutaneous follicular lymphoma, lymphogranulomatosis, primary mediastinal large B-cell lymphoma (thymus) , intravascular large B-cell lymphoma, ALK+ large B-cell lymphoma, large B-cell lymphoma arising from HHV8-associated multifocal Castleman disease, primary effusion lymphoma, B-cell lymphoma, acute myeloid leukemia (AML), or unclassifiable lymphoma. 66. The method of claim 65 wherein the cancer is selected from MCL, CLL, ALL, Hodgkin's lymphoma, AML, and multiple myeloma. 67. The use of a fusion protein according to claim 1 or 2 in the treatment of cancer associated with the expression of a tumor antigen directed by the CAR antigen-binding domain in said fusion protein, where said fusion protein is expressed by a mammalian immune effector cell in the presence of said stabilizing compound. 68. The use of a mammalian cell according to claim 44 in the treatment of cancer associated with the expression of a tumor antigen targeted by the CAR antigen-binding domain in said fusion protein, in the presence of said stabilizing compound.

Images