EA044325B1 - HETERODIMERIC ANTI-CD3xCD20 ANTIBODY, ITS PREPARATION AND APPLICATION - Google Patents

Description

This patent application claims priority under 35 U.S.C. 119(e) US Provisional Patent Application No. 62/085117, filed November 26, 2014, US Provisional Patent Application No. 62/084908, filed November 26, 2014, US Provisional Patent Application No. 62/085027, filed 26 November 2014, US Provisional Patent Application No. 62/085106, filed November 26, 2014, US Provisional Patent Application No. 62/159111, filed May 8, 2015, US Provisional Patent Application No. 62/251005, filed November 4, 2015, and U.S. Provisional Patent Application No. 62/250971, filed November 4, 2015, which are expressly incorporated herein by reference in their entirety with specific reference to the figures, legends and claims.

BACKGROUND OF THE INVENTION

Antibody-based therapeutics have been successfully used to treat a range of diseases, including cancer and autoimmune/inflammatory disorders. However, improvements in this class of drugs are still needed, especially with regard to increasing their clinical effectiveness. One promising aspect is to design additional and new antigen-binding sites in antibody-based drugs so that one immunoglobulin molecule contacts two different antigens simultaneously. Such non-native or alternative antibody formats that contact two different antigens are often called bispecific. Because significant diversity in the variable region (Fv) of an antibody allows one to obtain an Fv that recognizes virtually any molecule, a typical approach to creating a bispecific antibody is to introduce new variable regions into the antibody.

A number of alternative antibody formats have been explored for bispecific targeting (Chames & Baty, 2009, mAbs 1[6]:1-9; Holliger & Hudson, 2005, Nature Biotechnology 23[9]:1126-1136; Kontermann, mAbs 4( 2):182 (2012), all of which are expressly incorporated herein by reference). Originally, bispecific antibodies were produced by fusing two cell lines, each of which produced one monoclonal antibody (Milstein et al., 1983, Nature 305:537-540). Although the resulting hybridoma, or quadroma, did produce bispecific antibodies, they were only a minor population and lengthy purification was required to isolate the desired antibody. The technical solution for this was the use of antibody fragments to produce bispecific antibodies. Since such fragments lack the complex quaternary structure characteristic of a full-length antibody, the variable regions of the light and heavy chains can be linked in single genetic constructs. Antibody fragments have been produced in many different forms, including diabodies, single chain diabodies, tandem scFvs and bispecific Fab ₂ (Chames & Baty, 2009, mAbs 1[6]:1-9; Holliger & Hudson, 2005, Nature Biotechnology 23[9]: 1126-1136; expressly incorporated herein by reference). Although these formats can be expressed at high levels in bacteria and may have favorable permeation advantages due to their small size, they are rapidly eliminated in vivo and can present production and stability challenges. The main reason for these disadvantages is that antibody fragments typically do not have an antibody constant region with appropriate functional properties, including large size, high stability, and binding to various Fc receptors and ligands that maintain a long serum half-life (i.e., neonatal Fc receptor FcRn) or serve as binding sites for purification (ie, protein A and protein G).

More recent work has attempted to overcome the shortcomings of fragment-based bispecific antibodies by designing dual binding in full-length antibody-like formats (Wu et al., 2007, Nature Biotechnology 25[11]:1290-1297; USSN12/477.711; Michaelson et al. , 2009, mAbs 1[2]:128-141; PCT/US2008/074693; Zuo et al., 2000, Protein Engineering 13[5]:361-367; USSN09/865.198; Shen et al., 2006, J Biol Chem 281[16]:10706-10714; Lu et al., 2005, J Biol Chem 280[20]:19665-19672; PCT/US2005/025472; expressly incorporated herein by reference). These formats eliminate some of the complexities associated with bispecific antibody fragments, mainly due to the fact that they contain an Fc region. One significant disadvantage of these formats is that because they create new antigen-binding sites on top of the homodimeric constant chains, binding to the new antigen is always bivalent.

For many antigens that are attractive as co-targets in a therapeutic bispecific format, the desired binding is monovalent rather than bivalent. For many immune receptors, cellular activation is accomplished by cross-linking a monovalent binding interaction. The mechanism of cross-linking is typically mediated by antibody/antigen immune complexes or through an effector cell involving the target cell. For example, low-affinity Fc gamma receptors (FcyRs), such as FcyRIIa, FcyRIIb and FcyRIIIa, bind monovalently to the Fc region of an antibody. Monovalent binding is not

- 1 044325 activates cells expressing these FcyRs; however, upon formation of immune complexes or cell-to-cell contact, the receptors cross-link and cluster on the cell surface, resulting in activation. For receptors responsible for mediating cell killing, such as FcyRIIIa on natural killer (NK) cells, receptor cross-linking and cellular activation occur when the effector cell contacts the target cell in a highly avid format (Bowles & Weiner, 2005, J Immunol Methods 304:88-99, expressly incorporated by reference). Similarly, on B cells, the inhibitory receptor FcyRIIb suppresses B cell activation only when it is engaged in an immune complex with the B cell receptor (BCR) on the cell surface, a mechanism that is mediated by the formation of soluble IgG complexes with the same antigen that recognized by the BCR (Heyman 2003, Immunol Lett 88[2]:157161; Smith and Clatworthy, 2010, Nature Reviews Immunology 10:328-343; expressly incorporated by reference). As another example, activation of T cells by CD3 occurs only when the associated T cell receptor (TCR) is engaged by antigen-loaded MHC on antigen-presenting cells at a highly avid cell-to-cell synapse (Kuhns et al., 2006, Immunity 24:133-139). Indeed, nonspecific bivalent cross-linking of CD3 using an anti-CD3 antibody causes a cytokine storm and toxicity (Perruche et al., 2009, J Immunol 183[2]:953-61; Chatenoud & Bluestone, 2007, Nature Reviews Immunology 7:622-632 ; expressly incorporated by reference). Thus, for practical clinical use, the preferred form of CD3 co-engagement for redirected target cell killing is monovalent binding, which results in activation only upon contact with a co-engaged target.

CD38, also known as cyclic ADP-ribose hydrolase, is a type II transmembrane glycoprotein with a long C-terminal extracellular domain and a short N-terminal cytoplasmic domain. Among hematopoietic cells, a number of functional effects have been attributed to CD38-mediated signaling, including lymphocyte proliferation, cytokine release, regulation of B cell and myeloid cell development and survival, and induction of dendritic cell maturation. CD38 is dysregulated in many hematopoietic malignancies and in cell lines derived from various hematopoietic malignancies, including non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL), multiple myeloma (MM), B-cell chronic lymphocytic leukemia (B-cell). CLL), B- and T-cell acute lymphocytic leukemia (ALL), T-cell lymphoma (TCL), acute myeloid leukemia (AML), hairy cell leukemia (HCL), Hodgkin lymphoma (HL) and chronic myeloid leukemia (CML). On the other hand, most primitive pluripotent stem cells of the hematopoietic system are CD38-. Despite recent progress in the discovery and development of anticancer agents, many forms of cancer, including CD38-expressing tumors, still have a poor prognosis. Thus, there is a need for improved methods of treating such forms of cancer.

B cell antigen CD19 (CD19, also known as B cell surface antigen B4, Leu-12) is a surface marker of all human B cells that is expressed from the early stages of pre-B cell development until terminal differentiation into plasma cells. CD19 promotes proliferation and survival of mature B cells. It forms a complex with CD21 on the cell surface. It also combines with CD81 and Leu-13 and potentiates B cell receptor (BCR) signaling. CD19, together with the BCR, modulates intrinsic and antigen receptor-induced signaling checkpoints critical for B cell lineage and humoral immunity. Together with CD21, it links the adaptive and innate immune systems. Once activated, the cytoplasmic tail of CD19 becomes phosphorylated, resulting in binding by Src family kinases and recruitment of PI 3-kinase. It represents an attractive target for immunotherapy of cancers of lymphoid origin, since it is also expressed on the vast majority of NHL cells, as well as in some forms of leukemia.

A number of antibodies or antibody conjugates that target CD19 have been evaluated in preclinical studies or clinical trials for the treatment of forms of cancer. These CD19 antibodies or antibody conjugates include, but are not limited to, MT-103 (a single chain bispecific antibody to CD19/CD3; Hoffman et al., 2005 Int. J. Cancer 115:98-104; Schlereth et al., 2006 Cancer Immunol. Immunother. 55:503-514), anti-CD19/CD16 diabody (Schlenzka et al., 2004 Anti-cancer Drugs 15:915-919; Kipriyanov et al., 2002 J Immunol. 169:137-144), BU12-saporin (Flavell et al., 1995 Br. J. Cancer 72:1373-1379) and anti-CD19 antibody-idarubicin conjugate (Rowland et al., 1993 Cancer Immunol. Immunother. 55:503-514); all are expressly incorporated by reference.

CD123, also known as interleukin-3 receptor alpha (IL-3Ra), is expressed on dendritic cells, monocytes, eosinophils and basophils. CD123 is also constitutively expressed by committed hematopoietic stem/progenitor cells, most myeloid lineages (CD13+, CD14+, CD33+, CD15low) and some CD19+ cells. He's away

- 2 044325 acts on CD3+ cells.

Thus, while bispecific antibodies derived from antibody fragments have disadvantages in terms of biophysical and pharmacokinetic properties, antibodies generated in full-length antibody-like formats have the disadvantage that they contact common target antigens polyvalently in the absence of the primary antibody. target antigen, leading to nonspecific activation and potential toxicity. The present invention solves this problem by introducing new bispecific antibodies targeting CD3 and CD38.

Brief description of the invention

Accordingly, in one aspect, the present invention provides heterodimeric antibodies comprising: a) a first monomer comprising: i) a first heavy chain comprising: 1) a first heavy chain variable domain; 2) the first heavy chain constant domain containing the first Fc domain; 3) scFv containing a light chain scFv variable domain, a scFv linker and a heavy chain scFv variable domain; wherein said scFv is covalently linked to the C-terminus of said Fc domain via an interdomain linker; b) a second monomer containing a second heavy chain containing a second heavy chain variable domain and a second heavy chain constant domain containing a second Fc domain; and c) a common light chain comprising a light chain variable domain and a light chain constant domain.

In a further aspect, the present invention provides heterodimeric antibodies comprising: a) a first monomer comprising: i) a first heavy chain comprising: 1) a first heavy chain variable domain; 2) the first heavy chain constant domain containing the first Fc domain; and 3) a first light chain variable domain, wherein said first light chain variable domain is covalently connected to the C-terminus of said first Fc domain by an interdomain linker; b) a second monomer comprising: i) a second heavy chain variable domain; ii) a second heavy chain constant domain comprising a second Fc domain; and iii) a third heavy chain variable domain, wherein said second heavy chain variable domain is covalently linked to the C-terminus of said second Fc domain by an interdomain linker; c) a common light chain comprising a light chain variable domain and a light chain constant domain.

In a further aspect, the present invention provides heterodimeric antibodies comprising: a) a first monomer comprising: i) a first heavy chain comprising: 1) a first heavy chain variable domain; 2) the first constant domain of the heavy chain, containing the first CH1 domain and the first Fc domain; 3) scFv containing a light chain scFv variable domain, a scFv linker and a heavy chain scFv variable domain; wherein said scFv is covalently attached between the C-terminus of said CH1 domain and the N-terminus of said first Fc domain using interdomain linkers; b) a second monomer containing a second heavy chain containing a second heavy chain variable domain and a second heavy chain constant domain containing a second Fc domain; and c) a common light chain comprising a light chain variable domain and a light chain constant domain.

In a further aspect, the present invention provides heterodimeric antibodies comprising: a) a first monomer comprising: i) a first heavy chain comprising: 1) a first heavy chain variable domain; 2) the first heavy chain constant domain containing the first Fc domain; and 3) a first light chain variable domain, wherein said second light chain variable domain is covalently attached between the C-terminus of a CH1 domain of said first heavy chain constant domain and the N-terminus of said first Fc domain via interdomain linkers; b) a second monomer comprising: i) a second heavy chain variable domain; ii) a second heavy chain constant domain comprising a second Fc domain; and iii) a third heavy chain variable domain, wherein said second heavy chain variable domain is covalently linked to the C-terminus of said second Fc domain via an interdomain linker; c) a common light chain comprising a light chain variable domain and a light chain constant domain.

In a further aspect, the present invention provides heterodimeric antibodies comprising: a) a first monomer comprising: i) a first heavy chain comprising: 1) a first heavy chain variable domain; 2) the first constant domain of the heavy chain, containing the first CH1 domain and the first Fc domain; 3) scFv containing a light chain scFv variable domain, a scFv linker and a heavy chain scFv variable domain; wherein said scFv is covalently attached between the C-terminus of said CH1 domain and the N-terminus of said first Fc domain using interdomain linkers; b) a second monomer containing a second Fc domain; and c) a light chain comprising a light chain variable domain and a light chain constant domain.

In some aspects, the first and second Fc domains include a set of amino acid substitutions selected from the group consisting of S364K/E357Q: L368D/K370S; L368D/K370S: S364K; L368E/K370S: S364K; T411T/E360E/Q362E: D401K; L368D/K370S: S364K/E357L and K370S: S364K/E357Q. In addition, the heavy chain variable domain(s) and light chain variable domain(s) bind the first tumor target antigen (TTA), the scFv binds the second TTA or human CD3. In some embodiments, the TTA is selected from the group consisting of CD19, CD20, and CD123.

In a further aspect, the present invention provides antigen binding domains

- 3 044325 anti-CD3 antibodies containing the CDR and/or variable domain and/or scFv sequences shown in the figures for H1.32_L1.47, H1.89_L1.47, H1.90_L1.47, H1.33_L.1.47 and H1 .31_L1.47. The present invention further provides nucleic acid compositions, expression vector compositions and host cells.

In a further aspect, the present invention provides heterodimeric antibodies comprising a) a first monomer comprising: i) a first Fc domain; ii) an anti-CD3 scFv comprising a light chain scFv variable domain, a scFv linker and a heavy chain scFv variable domain; wherein said scFv is covalently linked to the N-terminus of said Fc domain via an interdomain linker; b) a second monomer containing a heavy chain containing: i) a heavy chain variable domain and ii) a heavy chain constant domain containing a second Fc domain; and c) a light chain comprising a light chain variable domain and a light chain variable constant domain; wherein the anti-CD3 scFv is selected from the group consisting of H1.32_L1.47 CD3 binding, H1.89_L1.47 CD3 binding, H1.90_L1.47 CD3 binding and H1.33_L1.47 CD3 binding ( SEQ ID NO: XX). The heavy chain variable domain and the light chain variable domain bind TTAs (including, but not limited to, CD19, CD20, CD38, and CD123).

In a further aspect, the present invention provides anti-CD20 antibody binding domains comprising a) a light chain variable domain comprising vlCDR1 having the sequence RASWSVSYIH (SEQ ID NO: XX), vlCDR2 having the sequence ATSNLAS (SEQ ID NO: XX), and vlCDR3, having the sequence QQWTHNPPT (SEQ ID NO: XX); and b) a heavy chain variable domain comprising vhCDR1 having the sequence SYNMH (SEQ ID NO: XX), vhCDR2 having the sequence AIYPGNGATSYSQKFQG (SEQ ID NO: XX), and vhCDR3 having the sequence SYYMGGDWYFDV (SEQ ID NO: XX). In some embodiments, the anti-CD20 antibody binding domains have the sequences C2B8 H1.202_L1.113.

In a further aspect, the present invention provides anti-CD20 antibody binding domains comprising: a) a light chain variable domain comprising vlCDR1 having the sequence RASSSVSYIH (SEQ ID NO: XX), vlCDR2 having the sequence ATSNLAS (SEQ ID NO: XX), and vlCDR3 having the sequence QQWTSNPPT (SEQ ID NO: XX); and b) a heavy chain variable domain comprising vhCDR1 having the sequence SYNMH (SEQ ID NO: XX), vhCDR2 having the sequence AIYPGNGDTSYNQKFQG (SEQ ID NO: XX), and vhCDR3 having the sequence STYYGGDWYFNV (SEQ ID NO: XX).

In some embodiments, the anti-CD20 antibody binding domains have the sequences C2B8_H1L1.

In a further aspect, the present invention provides heterodimeric antibodies comprising a) a first monomer comprising: i) a first Fc domain; ii) an anti-CD3 scFv comprising a light chain scFv variable domain, a scFv linker and a heavy chain scFv variable domain; wherein said scFv is covalently linked to the N-terminus of said Fc domain via an interdomain linker; b) a second monomer containing a heavy chain containing: i) a heavy chain variable domain and ii) a heavy chain constant domain containing a second Fc domain; and c) a light chain comprising a light chain variable domain and a light chain variable constant domain, wherein the heavy and light chain variable domains form a C2B8 H1.202_L1.113 or C2B8_H1L1 binding domain.

In a further aspect, the present invention provides heterodimeric antibodies comprising a) a first monomer comprising: i) a first Fc domain; ii) an anti-CD3 scFv comprising a light chain scFv variable domain, a scFv linker and a heavy chain scFv variable domain; wherein said scFv is covalently linked to the N-terminus of said Fc domain via an interdomain linker; b) a second monomer containing a heavy chain containing: i) a heavy chain variable domain and ii) a heavy chain constant domain containing a second Fc domain; and c) a light chain comprising a light chain variable domain and a light chain variable constant domain. In this embodiment, the variable domains bind CD123 and may have the sequence 7G3_H1.109_L1.47.

In additional aspects, the present invention provides heterodimeric antibodies selected from the group consisting of XENP15049, XENP15051; XENP15050, XENP13676, XENP14696, XENP15629, XENP15053, XENP15630, XENP15631, XENP15632, XENP15633, XENP15634, XENP15635, XENP15636, XENP15638, XENP15 639, XENP13677, XENP14388, XENP14389, XENP14390, XENP14391, XENP14392, XENP14393, XENP16366, XENP16367, XENP16368, XENP16369, XENP16370, XENP16371, XENP16372, XENP16373, XENP16375, XENP16376 and XENP16377. Nucleic acids, expression vectors and host cells are also provided in addition to methods for producing these proteins and treating patients with them.

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Brief description of graphic materials

In fig. 1A and 1B depict some formats of the present invention. Two forms of the opener format are provided, one with the anti-CD3 antigen binding domain containing the scFv and the TTA binding domain containing the Fab, and the other with these components swapped. All formats mAb-Fv, mAb-scFv, with central scFv and central Fv are shown. In addition, partial formats are shown where only one monomer contains an Fc domain, with both an incomplete central scFv and an incomplete central Fv. The double scFv format is also shown.

In fig. 2 depicts the sequences of the high affinity CD3 construct antiCD3_H1.30_L1.47, including the heavy and light chain variable domains (CDRs underlined), as well as individual vl and vhCDRs, and the scFv construct with a charged linker (double underlined). As is true for all sequences depicted in the figures, this charged linker can be replaced with an uncharged linker or another charged linker if desired.

In fig. 3 depicts the sequences of the high to medium affinity construct #1 Anti-CD3_H1.32_L1.47, including the heavy and light chain variable domains (CDR underlined), as well as individual vl and vhCDR, as well as the scFv construct with a charged linker (double underline) . As is true for all sequences depicted in the figures, this charged linker can be replaced with an uncharged linker or another charged linker if desired.

In fig. 4 shows the sequences of the high to medium affinity construct No. 2 Anti-CD3_H1.89_L1.47, including the heavy and light chain variable domains (CDR underlined), as well as individual vl and vhCDR, as well as the scFv construct with a charged linker (double underline) . As is true for all sequences depicted in the figures, this charged linker can be replaced with an uncharged linker or another charged linker if desired.

In fig. Figure 5 shows the sequences of the high to medium affinity construct No. 3 Anti-CD3_H1.90_L1.47, including the heavy and light chain variable domains (CDR underlined), as well as individual vl and vhCDR, as well as the scFv construct with a charged linker (double underline) . As is true for all sequences depicted in the figures, this charged linker can be replaced with an uncharged linker or another charged linker if desired.

In fig. 6 depicts the sequences of the intermediate affinity construct AntiCD3_H1.90_L1.47, including the heavy and light chain variable domains (CDR underlined), as well as individual vl and vhCDR, and the scFv construct with a charged linker (double underlined). As is true for all sequences depicted in the figures, this charged linker can be replaced with an uncharged linker or another charged linker if desired.

In fig. 7 depicts the sequences of the low affinity construct AntiCD3_H1.31_L1.47, including the heavy and light chain variable domains (CDR underlined), as well as individual vl and vhCDR, and the scFv construct with a charged linker (double underlined). As is true for all sequences depicted in the figures, this charged linker can be replaced with an uncharged linker or another charged linker if desired.

In fig. Figure 8 shows the sequences of the high affinity CD38 construct: OKT10_H1.77_L1.24, including the heavy and light chain variable domains (CDR underlined), as well as individual vl and vhCDR, and the scFv construct with a charged linker (double underlined).

In fig. Figure 9 shows the sequences of the intermediate affinity construct for CD38: OKT10_H1L1.24, including the heavy and light chain variable domains (CDRs underlined), as well as individual vl and vhCDRs, as well as the scFv construct with a charged linker (double underlining).

In fig. 10 depicts the sequences of the CD38 low affinity construct: OKT10_H1L1, including the heavy and light chain variable domains (CDR underlined), as well as the individual vl and vhCDR, and the scFv construct with a charged linker (double underlined).

In fig. 11 shows the sequences of XENP15331.

In fig. 12 shows the sequences of XENP13243.

In fig. 13 shows the sequences of XENP14702.

In fig. 14 shows the sequences of XENP15426.

In fig. 15 shows the sequences of XENP14701.

In fig. 16 shows the sequence of XENP14703.

In fig. 17 shows the sequence of XENP13243.

In fig. 18 shows the sequences of XENP18967.

In fig. 19 shows the sequences of XENP18971.

In fig. 20 shows the sequences of XENP18969.

In fig. 21 shows the sequences of XENP18970.

In fig. 22 shows the sequences of XENP18972.

In fig. 23 shows the sequences of XENP18973.

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In fig. 24 shows the sequences of XENP15055.

In fig. 25 shows the sequences of XENP13544.

In fig. 26 shows the sequences of XENP13694.

In fig. 27 depicts the sequence of human CD3ε.

In fig. 28 depicts the full-length (SEQ ID NO: 130) and extracellular domains (ECD; SEQ ID NO: 131) of the human CD38 protein.

In fig. 29A-29E depict suitable pairs of heterodimerization variant sets (including asymmetric and altered pI variants).

In fig. 30 depicts a list of constant regions of isosteric antibody variants and their corresponding substitutions, pI (-) denoting lower pI variants, while pI (+) denoting higher pI variants. They can optionally and independently be combined with other heterodimerization variants of the present invention (as well as other types of variants as described herein).

In fig. 31 depicts useful disrupted variants that are impaired in binding to FcyR (sometimes called knockout or KO variants).

In fig. 32 shows two particularly useful embodiments of the present invention.

In fig. 33 depicts a number of charged scFv linkers that find use in increasing or decreasing the pI of heterodimeric antibodies that use one or more scFvs as a component. One prior art scFv linker with a single charge is referred to as Whitlow from Whitlow et al., Protein Engineering 6(8):989-995 (1993). It should be noted that this linker was used to reduce aggregation and increase the proteolytic stability of scFv.

In fig. 34 depicts a list of asymmetrically engineered heterodimeric Fc variants with heterodimer yield (determined by HPLC-CIEX) and thermal stability (determined by DSC). Undetermined thermal stability is indicated as n.d..

Fig. 35. Expression yield values of bispecific antibodies after affinity purification using protein A.

Fig. 36. Chromatograms of cation exchange purification.

Fig. 37. Redirected T cell cytotoxicity assay, 24 h incubation, 10 thousand RPMI8226 cells, 400 thousand T cells. The drugs tested are bispecific antibodies to CD38 x CD3. Detection was performed using LDH.

Fig. 38. T-cell redirected cytotoxicity assay, 24 h incubation, 10 thousand RPMI8226 cells, 500 thousand human PBMC. The drugs tested are bispecific antibodies to CD38 x CD3. Detection was performed using LDH.

In fig. 39 shows the sequences of XENP14419.

In fig. 40 shows the sequences of XENP14420.

In fig. 41 shows the sequences of XENP14421.

In fig. 42 shows the sequences of XENP14422.

In fig. 43 shows the sequences of XENP14423.

Fig. 44. Redirected T-cell cytotoxicity assay, 96 h incubation, 40 thousand RPMI8226 cells, 400 thousand human PBMC. The drugs tested are Fab-scFv-Fc to CD38 x CD3. Detection was performed by flow cytometry, in particular regarding the disappearance of CD38+ cells.

Fig. 45. Additional examination of the results of the redirected T cell cytotoxicity assay described in FIG. 1. The first row shows the mean fluorescence intensity (MFI) of the activation marker CD69 on CD4+ and CD8+ T cells determined by flow cytometry. The second row shows the percentage of CD4+ and CD8+ T cells that are Ki-67+, a measure of cell proliferation. The third row shows the intracellular mean fluorescence intensity (MFI) of the granzyme B inhibitor PI-9 on CD4+ and CD8+ T cells determined by flow cytometry.

Fig. 46. Design of a study in mice to study the antitumor activity of bispecific antibodies Fab-scFv-Fc to CD38 x CD3.

Fig. 47. Tumor size measured by IVIS® as a function of time and treatment.

Fig. 48. IVIS® Bioluminescent Imaging (Day 10)

Fig. 49. Depletion of the CD38+ cell population in cynomolgus monkeys after single doses of these drugs.

Fig. 50. T cell activation measured by mean fluorescence intensity (MFI) of CD69 in cynomolgus monkeys, color coded as in FIG. 49.

Fig. 51. Serum IL-6 levels after single doses of the indicated test drugs.

In fig. 52 shows the sequences of XENP15427.

In fig. 53 shows the sequences of XENP15428.

In fig. 54 shows the sequences of XENP15429.

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In fig. 55 shows the sequences of XENP15430.

In fig. 56 shows the sequences of XENP15431.

In fig. 57 shows the sequences of XENP15432.

In fig. 58 shows the sequences of XENP15433.

In fig. 59 shows the sequences of XENP15434.

In fig. 60 shows the sequences of XENP15435.

In fig. 61 shows the sequences of XENP15436.

In fig. 62 shows the sequences of XENP15437.

In fig. 63 shows the sequences of XENP15438.

In fig. 64 shows the binding affinities in the Biacore assay.

In fig. 65 shows heterodimer purity when generating a stable pool using different ratios of light chain, Fab-Fc and scFv-Fc.

Fig. 66. Depletion of human IgM and IgG2 by anti-CD38 x CD3 bispecific antibodies in a huPBMC mouse model.

In fig. 67 depicts a stability-optimized humanized anti-CD3 scFv. Substitutions are given relative to the scFv H1_L1.4 sequence. Amino acid numbering is Kabat numbering.

Fig. 68. Amino acid sequences of the stability-optimized humanized anti-CD3 scFv variant. CDRs are underlined. For each heavy chain/light chain combination, four sequences are listed: (i) scFv with a C-terminal 6xHis tag, (ii) scFv only, (iii) VH only, (iv) VL only.

Fig. 69. T-cell redirected cytotoxicity assay, 24 h incubation, 10 thousand RPMI8226 cells, 500 thousand PBMC. The drugs tested are Fab-scFv-Fc anti-CD38 (OKT10_H1L1, OKT10_H1.77_L1.24) x CD3. Detection was performed using LDH.

Fig. 70. HuPBL-SCID Ig depletion study. Test drugs were administered 8 days after PBMC inoculation at a dose of 0.03, 0.3, or 3 mg/kg. The route of administration was intraperitoneal. Blood samples were collected 14 days after PBMC inoculation, processed to obtain serum, and analyzed for human IgM and IgG2.

In fig. 71 shows the sequences of XENP15049.

In fig. 72 shows the sequences of XENP15051.

In fig. 73 depicts the sequences of XENP15050.

In fig. 74 shows the sequences of XENP13676.

In fig. 75 shows the sequences of XENP14696.

In fig. 76 shows the sequences of XENP15629.

In fig. 77 shows the sequences of XENP15053.

In fig. 78 shows the sequences of XENP15630.

In fig. 79 shows the sequences of XENP15631.

In fig. 80 shows the sequences of XENP15632.

In fig. 81 shows the sequences of XENP15633.

In fig. 82 shows the sequences of XENP15634.

In fig. 83 depicts the sequences of XENP15635.

In fig. 84 shows the sequences of XENP15636.

In fig. 85 shows the sequences of XENP15638.

In fig. 86 shows the sequences of XENP15639.

In fig. 87 shows the sequences of XENP13677.

In fig. 88 shows the sequences of XENP14388.

In fig. 89 shows the sequences of XENP14389.

In fig. 90 depicts the sequences of XENP14390.

In fig. 91 depicts the sequences of XENP14391.

In fig. 92 depicts the sequences of XENP14392.

In fig. 93 depicts the sequences of XENP14393.

In fig. 94 shows the sequences of XENP16366.

In fig. 95 shows the sequences of XENP16367.

In fig. 96 shows the sequences of XENP16368.

In fig. 97 shows the sequences of XENP16369.

In fig. 98 shows the sequences of XENP16370.

In fig. 99 shows the sequences of XENP16371.

In fig. 100 depicts the sequences of XENP16372.

In fig. 101 shows the sequences of XENP16373.

In fig. 102 shows the sequences of XENP16374.

In fig. 103 depicts the sequences of XENP16375.

In fig. 104 shows the sequences of XENP16376.

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In fig. 105 shows the sequences of XENP16377.

In fig. 106 shows the sequences of the CD20 and CD123 antigens.

Fig. 107. Determination of affinity for CD3 using the surface plasmon resonance method. The drugs tested are Fab-scFv-Fc anti-CD20 (C2B8_H1.202_L1.113) x CD3. Human CD3δε-Fc (Sino Biological) was covalently linked to the surface of the chip. The tested drugs were passed at 3.125, 12.5, 50 and 200 nM.

Fig. 108. Determination of affinity for CD3 using the surface plasmon resonance method. The drugs tested are Fab-scFv-Fc anti-CD20 (C2B8_H1.202_L1.113) x CD3. Cynomolgus CD3δε-Fc (Sino Biological) was covalently linked to the surface of the chip. The tested drugs were passed at 3.125, 12.5, 50 and 200 nM.

Fig. 109. Determination of affinity for CD3 using the surface plasmon resonance method. The drugs tested are Fab-scFv-Fc anti-CD20 (C2B8_H1.202_L1.113) x CD3. Human CD3δε-Fc (Sino Biological) was covalently linked to the surface of the chip. The tested drugs were passed at 31.25, 125, 500 and 2000 nM.

Fig. 110. Determination of affinity for CD3 using the surface plasmon resonance method. The drugs tested are Fab-scFv-Fc anti-CD20 (C2B8_H1.202_L1.113) x CD3. Cynomolgus CD3δε-Fc (Sino Biological) was covalently linked to the surface of the chip. The tested drugs were passed at 31.25, 125, 500 and 2000 nM.

Fig. 111. Determination of affinity for CD3 using the surface plasmon resonance method. The drugs tested are Fab-scFv-Fc anti-CD20 (C2B8_H1.202_L1.113) x CD3. Cynomolgus CD3δε-Fc (Sino Biological) was covalently bound to the surface of the chip. The tested drugs were passed at 31.25, 125, 500 and 2000 nM.

Fig. 112. T-cell redirected cytotoxicity assay, 24 h incubation, 10 thousand Ramos cells, 250 thousand PBMC. The drugs tested are Fab-scFv-Fc anti-CD20 (C2B8_H1.202_L1.113) x CD3. Detection was performed using LDH.

Fig. 113. T-cell redirected cytotoxicity assay, 24 h incubation, 20 thousand Jeko cells, 200 thousand PBMC (CD19-depleted). The drugs tested are Fab-scFvFc anti-CD20 (C2B8_H1.202_L1.113) x CD3. Detection was performed using flow cytometry, particularly regarding the disappearance of CD19+ cells.

Fig. 114. IL-6 production after 2-4 hours. For the experiment described in FIG. 113.

Fig. 115. T-cell redirected cytotoxicity assay, 5 h incubation, 20 thousand Jeko cells, 500 thousand PBMC (CD19-depleted). The drugs tested are Fab-scFv-Fc anti-CD20 (C2B8_H1L1) x CD3. Detection was performed using flow cytometry, particularly regarding the disappearance of CD19+ cells.

Fig. 116. T-cell redirected cytotoxicity assay, 24 h incubation, 20 thousand Jeko cells, 500 thousand PBMC (CD19-depleted). The drugs tested are Fab-scFvFc anti-CD20 (C2B8_H1.202_L1.113) x CD3. Detection was performed using flow cytometry, particularly regarding the disappearance of CD19+ cells.

Fig. 117. IL-6 production after 2-4 hours. For the experiment described in FIG. 113.

Fig. 118. Redirected T-cell cytotoxicity assay, 24 h incubation, 10 thousand RPMI8226 cells, 500 thousand PBMC. The drugs tested are Fab-scFv-Fc anti-CD38 (OKT10_H1L1, OKT10_H1.77_L1.24) x CD3. Detection was performed using LDH.

Fig. 119. HuPBL-SCID Ig depletion study. The tested drugs were administered 1 and 8 days after inoculation of PBMC at a dose of 5 mg/kg. The route of administration was intraperitoneal. Blood samples were collected 14 days after PBMC inoculation, processed to obtain serum, and analyzed for human IgM and IgG2.

Fig. 120. HuPBL-SCID Ig depletion study. Test drugs were administered 8 days after PBMC inoculation at a dose of 0.03, 0.3, or 3 mg/kg. The route of administration was intraperitoneal. Blood samples were collected 14 days after PBMC inoculation, processed to obtain serum, and analyzed for human IgM and IgG2.

In fig. 121 shows sequences with high affinity for CD20 C2B8_H1.202_L1.113.

In fig. 122 shows low affinity sequences for CD20 C2B8_H1L1.

In fig. 123 shows the sequences for CD123 7G3_H1.109_L1.57.

In fig. 124 shows a matrix of possible combinations for the present invention. A means that the CDRs of the mentioned sequences to CD3 can be combined with the CDR to TTA on the right side. That is, the vhCDR from the CD3-binding heavy chain variable domain sequence H1.30 and the CD3-binding light chain variable domain sequence L1.57 vlCDR can be combined with the vhCDR from the CD38-binding OKT10 sequence H1.77 and the vlCDR from the sequence OKT10L1.24. B means that CDRs from CD3 binding constructs can be combined with heavy and light chain variable domains from TTA binding constructs

- 8 044325 hands. That is, vhCDR from CD3-binding heavy chain variable domain sequence H1.30 and vlCDR from CD3-binding light chain variable domain sequence L1.57 can be combined with CD38-binding heavy chain variable domain sequence OKT10 H1.77, and the sequence OKT10L1.24. C is the reverse situation, such that the heavy chain variable domain and the light chain variable domain from the CD3 binding sequences are used with the CDRs from the TTA binding constructs. D represents the situation where the heavy chain variable domains and the light chain variable domains from each construct are combined. E represents the situation where scFv from the CD3 binding sequence is used with CDRs from TTA binding constructs, and in the case of F, scFv from the CD3 binding sequence is used with heavy chain variable domains and light chain variable domains from the antigen binding domain antibodies to TTA.

Detailed Description of the Invention

I. Definitions.

To make this application clearer, certain definitions are set forth below. Such definitions are intended to cover grammatical equivalents.

The term disruption in this document refers to the reduction or elimination of activity. Thus, for example, the expression impaired binding to FcyR means that the amino acid variant of the Fc region has less than 50% binding of the original level, compared to an Fc region not containing this particular variant, with less than 70-80-90-95-98% loss of activity that is preferred, and generally with activity that is below the level of detectable binding in the Biacore assay. Particularly useful in disrupting FcyR binding are those shown in FIG. 16.

As used herein, ADCC or antibody-dependent cell-mediated cytotoxicity refers to a cell-mediated reaction in which nonspecific cytotoxic cells that express FcyR recognize bound antibody on a target cell and then cause lysis of that target cell. ADCC correlates with binding to FcyRIIIa; increased binding to FcyRIIIa leads to increased ADCC activity.

As used herein, the term ADCP or antibody-dependent cell-mediated phagocytosis refers to a cell-mediated reaction in which nonspecific cytotoxic cells that express FcyR recognize bound antibody on a target cell and then induce phagocytosis of that target cell.

By modification, as used herein, is meant an amino acid substitution, insertion and/or deletion in a polypeptide sequence, or a change in a moiety chemically linked to a protein. For example, the modification may be a modified carbohydrate or PEG structure attached to a protein. By amino acid modification as used herein is meant an amino acid substitution, insertion and/or deletion in a polypeptide sequence. For clarity, unless otherwise noted, an amino acid modification always corresponds to the amino acid encoded by DNA, for example, the 20 amino acids that have codons in DNA and RNA.

By amino acid substitution or substitution as used herein is meant the replacement of an amino acid at a specific position in the original polypeptide sequence with another amino acid. Specifically, in some embodiments, the substitution involves an amino acid that does not occur naturally at a particular position, or does not occur naturally in a given organism, or in any organism. For example, the E272Y substitution refers to a polypeptide variant, in this case an Fc variant, in which the glutamic acid at position 272 is replaced by tyrosine. For clarity, a protein that has been engineered to change the nucleic acid coding sequence, but without changing the original amino acid (for example, replacing CGG (encoding arginine) with CGA (still encoding arginine), in order to increase expression levels in the host), does not provide for amino acid replacement; those. Despite the creation of a new gene encoding the same protein, if the protein contains the same amino acid in the specific position at which it began, this is not an amino acid substitution.

By amino acid insertion or insertion as used herein is meant the addition of an amino acid sequence at a specific position in the original polypeptide sequence. For example, -233E or 233E indicates a glutamic acid insertion after position 233 and before position 234. Additionally, -233ADE or A233ADE indicates an AlaAspGlu insertion after position 233 and before position 234.

By amino acid deletion or deletion herein is meant the removal of an amino acid sequence at a specific position in the original polypeptide sequence. For example, E233- or E233# or E233() denotes a deletion of glutamic acid at position 233. Additionally, EDA233- or EDA233# denotes a deletion of the GluAspAla sequence that begins at position 233.

By variant protein, or protein variant, or variant as used herein

- 9 044325 document, refers to a protein that differs from the original protein due to at least one amino acid modification. A protein variant may refer to the protein itself, a composition containing the protein, or the amino acid sequence that encodes it. Preferably, the protein variant includes at least one amino acid modification compared to the parent protein, for example, from about one to about seventy amino acid modifications, and preferably from about one to about five amino acid modifications compared to the parent protein. As described below, in some embodiments, the parent polypeptide, such as the parent Fc polypeptide, is a wild-type human sequence, such as an Fc region from IgG1, IgG2, IgG3, or IgG4, although variant human sequences may also serve as parent polypeptides , for example, the IgG1/2 hybrid from FIG. 19. The sequence of the protein variant herein will preferably have at least about 80% identity to the original protein sequence, and most preferably at least about 90% identity, more preferably at least about 95-98-99% identity. A variant protein may refer to the variant protein itself, compositions containing the protein variant, or the DNA sequence that encodes it. Accordingly, by antibody variant or variant antibody as used herein is meant an antibody that differs from the parent by at least one amino acid modification, a variant IgG or variant IgG as used herein means an antibody that differs from the parent IgG (again - in many cases from the human IgG sequence) due to at least one amino acid modification, and a variant immunoglobulin or variant immunoglobulin as used herein means an immunoglobulin sequence that differs from the sequence of the parent immunoglobulin due to at least one amino acid modification. The term Fc variant or Fc variant as used herein means a protein having an amino acid modification in the Fc domain. Fc variants of the present invention are defined in accordance with the amino acid modifications that form them. Thus, for example, N434S or 434S is an Fc variant with a serine substitution at position 434 relative to the original Fc polypeptide, where the numbering corresponds to the EU index. Similarly, M428L/N434S defines an Fc variant with substitutions M428L and N434S relative to the original Fc polypeptide. The identity of the WT (wild type) amino acid may not be determined, in which case the above variant is referred to as 428L/434S. It is noted that the order in which substitutions are provided is arbitrary, i.e., 428L/434S is the same Fc variant as M428L/N434S, and so on. For all provisions discussed in the present invention that relate to antibodies, unless otherwise indicated, the numbering of amino acid positions corresponds to the EU index. The EU index, or Kabat EU index, or EU numbering scheme refers to the EU numbering of an antibody (Edelman et al., 1969, Proc Natl Acad Sci USA 63:78-85, incorporated herein by reference in its entirety). The modification may be an addition, deletion or substitution. Substitutions may include naturally occurring amino acids and, in some cases, synthetic amino acids. Examples include US Patent No. 6586207; WO 98/48032; WO 03/073238; US2004-0214988 A1; WO 05/35727 A2; WO 05/74524 A2; J. W. Chin et al., (2002), Journal of the American Chemical Society 124:9026-9027; J. W. Chin, & P. G. Schultz, (2002), Chem. BioChem. 11:1135-1137; J. W. Chin, et al., (2002), PICAS United States of America 99:1102011024; and L. Wang, & P. G. Schultz, (2002), Chem. 1-10, all incorporated by reference in their entirety.

As used herein, the term protein means at least two covalently linked amino acids, and the term includes proteins, polypeptides, oligopeptides and peptides. The peptidyl group may contain naturally occurring amino acids and peptide bonds or synthetic peptidomimetic structures, i.e. analogs such as peptoids (see Simon et al., PNAS USA 89(20):9367 (1992), incorporated by reference in its entirety). Amino acids can be either naturally occurring or synthetic (eg, non-amino acids that are encoded by DNA), as will be understood by those skilled in the art. For example, homophenylalanine, citrulline, ornithine and norleucine are considered synthetic amino acids for purposes of the present invention, and both D- and L- (R or S) configuration amino acids can be used. Embodiments of the present invention may include modifications that include the use of synthetic amino acids, including the use, for example, of technologies developed by Schultz and his colleagues, including, without limitation, the methods described by Cropp & Shultz, 2004, Trends Genet. 20(12):625-30, Anderson et al., 2004, Proc Natl Acad Sci USA 101(2):7566-71, Zhang et al., 2003, 303(5656):371-3 and Chin et al. , 2003, Science 301(5635):964-7, all incorporated by reference in their entirety. In addition, polypeptides may include synthetic derivatization of one or more side chains or ends, glycosylation, pegylation, cyclic rearrangement, cyclization, linkers with other molecules, fusion with proteins or protein domains, and the addition of peptide tags or tags.

The term residue as used herein refers to a position in the protein and

- 10 044325 associated amino acid identity. For example, asparagine 297 (also called Asn297 or N297) is the residue at position 297 in the human IgG1 antibody.

The term Fab or Fab region as used herein refers to a polypeptide that contains the VH, CH1, VL and CL domains of an immunoglobulin. Fab may refer to this region by itself or to this region in the context of a full-length antibody, antibody fragment, or Fab-based fusion protein. The term Fv, or Fv fragment, or Fv region, as used herein, refers to a polypeptide that contains the VL and VH domains of a single antibody. As will be appreciated by those skilled in the art, they typically consist of two circuits.

The expression "IgG subclass modification" or "isotype modification" as used herein refers to an amino acid modification that converts one amino acid of one IgG isotype to the corresponding amino acid of another aligned IgG isotype. For example, since IgG1 contains tyrosine and IgG2 contains phenylalanine at EU position 296, the F296Y substitution in IgG2 is considered a modification of the IgG subclass.

By the expression non-naturally occurring modification, as used herein, is meant an amino acid modification that is not isotypic. For example, since none of the IgGs contain a series at position 434, the 434S substitution in IgG1, IgG2, IgG3, or IgG4 (or their hybrids) is considered a non-naturally occurring modification.

The term amino acid and amino acid identity as used herein refers to one of the 20 naturally occurring amino acids that are encoded by DNA and RNA.

The term effector function as used herein refers to a biochemical event that results from the interaction of the Fc region of an antibody with an Fc receptor or ligand. Effector functions include, but are not limited to, ADCC, ADCP, and CDC.

The term IgG Fc ligand as used herein means a molecule, preferably a polypeptide, from any organism that binds to the Fc region of an IgG antibody to form an Fc/Fc ligand complex. Fc ligands include, but are not limited to, FcyRI, FcyRII, FcyRIII, FcRn, C1q, C3, MBL, mannose receptor, staphylococcal protein A, streptococcal protein G, and viral FcyR. Fc ligands also include Fc receptor homologues (FcRH), which are a family of Fc receptors homologous to FcyR (Davis et al., 2002, Immunological Reviews 190:123-136, incorporated by reference in its entirety). Fc ligands may include unknown molecules that bind Fc. Specific IgG Fc ligands are FcRn and Fc gamma receptors. The term Fc ligand as used herein means a molecule, preferably a polypeptide, from any organism that binds to the Fc region of an antibody to form an Fc/Fc ligand complex.

The term Fc gamma receptor, FcyR, or Fc gamma R as used herein refers to any member of a family of proteins that binds the Fc region of an IgG antibody and is encoded by the FcyR gene. In humans, this family includes, but is not limited to, FcyRI (CD64), including the FcyRIa, FcyRIb, and FcyRIc isoforms; FcyRII (CD32), including isoforms FcyRIIa (including allotypes H131 and R131), FcyRIIb (including FcyRIIb-1 and FcyRIIb-2) and FcyRIIc; and FcyRIII (CD16), including isoforms FcyRIIIa (including allotypes V158 and F158) and FcyRIIIb (including allotypes FcyRIIb-NA1 and FcyRIIbNA2) (Jefferis et al., 2002, Immunol Lett 82:57-65, incorporated by reference in its entirety) , as well as any unknown FcyR or human FcyR isoforms or allotypes. FcyR can be derived from any organism, including, but not limited to, humans, mice, rats, rabbits and monkeys. Mouse FcyRs include, but are not limited to, FcyRI (CD64), FcyRII (CD32), FcyRIII (CD16), and FcyRIII-2 (CD16-2), as well as any unknown mouse FcyRs or FcyR isoforms or allotypes.

The term FcRn or neonatal Fc receptor as used herein refers to a protein that binds to the Fc region of an IgG antibody and is encoded, at least in part, by the FcRn gene. FcRn can be derived from any organism, including, but not limited to, humans, mice, rats, rabbits and monkeys. As is known in the art, a functional FcRn protein contains two polypeptides, often referred to as a heavy chain and a light chain. The light chain is beta-2-microglobulin and the heavy chain is encoded by the FcRn gene. Unless otherwise specified herein, FcRn or FcRn protein refers to the FcRn heavy chain beta-2-microglobulin complex. Various FcRn variants used to enhance FcRn receptor binding and, in some cases, to increase serum half-life are shown in the figure legend referring to FIG. 83.

The term parent polypeptide as used herein refers to the starting polypeptide that is then modified to produce a variant. The parent polypeptide may be a naturally occurring polypeptide, or a variant or engineered version of a naturally occurring polypeptide. The parent polypeptide may refer to the polypeptide itself, compositions containing the parent polypeptide, or the amino acid sequence that encodes it. Accordingly, under the term original

- 11 044325 munoglobulin as used herein refers to an unmodified immunoglobulin polypeptide that is modified to produce a variant, and the term parent antibody as used herein refers to an unmodified antibody that is modified to produce a variant antibody. It should be noted that the parent antibody includes the known recombinantly produced commercial antibodies described below.

By Fc or Fc region or Fc domain, as used herein, is meant a polypeptide comprising an antibody constant region other than the first immunoglobulin constant region domain and, in some cases, a hinge portion. Thus, Fc refers to the last two constant region domains of the immunoglobulins IgA, IgD and IgG, the last three constant region domains of the immunoglobulins IgE and IgM, and the flexible hinge at the N-terminus of these domains. In the case of IgA and IgM, the Fc may include a J chain. In the case of IgG, the Fc domain contains the immunoglobulin domains Cy2 and Cy3 (Cy2 and Cy3) and the lower hinge region between Cy1 (Cy1) and Cy2 (Cy2). Although the boundaries of the Fc region may vary, the Fc region of the human IgG heavy chain is generally defined as containing residues C226 or P230 at its carboxyl terminus, numbered according to Kabat's EU index. In some embodiments, as described in more detail below, amino acid modifications are made to the Fc region, for example, to alter binding to one or more FcyR receptors or an FcRn receptor.

The term heavy chain constant region as used herein refers to the CH1-hinge-CH2-CH3 portion of an antibody.

The term Fc-fusion protein or immunoadhesin as used herein refers to a protein containing an Fc region typically linked (optionally via a linker moiety as described herein) to another protein, such as a target protein binding moiety as described in this document. In some cases, one monomer of a heterodimeric antibody contains an antibody heavy chain (including scFv or additionally including a light chain) and the other monomer is an Fc hybrid containing a variant Fc domain and a ligand. In some embodiments, these half antibody-half fusion proteins are referred to as fusion antibodies.

The term position as used herein refers to a location in a protein sequence. The provisions may be numbered sequentially or according to a specified format, such as the EU index for antibody numbering.

The term target antigen as used herein refers to a molecule that is specifically bound by the variable region of a given antibody. The target antigen may be a protein, carbohydrate, lipid, or other chemical compound. A large number of suitable target antigens are described below.

By the term strand structure in the context of heterodimeric antibody monomers of the present invention, it is meant herein that, like two strands of DNA that match, heterodimerization variants are included in each monomer so as to retain the ability to match to form heterodimers. For example, if some pI-altered variants are designed to form monomer A (e.g., providing a higher pI), then steric variants that are charge pairs that can also be used do not disrupt the function of the pI-altered variants, e.g., charged variants that make the pI higher are placed on the same strand or monomer to preserve both functionality. Likewise, for asymmetric variants that are included in set pairs, as described in more detail below, one skilled in the art will take the pI into account when deciding on which strand or monomer one set of the pair will be included so that separation by pI is also maximized using pI asymmetry structures.

The term target cell as used herein refers to a cell that expresses the target antigen.

The term variable region, as used herein, refers to a region in an immunoglobulin that contains one or more Ig domains, primarily encoded by any of the V. kappa., V. lamda genes. and/or VH, which constitute the kappa, lambda and immunoglobulin heavy chain genetic loci, respectively.

The term wild type or WT as used herein means an amino acid sequence or nucleotide sequence that is found in natural conditions, including allelic variants. The WT protein has an amino acid sequence or nucleotide sequence that has not been intentionally modified.

Antibodies of the present invention are typically isolated or recombinant. Isolated, when used to describe the various polypeptides disclosed herein, means a polypeptide that has been identified and isolated and/or recovered from the cell or cell culture in which it was expressed. Typically, the isolated polypeptide will be obtained through at least one purification step. The isolated antibody refers to the antibody that

- 12 044325 swarm practically does not contain other antibodies with different antigenic specificity. Recombinant means that antibodies are produced using recombinant nucleic acid techniques in exogenous host cells.

Specific binding or specifically binds to or is specific for a particular antigen or epitope means binding which is markedly different from non-specific interaction. Specific binding can be measured, for example, by determining the binding of a molecule compared to the binding of a control molecule, which is typically a molecule with a similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target.

Specific binding for a particular antigen or epitope can be demonstrated, for example, by an antibody having a KD for the antigen or epitope of at least about 10-4 M, at least about 10-5 M, at least about 10-6 M, at least at least about 10-7 M, at least about 10-8 M, at least about 10-9 M, alternatively at least about 10-10 M, at least about 10-11 M, at least about 10 -12 M or greater, where KD denotes the rate of dissociation of a particular antibody-antigen interaction. Typically, an antibody that specifically binds an antigen will have a KD that is 20, 50, 100, 500, 1000, 5000, 10,000 or more times higher for the control molecule compared to the antigen or epitope.

In addition, specific binding of a particular antigen or epitope can be demonstrated, for example, by an antibody characterized by a KA or Ka for the antigen or epitope at least 20, 50, 100, 500, 1000, 5000, 10,000 or more times higher for the epitope compared with control, where KA or Ka denotes the rate of association of a particular antibody-antigen interaction.

II. Short review.

Bispecific antibodies that co-contact CD3 and a target tumor antigen have been designed and used to redirect T cells to attack and lyse target tumor cells. Examples include the BiTE and DART formats, which monovalently contact CD3 and tumor antigen. Although the CD3 targeting approach has shown significant promise, a common side effect of these therapies is related to the production of cytokines, often resulting in toxic cytokine release syndrome. Because the CD3 bispecific antibody binding domain contacts all T cells, a subpopulation of CD4 T cells is recruited and produces high levels of cytokines. Moreover, the CD4 T cell subset includes regulatory T cells, the recruitment and expansion of which can potentially lead to immune suppression and have a negative impact on long-term tumor suppression. In addition, these formats do not contain Fc domains and have very short half-lives in patient serum.

Although the CD3 targeting approach has shown significant promise, a common side effect of these therapies is related to the production of cytokines, often leading to toxic cytokine release syndrome. Because the CD3 bispecific antibody binding domain contacts all T cells, a subpopulation of CD4 T cells is recruited and produces high levels of cytokines. Moreover, the CD4 T cell subset includes regulatory T cells, the recruitment and expansion of which can potentially lead to immune suppression and have a negative impact on long-term tumor suppression. One such possible way to reduce cytokine production and possibly reduce CD4 T cell activation is to reduce the affinity of the CD3 binding domain for CD3.

Accordingly, in some embodiments, the present invention provides antibody constructs comprising anti-CD3 antibody antigen binding domains that are strong or high affinity CD3 binders (e.g., one example is the heavy and light chain variable domains depicted as H1.30_L1.47 (optional , including the corresponding charged linker)), and also bind to CD38. In other embodiments, the present invention provides antibody constructs comprising anti-CD3 antibody antigen binding domains that are weak or lower affinity CD3 binders. Additional embodiments provide antibody constructs comprising anti-CD3 antibody antigen-binding domains that have intermediate or intermediate affinity for CD3 that also bind CD38.

It should be understood that the high, intermediate, low affinity CD3 sequences of the present invention can be used in various heterodimerization formats. Although most of the disclosure herein utilizes a bottle opener heterodimer format, these heavy and light chain variable sequences, as well as scFv sequences (and Fab sequences containing these heavy and light chain variable sequences) may be used in other formats, such as those shown in fig. 2 from WO 2014/145806, the figures, formats and explanations of the symbols of which are expressly incorporated herein by

- 13 044325 vom links.

Accordingly, the present invention provides heterodimeric antibodies that bind to two different antigens, for example, antibodies that are bispecific in the sense that they bind two different target antigens, typically tumor target antigens (TTA), described below. These heterodimeric antibodies can bind these target antigens either monovalently (eg, there is one antigen binding domain, such as a pair of heavy and light chain variable domains) or bivalently (there are two antigen binding domains, each of which independently binds the antigen). The structure of the heterodimeric antibodies of the present invention is based on the use of different monomers providing amino acid substitutions that bias the formation of heterodimers relative to homodimers, as described in more detail below, in combination with variants with altered pI, which facilitates the purification of heterodimers from homodimers, as also described below. With respect to the heterodimeric bispecific antibodies of the present invention, the present invention is generally based on the use of engineered or variant Fc domains that can self-assemble in production cells to produce heterodimeric proteins, as well as methods for preparing and purifying such heterodimeric proteins.

III. Antibodies.

The present invention relates to the production of bispecific antibodies that bind two different antigens, for example, CD3 and a target tumor antigen such as CD20, CD38 and CD123, and are typically therapeutic antibodies. As discussed below, the term antibody is used in a general sense. Antibodies that find use in the present invention can take a number of formats described herein, including traditional antibodies, as well as antibody derivatives, fragments and mimetics described herein.

Traditional antibody structural units typically include a tetramer. Each tetramer typically consists of two identical pairs of polypeptide chains, each pair having one light chain (typically with a molecular weight of approximately 25 kDa) and one heavy chain (typically with a molecular weight of approximately 50-70 kDa) Human light chains classified as kappa and lambda light chains. The present invention relates to the IgG class, which has several subclasses including, but not limited to, IgG1, IgG2, IgG3 and IgG4. Thus, as used herein, the term isotype means any of the subclasses of immunoglobulins defined by the chemical and antigenic characteristics of their constant regions. It should be understood that therapeutic antibodies may also include isotype and/or subclass hybrids. For example, as shown in US 2009/0163699, incorporated by reference, the present invention covers the construction of IgG1/G2 hybrids based on pI.

The amino-terminal portion of each chain includes a variable region of about 100 to 110 or more amino acids that are primarily responsible for antigen recognition, commonly referred to in the art and herein as the Fv domain or Fv region. In the variable region, three loops are assembled for each of the heavy chain and light chain V domains to form an antigen binding region. Each of the loops is referred to as a complementarity determining region (hereinafter referred to as CDR) in which the amino acid sequence change is most significant. The change refers to the fact that certain variable region segments vary greatly in sequence between antibodies. Variability within a variable region is not evenly distributed. In contrast, V regions are composed of relatively invariant stretches called framework regions (FRs) of 15–30 amino acids separated by shorter regions of exceptional variability called hypervariable regions, each 9–15 amino acids long or longer.

Each VH and VL consists of three hypervariable regions (complementarity determining regions, CDRs) and four FRs, located from the amino terminus to the carboxy terminus in the following order: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4.

The hypervariable region typically covers amino acid residues from approximately amino acid residues 24-34 (LCDR1; L denotes light chain), 50-56 (LCDR2) and 89-97 (LCDR3) in the light chain variable region and nearby approximately 31-35B (HCDR1; H stands for heavy chain), 50-65 (HCDR2) and 95-102 (HCDR3) in the heavy chain variable region; Kabat et al., SEQUENCES OF PROTEINS OF IMMUNOLOGICAL INTEREST, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991) and/or those residues that form a hypervariable loop (for example, residues 26-32 (LCDR1), 50-52 (LCDR2) and 91-96 (LCDR3) in the light chain variable region and 26-32 (HCDR1), 53-55 (HCDR2) and 96-101 (HCDR3) in the heavy chain variable region Chothia and Lesk (1987) J Mol Biol 196:901-917 Specific CDRs of the present invention are described below.

The present specification generally uses the Kabat numbering system when referring to a residue in the variable domain (approximately light chain variable region residues 1-107 and heavy chain variable region residues 1-113), and the EU numbering system for Fc regions (eg, Kabat et al. al., supra (1991)).

- 14 044325

The present invention provides a large number of different sets of CDRs. In this case, the complete set of CDRs includes three light chain variable region CDRs and three heavy chain variable region CDRs, for example, vlCDR1, vlCDR2, vlCDR3, vhCDR1, vhCDR2 and vhCDR3. They may be part of a larger light chain variable domain or a heavy chain variable domain, respectively. In addition, as described in more detail herein, the heavy chain variable domains and the light chain variable domains may be on separate polypeptide chains, in the case of heavy and light chains (eg, when using Fab), or on the same polypeptide chain in the case of sequences scFv.

CDRs are involved in the formation of the antigen-binding or, more specifically, epitope-binding region of antibodies. An epitope refers to a determinant that interacts with a specific antigen-binding region in the variable region of an antibody molecule, known as a paratope. Epitopes are groups of molecules, such as amino acids or sugar side chains, and usually have certain structural characteristics as well as certain charge characteristics. One antigen can have more than one epitope.

An epitope may include amino acid residues directly involved in binding (also called the immunodominant component of the epitope) and other amino acid residues that are not directly involved in binding, such as amino acid residues that are effectively blocked by a specific antigen binding peptide; in other words, the amino acid residue is within the recognition region of the specific antigen binding peptide.

Epitopes can be either conformational or linear. A conformational epitope is formed by spatially adjacent amino acids from different segments of a linear polypeptide chain. A linear epitope is an epitope formed by adjacent amino acid residues in a polypeptide chain. Conformational and non-conformational epitopes can be distinguished by the fact that binding to the former, but not the latter, is lost in the presence of denaturing solvents.

An epitope typically includes at least 3 and, more often, at least 5 or 8-10 amino acids in a unique spatial conformation. Antibodies that recognize the same epitope can be identified in a simple immunoassay showing the ability of one antibody to block the binding of another antibody to a target antigen, such as sorting.

The carboxy-terminal portion of each chain defines a constant region primarily responsible for effector function. Kabat et al. obtained multiple primary sequences of heavy chain and light chain variable regions. Based on the degree of sequence conservation, they classified and inventoried individual primary sequences into CDRs and scaffolds (see SEQUENCES OF IMMUNOLOGICAL INTEREST, 5th ed., NIH Publication No. 91-3242, E.A. Kabat et al., included in its entirety via link).

In the IgG subclass of immunoglobulins, the heavy chain has several immunoglobulin domains. An immunoglobulin (Ig) domain as used herein means a region of an immunoglobulin having a specific tertiary structure. Of interest in the present invention are heavy chain domains, including heavy chain constant (CH) domains and hinge domains. As for IgG antibodies, IgG isotypes have three CH regions. Accordingly, the CH domains in relation to IgG are as follows: CH1 refers to positions 118-220 according to the Kabat EU index. CH2 refers to positions 237-340 according to the Kabat EU index and CH3 refers to positions 341-447 according to the Kabat EU index. As shown herein and described below, variants with altered pI may be in one or more CH regions, as well as in the hinge region discussed below.

It should be noted that the sequences presented herein begin with the CH1 region at position 118; variable regions are not included unless otherwise noted. For example, the first amino acid of SEQ ID NO: 2, designated as position 1 in the sequence listing, corresponds to position 118 of the CH1 region according to EU numbering.

Another type of heavy chain Ig domain is the hinge region. The term hinge or hinge region or antibody hinge region or immunoglobulin hinge region as used herein refers to a flexible polypeptide including the amino acids between the first and second constant domains of an antibody. Structurally, the CH1 domain of IgG ends at EU position 220, and the CH2 domain of IgG begins at EU position 237. Thus, for IgG, the antibody hinge is defined herein to include positions 221 (D221 in IgG1) to 236 (G236 in IgG1), where the numbering corresponds to the Kabat EU index. In some embodiments, such as the Fc region, a lower hinge is included, the lower hinge typically being at positions 226 or 230. As noted herein, modified pI variants may also be implemented in the hinge region.

A light chain typically contains two domains, a light chain variable domain (containing the light chain CDR and, together with the heavy chain variable domains, forming the Fv region) and a light chain constant region (often referred to as CL or Ck).

- 15 044325

Another region of interest for additional substitutions described below is the Fc region.

Thus, the present invention provides various antibody domains. As described herein and known in the art, the heterodimeric antibodies of the present invention contain different domains within the heavy and light chains, which may also overlap. These domains include, but are not limited to, Fc domain, CH1 domain, CH2 domain, CH3 domain, hinge domain, heavy chain constant domain (CH1 hinge-Fc domain or CH1 hinge-CH2-CH3), heavy chain variable domain , light chain variable domain, light chain constant domain, FAb domains and scFv domains.

Thus, the Fc domain includes a -CH2-CH3 domain and optionally a hinge domain. The heavy chain includes a heavy chain variable domain and a constant domain, which includes an optional CH1-containing hinge-Fc domain containing CH2-CH3. The light chain includes a light chain variable domain and a light chain constant domain.

Some embodiments of the present invention include at least one scFv domain, which, although not naturally occurring, typically includes a heavy chain variable domain and a light chain variable domain joined together by a scFv linker. As shown herein, there are a number of suitable scFv linkers that can be used, including traditional peptide bonds produced using recombinant techniques.

The linker peptide may advantageously comprise the following amino acid residues: Gly, Ser, Ala or Thr. The linker peptide must be long enough to link the two molecules so that they assume the correct conformation relative to each other so that they retain the desired activity. In one embodiment, the linker is from about 1 to 50 amino acids in length, preferably from about 1 to 30 amino acids in length. In one embodiment, linkers ranging from 1 to 20 amino acids in length can be used, with some embodiments finding use from about 5 to about 10 amino acids. Suitable linkers include glycine-serine polymers, including, for example, (GS)n, (GSGGS)n, (GGGGS)n and (GGGS)n, where n is an integer equal to at least one (and usually 3 to 4), glycine-alanine polymers, alanine-serine polymers and other flexible linkers. Alternatively, various non-protein polymers can be used as linkers, including, but not limited to, polyethylene glycol (PEG), polypropylene glycol, polyoxyalkylenes, or copolymers of polyethylene glycol and polypropylene glycol, i.e. they may find use as linkers.

Other linker sequences may include any sequence of any length of the CL/CH1 domain, but not all residues of the CL/CH1 domain; for example, the first 5-12 amino acid residues of the CL/CH1 domains. Linkers can be derived from an immunoglobulin light chain, such as CK or Cλ. Linkers can be derived from immunoglobulin heavy chains of any isotype, including, for example, Cy1, Cy2, Cy3, Cy4, Ca1, Ca2, Cδ, Cε and Cμ. Linker sequences may also be derived from other proteins, such as Ig-like proteins (eg, TCR, FcR, KIR), hinge region-derived sequences, and other natural sequences from other proteins.

In some embodiments, the linker is an interdomain linker used to link any two domains, as further described herein. Although any suitable linker can be used, in many embodiments a glycineserine polymer is used, including, for example, (GS)n, (GSGGS)n, (GGGGS)n and (GGGS)n, where n is an integer equal to at least unit (and typically 3 to 4 to 5), as well as any peptide sequence that allows two domains to be joined recombinantly with sufficient length and flexibility to ensure that each domain retains its biological function. In some cases, and with particular attention to strand structure, as described below, charged interdomain linkers can be used, as used in some embodiments of scFv linkers.

In some embodiments, the scFv linker is a charged scFv linker, a number of which are shown in FIG. 33. Accordingly, the present invention further provides charged scFv linkers to facilitate pI separation of the first and second monomers. That is, by incorporating a charged scFv linker, either positive or negative (or both, in the case of scaffolds that use scFv in different monomers), this allows the monomer containing the charged linker to change the pI without making additional changes to the Fc domains. These charged linkers can be replaced in any scFv containing standard linkers. Additionally, as those skilled in the art will appreciate, charged scFv linkers are applied to the appropriate strand or monomer according to the desired changes in pI ratio. For example, as discussed herein, to produce a heterodimeric antibody in triple F format, the initial pI of the Fv region for each of the desired antigen binding domains is calculated and one is selected to produce the scFv, and depending on the pI, either positively or negatively charged

- 16 044325 linkers.

Charged interdomain linkers can also be used to increase the pI separation of the monomers of the present invention, and thus those included in FIG. 33 can be used in any embodiment herein where a linker is used.

In some embodiments, the antibodies are full-length. The term "full-length antibody" as used herein means a structure that represents the natural biological form of the antibody, including variable and constant regions, including one or more of the modifications described herein, particularly in the Fc domains, allowing either heterodimerization to occur, or purification of heterodimers from homodimers. Full length antibodies typically include Fab and Fc domains and may additionally contain additional antigen binding domains such as scFv, as generally shown in the figures.

In one embodiment, the antibody is an antibody fragment when it contains at least one constant domain that can be engineered to form heterodimers, such as pI-designed ones. Other antibody fragments that can be used include fragments that contain one or more of the CH1, CH2, CH3, hinge, and CL domains of the present invention that have been designed to match the pI. For example, Fc hybrids are hybrids of an Fc region (CH2 and CH3, optionally with a hinge region) linked to another protein. A number of Fc hybrids are known in the art and can be improved by adding heterodimerization variants of the present invention. In this case, fusion antibodies containing CH1 can be obtained; CH1, CH2 and CH3; CH2; CH3; CH2 and CH3; CH1 and CH3, any or all of which may be produced, optionally with a hinge region, using any combination of heterodimerization options described herein.

In particular, the formats shown in FIGS. 1 are antibodies commonly referred to as heterodimeric antibodies, which means that the protein has at least two associated Fc sequences that self-assemble into a heterodimeric Fc domain.

Chimeric and humanized antibodies.

In some embodiments, the antibody may be a combination from different species, for example, a chimeric antibody and/or a humanized antibody. In general, both chimeric antibodies and humanized antibodies refer to antibodies that combine regions from more than one species. For example, chimeric antibodies traditionally contain variable region(s) from mouse (or in some cases rat) and constant region(s) from human. Humanized antibodies generally refer to non-human antibodies in which the variable domain framework regions are replaced with sequences found in human antibodies. Typically, in the case of a humanized antibody, all of the antibody, except for the CDR, is encoded by a polynucleotide of human origin or is identical to such an antibody, except for its CDR. CDRs, some or all of which are encoded by nucleic acids originating from a non-human organism, are grafted into a human antibody variable region beta sheet framework to create an antibody whose specificity is determined by the grafted CDRs. The creation of such antibodies is described, for example, in WO 92/11018, Jones, 1986, Nature 321:522-525, Verhoeyen et al., 1988, Science 239:1534-1536, all incorporated by reference in their entirety. Back mutation of selected scaffold acceptor residues to corresponding donor residues is often required to restore affinity that is lost in the original graft construct (US 5530101; US 5585089; US 5693761; US 5693762; US 6180370; US 5859205; US 5821337; US 60542 97; US 6407213, all incorporated by reference in their entirety). The humanized antibody will optimally also contain at least a portion of an immunoglobulin constant region, typically human immunoglobulin, and thus will typically contain a human Fc region. Humanized antibodies can also be produced using mice with genetically engineered immune cells. Roque et al., 2004, Biotechnol. Prog. 20:639-654, incorporated by reference in its entirety. Various techniques and methods for humanizing and reconstituting non-human antibodies are well known in the art (see Tsurushita & Vasquez, 2004, Humanization of Monoclonal Antibodies, Molecular Biology of B Cells, 533-545, Elsevier Science (USA) and references, quoted herein are all incorporated by reference in their entirety). Humanization methods include, but are not limited to, those described in Jones et al., 1986, Nature 321:522-525; Riechmann et al., 1988; Nature 332:323-329; Verhoeyen et al., 1988, Science, 239:15341536; Queen et al., 1989, Proc Natl Acad Sci, USA 86:10029-33; He et al., 1998, J. Immunol. 160:1029-1035; Carter et al., 1992, Proc Natl Acad Sci USA 89:4285-9, Presta et al., 1997, Cancer Res. 57(20):4593-9; Gorman et al., 1991, Proc. Natl. Acad. Sci. USA 88:4181-4185; O'Connor et al., 1998, Protein Eng 11:321-8, all incorporated by reference in their entirety. Humanization or other methods of reducing the immunogenicity of non-human antibody variable regions may include surface modification methods, as described, for example, in Roguska et al., 1994, Proc. Natl. Acad. Sci. USA 91:969-973, incorporated by reference in its entirety. In one embodiment, the parent antibody was affinity matured, as known in the art. Structure-based methods can be used

- 17 044325 call for humanization and affinity maturation, for example, as described in USSN 11/004590. Selection-based methods can be used to humanize and/or promote affinity maturation of antibody variable regions, including, but not limited to, the methods described in Wu et al., 1999, J. Mol. Biol. 294:151-162; Baca et al., 1997, J. Biol. Chem. 272(16):10678-10684; Rosok et al., 1996, J. Biol. Chem. 271(37):22611-22618; Rader et al., 1998, Proc. Natl. Acad. Sci. USA 95:8910-8915; Krauss et al., 2003, Protein Engineering 16(10):753-759, all incorporated by reference in their entirety. Other humanization methods may include grafting only part of the CDR, including without limitation the methods described in USSN 09/810,510; Tan et al., 2002, J. Immunol. 169:1119-1125; De Pascalis et al., 2002, J. Immunol. 169:3076-3084, all incorporated by reference in their entirety.

IV. Heterodimeric antibodies.

Accordingly, in some embodiments, the present invention provides heterodimeric antibodies that rely on the use of two different heavy chain variant Fc sequences that will self-assemble to form heterodimeric Fc domains and heterodimeric antibodies.

The present invention relates to new constructs for the production of heterodimeric antibodies that provide binding to more than one antigen or ligand, for example, provide bispecific binding. Heterodimeric antibody designs rely on the self-assembled nature of the two Fc domains of the antibody heavy chains, for example, two monomers that assemble into a dimer. Heterodimeric antibodies are prepared by changing the amino acid sequence of each monomer, as described in more detail below. Thus, the present invention generally relates to the creation of heterodimeric antibodies that can co-contact antigens in multiple ways due to amino acid variants in constant regions that differ on each chain, with the purpose of promoting heterodimer formation and/or allowing heterodimers to be easily purified from homodimers.

Thus, the present invention provides bispecific antibodies. A current challenge in antibody technologies is the desire to produce bispecific antibodies that bind to two different antigens simultaneously, generally bringing different antigens into close proximity and leading to new functional characteristics and new therapies. In general, these antibodies are produced by incorporating genes for each heavy and light chain into host cells. This usually results in the formation of the desired heterodimer (A-B), as well as two homodimers (A-A and B-B (not counting the output of light chain heterodimers)). However, the main obstacle in the formation of bispecific antibodies is the difficulty of purifying heterodimeric antibodies from homodimeric antibodies and/or bias towards the formation of a heterodimer relative to the formation of homodimers.

There are a number of mechanisms that can be used to obtain the heterodimers of the present invention. Moreover, as those skilled in the art will appreciate, these mechanisms can be combined to provide a high degree of heterodimerization. Thus, amino acid variants that result in heterodimers are referred to as heterodimerization variants. As discussed below, heterodimerization variants may include steric variants (eg, peak-and-valley or asymmetric variants, described below, and charge-pair variants, described below), as well as variants with altered pI, which allow the purification of heterodimers from homodimers. As generally described in WO2014/145806, incorporated herein by reference in its entirety, and in particular for the discussion of heterodimerization options below, suitable heterodimerization mechanisms include knobs and indentations (KIH; sometimes herein asymmetric variants ( see discussion in WO2014/145806), electrostatic guidance or charge couples described in WO2014/145806, modified pI variants described in WO2014/145806, and general additional Fc variants described in WO2014/145806 and below.

In the present invention, there are several basic mechanisms that can provide easy purification of heterodimeric antibodies; one is based on the use of variants with an altered pI such that each monomer has a different pI, allowing purification based on the isoelectric point of dimeric proteins A-A, A-B and B-B. Alternatively, some frame formats, such as the triple F format, also allow separation by size. As further described below, it is also possible to bias the formation of heterodimers relative to homodimers. Thus, the combination of steric heterodimerization variants and pI or charge pair variants finds particular use in the present invention.

In general, embodiments of specific use in the present invention are based on variant sets that include asymmetric variants that cause heterodimerization instead of homodimerization, in combination with altered pI variants that increase the pI difference between two monomers.

Additionally, as described in more detail below, depending on the format of the heterodimeric antibody, altered pI variants may be contained in either constant and/or Fc domains of the monomer or charged linkers, or interdomain linkers or scFv linkers may be used. That is, scaffolds that use scFvs, such as the triple F format, may include charged linkers

- 18 044325 scFv (positive or negative), which provide an additional increase in pI for purification purposes. As will be appreciated by those skilled in the art, some ternary F formats are useful with just charged scFv linkers and no additional pI adjustments, although the present invention does provide for variants with altered pI that are in one or both monomers and/or also charged interdomain linkers. In addition, additional amino acid engineering to obtain alternative functional characteristics can also provide changes in pI, for example, in the case of Fc-, FcRn- and KO-variants.

In the present invention, which uses pI as a separation mechanism to provide purification of heterodimeric proteins, amino acid variants can be introduced into one or both monomeric polypeptides; those. The pI of one of the monomers (referred to herein as monomer A for simplicity) can be engineered separately from monomer B, or both shifts of monomers A and B can be altered to increase the pI of monomer A and decrease the pI of monomer B. As described in more detail below, changes to the pI of either or of both monomers can be accomplished by removing or adding a charged residue (e.g., a neutral amino acid is replaced by a positively or negatively charged amino acid residue, such as glycine to glutamic acid), replacing a charged residue from positive or negative to the opposite charge (aspartic acid to lysine), or replacing a charged residue to a neutral residue (e.g. loss of charge; lysine to serine). A number of these options are shown in the figures.

Accordingly, this embodiment of the present invention involves creating a sufficient change in the pI of at least one of the monomers such that heterodimers can be separated from homodimers. As will be appreciated by those skilled in the art and as discussed below, this can be accomplished using a wild-type heavy chain constant region and a variable region that has been engineered to increase or decrease its pI (wt A- +B or wt A- -B), or by increasing one area and decreasing another area (A+ -B- or A-B+).

Thus, in general, a component of some embodiments of the present invention are amino acid variants in the constant regions of antibodies that are directed to change the isoelectric point (pI) of at least one, if not both, of the dimeric protein monomers to produce antibodies with an altered pI by incorporating amino acid substitutions (variants with a changed pI or substitutions with a change in pI) into one or both monomers. As shown herein, separation of heterodimers from two homodimers can be achieved if the pI of the two monomers differ by only 0.1 pH unit, with each of 0.2, 0.3, 0.4 and 0.5 or higher being found application in the present invention.

As will be appreciated by those skilled in the art, the number of pI-altered variants that must be included in each or both monomers to obtain good resolution will depend in part on the original pI of the components, e.g., in the triple F format, the original pI of scFv and Fab , of interest. That is, to determine which monomer needs to be designed or in which direction (eg, more positive or more negative), the Fv sequences for the two target antigens are calculated and a decision is made based on this. As is known in the art, different Fv will have different initial pI, which are used in the present invention. In general, as described herein, the pI is adjusted to obtain an overall pI difference for each monomer of at least about 0.1 log, with 0.2-0.5 being preferred, as described herein.

Additionally, as will be appreciated by those skilled in the art and as described herein, in some embodiments, heterodimers can be separated from homodimers based on size. As shown, for example, in FIG. 1, some of the formats allow separation of heterodimers and homodimers based on size.

When altered pI variants are used to achieve heterodimerization, the use of heavy chain constant region(s) provides a more modular approach to the design and purification of bispecific proteins, including antibodies. Thus, in some embodiments, heterodimerization variants (including asymmetric and purified heterodimerization variants) are not included in the variable regions such that each individual antibody must be designed. Additionally, in some embodiments, the likelihood of immunogenicity resulting from the use of altered pI variants is significantly reduced by introducing altered pI variants from different IgG isotypes such that the pI is altered without introducing significant immunogenicity. Thus, an additional problem that must be solved is the identification of constant domains with low pI and high human sequence content, for example, minimizing or eliminating non-human residues at any particular position.

An additional benefit that may arise from this pI adjustment is also increased serum half-life and increased FcRn binding. That is, as described in USSN 13/194904 (incorporated by reference in its entirety), lowering the pI of antibody constant domains (including domains found in fusion antibodies and Fc hybrids) may

- 19 044325 lead to longer retention in serum in vivo. These variants with altered pI to increase serum half-life also contribute to altered pI for purification.

In addition, it should be noted that the altered pI variants of heterodimerization variants provide an additional advantage for the analytical methods and quality control process of bispecific antibodies, since the ability to eliminate, minimize and recognize the presence of homodimers is essential. Likewise, the ability to reliably test the reproducibility of heterodimeric antibody production is important.

Heterodimerization options.

The present invention provides heterodimeric proteins, including heterodimeric antibodies in a variety of formats, for which heterodimeric variants are used to provide heterodimer formation and/or purification from homodimers.

There are a number of suitable pairs of sets of asymmetric heterodimerization variants. These options come in a couple of sets. That is, one set of the pair is included in the first monomer, and the other set of the pair is included in the second monomer. It should be noted that these arrays do not necessarily behave as peak-and-trough variants with a mutual correspondence between a residue in one monomer and a residue in another; those. these pairs of sets form a contact surface between the two monomers that promotes heterodimer formation and inhibits homodimer formation, ensuring the percentage of heterodimers that spontaneously form under biological conditions exceeds 90% rather than the expected 50% (25% A/A homodimer: 50% heterodimer A/B: 25% homodimer B/B).

Steric variations.

In some embodiments, the formation of heterodimers can be facilitated by the addition of steric variations. That is, when the amino acids in each heavy chain change, different heavy chains are more likely to bind to form a heterodimeric structure than to form homodimers with the same Fc amino acid sequences. Suitable steric variations are shown in FIG. 29.

It is also optionally possible to employ one of the mechanisms commonly referred to in the art as peaks and valleys and related to amino acid design that creates steric influences to favor heterodimer formation and disfavor homodimer formation; it is sometimes called ridges and valleys, as described in USSN 61/596846, Ridgway et al., Protein Engineering 9(7):617 (1996); Atwell et al., J. Mol. Biol. 1997 270:26; in US Pat. No. 8,216,805, all of which are incorporated herein by reference in their entirety. A number of monomer A-monomer B pairs are identified in the figures, which refer to peaks and valleys. Additionally, as described in Merchant et al., Nature Biotech. 16:677 (1998), these mutational peaks and valleys can be combined with disulfide bonds to form heterodimerization asymmetries.

An additional mechanism that finds use in the preparation of heterodimers is sometimes called electrostatic targeting, as described in Gunasekaran et al., J. Biol. Chem. 285(25):19637 (2010), incorporated herein by reference in its entirety. These are sometimes referred to herein as charge pairs. In this embodiment, the phenomenon of electrostatics is used to shift the formation towards heterodimerization. As will be appreciated by those skilled in the art, they may also have an impact on the pI and therefore the purification, and may therefore also be considered as altered pI variants in some cases. However, because they were designed to enhance heterodimerization and were not used as a purification tool, they are classified as steric variants. These include, but are not limited to, D221E/P228E/L368E paired with D221R/P228R/K409R (i.e., they are monomer-matched sets) and C220E/P228E/368E paired with C220R/E224R/P228R/K409R.

Additional variants of Monomer A and Monomer B, which can be combined with other variants, optionally and independently in any amount, such as the altered pI variants described herein or other steric variants, are shown in FIG. 37 in US 2012/0149876, the figure and legend and SEQ ID NO of which are specifically incorporated herein by reference.

In some embodiments, the steric variants described herein may be optionally and independently included with any altered pI variant (or other variants such as Fc variants, FcRn variants, etc.) in one or both monomers and may be independently and optionally included or excluded from the proteins of the present invention.

A list of suitable asymmetrical options is presented in FIG. 29, and in fig. 34 shows some pairs particularly useful in many embodiments. Particularly useful in many embodiments are pairs of sets including, but not limited to, S364K/E357Q:L368D/K370S; L368D/K370S:S364K; L368E/K370S:S364K; T411T/E360E/Q362E:D401K; L368D/K370S:S364K/E357L and K370S: S364K/E357Q. Regarding steam nomenclature

S364K/E357Q:L368D/K370S means that one of the monomers has a double set of S364K/E357Q variants and the other has a double set of L368D/K370S variants.

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Options based on pI (isoelectric point) for heterodimers.

In general, as will be appreciated by those skilled in the art, there are two general categories of pI-based variants: those that increase the pI of the protein (alkaline changes) and those that decrease the pI of the protein (acidic changes). As described herein, all combinations of these variants can be performed: one monomer can be wild type or a variant that does not show significant pI differences compared to wild type, and the other can be either more alkaline or more acidic. Alternatively, each monomer is changed, one to be more alkaline and the other to be more acidic.

Preferred combinations of modified pI variants are shown in FIG. 30. As stated herein and shown in the figures, these changes are shown relative to IgG1, but all isotypes can be changed in this way, as well as isotype hybrids. In the case where the heavy chain constant domain is derived from IgG2-4, R133E and R133Q can also be used.

Light chain variants of heterodimer antibodies.

In the case of antibody-based heterodimers, for example, where at least one of the monomers contains a light chain in addition to a heavy chain domain, altered pI variants can also be made in the light chain. Amino acid substitutions to lower the light chain pI include, but are not limited to, K126E, K126Q, K145E, K145Q, N152D, S156E, K169E, S202E, K2O7E, and the addition of the DEDE peptide at the C-terminus of the light chain. Changes in this category based on the lambda light chain constant domain include one or more substitutions at R108Q, Q124E, K126Q, N138D, K145T, and Q199E. In addition, the pI of the light chains can also be increased.

Isotypic options.

In addition, many embodiments of the present invention rely on the import of pI-affecting amino acids at specific positions from one IgG isotype to another, thereby reducing or eliminating the likelihood of introducing unwanted immunogenicity into the variants. Some of them are shown in Fig. 21 from US Patent Application Publication 2014/0370013, incorporated herein by reference. That is, IgG1 is a common isotype for therapeutic antibodies for a variety of reasons, including high effector function. However, the heavy chain constant region of IgG1 has a higher pI than that of IgG2 (8.10 versus 7.31). By introducing IgG2 residues at specific positions in the IgG1 backbone, the pI of the resulting monomer is lowered (or increased) and additionally has a longer serum half-life. For example, IgG1 contains glycine (pI 5.97) at position 137, and IgG2 contains glutamic acid (pI 3.22); the introduction of glutamic acid will affect the pI of the resulting protein. As described below, a number of amino acid substitutions are typically required to significantly affect the pI of a variant antibody. However, it should be noted, as discussed below, that even changes in IgG2 molecules allow for an increase in serum half-life.

In other embodiments, non-isotypic amino acid changes are made to either reduce the overall charge state of the resulting protein (e.g., by replacing an amino acid with a higher pI with an amino acid with a lower pI), or to provide structure adaptation with respect to stability, etc., as more described in detail below.

In addition, by designing the constant domains of both the heavy and light chains based on the pI, significant changes can be observed in each monomer of the heterodimer. As discussed herein, pIs of two monomers that differ by at least 0.5 may allow separation by ion exchange chromatography or isoelectric focusing or other isoelectric point sensitive techniques.

Calculation of pI.

The pI value of each monomer may depend on the pI of the variant heavy chain constant domain and the pI of the entire monomer, including the variant heavy chain constant domain and the fusion partner. Thus, in some embodiments, the change in pI is calculated from the heavy chain constant domain of the variant using the table shown in FIG. 19 US Patent Application Publication 2014/0370013. As discussed herein, the choice of monomer to design is typically determined by the pI characteristic of the Fv and framework regions. Alternatively, the pI of each monomer can be compared.

Variants with altered pI that also provide better FcRn binding in vivo.

In the case where the modified pI variant reduces the pI of the monomer, it may have the additional benefit of improved serum retention in vivo.

Although Fc regions are still being investigated, they are thought to have a longer half-life in vivo because binding to FcRn at pH 6 in the endosome sequesters the Fc (Ghetie and Ward, 1997 Immunol Today. 18(12):592 -598, incorporated by reference in its entirety). The endosomal compartment then returns Fc to the cell surface. Once the compartment opens into the extracellular space, the higher pH, ~7.4, causes the release of Fc back into the blood. Dall' Acqua et al showed that in mice, Fc mutants with increased FcRn binding at pH 6 and pH 7.4 were actually observed at reduced concentrations in serum.

- 21 044325 rotka and had the same half-life as wild-type Fc (Dall' Acqua et al. 2002, J. Immunol. 169:5171-5180, incorporated by reference in its entirety). The increased affinity of Fc for FcRn at pH 7.4 is thought to prevent the release of Fc back into the blood. Therefore, Fc mutations that will increase the half-life of Fc in vivo will ideally increase the extent of FcRn binding at lower pH while allowing Fc release at higher pH. The amino acid histidine changes its charge state in the pH range from 6.0 to 7.4. It is therefore not surprising that His residues can be found at important positions in the Fc/FcRn complex.

It has recently been suggested that antibodies with variable regions that are characterized by lower isoelectric points may also have a longer serum half-life (Igawa et al., 2010 PEDS. 23(5):385-392, incorporated by reference in its entirety) . However, the mechanism of this phenomenon is still poorly understood. Moreover, the variable regions differ from antibody to antibody. Constant region variants with reduced pI and increased half-life would provide a more modular approach to improve the pharmacokinetic properties of the antibodies described herein.

Additional Fc options for additional functionality.

In addition to amino acid variants with altered pI, there are a number of useful Fc amino acid modifications that can be made for a variety of reasons including, but not limited to, altered binding to one or more FcyR receptors/ altered binding to FcRn receptors, etc.

Accordingly, the proteins of the present invention may include amino acid modifications, including heterodimerization variants described herein, which include altered pI variants and steric variants. Each set of variants may be independently and optionally included or excluded from any particular heterodimeric protein.

FcγR variants.

Accordingly, there are a number of useful Fc substitutions that can be made to alter binding to one or more FcyR receptors. Substitutions that result in increased binding as well as decreased binding may be suitable. For example, it is known that increased binding to GcRIIIa typically results in increased ADCC (antibody-dependent cell-mediated cytotoxicity, a cell-mediated reaction in which nonspecific cytotoxic cells that express FcyR recognize bound antibody on a target cell and subsequently cause lysis of the target cell). Likewise, reducing the degree of binding to FcyRIIb (inhibitory receptor) may also be beneficial in some cases. Amino acid substitutions that find use in the present invention include those listed in USSN 11/124620 (specifically, Figure 41), 11/174287, 11/396,495, 11/538406, all of which are expressly incorporated herein by reference in its entirety and, in particular, for the embodiments disclosed herein. Specific embodiments that find use include, but are not limited to, 236A, 239D, 239E, 332E, 332D, 239D/332E, 267D, 267E, 328F, 267E/328F, 236A/332E, 239D/332E/330Y, 239D, 332E/ 330L, 243A, 243L, 264A, 264V and 299T.

In addition, there are additional substitutions in Fc that are used to increase FcRn receptor binding and serum half-life, as particularly disclosed in USSN 12/341769, incorporated herein by reference in its entirety. including without limitation 434S, 434A, 428L, 308F, 259I, 428L/434S, 259I/308F, 436I/428L, 436I or V/434S, 436V/428L and 259I/308F/428L.

Options with violation.

Similarly, another category of functional variants are variants with impaired binding to FcyR or Fc knockout (FcKO or KO) variants. In these embodiments, for some therapeutic applications, it is desirable to reduce or eliminate the extent of normal Fc domain binding to one or more or all of the Fcy receptors (e.g., FcyRl, FcyRIIa, FcyRIIb, FcyRHIa, etc.) to avoid additional mechanisms of action. That is, for example, in many embodiments, especially when using bispecific antibodies that monovalently bind CD3, it is generally desirable to disrupt FcyRIIIa binding to eliminate or significantly reduce ADCC activity, where one of the Fc domains contains one or more variants that disrupt Fcy binding -receptor. These disrupted variants are shown in FIG. 31, and each of them may be independently and optionally included or excluded, with preferred aspects using disrupted variants selected from the group consisting of G236R/L328R, E233P/L234V/L235A/G236del/S239K, E233P/L234V/L235A/ G236del/S267K,

E233P/L234V/L235A/G236del/S239K/A327G, E233P/L234V/L235A/G236del/S267K/A327G and

E233P/L234V/L235A/G236del. It should be noted that the disrupted variants referred to herein disrupt FcyR binding but typically not FcRn binding.

Combination of heterodimeric and Fc variants.

As will be clear to those skilled in the art, all of the listed heterodimerization variants

- 22 044325 tions (including asymmetric and/or variants with altered pI) can optionally and independently be combined in any way, provided that they retain their filamentous structure or monomerization. In addition, all of these options can be combined in any of the heterodimerization formats.

In the case of modified pI variants, although embodiments having specific applications are shown in the figures, other combinations can be created by following the basic rule of changing the pI difference between two monomers to facilitate purification.

In addition, any of the heterodimerization variants, asymmetric and pI altered, are also independently and optionally combined with Fc deletion variants, Fc variants, FcRn variants, as generally set forth herein.

Suitable formats for the present invention.

As will be appreciated by those skilled in the art and discussed in more detail below, the heterodimeric fusion proteins of the present invention can take on a wide variety of configurations, as generally illustrated in FIG. 1. Some figures depict one-sided configurations where one type of specificity is due to one arm of the molecule and a different specificity is due to the other arm. Other figures depict two-way configurations where there is at least one type of specificity due to the upper part of the molecule and one or more other types of specificity due to the lower part of the molecule. Thus, the present invention relates to new immunoglobulin compositions that contact different first and second antigens.

As will be appreciated by those skilled in the art, the heterodimeric formats of the present invention may have different valencies, as well as be bispecific. That is, the heterodimeric antibodies of the present invention can be bivalent and bispecific, where one target tumor antigen (e.g., CD3) is bound by one binding domain, and another target tumor antigen (e.g., CD20, CD19, CD38, CD123, etc.) ) is bound by a second binding domain. Heterodimeric antibodies can also be trivalent and bispecific, where the first antigen is bound by two binding domains and the second antigen is bound by a second binding domain. As described herein, when CD3 is one of the target antigens, it is preferable that CD3 binds only monovalently to reduce possible side effects.

The present invention uses the antigen binding domains of an anti-CD3 antibody in combination with domains that bind to a tumor target antigen (TTA). As will be appreciated by those skilled in the art, any variety of CD3-binding CDRs, light and heavy chain variable domains, Fabs, and CD3-binding scFvs may be used, as shown in any of the Figures (see particularly FIG. 2- 7 and Fig. 68). Likewise, any of the antigen-binding domains of an anti-TTA antibody may be used, for example, the antigen-binding domains CD38, CD20, CD19, and CD123, and any of the CDRs, light and heavy chain variable domains, Fabs, and scFvs depicted in any one may be used. of figures, optionally and independently combined in any combination.

Opener format.

One heterodimer scaffold that finds particular use in the present invention is the triple F or opener scaffold format, as shown in FIG. 1A, A and B. In this embodiment, one heavy chain of the antibody contains a single chain Fv (scFv, as defined below) and the other heavy chain is a conventional FAb format containing a heavy chain variable domain and a light chain. This structure is sometimes referred to herein as the triple F format (scFv-FAb-Fc) or bottle opener format due to its rough visual resemblance to a bottle opener (see FIG. 1). The two chains are combined by using amino acid variants in constant regions (eg, Fc domain, CH1 domain and/or hinge region) that promote the formation of heterodimeric antibodies, as described in more detail below.

There are several obvious advantages to the triple F'' format of the present invention. As is known in the art, antibody analogues based on two scFv constructs often have problems with stability and aggregation, which can be reduced according to the present invention by adding conventional heavy-light chain pairing. Additionally, unlike two-heavy-two-light-chain formats, there is no problem associated with incorrect pairing of heavy and light chains (e.g., pairing heavy chain 1 with light chain 2, etc.).

Many of the embodiments set forth herein are generally based on an opener format that contains a first scFv-containing monomer containing a heavy chain variable domain and a light chain variable domain covalently linked by an scFv linker (charged in many but not in all cases), where the scFv is covalently attached to the N-terminus of the first Fc domain, typically through an interdomain linker (which, as described herein, can be uncharged or charged). The second monomer of the opener format is a heavy chain, and the composition further contains a light chain.

- 23 044325

In general, in many preferred embodiments, the scFv is a domain that binds CD3, with the heavy and light chain Fabs binding to another TTA. In addition, the Fc domains of the present invention typically contain asymmetric variants (eg, a set of amino acid substitutions, as shown in Fig. 29 and Fig. 34, with particularly useful asymmetric variants selected from the group consisting of S364K/E357Q: L368D/K370S; L368D/K370S: S364K; L368E/K370S: S364K; T411T/E360E/Q362E: D401K; L368D/K370S: S364K/E357L and K370S: S364K/E357Q), optional, variants with violation (including those shown in Fig. 31), not necessarily , charged scFv linkers (including those shown in Fig. 33), and the heavy chain contains variants with altered pI (including those shown in Fig. 30).

The present invention provides opener formats in which the anti-CD3 scFv sequences are as shown in FIG. 2-7 and fig. 68.

The present invention provides opener formats with anti-CD38 antibody antigen binding domains, wherein the CD38 binding sequences are as shown in the figures, including FIGS. 8-10.

The present invention provides opener formats with anti-CD20 antibody antigen binding domains, wherein the CD20 binding sequences are as shown in the figures.

The present invention provides opener formats with anti-CD19 antibody antigen binding domains, wherein the CD19 binding sequences are as shown in the figures.

The present invention provides opener formats with anti-CD123 antibody antigen binding domains, wherein the sequences that bind to CD123 are as shown in the figures.

mAb-Fv format.

One heterodimer scaffold that finds particular use in the present invention is the mAb-Fv format shown in FIG. 1. In this embodiment, the format is based on the use of a C-terminal attachment of an additional heavy chain variable domain to one monomer and a C-terminal attachment of an additional light chain variable domain to another monomer, thereby forming a third antigen binding domain, where the Fab fragments of the two monomers are bound by TTA, and an additional scFv domain binds CD3.

In this embodiment, the first monomer comprises a first heavy chain containing a first heavy chain variable domain and a first heavy chain constant domain containing a first Fc domain, with a first light chain variable domain covalently attached to the C terminus of the first Fc domain via an interdomain linker. The second monomer contains a second heavy chain variable domain and a second heavy chain constant domain containing a second Fc domain, and a third heavy chain variable domain covalently attached to the C-terminus of the second Fc domain via an interdomain linker. Two variable domains attached to the C-terminus constitute scFv, which binds CD3. This embodiment further utilizes a common light chain comprising a light chain variable domain and a light chain constant domain that couples to the heavy chains to form two identical Fabs that bind TTA. With respect to the many embodiments herein, these designs include asymmetric variants, altered pI variants, disrupted variants, additional Fc variants, etc., as are desirable and described herein.

The present invention provides mAb-Fv formats in which the anti-CD3 scFv sequences are as shown in FIG. 2-7 and fig. 68.

The present invention provides mAb-Fv formats in which the CD38 binding sequences are as shown in FIG. 8-10.

The present invention provides mAb-Fv formats with anti-CD20 antibody antigen binding domains, wherein the CD20 binding sequences are as shown in the figures.

The present invention provides mAb-Fv formats with anti-CD19 antibody antigen binding domains, wherein the CD19 binding sequences are as shown in the figures.

The present invention provides mAb-Fv formats with anti-CD123 antibody antigen binding domains, wherein the CD123 binding sequences are as shown in the figures.

The present invention provides mAb-Fv formats containing disrupted variants, as shown in FIG. 31.

The present invention provides mAb-Fv formats containing asymmetric variants, as shown in FIG. 29 and 34.

- 24 044325 mAb-scFv.

One heterodimer scaffold that finds particular use in the present invention is the mAb-Fv format shown in FIG. 1. In this embodiment, the format is based on the C-terminal attachment of a scFv to one of the monomers, thereby forming a third antigen binding domain, where the Fab fragments of the two monomers bind TTA and the additional scFv domain binds CD3. Thus, the first monomer comprises a first heavy chain (comprising a heavy chain variable domain and a constant domain) with a scFv covalently attached to the C-terminus comprising a light chain scFv variable domain, a scFv linker, and a heavy chain scFv variable domain. This embodiment further utilizes a common light chain comprising a light chain variable domain and a light chain constant domain that couples to the heavy chains to form two identical Fabs that bind TTA. With respect to the many embodiments herein, these designs include asymmetric variants, altered pI variants, disrupted variants, additional Fc variants, etc., as are desirable and described herein.

The present invention provides mAb-Fv formats in which the anti-CD3 scFv sequences are as shown in FIG. 2 - fig. 7 and fig. 68.

The present invention provides mAb-Fv formats in which the CD38 binding sequences are as shown in FIG. 8-10.

The present invention provides mAb-Fv formats with anti-CD20 antibody antigen binding domains, wherein the CD20 binding sequences are as shown in the figures.

The present invention provides mAb-Fv formats with anti-CD19 antibody antigen binding domains, wherein the CD19 binding sequences are as shown in the figures.

The present invention provides mAb-Fv formats with anti-CD123 antibody antigen binding domains, wherein the CD123 binding sequences are as shown in the figures.

The present invention provides mAb-Fv formats containing disrupted variants, as shown in FIG. 31.

The present invention provides mAb-Fv formats containing asymmetric variants, as shown in FIG. 29 and 34.

Central scFv.

One heterodimer scaffold that finds particular use in the present invention is the scFv-centered format shown in FIG. 1. In this embodiment, the format is based on the use of an inserted scFv domain, thereby forming a third antigen binding domain, where the Fab fragments of the two monomers bind TTA, and the additional scFv domain binds CD3. The scFv domain is inserted between the Fc domain and the CH1-Fv region of one of the monomers, thereby providing a third antigen binding domain.

In this embodiment, one monomer comprises a first heavy chain comprising a first heavy chain variable domain, a CH1 domain and an Fc domain, wherein the scFv comprises a light chain scFv variable domain, a scFv linker and a heavy chain scFv variable domain. scFv is covalently attached between the C-terminus of the CH1 domain of the heavy chain constant domain and the N-terminus of the first Fc domain using interdomain linkers. This embodiment further utilizes a common light chain comprising a light chain variable domain and a light chain constant domain that couples to the heavy chains to form two identical Fabs that bind TTA. With respect to the many embodiments herein, these designs include asymmetric variants, altered pI variants, disrupted variants, additional Fc variants, etc., as are desirable and described herein.

The present invention provides core scFv formats in which the anti-CD3 scFv sequences are as shown in FIG. 2 - fig. 7 and fig. 68.

The present invention provides core scFv formats in which the CD38 binding sequences are as shown in FIG. 8-10.

The present invention provides formats with a central scFv with antigen binding domains of an anti-CD20 antibody, wherein the CD20 binding sequences are as shown in the figures.

The present invention provides formats with a central scFv with antigen binding domains of an anti-CD19 antibody, wherein the CD19 binding sequences are as shown in the figures.

The present invention provides formats with a central scFv with antigen binding domains of an anti-CD123 antibody, wherein the sequences that bind to CD123 are as shown in the figures.

The present invention provides central scFv formats containing variants with

- 25 044325 violation, as shown in FIG. 31.

The present invention provides central scFv formats containing asymmetric variants, as shown in FIG. 29 and 34.

Format with central Fv.

One heterodimer scaffold that finds particular use in the present invention is the Fv-centered format shown in FIG. 1. In this embodiment, the format is based on the use of an inserted scFv domain, thereby forming a third antigen binding domain, where the Fab fragments of the two monomers bind TTA, and the additional scFv domain binds CD3. The scFv domain is inserted between the Fc domain and the CH1-Fv region of one of the monomers, thereby providing a third antigen binding domain, where each monomer contains a scFv component (eg, one monomer contains a heavy chain variable domain and the other contains a light chain variable domain).

In this embodiment, one monomer comprises a first heavy chain comprising a first heavy chain variable domain, a CH1 domain and an Fc domain, and an additional light chain variable domain. The light chain domain is covalently attached between the C-terminus of the CH1 domain of the heavy chain constant domain and the N-terminus of the first Fc domain using interdomain linkers. The other monomer contains a first heavy chain containing a first heavy chain variable domain, a CH1 domain and an Fc domain, and an additional heavy chain variable domain. The light chain domain is covalently attached between the C-terminus of the CH1 domain of the heavy chain constant domain and the N-terminus of the first Fc domain using interdomain linkers.

This embodiment further utilizes a common light chain comprising a light chain variable domain and a light chain constant domain that couples to the heavy chains to form two identical Fabs that bind TTA. With respect to the many embodiments herein, these designs include asymmetric variants, altered pI variants, disrupted variants, additional Fc variants, etc., as are desirable and described herein.

The present invention provides Fv-core formats in which the CD3-binding scFv sequences are as shown in FIG. 2 - fig. 7 and fig. 68.

The present invention provides Fv-centered formats in which the CD38 binding sequences are as shown in FIG. 8-10.

The present invention provides central Fv formats with CD20 antibody antigen binding domains, wherein the CD20 binding sequences are as shown in the figures.

The present invention provides central Fv formats with CD19 antibody antigen binding domains, wherein the CD19 binding sequences are as shown in the figures.

The present invention provides central Fv formats with anti-CD123 antibody antigen binding domains, wherein the CD123 binding sequences are as shown in the figures.

The present invention provides Fv-centered formats containing disrupted variants, as shown in FIG. 31.

The present invention provides center Fv formats containing asymmetrical variants, as shown in FIG. 29 and 34.

Incomplete central scFv.

One heterodimer scaffold that finds particular use in the present invention is the partial core scFv format shown in FIG. 1. In this embodiment, one monomer contains only an Fc domain, while the other monomer uses an inserted scFv domain, thereby forming a second antigen binding domain. In this format, either the Fab fragment binds TTA and the scFv binds CD3, or vice versa. The scFv domain is inserted between the Fc domain and the CH1-Fv region of one of the monomers.

In this embodiment, one monomer comprises a first heavy chain comprising a first heavy chain variable domain, a CH1 domain and an Fc domain, wherein the scFv comprises a light chain scFv variable domain, a scFv linker and a heavy chain scFv variable domain. scFv is covalently attached between the C-terminus of the CH1 domain of the heavy chain constant domain and the N-terminus of the first Fc domain using interdomain linkers. The second monomer contains an Fc domain. In this embodiment, a light chain is further used, comprising a light chain variable domain and a light chain constant domain, which is coupled to a heavy chain to form a Fab. With respect to the many embodiments herein, these designs include asymmetric variants, altered pI variants, disrupted variants, additional Fc variants, etc., as are desirable and described herein.

The present invention provides partial core scFv formats where the CD3 binding scFv sequences are as shown in FIG. 2-fig. 7 and fig. 68.

- 26 044325

The present invention provides partial core scFv formats in which the CD38 binding sequences are as shown in FIG. 8-10.

The present invention provides formats with a partial core scFv with antigen binding domains of an anti-CD20 antibody, wherein the CD20 binding sequences are as shown in the figures.

The present invention provides formats with a partial core scFv with antigen binding domains of an anti-CD19 antibody, wherein the CD19 binding sequences are as shown in the figures.

The present invention provides formats with a partial core scFv with antigen binding domains of an anti-CD123 antibody, wherein the sequences that bind to CD123 are as shown in the figures.

The present invention provides partial core scFv formats containing disrupted variants, as shown in FIG. 31.

The present invention provides partial central scFv formats containing asymmetric variants, as shown in FIG. 29 and 34.

Double scFv formats.

The present invention provides dual scFv formats known in the art and shown in FIG. 1.

The present invention provides dual scFv formats in which the anti-CD3 scFv sequences are as shown in FIG. 2 - fig. 7 and fig. 68.

The present invention provides dual scFv formats in which the CD38 binding sequences are as shown in FIG. 8-10.

The present invention provides dual scFv formats with anti-CD20 antibody antigen binding domains, wherein the CD20 binding sequences are as shown in the figures.

The present invention provides dual scFv formats with CD19 antibody antigen binding domains, wherein the CD19 binding sequences are as shown in the figures.

The present invention provides dual scFv formats with anti-CD123 antibody antigen binding domains, wherein the CD123 binding sequences are as shown in the figures.

The present invention provides dual scFv formats containing disrupted variants, as shown in FIG. 31.

The present invention provides dual scFv formats containing asymmetric variants, as shown in FIG. 2 9 and 34.

Target antigens.

The bispecific antibodies of the present invention have two different antigen binding domains: one that binds CD3 (usually monovalently) and another that binds the target tumor antigen (sometimes referred to herein as TTA). Suitable tumor target antigens include, but are not limited to, CD20, CD38, CD123; ROR1, ROR2, BCMA; PSMA; SSTR2; SSTR5, CD19, FLT3, CD33, PSCA, ADAM 17, CEA, Her2, EGFR, EGFR-vIII, CD30, FOLR1, GD-2, CA-IX, Trop-2, CD70, CD38, mesothelin, EphA2, CD22, CD79b , GPNMB, CD56, CD138, CD52, CD74, CD30, CD123, RON, ERBB2 and EGFR.

The Triple F format is particularly useful when targeting two (or more) different antigens. (As described herein, this targeting can be any combination of monovalent and bivalent binding depending on the format). Thus, the immunoglobulins herein preferentially contact two target antigens. The specificity of each monomer can be selected from the lists provided herein. Additional suitable bispecific formats for use with the anti-CD3 antibody binding domain are shown in FIG. 1.

Specific suitable applications of heterodimeric antibodies herein are co-targeted pairs for which it is advantageous or essential to contact each target antigen monovalently. Such antigens can be, for example, immune receptors that are activated during the formation of an immune complex. Cellular activation of many immune receptors occurs solely through cross-linking, usually through antibody/antigen immune complexes, or through an effector cell involving target cells. For some immune receptors, such as the CD3 signaling receptor on T cells, activation solely upon contact with a co-engaged target is critical, as nonspecific cross-linking can cause cytokine storm and toxicity in clinical settings. From a therapeutic point of view, by contacting such antigens monovalently rather than polyvalently with the immunoglobulins described herein, such activation occurs only in response to cross-linking only in the microenvironment

- 27 044325 research of the primary target antigen. The ability to target two different antigens with different valencies is a novel and useful aspect of the present invention. Examples of target antigens for which monovalent co-contacting may be therapeutically useful or necessary include, but are not limited to, immune-activated receptors such as CD3, FcyR, toll-like receptors (TLRs) such as TLR4 and TLR9, cytokines, chemokines, cytokine receptors, and chemokine receptors. . In many embodiments, one of the antigen binding sites binds to CD3, and in some embodiments, it is a scFv-containing monomer.

Virtually any antigen can be targeted by immunoglobulins herein, including, but not limited to, proteins, subunits, domains, motifs, and/or epitopes belonging to the following list of target antigens, which includes both soluble factors such as cytokines and membrane-bound factors, including transmembrane factors receptors: 17-IA, 4-1BB, 4Dc, 6-keto-PGF1a, 8iso-PGF2a, 8-oxo-dG, adenosine receptor A1, A33, ACE, ACE-2, activin, activin A, activin AB, activin B , activin C, activin RIA, activin RIA ALK-2, activin RIB ALK-4, activin RIIA, activin RIIB, ADAM, ADAM10, ADAM12, ADAM15, ADAM17/TACE, ADAM8, ADAM9, ADAMTS, ADAMTS4, ADAMTS5, addressins, aFGF , ALCAM, ALK, ALK-1, ALK-7, alpha-1-antitrypsin, alphaV/beta-1 antagonist, ANG, Ang, APAF-1, APE, APJ, APP, APRIL, AR, ARC, ART, artemin, anti-Id, ASPARTIC, atrial natriuretic factor, integrin av/b3, Ax1, b2M, B7-1, B7-2, B7-H, Blymphocyte stimulator (BlyS), BACE, BACE-1, Bad, BAFF, BAFF-R , Bag-1, BAK, Bax, BCA-1, BCAM, Bcl, BCMA, BDNF, b-ECGF, bFGF, BID, Bik, BIM, BLC, BL-CAM, BLK, BMP, BMP-2 BMP-2a, osteogenin BMP-3, BMP-4 BMP-2b, BMP-5, BMP-6 Vgr-1, BMP-7 (OP-1), BMP-8 (BMP-8a, OP-2), BMPR, BMPR-IA (ALK-3), BMPR-IB (ALK-6), BRK-2, RPK-1, BMPR-II (BRK-3), BMPs, b-NGF, BOK, bombesin, brain-derived neurotrophic factor, BPDE, BPDE- DNA, BTC, complement factor 3 (C3), C3a, C4, C5, C5a, C10, CA125, CAD8, calcitonin, cAMP, carcinoembryonic antigen (CEA), carcinoma-associated antigen, cathepsin A, cathepsin B, cathepsin C /DPPI, cathepsin D, cathepsin E, cathepsin H, cathepsin L, cathepsin O, cathepsin S, cathepsin V, cathepsin X/Z/P, CBL, CCI, CCK2, CCL, CCL1, CCL11, CCL12, CCL13, CCL14, CCL15 , CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9/10, CCR, CCR1, CCR10 , CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CD1, CD2, CD3, CD3E, CD4, CD5, CD6, CD7, CD8, CD10, CD11a, CD11b, CD11c, CD13, CD14, CD15 , CD16, CD18, CD19, CD20, CD21, CD22, CD23, CD25, CD27L, CD28, CD29, CD30, CD30L, CD32, CD33 (p67 proteins), CD34, CD38, CD40, CD40L, CD44, CD45, CD46, CD49a , CD52, CD54, CD55, CD56, CD61, CD64, CD66e, CD74, CD80 (B7-1), CD89, CD95, CD123, CD137, CD138, CD140a, CD146, CD147, CD148, CD152, CD164, CEACAM5, CFTR, cGMP, CINC, Clostridium botulinum toxin, Clostridium perfringens toxin, CKb8-l, CLC, CMV, CMV UL, CNTF, CNTN-1, COX, C-Ret, CRG-2, CT-1, CTACK, CTGF, CTLA-4 , CX3CL1, CX3CR1, CXCL, CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL15, CXCL16, CXCR, CXCR1, CXCR2, CXCR 3, CXCR4, CXCR5 , CXCR6, cytokeratin tumor-associated antigen, DAN, DCC, DcR3, DC-SIGN, complement accelerating factor, des(1-3)-IGF-I (brain IGF-1), Dhh, digoxin, DNAM-1, DNase, Dpp , DPPIV/CD26, Dtk, ECAD, EDA, EDA-A1, EDA-A2, EDAR, EGF, EGFR (ErbB-1), EMA, EMMPRIN, ENA, endothelin receptor, enkephalinase, eNOS, Eot, eotaxin 1, EpCAM, ephrin B2/EphB4, EPO, ERCC, E-selectin, ET-1, factor IIa, factor VII, factor VIIIc, factor IX, fibroblast activation protein (FAP), Fas, FcR1, FEN-1, ferritin, FGF, FGF- 19, fGf-2, FGF3, fGf-8, FGFR, FGFR-3, fibrin, FL, FLIP, Flt-3, Flt-4, follicle-stimulating hormone, fractalkine, FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7 , FZD8, FZD9, FZD10, G250, Gas 6, GCP-2, GCSF, GD2, GD3, GDF, GDF-1, GDF-3 (Vgr-2), GDF-5 (BMP-14, CDMP-1), GDF-6 (BMP-13, CDMP-2), GDF-7 (BMP-12, CDMP-3), GDF-8 (myostatin), GDF-9, GDF-15 (MIC-1), GDNF, GDNF, GFAP, GFRa-1, GFR-alpha1, GFR-alpha2, GFR-alpha3, GITR, glucagon, Glut 4, glycoprotein IIb/IIIa (GP IIb/IIIa), GM-CSF, gp130, gp72, GRO, somatoliberin, hapten ( NP-cap or NIP-cap), HB-EGF, HCC, HCMV envelope glycoprotein gB, HCMV envelope glycoprotein gH, HCMV UL, hematopoietic growth factor (HGF), Hep B gp120, heparanase, Her2, Her2/neu (ErbB-2 ), Her3 (ErbB-3), Her4 (ErbB-4), herpes simplex virus (HSV) gB glycoprotein, HSV gD glycoprotein, HGFA, high molecular weight melanoma-associated antigen (HMW-MAA), HIV gp120, V3-loop gp 120 HIV IIIB , HLA, HLA-DR, HM1.24, HMFG PEM, HRG, Hrk, human cardiac myosin, human cytomegalovirus (HCMV), human growth hormone (HGH), HVEM, I-309, IAP, ICAM, ICAM-1, ICAM -3, ICE, ICOS, IFNg, Ig, IgA receptor, IgE, IGF, IGF-binding proteins, IGF-1R, IGFBP, IGF-I, IGF-II, IL, IL-1, IL-1R, IL-2 , IL-2R, IL-4, IL-4R, IL-5, IL-5R, IL-6, IL-6R, IL-8, IL-9, IL-10, IL-12, IL-13, IL -15, IL-18, IL-18R, IL-23, interferon (INF)-alpha, INF-beta, INF-gamma, inhibin, iNOS, insulin A chain, insulin B chain, insulin-like growth factor 1, integrin alpha-2, alpha-3 integrin, alpha-4 integrin, alpha-4/beta-1 integrin, alpha-4/beta-7 integrin, alpha-5 integrin (alpha-V), alpha-5/beta-1 integrin , integrin alpha 5/beta 3, integrin alpha 6, integrin beta 1, integrin beta 2, interferon gamma, IP-10, I-TAC, JE, kallikrein 2, kallikrein 5, kallikrein 6, kallikrein 11, kallikrein 12, kallikrein 14, kallikrein 15, kallikrein L1, kallikrein L2, kallikrein L3, kallikrein L4, KC, KDR, keratinocyte growth factor (KGF), laminin 5,

- 28 044325

LAMP, LAP, LAP (TGF-1), latent TGF-1, latent TGF-1 bp1, LBP, LDGF, LECT2, Lefty, Lewis-Y antigen, Lewis-Y-related antigen, LFA-1, LFA-3, Lfo, LIF, LIGHT, lipoproteins, LIX, LKN, Lptn, L-selectin, LT-a, LT-b, LTB4, LTBP-1, pulmonary surfactant, luteinizing hormone, lymphotoxin beta receptor, Mac-1, MAdCAM, MAG, MAP2, MARC, MCAM, MCAM, MCK-2, MCP, M-CSF, MDC, Mer, metalloproteases, MGDF receptor, MGMT, MHC (HLA-DR), MIF, MIG, MIP, MIP-1-alpha, MK, MMAC1, MMP, MMP-1, MMP-10, MMP-11, MMP-12, MMP-13, MMP-14, MMP-15, MMP-2, MMP-24, MMP-3, MMP-7, MMP- 8, MMP-9, MPIF, Mpo, MSK, MSP, mucin (Muc1), MUC18, Mullerian inhibitory substance, Mug, MuSK, NAIP, NAP, NCAD, N-cadherin, NCA 90, NCAM, NCAM, neprilysin, neurotrophin- 3, -4 or -6, neurturin, nerve growth factor (NGF), NGFR, NGF-beta, nNOS, NO, NOS, Npn, NRG-3, NT, NTN, OB, OGG1, OPG, OPN, OSM, OX40L , OX40R, p150, p95, PADPr, parathyroid hormone, PARC, PARP, PBR, PBSF, PCAD, P-cadherin, PCNA, PDGF, PDGF, PDK-1, PECAM, PEM, PF4, pGe, PGF, PGI2, PGJ2, PIN, PLA2, placental alkaline phosphatase (PLAP), PlGF, PLP, PP14, proinsulin, prorelaxin, protein C, PS, PSA, PSCA, prostate specific membrane antigen (PSMA), PTEN, PTHrp, Ptk, PTN, R51, RANK, RANKL, RANTES, RANTES, relaxin A chain, relaxin B chain, renin, respiratory syncytial virus (RSV) F, RSV Fgp, Ret, rheumatoid factors, RLIP76, RPA2, RSK, S100, SCF/KL, SDF-1, SERINE, serum albumin, sFRP-3, Shh, SIGIRR, SK-1, SLAM, SLPI, SMAC, SMDF, SMOH, SOD, SPARC, Stat, STEAP, STEAP-II, TACE, TACI, TAG-72 (tumor-associated glycoprotein- 72), TARC, TCA-3, T cell receptors (eg T cell receptor alpha/beta), TdT, TECK, TEM1, TEM5, TEM7, TEM8, TERT, PLAP-like testicular alkaline phosphatase, TfR, TGF, TGF-alpha, TGF-beta, polyspecific TGF-beta, TGF-beta RI (ALK-5), TGF-beta RII, TGF-beta RIIb, TGF-beta RIII, TGF-beta1, TGF-beta2, TGF-beta3, TGF-beta4, TGF-beta5, thrombin, thymic Ck-1, thyroid-stimulating hormone, Tie, TIMP, TIQ, tissue factor, TMEFF2, Tmpo, TMPRSS2, TNF, TNF-alpha, TNF-alpha beta, TNF-beta-2, TNFc, TNF-RI, TNF-RII, TNFRSF10A (TRAIL R1 Apo-2, DR4), TNFRSF10B (TRAIL R2 DR5, KILLER, TRICK-2A, TRICK-B), TNFRSF10C (TRAIL R3 DcR1, LIT, TRID), TNFRSF10D (TRAIL R4 DcR2, TRUNDD), TNFRSF11A (RANK ODF R, TRANCE R), TNFRSF11B (OPG OCIF, TR1), TNFRSF12 (TWEAK R FN14), TNFRSF13B (TACI), TNFRSF13C (BAFF R), TNFRSF14 (HVEM ATAR, HveA , LIGHT R, TR2), TNFRSF16 (NGFR p75NTR), TNFRSF17 (BCMA), TNFRSF18 (GITR AITR), TNFRSF19 (TROY TAJ, TRADE), TNFRSF19L (RELT), TNFRSF1A (TNF RI CD120a, p5560), TNFRSF1B (TNF RII CD120b, p75-80), TNFRSF26 (TNFRH3), TNFRSF3 (LTbR TNF RIII, TNFC R), TNFRSF4 (OX40 ACT35, TXGP1 R), TNFRSF5 (CD40 p50), TNFRSF6 (Fas Apo-1, APT1, CD95), TNFRSF6B (DcR3 M68, TR6), TNFRSF7 (CD27), TNFRSF8 (CD30), TNFRSF9 (4-1BB CD137, ILA), TNFRSF21 (DR6), TNFRSF22 (DcTRAIL R2 TNFRH2), TNFRST23 (DcTRAIL R1 TNFRH1), TNFRSF25 (DR3 Apo -3, LARD, TR-3, TRAMP, WSL-1), TNFSF10 (TRAIL Apo-2 ligand, TL2), TNFSF11 (TRANCE/RANK ligand, ODF, OPG ligand), TNFSF12 (TWEAK Apo-3- ligand, DR3-ligand), TNFSF13 (APRIL TALL2), TNFSF13B (BAFF BLYS, TALL1, THANK, TNFSF20), TNFSF14 (LIGHT HVEM-ligand, LTg), TNFSF15 (TL1A/VEGI), TNFSF18 (GITR-ligand, AITR- ligand, TL6), TNFSF1A (TNF-a connectin, DIF, TNFSF2), TNFSF1B (TNF-b LTa, TNFSF1), TNFSF3 (LTb TNFC, p33), TNFSF4 (OX40 ligand gp34, TXGP1), TNFSF5 (CD40 ligand CD154, gp39, HIGM1, IMD3, TRAP), TNFSF6 (Fas ligand, Apo-1 ligand, APT1 ligand), TNFSF7 (CD27 ligand CD70), TNFSF8 (CD30 ligand CD153), TNFSF9 (4-1BB- ligand, CD137-ligand), TP-1, t-PA, Tpo, TRAIL, TRAIL R, TRAIL-R1, TRAIL-R2, TRANCE, transferrin receptor, TRF, Trk, TROP-2, TSG, TSLP, tumor-associated antigen CA 125, tumor-associated Lewis Y-related carbohydrate antigen, TWEAK, TXB2, Ung, uPAR, uPAR-1, urokinase, VCAM, VCAM-1, VECAD, VE-cadherin, VE-cadherin-2, VEFGR-1 (ft-1) , VEGF, VEGFR, VEGFR-3 (ft-4), VEGI, VIM, viral antigens, VLA, VLA-1, VLA-4, VNR integrin, von Willebrand factor, WIF-1, WNT1, WNT2, WNT2B/13, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9A, WNT9B, WNT10A, WNT10B, WNT11, WNT16, XCL1, XCL2, XCR1, XCR1, XEDAR, XIAP, XPD and hormone receptors and growth factors.

Exemplary antigens that may be specifically targeted by immunoglobulins of the present invention include, but are not limited to: CD20, CD19, Her2, EGFR, EpCAM, CD3, FcyRIIIa (CD16), FcyRIIa (CD32a), FcyRIIb (CD32b), FcyRI (CD64), toll -like receptors (TLRs) such as TLR4 and TLR9, cytokines such as IL-2, IL-5, IL-13, IL-12, IL-23 and TNFa, cytokine receptors such as IL-2R, chemokines, chemokine receptors, growth factors such as VEGF and HGF, etc. To obtain the bispecific antibodies of the present invention, antibodies to any combination of these antigens can be generated; those. each of these antigens may optionally and independently be included or excluded from the spectrum of action of the bispecific antibody of the present invention.

Particularly preferred combinations for bispecific antibodies are a CD3 antigen binding domain and an antigen binding domain selected from the domain that binds CD19, CD20, CD38 and CD123, the sequences of which are shown in the figures.

Nucleic acids of the present invention.

The present invention further provides nucleic acid compositions encoding the bispecific antibodies of the present invention. As will be clear to specialists in

- 29 044325 of the art, the composition of nucleic acids will depend on the format and framework of the heterodimeric protein. So, for example, if a format requires three amino acid sequences, such as for a triple F format (e.g., a first amino acid monomer containing the Fc domain and scFv, a second amino acid monomer containing a heavy chain and a light chain), then the three nucleic acid sequences can be include in one or more expression vectors for expression. Likewise, in some formats (eg, dual scFv formats such as those disclosed in FIG. 1) only two nucleic acids are required; again, these can be placed into one or two expression vectors.

As is known in the art, nucleic acids encoding the components of the present invention can be incorporated into expression vectors known in the art and depending on the host cells used to produce the heterodimeric antibodies of the present invention. Typically, nucleic acids are functionally linked to any number of regulatory elements (promoters, origins of replication, selectable markers, ribosome binding sites, inducers, etc.). Expression vectors can be extrachromosomal or integrating vectors.

The nucleic acids and/or expression vectors of the present invention are then transformed into any number of different types of host cells, as is well known in the art, including mammalian, bacterial, yeast, insect and/or fungal cells, wherein mammalian cells (e.g. CHO) find use in many embodiments.

In some embodiments, each of the nucleic acids encoding each monomer, and optionally the nucleic acid encoding the light chain used depending on the format, are contained within a single expression vector, typically under the control of a different or the same promoter. In embodiments particularly useful in the present invention, each of these two or three nucleic acids is contained in a different expression vector. As shown herein and in No. 62/025931, incorporated herein by reference, various ratios of vectors can be used to control heterodimer formation. That is, and surprisingly, although the proteins contain the first monomer:second monomer:light chains (in the case of many embodiments herein where a three-polypeptide heterodimeric antibody is provided) in a ratio of 1:1:2, this is not a ratio that gives the best results.

The heterodimeric antibodies of the present invention are produced by culturing host cells containing expression vector(s), as is well known in the art. Once produced, conventional antibody purification steps are performed, including an ion exchange chromatography step. As discussed herein, pIs of two monomers that differ by at least 0.5 may allow separation by ion exchange chromatography or isoelectric focusing or other isoelectric point sensitive techniques. That is, the inclusion of pI substitutions that provide a change in the isoelectric point (pI) of each monomer such that each monomer has a different pI and the heterodimer also has a different pI, thereby facilitating purification based on the isoelectric point of the heterodimer in the triple F format (for example, using anion exchange columns, cation exchange columns). These substitutions also assist in identifying and monitoring any contamination following purification of dual scFv-Fc and mAb homodimers (e.g., using IEF gels, cIEF, and IEX analytical columns).

Treatment methods.

Once prepared, the compositions of the present invention find use in a number of applications. CD20, CD38 and CD123 are dysregulated in many hematopoietic malignancies and in cell lines derived from various hematopoietic malignancies, accordingly, the heterodimeric antibodies of the present invention find use in the treatment of cancer, including without limitation all B-cell lymphomas and leukemias, including but not limited to non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL), multiple myeloma (MM), B-cell chronic lymphocytic leukemia (B-CLL), B- and T-cell acute lymphocytic leukemia (ALL), T-cell lymphoma (TCL), acute myeloid leukemia (AML), hairy cell leukemia (HCL), Hodgkin's lymphoma (HL), chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma and chronic myeloid leukemia (CML).

Accordingly, the heterodimeric compositions of the present invention find use in the treatment of these forms of cancer.

Antibody compositions for in vivo administration.

The antibody compositions used in accordance with the present invention are prepared for storage by mixing the antibody of the required purity with optional pharmaceutically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. [1980]) in the form lyophilized formulations or aqueous solutions. Acceptable carriers, excipients, or stabilizers are nontoxic to patients at the dosages and concentrations used and include buffers such as phosphate, citrate, and

- 30 044325 other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzylammonium chloride, hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl or benzyl alcohol, alkylparabens such as methyl or propylparaben, catechol, resorcinol, cyclohexanol, 3-pentanol and m-cresol); low molecular weight polypeptides (less than about 10 residues); proteins such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine or lysine; monosaccharides, disaccharides and other carbohydrates, including glucose, mannose or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counterions such as sodium; metal complexes (eg, Zn-protein complexes) and/or nonionic surfactants such as TWEEN™, PLURONICS™ or polyethylene glycol (PEG).

The formulation herein may also contain more than one active compound as needed for the particular indication being treated, preferably compounds with complementary activities that do not adversely affect each other. For example, it may be necessary to provide antibodies with other specificities. Alternatively or additionally, the composition may contain a cytotoxic agent, cytokine, growth inhibitor and/or small molecule antagonist. Such molecules are suitably present in combination in amounts that are effective for the intended purpose.

The active ingredients can also be encapsulated in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, e.g. hydroxymethylcellulose, or gelatin microcapsules and poly(methyl methacrylate) microcapsules, respectively, in colloidal drug delivery systems (e.g. liposomes, albumin microspheres , microemulsions, nanoparticles and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980).

Formulations used for in vivo administration must be sterile or nearly sterile. This is easily accomplished by filtration through sterilizing filtration membranes.

Slow-release formulations can be obtained. Suitable examples of sustained release formulations include semi-permeable matrices of solid hydrophobic polymers containing the antibody, these matrices being in the form of molded articles such as films or microcapsules. Examples of sustained release matrices include polyesters, hydrogels (e.g., poly(2-hydroxyethyl methacrylate) or poly(vinyl alcohol)), polylactides (US Pat. No. 3,773,919), copolymers of L-glutamic acid and gamma-ethyl-L-glutamate, non-degradable ethylene vinyl acetate, degradable lactic acid-glycolic acid copolymers such as LUPRON DEPOT™ (injectable microspheres consisting of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-O-(-)-3-hydroxybutyric acid. While polymers such as ethylene vinyl acetate and lactic acid-glycolic acid release molecules over 100 days, certain hydrogels release proteins over a shorter period of time.

When encapsulated antibodies remain in the body for long periods of time, they may denature or aggregate as a result of exposure to moisture at 37°C, resulting in loss of biological activity and possible changes in immunogenicity. Rational strategies for stabilization can be developed depending on the mechanism involved. For example, if the mechanism of aggregation has been found to be the formation of intermolecular S--S bonds via thiodisulfide exchange, stabilization can be achieved by modification of sulfhydryl moieties, lyophilization from acidic solutions, control of moisture content, use of appropriate additives, and development of specific polymer matrix formulations .

Methods of administration.

The antibodies and chemotherapeutic agents of the present invention are administered to a subject in accordance with known methods, such as intravenous administration as a bolus or by continuous infusion over a period of time, intramuscular, intraperitoneal, intracerebrospinal, subcutaneous, intraarticular, intrasynovial, intrathecal, oral, topical or by inhalation. Intravenous or subcutaneous administration of the antibody is preferred.

Methods of treatment.

In the methods of the present invention, therapy is used to provide a positive therapeutic response to a disease or condition. By positive therapeutic response is meant an improvement in the disease or condition and/or an improvement in the symptoms associated with the disease or condition. For example, a positive therapeutic response would refer to one or more of the following improvements in disease: (1) reduction in the number of neoplastic cells; (2) increased levels of neoplastic cell death; (3) inhibition of neoplastic cell survival; (5) inhibition (i.e. slowing down to some extent, preferably

- 31 044325 stopping) tumor growth; (6) improved patient survival; and (7) some relief of one or more symptoms associated with the disease or condition.

Positive therapeutic responses for any particular disease or condition can be determined by standardized response criteria specific to that disease or condition. Tumor response can be assessed by changes in tumor morphology (i.e. total tumor burden, tumor size, etc.) using screening techniques such as magnetic resonance imaging (MRI) scanning, radiographic imaging, computed tomography (CT) scanning , osteoscintigraphic imaging, endoscopy and tumor biopsy, including bone marrow aspiration (BMA) and counting of tumor cells in the bloodstream.

In addition to these positive therapeutic responses, the subject undergoing therapy may experience the beneficial effect of reducing symptoms associated with the disease.

Relief of the disease can be characterized as a complete response. A complete response is defined as the absence of clinically detectable disease with normalization of any abnormal findings on previous x-rays of bone marrow and cerebrospinal fluid (CSF) or abnormal monoclonal protein in the case of myeloma.

Such a response may persist for at least 4-8 weeks or sometimes 6-8 weeks after treatment in accordance with the methods of the present invention. Alternatively, improvement in disease may be classified as a partial response. A partial response is defined as at least approximately a 50% reduction in the total measurable tumor burden (i.e., the number of malignant cells present in the subject or the measured volume of tumor mass or the amount of abnormal monoclonal protein) in the absence of new lesions, which may persist for 4 -8 weeks or 6-8 weeks.

Treatment in accordance with the present invention includes a therapeutically effective amount of drugs administered. A therapeutically effective amount refers to an amount effective in doses and for periods of time necessary to achieve the desired therapeutic result.

The therapeutically effective amount may vary depending on factors such as the course of the disease, the age, sex and weight of the individual, as well as the ability of the drugs to produce the desired response in the individual. A therapeutically effective amount is also one in which the therapeutically beneficial effects outweigh any toxic or harmful effects of the antibody or antibody portion.

A therapeutically effective amount for treating tumors can also be measured by its ability to stabilize disease progression. The ability of a compound to inhibit cancer can be assessed in an animal model system predictive of efficacy in human tumors.

Alternatively, this property of the composition can be assessed by examining the ability of the compound to inhibit cell growth or induce apoptosis in in vitro assays known to the practitioner. A therapeutically effective amount of a therapeutic compound may reduce tumor size or otherwise alleviate symptoms in a subject. One skilled in the art will be able to determine these amounts based on factors such as the size of the subject, the severity of the subject's symptoms, and the specific composition or route of administration chosen.

Dosing regimens are adjusted to provide the optimal desired response (eg, therapeutic response). For example, a single bolus dose may be administered, multiple divided doses may be administered over a period, or the dose may be proportionally decreased or increased as determined by the requirements of the therapeutic situation. Parenteral compositions may be formulated in unit dosage form for ease of administration and uniformity of dosage. Unit dosage form as used herein refers to physically discrete units suitable as unit dosages for subjects to be treated; each unit contains a predetermined amount of active compound calculated to produce the desired therapeutic effect, in combination with the required pharmaceutical carrier.

The specification for unit dosage forms of the present invention is conditional on and is directly dependent on (a) the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and (b) the limitations in the art associated with the formulation of such active compound for the treatment of sensitivity in individuals.

Effective dosages and dosage regimens of the bispecific antibodies used in the present invention depend on the disease or condition being treated and can be determined by those skilled in the art.

An exemplary non-limiting range for a therapeutically effective amount of a bispecific antibody used in the present invention is about 0.1-100 mg/kg, such as about 0.1-50 mg/kg, such as about 0.1-20 mg/kg kg, such as about 0.1-10 mg/kg, for example about 0.5, for example about 0.3, about 1 or about 3 mg/kg. In another embodiment, the antibody is administered in a dose of 1

- 32 044325 mg/kg or more, for example the dose is 1 to 20 mg/kg, for example the dose is 5 to 20 mg/kg, for example the dose is 8 mg/kg.

A healthcare professional skilled in the art can readily determine and prescribe an effective amount of the required pharmaceutical composition. For example, a physician or veterinarian may begin with doses of the drug used in a pharmaceutical composition at levels lower than required to achieve the desired therapeutic effect and gradually increase the dose until the desired effect is achieved.

In one embodiment, the bispecific antibody is administered by infusion at a weekly dose of 10 to 500 mg/kg, such as 200 to 400 mg/kg. Such administration can be repeated, for example, 1 to 8 times, for example, 3 to 5 times. Administration can be by continuous infusion over a period of 2 to 24 hours, such as 2 to 12 hours.

In one embodiment, the bispecific antibody is administered by slow continuous infusion over an extended period of time, such as more than 24 hours, if desired to reduce the occurrence of side effects, including toxicity.

In one embodiment, the bispecific antibody is administered at a weekly dose of 250 mg to 2000 mg, such as, for example, 300 mg, 500 mg, 700 mg, 1000 mg, 1500 mg, or 2000 mg, up to 8 times, such as 4 to 6 times . Administration can be by continuous infusion over a period of 2 to 24 hours, such as 2 to 12 hours. This scheme can be repeated one or more times as necessary, for example, after 6 months or 12 months. The dosage can be determined or adjusted by measuring the amount of a compound of the present invention in the blood after administration, for example, by collecting a biological sample and using anti-idiotypic antibodies that target the antigen-binding region of the bispecific antibody.

In a further embodiment, the bispecific antibody is administered once a week for 2 to 12 weeks, such as 3 to 10 weeks, such as 4 to 8 weeks.

In one embodiment, the bispecific antibody is administered as maintenance therapy, such as, for example, once a week for a period of 6 months or more.

In one embodiment, the bispecific antibody is administered in a regimen comprising one infusion of the bispecific antibody followed by an infusion of the bispecific antibody conjugated to a radioactive isotope. The scheme can be repeated, for example, after 7-9 days.

By way of non-limiting examples, the treatment of the present invention may be provided as a daily dose of antibody in an amount of approximately 0.1-100 mg/kg, such as 0.5, 0.9, 1.0, 1.1, 1.5, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 , 28, 29, 30, 40, 45, 50, 60, 70, 80, 90 or 100 mg/kg per day, at least every 1, 2, 3, 4, 5, 6, 7, 8, 9 , 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 , 35, 36, 37, 38, 39 or 40 days, or, alternatively, at least once every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 , 14, 15, 16, 17, 18, 19, or 20 weeks after initiation of treatment, or any combination thereof, using single or divided doses every 24, 12, 8, 6, 4, or 2 hours, or any combination thereof.

In some embodiments, the bispecific antibody molecule is used in combination with one or more additional therapeutic agents, such as a chemotherapeutic agent. Non-limiting examples of DNA-damaging chemotherapeutic agents include topoisomerase I inhibitors (eg, irinotecan, topotecan, camptothecin and their analogs or metabolites, and doxorubicin); topoisomerase II inhibitors (eg etoposide, teniposide and daunorubicin); alkylating agents (eg, melphalan, chlorambucil, busulfan, thiotepa, ifosfamide, carmustine, lomustine, semustine, streptozocin, decarbazine, methotrexate, mitomycin C and cyclophosphamide); DNA intercalators (eg, cisplatin, oxaliplatin and carboplatin); DNA intercalators and free radical generators such as bleomycin; and nucleoside mimetics (eg, 5-fluorouracil, capecitibine, gemcitabine, fludarabine, cytarabine, mercaptopurine, thioguanine, pentostatin, and hydroxyurea).

Chemotherapeutic agents that interfere with cell proliferation include paclitaxel, docetaxel, and related analogs; vincristine, vinblastine and related analogues; thalidomide, lenalidomide and related analogues (eg, CC-5013 and CC-4047); protein tyrosine kinase inhibitors (eg, imatinib mesylate and gefitinib); proteasome inhibitors (for example, bortezomib); NF-kB inhibitors, including IkB kinase inhibitors; antibodies that bind to proteins overexpressed in cancers and therefore inhibit cell proliferation (for example, trastuzumab, rituximab, cetuximab and bevacizumab); and other inhibitors of proteins or enzymes known to be stimulated, overexpressed or activated in cancers, the inhibition of which results in suppression of cell proliferation.

In some embodiments, the antibodies of the present invention can be used before, concurrently with, or after treatment with Velcade® (bortezomib).

All references cited are expressly incorporated herein by reference in their entirety.

While specific embodiments of the present invention have been described above in

- 33 044325 for illustrative purposes, those skilled in the art will appreciate that numerous variations of parts can be made without departing from the present invention as described in the accompanying claims.

Examples

The following are examples to illustrate the present invention. These examples are not intended to limit the present invention to any particular application or technique of application. For all positions in the constant regions discussed in the present invention, the numbering corresponds to the EU index according to Kabat (Kabat et al., 1991, Sequences of Proteins of Immunological Interest, 5th ed., United States Public Health Service, National Institutes of Health , Bethesda, incorporated by reference in its entirety). Those skilled in the art of antibodies will appreciate that this convention includes non-sequential numbering in certain regions of the immunoglobulin sequence, which allows for standardized reference to conserved positions within immunoglobulin families. Accordingly, the positions for any given immunoglobulin determined by the EU index will not necessarily correspond to its sequential sequence.

General and specific scientific techniques are set forth in US Patent Application Publications 2015/0307629, 2014/0288275 and WO 2014/145806, which are expressly incorporated by reference in their entirety and in particular for the techniques set forth therein.

Example 1: Alternative formats.

Preparation of bispecific antibodies.

Schematic representations of anti-CD38 x CD3 bispecific antibodies are shown in FIG. 1. Amino acid sequences for alternative format anti-CD38 x CD3 bispecific antibodies are listed in FIG. 39-43. DNA encoding the three strands required for bispecific antibody expression was obtained by gene synthesis (Blue Heron Biotechnology, Bothell, WA) and subcloned using standard molecular biology techniques into the pTT5 expression vector. Substitutions were introduced using either site-directed mutagenesis (QuikChange, Stratagene, Cedar Creek, TX) or additional gene synthesis and subcloning. DNA was transfected into HEK293E cells for expression and the resulting proteins were purified from the supernatant using protein A affinity chromatography (GE Healthcare) and cation exchange chromatography. The yields after affinity purification using Protein A are shown in FIG. 35. Purification by cation exchange chromatography was performed using a HiTrap SP HP column (GE Healthcare) with wash/equilibration buffer 50 mM MES, pH 6.0 and elution buffer 50 mM MES, pH 6.0 + 1 M NaCl with linear gradient (see Fig. 36 for chromatograms).

Redirected T cell cytotoxicity.

The characteristics of anti-CD38 x CD3 bispecific antibodies were determined in vitro against redirected T-cell cytotoxicity (RTCC) of the CD38+ myeloma cell line RPMI8266. 10 thousand RPMI8266 cells were incubated for 24 hours with 500 thousand human PBMCs. RTCC was measured using LDH fluorescence as indicated (see Fig. 37).

Example 2.

Redirected T cell cytotoxicity.

The characteristics of anti-CD38 x CD3 bispecific Fab-scFv-Fc were determined in vitro against redirected T cell cytotoxicity (RTCC) of the CD38+ myeloma cell line RPMI8266. 40 thousand RPMI8266 cells were incubated for 96 hours with 400 thousand human PBMCs. RTCC was measured by flow cytometry as indicated (see FIG. 44). The expression patterns of CD69, Ki-67, and PI-9 in CD4+ and CD8+ T cells were also determined by flow cytometry, as shown in FIG. 45.

Mouse model of antitumor activity.

Four groups of five NOD scid gamma (NSG) mice each were inoculated with 5x106 RPMI8226TrS (luciferase-expressing multiple myeloma) tumor cells by intravenous tail vein injection on day -23. On day 0, mice were inoculated intraperitoneally with 10x106 human PBMCs. After inoculation of PBMCs on day 0, test drugs were administered weekly (days 0, 7) via intraperitoneal injection at the doses indicated in FIG. 4. The study design is further shown in Fig. 46. Tumor growth was monitored by measuring total flux per mouse using an in vivo imaging system (IVIS®). Both XmAb13551 and XmAb15426 demonstrated significant antitumor effects (see Fig. 47 and Fig. 48).

Studies on cynomolgus macaques.

Cynomolgus monkeys were administered a single dose of anti-CD38 x CD3 bispecific antibodies. An anti-RSV x CD3 bispecific control antibody was also included. Dose levels were: 20 μg/kg XmAb13551 (n=2), 0.5 mg/kg XmAb15426 (n=3), 3 mg/kg XmAb14702 (n=3) or 3 mg/kg XmAb13245 (control anti-RSV x CD3, n=3) (in 3 independent studies). Bispecific antibodies to CD38 x CD3 provided rapid depletion of CD38+ cells in peripheral blood (see Fig. 49). CD38 x CD3 bispecific antibodies resulted in T cell activation as measured by CD69 expression (see FIG. 50). Serum IL-6 levels were also measured (see FIG. 51). It should be noted that compared

- 34 044325 compared with XmAb13551 XmAb15426 was characterized by an increased duration of CD38+ cell depletion and lower levels of T cell activation and IL-6 production.

XmAb15426 and XmAb14702 were tested at single doses of 0.5 mg/kg and 3 mg/kg, respectively. Both antibodies were well tolerated at these higher doses, consistent with the moderate levels of IL6 observed in the serum of treated monkeys. Moreover, intermediate-affinity CD3 XmAb15426 was more effective in depleting CD38+ cells at a dose of 0.5 mg/kg compared with the parent high-affinity XmAb13551 at 2, 5, or 20 μg/kg. Depletion with XmAb15426 was more persistent compared with XmAb13551 at the highest dose in the previous study (7 versus 2 days, respectively). Notably, although target cell depletion was greater with XmAb15426, T cell activation (induction of CD69, CD25 and PD1) in monkeys treated with XmAb15426 was significantly lower even at a dose 25 times higher than in the 20 μg group /kg XmAb13551. XmAb14702, with very low affinity for CD3, had little effect on CD38+ cells and T cell activation.

These results demonstrate that modulating T cell activation by attenuating CD3 affinity is a promising way to increase the therapeutic window for bispecific T cell binding antibodies. This strategy has the potential to expand the repertoire of antigens amenable to targeted T-cell immunotherapy by improving tolerability and allowing higher dosing to overcome antigen-dependent clearance of targets such as CD38. We have shown that by reducing CD3 affinity, XmAb 15426 effectively depletes CD38+ cells while minimizing the CRS effects expected at comparable doses of its high-affinity counterpart, XmAb13551.

Sequence Listing <110> XENCOR, INC.

< 12 0> HETERODIMERIC ANTIBODIES THAT BIND CD3 AND TUMOR ANTIGENS < 130> 067461-5180-WO <140> PCT/US2015/062772 <141> 2015-11-25 <150> 62/251,005 < 151>2015-11- 04 <150> 62/250,971 <151> 2015-11-04 <150> 62/159,111 <151> 2015-05-08 <150> 62/085,117 <151> 2014-11-26 <150> 62/085,106 < 151> 2014-11-26 <150> 62/085,027 <151> 2014-11-26 <150> 62/084,908 <151> 2014-11-26 <160> 452 <170> PatentIn version 3.5 <210> 1 < 211> 125 < 212> PROTEIN < 213> Artificial sequence

- 35 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 1

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115120

Ser Ser

125 <210> 2 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 2

Thr Tyr Ala Met Asn 1 5 <210> 3 <211> 19 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide

- 36 044325 <400> 3

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser

5 10 15

Val Lys Gly <210> 4 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 4

His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr

5 10 <210> 5 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 5

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105

- 37 044325 <210> 6 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 6

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

5 10 <210> 7 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 7

Gly Thr Asn Lys Arg Ala Pro

5 <210> 8 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 8

Ala Leu Trp Tyr Ser Asn His Trp Val

5 <210> 9 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 9

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

- 38 044325

Ala Met Asn Trp Val 35

Arg Gln

Gly Arg Ile Arg Ser 50

Lys Tyr 55

Ser Val Lys Gly Arg 65

Ph Thr 70

Leu Tyr Leu Gln Met 85

Asn Ser

Ala Pro 40

Asn Asn

Ile Ser

Leu Arg

Gly Lys

Tyr Ala

Arg Asp

Ala Glu 90

Gly Leu 45

Thr Tyr 60

Asp Ser

Asp Thr

Glu Trp

Tyr Ala

Lys Asn

Ala Val

Tyr Cys Val Arg His

100

Gly Asn

Phe Gly

105

Asp Ser

Tyr Val

Ser Trp 110

Ala Tyr Trp Gly Gln 115

Gly Thr

Leu Val 120

Thr Val

Ser Ser

125

Gly Lys

Gly Ser Gly Lys Pro 130

Gly Ser

135

Gly Lys

Pro Gly

Ser Gly 140

Lys Pro

Ser Gln Ala Val Val 145

Thr Gln 150

Glu Pro

Ser Leu

155

Thr Val

Ser Pro

Gly Thr Val Thr Leu

165

Thr Cys

Gly Ser

Ser Thr 170

Gly Ala

Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val

Gln Gln

185

Lys Pro

Gly Lys

Ser Pro 190

Gly Leu Ile Gly Gly

195

Thr Asn

Lys Arg 200

Ala Pro

Gly Val

205

Pro Ala

Phe Ser Gly Ser Leu 210

Leu Gly

215

Gly Lys

Ala Ala

Leu Thr

220

Ile Ser

Ala Gln Pro Glu Asp 225

Glu Ala

230

Asp Tyr

Tyr Cys

235

Ala Leu

Trp Tyr

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Asn His Trp Val Phe

245

Gly Gly

Gly Thr

Lys Leu 250

Thr Val

Leu <210> 10 <211> 125 <212> PROTEIN <213> Artificial sequence

- 39 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 10

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115120

Ser Ser

125 <210> 11 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 11

Thr Tyr Ala Met Asn

5 <210> 12 <211> 19 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide

- 40 044325 <400> 12

Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser

5 10 15

Val Lys Gly <210> 13 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 13

His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr

5 10 <210> 14 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 14

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr ThrSer

2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser GlyAla

70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr SerAsn

9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105

- 41 044325 <210> 15 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 15

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

5 10 <210> 16 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 16

Gly Thr Asn Lys Arg Ala Pro

5 <210> 17 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 17

Ala Leu Trp Tyr Ser Asn His Trp Val

5 <210> 18 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 18

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

- 42 044325

Ala Met Asn Trp Val 35

Arg Gln

Gly Arg Ile Arg Ser 50

Lys Ala

Ser Val Lys Gly Arg 65

Ph Thr 70

Leu Tyr Leu Gln Met 85

Asn Ser

Ala Pro 40

Asn Asn

Ile Ser

Leu Arg

Gly Lys

Tyr Ala

Arg Asp

Ala Glu 90

Gly Leu 45

Thr Tyr 60

Asp Ser

Asp Thr

Glu Trp

Tyr Ala

Lys Asn

Ala Val

Tyr Cys Val Arg His

100

Gly Asn

Phe Gly

105

Asp Ser

Tyr Val

Ser Trp 110

Ala Tyr Trp Gly Gln 115

Gly Thr

Leu Val 120

Thr Val

Ser Ser

125

Gly Lys

Gly Ser Gly Lys Pro 130

Gly Ser

135

Gly Lys

Pro Gly

Ser Gly 140

Lys Pro

Ser Gln Ala Val Val 145

Thr Gln 150

Glu Pro

Ser Leu

155

Thr Val

Ser Pro

Gly Thr Val Thr Leu

165

Thr Cys

Gly Ser

Ser Thr 170

Gly Ala

Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val

Gln Gln

185

Lys Pro

Gly Lys

Ser Pro 190

Gly Leu Ile Gly Gly

195

Thr Asn

Lys Arg 200

Ala Pro

Gly Val

205

Pro Ala

Phe Ser Gly Ser Leu 210

Leu Gly

215

Gly Lys

Ala Ala

Leu Thr

220

Ile Ser

Ala Gln Pro Glu Asp 225

Glu Ala

230

Asp Tyr

Tyr Cys

235

Ala Leu

Trp Tyr

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Asn His Trp Val Phe

245

Gly Gly

Gly Thr

Lys Leu 250

Thr Val

Leu <210> 19 <211> 125 <212> PROTEIN <213> Artificial <220>

subsequence

- 43 044325 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 19

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115120

Ser Ser

125 <210> 20 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 20

Thr Tyr Ala Met Asn 1 5 <210> 21 <211> 19 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 21

- 44 044325

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser 1 5 10 15

Val Lys Gly <210> 22 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 22

His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe Ala Tyr

5 10 <210> 23 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 23

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 24

- 45 044325 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 24

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn < 210> 25 < 211> 7 < 212> PROTEIN < 213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 25 Gly Thr Asn Lys Arg Ala Pro 1 5 <210> 26 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 26 Ala Leu Trp Tyr Ser Asn His Trp Val 1 5 <210> 27 <211> 254 <212> PROTEIN <213> Artificial sequence <220 >

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 27

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

- 46 044325

Ala Met Asn Trp Val 35

Arg Gln

Gly Arg Ile Arg Ser 50

Lys Tyr 55

Ser Val Lys Gly Arg 65

Ph Thr 70

Leu Tyr Leu Gln Met 85

Asn Ser

Ala Pro 40

Asn Asn

Ile Ser

Leu Arg

Gly Lys

Tyr Ala

Arg Asp

Ala Glu 90

Gly Leu 45

Thr Tyr 60

Asp Ser

Asp Thr

Glu Trp

Tyr Ala

Lys Asn

Ala Val

Tyr Cys Val Arg His

100

Gly Asn

Phe Gly

105

Asp Glu

Tyr Val

Ser Trp 110

Ala Tyr Trp Gly Gln 115

Gly Thr

Leu Val 120

Thr Val

Ser Ser

125

Gly Lys

Gly Ser Gly Lys Pro

130

Gly Ser

135

Gly Lys

Pro Gly

Ser Gly 140

Lys Pro

Ser Gln Ala Val Val 145

Thr Gln 150

Glu Pro

Ser Leu

155

Thr Val

Ser Pro

Gly Thr Val Thr Leu

165

Thr Cys

Gly Ser

Ser Thr 170

Gly Ala

Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val

Gln Gln

185

Lys Pro

Gly Lys

Ser Pro 190

Gly Leu Ile Gly Gly

195

Thr Asn

Lys Arg 200

Ala Pro

Gly Val

205

Pro Ala

Phe Ser Gly Ser Leu 210

Leu Gly

215

Gly Lys

Ala Ala

Leu Thr

220

Ile Ser

Ala Gln Pro Glu Asp 225

Glu Ala

230

Asp Tyr

Tyr Cys

235

Ala Leu

Trp Tyr

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Asn His Trp Val Phe

245

Gly Gly

Gly Thr

Lys Leu 250

Thr Val

Leu <210> 28 <211> 125 <212> PROTEIN <213> Artificial <220>

<221> source sequence

- 47 044325 <223> /note=Description of artificial sequence: synthetic polypeptide <400> 28

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 29 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 29

Thr Tyr Ala Met Asn 1 5 <210> 30 <211> 19 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 30

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser

- 48 044325

Val Lys Gly <210> 31 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 31

His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe Ala Tyr

5 10 <210> 32 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 32

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100

105 <210> 33 <211> 14

- 49 044325 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 33

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

5 10 <210> 34 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 34

Gly Thr Asn Lys Arg Ala Pro

5 <210> 35 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 35

Ala Leu Trp Tyr Ser Asn His Trp Val

5 <210> 36 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 36

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

- 50 044325

Gly

Arg 50

Ile

Arg

Ser

Lys

Tyr 55

Asn

Asn

Tyr

Ala

Thr 60

Tyr

Tyr

Ala

Asp

Ser 65

Val

Lys

Gly

Arg

Phe 70

Thr

Ile

Ser

Arg

Asp 75

Asp

Ser

Lys

Asn

Thr 80

Leu

Tyr

Leu

Gln

Met 85

Asn

Ser

Leu

Arg

Ala 90

Glu

Asp

Thr

Ala

Val 95

Tyr

Tyr

Cys

Val

Arg 100

His

Gly

Asn

Phe

Gly 105

Asp

Pro

Tyr

Val

Ser

110

Trp

Phe

Ala

Tyr

Trp

115

Gly

Gln

Gly

Thr

Leu

120

Val

Thr

Val

Ser

Ser

125

Gly

Lys

Pro

Gly

Ser

130

Gly

Lys

Pro

Gly

Ser

135

Gly

Lys

Pro

Gly

Ser

140

Gly

Lys

Pro

Gly

Ser

145

Gln

Ala

Val

Val

Thr

150

Gln

Glu

Pro

Ser

Leu

155

Thr

Val

Ser

Pro

Gly 160

Gly

Thr

Val

Thr

Leu

165

Thr

Cys

Gly

Ser

Ser

170

Thr

Gly

Ala

Val

Thr

175

Thr

Ser

Asn

Tyr

Ala

180

Asn

Trp

Val

Gln

Gln

185

Lys

Pro

Gly

Lys

Ser

190

Pro

Arg

Gly

Leu

Ile

195

Gly

Gly

Thr

Asn

Lys 200

Arg

Ala

Pro

Gly

Val

205

Pro

Ala

Arg

Phe

Ser

210

Gly

Ser

Leu

Leu

Gly

215

Gly

Lys

Ala

Ala

Leu

220

Thr

Ile

Ser

Gly

Ala

225

Gln

Pro

Glu

Asp

Glu 230

Ala

Asp

Tyr

Tyr

Cys 235

Ala

Leu

Trp

Tyr

Ser

240

Asn

His

Trp

Val

Phe

245

Gly

Gly

Gly

Thr

Lys 250

Leu

Thr

Val

Leu <210>

<211>

<212>

<213>

125

PROTEIN

Artificial sequence <220>

<221>

<223>

source/note=Description of artificial sequence: synthetic

- 51 044325 polypeptide <400> 37

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr Phe

Ser Thr Tyr 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115120

Ser Ser

125 <210> 38 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 38

Thr Tyr Ala Met Asn 1 5 <210> 39 <211> 19 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 39

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser

5 10 15

- 52 044325

Val Lys Gly <210> 40 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 40

His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Asp Tyr

5 10 <210> 41 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 41

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 42 <211> 14 <212> PROTEIN

- 53 044325 <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 42

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

5 10 <210> 43 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 43

Gly Thr Asn Lys Arg Ala Pro

5 <210> 44 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 44

Ala Leu Trp Tyr Ser Asn His Trp Val

5 <210> 45 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 45

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val

- 54 044325

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245250 <210> 46 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide

- 55 044325 <400> 46

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115120

Ser Ser

125 <210> 47 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 47

Thr Tyr Ala Met Ser 1 5 <210> 48 <211> 19 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 48

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser

5 10 15

- 56 044325

Val Lys Gly <210> 49 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 49

His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr

5 10 <210> 50 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 50

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 51 <211> 14 <212> PROTEIN <213> Artificial sequence

- 57 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 51

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn

5 10 <210> 52 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 52

Gly Thr Asn Lys Arg Ala Pro

5 <210> 53 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 53

Ala Leu Trp Tyr Ser Asn His Trp Val

5 <210> 54 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 54

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Ser Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val

- 58 044325

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245250 <210> 55 <211> 116 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide

- 59 044325 <400> 55

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser

115 <210> 56 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 56

Tyr Ser Trp Met Asn

5 <210> 57 <211> 17 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 57

Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val Lys

- 60 044325

Gly < 210> 58 < 211> 7 < 212> PROTEIN < 213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 58

Tyr Gly Asn Trp Phe Pro Tyr

5 <210> 59 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 59

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Trp 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100105 <210> 60 <211> 11 <212> PROTEIN <213> Artificial sequence

- 61 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 60

Arg Ala Ser Gln Asn Val Asp Thr Trp Val Ala

5 10 <210> 61 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 61

Ser Ala Ser Tyr Arg Tyr Ser

5 <210> 62 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial peptide sequence: synthetic <400> 62

Gln Gln Tyr Asp Ser Tyr Pro Leu Thr 1 5 <210> 63 <211> 243 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 63

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Tyr Ser 30

Trp Met Asn Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val

- 62 044325

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys

115 120125

Pro Gly Ser Gly Lys Pro Gly Ser Asp Ile Val Met Thr Gln Ser Pro

130 135140

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

145 150 155160

Ala Ser Gln Asn Val Asp Thr Trp Val Ala Trp Tyr Gln Gln Lys Pro

165 170175

Gly Gln Ser Pro Lys Ala Leu Ile Tyr Ser Ala Ser Tyr Arg Tyr Ser

180 185190

Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr

195 200205

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys

210 215220

Gln Gln Tyr Asp Ser Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Leu

225 230 235240

Glu Ile Lys <210> 64 <211> 116 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 64

- 63 044325

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Asp 25

Phe Ser Arg Ser 30

Trp Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Glu Ile Asn

Pro Asp Ser Ser 55

Thr Ile Asn Tyr 60

Ala Thr Ser Val

Lys Gly Arg Phe 65

Thr Ile Ser Arg 70

Asp Asn Ser Lys 75

Asn Thr Leu Tyr 80

Leu Gln Met Asn

Ser Leu Arg Ala 85

Glu Asp Thr Ala 90

Val Tyr Tyr Cys

Ala Arg Tyr Gly

100

Asn Trp Phe Pro

Tyr Trp Gly Gln 105

Gly Thr Leu Val

110

Thr Val Ser Ser

115 <210> 65 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 65

Arg Ser Trp Met Asn 1 5 <210> 66 <211> 17 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 66

Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val Lys

5 10 15

Gly

- 64 044325 <210> 67 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 67

Tyr Gly Asn Trp Phe Pro Tyr

5 <210> 68 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 68

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Trp 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100105 <210> 69 <211> 11 <212> PROTEIN <213> Artificial sequence <220>

- 65 044325 <221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 69

Arg Ala Ser Gln Asn Val Asp Thr Trp Val Ala <210> 70 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 70 Ser Ala Ser Tyr Arg Tyr Ser 1 5 <210> 71 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 71 Gln Gln Tyr Asp Ser Tyr Pro Leu Thr 1 5 <210> 72 <211> 243 <212> PROTEIN <213> Artificial sequence <220 >

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 72 Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val

- 66 044325

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

75 80

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 90 95

Ala Arg Tyr Gly Asn

100

Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

105 110

Thr

Val

Ser

115

Ser

Gly

Lys

Pro

Gly 120

Ser

Gly

Lys

Pro

Gly 125

Ser

Gly

Lys

Pro

Gly 130

Ser

Gly

Lys

Pro

Gly 135

Ser

Asp

Ile

Val

Met

140

Thr

Gln

Ser

Pro

Ser

145

Ser

Leu

Ser

Ala

Ser

150

Val

Gly

Asp

Arg

Val

155

Thr

Ile

Thr

Cys

Arg 160

Ala Ser

Gln Asn Val Asp

165

Gly Gln

Ser Pro Lys Ala 180

Gly Val

Pro Asp Arg Phe 195

Leu Thr

210

Ile Ser Ser Leu

Gln Gln

225

Tyr Asp Ser Tyr

230

Thr

Leu

Thr

Gln 215

Pro

Trp Val Ala Trp Tyr Gln Gln Lys Pro

170 175

Ile Tyr Ser Ala Ser Tyr Arg Tyr Ser

185 190

Gly Ser Gly Ser Gly Thr Asp Phe Thr

200 205

Pro Glu Asp Phe Ala Thr Tyr Phe Cys

220

Leu Thr Phe Gly Gly Gly Thr Lys Leu

235 240

Glu Ile Lys <210> 73 <211> 116 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 73

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

- 67 044325

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Asp Phe Ser Arg Ser 25 30

Trp Met Asn Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Glu Ile Asn Pro Asp Ser Ser

55

Thr Ile Asn Tyr Ala Thr Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ser Lys Asn Thr Leu Tyr

80

Leu Gln Met Asn Ser Leu Arg Ala 85

Glu Asp Thr Ala Val Tyr Tyr Cys

95

Ala Arg Tyr Gly Asn Trp Phe Pro

100

Tyr Trp Gly Gln Gly Thr Leu Val

105 110

Thr Val Ser Ser

115 <210> 74 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 74

Arg Ser Trp Met Asn 1 5 <210> 75 <211> 17 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 75

Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val Lys

5 10 15

Gly

- 68 044325 <210> 76 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 76

Tyr Gly Asn Trp Phe Pro Tyr

5 <210> 77 <211> 116 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 77

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser

115 <210> 78 <211> 11 <212> PROTEIN

- 69 044325 <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 78

Arg Ala Ser Gln Asn Val Asp Thr Asn Val Ala <210> 79 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 79

Ser Ala Ser Tyr Arg Tyr Ser

5 <210> 80 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 80

Gln Gln Tyr Asp Ser Tyr Pro Leu Thr

5 <210> 81 <211> 252 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 81

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

- 70 044325

Ser Glu Ile Asn Pro Asp Ser Ser

55

Thr Ile Asn Tyr Ala Thr Ser Val 60

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn Ser Lys Asn Thr 70 75

Leu Tyr 80

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp Thr Ala Val Tyr 90

Tyr Cys 95

Ala Arg Tyr Gly Asn

100

Trp Phe Pro Tyr Trp Gly Gln Gly Thr

105 110

Leu Val

Thr Val Ser Ser Gly 115

Lys Pro Gly Ser Gly Lys Pro Gly Ser

120 125

Gly Lys

Pro Gly Ser Gly Lys 130

Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly

135 140

Gly Gly Leu Val Gln 145

Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala

150 155 160

Ser Gly Phe Asp Phe

165

Ser Arg Ser Trp Met Asn Trp Val Arg Gln Ala

170 175

Pro Gly Lys Gly Leu

180

Glu Trp Val Ser Glu Ile Asn Pro Asp Ser Ser

185 190

Thr Ile Asn Tyr Ala 195

Thr Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

200 205

Asp Asn Ser Lys Asn 210

Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala

215 220

Glu Asp Thr Ala Val 225

Tyr Tyr Cys Ala Arg Tyr Gly Asn Trp Phe Pro

230 235 240

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

245 250

Ser Ser <210> 82 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide

- 71 044325 <400> 82 Glu Val Gln 1

Ser Leu Arg

Trp Met Asn

Ser Glu Ile

Lys Gly Arg 65

Leu Val 5

Leu Ser 20

Trp Val

Asn Pro

Phe Thr

Glu Ser

Cys Ala

Arg Gln

Gln Ser

Ile Ser 70

Gly Gly

Ala Ser

Ala Pro 40

Ser Thr

Arg Asp

Leu Gln Met

Asn Ser

Leu Arg

Ala Glu

Ala Arg Tyr

Gly Asn 100

Trp Phe

Pro Tyr

105

Thr Val Ser

115

Ser Ala

Ser Thr

Lys Gly 120

Pro Ser Ser

130

Lys Ser

Thr Ser

135

Gly Gly

Val Lys Asp 145

Tyr Phe

Pro Glu 150

Pro Val

Ala Leu Thr

Ser Gly

165

Val His

Thr Phe

Gly Leu Tyr

Ser Leu 180

Ser Ser

Val Val

185

Gly Thr Gln

195

Thr Tyr

Ile Cys

Asn Val 200

Lys Val Asp

210

Lys Lys

Val Glu

215

Pro Lys

Cys Pro Pro 225

Cys Pro

Ala Pro 230

Pro Val

Gly Leu 10

Gly Phe

Gly Lys

Ile Asn

Asn Ser 75

Asp Thr 90

Trp Gly

Pro Ser

Thr Ala

Thr Val

155

Pro Ala 170

Thr Val

Asn His

Ser Cys

Ala Gly

235

Met Ile

Val Gln

Thr Phe

Gly Leu 45

Tyr Ala 60

Lys Asn

Ala Val

Gln Gly

Val Phe

125

Ala Leu

140

Ser Trp

Val Leu

Pro Ser

Lys Pro

205

Asp Lys 220

Pro Ser

Pro Gly 15

Ser Tyr 30

Glu Trp

Thr Ser

Thr Leu

Tyr Tyr

Thr Leu 110

ProLeu

Gly Cys

Asn Ser

Gln Ser

175

Ser Ser 190

Ser Asp

Thr His

Val Phe

Gly

Ser

Val

Val

Tyr 80

Cys

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Leu 240

Glu

Phe Pro Pro

Lys Pro

Lys Asp

Thr Leu

Ser Arg

Thr Pro

- 72 044325

245 250 255

Val Thr Cys Val Val Val Asp Val 260

Phe Asn Trp Tyr Val Asp Gly Val 275 280

Lys His Glu Asp Pro Glu Val Lys

265 270

Glu Val His Asn Ala Lys Thr Lys

285

Pro

Arg 290

Glu

Glu

Glu

Tyr

Asn

295

Ser

Thr

Tyr

Arg

Val

300

Val

Ser

Val

Leu

Thr

305

Val

Leu

His

Gln

Asp 310

Trp

Leu

Asn

Gly

Lys 315

Glu

Tyr

Lys

Cys

Lys 320

Val

Ser

Asn

Lys

Ala

325

Leu

Pro

Ala

Pro

Ile

330

Glu

Lys

Thr

Ile

Ser

335

Lys

Ala

Lys

Gly

Gln

340

Pro

Arg

Glu

Pro

Gln

345

Val

Tyr

Thr

Leu

Pro

350

Pro

Ser

Arg Glu Glu Met

355

Thr Lys Asn Gln Val Ser Leu 360

Thr Cys Asp Val Ser

365

Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp

375

Glu Ser Asp Gly Gln 380

Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro Pro Val

390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu

Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys 420

Ser Val Met His Glu Ala Leu His Asn

425 430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445 <210> 83 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 83

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

- 73 044325

Ser

Ala

Gly

Ser 65

Leu

Tyr

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Leu Arg Leu 20

Ser Cys Ala

Ala Ser Gly 25

Phe Thr Phe

Ser Thr Tyr 30

Met Asn Trp 35

Arg Ile Arg 50

Val Lys Gly

Tyr Leu Gln

Cys Val Arg

100

Tyr Trp Gly 115

Ser Gly Lys 130

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Val Arg Gln

Ala Pro Gly 40

Lys Gly Leu 45

Glu Trp Val

Ser Lys Tyr

Arg Phe Thr 70

Met Asn Ser 85

His Gly Asn

Gln Gly Thr

Pro Gly Ser

135

Val Thr Gln

150

Leu Thr Cys 165

Asn Trp Val

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Asn Asn Tyr

Ala Thr Tyr 60

Tyr Ala Asp

Ile Ser Arg

Leu Arg Ala

Phe Gly Asp

105

Leu Val Thr 120

Gly Lys Pro

Glu Pro Ser

Gly Ser Ser

170

Gln Gln Lys

185

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys

250

Asp Asp Ser 75

Lys Asn Thr 80

Glu Asp Thr

Ser Tyr Val

Val Ser Ser

125

Gly Ser Gly

140

Leu Thr Val 155

Thr Gly Ala

Pro Gly Lys

Pro Gly Val

205

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Ala Val Tyr 95

Ser Trp Phe 110

Gly Lys Pro

Lys Pro Gly

Ser Pro Gly

160

Val Thr Thr

175

Ser Pro Arg 190

Pro Ala Arg

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

- 74 044325

Lys Ser Ser Asp Lys Thr His Thr 260

Val Ala Gly Pro Ser Val Phe Leu 275 280

Cys Pro Pro 265

Phe Pro Pro

Cys Pro Ala Pro Pro

270

Lys Pro Lys Asp Thr

285

Leu Met

290

Lys His 305

Ile Ser Arg Thr Pro 295

Glu Asp Pro Glu Val 310

Glu Val Thr Cys Val Val Val Asp Val 300

Lys Phe Asn Trp Tyr Val Asp Gly Val

315 320

Glu Val His Asn Ala

325

Thr Tyr Arg Val Val

340

Asn Gly Lys Glu Tyr

355

Pro Ile Glu Lys Thr 370

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 330335

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 345350

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 360365

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 375380

Gln Val 385

Val Lys

Tyr

Thr

Leu Pro Pro

390

Leu

Thr

Cys Leu Val 405

Ser Arg Glu Gln Met Thr Lys Asn Gln 395 400

Lys Gly Phe Tyr Pro Ser Asp Ile Ala 410 415

Val Glu Trp

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 420 425

Pro Pro Val

435

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

440 445

Lys Thr Thr 430

Ser Lys Leu

Thr Val Asp

450

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe

455 460

Ser Cys Ser

Val Met His 465

Glu Ala Leu His Asn His Tyr Thr Gln Lys

470 475

Ser Leu Ser

480

Leu Ser Pro Gly Lys

485 <210> 84 <211> 214 <212> PROTEIN

- 75 044325 <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 84

Asp Ile Val Met 1

Thr Gln Ser Pro 5

Ser Ser Leu Ser 10

Ala Ser Val Gly 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Gln Asn 25

Val Asp Thr Trp 30

Val Ala Trp Tyr

Gln Gln Lys Pro 40

Gly Gln Ser Pro

Lys Ala Leu Ile 45

Tyr Ser Ala Ser 50

Tyr Arg Tyr Ser

Gly Val Pro Asp 60

Arg Phe Thr Gly

Ser Gly Ser Gly 65

Thr Asp Phe Thr 70

Leu Thr Ile Ser

Ser Leu Gln Pro

Glu Asp Phe Ala

Thr Tyr Phe Cys 85

Gln Gln Tyr Asp 90

Ser Tyr Pro Leu 95

Thr Phe Gly Gly

100

Gly Thr Lys Leu

Glu Ile Lys Arg 105

Thr Val Ala Ala

110

Pro Ser Val Phe

115

Ile Phe Pro Pro

120

Ser Asp Glu Gln

Leu Lys Ser Gly 125

Thr Ala Ser Val

130

Val Cys Leu Leu

135

Asn Asn Phe Tyr

140

Pro Arg Glu Ala

Lys Val Gln Trp 145

Lys Val Asp Asn

150

Ala Leu Gln Ser

155

Gly Asn Ser Gln

160

Glu Ser Val Thr

Glu Gln Asp Ser 165

Lys Asp Ser Thr 170

Tyr Ser Leu Ser

175

Ser Thr Leu Thr

180

Leu Ser Lys Ala

Asp Tyr Glu Lys 185

His Lys Val Tyr 190

Ala Cys Glu Val

195

Thr His Gln Gly

200

Leu Ser Ser Pro

Val Thr Lys Ser 205

Phe Asn Arg Gly Glu Cys

210

- 76 044325 <210> 85 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 85

Glu 1 Val Gln Leu Val 5 Glu Ser Gly Gly Gly 10 Leu Val Gln Pro Gly 15 Gly Ser Leu Arg Leu 20 Ser Cys Ala Ala Ser 25 Gly Phe Asp Phe Ser 30 Arg Ser Trp Met Asn 35 Trp Val Arg Gln Ala 40 Pro Gly Lys Gly Leu 45 Glu Trp Val Ser Glu 50 Ile Asn Pro Asp Ser 55 Ser Thr Ile Asn Tyr 60 Ala Thr Ser Val Lys 65 Gly Arg Phe Thr Ile 70 Ser Arg Asp Asn Ser 75 Lys Asn Thr Leu Tyr 80 Leu Gln Met Asn Ser 85 Leu Arg Ala Glu Asp 90 Thr Ala Val Tyr Tyr 95 Cys Ala Arg Tyr Gly 100 Asn Trp Phe Pro Tyr 105 Trp Gly Gln Gly Thr 110 Leu Val Thr Val Ser 115 Ser Ala Ser Thr Lys 120 Gly Pro Ser Val Phe 125 Pro Leu Ala Pro Ser 130 Ser Lys Ser Thr Ser 135 Gly Gly Thr Ala Ala 140 Leu Gly Cys Leu Val 145 Lys Asp Tyr Phe Pro 150 Glu Pro Val Thr Val 155 Ser Trp Asn Ser Gly 160 Ala Leu Thr Ser Gly 165 Val His Thr Phe Pro 170 Ala Val Leu Gln Ser 175 Ser Gly Leu Tyr Ser 180 Leu Ser Ser Val Val 185 Thr Val Pro Ser Ser 190 Ser Leu Gly Thr Gln 195 Thr Tyr Ile Cys Asn 200 Val Asn His Lys Pro 205 Ser Asp Thr

- 77 044325

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Asp Lys Thr His

220

Cys Pro Pro Cys Pro 225

Ala Pro Pro Val Ala 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Lys His

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Glu 290

Tyr Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Val Ser Asn Lys Ala

325

Leu Pro Ala Pro Ile

330

Glu Lys Thr Ile Ser

335

Ala Lys Gly Gln Pro

340

Arg Glu Pro Gln Val

345

Tyr Thr Leu Pro Pro

350

Arg Glu Glu Met Thr

355

Lys Asn Gln Val Ser 360

Leu Thr Cys Asp Val

365

Gly Phe Tyr Pro Ser

370

Asp Ile Ala Val Glu

375

Trp Glu Ser Asp Gly

380

Pro Glu Asn Asn Tyr 385

Lys Thr Thr Pro Pro 390

Val Leu Asp Ser Asp 395

Ser Phe Phe Leu Tyr

405

Ser Lys Leu Thr Val

410

Asp Lys Ser Arg Trp

415

Gln Gly Asp Val Phe

420

Ser Cys Ser Val Met

425

His Glu Ala Leu His

430

Thr

Leu 240

Glu

Lys

Lys

Leu

Lys 320

Lys

Ser

Ser

Gln

Gly 400

Glu

Asn

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser

440

Pro Gly Lys

445 <210> 86 <211> 485

- 78 044325 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 86

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Gln Pro Gly Gly 15

Phe Ser Thr Tyr 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

- 79 044325

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Glu Pro

245 250255

Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro

260 265270

Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

275 280285

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

- 80 044325

465

470

475

480

Leu Ser Pro Gly Lys

485 <210> 87 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 87

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

- 81 044325

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210 <210> 88 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 88

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

- 82 044325

165

170

175

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Gly

Pro 385

Ser

Leu Tyr Ser Leu Ser 180

Thr Gln Thr Tyr Ile 195

Val Asp Lys Lys Val 210

Pro Pro Cys Pro Ala

230

Pro Pro Lys Pro Lys

245

Thr Cys Val Val Val

260

Asn Trp Tyr Val Asp

275

Arg Glu Glu Glu Tyr 290

Val Leu His Gln Asp

310

Ser Asn Lys Ala Leu

325

Lys Gly Gln Pro Arg 340

Glu Glu Met Thr Lys

355

Phe Tyr Pro Ser Asp 370

Glu Asn Asn Tyr Lys

390

Phe Phe Leu Tyr Ser

405

Ser Val Val Thr Val

185

Cys Asn Val Asn His

200

Glu Pro Lys Ser Cys 215

Pro Pro Val Ala Gly

235

Asp Thr Leu Met Ile

250

Asp Val Lys His Glu 265

Gly Val Glu Val His

280

Asn Ser Thr Tyr Arg 295

Trp Leu Asn Gly Lys

315

Pro Ala Pro Ile Glu

330

Glu Pro Gln Val Tyr

345

Asn Gln Val Ser Leu

360

Ile Ala Val Glu Trp 375

Thr Thr Pro Pro Val

395

Lys Leu Thr Val Asp

410

Pro Ser Ser Ser Leu

190

Lys Pro Ser Asp Thr

205

Asp Lys Thr His Thr 220

Pro Ser Val Phe Leu

240

Ser Arg Thr Pro Glu

255

Asp Pro Glu Val Lys 270

Asn Ala Lys Thr Lys

285

Val Val Ser Val Leu 300

Glu Tyr Lys Cys Lys

320

Lys Thr Ile Ser Lys

335

Thr Leu Pro Pro Ser

350

Thr Cys Asp Val Ser

365

Glu Ser Asp Gly Gln 380

Leu Asp Ser Asp Gly

400

Lys Ser Arg Trp Glu

415

- 83 044325

Gln Gly Asp Val Phe Ser Cys Ser

420

Val Met His 425

Glu Ala Leu His Asn

430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445 <210> 89 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 89

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 84 044325

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Glu Trp

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Glu Ser 420

Trp Val

Thr Asn

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Asn Gly

Gln Gln 185

Lys Arg 200

Gly Lys

Asp Tyr

Gly Thr

Lys Pro

Gly Lys

Ala Pro

Ala Ala

Tyr Cys

235

Lys Leu 250

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Glin Pro

425

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Glu Asn

Gly Val

205

Leu Thr

220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Asn Tyr

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Lys Thr 430

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

- 85 044325

Pro Pro Val Leu Asp Ser Asp Gly Ser

435440

Thr Val Asp Lys Ser Arg Trp Gln Gln

450455

Val Met His Glu Ala Leu His Asn His

465470

Phe Phe Leu Tyr 445 Ser Lys Leu Gly Asn Val 460 Phe Ser Cys Ser Tyr Thr 475 Gln Lys Ser Leu Ser 480

Leu Ser Pro Gly Lys

485 <210> 90 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 90

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Trp 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

- 86 044325

Lys Val Gln Trp 145

Lys Val Asp Asn Ala Leu 150

Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr

Glu Gln Asp Ser Lys Asp

165 170

Ser Thr Leu Thr

180

Leu Ser Lys Ala Asp Tyr

185

Ala Cys Glu Val

195

Thr His Gln Gly Leu Ser

200

Ser Thr Tyr Ser Leu Ser 175

Glu Lys His Lys Val Tyr 190

Ser Pro Val Thr Lys Ser 205

Phe Asn Arg Gly Glu Cys

210 <210> 91 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 91

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

- 87 044325

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Gly

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

340

Glu Glu Met

355

Phe Tyr Pro 370

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Glu Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Arg Glu

Thr Lys Asn

Ser Asp Ile

375

Gly Gly Thr

Pro Val Thr

Thr Phe Pro 170

Val Val Thr 185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Pro Gln Val

345

Gln Val Ser 360

Ala Val Glu

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Leu Thr Cys

365

Trp Glu Ser

380

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asp Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser 350

Asp Val Ser

Asp Gly Gln

- 88 044325

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His

420 425

Glu Ala Leu His Asn

430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440

Gly Lys

445 <210> 92 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 92

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

- 89 044325

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys 370

Val Tyr Thr

Val Thr Gln

150

Leu Thr Cys 165

Asn Trp Val

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

375

Leu Pro Pro

Glu Pro Ser

Gly Ser Ser

170

Gln Gln Lys

185

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys

250

Thr Cys Pro

265

Leu Phe Pro 280

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Lys Ala Lys

Ser Arg Glu

Leu Thr Val 155

Thr Gly Ala

Pro Gly Lys

Pro Gly Val

205

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Asn Lys Ala

365

Gly Gln Pro

380

Gln Met Thr

Ser Pro Gly

160

Val Thr Thr

175

Ser Pro Arg 190

Pro Ala Arg

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

- 90 044325

385

390

395

400

Val Lys Leu

Thr Cys Leu Val Lys Gly Phe Tyr Pro

405 410

Ser Asp Ile Ala

415

Val Glu Trp

Glu Ser Asn Gly Gln Pro Glu Asn Asn

420 425

Tyr Lys Thr Thr 430

Pro Pro Val

435

Leu Asp Ser Asp Gly Ser Phe Phe Leu

440

Tyr Ser Lys Leu 445

Thr Val Asp

450

Lys Ser Arg Trp Gln Gln Gly Asn Val

455 460

Phe Ser Cys Ser

Val Met His 465

Glu Ala Leu His Asn His Tyr Thr Gln

470 475

Lys Ser Leu Ser

480

Leu Ser Pro Gly Lys

485 <210> 93 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 93

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Trp 20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

- 91 044325

100

105

110

Pro Ser Val Phe Ile Phe Pro Pro

115 120

Ser Asp Glu Gln Leu Lys Ser Gly

125

Thr Ala Ser Val Val Cys Leu Leu

130 135

Asn Asn Phe Tyr Pro Arg Glu Ala

140

Lys Val Gln Trp Lys Val Asp Asn

145 150

Ala Leu Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr Glu Gln Asp Ser

165

Lys Asp Ser Thr Tyr Ser Leu Ser

170 175

Ser Thr Leu Thr Leu Ser Lys Ala 180

Asp Tyr Glu Lys His Lys Val Tyr

185 190

Ala Cys Glu Val Thr His Gln Gly

195 200

Leu Ser Ser Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210 <210> 94 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 94

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

- 92 044325

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Arg Tyr Gly

100

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Asn Trp Phe

Ala Ser Thr

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Glu Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Tyr Trp

105

Lys Gly Pro 120

Gly Gly Thr

Pro Val Thr

Thr Phe Pro

170

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Gly Gln Gly

Thr Leu Val 110

Ser Val Phe

125

Pro Leu Ala

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asp Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

- 93 044325

Ala Lys Gly Gln Pro Arg Glu Pro 340

Gln Val Tyr Thr Leu Pro Pro Ser

345 350

Arg Glu Glu Met

355

Thr Lys Asn Gln Val Ser Leu 360

Thr Cys Asp Val Ser

365

Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp

375

Glu Ser Asp Gly Gln 380

Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro Pro Val

390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu

Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys 420

Ser Val Met His Glu Ala Leu His Asn

425 430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440 445 <210> 95 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 95

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

- 94 044325

Tyr

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Cys Val

Tyr Trp

115

Ser Gly 130

Gln Ala

Thr Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Arg His 100

Gly Gln

Lys Pro

Val Val

Thr Leu

165

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Gly Asn

Gly Thr

Gly Ser

135

Thr Gln 150

Thr Cys

Trp Val

Thr Asn

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Phe Gly

105

Asp Ser

Tyr Val

Leu Val 120

Gly Lys

Glu Pro

Gly Ser

Gln Gln

185

Lys Arg 200

Gly Lys

Asp Tyr

Gly Thr

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Thr Val

Ser Ser

125

Pro Gly

Ser Leu

155

Ser Thr 170

Lys Pro

Ala Pro

Ala Ala

Tyr Cys

235

Lys Leu 250

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Gly 140

Thr Val

Gly Ala

Gly Lys

Gly Val

205

Leu Thr

220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Ser Trp 110

Gly Lys

Lys Pro

Ser Pro

Val Thr

175

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

- 95 044325

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 96 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 96

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp ThrAsn

2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly

5560

- 96 044325

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys

Glu Val Thr His 195

Gln Gly Leu

200

Ser Ser Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210 <210> 97 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 97

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

- 97 044325

Ser

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Glu Ile 50

Gly Arg

Gln Met

Arg Tyr

Val Ser

115

Ser Ser 130

Lys Asp

Leu Thr

Leu Tyr

Thr Gln

195

Val Asp 210

Pro Pro

Pro Pro

Thr Cys

Asn Trp

275

Arg Glu 290

Asn Pro

Phe Thr

Asn Ser

Gly Asn 100

Ser Ala

Lys Ser

Tyr Phe

Ser Gly

165

Ser Leu 180

Thr Tyr

Lys Lys

Cys Pro

Lys Pro

245

Val Val 260

Tyr Val

Glu Glu

Asp Ser 55

Ile Ser 70

Leu Arg

Trp Phe

Ser Thr

Thr Ser

135

Pro Glu 150

Val His

Ser Ser

Ile Cys

Val Glu

215

Ala Pro 230

Lys Asp

Val Asp

Asp Gly

Tyr Asn

295

Ser Thr

Ile Asn

Arg Asp

Asn Ser

Ala Glu

Asp Thr 90

Pro Tyr

105

Lys Gly 120

Gly Gly

Pro Val

Thr Phe

Val Val

185

Asn Val 200

Pro Lys

Pro Val

Thr Leu

Val Lys

265

Val Glu 280

Ser Thr

Trp Gly

Pro Ser

Thr Ala

Thr Val

155

Pro Ala 170

Thr Val

Asn His

Ser Cys

Ala Gly

235

Met Ile 250

His Glu

Val His

Tyr Arg

Tyr Ala 60

Lys Asn

Ala Val

Gln Gly

Val Phe

125

Ala Leu 140

Ser Trp

Val Leu

Pro Ser

Lys Pro

205

Asp Lys 220

Pro Ser

Ser Arg

Asp Pro

Asn Ala

285

Val Val 300

Thr Ser

Thr Leu

Tyr Tyr

Thr Leu 110

ProLeu

Gly Cys

Asn Ser

Gln Ser

175

Ser Ser 190

Ser Asp

Thr His

Val Phe

Thr Pro

255

Glu Val

270

Lys Thr

Ser Val

Val

Tyr 80

Cys

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Leu 240

Glu

Lys

Lys

Leu

- 98 044325

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315

Glu Tyr Lys Cys Lys

320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

325 330

Ile Ser Lys

335

Ala Lys

Gly Gln Pro Arg Glu Pro Gln Val

340 345

Tyr Thr Leu Pro Pro Ser

350

Arg Glu Glu Met

355

Thr Lys Asn Gln Val Ser Leu 360

Thr Cys Asp Val Ser

365

Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp 375

Glu Ser Asp Gly Gln 380

Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro Pro Val

390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu

Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys 420

Ser Val Met His Glu Ala Leu His Asn

425 430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440 445 <210> 98 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 98

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

5560

- 99 044325

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Ser Tyr Val Ser Trp

110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys

125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala

200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Leu Met Ile Ser Arg

290

Thr Pro Glu Val Thr

295

Cys Val Val Val Asp

300

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val

Lys His Glu Asp Pro

Glu Val Lys Phe Asn

Trp Tyr Val Asp Gly

- 100 044325

305

310

315

320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 99 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 99

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn

- 101 044325

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln 3540

Ser Pro Lys Ala Leu Ile 45

Tyr Ser Ala Ser Tyr Arg Lys Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210> 100 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 100

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

- 102 044325

Ser

Trp

Ser

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Leu Arg Leu Ser Cys 20

Met Asn Trp Val Arg 35

Glu Ile Asn Pro Asp 50

Gly Arg Phe Thr Ile 70

Gln Met Asn Ser Leu

Arg Tyr Gly Asn Trp 100

Val Ser Ser Ala Ser

115

Ser Ser Lys Ser Thr 130

Lys Asp Tyr Phe Pro

150

Leu Thr Ser Gly Val

165

Leu Tyr Ser Leu Ser 180

Thr Gln Thr Tyr Ile 195

Val Asp Lys Lys Val 210

Pro Pro Cys Pro Ala

230

Pro Pro Lys Pro Lys

245

Ala Ala Ser Gly Phe 25

Gln Ala Pro Gly Lys 40

Ser Ser Thr Ile Asn 55

Ser Arg Asp Asn Ser 75

Arg Ala Glu Asp Thr

Phe Pro Tyr Trp Gly 105

Thr Lys Gly Pro Ser 120

Ser Gly Gly Thr Ala 135

Glu Pro Val Thr Val

155

His Thr Phe Pro Ala

170

Ser Val Val Thr Val

185

Cys Asn Val Asn His

200

Glu Pro Lys Ser Cys 215

Pro Pro Val Ala Gly

235

Asp Thr Leu Met Ile

250

Asp Phe Ser Arg Ser 30

Gly Leu Glu Trp Val 45

Tyr Ala Thr Ser Val 60

Lys Asn Thr Leu Tyr 80

Ala Val Tyr Tyr Cys 95

Gln Gly Thr Leu Val 110

Val Phe Pro Leu Ala

125

Ala Leu Gly Cys Leu 140

Ser Trp Asn Ser Gly

160

Val Leu Gln Ser Ser

175

Pro Ser Ser Ser Leu

190

Lys Pro Ser Asp Thr

205

Asp Lys Thr His Thr 220

Pro Ser Val Phe Leu

240

Ser Arg Thr Pro Glu

255

- 103 044325

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265 270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280 285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330 335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345 350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360 365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375 380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395 400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410 415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425 430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440 445 <210> 101 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 101

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

- 104 044325

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Thr Phe Ser Thr

Ala Met Asn Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Gly Arg Ile Arg Ser 50

Lys Tyr Asn Asn Tyr 55

Ala Thr Tyr Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Ser Tyr Val Ser Trp

110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys

125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala

200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Tyr

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

- 105 044325

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

280 285

Leu Met Ile Ser Arg

290

Thr Pro Glu Val Thr Cys Val Val Val Asp

295 300

Lys His Glu Asp Pro 305

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 310 315

Glu Val His Asn Ala

325

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

330 335

Thr Tyr Arg Val Val

340

Ser Val Leu Thr Val Leu His Gln Asp Trp

345 350

Asn Gly Lys Glu Tyr 355

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

360 365

Pro Ile Glu Lys Thr 370

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

375 380

Gln Val Tyr Thr Leu 385

Pro Pro Ser Arg Glu Gln Met Thr Lys Asn 390 395

Val Lys Leu Thr Cys

405

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

410 415

Val Glu Trp Glu Ser

420

Asn Gly Gln Pro Glu Asn Asn Tyr 425

Pro Pro Val Leu Asp

435

Ser Asp Gly Ser Phe Phe Leu Tyr

440 445

Thr Val Asp Lys Ser 450

Arg Trp Gln Gln Gly Asn Val Phe

455 460

Val Met His Glu Ala 465

Leu His Asn His Tyr Thr Gln Lys

470 475

Lys Thr 430

Ser Lys

Ser Cys

Ser Leu

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

Leu

Ser

Ser 480

Leu Ser Pro Gly Lys

485 <210> 102 <211> 214 <212> PROTEIN <213> Artificial <220>

subsequence

- 106 044325 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 102

Asp Ile Val Met 1

Thr Gln Ser Pro 5

Ser Ser Leu Ser 10

Ala Ser Val Gly 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Gln Asn 25

Val Asp Thr Asn 30

Val Ala Trp Tyr

Gln Gln Lys Pro 40

Gly Gln Ser Pro

Lys Ala Leu Ile 45

Tyr Ser Ala Ser 50

Tyr Arg Tyr Ser

Gly Val Pro Asp 60

Arg Phe Thr Gly

Ser Gly Ser Gly 65

Thr Asp Phe Thr 70

Leu Thr Ile Ser

Ser Leu Gln Pro

Glu Asp Phe Ala

Thr Tyr Phe Cys 85

Gln Gln Tyr Asp 90

Ser Tyr Pro Leu 95

Thr Phe Gly Gly

100

Gly Thr Lys Leu

Glu Ile Lys Arg 105

Thr Val Ala Ala

110

Pro Ser Val Phe

115

Ile Phe Pro Pro

120

Ser Asp Glu Gln

Leu Lys Ser Gly 125

Thr Ala Ser Val

130

Val Cys Leu Leu

135

Asn Asn Phe Tyr

140

Pro Arg Glu Ala

Lys Val Gln Trp 145

Lys Val Asp Asn 150

Ala Leu Gln Ser

155

Gly Asn Ser Gln

160

Glu Ser Val Thr

Glu Gln Asp Ser 165

Lys Asp Ser Thr 170

Tyr Ser Leu Ser

175

Ser Thr Leu Thr

180

Leu Ser Lys Ala

Asp Tyr Glu Lys 185

His Lys Val Tyr

190

Ala Cys Glu Val

195

Thr His Gln Gly

200

Leu Ser Ser Pro

Val Thr Lys Ser 205

Phe Asn Arg Gly Glu Cys

210 <210> 103 <211> 445

- 107 044325 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 103

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser TyrSer

2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val

5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

195 200205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215220

- 108 044325

Cys Pro Pro Cys Pro 225

Phe Pro Pro Lys Pro

245

Val Thr Cys Val Val

260

Phe Asn Trp Tyr Val

275

Ala Pro 230

Lys Asp

Val Asp

Asp Gly

Pro Val

Thr Leu

Val Lys

265

Val Glu 280

Ala Gly

235

Met Ile 250

His Glu

Val His

Pro Ser

Ser Arg

Asp Pro

Asn Ala

285

Val Phe

Thr Pro

255

Glu Val

270

Lys Thr

Pro Arg Glu Glu Glu 290

Tyr Asn

295

Ser Thr

Tyr Arg

Val Val 300

Ser Val

Thr Val Leu His Gln 305

Asp Trp 310

Leu Asn

Gly Lys

315

Glu Tyr

Lys Cys

Val Ser Asn Lys Ala

325

Leu Pro

Ala Pro

Ile Glu

330

Lys Thr

Ile Ser

335

Ala Lys Gly Gln Pro

340

Arg Glu

Pro Gln

345

Val Tyr

Thr Leu

Pro Pro 350

Arg Glu Glu Met Thr

355

Lys Asn

Gln Val 360

Ser Leu

Thr Cys

365

Asp Val

Gly Phe Tyr Pro Ser

370

Asp Ile

375

Ala Val

Glu Trp

Glu Ser 380

Asp Gly

Pro Glu Asn Asn Tyr 385

Lys Thr 390

Thr Pro

Pro Val

395

Leu Asp

Ser Asp

Ser Phe Phe Leu Tyr

405

Ser Lys

Leu Thr

Val Asp 410

Lys Ser

Arg Trp

415

Gln Gly Asp Val Phe

420

Ser Cys

Ser Val

425

Met His

Glu Ala

Leu His 430

Leu 240

Glu

Lys

Lys

Leu

Lys 320

Lys

Ser

Ser

Gln

Gly 400

Glu

Asn

His Tyr Thr Gln Lys

435

Ser Leu

Ser Leu

440

Ser Pro

Gly Lys

445 <210> 104 <211> 485 <212> PROTEIN <213> Artificial sequence

- 109 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 104

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp

Tyr Tyr Cys Ala Leu Trp Tyr Ser

- 110 044325

225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Val 465

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys 370

Val Tyr Thr

Lys Leu Thr

Glu Trp Glu

420

Pro Val Leu

435

Val Asp Lys 450

Met His Glu

230

235

240

Phe Gly Gly 245

Gly Thr Lys

250

Leu Thr Val

Leu Glu Pro

255

Lys Thr His

Thr Cys Pro

265

Pro Cys Pro

Ala Pro Pro 270

Ser Val Phe

Leu Phe Pro 280

Pro Lys Pro

285

Lys Asp Thr

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

375

Leu Pro Pro

390

Cys Leu Val 405

Ser Asn Gly

Asp Ser Asp

Ser Arg Trp

455

Ala Leu His

470

Glu Val Thr

Cys Val Val

300

Val Asp Val

Lys Phe Asn

Trp Tyr Val 315

Asp Gly Val

320

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Lys Ala Lys

Ser Arg Glu

Lys Gly Phe

410

Gln Pro Glu

425

Gly Ser Phe 440

Gln Gln Gly

Asn His Tyr

Glu Glu Gln

Tyr Asn Ser

335

Leu His Gln

Asn Lys Ala

365

Gly Gln Pro

380

Gln Met Thr 395

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

445

Asn Val Phe

460

Thr Gln Lys 475

Asp Trp Leu 350

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

400

Asp Ile Ala 415

Lys Thr Thr 430

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

480

- 111 044325

Leu Ser Pro Gly Lys

485 <210> 105 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 105

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Trp 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

- 112 044325

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210 <210> 106 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 106

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170175

- 113 044325

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Gly

Pro 385

Ser

Gln

Leu Tyr

Thr Gln

195

Val Asp 210

Pro Pro

Pro Pro

Thr Cys

Asn Trp

275

Arg Glu 290

Val Leu

Ser Asn

Lys Gly

Glu Glu

355

Phe Tyr 370

Glu Asn

Phe Phe

Gly Asp

Ser Leu 180

Thr Tyr

Lys Lys

Cys Pro

Lys Pro

245

Val Val 260

Tyr Val

Glu Glu

His Gln

Lys Ala

325

Glin Pro 340

Met Thr

Pro Ser

Asn Tyr

Leu Tyr

405

Val Phe 420

Ser Ser

Ile Cys

Val Glu

215

Ala Pro 230

Lys Asp

Val Asp

Asp Gly

Tyr Asn

295

Asp Trp 310

Leu Pro

Arg Glu

Lys Asn

Asp Ile

375

Lys Thr 390

Ser Lys

Ser Cys

Val Val

185

Asn Val 200

Pro Lys

Pro Val

Thr Leu

Val Lys

265

Val Glu 280

Ser Thr

Leu Asn

Ala Pro

Pro Gln

345

Gln Val 360

Ala Val

Thr Pro

Leu Thr

Ser Val

425

Thr Val

Pro Ser

Asn His

Lys Pro

205

Ser Cys

Ala Gly

235

Met Ile 250

His Glu

Val His

Tyr Arg

Gly Lys

315

Ile Glu

330

Val Tyr

Ser Leu

Glu Trp

Pro Val

395

Val Asp 410

Met His

Asp Lys 220

Pro Ser

Ser Arg

Asp Pro

Asn Ala

285

Val Val 300

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

365

Glu Ser 380

Leu Asp

Lys Ser

Glu Ala

Ser Ser 190

Ser Asp

Thr His

Val Phe

Thr Pro

255

Glu Val

270

Lys Thr

Ser Val

Lys Cys

Ile Ser

335

Pro Pro 350

Asp Val

Asp Gly

Ser Asp

Arg Trp

415

Leu His 430

Leu

Thr

Thr

Leu 240

Glu

Lys

Lys

Leu

Lys 320

Lys

Ser

Ser

Gln

Gly 400

Glu

Asn

- 114 044325

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445 <210> 107 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 107

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

- 115 044325

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys 370

Val Tyr Thr

Lys Leu Thr

Glu Trp Glu

420

Pro Val Leu

435

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

375

Leu Pro Pro

390

Cys Leu Val 405

Ser Asn Gly

Asp Ser Asp

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys

250

Thr Cys Pro

265

Leu Phe Pro 280

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Lys Ala Lys

Ser Arg Glu

Lys Gly Phe

410

Gln Pro Glu

425

Gly Ser Phe 440

Pro Gly Val

205

Pro Ala Arg

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Asn Lys Ala

365

Gly Gln Pro

380

Gln Met Thr 395

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

445

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

400

Asp Ile Ala 415

Lys Thr Thr 430

Ser Lys Leu

- 116 044325

Thr Val Asp Lys Ser Arg Trp Gln

450 455

Gln Gly Asn

Val Phe Ser Cys Ser 460

Val Met His 465

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

470 475 480

Leu Ser Pro Gly Lys

485 <210> 108 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 108

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

- 117 044325

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 165170

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 180185

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 195200

Thr Tyr Ser Leu Ser

175

Lys His Lys Val Tyr 190

Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210 <210> 109 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 109

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135140

- 118 044325

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Gly

Pro

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

340

Glu Glu Met

355

Phe Tyr Pro 370

Glu Asn Asn

Phe Pro Glu

150

Pro Val Thr

Val Ser Trp 155

Asn Ser Gly

160

Gly Val His 165

Thr Phe Pro

170

Ala Val Leu

Gln Ser Ser

175

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Glu Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Arg Glu

Thr Lys Asn

Ser Asp Ile

375

Tyr Lys Thr

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Pro Gln Val

345

Gln Val Ser 360

Ala Val Glu

Thr Pro Pro

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Leu Thr Cys

365

Trp Glu Ser

380

Val Leu Asp

Ser Ser Leu 190

Ser Asp Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser 350

Asp Val Ser

Asp Gly Gln

Ser Asp Gly

- 119 044325

385 390 395 400

Ser Phe Phe Leu

Tyr Ser Lys Leu 405

Thr Val Asp Lys 410

Ser Arg Trp Glu

415

Gln Gly Asp Val

420

Phe Ser Cys Ser

Val Met His Glu 425

Ala Leu His Asn

430

His Tyr Thr Gln

435

Lys Ser Leu Ser

440

Leu Ser Pro Gly

Lys 445 <210> 110 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 110

Glu 1 Val Gln Leu Val 5 Glu Ser Gly Gly Gly 10 Leu Val Gln Pro Gly 15 Gly Ser Leu Arg Leu 20 Ser Cys Ala Ala Ser 25 Gly Phe Thr Phe Ser 30 Thr Tyr Ala Met Asn 35 Trp Val Arg Gln Ala 40 Pro Gly Lys Gly Leu 45 Glu Trp Val Gly Arg 50 Ile Arg Ser Lys Tyr 55 Asn Asn Tyr Ala Thr 60 Tyr Tyr Ala Asp Ser 65 Val Lys Gly Arg Phe 70 Thr Ile Ser Arg Asp 75 Asp Ser Lys Asn Thr 80 Leu Tyr Leu Gln Met 85 Asn Ser Leu Arg Ala 90 Glu Asp Thr Ala Val 95 Tyr Tyr Cys Val Arg 100 His Gly Asn Phe Gly 105 Asp Ser Tyr Val Ser 110 Trp Phe Asp Tyr Trp 115 Gly Gln Gly Thr Leu 120 Val Thr Val Ser Ser 125 Gly Lys Pro Gly Ser 130 Gly Lys Pro Gly Ser 135 Gly Lys Pro Gly Ser 140 Gly Lys Pro Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

- 120 044325

145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys 370

Val Tyr Thr

150

155

160

Leu Thr Cys 165

Gly Ser Ser

170

Thr Gly Ala

Val Thr Thr

175

Asn Trp Val

Gln Gln Lys

185

Pro Gly Lys

Ser Pro Arg 190

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

375

Leu Pro Pro

390

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys

250

Thr Cys Pro

265

Leu Phe Pro 280

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Lys Ala Lys

Ser Arg Glu

Pro Gly Val

205

Pro Ala Arg

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Asn Lys Ala

365

Gly Gln Pro

380

Gln Met Thr 395

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

400

- 121 044325

Val Lys Leu

Thr Cys Leu Val Lys Gly Phe Tyr Pro

405 410

Ser Asp Ile Ala

415

Val Glu Trp

Glu Ser Asn Gly Gln Pro Glu Asn Asn 420 425

Tyr Lys Thr Thr 430

Pro Pro Val

435

Leu Asp Ser Asp Gly Ser Phe Phe Leu

440

Tyr Ser Lys Leu 445

Thr Val Asp

450

Lys Ser Arg Trp Gln Gln Gly Asn Val

455 460

Phe Ser Cys Ser

Val Met His 465

Glu Ala Leu His Asn His Tyr Thr Gln

470 475

Lys Ser Leu Ser

480

Leu Ser Pro Gly Lys

485 <210> 111 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 111

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Trp 20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 40 45

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

- 122 044325

Pro Ser Val Phe Ile Phe Pro Pro

115 120

Ser Asp Glu Gln Leu Lys Ser Gly

125

Thr Ala Ser Val Val Cys Leu Leu

130 135

Asn Asn Phe Tyr Pro Arg Glu Ala

140

Lys Val Gln Trp Lys Val Asp Asn

145 150

Ala Leu Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr Glu Gln Asp Ser

165

Lys Asp Ser Thr Tyr Ser Leu Ser

170 175

Ser Thr Leu Thr Leu Ser Lys Ala 180

Asp Tyr Glu Lys His Lys Val Tyr

185 190

Ala Cys Glu Val Thr His Gln Gly

195 200

Leu Ser Ser Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210 <210> 112 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 112

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

- 123 044325

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg Tyr

Val Ser

115

Ser Ser 130

Lys Asp

Leu Thr

Leu Tyr

Thr Gln

195

Val Asp 210

Pro Pro

Pro Pro

Thr Cys

Asn Trp

275

Arg Glu 290

Val Leu

Ser Asn

Lys Gly

Gly Asn 100

Ser Ala

Lys Ser

Tyr Phe

Trp Phe

Ser Thr

Thr Ser

135

Pro Glu 150

Ser Gly

165

Ser Leu 180

Thr Tyr

Lys Lys

Cys Pro

Lys Pro

245

Val Val 260

Tyr Val

Glu Glu

His Gln

Lys Ala

325

Glin Pro 340

Val His

Ser Ser

Ile Cys

Val Glu

215

Ala Pro 230

Lys Asp

Val Asp

Asp Gly

Tyr Asn

295

Asp Trp 310

Leu Pro

Arg Glu

Pro Tyr

105

Lys Gly 120

Gly Gly

Pro Val

Thr Phe

Val Val

185

Asn Val 200

Pro Lys

Pro Val

Thr Leu

Val Lys

265

Val Glu 280

Ser Thr

Leu Asn

Ala Pro

Pro Gln

345

Trp Gly

Gln Gly

Pro Ser

Thr Ala

Thr Val

155

Pro Ala 170

Thr Val

Asn His

Ser Cys

Ala Gly

235

Met Ile 250

His Glu

Val His

Tyr Arg

Gly Lys

315

Ile Glu

330

Val Tyr

Val Phe

125

Ala Leu 140

Ser Trp

Val Leu

Pro Ser

Lys Pro

205

Asp Lys 220

Pro Ser

Ser Arg

Asp Pro

Asn Ala

285

Val Val 300

Glu Tyr

Lys Thr

Thr Leu

Thr Leu 110

ProLeu

Gly Cys

Asn Ser

Gln Ser

175

Ser Ser 190

Ser Asp

Thr His

Val Phe

Thr Pro

255

Glu Val

270

Lys Thr

Ser Val

Lys Cys

Ile Ser

335

Pro Pro 350

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Leu 240

Glu

Lys

Lys

Leu

Lys 320

Lys

Ser

- 124 044325

Arg Glu Glu Met

355

Thr Lys Asn Gln Val Ser Leu 360

Thr Cys Asp Val Ser

365

Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp

375

Glu Ser Asp Gly Gln 380

Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro Pro Val

390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu

Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys 420

Ser Val Met His Glu Ala Leu His Asn

425 430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440 445 <210> 113 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 113

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

- 125 044325

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Tyr Trp Gly 115

Gln Gly Thr

Leu Val Thr 120

Val Ser Ser

125

Gly Lys Pro

Ser Gly Lys 130

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Pro Gly Ser

135

Gly Lys Pro

Gly Ser Gly

140

Lys Pro Gly

Val Thr Gln

150

Leu Thr Cys 165

Asn Trp Val

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Glu Pro Ser

Gly Ser Ser

170

Gln Gln Lys

185

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys

250

Thr Cys Pro

265

Leu Phe Pro 280

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Leu Thr Val 155

Thr Gly Ala

Pro Gly Lys

Pro Gly Val

205

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Asn Lys Ala

365

Ser Pro Gly

160

Val Thr Thr

175

Ser Pro Arg 190

Pro Ala Arg

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

Leu Pro Ala

- 126 044325

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 114 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 114

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Trp 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

- 127 044325

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210> 115 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 115

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser ArgSer

2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val

5560

- 128 044325

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr

Gly Arg Phe Thr Ile 70

Gln Met Asn Ser Leu

Arg Tyr Gly Asn Trp 100

Val Ser Ser Ala Ser

115

Ser Ser Lys Ser Thr 130

Lys Asp Tyr Phe Pro

150

Leu Thr Ser Gly Val

165

Leu Tyr Ser Leu Ser 180

Thr Gln Thr Tyr Ile 195

Val Asp Lys Lys Val 210

Pro Pro Cys Pro Ala

230

Pro Pro Lys Pro Lys

245

Thr Cys Val Val Val

260

Asn Trp Tyr Val Asp

275

Arg Glu Glu Glu Tyr 290

Val Leu His Gln Asp

Ser Arg Asp Asn Ser 75

Lys Asn Thr Leu Tyr 80

Arg Ala Glu Asp Thr

Ala Val Tyr Tyr Cys 95

Phe Pro Tyr Trp Gly 105

Gln Gly Thr Leu Val 110

Thr Lys Gly Pro Ser

120

Ser Gly Gly Thr Ala 135

Glu Pro Val Thr Val

155

His Thr Phe Pro Ala

170

Ser Val Val Thr Val

185

Cys Asn Val Asn His

200

Glu Pro Lys Ser Cys 215

Pro Pro Val Ala Gly

235

Asp Thr Leu Met Ile

250

Asp Val Lys His Glu 265

Gly Val Glu Val His

280

Asn Ser Thr Tyr Arg 295

Trp Leu Asn Gly Lys

Val Phe Pro Leu Ala

125

Ala Leu Gly Cys Leu 140

Ser Trp Asn Ser Gly

160

Val Leu Gln Ser Ser

175

Pro Ser Ser Ser Leu

190

Lys Pro Ser Asp Thr

205

Asp Lys Thr His Thr 220

Pro Ser Val Phe Leu

240

Ser Arg Thr Pro Glu

255

Asp Pro Glu Val Lys

270

Asn Ala Lys Thr Lys

285

Val Val Ser Val Leu 300

Glu Tyr Lys Cys Lys

- 129 044325

305

310

315

320

Val Ser Asn Lys Ala Leu Pro Ala Pro

325

Ile Glu Lys Thr 330

Ile Ser Lys

335

Ala Lys

Gly Gln Pro Arg Glu Pro Gln Val

340 345

Tyr Thr Leu Pro Pro Ser

350

Arg Glu Glu Met

355

Thr Lys Asn Gln Val Ser Leu 360

Thr Cys Asp Val Ser

365

Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp

375

Glu Ser Asp Gly Gln 380

Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro Pro Val

390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu

Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys 420

Ser Val Met His Glu Ala Leu His Asn

425 430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440 445 <210> 116 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 116

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr

- 130 044325

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Ser Tyr Val Ser Trp

110

Asp Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Leu Met Ile Ser Arg

290

Thr Pro Glu Val Thr

295

Cys Val Val Val Asp

300

Lys His Glu Asp Pro 305

Glu Val Lys Phe Asn 310

Trp Tyr Val Asp Gly 315

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

- 131 044325

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 117 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 117

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala 20 25

Ser Gln Asn Val Asp Thr Asn 30

- 132 044325

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210> 118 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 118

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

- 133 044325

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys 65

Gly

Arg

Phe

Thr

Ile 70

Ser

Arg

Asp

Asn

Ser 75

Lys

Asn

Thr

Leu

Tyr 80

Leu

Gln

Met

Asn

Ser 85

Leu

Arg

Ala

Glu

Asp 90

Thr

Ala

Val

Tyr

Tyr 95

Cys

Ala

Arg

Tyr

Gly 100

Asn

Trp

Phe

Pro

Tyr 105

Trp

Gly

Gln

Gly

Thr

110

Leu

Val

Thr

Val

Ser

115

Ser

Ala

Ser

Thr

Lys 120

Gly

Pro

Ser

Val

Phe

125

Pro

Leu

Ala

Pro

Ser

130

Ser

Lys

Ser

Thr

Ser

135

Gly

Gly

Thr

Ala

Ala

140

Leu

Gly

Cys

Leu

Val

145

Lys

Asp

Tyr

Phe

Pro

150

Glu

Pro

Val

Thr

Val

155

Ser

Trp

Asn

Ser

Gly 160

Ala

Leu

Thr

Ser

Gly 165

Val

His

Thr

Phe

Pro

170

Ala

Val

Leu

Gln

Ser

175

Ser

Gly

Leu

Tyr

Ser

180

Leu

Ser

Ser

Val

Val

185

Thr

Val

Pro

Ser

Ser

190

Ser

Leu

Gly

Thr

Gln

195

Thr

Tyr

Ile

Cys

Asn

200

Val

Asn

His

Lys

Pro

205

Ser

Asp

Thr

Lys

Val

210

Asp

Lys

Lys

Val

Glu

215

Pro

Lys

Ser

Cys

Asp 220

Lys

Thr

His

Thr

Cys 225

Pro

Pro

Cys

Pro

Ala

230

Pro

Pro

Val

Ala

Gly 235

Pro

Ser

Val

Phe

Leu 240

Phe Pro Pro Lys Pro 245 Lys Asp Thr Val Thr Cys Val 260 Val Val Asp Val

Leu Met Ile Ser Arg Thr Pro Glu

250 255

Lys His Glu Asp Pro Glu Val Lys

265 270

- 134 044325

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440445 <210> 119 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 119

Glu Val Gln Leu Val Glu Ser Gly Gly 1 5

Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25

Gly Leu Val Gln Pro Gly Gly

15

Gly Phe Thr Phe Ser Thr Tyr 30

- 135 044325

Ala

Gly

Ser 65

Leu

Tyr

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Met Ser

Arg Ile 50

Val Lys

Tyr Leu

Cys Val

Tyr Trp

115

Ser Gly 130

Gln Ala

Thr Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Trp Val

Arg Ser

Gly Arg

Gln Met

Arg His 100

Gly Gln

Lys Pro

Val Val

Thr Leu

165

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Arg Gln

Lys Tyr 55

Ph Thr 70

Asn Ser

Gly Asn

Gly Thr

Gly Ser

135

Thr Gln 150

Thr Cys

Trp Val

Thr Asn

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Ala Pro 40

Asn Asn

Ile Ser

Leu Arg

Phe Gly

105

Leu Val 120

Gly Lys

Glu Pro

Gly Ser

Gln Gln

185

Lys Arg 200

Gly Lys

Asp Tyr

Gly Thr

Thr Cys

265

Leu Phe

280

Gly Lys

Tyr Ala

Arg Asp

Ala Glu 90

Asp Ser

Thr Val

Pro Gly

Ser Leu

155

Ser Thr 170

Lys Pro

Ala Pro

Ala Ala

Tyr Cys

235

Lys Leu 250

Pro Pro

Pro Pro

Gly Leu 45

Thr Tyr 60

Asp Ser

Asp Thr

Tyr Val

Ser Ser

125

Ser Gly 140

Thr Val

Gly Ala

Gly Lys

Gly Val

205

Leu Thr

220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Glu Trp

Tyr Ala

Lys Asn

Ala Val

Ser Trp 110

Gly Lys

Lys Pro

Ser Pro

Val Thr

175

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

- 136 044325

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 120 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide

- 137 044325 <400> 120

Asp Ile Val Met Thr 1 5

Gln Ser Pro Ser Ser

Leu Ser Ala Ser Val

Asp Arg Val Thr Ile

Thr Cys Arg Ala Ser

Gln Asn Val Asp Thr 30

Val Ala Trp Tyr Gln 35

Gln Lys Pro Gly Gln 40

Ser Pro Lys Ala Leu 45

Tyr Ser Ala Ser Tyr 50

Arg Tyr Ser Gly Val 55

Pro Asp Arg Phe Thr 60

Ser Gly Ser Gly Thr 65

Asp Phe Thr Leu Thr 70

Ile Ser Ser Leu Gln 75

Glu Asp Phe Ala Thr 85

Tyr Phe Cys Gln Gln 90

Tyr Asp Ser Tyr Pro 95

Thr Phe Gly Gly Gly

100

Thr Lys Leu Glu Ile

105

Lys Arg Thr Val Ala

110

Pro Ser Val Phe Ile

115

Phe Pro Pro Ser Asp 120

Glu Gln Leu Lys Ser 125

Thr Ala Ser Val Val

130

Cys Leu Leu Asn Asn

135

Phe Tyr Pro Arg Glu

140

Lys Val Gln Trp Lys 145

Val Asp Asn Ala Leu 150

Gln Ser Gly Asn Ser 155

Glu Ser Val Thr Glu

165

Gln Asp Ser Lys Asp

170

Ser Thr Tyr Ser Leu

175

Ser Thr Leu Thr Leu

180

Ser Lys Ala Asp Tyr

185

Glu Lys His Lys Val

190

Ala Cys Glu Val Thr 195

His Gln Gly Leu Ser 200

Ser Pro Val Thr Lys

205

Gly

Asn

Ile

Gly

Pro 80

Leu

Ala

Gly

Ala

Gln 160

Ser

Tyr

Ser

Phe Asn Arg Gly Glu

210

Cys <210> 121 <211> 445 <212> PROTEIN <213> Artificial sequence

- 138 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 121

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Asp 25

Phe Ser Arg Ser 30

Trp Met Asn Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Glu Ile Asn

Pro Asp Ser Ser 55

Thr Ile Asn Tyr 60

Ala Thr Ser Val

Lys Gly Arg Phe 65

Thr Ile Ser Arg 70

Asp Asn Ser Lys 75

Asn Thr Leu Tyr 80

Leu Gln Met Asn

Ser Leu Arg Ala 85

Glu Asp Thr Ala 90

Val Tyr Tyr Cys

Ala Arg Tyr Gly

100

Asn Trp Phe Pro

Tyr Trp Gly Gln 105

Gly Thr Leu Val 110

Thr Val Ser Ser

115

Ala Ser Thr Lys

120

Gly Pro Ser Val

Phe Pro Leu Ala 125

Pro Ser Ser Lys 130

Ser Thr Ser Gly

135

Gly Thr Ala Ala

140

Leu Gly Cys Leu

Val Lys Asp Tyr 145

Phe Pro Glu Pro

150

Val Thr Val Ser

155

Trp Asn Ser Gly

160

Ala Leu Thr Ser

Gly Val His Thr 165

Phe Pro Ala Val

170

Leu Gln Ser Ser

175

Gly Leu Tyr Ser

180

Leu Ser Ser Val

Val Thr Val Pro 185

Ser Ser Ser Leu

190

Gly Thr Gln Thr

195

Tyr Ile Cys Asn

200

Val Asn His Lys

Pro Ser Asp Thr 205

Lys Val Asp Lys

210

Lys Val Glu Pro

215

Lys Ser Cys Asp

220

Lys Thr His Thr

Cys Pro Pro Cys Pro Ala Pro Pro Val

Ala Gly Pro Ser Val Phe Leu

- 139 044325

225 230 235240

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

245 250255

Val Thr Cys Val Val Val Asp Val Lys His Glu Asp Pro Glu Val Lys

260 265270

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440445 <210> 122 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic

- 140 044325 polypeptide <400> 122

Glu Val Gln Leu Val 1 5

Glu Ser Gly Gly Gly

Leu Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Thr Phe Ser Thr

Ala Met Asn Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Gly Arg Ile Arg Ser 50

Lys Tyr Asn Asn Tyr 55

Ala Thr Tyr Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Ser Tyr Val Ser Trp

110

Asp Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Gly

Tyr

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

- 141 044325

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Val 465

Leu

His Trp Val

Phe Gly Gly 245

Gly Thr Lys

250

Leu Thr Val

Leu Glu Pro

255

Ser Ser Asp

260

Lys Thr His

Thr Cys Pro

265

Pro Cys Pro

Ala Pro Pro 270

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys 370

Val Tyr Thr

Lys Leu Thr

Glu Trp Glu

420

Pro Val Leu

435

Val Asp Lys 450

Met His Glu

Ser Val Phe

Leu Phe Pro 280

Pro Lys Pro

285

Lys Asp Thr

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

375

Leu Pro Pro

390

Cys Leu Val 405

Ser Asn Gly

Asp Ser Asp

Ser Arg Trp

455

Ala Leu His

470

Ser Pro Gly Lys

485

Glu Val Thr

Cys Val Val

300

Val Asp Val

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Lys Ala Lys

Ser Arg Glu

Lys Gly Phe

410

Gln Pro Glu

425

Gly Ser Phe 440

Gln Gln Gly

Asn His Tyr

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Asn Lys Ala

365

Gly Gln Pro

380

Gln Met Thr 395

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

445

Asn Val Phe

460

Thr Gln Lys 475

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

400

Asp Ile Ala 415

Lys Thr Thr 430

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

480

- 142 044325 <210> 123 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 123

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

- 143 044325

Phe Asn Arg Gly Glu Cys

210 <210> 124 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 124

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185190

- 144 044325

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Gly

Pro 385

Ser

Gln

His

Thr Gln Thr Tyr Ile 195

Val Asp Lys Lys Val 210

Pro Pro Cys Pro Ala

230

Pro Pro Lys Pro Lys

245

Thr Cys Val Val Val

260

Asn Trp Tyr Val Asp

275

Arg Glu Glu Glu Tyr 290

Val Leu His Gln Asp

310

Ser Asn Lys Ala Leu

325

Lys Gly Gln Pro Arg 340

Glu Glu Met Thr Lys

355

Phe Tyr Pro Ser Asp 370

Glu Asn Asn Tyr Lys

390

Phe Phe Leu Tyr Ser

405

Gly Asp Val Phe Ser 420

Tyr Thr Gln Lys Ser 435

Cys Asn Val Asn His

200

Glu Pro Lys Ser Cys 215

Pro Pro Val Ala Gly

235

Asp Thr Leu Met Ile

250

Asp Val Lys His Glu 265

Gly Val Glu Val His

280

Asn Ser Thr Tyr Arg 295

Trp Leu Asn Gly Lys

315

Pro Ala Pro Ile Glu

330

Glu Pro Gln Val Tyr

345

Asn Gln Val Ser Leu

360

Ile Ala Val Glu Trp 375

Thr Thr Pro Pro Val

395

Lys Leu Thr Val Asp

410

Cys Ser Val Met His

425

Leu Ser Leu Ser Pro

440

Lys Pro Ser Asp Thr

205

Asp Lys Thr His Thr 220

Pro Ser Val Phe Leu

240

Ser Arg Thr Pro Glu

255

Asp Pro Glu Val Lys

270

Asn Ala Lys Thr Lys

285

Val Val Ser Val Leu 300

Glu Tyr Lys Cys Lys

320

Lys Thr Ile Ser Lys

335

Thr Leu Pro Pro Ser

350

Thr Cys Asp Val Ser

365

Glu Ser Asp Gly Gln 380

Leu Asp Ser Asp Gly

400

Lys Ser Arg Trp Glu

415

Glu Ala Leu His Asn

430

Gly Lys

445

- 145 044325 <210> 125 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 125

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

- 146 044325

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys 370

Val Tyr Thr

Lys Leu Thr

Glu Trp Glu

420

Pro Val Leu

435

Val Asp Lys

Leu Leu Gly

215

Gly Lys Ala

Ala Leu Thr

220

Ile Ser Gly

Asp Glu Ala

230

Asp Tyr Tyr

Cys Ala Leu 235

Trp Tyr Ser

240

Phe Gly Cys 245

Gly Thr Lys

250

Leu Thr Val

Leu Glu Pro

255

Lys Thr His

Thr Cys Pro

265

Pro Cys Pro

Ala Pro Pro 270

Ser Val Phe

Leu Phe Pro 280

Pro Lys Pro

285

Lys Asp Thr

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

375

Leu Pro Pro

390

Cys Leu Val 405

Ser Asn Gly

Asp Ser Asp

Ser Arg Trp

Glu Val Thr

Cys Val Val

300

Val Asp Val

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Lys Ala Lys

Ser Arg Glu

Lys Gly Phe

410

Gln Pro Glu

425

Gly Ser Phe 440

Gln Gln Gly

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Asn Lys Ala

365

Gly Gln Pro

380

Gln Met Thr 395

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

445

Asn Val Phe

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

400

Asp Ile Ala 415

Lys Thr Thr 430

Ser Lys Leu

Ser Cys Ser

- 147 044325

450 455 460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485 <210> 126 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 126

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

- 148 044325

165 170 175 Ser Thr Leu Thr 180 Leu Ser Lys Ala Asp 185 Tyr Glu Lys His Lys 190 Val Tyr Ala Cys Glu 195 Val Thr His Gln Gly 200 Leu Ser Ser Pro Val 205 Thr Lys Ser Phe Asn 210 Arg Gly Glu Cys

<210> 127 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 127

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Tyr Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Gln Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

- 149 044325

145

150

155

Ala Leu Thr Ser Gly

165

Val His Thr Phe Pro

170

Ala Val Leu Gln Ser

175

Gly Leu Tyr Ser Leu

180

Ser Ser Val Val Thr

185

Val Pro Ser Ser Ser

190

Gly Thr Gln Thr Tyr 195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asp

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Asp Lys Thr His

220

Cys Pro Pro Cys Pro 225

Ala Pro Pro Val Ala 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Lys His

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Glu

290

Tyr Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Val Ser Asn Lys Ala

325

Leu Pro Ala Pro Ile

330

Glu Lys Thr Ile Ser

335

Ala Lys Gly Gln Pro

340

Arg Glu Pro Gln Val

345

Tyr Thr Leu Pro Pro

350

Arg Glu Glu Met Thr

355

Lys Asn Gln Val Ser 360

Leu Thr Cys Asp Val

365

Gly Phe Tyr Pro Ser

370

Asp Ile Ala Val Glu

375

Trp Glu Ser Asp Gly

380

Pro Glu Asn Asn Tyr 385

Lys Thr Thr Pro Pro 390

Val Leu Asp Ser Asp 395

160

Ser

Leu

Thr

Thr

Leu 240

Glu

Lys

Lys

Leu

Lys 320

Lys

Ser

Ser

Gln

Gly 400

- 150 044325

Ser Phe Phe Leu

Tyr Ser Lys Leu 405

Thr Val Asp Lys 410

Ser Arg Trp Glu

415

Gln Gly Asp Val

420

Phe Ser Cys Ser

Val Met His Glu 425

Ala Leu His Asn

430

His Tyr Thr Gln

435

Lys Ser Leu Ser

440

Leu Ser Pro Gly

Lys 445 <210> 128 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 128

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

- 151 044325

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Thr Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Thr Leu

165

Thr Cys

Gly Ser

Ala Asn

180

Trp Val

Gln Gln

185

Gly Gly

Thr Asn

Lys Arg 200

Ser Leu

Leu Gly

215

Gly Lys

Ser Thr 170

Lys Pro

Ala Pro

Ala Ala

Gly Ala

Gly Lys

Gly Val

205

Leu Thr

220

Glu Asp

Glu Ala

230

Asp Tyr

Tyr Cys

235

Ala Leu

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Gly Cys

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Gly Thr

Lys Leu 250

Thr Val

Val Thr

175

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

- 152 044325

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 129 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 129

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Trp 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

- 153 044325

Thr Ala Ser Val Val

130

Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu

135 140

Lys Val Gln Trp Lys 145

Val Asp Asn Ala Leu Gln Ser Gly Asn Ser

150 155

Glu Ser Val Thr Glu

165

Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu

170 175

Ser Thr Leu Thr Leu

180

Ser Lys Ala Asp Tyr Glu Lys His Lys Val

185 190

Ala Cys Glu Val Thr 195

His Gln Gly Leu Ser Ser Pro Val Thr Lys

200 205

Ala

Gln 160

Ser

Tyr

Ser

Phe Asn Arg Gly Glu 210

Cys <210> 130 <211> 207 <212> PROTEIN <213> Homo sapiens <400> 130

Met Gln Ser Gly Thr 1 5

His Trp Arg Val Leu Gly Leu Cys Leu Leu

15

Val Gly Val Trp Gly

Gln Asp Gly Asn Glu Glu Met Gly Gly Ile

thirty

Gln Thr Pro Tyr Lys 35

Val Ser Ile Ser Gly Thr Thr Val Ile Leu 40 45

Cys Pro Gln Tyr Pro 50

Gly Ser Glu Ile Leu Trp Gln His Asn Asp

60

Asn Ile Gly Gly Asp 65

Glu Asp Asp Lys Asn Ile Gly Ser Asp Glu 70 75

His Leu Ser Leu Lys 85

Glu Phe Ser Glu Leu Glu Gln Ser Gly Tyr 90 95

Val Cys Tyr Pro Arg

100

Gly Ser Lys Pro Glu Asp Ala Asn Phe Tyr

105 110

Tyr Leu Arg Ala Arg 115

Val Cys Glu Asn Cys Met Glu Met Asp Val

120 125

Ser

Thr

Thr

Lys

Asp 80

Tyr

Leu

Met

- 154 044325

Ser Val Ala Thr Ile

130

Val Ile Val Asp Ile

135

Cys Ile Thr Gly Gly 140

Leu Leu Leu Val Tyr 145

Tyr Trp Ser Lys Asn 150

Arg Lys Ala Lys Ala 155

Pro Val Thr Arg Gly

165

Ala Gly Ala Gly Gly

170

Arg Gln Arg Gly Gln

175

Lys Glu Arg Pro Pro

180

Pro Val Pro Asn Pro

185

Asp Tyr Glu Pro Ile

190

Leu

Lys 160

Asn

Arg

Lys Gly Gln Arg Asp

195

Leu Tyr Ser Gly Leu 200

Asn Gln Arg Arg Ile 205 <210> 131 <211> 300 <212> PROTEIN <213> Homo sapiens <400> 131

Met Ala Asn Cys Glu 1 5

Phe Ser Pro Val Ser

Gly Asp Lys Pro Cys

Arg Leu Ser Arg Arg 20

Ala Gln Leu Cys Leu

Gly Val Ser Ile Leu 30

Leu Ile Leu Val Val

Val Leu Ala Val Val

Val Pro Arg Trp Arg 45

Gln Trp Ser Gly Pro 50

Gly Thr Thr Lys Arg 55

Phe Pro Glu Thr Val 60

Ala Arg Cys Val Lys 65

Tyr Thr Glu Ile His 70

Pro Glu Met Arg His 75

Asp Cys Gln Ser Val 85

Trp Asp Ala Phe Lys 90

Gly Ala Phe Ile Ser 95

His Pro Cys Asn Ile

100

Thr Glu Glu Asp Tyr

105

Gln Pro Leu Met Lys

110

Gly Thr Gln Thr Val 115

Pro Cys Asn Lys Ile 120

Leu Leu Trp Ser Arg

125

Lys Asp Leu Ala His 130

Gln Phe Thr Gln Val

135

Gln Arg Asp Met Phe 140

Cys

Val

Gln

Leu

Val 80

Lys

Leu

Ile

Thr

Cys

Leu Glu Asp Thr Leu

Leu Gly Tyr Leu Ala

Asp Asp Leu Thr Trp

- 155 044325

145

150

155

Gly Glu Phe Asn Thr

165

Ser Lys Ile Asn Tyr

170

Gln Ser Cys Pro Asp

175

Arg Lys Asp Cys Ser

180

Asn Asn Pro Val Ser

185

Val Phe Trp Lys Thr

190

Ser Arg Arg Phe Ala

195

Glu Ala Ala Cys Asp 200

Val Val His Val Met

205

Asn Gly Ser Arg Ser

210

Lys Ile Phe Asp Lys

215

Asn Ser Thr Phe Gly 220

Val Glu Val His Asn 225

Leu Gln Pro Glu Lys 230

Val Gln Thr Leu Glu 235

Trp Val Ile His Gly

245

Gly Arg Glu Asp Ser

250

Arg Asp Leu Cys Gln

255

Pro Thr Ile Lys Glu

260

Leu Glu Ser Ile Ile

265

Ser Lys Arg Asn Ile

270

Phe Ser Cys Lys Asn

275

Ile Tyr Arg Pro Asp

280

Lys Phe Leu Gln Cys

285

160

Trp

Val

Leu

Ser

Ala 240

Asp

Gln

Val

Lys Asn Pro Glu Asp

290

Ser Ser Cys Thr Ser

295

Glu Ile

300 <210> 132 <211> 258 <212> PROTEIN <213> Homo sapiens <400> 132

Val Pro Arg Trp Arg 1 5

Gln Gln Trp Ser Gly

Pro Gly Thr Thr Lys

Phe Pro Glu Thr Val

Leu Ala Arg Cys Val

Lys Tyr Thr Glu Ile 30

Pro Glu Met Arg His 35

Val Asp Cys Gln Ser 40

Val Trp Asp Ala Phe 45

Gly Ala Phe Ile Ser 50

Lys His Pro Cys Asn 55

Ile Thr Glu Glu Asp 60

Gln Pro Leu Met Lys 65

Leu Gly Thr Gln Thr 70

Val Pro Cys Asn Lys 75

Arg

His

Lys

Tyr

Ile 80

- 156 044325

Leu Leu Trp Ser Arg Ile Lys Asp Leu Ala His Gln Phe Thr Gln Val 85 9095

Gln Arg Asp Met Phe Thr Leu Glu Asp Thr Leu Leu Gly Tyr Leu Ala

100 105110

Asp Asp Leu Thr Trp Cys Gly Glu Phe Asn Thr Ser Lys Ile Asn Tyr

115 120125

Gln Ser Cys Pro Asp Trp Arg Lys Asp Cys Ser Asn Asn Pro Val Ser

130 135140

Val Phe Trp Lys Thr Val Ser Arg Arg Phe Ala Glu Ala Ala Cys Asp

145 150 155160

Val Val His Val Met Leu Asn Gly Ser Arg Ser Lys Ile Phe Asp Lys

165 170175

Asn Ser Thr Phe Gly Ser Val Glu Val His Asn Leu Gln Pro Glu Lys

180 185190

Val Gln Thr Leu Glu Ala Trp Val Ile His Gly Gly Arg Glu Asp Ser

195 200205

Arg Asp Leu Cys Gln Asp Pro Thr Ile Lys Glu Leu Glu Ser Ile Ile

210 215220

Ser Lys Arg Asn Ile Gln Phe Ser Cys Lys Asn Ile Tyr Arg Pro Asp

225 230 235240

Lys Phe Leu Gln Cys Val Lys Asn Pro Glu Asp Ser Ser Cys Thr Ser

245 250255

Glu Ile <210> 133 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 133

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15

- 157 044325 <210> 134 <211> 18 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 134

Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr

5 10 15

Lys Gly <210> 135 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 135

Ile Arg Pro Arg Ala Ile Gly Gly Ser Lys Pro Arg Val Ala

5 10 <210> 136 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 136

Gly Lys Gly Gly Ser Gly Lys Gly Gly Ser Gly Lys Gly Gly Ser

5 10 15 <210> 137 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 137

Gly Gly Lys Gly Ser Gly Gly Lys Gly Ser Gly Gly Lys Gly Ser

- 158 044325 <210> 138 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 138

Gly Gly Gly Lys Ser Gly Gly Gly Lys Ser Gly Gly Gly Lys Ser

5 10 15 <210> 139 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 139

Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser

5 10 15 <210> 140 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 140

Gly Gly Gly Lys Ser Gly Gly Lys Gly Ser Gly Lys Gly Gly Ser

5 10 15 <210> 141 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 141

Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser

5 10 15

- 159 044325 <210> 142 <211> 20 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 142

Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly

5 10 15

Lys Pro Gly Ser 20 <210> 143 <211> 20 <212> PROTEIN <213> Artificial Sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 143

Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser Gly Lys Gly Lys Ser Gly

5 10 15

Lys Gly Lys Ser 20 <210> 144 <211> 20 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 144

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

5 10 15

Gly Gly Gly Ser 20 <210> 145 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

- 160 044325 <221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 145

Ser Thr Ala Gly Asp Thr His Leu Gly Gly Glu Asp Phe Asp

5 10 <210> 146 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 146

Gly Glu Gly Gly Ser Gly Glu Gly Gly Ser Gly Glu Gly Gly Ser

5 10 15 <210> 147 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 147

Gly Gly Glu Gly Ser Gly Gly Glu Gly Ser Gly Gly Glu Gly Ser

5 10 15 <210> 148 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 148

Gly Gly Gly Glu Ser Gly Gly Gly Glu Ser Gly Gly Gly Glu Ser

5 10 15 <210> 149 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide

- 161 044325 <400> 149

Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser 1 5 10 15 <210> 150 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 150

Gly Gly Gly Glu Ser Gly Gly Glu Gly Ser Gly Glu Gly Gly Ser

5 10 15 <210> 151 <211> 20 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 151

Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser Gly Glu Gly Glu Ser Gly

5 10 15

Glu Gly Glu Ser 20 <210> 152 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 152

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

5 10 15 <210> 153 <211> 20 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic

- 162 044325 peptide <400> 153

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

15

Gly Gly Gly Ser 20 <210> 154 <211> 18 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 154

Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr

5 10 15

Lys Gly <210> 155 <211> 19 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 155

Pro Arg Gly Ala Ser Lys Ser Gly Ser Ala Ser Gln Thr Gly Ser Ala

5 10 15

Pro Gly Ser <210> 156 <211> 19 <212> PROTEIN <213> Artificial Sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 156

Gly Thr Ala Ala Ala Gly Ala Gly Ala Ala Gly Gly Ala Ala Ala Gly

5 10 15

- 163 044325

Ala Ala Gly <210> 157 <211> 19 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 157

Gly Thr Ser Gly Ser Ser Gly Ser Gly Ser Gly Gly Ser Gly Ser Gly

5 10 15

Gly Gly Gly <210> 158 <211> 20 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 158

Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly

Lys Pro Gly Ser 20 <210> 159 <211> 445 <212> PROTEIN <213> Artificial Sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 159

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

- 164 044325

Ser Glu Ile Asn Pro 50

Asp Ser Ser Thr Ile 55

Asn Tyr Ala Thr Ser 60

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn 70

Ser Lys Asn Thr Leu 75

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Arg Tyr Gly Asn

100

Trp Phe Pro Tyr Trp

105

Gly Gln Gly Thr Leu

110

Thr Val Ser Ser Ala

115

Ser Thr Lys Gly Pro

120

Ser Val Phe Pro Leu

125

Pro Ser Ser Lys Ser 130

Thr Ser Gly Gly Thr

135

Ala Ala Leu Gly Cys 140

Val Lys Asp Tyr Phe 145

Pro Glu Pro Val Thr 150

Val Ser Trp Asn Ser 155

Ala Leu Thr Ser Gly

165

Val His Thr Phe Pro

170

Ala Val Leu Gln Ser

175

Gly Leu Tyr Ser Leu

180

Ser Ser Val Val Thr

185

Val Pro Ser Ser Ser

190

Gly Thr Gln Thr Tyr

195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asp

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Asp Lys Thr His

220

Cys Pro Pro Cys Pro 225

Ala Pro Pro Val Ala 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Lys His

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val

280

His Asn Ala Lys Thr

285

Val

Tyr 80

Cys

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Leu 240

Glu

Lys

Lys

- 165 044325

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440445 <210> 160 <211> 714 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 160

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

- 166 044325

Ser

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Glu Ile Asn 50

Gly Arg Phe

Gln Met Asn

Arg Tyr Gly

100

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Pro Asp Ser

Thr Ile Ser

Ser Leu Arg 85

Asn Trp Phe

Ala Ser Thr

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Gln Tyr Asn

295

Ser Thr Ile

Arg Asp Asn

Ala Glu Asp 90

Pro Tyr Trp 105

Lys Gly Pro 120

Gly Gly Thr

Pro Val Thr

Thr Phe Pro 170

Val Val Thr 185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Asn Tyr Ala 60

Ser Lys Asn 75

Thr Ala Val

Gly Gln Gly

Ser Val Phe

125

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Thr Ser Val

Thr Leu Tyr

Tyr Tyr Cys 95

Thr Leu Val 110

Pro Leu Ala

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asn Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

- 167 044325

Thr 305

Val

Ala

Arg

Gly

Pro 385

Ser

Gln

His

Gly

Val 465

Ser

Val

Ser

Arg

Met 545

Val Leu

Ser Asn

Lys Gly

Glu Gln

355

Phe Tyr 370

Glu Asn

Phe Phe

Gly Asn

Tyr Thr

435

Ser Gly 450

Glu Ser

Cys Ala

Arg Gln

Lys Tyr

515

Ph Thr 530

Asn Ser

His Gln

Lys Ala

325

Glin Pro 340

Met Thr

Pro Ser

Asn Tyr

Leu Tyr

405

Val Phe 420

Gln Lys

Gly Gly

Gly Gly

Ala Ser

485

Ala Pro 500

Asn Asn

Ile Ser

Leu Arg

Asp Trp 310

Leu Pro

Arg Glu

Lys Asn

Asp Ile

375

Lys Thr 390

Ser Lys

Ser Cys

Ser Leu

Gly Ser

455

Gly Leu 470

Gly Phe

Gly Lys

Tyr Ala

Arg Asp

535

Ala Glu 550

Leu Asn

Ala Pro

Pro Gln

345

Gln Val 360

Ala Val

Thr Pro

Leu Thr

Ser Val

425

Ser Leu

440

Gly Gly

Val Gln

Thr Phe

Gly Leu

505

Thr Tyr 520

Asp Ser

Asp Thr

Gly Lys

315

Glu Tyr

Lys Cys

Ile Glu

330

Lys Thr

Ile Ser

335

Val Tyr

Thr Leu

Pro Pro 350

Lys Leu

Thr Cys

365

Leu Val

Glu Trp

Glu Ser 380

Asn Gly

Pro Val

395

Leu Asp

Ser Asp

Val Asp 410

Met His

Ser Pro

Gly Gly

Pro Gly

475

Ser Thr

490

Glu Trp

Tyr Ala

Lys Asn

Ala Val

555

Lys Ser

Glu Ala

Gly Lys

445

Ser Glu

460

Gly Ser

Tyr Ala

Val Gly

Asp Ser

525

Thr Leu 540

Tyr Tyr

Arg Trp

415

Leu His 430

Gly Gly

Val Gln

Leu Arg

Met Asn

495

Arg Ile 510

Val Lys

Tyr Leu

Cys Val

Lys 320

Lys

Ser

Lys

Gln

Gly 400

Gln

Asn

Gly

Leu

Leu 480

Trp

Arg

Gly

Gln

Arg 560

- 168 044325

His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp

565 570

Phe Ala Tyr Trp Gly

575

Gln Gly Thr Leu Val Thr Val 580

Ser Ser Gly Lys Pro Gly Ser Gly Lys

585 590

Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gln Ala Val

595 600 605

Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr

610 615 620

Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala

625 630 635 640

Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly

645 650 655

Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser

660 665 670

Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu

675 680 685

Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val

690 695 700

Phe Gly Gly Gly Thr

Lys Leu Thr Val Leu

705

710 <210> 161 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 161

Asp Ile Val Met 1

Thr Gln Ser Pro 5

Ser Ser Leu Ser 10

Ala Ser Val Gly 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Gln Asn 25

Val Asp Thr Asn 30

Val Ala Trp Tyr

Gln Gln Lys Pro 40

Gly Gln Ser Pro

Lys Ala Leu Ile 45

- 169 044325

Tyr

Ser Ala Ser Tyr Arg Tyr Ser

55

Gly Val Pro

Asp Arg Phe Thr Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu 210

Cys <210> 162 <211> 585 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 162

Glu Val Gln Leu Val Glu Ser Gly Gly 1 5

Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu 20

Ser Cys Ala Ala Ser

Gly Phe Asp Phe Ser Arg Ser 30

- 170 044325

Trp Met Asn 35 Trp Val Arg Gln Ala 40 Pro Gly Lys Gly Leu 45 Glu Trp Val Ser Glu 50 Ile Asn Pro Asp Ser 55 Ser Thr Ile Asn Tyr 60 Ala Thr Ser Val Lys 65 Gly Arg Phe Thr Ile 70 Ser Arg Asp Asn Ser 75 Lys Asn Thr Leu Tyr 80 Leu Gln Met Asn Ser 85 Leu Arg Ala Glu Asp 90 Thr Ala Val Tyr Tyr 95 Cys Ala Arg Tyr Gly 100 Asn Trp Phe Pro Tyr 105 Trp Gly Gln Gly Thr 110 Leu Val Thr Val Ser 115 Ser Ala Ser Thr Lys 120 Gly Pro Ser Val Phe 125 Pro Leu Ala Pro Ser 130 Ser Lys Ser Thr Ser 135 Gly Gly Thr Ala Ala 140 Leu Gly Cys Leu Val 145 Lys Asp Tyr Phe Pro 150 Glu Pro Val Thr Val 155 Ser Trp Asn Ser Gly 160 Ala Leu Thr Ser Gly 165 Val His Thr Phe Pro 170 Ala Val Leu Gln Ser 175 Ser Gly Leu Tyr Ser 180 Leu Ser Ser Val Val 185 Thr Val Pro Ser Ser 190 Ser Leu Gly Thr Gln 195 Thr Tyr Ile Cys Asn 200 Val Asn His Lys Pro 205 Ser Asp Thr Lys Val 210 Asp Lys Lys Val Glu 215 Pro Lys Ser Cys Asp 220 Lys Thr His Thr Cys 225 Pro Pro Cys Pro Ala 230 Pro Pro Val Ala Gly 235 Pro Ser Val Phe Leu 240 Phe Pro Pro Lys Pro 245 Lys Asp Thr Leu Met 250 Ile Ser Arg Thr Pro 255 Glu Val Thr Cys Val 260 Val Val Asp Val Lys 265 His Glu Asp Pro Glu 270 Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

- 171 044325

275

280

285

Pro Arg Glu Glu Glu 290

Tyr Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Val Ser Asn Lys Ala

325

Leu Pro Ala Pro Ile

330

Glu Lys Thr Ile Ser

335

Ala Lys Gly Gln Pro

340

Arg Glu Pro Gln Val

345

Tyr Thr Leu Pro Pro

350

Arg Glu Glu Met Thr

355

Lys Asn Gln Val Ser

360

Leu Thr Cys Asp Val

365

Gly Phe Tyr Pro Ser

370

Asp Ile Ala Val Glu

375

Trp Glu Ser Asp Gly

380

Pro Glu Asn Asn Tyr 385

Lys Thr Thr Pro Pro 390

Val Leu Asp Ser Asp 395

Ser Phe Phe Leu Tyr

405

Ser Lys Leu Thr Val

410

Asp Lys Ser Arg Trp

415

Gln Gly Asp Val Phe

420

Ser Cys Ser Val Met

425

His Glu Ala Leu His

430

His Tyr Thr Gln Lys 435

Ser Leu Ser Leu Ser

440

Pro Gly Lys Gly Gly 445

Gly Ser Gly Gly Gly 450

Gly Ser Gly Gly Gly 455

Gly Ser Glu Val Gln 460

Val Glu Ser Gly Gly 465

Gly Leu Val Gln Pro 470

Gly Gly Ser Leu Arg 475

Ser Cys Ala Ala Ser

485

Gly Phe Thr Phe Ser

490

Thr Tyr Ala Met Asn

495

Val Arg Gln Ala Pro

500

Gly Lys Gly Leu Glu

505

Trp Val Gly Arg Ile

510

Ser Lys Tyr Asn Asn

515

Tyr Ala Thr Tyr Tyr

520

Ala Asp Ser Val Lys

525

Leu

Lys 320

Lys

Ser

Ser

Gln

Gly 400

Glu

Asn

Gly

Leu

Leu 480

Trp

Arg

Gly

- 172 044325

Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn

530 535

Thr Leu Tyr Leu Gln 540

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val

545 550 555

Tyr Tyr Cys Val Arg

560

His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp

565 570

Phe Ala Tyr Trp Gly

575

Gln Gly Thr Leu Val Thr Val Ser Ser

580 585 <210> 163 <211> 569 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 163

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120 125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135 140

- 173 044325

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Gly

Pro 385

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

340

Glu Gln Met

355

Phe Tyr Pro 370

Glu Asn Asn

Phe Pro Glu

150

Pro Val Thr

Val Ser Trp 155

Asn Ser Gly

160

Gly Val His 165

Thr Phe Pro

170

Ala Val Leu

Gln Ser Ser

175

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Gln Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Arg Glu

Thr Lys Asn

Ser Asp Ile

375

Tyr Lys Thr

390

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Pro Gln Val

345

Gln Val Lys 360

Ala Val Glu

Thr Pro Pro

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Leu Thr Cys

365

Trp Glu Ser

380

Val Leu Asp 395

Ser Ser Leu 190

Ser Asn Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser 350

Leu Val Lys

Asn Gly Gln

Ser Asp Gly

400

- 174 044325

Ser

Phe

Phe

Leu

Tyr 405

Ser

Lys

Leu

Thr

Val

410

Asp

Lys

Ser

Arg

Trp 415

Gln

Gln

Gly

Asn

Val

420

Phe

Ser

Cys

Ser

Val

425

Met

His

Glu

Ala

Leu

430

His

Asn

His

Tyr

Thr

435

Gln

Lys

Ser

Leu

Ser

440

Leu

Ser

Pro

Gly

Lys

445

Gly

Gly

Gly

Gly

Ser 450

Gly

Gly

Gly

Gly

Ser

455

Gly

Gly

Gly

Gly

Ser 460

Gln

Ala

Val

Val

Thr

465

Gln

Glu

Pro

Ser

Leu

470

Thr

Val

Ser

Pro

Gly 475

Gly

Thr

Val

Thr

Leu

480

Thr

Cys

Gly

Ser

Ser

485

Thr

Gly

Ala

Val

Thr

490

Thr

Ser

Asn

Tyr

Ala

495

Asn

Trp

Val

Gln

Gln

500

Lys

Pro

Gly

Lys

Ser

505

Pro

Arg

Gly

Leu

Ile

510

Gly

Gly

Thr

Asn

Lys

515

Arg

Ala

Pro

Gly

Val

520

Pro

Ala

Arg

Phe

Ser

525

Gly

Ser

Leu

Leu

Gly 530

Gly

Lys

Ala

Ala

Leu

535

Thr

Ile

Ser

Gly

Ala

540

Gln

Pro

Glu

Asp

Glu

545

Ala

Asp

Tyr

Tyr

Cys 550

Ala

Leu

Trp

Tyr

Ser

555

Asn

His

Trp

Val

Phe

560

Gly

Gly

Gly

Thr

Lys 565

Leu

Thr

Val

Leu <210> 164 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 164

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr 20

Ile Thr Cys Arg Ala

Ser Gln Asn Val Asp Thr Asn 30

- 175 044325

Val Ala Trp Tyr Gln Gln Lys Pro

40

Tyr Ser Ala Ser Tyr Arg Tyr Ser

55

Gly Gln Ser Pro Lys Ala Leu Ile 45

Gly Val Pro Asp Arg Phe Thr Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210> 165 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 165

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

- 176 044325

Ser

Trp

Ser

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Leu Arg Leu Ser Cys 20

Met Asn Trp Val Arg 35

Glu Ile Asn Pro Asp 50

Gly Arg Phe Thr Ile 70

Gln Met Asn Ser Leu

Arg Tyr Gly Asn Trp 100

Val Ser Ser Ala Ser

115

Ser Ser Lys Ser Thr 130

Lys Asp Tyr Phe Pro

150

Leu Thr Ser Gly Val

165

Leu Tyr Ser Leu Ser 180

Thr Gln Thr Tyr Ile 195

Val Asp Lys Lys Val 210

Pro Pro Cys Pro Ala

230

Pro Pro Lys Pro Lys

245

Thr Cys Val Val Val

260

Ala Ala Ser Gly Phe 25

Gln Ala Pro Gly Lys 40

Ser Ser Thr Ile Asn 55

Ser Arg Asp Asn Ser 75

Arg Ala Glu Asp Thr

Phe Pro Tyr Trp Gly 105

Thr Lys Gly Pro Ser 120

Ser Gly Gly Thr Ala 135

Glu Pro Val Thr Val

155

His Thr Phe Pro Ala

170

Ser Val Val Thr Val

185

Cys Asn Val Asn His

200

Glu Pro Lys Ser Cys 215

Pro Pro Val Ala Gly

235

Asp Thr Leu Met Ile

250

Asp Val Lys His Glu 265

Asp Phe Ser Arg Ser 30

Gly Leu Glu Trp Val 45

Tyr Ala Thr Ser Val 60

Lys Asn Thr Leu Tyr 80

Ala Val Tyr Tyr Cys 95

Gln Gly Thr Leu Val 110

Val Phe Pro Leu Ala

125

Ala Leu Gly Cys Leu 140

Ser Trp Asn Ser Gly

160

Val Leu Gln Ser Ser

175

Pro Ser Ser Ser Leu

190

Lys Pro Ser Asp Thr

205

Asp Lys Thr His Thr 220

Pro Ser Val Phe Leu

240

Ser Arg Thr Pro Glu

255

Asp Pro Glu Val Lys 270

- 177 044325

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

275 280285

Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

290 295300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440445 <210> 166 <211> 718 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 166

Glu Val Gln Leu Val Glu Ser Gly Gly 1 5

Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25

Gly Leu Val Gln Pro Gly Gly

15

Gly Phe Asp Phe Ser Arg Ser 30

- 178 044325

Trp Met Asn Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Glu Ile Asn Pro 50

Asp Ser Ser Thr Ile 55

Asn Tyr Ala Thr Ser 60

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn 70

Ser Lys Asn Thr Leu 75

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Arg Tyr Gly Asn

100

Trp Phe Pro Tyr Trp

105

Gly Gln Gly Thr Leu

110

Thr Val Ser Ser Ala

115

Ser Thr Lys Gly Pro 120

Ser Val Phe Pro Leu

125

Pro Ser Ser Lys Ser 130

Thr Ser Gly Gly Thr

135

Ala Ala Leu Gly Cys 140

Val Lys Asp Tyr Phe 145

Pro Glu Pro Val Thr 150

Val Ser Trp Asn Ser 155

Ala Leu Thr Ser Gly

165

Val His Thr Phe Pro

170

Ala Val Leu Gln Ser

175

Gly Leu Tyr Ser Leu

180

Ser Ser Val Val Thr

185

Val Pro Ser Ser Ser

190

Gly Thr Gln Thr Tyr 195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asn

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Gly Gly Gly Gly

220

Gly Gly Gly Gly Ser 225

Glu Val Gln Leu Val 230

Glu Ser Gly Gly Gly 235

Val Gln Pro Gly Gly

245

Ser Leu Arg Leu Ser

250

Cys Ala Ala Ser Gly

255

Thr Phe Ser Thr Tyr

260

Ala Met Asn Trp Val

265

Arg Gln Ala Pro Gly

270

Gly Leu Glu Trp Val

Gly Arg Ile Arg Ser

Lys Tyr Asn Asn Tyr

Val

Val

Tyr 80

Cys

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Ser

Leu 240

Phe

Lys

Ala

- 179 044325

275

280

285

Thr

Asp 305

Asp

Tyr

Ser

Ser

Thr 385

Gly

Gly

Gly

Leu

Ala 465

Thr

Thr

Leu

Tyr Tyr Ala Asp Ser 290

Ser Lys Asn Thr Leu

310

Thr Ala Val Tyr Tyr

325

Val Ser Trp Phe Ala

340

Ser Gly Lys Pro Gly

355

Gly Lys Pro Gly Ser 370

Val Ser Pro Gly Gly

390

Ala Val Thr Thr Ser

405

Lys Ser Pro Arg Gly 420

Val Pro Ala Arg Phe

435

Thr Ile Ser Gly Ala 450

Leu Trp Tyr Ser Asn

470

Val Leu Gly Gly Gly

485

Cys Pro Pro Cys Pro 500

Phe Pro Pro Lys Pro 515

Val Lys Gly Arg Phe 295

Tyr Leu Gln Met Asn

315

Cys Val Arg His Gly

330

Tyr Trp Gly Gln Gly

345

Ser Gly Lys Pro Gly

360

Gln Ala Val Val Thr 375

Thr Val Thr Leu Thr

395

Asn Tyr Ala Asn Trp

410

Leu Ile Gly Gly Thr

425

Ser Gly Ser Leu Leu

440

Gln Pro Glu Asp Glu 455

His Trp Val Phe Gly

475

Gly Ser Gly Gly Gly

490

Ala Pro Pro Val Ala

505

Lys Asp Thr Leu Met

520

Thr Ile Ser Arg Asp 300

Ser Leu Arg Ala Glu

320

Asn Phe Gly Asp Ser

335

Thr Leu Val Thr Val

350

Ser Gly Lys Pro Gly

365

Gln Glu Pro Ser Leu 380

Cys Gly Ser Ser Thr

400

Val Gln Gln Lys Pro

415

Asn Lys Arg Ala Pro 430

Gly Gly Lys Ala Ala 445

Ala Asp Tyr Tyr Cys 460

Gly Gly Thr Lys Leu

480

Gly Ser Lys Thr His

495

Gly Pro Ser Val Phe 510

Ile Ser Arg Thr Pro

525

- 180 044325

Glu Val Thr Cys Val Val Val Asp Val

530 535

Lys Phe Asn Trp Tyr Val Asp Gly Val 545 550

Lys His Glu Asp Pro Glu Val 540

Glu Val His Asn Ala Lys Thr

555 560

Lys Pro Arg Glu Glu Gln Tyr Asn Ser

565

Thr Tyr Arg Val Val Ser Val

570 575

Leu Thr Val

Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

580 585 590

Lys Val

Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

595 600 605

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

610 615 620

Ser Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val

625 630 635 640

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

645 650 655

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

660 665 670

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

675 680 685

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

690 695 700

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 705 710 715 <210> 167 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 167

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

- 181 044325

Asp Arg Val

Val Ala Trp

Tyr Ser Ala 50

Thr 20

Tyr

Ser

Ile Thr Cys Arg Ala Ser 25

Gln Gln Lys Pro Gly Gln 40

Tyr Arg Tyr Ser Gly Val 55

Gln Asn Val Asp Thr Asn 30

Ser Pro Lys Ala Leu Ile 45

Pro Asp Arg Phe Thr Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70

Ile Ser Ser Leu Gln Pro

80

Glu Asp Phe Ala Thr Tyr Phe Cys 85

Gln Gln Tyr Asp 90

Ser Tyr Pro Leu 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile

100 105

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120

Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135

Lys Arg Thr Val Ala Ala 110

Glu Gln Leu Lys Ser Gly 125

Phe Tyr Pro Arg Glu Ala 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu 145 150

Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170

Ser Thr Tyr Ser Leu Ser

175

Ser Thr

Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185

Ala Cys

Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Lys Val Tyr 190

Thr Lys Ser

Phe Asn Arg Gly Glu Cys

210 <210> 168 <211> 231 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 168

- 182 044325

Glu Pro Lys Ser Ser Asp Lys Thr His 1 5

Pro Pro Val Ala Gly Pro Ser Val Phe 20 25

Asp Thr Leu Met Ile Ser Arg Thr Pro

40

Asp Val Lys His Glu Asp Pro Glu Val

55

Gly Val Glu Val His Asn Ala Lys Thr 65 70

Asn Ser Thr Tyr Arg Val Val Ser Val 85

Trp Leu Asn Gly Lys Glu Tyr Lys Cys

100 105

Pro Ala Pro Ile Glu Lys Thr Ile Ser

115 120

Glu Pro Gln Val Tyr Thr Leu Pro Pro

130 135

Asn Gln Val Ser Leu Thr Cys Asp Val

145 150

Ile Ala Val Glu Trp Glu Ser Asp Gly

165

Thr Thr Pro Pro Val Leu Asp Ser Asp

180 185

Lys Leu Thr Val Asp Lys Ser Arg Trp

195 200

Cys Ser Val Met His Glu Ala Leu His

210 215

Cys Pro Pro Cys Pro Ala

Phe Pro Pro Lys Pro Lys 30

Val Thr Cys Val Val Val 45

Phe Asn Trp Tyr Val Asp 60

Pro Arg Glu Glu Glu Tyr 75 80

Thr Val Leu His Gln Asp 95

Val Ser Asn Lys Ala Leu

110

Ala Lys Gly Gln Pro Arg

125

Arg Glu Glu Met Thr Lys

140

Gly Phe Tyr Pro Ser Asp

155 160

Pro Glu Asn Asn Tyr Lys

175

Ser Phe Phe Leu Tyr Ser

190

Gln Gly Asp Val Phe Ser

205

His Tyr Thr Gln Lys Ser 220

Leu Ser Leu Ser Pro Gly Lys

225 230 <210> 169 <211> 718 <212> PROTEIN

- 183 044325 <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 169

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Asp 25

Phe Ser Arg Ser 30

Trp Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Glu Ile Asn

Pro Asp Ser Ser 55

Thr Ile Asn Tyr 60

Ala Thr Ser Val

Lys Gly Arg Phe 65

Thr Ile Ser Arg 70

Asp Asn Ser Lys 75

Asn Thr Leu Tyr 80

Leu Gln Met Asn

Ser Leu Arg Ala 85

Glu Asp Thr Ala 90

Val Tyr Tyr Cys

Ala Arg Tyr Gly

100

Asn Trp Phe Pro

Tyr Trp Gly Gln 105

Gly Thr Leu Val 110

Thr Val Ser Ser

115

Ala Ser Thr Lys

120

Gly Pro Ser Val

Phe Pro Leu Ala 125

Pro Ser Ser Lys 130

Ser Thr Ser Gly

135

Gly Thr Ala Ala

140

Leu Gly Cys Leu

Val Lys Asp Tyr 145

Phe Pro Glu Pro

150

Val Thr Val Ser

155

Trp Asn Ser Gly

160

Ala Leu Thr Ser

Gly Val His Thr 165

Phe Pro Ala Val

170

Leu Gln Ser Ser

175

Gly Leu Tyr Ser

180

Leu Ser Ser Val

Val Thr Val Pro 185

Ser Ser Ser Leu

190

Gly Thr Gln Thr Tyr

195

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr

200 205

Lys Val Asp Lys Lys Val Glu Pro

210 215

Lys

Ser Cys Gly Gly Gly Gly Ser 220

- 184 044325

Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly

225 230 235

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly

245 250 255

Thr Phe Ser Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly

260 265 270

Gly Leu Glu Trp Val Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr

275 280 285

Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg

290 295 300

Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala

305 310 315

Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asp

325 330 335

Tyr Val Ser Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr

340 345 350

Ser Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro

355 360 365

Ser Gly Lys Pro Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser

370 375 380

Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser

385 390 395

Gly Ala Val Thr Thr Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys

405 410 415

Gly Lys Ser Pro Arg Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala

420 425 430

Gly Val Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala

435 440 445

Leu Thr Ile Ser Gly Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr

450 455 460

Ala Leu Trp Tyr Ser Asn His Trp Val Phe Gly Gly Gly Thr Lys

465 470 475

Leu 240

Phe

Lys

Ala

Asp

Glu 320

Ser

Val

Gly

Leu

Thr 400

Pro

Pro

Ala

Cys

Leu 480

- 185 044325

Thr Val Leu Gly Gly

485

Gly Gly Ser Gly Gly

490

Gly Gly Ser Lys Thr

495

Thr Cys Pro Pro Cys

500

Pro Ala Pro Pro Val

505

Ala Gly Pro Ser Val

510

Leu Phe Pro Pro Lys 515

Pro Lys Asp Thr Leu

520

Met Ile Ser Arg Thr

525

Glu Val Thr Cys Val

530

Val Val Asp Val Lys

535

His Glu Asp Pro Glu

540

Lys Phe Asn Trp Tyr 545

Val Asp Gly Val Glu 550

Val His Asn Ala Lys 555

Lys Pro Arg Glu Glu

565

Gln Tyr Asn Ser Thr

570

Tyr Arg Val Val Ser

575

Leu Thr Val Leu His

580

Gln Asp Trp Leu Asn

585

Gly Lys Glu Tyr Lys

590

Lys Val Ser Asn Lys

595

Ala Leu Pro Ala Pro

600

Ile Glu Lys Thr Ile 605

Lys Ala Lys Gly Gln

610

Pro Arg Glu Pro Gln

615

Val Tyr Thr Leu Pro

620

Ser Arg Glu Gln Met 625

Thr Lys Asn Gln Val 630

Lys Leu Thr Cys Leu 635

Lys Gly Phe Tyr Pro

645

Ser Asp Ile Ala Val

650

Glu Trp Glu Ser Asn

655

Gln Pro Glu Asn Asn

660

Tyr Lys Thr Thr Pro 6 65

Pro Val Leu Asp Ser

670

Gly Ser Phe Phe Leu

675

Tyr Ser Lys Leu Thr 680

Val Asp Lys Ser Arg

685

Gln Gln Gly Asn Val

690

Phe Ser Cys Ser Val

695

Met His Glu Ala Leu

700

His

Phe

Pro

Val

Thr 560

Val

Cys

Ser

Pro

Val 640

Gly

Asp

Trp

His

Asn His Tyr Thr Gln 705

Lys Ser Leu Ser Leu 710

Ser Pro Gly Lys 715 <210> 170

- 186 044325 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 170

Asp Ile Val Met

Thr Gln Ser Pro 5

Ser Ser Leu Ser 10

Ala Ser Val Gly 15

Asp Arg Val Thr

Ile Thr Cys Arg

Ala Ser Gln Asn 25

Val Asp Thr Asn 30

Val Ala Trp Tyr

Gln Gln Lys Pro 40

Gly Gln Ser Pro

Lys Ala Leu Ile 45

Tyr Ser Ala Ser 50

Tyr Arg Tyr Ser

Gly Val Pro Asp 60

Arg Phe Thr Gly

Ser Gly Ser Gly 65

Thr Asp Phe Thr 70

Leu Thr Ile Ser

Ser Leu Gln Pro

Glu Asp Phe Ala

Thr Tyr Phe Cys 85

Gln Gln Tyr Asp 90

Ser Tyr Pro Leu 95

Thr Phe Gly Gly

100

Gly Thr Lys Leu

Glu Ile Lys Arg 105

Thr Val Ala Ala

110

Pro Ser Val Phe

115

Ile Phe Pro Pro

120

Ser Asp Glu Gln

Leu Lys Ser Gly 125

Thr Ala Ser Val

130

Val Cys Leu Leu

135

Asn Asn Phe Tyr

140

Pro Arg Glu Ala

Lys Val Gln Trp 145

Lys Val Asp Asn 150

Ala Leu Gln Ser

155

Gly Asn Ser Gln

160

Glu Ser Val Thr

Glu Gln Asp Ser 165

Lys Asp Ser Thr 170

Tyr Ser Leu Ser

175

Ser Thr Leu Thr

180

Leu Ser Lys Ala

Asp Tyr Glu Lys 185

His Lys Val Tyr

190

Ala Cys Glu Val

195

Thr His Gln Gly

200

Leu Ser Ser Pro

Val Thr Lys Ser 205

Phe Asn Arg Gly Glu Cys

- 187 044325

210 <210> 171 <211> 589 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 171

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asp Thr

- 188 044325

195

200

205

Lys

Val

210

Asp

Lys

Lys

Val

Glu

215

Pro

Lys

Ser

Cys

Gly 220

Gly

Gly

Gly

Gly 225

Gly

Gly

Gly

Ser

Glu

230

Val

Gln

Leu

Val

Glu

235

Ser

Gly

Gly

Gly

Val

Gln

Pro

Gly

Gly 245

Ser

Leu

Arg

Leu

Ser 250

Cys

Ala

Ala

Ser

Gly 255

Thr

Phe

Ser

Thr 260

Tyr

Ala

Met

Asn

Trp 265

Val

Arg

Gln

Ala

Pro

270

Gly

Gly

Leu

Glu

275

Trp

Val

Gly

Arg

Ile

280

Arg

Ser

Lys

Tyr

Asn

285

Asn

Tyr

Thr

Tyr 290

Tyr

Ala

Asp

Ser

Val

295

Lys

Gly

Arg

Phe

Thr

300

Ile

Ser

Arg

Asp

305

Ser

Lys

Asn

Thr

Leu

310

Tyr

Leu

Gln

Met

Asn

315

Ser

Leu

Arg

Ala

Asp

Thr

Ala

Val

Tyr

325

Tyr

Cys

Val

Arg

His

330

Gly

Asn

Phe

Gly

Asp 335

Tyr

Val

Ser

Trp 340

Phe

Ala

Tyr

Trp

Gly 345

Gln

Gly

Thr

Leu

Val

350

Thr

Ser

Ser

Gly 355

Gly

Gly

Gly

Ser

Gly 360

Gly

Gly

Gly

Ser

Lys

365

Thr

His

Cys

Pro

370

Pro

Cys

Pro

Ala

Pro

375

Pro

Val

Ala

Gly

Pro

380

Ser

Val

Phe

Phe

385

Pro

Pro

Lys

Pro

Lys 390

Asp

Thr

Leu

Met

Ile

395

Ser

Arg

Thr

Pro

Val

Thr

Cys

Val

Val

405

Val

Asp

Val

Lys

His

410

Glu

Asp

Pro

Glu

Val

415

Phe

Asn

Trp

Tyr 420

Val

Asp

Gly

Val

Glu

425

Val

His

Asn

Ala

Lys 430

Thr

Pro

Arg

Glu

435

Glu

Glu

Tyr

Asn

Ser

440

Thr

Tyr

Arg

Val

Val

445

Ser

Val

Ser

Leu 240

Phe

Lys

Ala

Asp

Glu 320

Ser

Val

Thr

Leu

Glu 400

Lys

Lys

Leu

- 189 044325

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

450 455460

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

465 470 475480

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

485 490495

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

500 505510

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

515 520525

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

530 535540

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

545 550 555560

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

565 570575

His Tyr Thr Gln Lys

580

Ser Leu Ser Leu Ser Pro Gly Lys

585 <210> 172 <211> 573 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 172

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser ArgSer

2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val

5560

- 190 044325

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Gly 225

Val

Ala

Lys

Val

Thr 305

Gly Arg Phe

Gln Met Asn

Arg Tyr Gly

100

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Gly Gly Gly

Ser Pro Gly

Val Thr Thr

260

Ser Pro Arg

275

Pro Ala Arg 290

Ile Ser Gly

Thr Ile Ser

Ser Leu Arg 85

Asn Trp Phe

Ala Ser Thr

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Ser Gln Ala

230

Gly Thr Val 245

Ser Asn Tyr

Gly Leu Ile

Phe Ser Gly

295

Ala Gln Pro

310

Arg Asp Asn

Ala Glu Asp

Pro Tyr Trp

105

Lys Gly Pro 120

Gly Gly Thr

Pro Val Thr

Thr Phe Pro

170

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Val Val Thr

Thr Leu Thr

250

Ala Asn Trp

265

Gly Gly Thr 280

Ser Leu Leu

Glu Asp Glu

Ser Lys Asn 75

Thr Ala Val

Gly Gln Gly

Ser Val Phe

125

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Gly Gly

220

Gln Glu Pro 235

Cys Gly Ser

Val Gln Gln

Asn Lys Arg

285

Gly Gly Lys

300

Ala Asp Tyr 315

Thr Leu Tyr

Tyr Tyr Cys 95

Thr Leu Val 110

Pro Leu Ala

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asn Thr

Gly Gly Ser

Ser Leu Thr

240

Ser Thr Gly

255

Lys Pro Gly 270

Ala Pro Gly

Ala Ala Leu

Tyr Cys Ala

320

- 191 044325

Leu Trp Tyr Ser Asn

325

His Trp Val Phe Gly

330

Gly Gly Thr Lys Leu

335

Val Leu Gly Gly Gly

340

Gly Ser Gly Gly Gly

345

Gly Ser Lys Thr His

350

Cys Pro Pro Cys Pro

355

Ala Pro Pro Val Ala

360

Gly Pro Ser Val Phe

365

Phe Pro Pro Lys Pro

370

Lys Asp Thr Leu Met

375

Ile Ser Arg Thr Pro

380

Val Thr Cys Val Val 385

Val Asp Val Lys His 390

Glu Asp Pro Glu Val 395

Phe Asn Trp Tyr Val

405

Asp Gly Val Glu Val

410

His Asn Ala Lys Thr

415

Pro Arg Glu Glu Gln

420

Tyr Asn Ser Thr Tyr

425

Arg Val Val Ser Val

430

Thr Val Leu His Gln

435

Asp Trp Leu Asn Gly

440

Lys Glu Tyr Lys Cys 445

Val Ser Asn Lys Ala

450

Leu Pro Ala Pro Ile

455

Glu Lys Thr Ile Ser 460

Ala Lys Gly Gln Pro 465

Arg Glu Pro Gln Val 470

Tyr Thr Leu Pro Pro 475

Arg Glu Gln Met Thr

485

Lys Asn Gln Val Lys

490

Leu Thr Cys Leu Val

495

Gly Phe Tyr Pro Ser

500

Asp Ile Ala Val Glu

505

Trp Glu Ser Asn Gly

510

Pro Glu Asn Asn Tyr 515

Lys Thr Thr Pro Pro

520

Val Leu Asp Ser Asp

525

Ser Phe Phe Leu Tyr

530

Ser Lys Leu Thr Val

535

Asp Lys Ser Arg Trp 540

Gln Gly Asn Val Phe 545

Ser Cys Ser Val Met 550

His Glu Ala Leu His 555

Thr

Thr

Leu

Glu

Lys 400

Lys

Leu

Lys

Lys

Ser 480

Lys

Gln

Gly

Gln

Asn 560

His Tyr Thr Gln Lys

565

Ser Leu Ser Leu Ser

570

Pro Gly Lys

- 192 044325 <210> 173 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 173

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

- 193 044325

Phe Asn Arg Gly Glu Cys

210 <210> 174 <211> 231 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 174

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

5 1015

Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 20 2530

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 35 4045

Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 50 5560

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Tyr 65 70 7580

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 85 9095

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

100 105110

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

115 120125

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys

130 135140

Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp

145 150 155160

Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

165 170175

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

180 185190

- 194 044325

Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln 195200

Cys Ser Val Met His Glu Ala Leu His Asn His 210215

Gly Asp Val Phe Ser

205

Tyr Thr Gln Lys Ser 220

Leu Ser Leu Ser Pro Gly Lys

225230 <210> 175 <211> 714 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 175

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155160

- 195 044325

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Gly

Pro 385

Ser

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

340

Glu Gln Met

355

Phe Tyr Pro 370

Glu Asn Asn

Phe Phe Leu

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Gln Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Arg Glu

Thr Lys Asn

Ser Asp Ile

375

Tyr Lys Thr

390

Tyr Ser Lys

Thr Phe Pro

170

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Pro Gln Val

345

Gln Val Lys 360

Ala Val Glu

Thr Pro Pro

Leu Thr Val

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Leu Thr Cys

365

Trp Glu Ser

380

Val Leu Asp 395

Asp Lys Ser

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asn Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser 350

Leu Val Lys

Asn Gly Gln

Ser Asp Gly

400

Arg Trp Gln

- 196 044325

405 410 415

Gln

His

Gly

Val 465

Ser

Val

Ser

Arg

Met 545

His

Gln

Pro

Val

Leu 625

Asn

Gly Asn Val

420

Tyr Thr Gln

435

Ser Gly Gly 450

Glu Ser Gly

Cys Ala Ala

Arg Gln Ala

500

Lys Tyr Asn

515

Phe Thr Ile 530

Asn Ser Leu

Gly Asn Phe

Gly Thr Leu

580

Gly Ser Gly

595

Thr Gln Glu 610

Thr Cys Gly

Trp Val Gln

Phe Ser Cys

Lys Ser Leu

Gly Gly Ser

455

Gly Gly Leu

470

Ser Gly Phe 485

Pro Gly Lys

Asn Tyr Ala

Ser Arg Asp

535

Arg Ala Glu

550

Gly Asp Ser 565

Val Thr Val

Lys Pro Gly

Pro Ser Leu

615

Ser Ser Thr

630

Gln Lys Pro 645

Ser Val Met

425

Ser Leu Ser 440

Gly Gly Gly

Val Gln Pro

Thr Phe Ser

490

Gly Leu Glu

505

Thr Tyr Tyr 520

Asp Ser Lys

Asp Thr Ala

Tyr Val Ser

570

Ser Ser Gly

585

Ser Gly Lys 600

Thr Val Ser

Gly Ala Val

Gly Lys Ser

650

His Glu Ala

Pro Gly Lys

445

Gly Ser Glu

460

Gly Gly Ser 475

Thr Tyr Ala

Trp Val Gly

Ala Asp Ser

525

Asn Thr Leu

540

Val Tyr Tyr 555

Trp Phe Ala

Lys Pro Gly

Pro Gly Ser

605

Pro Gly Gly

620

Thr Thr Ser 635

Pro Arg Gly

Leu His Asn 430

Gly Gly Gly

Val Gln Leu

Leu Arg Leu

480

Met Ser Trp

495

Arg Ile Arg 510

Val Lys Gly

Tyr Leu Gln

Cys Val Arg

560

Tyr Trp Gly

575

Ser Gly Lys 590

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

640

Leu Ile Gly

655

- 197 044325

Gly Thr Asn Lys 660 Arg Ala Pro Gly Val 665 Pro Ala Arg Phe Ser 670 Gly Ser Leu Leu Gly 675 Gly Lys Ala Ala Leu 680 Thr Ile Ser Gly Ala 685 Gln Pro Glu Asp Glu 690 Ala Asp Tyr Tyr Cys 695 Ala Leu Trp Tyr Ser 700 Asn His Trp Val

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 705 710 <210> 176 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 176

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

- 198 044325

Lys Val Gln Trp 145

Lys Val Asp Asn Ala Leu 150

Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr

Glu Gln Asp Ser Lys Asp

165 170

Ser Thr Tyr Ser Leu Ser

175

Ser Thr Leu Thr

180

Leu Ser Lys Ala Asp Tyr

185

Glu Lys His Lys Val Tyr

190

Ala Cys Glu Val

195

Thr His Gln Gly Leu Ser

200

Ser Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210 <210> 177 <211> 231 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 177

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

5 1015

Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 20 2530

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 35 4045

Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 50 5560

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Tyr 65 70 7580

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 85 9095

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

100 105110

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

115 120125

- 199 044325

Glu Pro Gln Val

130

Tyr

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys

135 140

Asn Gln Val Ser 145

Leu

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp

150 155 160

Ile Ala Val Glu

Trp 165

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

170 175

Thr Thr Pro Pro Val

180

Lys Leu Thr Val Asp 195

Cys Ser Val Met His

210

Leu Asp Ser Asp Gly Ser 185

Lys Ser Arg Trp Glu Gln 200

Glu Ala Leu His Asn His 215

Phe Phe Leu Tyr Ser 190

Gly Asp Val Phe Ser

205

Tyr Thr Gln Lys Ser 220

Leu Ser Leu Ser Pro Gly Lys

225 230 <210> 178 <211> 714 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 178

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

- 200 044325

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg Tyr

Val Ser

115

Ser Ser 130

Lys Asp

Leu Thr

Leu Tyr

Thr Gln

195

Val Asp 210

Pro Pro

Pro Pro

Thr Cys

Asn Trp

275

Arg Glu 290

Val Leu

Ser Asn

Lys Gly

Gly Asn 100

Ser Ala

Lys Ser

Tyr Phe

Trp Phe

Ser Thr

Thr Ser

135

Pro Glu 150

Ser Gly

165

Ser Leu 180

Thr Tyr

Lys Lys

Cys Pro

Lys Pro

245

Val Val 260

Tyr Val

Glu Gln

His Gln

Lys Ala

325

Glin Pro 340

Val His

Ser Ser

Ile Cys

Val Glu

215

Ala Pro 230

Lys Asp

Val Asp

Asp Gly

Tyr Asn

295

Asp Trp 310

Leu Pro

Arg Glu

Pro Tyr

105

Lys Gly 120

Gly Gly

Pro Val

Thr Phe

Val Val

185

Asn Val 200

Pro Lys

Pro Val

Thr Leu

Val Lys

265

Val Glu 280

Ser Thr

Leu Asn

Ala Pro

Pro Gln

345

Trp Gly

Gln Gly

Pro Ser

Thr Ala

Thr Val

155

Pro Ala 170

Thr Val

Asn His

Ser Cys

Ala Gly

235

Met Ile 250

His Glu

Val His

Tyr Arg

Gly Lys

315

Ile Glu

330

Val Tyr

Val Phe

125

Ala Leu 140

Ser Trp

Val Leu

Pro Ser

Lys Pro

205

Asp Lys 220

Pro Ser

Ser Arg

Asp Pro

Asn Ala

285

Val Val 300

Glu Tyr

Lys Thr

Thr Leu

Thr Leu 110

ProLeu

Gly Cys

Asn Ser

Gln Ser

175

Ser Ser 190

Ser Asn

Thr His

Val Phe

Thr Pro

255

Glu Val

270

Lys Thr

Ser Val

Lys Cys

Ile Ser

335

Pro Pro 350

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Leu 240

Glu

Lys

Lys

Leu

Lys 320

Lys

Ser

- 201 044325

Arg

Gly

Pro 385

Ser

Gln

His

Gly

Val 465

Ser

Val

Ser

Arg

Met 545

His

Gln

Pro

Glu Gln Met

355

Thr Lys Asn

Gln Val Lys 360

Leu Thr Cys

365

Leu Val Lys

Phe Tyr Pro 370

Glu Asn Asn

Phe Phe Leu

Gly Asn Val

420

Tyr Thr Gln

435

Ser Gly Gly 450

Glu Ser Gly

Cys Ala Ala

Arg Gln Ala

500

Lys Tyr Asn

515

Phe Thr Ile 530

Asn Ser Leu

Gly Asn Phe

Gly Thr Leu

580

Gly Ser Gly

595

Ser Asp Ile

375

Tyr Lys Thr

390

Tyr Ser Lys 405

Phe Ser Cys

Lys Ser Leu

Gly Gly Ser

455

Gly Gly Leu

470

Ser Gly Phe 485

Pro Gly Lys

Asn Tyr Ala

Ser Arg Asp

535

Arg Ala Glu

550

Gly Asp Ser 565

Val Thr Val

Lys Pro Gly

Ala Val Glu

Trp Glu Ser

380

Asn Gly Gln

Thr Pro Pro

Leu Thr Val

410

Ser Val Met

425

Ser Leu Ser 440

Gly Gly Gly

Val Gln Pro

Thr Phe Ser

490

Gly Leu Glu

505

Thr Tyr Tyr 520

Asp Ser Lys

Asp Thr Ala

Tyr Val Ser

570

Ser Ser Gly

585

Ser Gly Lys 600

Val Leu Asp 395

Asp Lys Ser

His Glu Ala

Pro Gly Lys

445

Gly Ser Glu

460

Gly Gly Ser 475

Thr Tyr Ala

Trp Val Gly

Ala Asp Ser

525

Asn Thr Leu

540

Val Tyr Tyr 555

Trp Phe Asp

Lys Pro Gly

Pro Gly Ser

605

Ser Asp Gly

400

Arg Trp Gln 415

Leu His Asn 430

Gly Gly Gly

Val Gln Leu

Leu Arg Leu

480

Met Asn Trp

495

Arg Ile Arg 510

Val Lys Gly

Tyr Leu Gln

Cys Val Arg

560

Tyr Trp Gly

575

Ser Gly Lys 590

Gln Ala Val

- 202 044325

Val Thr Gln Glu Pro Ser Leu Thr

610 615

Val Ser Pro Gly Gly Thr Val Thr 620

Leu Thr Cys Gly Ser Ser Thr Gly

625 630

Ala Val Thr Thr Ser Asn Tyr Ala

635 640

Asn Trp Val Gln Gln Lys Pro Gly 645

Lys Ser Pro Arg Gly Leu Ile Gly

650 655

Gly Thr Asn Lys Arg Ala Pro Gly 660

Val Pro Ala Arg Phe Ser Gly Ser

665 670

Leu Leu Gly Gly Lys Ala Ala Leu

675 680

Thr Ile Ser Gly Ala Gln Pro Glu 685

Asp Glu Ala Asp Tyr Tyr Cys Ala

690 695

Leu Trp Tyr Ser Asn His Trp Val 700

Phe Gly Gly Gly Thr Lys Leu Thr

705 710

Val Leu <210> 179 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 179

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile

4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

- 203 044325

Thr Phe Gly Gly

100

Gly Thr Lys Leu

Glu Ile Lys Arg 105

Thr Val Ala Ala

110

Pro Ser Val Phe

115

Ile Phe Pro Pro

120

Ser Asp Glu Gln

Leu Lys Ser Gly 125

Thr Ala Ser Val

130

Val Cys Leu Leu

135

Asn Asn Phe Tyr

140

Pro Arg Glu Ala

Lys Val Gln Trp 145

Lys Val Asp Asn

150

Ala Leu Gln Ser

155

Gly Asn Ser Gln

160

Glu Ser Val Thr

Glu Gln Asp Ser 165

Lys Asp Ser Thr 170

Tyr Ser Leu Ser

175

Ser Thr

Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His

180 185

Ala Cys

Glu Val Thr His Gln Gly Leu Ser Ser Pro Val

195 200 205

Lys Val Tyr 190

Thr Lys Ser

Phe Asn Arg Gly Glu Cys

210 <210> 180 <211> 231 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 180

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

5 1015

Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys ProLys

2530

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 35 4045

Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 50 5560

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Tyr

70 7580

- 204 044325

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 85 9095

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

100 105110

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

115 120125

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys

130 135140

Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp

145 150 155160

Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

165 170175

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

180 185190

Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

195 200205

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

210 215220

Leu Ser Leu Ser Pro Gly Lys

225230 <210> 181 <211> 714 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 181

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

- 205 044325

Ser

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Glu Ile Asn Pro Asp 50

Gly Arg Phe Thr Ile 70

Gln Met Asn Ser Leu

Arg Tyr Gly Asn Trp 100

Val Ser Ser Ala Ser

115

Ser Ser Lys Ser Thr 130

Lys Asp Tyr Phe Pro

150

Leu Thr Ser Gly Val

165

Leu Tyr Ser Leu Ser 180

Thr Gln Thr Tyr Ile 195

Val Asp Lys Lys Val 210

Pro Pro Cys Pro Ala

230

Pro Pro Lys Pro Lys

245

Thr Cys Val Val Val

260

Asn Trp Tyr Val Asp

275

Arg Glu Glu Gln Tyr

Ser Ser Thr Ile Asn 55

Ser Arg Asp Asn Ser 75

Arg Ala Glu Asp Thr

Phe Pro Tyr Trp Gly

105

Thr Lys Gly Pro Ser 120

Ser Gly Gly Thr Ala 135

Glu Pro Val Thr Val

155

His Thr Phe Pro Ala

170

Ser Val Val Thr Val

185

Cys Asn Val Asn His

200

Glu Pro Lys Ser Cys 215

Pro Pro Val Ala Gly

235

Asp Thr Leu Met Ile

250

Asp Val Lys His Glu

265

Gly Val Glu Val His

280

Asn Ser Thr Tyr Arg

Tyr Ala Thr Ser Val 60

Lys Asn Thr Leu Tyr 80

Ala Val Tyr Tyr Cys 95

Gln Gly Thr Leu Val

110

Val Phe Pro Leu Ala

125

Ala Leu Gly Cys Leu 140

Ser Trp Asn Ser Gly

160

Val Leu Gln Ser Ser

175

Pro Ser Ser Ser Leu

190

Lys Pro Ser Asn Thr

205

Asp Lys Thr His Thr 220

Pro Ser Val Phe Leu

240

Ser Arg Thr Pro Glu

255

Asp Pro Glu Val Lys

270

Asn Ala Lys Thr Lys

285

Val Val Ser Val Leu

- 206 044325

290

295

300

Thr 305

Val

Ala

Arg

Gly

Pro 385

Ser

Gln

His

Gly

Val 465

Ser

Val

Ser

Arg

Val Leu His

Gln Asp Trp

310

Leu Asn Gly

Lys Glu Tyr 315

Lys Cys Lys

320

Ser Asn Lys

Lys Gly Gln

340

Glu Gln Met

355

Phe Tyr Pro 370

Glu Asn Asn

Phe Phe Leu

Gly Asn Val

420

Tyr Thr Gln

435

Ser Gly Gly 450

Glu Ser Gly

Cys Ala Ala

Arg Gln Ala

500

Lys Tyr Asn

515

Phe Thr Ile 530

Ala Leu Pro 325

Ala Pro Ile

330

Glu Lys Thr

Ile Ser Lys

335

Pro Arg Glu

Pro Gln Val

345

Tyr Thr Leu

Pro Pro Ser 350

Thr Lys Asn

Gln Val Lys 360

Leu Thr Cys

365

Leu Val Lys

Ser Asp Ile

375

Tyr Lys Thr

390

Tyr Ser Lys 405

Phe Ser Cys

Lys Ser Leu

Gly Gly Ser

455

Gly Gly Leu

470

Ser Gly Phe 485

Pro Gly Lys

Asn Tyr Ala

Ser Arg Asp

535

Ala Val Glu

Trp Glu Ser

380

Asn Gly Gln

Thr Pro Pro

Leu Thr Val

410

Ser Val Met

425

Ser Leu Ser 440

Gly Gly Gly

Val Gln Pro

Thr Phe Ser

490

Gly Leu Glu

505

Thr Tyr Tyr 520

Asp Ser Lys

Val Leu Asp 395

Asp Lys Ser

His Glu Ala

Pro Gly Lys

445

Gly Ser Glu

460

Gly Gly Ser 475

Thr Tyr Ala

Trp Val Gly

Ala Asp Ser

525

Asn Thr Leu

540

Ser Asp Gly

400

Arg Trp Gln 415

Leu His Asn 430

Gly Gly Gly

Val Gln Leu

Leu Arg Leu

480

Met Asn Trp

495

Arg Ile Arg 510

Val Lys Gly

Tyr Leu Gln

- 207 044325

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg

545 550 555560

His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe Ala Tyr Trp Gly

565 570575

Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro Gly Ser Gly Lys

580 585590

Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gln Ala Val

595 600605

Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr

610 615620

Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala

625 630 635640

Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly

645 650655

Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser

660 665670

Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu

675 680685

Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val

690 695700

Phe Gly Gly Gly Thr

Lys Leu Thr Val Leu

705

710 <210> 182 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 182

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala 20 25

Ser Gln Asn Val Asp Thr Asn 30

- 208 044325

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210> 183 <211> 231 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 183

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

- 209 044325

Pro Pro Val Ala Gly

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

thirty

Asp Thr Leu Met Ile 35

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

45

Asp Val Lys His Glu 50

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp

60

Gly Val Glu Val His 65

Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Tyr 70 75 80

Asn Ser Thr Tyr Arg 85

Val Val Ser Val Leu Thr Val Leu His Gln Asp 90 95

Trp Leu Asn Gly Lys

100

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

105 110

Pro Ala Pro Ile Glu

115

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

120 125

Glu Pro Gln Val Tyr

130

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys

135 140

Asn Gln Val Ser Leu 145

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp

150 155 160

Ile Ala Val Glu Trp

165

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

170 175

Thr Thr Pro Pro Val

180

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

185 190

Lys Leu Thr Val Asp

195

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

200 205

Cys Ser Val Met His

210

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

215 220

Leu Ser Leu Ser Pro 225

Gly Lys 230 <210> 184 <211> 718 <212> PROTEIN <213> Artificial <220>

<221> source sequence

- 210 044325 <223> /note=Description of artificial sequence: synthetic polypeptide <400> 184

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys

3540

Gly Leu Glu Trp Val

Ser Glu Ile Asn

Pro Asp Ser Ser 55

Thr Ile Asn Tyr 60

Ala Thr Ser Val

Lys Gly Arg Phe 65

Thr Ile Ser Arg 70

Asp Asn Ser Lys 75

Asn Thr Leu Tyr 80

Leu Gln Met Asn

Ser Leu Arg Ala 85

Glu Asp Thr Ala 90

Val Tyr Tyr Cys

Ala Arg Tyr Gly

100

Asn Trp Phe Pro

Tyr Trp Gly Gln 105

Gly Thr Leu Val

110

Thr Val

Pro Ser

130

Ser 115

Ser

Ser Ala

Lys Ser

Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 120 125

Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 135 140

Val Lys Asp Tyr 145

Phe Pro Glu Pro

150

Val Thr Val Ser

155

Trp Asn Ser Gly

160

Ala Leu Thr Ser

Gly Val His Thr 165

Phe Pro Ala Val

170

Leu Gln Ser Ser

175

Gly Leu Tyr Ser

180

Leu Ser Ser Val

Val Thr Val Pro 185

Ser Ser Ser Leu

190

Gly Thr Gln Thr

195

Tyr Ile Cys Asn

200

Val Asn His Lys

Pro Ser Asn Thr 205

Lys Val Asp Lys

210

Lys Val Glu Pro

215

Lys Ser Cys Gly

220

Gly Gly Gly Ser

Gly Gly Gly Gly Ser Glu Val Gln Leu Val Glu

225 230 235

Ser Gly Gly Gly Leu

240

- 211 044325

Val Gln Pro Gly Gly

245

Ser Leu Arg Leu Ser

250

Cys Ala Ala Ser Gly

255

Thr Phe Ser Thr Tyr

260

Ala Met Ser Trp Val

265

Arg Gln Ala Pro Gly

270

Gly Leu Glu Trp Val

275

Gly Arg Ile Arg Ser

280

Lys Tyr Asn Asn Tyr

285

Thr Tyr Tyr Ala Asp

290

Ser Val Lys Gly Arg

295

Phe Thr Ile Ser Arg 300

Asp Ser Lys Asn Thr 305

Leu Tyr Leu Gln Met 310

Asn Ser Leu Arg Ala 315

Asp Thr Ala Val Tyr

325

Tyr Cys Val Arg His

330

Gly Asn Phe Gly Asp

335

Tyr Val Ser Trp Phe

340

Ala Tyr Trp Gly Gln

345

Gly Thr Leu Val Thr

350

Ser Ser Gly Lys Pro

355

Gly Ser Gly Lys Pro

360

Gly Ser Gly Lys Pro

365

Ser Gly Lys Pro Gly

370

Ser Gln Ala Val Val

375

Thr Gln Glu Pro Ser

380

Thr Val Ser Pro Gly 385

Gly Thr Val Thr Leu 390

Thr Cys Gly Ser Ser 395

Gly Ala Val Thr Thr

405

Ser Asn Tyr Ala Asn

410

Trp Val Gln Gln Lys

415

Gly Lys Ser Pro Arg

420

Gly Leu Ile Gly Gly

425

Thr Asn Lys Arg Ala

430

Gly Val Pro Ala Arg

435

Phe Ser Gly Ser Leu 440

Leu Gly Gly Lys Ala

445

Leu Thr Ile Ser Gly 450

Ala Gln Pro Glu Asp 455

Glu Ala Asp Tyr Tyr 460

Ala Leu Trp Tyr Ser 465

Asn His Trp Val Phe 470

Gly Gly Gly Thr Lys 475

Thr Val Leu Gly Gly

485

Gly Gly Ser Gly Gly

490

Gly Gly Ser Lys Thr

495

Phe

Lys

Ala

Asp

Glu 320

Ser

Val

Gly

Leu

Thr 400

Pro

Pro

Ala

Cys

Leu 480

His

- 212 044325

Thr Cys Pro Pro Cys

500

Pro Ala Pro Pro Val

505

Ala Gly Pro Ser Val

510

Leu Phe Pro Pro Lys 515

Pro Lys Asp Thr Leu

520

Met Ile Ser Arg Thr

525

Glu Val Thr Cys Val

530

Val Val Asp Val Lys

535

His Glu Asp Pro Glu

540

Lys Phe Asn Trp Tyr 545

Val Asp Gly Val Glu 550

Val His Asn Ala Lys 555

Lys Pro Arg Glu Glu

565

Gln Tyr Asn Ser Thr

570

Tyr Arg Val Val Ser

575

Leu Thr Val Leu His

580

Gln Asp Trp Leu Asn

585

Gly Lys Glu Tyr Lys

590

Lys Val Ser Asn Lys

595

Ala Leu Pro Ala Pro

600

Ile Glu Lys Thr Ile 605

Lys Ala Lys Gly Gln 610

Pro Arg Glu Pro Gln 615

Val Tyr Thr Leu Pro

620

Ser Arg Glu Gln Met 625

Thr Lys Asn Gln Val 630

Lys Leu Thr Cys Leu 635

Lys Gly Phe Tyr Pro

645

Ser Asp Ile Ala Val

650

Glu Trp Glu Ser Asn

655

Gln Pro Glu Asn Asn

660

Tyr Lys Thr Thr Pro 6 65

Pro Val Leu Asp Ser

670

Gly Ser Phe Phe Leu

675

Tyr Ser Lys Leu Thr 680

Val Asp Lys Ser Arg

685

Gln Gln Gly Asn Val 690

Phe Ser Cys Ser Val

695

Met His Glu Ala Leu

700

Phe

Pro

Val

Thr 560

Val

Cys

Ser

Pro

Val 640

Gly

Asp

Trp

His

Asn His Tyr Thr Gln 705

Lys Ser Leu Ser Leu 710

Ser Pro Gly Lys 715 <210> 185 <211> 214 <212> PROTEIN <213> Artificial sequence

- 213 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 185

Asp Ile Val Met 1

Thr Gln Ser Pro 5

Ser Ser Leu Ser 10

Ala Ser Val Gly 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Gln Asn 25

Val Asp Thr Asn 30

Val Ala Trp Tyr

Gln Gln Lys Pro 40

Gly Gln Ser Pro

Lys Ala Leu Ile 45

Tyr Ser Ala Ser 50

Tyr Arg Tyr Ser

Gly Val Pro Asp 60

Arg Phe Thr Gly

Ser Gly Ser Gly 65

Thr Asp Phe Thr 70

Leu Thr Ile Ser

Ser Leu Gln Pro

Glu Asp Phe Ala

Thr Tyr Phe Cys 85

Gln Gln Tyr Asp 90

Ser Tyr Pro Leu 95

Thr Phe Gly Gly

100

Gly Thr Lys Leu

Glu Ile Lys Arg 105

Thr Val Ala Ala

110

Pro Ser Val Phe

115

Ile Phe Pro Pro

120

Ser Asp Glu Gln

Leu Lys Ser Gly 125

Thr Ala Ser Val

130

Val Cys Leu Leu

135

Asn Asn Phe Tyr

140

Pro Arg Glu Ala

Lys Val Gln Trp 145

Lys Val Asp Asn 150

Ala Leu Gln Ser

155

Gly Asn Ser Gln

160

Glu Ser Val Thr

Glu Gln Asp Ser 165

Lys Asp Ser Thr 170

Tyr Ser Leu Ser

175

Ser Thr Leu Thr

180

Leu Ser Lys Ala

Asp Tyr Glu Lys 185

His Lys Val Tyr 190

Ala Cys Glu Val

195

Thr His Gln Gly

200

Leu Ser Ser Pro

Val Thr Lys Ser 205

Phe Asn Arg

210

Gly Glu Cys <210> 186

- 214 044325 <211> 231 < 212> PROTEIN < 213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 186

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

5 1015

Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys ProLys

2530

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 35 4045

Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 50 5560

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu GluTyr

70 7580

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His GlnAsp

9095

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

100 105110

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

115 120125

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys

130 135140

Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro SerAsp

145 150 155160

Ile Ala Val Glu Trp Glu Ser Asp Gly Gln Pro Glu Asn Asn TyrLys

165 170175

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 180 185190

Lys Leu Thr Val Asp Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser 195 200205

Cys Ser Val Met His Glu Ala Leu His Asn His

Tyr Thr Gln Lys Ser

- 215 044325

210

215

220

Leu Ser Leu Ser Pro Gly Lys

225

230 <210> 187 <211> 718 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 187

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu

130 135140

Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly

145 150 155160

Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser

165 170175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

- 216 044325

180

185

190

Gly Thr Gln Thr Tyr 195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asn

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Gly Gly Gly Gly

220

Gly Gly Gly Gly Ser 225

Glu Val Gln Leu Val 230

Glu Ser Gly Gly Gly 235

Val Gln Pro Gly Gly

245

Ser Leu Arg Leu Ser

250

Cys Ala Ala Ser Gly

255

Thr Phe Ser Thr Tyr

260

Ala Met Ser Trp Val

265

Arg Gln Ala Pro Gly

270

Gly Leu Glu Trp Val

275

Gly Arg Ile Arg Ser 280

Lys Tyr Asn Asn Tyr

285

Thr Tyr Tyr Ala Asp

290

Ser Val Lys Gly Arg

295

Phe Thr Ile Ser Arg 300

Asp Ser Lys Asn Thr 305

Leu Tyr Leu Gln Met 310

Asn Ser Leu Arg Ala 315

Asp Thr Ala Val Tyr

325

Tyr Cys Val Arg His

330

Gly Asn Phe Gly Asp

335

Tyr Val Ser Trp Phe

340

Ala Tyr Trp Gly Gln

345

Gly Thr Leu Val Thr

350

Ser Ser Gly Lys Pro

355

Gly Ser Gly Lys Pro 360

Gly Ser Gly Lys Pro

365

Ser Gly Lys Pro Gly

370

Ser Gln Ala Val Val

375

Thr Gln Glu Pro Ser

380

Thr Val Ser Pro Gly 385

Gly Thr Val Thr Leu 390

Thr Cys Gly Ser Ser 395

Gly Ala Val Thr Thr

405

Ser Asn Tyr Ala Asn

410

Trp Val Gln Gln Lys

415

Gly Lys Ser Pro Arg

420

Gly Leu Ile Gly Gly

425

Thr Asn Lys Arg Ala

430

Thr

Ser

Leu 240

Phe

Lys

Ala

Asp

Glu 320

Ser

Val

Gly

Leu

Thr 400

Pro

Pro

- 217 044325

Gly

Leu

Ala 465

Thr

Thr

Leu

Glu

Lys 545

Lys

Leu

Lys

Lys

Ser 625

Lys

Gln

Gly

Val Pro Ala

435

Arg Phe Ser

Gly Ser Leu 440

Leu Gly Gly

445

Lys Ala Ala

Thr Ile Ser 450

Gly Ala Gln

455

Pro Glu Asp

Glu Ala Asp

460

Tyr Tyr Cys

Leu Trp Tyr

Ser Asn His

470

Trp Val Phe

Gly Gly Gly 475

Thr Lys Leu

480

Val Leu Gly

Cys Pro Pro

500

Phe Pro Pro

515

Val Thr Cys 530

Phe Asn Trp

Pro Arg Glu

Thr Val Leu

580

Val Ser Asn

595

Ala Lys Gly 610

Arg Glu Gln

Gly Phe Tyr

Pro Glu Asn

660

Ser Phe Phe

675

Gly Gly Gly 485

Cys Pro Ala

Lys Pro Lys

Val Val Val

535

Tyr Val Asp

550

Glu Gln Tyr 565

His Gln Asp

Lys Ala Leu

Gln Pro Arg

615

Met Thr Lys 630

Pro Ser Asp 645

Asn Tyr Lys

Leu Tyr Ser

Ser Gly Gly

490

Gly Gly Ser

Lys Thr His

495

Pro Pro Val

505

Asp Thr Leu 520

Asp Val Lys

Gly Val Glu

Asn Ser Thr

570

Trp Leu Asn

585

Pro Ala Pro 600

Glu Pro Gln

Asn Gln Val

Ile Ala Val

650

Thr Thr Pro

65

Lys Leu Thr 680

Ala Gly Pro

Met Ile Ser

525

His Glu Asp

540

Val His Asn 555

Tyr Arg Val

Gly Lys Glu

Ile Glu Lys

605

Val Tyr Thr

620

Lys Leu Thr 635

Glu Trp Glu

Pro Val Leu

Val Asp Lys

685

Ser Val Phe 510

Arg Thr Pro

Pro Glu Val

Ala Lys Thr

560

Val Ser Val

575

Tyr Lys Cys 590

Thr Ile Ser

Leu Pro Pro

Cys Leu Val

640

Ser Asn Gly

655

Asp Ser Asp 670

Ser Arg Trp

- 218 044325

Gln Gln Gly Asn Val Phe Ser Cys

690 695

Ser Val Met His Glu Ala Leu His

700

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

705 710 715 <210> 188 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 188

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

- 219 044325

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

180 185

Lys His Lys Val Tyr 190

Ala Cys Glu Val

195

Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

200 205

Phe Asn Arg Gly Glu Cys

210 <210> 189 <211> 231 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 189

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

5 1015

Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 20 2530

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 35 4045

Asp Val Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 50 5560

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Tyr 65 70 7580

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 85 9095

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

100 105110

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

115 120125

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys

130 135140

Asn Gln Val Ser Leu Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp

145 150 155160

- 220 044325

Ile Ala Val Glu

Trp Glu Ser Asp 165

Gly Gln Pro Glu 170

Asn Asn Tyr Lys

175

Thr Thr Pro Pro

180

Val Leu Asp Ser

Asp Gly Ser Phe 185

Phe Leu Tyr Ser 190

Lys Leu Thr Val

195

Asp Lys Ser Arg

200

Trp Glu Gln Gly

Asp Val Phe Ser 205

Cys Ser Val Met

210

His Glu Ala Leu

215

His Asn His Tyr

220

Thr Gln Lys Ser

Leu Ser Leu Ser Pro Gly Lys

225 230 <210> 190 <211> 718 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 190

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala

115 120125

- 221 044325

Pro

Val 145

Ala

Gly

Gly

Lys

Gly 225

Val

Thr

Gly

Thr

Asp 305

Asp

Tyr

Ser

Ser

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Gly Gly Gly

Gln Pro Gly

Phe Ser Thr

260

Leu Glu Trp

275

Tyr Tyr Ala 290

Ser Lys Asn

Thr Ala Val

Val Ser Trp

340

Ser Gly Lys

355

Gly Lys Pro 370

Ser Thr Ser

135

Gly Gly Thr

Ala Ala Leu

140

Gly Cys Leu

Phe Pro Glu

150

Pro Val Thr

Val Ser Trp 155

Asn Ser Gly

160

Gly Val His 165

Thr Phe Pro

170

Ala Val Leu

Gln Ser Ser

175

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Ser Glu Val

230

Gly Ser Leu 245

Tyr Ala Met

Val Gly Arg

Asp Ser Val

295

Thr Leu Tyr

310

Tyr Tyr Cys 325

Phe Ala Tyr

Pro Gly Ser

Gly Ser Gln

375

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Gln Leu Val

Arg Leu Ser

250

Asn Trp Val

265

Ile Arg Ser 280

Lys Gly Arg

Leu Gln Met

Val Arg His

330

Trp Gly Gln

345

Gly Lys Pro 360

Ala Val Val

Val Pro Ser

His Lys Pro

205

Cys Gly Gly

220

Glu Ser Gly 235

Cys Ala Ala

Arg Gln Ala

Lys Tyr Asn

285

Phe Thr Ile

300

Asn Ser Leu 315

Gly Asn Phe

Gly Thr Leu

Gly Ser Gly

365

Thr Gln Glu

380

Ser Ser Leu 190

Ser Asn Thr

Gly Gly Ser

Gly Gly Leu

240

Ser Gly Phe

255

Pro Gly Lys 270

Asn Tyr Ala

Ser Arg Asp

Arg Ala Glu

320

Gly Asp Ser

335

Val Thr Val 350

Lys Pro Gly

Pro Ser Leu

- 222 044325

Thr Val Ser Pro Gly 385

Gly Thr Val Thr Leu 390

Thr Cys Gly Ser Ser 395

Gly Ala Val Thr Thr

405

Ser Asn Tyr Ala Asn

410

Trp Val Gln Gln Lys

415

Gly Lys Ser Pro Arg

420

Gly Leu Ile Gly Gly

425

Thr Asn Lys Arg Ala

430

Gly Val Pro Ala Arg

435

Phe Ser Gly Ser Leu 440

Leu Gly Gly Lys Ala

445

Leu Thr Ile Ser Gly 450

Ala Gln Pro Glu Asp

455

Glu Ala Asp Tyr Tyr 460

Ala Leu Trp Tyr Ser 465

Asn His Trp Val Phe 470

Gly Gly Gly Thr Lys 475

Thr Val Leu Gly Gly

485

Gly Gly Ser Gly Gly

490

Gly Gly Ser Lys Thr

495

Thr Cys Pro Pro Cys

500

Pro Ala Pro Pro Val

505

Ala Gly Pro Ser Val

510

Leu Phe Pro Pro Lys

515

Pro Lys Asp Thr Leu

520

Met Ile Ser Arg Thr

525

Glu Val Thr Cys Val

530

Val Val Asp Val Lys

535

His Glu Asp Pro Glu 540

Lys Phe Asn Trp Tyr 545

Val Asp Gly Val Glu 550

Val His Asn Ala Lys 555

Lys Pro Arg Glu Glu

565

Gln Tyr Asn Ser Thr

570

Tyr Arg Val Val Ser

575

Leu Thr Val Leu His

580

Gln Asp Trp Leu Asn

585

Gly Lys Glu Tyr Lys

590

Lys Val Ser Asn Lys

595

Ala Leu Pro Ala Pro

600

Ile Glu Lys Thr Ile

605

Lys Ala Lys Gly Gln 610

Pro Arg Glu Pro Gln 615

Val Tyr Thr Leu Pro

620

Thr 400

Pro

Pro

Ala

Cys

Leu 480

His

Phe

Pro

Val

Thr 560

Val

Cys

Ser

Pro

Val

Ser Arg Glu Gln Met

Thr Lys Asn Gln Val

Lys Leu Thr Cys Leu

- 223 044325

625 630 635 640

Lys Gly Phe Tyr

Pro Ser Asp Ile 645

Ala Val Glu Trp

650

Glu Ser Asn Gly

655

Gln Pro Glu Asn

660

Asn Tyr Lys Thr

Thr Pro Pro Val 665

Leu Asp Ser Asp 670

Gly Ser Phe Phe

675

Leu Tyr Ser Lys

680

Leu Thr Val Asp

Lys Ser Arg Trp 685

Gln Gln Gly Asn 690

Val Phe Ser Cys

695

Ser Val Met His

700

Glu Ala Leu His

Asn His Tyr Thr 705

Gln Lys Ser Leu 710

Ser Leu Ser Pro

715

Gly Lys <210> 191 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 191

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

- 224 044325

115

120

125

Thr Ala Ser Val Val Cys Leu Leu

130 135

Asn Asn Phe Tyr Pro Arg Glu Ala

140

Lys Val Gln Trp Lys Val Asp Asn

145 150

Ala Leu Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr Glu Gln Asp Ser

165

Lys Asp Ser Thr Tyr Ser Leu Ser

170 175

Ser Thr Leu Thr Leu Ser Lys Ala 180

Asp Tyr Glu Lys His Lys Val Tyr

185 190

Ala Cys Glu Val Thr His Gln Gly

195 200

Leu Ser Ser Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210 <210> 192 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 192

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

- 225 044325

100

105

110

Thr Val Ser Ser Ala

115

Ser Thr Lys Gly Pro 120

Ser Val Phe Pro Leu

125

Pro Ser Ser Lys Ser 130

Thr Ser Gly Gly Thr

135

Ala Ala Leu Gly Cys 140

Val Lys Asp Tyr Phe 145

Pro Glu Pro Val Thr 150

Val Ser Trp Asn Ser 155

Ala Leu Thr Ser Gly

165

Val His Thr Phe Pro

170

Ala Val Leu Gln Ser

175

Gly Leu Tyr Ser Leu

180

Ser Ser Val Val Thr

185

Val Pro Ser Ser Ser

190

Gly Thr Gln Thr Tyr

195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asp

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Asp Lys Thr His

220

Cys Pro Pro Cys Pro 225

Ala Pro Pro Val Ala 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Lys His

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Glu

290

Tyr Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Val Ser Asn Lys Ala

325

Leu Pro Ala Pro Ile

330

Glu Lys Thr Ile Ser

335

Ala Lys Gly Gln Pro

340

Arg Glu Pro Gln Val

345

Tyr Thr Leu Pro Pro

350

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Leu 240

Glu

Lys

Lys

Leu

Lys 320

Lys

Ser

- 226 044325

Arg Glu Glu Met

355

Thr Lys Asn Gln Val Ser Leu 360

Thr Cys Asp Val Ser

365

Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp

375

Glu Ser Asp Gly Gln 380

Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro Pro Val

390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu

Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys 420

Ser Val Met His Glu Ala Leu His Asn

425 430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440 445 <210> 193 <211> 714 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 193

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

- 227 044325

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

340

Glu Gln Met

355

Ala Ser Thr

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Gln Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Arg Glu

Thr Lys Asn

Lys Gly Pro 120

Gly Gly Thr

Pro Val Thr

Thr Phe Pro 170

Val Val Thr 185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Pro Gln Val

345

Gln Val Lys 360

Ser Val Phe

125

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Leu Thr Cys

365

Pro Leu Ala

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asn Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser 350

Leu Val Lys

- 228 044325

Gly

Pro 385

Ser

Gln

His

Gly

Val 465

Ser

Val

Ser

Arg

Met 545

His

Gln

Pro

Val

Phe Tyr Pro 370

Glu Asn Asn

Phe Phe Leu

Gly Asn Val

420

Tyr Thr Gln

435

Ser Gly Gly 450

Glu Ser Gly

Cys Ala Ala

Arg Gln Ala

500

Lys Tyr Asn

515

Phe Thr Ile 530

Asn Ser Leu

Gly Asn Phe

Gly Thr Leu

580

Gly Ser Gly

595

Thr Gln Glu 610

Ser Asp Ile

375

Tyr Lys Thr 390

Tyr Ser Lys 405

Phe Ser Cys

Lys Ser Leu

Gly Gly Ser

455

Gly Gly Leu

470

Ser Gly Phe 485

Pro Gly Lys

Asn Tyr Ala

Ser Arg Asp

535

Arg Ala Glu

550

Gly Asp Ser 565

Val Thr Val

Lys Pro Gly

Pro Ser Leu

615

Ala Val Glu

Thr Pro Pro

Leu Thr Val

410

Ser Val Met

425

Ser Leu Ser 440

Gly Gly Gly

Val Gln Pro

Thr Phe Ser

490

Gly Leu Glu

505

Thr Tyr Tyr 520

Asp Ser Lys

Asp Thr Ala

Tyr Val Ser

570

Ser Ser Gly

585

Ser Gly Lys 600

Thr Val Ser

Trp Glu Ser

380

Val Leu Asp 395

Asp Lys Ser

His Glu Ala

Pro Gly Lys

445

Gly Ser Glu

460

Gly Gly Ser 475

Thr Tyr Ala

Trp Val Gly

Ala Asp Ser

525

Asn Thr Leu

540

Val Tyr Tyr 555

Trp Phe Ala

Lys Pro Gly

Pro Gly Ser

605

Pro Gly Gly

620

Asn Gly Gln

Ser Asp Gly

400

Arg Trp Gln

415

Leu His Asn 430

Gly Gly Gly

Val Gln Leu

Leu Arg Leu

480

Met Ser Trp

495

Arg Ile Arg 510

Val Lys Gly

Tyr Leu Gln

Cys Val Arg

560

Tyr Trp Gly

575

Ser Gly Lys 590

Gln Ala Val

Thr Val Thr

- 229 044325

Leu Thr Cys Gly Ser Ser Thr Gly

625 630

Ala Val Thr Thr Ser Asn Tyr Ala

635 640

Asn Trp Val Gln Gln Lys Pro Gly 645

Lys Ser Pro Arg Gly Leu Ile Gly

650 655

Gly Thr Asn Lys Arg Ala Pro Gly 660

Val Pro Ala Arg Phe Ser Gly Ser

665 670

Leu Leu Gly Gly Lys Ala Ala Leu

675 680

Thr Ile Ser Gly Ala Gln Pro Glu 685

Asp Glu Ala Asp Tyr Tyr Cys Ala

690 695

Leu Trp Tyr Ser Asn His Trp Val 700

Phe Gly Gly Gly Thr Lys Leu Thr

705 710

Val Leu <210> 194 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 194

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

- 230 044325

Pro Ser Val Phe Ile Phe Pro Pro

115 120

Ser Asp Glu Gln Leu Lys Ser Gly

125

Thr Ala Ser Val Val Cys Leu Leu

130 135

Asn Asn Phe Tyr Pro Arg Glu Ala

140

Lys Val Gln Trp Lys Val Asp Asn

145 150

Ala Leu Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr Glu Gln Asp Ser

165

Lys Asp Ser Thr Tyr Ser Leu Ser

170 175

Ser Thr Leu Thr Leu Ser Lys Ala 180

Asp Tyr Glu Lys His Lys Val Tyr

185 190

Ala Cys Glu Val Thr His Gln Gly

195 200

Leu Ser Ser Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210 <210> 195 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 195

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

- 231 044325

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg Tyr Gly

100

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

Asn Trp Phe

Ala Ser Thr

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Glu Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Arg Glu

Pro Tyr Trp

105

Lys Gly Pro 120

Gly Gly Thr

Pro Val Thr

Thr Phe Pro

170

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Pro Gln Val

Gly Gln Gly

Thr Leu Val 110

Ser Val Phe

125

Pro Leu Ala

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asp Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser

- 232 044325

340

345

350

Arg Glu Glu Met

355

Thr Lys Asn Gln Val Ser Leu 360

Thr Cys Asp Val Ser

365

Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp

375

Glu Ser Asp Gly Gln 380

Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro Pro Val

390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu

Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys 420

Ser Val Met His Glu Ala Leu His Asn

425 430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440 445 <210> 196 <211> 714 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 196

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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 Tyr Gly Asn Trp Phe Pro Tyr Trp Gly Gln Gly Thr Leu Val

- 233 044325

100

105

110

Thr Val Ser Ser Ala

115

Ser Thr Lys Gly Pro 120

Ser Val Phe Pro Leu

125

Pro Ser Ser Lys Ser 130

Thr Ser Gly Gly Thr

135

Ala Ala Leu Gly Cys 140

Val Lys Asp Tyr Phe 145

Pro Glu Pro Val Thr 150

Val Ser Trp Asn Ser 155

Ala Leu Thr Ser Gly

165

Val His Thr Phe Pro

170

Ala Val Leu Gln Ser

175

Gly Leu Tyr Ser Leu

180

Ser Ser Val Val Thr

185

Val Pro Ser Ser Ser

190

Gly Thr Gln Thr Tyr

195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asn

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Asp Lys Thr His

220

Cys Pro Pro Cys Pro 225

Ala Pro Pro Val Ala 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Lys His

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Gln

290

Tyr Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Val Ser Asn Lys Ala

325

Leu Pro Ala Pro Ile

330

Glu Lys Thr Ile Ser

335

Ala Lys Gly Gln Pro

340

Arg Glu Pro Gln Val

345

Tyr Thr Leu Pro Pro

350

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Leu 240

Glu

Lys

Lys

Leu

Lys 320

Lys

Ser

- 234 044325

Arg

Gly

Pro 385

Ser

Gln

His

Gly

Val 465

Ser

Val

Ser

Arg

Met 545

His

Gln

Pro

Glu Gln Met

355

Thr Lys Asn

Gln Val Lys 360

Leu Thr Cys

365

Leu Val Lys

Phe Tyr Pro 370

Glu Asn Asn

Phe Phe Leu

Gly Asn Val

420

Tyr Thr Gln

435

Ser Gly Gly 450

Glu Ser Gly

Cys Ala Ala

Arg Gln Ala

500

Lys Tyr Asn

515

Phe Thr Ile 530

Asn Ser Leu

Gly Asn Phe

Gly Thr Leu

580

Gly Ser Gly

595

Ser Asp Ile

375

Tyr Lys Thr 390

Tyr Ser Lys 405

Phe Ser Cys

Lys Ser Leu

Gly Gly Ser

455

Gly Gly Leu

470

Ser Gly Phe 485

Pro Gly Lys

Asn Tyr Ala

Ser Arg Asp

535

Arg Ala Glu

550

Gly Asp Ser 565

Val Thr Val

Lys Pro Gly

Ala Val Glu

Trp Glu Ser

380

Asn Gly Gln

Thr Pro Pro

Leu Thr Val

410

Ser Val Met

425

Ser Leu Ser 440

Gly Gly Gly

Val Gln Pro

Thr Phe Ser

490

Gly Leu Glu

505

Thr Tyr Tyr 520

Asp Ser Lys

Asp Thr Ala

Tyr Val Ser

570

Ser Ser Gly

585

Ser Gly Lys 600

Val Leu Asp 395

Asp Lys Ser

His Glu Ala

Pro Gly Lys

445

Gly Ser Glu

460

Gly Gly Ser 475

Thr Tyr Ala

Trp Val Gly

Ala Asp Ser

525

Asn Thr Leu

540

Val Tyr Tyr 555

Trp Phe Asp

Lys Pro Gly

Pro Gly Ser

605

Ser Asp Gly

400

Arg Trp Gln 415

Leu His Asn 430

Gly Gly Gly

Val Gln Leu

Leu Arg Leu

480

Met Asn Trp

495

Arg Ile Arg 510

Val Lys Gly

Tyr Leu Gln

Cys Val Arg

560

Tyr Trp Gly

575

Ser Gly Lys 590

Gln Ala Val

- 235 044325

Val Thr Gln Glu Pro Ser Leu Thr

610 615

Val Ser Pro Gly Gly Thr Val Thr 620

Leu Thr Cys Gly Ser Ser Thr Gly

625 630

Ala Val Thr Thr Ser Asn Tyr Ala

635 640

Asn Trp Val Gln Gln Lys Pro Gly 645

Lys Ser Pro Arg Gly Leu Ile Gly

650 655

Gly Thr Asn Lys Arg Ala Pro Gly 660

Val Pro Ala Arg Phe Ser Gly Ser

665 670

Leu Leu Gly Gly Lys Ala Ala Leu

675 680

Thr Ile Ser Gly Ala Gln Pro Glu 685

Asp Glu Ala Asp Tyr Tyr Cys Ala

690 695

Leu Trp Tyr Ser Asn His Trp Val 700

Phe Gly Gly Gly Thr Lys Leu Thr

705 710

Val Leu <210> 197 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 197

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

- 236 044325

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210> 198 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 198

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

- 237 044325

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Gln Met Asn

Arg Tyr Gly

100

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Ser Leu Arg 85

Asn Trp Phe

Ala Ser Thr

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Glu Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Ala Glu Asp

Pro Tyr Trp

105

Lys Gly Pro 120

Gly Gly Thr

Pro Val Thr

Thr Phe Pro

170

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Thr Ala Val

Gly Gln Gly

Ser Val Phe

125

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Tyr Cys 95

Thr Leu Val 110

Pro Leu Ala

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asp Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

- 238 044325

Ala Lys Gly Gln Pro Arg Glu Pro 340

Gln Val Tyr Thr Leu Pro Pro Ser

345 350

Arg Glu Glu Met

355

Thr Lys Asn Gln Val Ser Leu 360

Thr Cys Asp Val Ser

365

Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp

375

Glu Ser Asp Gly Gln 380

Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro Pro Val

390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu

Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys 420

Ser Val Met His Glu Ala Leu His Asn

425 430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440 445 <210> 199 <211> 714 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 199

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr 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

- 239 044325

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg Tyr Gly

100

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

Asn Trp Phe

Ala Ser Thr

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Gln Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Arg Glu

Pro Tyr Trp

105

Lys Gly Pro 120

Gly Gly Thr

Pro Val Thr

Thr Phe Pro

170

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Pro Val Ala

Thr Leu Met

250

Val Lys His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Pro Gln Val

Gly Gln Gly

Thr Leu Val 110

Ser Val Phe

125

Pro Leu Ala

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asn Thr

Thr His Thr

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser

- 240 044325

340

345

350

Arg

Gly

Pro 385

Ser

Gln

His

Gly

Val 465

Ser

Val

Ser

Arg

Met 545

His

Gln

Glu Gln Met

355

Thr Lys Asn

Gln Val Lys 360

Leu Thr Cys

365

Leu Val Lys

Phe Tyr Pro 370

Glu Asn Asn

Phe Phe Leu

Gly Asn Val

420

Tyr Thr Gln

435

Ser Gly Gly 450

Glu Ser Gly

Cys Ala Ala

Arg Gln Ala

500

Lys Tyr Asn

515

Phe Thr Ile 530

Asn Ser Leu

Gly Asn Phe

Gly Thr Leu

580

Ser Asp Ile

375

Tyr Lys Thr 390

Tyr Ser Lys 405

Phe Ser Cys

Lys Ser Leu

Gly Gly Ser

455

Gly Gly Leu

470

Ser Gly Phe 485

Pro Gly Lys

Asn Tyr Ala

Ser Arg Asp

535

Arg Ala Glu

550

Gly Asp Ser 565

Val Thr Val

Ala Val Glu

Trp Glu Ser

380

Asn Gly Gln

Thr Pro Pro

Leu Thr Val

410

Ser Val Met

425

Ser Leu Ser 440

Gly Gly Gly

Val Gln Pro

Thr Phe Ser

490

Gly Leu Glu

505

Thr Tyr Tyr 520

Asp Ser Lys

Asp Thr Ala

Tyr Val Ser

570

Ser Ser Gly

585

Val Leu Asp 395

Asp Lys Ser

His Glu Ala

Pro Gly Lys

445

Gly Ser Glu

460

Gly Gly Ser 475

Thr Tyr Ala

Trp Val Gly

Ala Asp Ser

525

Asn Thr Leu

540

Val Tyr Tyr 555

Trp Phe Ala

Lys Pro Gly

Ser Asp Gly

400

Arg Trp Gln 415

Leu His Asn 430

Gly Gly Gly

Val Gln Leu

Leu Arg Leu

480

Met Asn Trp

495

Arg Ile Arg 510

Val Lys Gly

Tyr Leu Gln

Cys Val Arg

560

Tyr Trp Gly

575

Ser Gly Lys 590

- 241 044325

Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gln Ala Val

595 600605

Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr

610 615620

Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser Asn Tyr Ala

625 630 635640

Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly Leu Ile Gly

645 650655

Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe Ser Gly Ser

660 665670

Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala Gln Pro Glu

675 680685

Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn His Trp Val

690 695700

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 705710 <210> 200 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 200

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp Thr Asn 20 2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

- 242 044325

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210> 201 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 201

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser ArgSer

2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val

5560

- 243 044325

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn 70

Ser Lys Asn Thr Leu 75

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Arg Tyr Gly Asn

100

Trp Phe Pro Tyr Trp

105

Gly Gln Gly Thr Leu

110

Thr Val Ser Ser Ala

115

Ser Thr Lys Gly Pro 120

Ser Val Phe Pro Leu

125

Pro Ser Ser Lys Ser 130

Thr Ser Gly Gly Thr

135

Ala Ala Leu Gly Cys 140

Val Lys Asp Tyr Phe 145

Pro Glu Pro Val Thr 150

Val Ser Trp Asn Ser 155

Ala Leu Thr Ser Gly

165

Val His Thr Phe Pro

170

Ala Val Leu Gln Ser

175

Gly Leu Tyr Ser Leu

180

Ser Ser Val Val Thr

185

Val Pro Ser Ser Ser

190

Gly Thr Gln Thr Tyr 195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asp

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Asp Lys Thr His

220

Cys Pro Pro Cys Pro 225

Ala Pro Pro Val Ala 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Lys His

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Glu 290

Tyr Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Tyr 80

Cys

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Leu 240

Glu

Lys

Lys

Leu

Lys 320

- 244 044325

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440445 <210> 202 <211> 718 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 202

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 65 70 7580

- 245 044325

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Gly 225

Val

Thr

Gly

Thr

Asp 305

Asp

Gln Met Asn

Arg Tyr Gly

100

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Gly Gly Gly

Gln Pro Gly

Phe Ser Thr

260

Leu Glu Trp

275

Tyr Tyr Ala 290

Ser Lys Asn

Thr Ala Val

Ser Leu Arg 85

Asn Trp Phe

Ala Ser Thr

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Ser Glu Val

230

Gly Ser Leu 245

Tyr Ala Met

Val Gly Arg

Asp Ser Val

295

Thr Leu Tyr

310

Tyr Tyr Cys 325

Ala Glu Asp

Pro Tyr Trp

105

Lys Gly Pro 120

Gly Gly Thr

Pro Val Thr

Thr Phe Pro

170

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Gln Leu Val

Arg Leu Ser

250

Ser Trp Val

265

Ile Arg Ser 280

Lys Gly Arg

Leu Gln Met

Val Arg His

330

Thr Ala Val

Gly Gln Gly

Ser Val Phe

125

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Gly Gly

220

Glu Ser Gly 235

Cys Ala Ala

Arg Gln Ala

Lys Tyr Asn

285

Phe Thr Ile

300

Asn Ser Leu 315

Gly Asn Phe

Tyr Tyr Cys 95

Thr Leu Val 110

Pro Leu Ala

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asn Thr

Gly Gly Ser

Gly Gly Leu

240

Ser Gly Phe

255

Pro Gly Lys 270

Asn Tyr Ala

Ser Arg Asp

Arg Ala Glu

320

Gly Asp Ser

335

- 246 044325

Tyr

Ser

Ser

Thr 385

Gly

Gly

Gly

Leu

Ala 465

Thr

Thr

Leu

Glu

Lys 545

Lys

Leu

Val Ser Trp

340

Phe Ala Tyr

Trp Gly Gln

345

Gly Thr Leu

Val Thr Val 350

Ser Gly Lys

355

Gly Lys Pro 370

Val Ser Pro

Ala Val Thr

Lys Ser Pro

420

Val Pro Ala

435

Thr Ile Ser 450

Leu Trp Tyr

Val Leu Gly

Cys Pro Pro

500

Phe Pro Pro

515

Val Thr Cys 530

Phe Asn Trp

Pro Arg Glu

Thr Val Leu

Pro Gly Ser

Gly Ser Gln

375

Gly Gly Thr

390

Thr Ser Asn 405

Arg Gly Leu

Arg Phe Ser

Gly Ala Gln

455

Ser Asn His

470

Gly Gly Gly 485

Cys Pro Ala

Lys Pro Lys

Val Val Val

535

Tyr Val Asp

550

Glu Gln Tyr 565

His Gln Asp

Gly Lys Pro 360

Gly Ser Gly

365

Lys Pro Gly

Ala Val Val

Val Thr Leu

Tyr Ala Asn

410

Ile Gly Gly

425

Gly Ser Leu 440

Pro Glu Asp

Trp Val Phe

Ser Gly Gly

490

Pro Pro Val

505

Asp Thr Leu 520

Asp Val Lys

Gly Val Glu

Asn Ser Thr

570

Trp Leu Asn

Thr Gln Glu

380

Thr Cys Gly 395

Trp Val Gln

Thr Asn Lys

Leu Gly Gly

445

Glu Ala Asp

460

Gly Gly Gly 475

Gly Gly Ser

Ala Gly Pro

Met Ile Ser

525

His Glu Asp

540

Val His Asn 555

Tyr Arg Val

Gly Lys Glu

Pro Ser Leu

Ser Ser Thr

400

Gln Lys Pro

415

Arg Ala Pro 430

Lys Ala Ala

Tyr Tyr Cys

Thr Lys Leu

480

Lys Thr His

495

Ser Val Phe 510

Arg Thr Pro

Pro Glu Val

Ala Lys Thr

560

Val Ser Val

575

Tyr Lys Cys

- 247 044325

580

585

590

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

595 600605

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

610 615620

Ser Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val

625 630 635640

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

645 650655

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

660 665670

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

675 680685

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

690 695700

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

705 710715 <210> 203 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 203

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp ThrAsn

2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly

5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

- 248 044325

70

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210> 204 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 204

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val

- 249 044325

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Gly Arg Phe Thr Ile 70

Gln Met Asn Ser Leu

Arg Tyr Gly Asn Trp 100

Val Ser Ser Ala Ser

115

Ser Ser Lys Ser Thr 130

Lys Asp Tyr Phe Pro

150

Leu Thr Ser Gly Val

165

Leu Tyr Ser Leu Ser 180

Thr Gln Thr Tyr Ile 195

Val Asp Lys Lys Val 210

Pro Pro Cys Pro Ala

230

Pro Pro Lys Pro Lys

245

Thr Cys Val Val Val

260

Asn Trp Tyr Val Asp

275

Arg Glu Glu Glu Tyr 290

Ser Arg Asp Asn Ser 75

Lys Asn Thr Leu Tyr 80

Arg Ala Glu Asp Thr

Ala Val Tyr Tyr Cys 95

Phe Pro Tyr Trp Gly 105

Gln Gly Thr Leu Val 110

Thr Lys Gly Pro Ser 120

Ser Gly Gly Thr Ala 135

Glu Pro Val Thr Val

155

His Thr Phe Pro Ala

170

Ser Val Val Thr Val

185

Cys Asn Val Asn His

200

Glu Pro Lys Ser Cys 215

Pro Pro Val Ala Gly

235

Asp Thr Leu Met Ile

250

Asp Val Lys His Glu 265

Gly Val Glu Val His

280

Asn Ser Thr Tyr Arg 295

Val Phe Pro Leu Ala

125

Ala Leu Gly Cys Leu 140

Ser Trp Asn Ser Gly

160

Val Leu Gln Ser Ser

175

Pro Ser Ser Ser Leu

190

Lys Pro Ser Asp Thr

205

Asp Lys Thr His Thr 220

Pro Ser Val Phe Leu

240

Ser Arg Thr Pro Glu

255

Asp Pro Glu Val Lys

270

Asn Ala Lys Thr Lys

285

Val Val Ser Val Leu 300

- 250 044325

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

325 330335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345350

Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Asp Val Ser

355 360365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asp Gly Gln

370 375380

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

385 390 395400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Glu

405 410415

Gln Gly Asp Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440445 <210> 205 <211> 718 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 205

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser ArgSer

2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val

5560

- 251 044325

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Gly 225

Val

Thr

Gly

Thr

Asp 305

Gly Arg Phe

Gln Met Asn

Arg Tyr Gly

100

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Gly Gly Gly

Gln Pro Gly

Phe Ser Thr

260

Leu Glu Trp

275

Tyr Tyr Ala 290

Ser Lys Asn

Thr Ile Ser

Ser Leu Arg 85

Asn Trp Phe

Ala Ser Thr

Ser Thr Ser

135

Phe Pro Glu

150

Gly Val His 165

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Ser Glu Val

230

Gly Ser Leu 245

Tyr Ala Met

Val Gly Arg

Asp Ser Val

295

Thr Leu Tyr

310

Arg Asp Asn

Ala Glu Asp

Pro Tyr Trp

105

Lys Gly Pro 120

Gly Gly Thr

Pro Val Thr

Thr Phe Pro

170

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Gln Leu Val

Arg Leu Ser

250

Ser Trp Val

265

Ile Arg Ser 280

Lys Gly Arg

Leu Gln Met

Ser Lys Asn 75

Thr Ala Val

Gly Gln Gly

Ser Val Phe

125

Ala Ala Leu

140

Val Ser Trp 155

Ala Val Leu

Val Pro Ser

His Lys Pro

205

Cys Gly Gly

220

Glu Ser Gly 235

Cys Ala Ala

Arg Gln Ala

Lys Tyr Asn

285

Phe Thr Ile

300

Asn Ser Leu 315

Thr Leu Tyr

Tyr Tyr Cys 95

Thr Leu Val 110

Pro Leu Ala

Gly Cys Leu

Asn Ser Gly

160

Gln Ser Ser

175

Ser Ser Leu 190

Ser Asn Thr

Gly Gly Ser

Gly Gly Leu

240

Ser Gly Phe

255

Pro Gly Lys 270

Asn Tyr Ala

Ser Arg Asp

Arg Ala Glu

320

- 252 044325

Asp

Tyr

Ser

Ser

Thr 385

Gly

Gly

Gly

Leu

Ala 465

Thr

Thr

Leu

Glu

Lys 545

Lys

Thr Ala Val

Tyr Tyr Cys 325

Val Arg His

330

Gly Asn Phe

Gly Asp Ser

335

Val Ser Trp

340

Phe Ala Tyr

Trp Gly Gln

345

Gly Thr Leu

Val Thr Val 350

Ser Gly Lys

355

Gly Lys Pro 370

Val Ser Pro

Ala Val Thr

Lys Ser Pro

420

Val Pro Ala

435

Thr Ile Ser 450

Leu Trp Tyr

Val Leu Gly

Cys Pro Pro

500

Phe Pro Pro

515

Val Thr Cys 530

Phe Asn Trp

Pro Arg Glu

Pro Gly Ser

Gly Lys Pro 360

Gly Ser Gly

365

Lys Pro Gly

Gly Ser Gln

375

Gly Gly Thr

390

Thr Ser Asn 405

Arg Gly Leu

Arg Phe Ser

Gly Ala Gln

455

Ser Asn His

470

Gly Gly Gly 485

Cys Pro Ala

Lys Pro Lys

Val Val Val

535

Tyr Val Asp

550

Glu Gln Tyr 565

Ala Val Val

Val Thr Leu

Tyr Ala Asn

410

Ile Gly Gly

425

Gly Ser Leu 440

Pro Glu Asp

Trp Val Phe

Ser Gly Gly

490

Pro Pro Val

505

Asp Thr Leu 520

Asp Val Lys

Gly Val Glu

Asn Ser Thr

570

Thr Gln Glu

380

Thr Cys Gly 395

Trp Val Gln

Thr Asn Lys

Leu Gly Gly

445

Glu Ala Asp

460

Gly Gly Gly 475

Gly Gly Ser

Ala Gly Pro

Met Ile Ser

525

His Glu Asp

540

Val His Asn 555

Tyr Arg Val

Pro Ser Leu

Ser Ser Thr

400

Gln Lys Pro

415

Arg Ala Pro 430

Lys Ala Ala

Tyr Tyr Cys

Thr Lys Leu

480

Lys Thr His

495

Ser Val Phe 510

Arg Thr Pro

Pro Glu Val

Ala Lys Thr

560

Val Ser Val

575

- 253 044325

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

580 585590

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

595 600605

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

610 615620

Ser Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val

625 630 635640

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

645 650655

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

660 665670

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

675 680685

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

690 695700

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 705 710715 <210> 206 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 206

Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asn Val Asp ThrAsn

2530

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Ala Leu Ile 35 4045

Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly

5560

- 254 044325

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210> 207 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 207

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 2530

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

- 255 044325

Ser

Lys 65

Leu

Ala

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Phe

Val

Phe

Pro

Glu Ile Asn Pro Asp 50

Gly Arg Phe Thr Ile 70

Gln Met Asn Ser Leu

Arg Tyr Gly Asn Trp 100

Val Ser Ser Ala Ser

115

Ser Ser Lys Ser Thr 130

Lys Asp Tyr Phe Pro

150

Leu Thr Ser Gly Val

165

Leu Tyr Ser Leu Ser 180

Thr Gln Thr Tyr Ile 195

Val Asp Lys Lys Val 210

Pro Pro Cys Pro Ala

230

Pro Pro Lys Pro Lys

245

Thr Cys Val Val Val

260

Asn Trp Tyr Val Asp

275

Arg Glu Glu Glu Tyr

Ser Ser Thr Ile Asn 55

Ser Arg Asp Asn Ser 75

Arg Ala Glu Asp Thr

Phe Pro Tyr Trp Gly

105

Thr Lys Gly Pro Ser 120

Ser Gly Gly Thr Ala 135

Glu Pro Val Thr Val

155

His Thr Phe Pro Ala

170

Ser Val Val Thr Val

185

Cys Asn Val Asn His

200

Glu Pro Lys Ser Cys 215

Pro Pro Val Ala Gly

235

Asp Thr Leu Met Ile

250

Asp Val Lys His Glu

265

Gly Val Glu Val His

280

Asn Ser Thr Tyr Arg

Tyr Ala Thr Ser Val 60

Lys Asn Thr Leu Tyr 80

Ala Val Tyr Tyr Cys 95

Gln Gly Thr Leu Val

110

Val Phe Pro Leu Ala

125

Ala Leu Gly Cys Leu 140

Ser Trp Asn Ser Gly

160

Val Leu Gln Ser Ser

175

Pro Ser Ser Ser Leu

190

Lys Pro Ser Asp Thr

205

Asp Lys Thr His Thr 220

Pro Ser Val Phe Leu

240

Ser Arg Thr Pro Glu

255

Asp Pro Glu Val Lys

270

Asn Ala Lys Thr Lys

285

Val Val Ser Val Leu

- 256 044325

290 295 300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315 320

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

325 330

Ile Ser Lys

335

Ala Lys

Gly Gln Pro Arg Glu Pro Gln Val

340 345

Tyr Thr Leu Pro Pro Ser

350

Arg Glu Glu Met

355

Thr Lys Asn Gln Val Ser Leu 360

Thr Cys Asp Val Ser

365

Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp 375

Glu Ser Asp Gly Gln 380

Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro Pro Val

390 395

Leu Asp Ser Asp Gly

400

Ser Phe Phe Leu

Tyr Ser Lys Leu Thr Val Asp

405 410

Lys Ser Arg Trp Glu

415

Gln Gly Asp Val Phe Ser Cys 420

Ser Val Met His Glu Ala Leu His Asn

425 430

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser Pro Gly Lys

440 445 <210> 208 <211> 718 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 208

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Ser 20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Ser Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Thr Ser Val

- 257 044325

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn 70

Ser Lys Asn Thr Leu 75

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Arg Tyr Gly Asn

100

Trp Phe Pro Tyr Trp

105

Gly Gln Gly Thr Leu

110

Thr Val Ser Ser Ala

115

Ser Thr Lys Gly Pro 120

Ser Val Phe Pro Leu

125

Pro Ser Ser Lys Ser 130

Thr Ser Gly Gly Thr

135

Ala Ala Leu Gly Cys

140

Val Lys Asp Tyr Phe 145

Pro Glu Pro Val Thr 150

Val Ser Trp Asn Ser 155

Ala Leu Thr Ser Gly

165

Val His Thr Phe Pro

170

Ala Val Leu Gln Ser

175

Gly Leu Tyr Ser Leu

180

Ser Ser Val Val Thr

185

Val Pro Ser Ser Ser

190

Gly Thr Gln Thr Tyr 195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asn

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Gly Gly Gly Gly

220

Gly Gly Gly Gly Ser 225

Glu Val Gln Leu Val 230

Glu Ser Gly Gly Gly 235

Val Gln Pro Gly Gly

245

Ser Leu Arg Leu Ser

250

Cys Ala Ala Ser Gly

255

Thr Phe Ser Thr Tyr

260

Ala Met Asn Trp Val

265

Arg Gln Ala Pro Gly

270

Gly Leu Glu Trp Val

275

Gly Arg Ile Arg Ser 280

Lys Tyr Asn Asn Tyr

285

Thr Tyr Tyr Ala Asp

290

Ser Val Lys Gly Arg

295

Phe Thr Ile Ser Arg

300

Tyr 80

Cys

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Ser

Leu 240

Phe

Lys

Ala

Asp

- 258 044325

Asp 305

Asp

Tyr

Ser

Ser

Thr 385

Gly

Gly

Gly

Leu

Ala 465

Thr

Thr

Leu

Glu

Lys 545

Ser Lys Asn

Thr Ala Val

Val Ser Trp

340

Ser Gly Lys

355

Gly Lys Pro 370

Val Ser Pro

Ala Val Thr

Lys Ser Pro

420

Val Pro Ala

435

Thr Ile Ser 450

Leu Trp Tyr

Val Leu Gly

Cys Pro Pro

500

Phe Pro Pro

515

Val Thr Cys 530

Phe Asn Trp

Thr Leu Tyr

310

Tyr Tyr Cys 325

Phe Ala Tyr

Pro Gly Ser

Gly Ser Gln

375

Gly Gly Thr

390

Thr Ser Asn 405

Arg Gly Leu

Arg Phe Ser

Gly Ala Gln

455

Ser Asn His

470

Gly Gly Gly 485

Cys Pro Ala

Lys Pro Lys

Val Val Val

535

Tyr Val Asp

550

Leu Gln Met

Val Arg His

330

Trp Gly Gln

345

Gly Lys Pro 360

Ala Val Val

Val Thr Leu

Tyr Ala Asn

410

Ile Gly Gly

425

Gly Ser Leu 440

Pro Glu Asp

Trp Val Phe

Ser Gly Gly

490

Pro Pro Val

505

Asp Thr Leu 520

Asp Val Lys

Gly Val Glu

Asn Ser Leu 315

Gly Asn Phe

Gly Thr Leu

Gly Ser Gly

365

Thr Gln Glu

380

Thr Cys Gly 395

Trp Val Gln

Thr Asn Lys

Leu Gly Gly

445

Glu Ala Asp

460

Gly Gly Gly 475

Gly Gly Ser

Ala Gly Pro

Met Ile Ser

525

His Glu Asp

540

Val His Asn 555

Arg Ala Glu

320

Gly Asp Ser

335

Val Thr Val 350

Lys Pro Gly

Pro Ser Leu

Ser Ser Thr

400

Gln Lys Pro

415

Arg Ala Pro 430

Lys Ala Ala

Tyr Tyr Cys

Thr Lys Leu

480

Lys Thr His

495

Ser Val Phe 510

Arg Thr Pro

Pro Glu Val

Ala Lys Thr

560

- 259 044325

Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val

565 570575

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

580 585590

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

595 600605

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

610 615620

Ser Arg Glu Gln Met Thr Lys Asn Gln Val Lys Leu Thr Cys Leu Val

625 630 635640

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

645 650655

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

660 665670

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

675 680685

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

690 695700

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

705 710715 <210> 209 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 209

Asp Ile Val Met 1

Thr Gln Ser Pro 5

Ser Ser Leu Ser 10

Ala Ser Val Gly 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Gln Asn 25

Val Asp Thr Asn 30

Val Ala Trp Tyr

Gln Gln Lys Pro 40

Gly Gln Ser Pro

Lys Ala Leu Ile 45

- 260 044325

Tyr Ser Ala Ser Tyr Arg Tyr Ser

55

Gly Val Pro

Asp Arg Phe Thr Gly 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 Phe Cys Gln Gln Tyr Asp Ser Tyr Pro Leu 85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105 110

Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210 <210> 210 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 210

Glu Val Gln Leu Val Glu Ser Gly Gly 1 5

Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25

Gly Phe Thr Phe Ser Thr Tyr 30

- 261 044325

Ala

Gly

Ser 65

Leu

Tyr

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

His

Met Asn Trp Val Arg 35

Arg Ile Arg Ser Lys 50

Val Lys Gly Arg Phe 70

Tyr Leu Gln Met Asn 85

Cys Val Arg His Gly 100

Tyr Trp Gly Gln Gly 115

Ser Gly Lys Pro Gly 130

Gln Ala Val Val Thr

150

Thr Val Thr Leu Thr

165

Asn Tyr Ala Asn Trp 180

Leu Ile Gly Gly Thr

195

Ser Gly Ser Leu Leu 210

Gln Pro Glu Asp Glu

230

His Trp Val Phe Gly

245

His His His His

260

Gln Ala Pro Gly Lys 40

Tyr Asn Asn Tyr Ala 55

Thr Ile Ser Arg Asp

Ser Leu Arg Ala Glu 90

Asn Phe Gly Asp Ser 105

Thr Leu Val Thr Val

120

Ser Gly Lys Pro Gly 135

Gln Glu Pro Ser Leu

155

Cys Gly Ser Ser Thr

170

Val Gln Gln Lys Pro 185

Asn Lys Arg Ala Pro 200

Gly Gly Lys Ala Ala 215

Ala Asp Tyr Tyr Cys

235

Gly Gly Thr Lys Leu

250

Gly Leu Glu Trp Val 45

Thr Tyr Tyr Ala Asp 60

Asp Ser Lys Asn Thr 80

Asp Thr Ala Val Tyr 95

Tyr Val Ser Trp Phe

110

Ser Ser Gly Lys Pro

125

Ser Gly Lys Pro Gly 140

Thr Val Ser Pro Gly

160

Gly Ala Val Thr Thr

175

Gly Lys Ser Pro Arg 190

Gly Val Pro Ala Arg

205

Leu Thr Ile Ser Gly 220

Ala Leu Trp Tyr Ser

240

Thr Val Leu Gly Ser

255 <210> 211 <211> 254

- 262 044325 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 211

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Gly Arg Ile Arg 50

Ser Lys Tyr Asn 55

Asn Tyr Ala Thr 60

Tyr Tyr Ala Asp

Ser Val Lys Gly 65

Arg Phe Thr Ile 70

Ser Arg Asp Asp 75

Ser Lys Asn Thr 80

Leu Tyr Leu Gln

Met Asn Ser Leu 85

Arg Ala Glu Asp 90

Thr Ala Val Tyr 95

Tyr Cys Val Arg

100

His Gly Asn Phe

Gly Asp Ser Tyr 105

Val Ser Trp Phe

110

Ala Tyr Trp Gly

115

Gln Gly Thr Leu

120

Val Thr Val Ser

Ser Gly Lys Pro 125

Gly Ser Gly Lys 130

Pro Gly Ser Gly

135

Lys Pro Gly Ser

140

Gly Lys Pro Gly

Ser Gln Ala Val 145

Val Thr Gln Glu

150

Pro Ser Leu Thr

155

Val Ser Pro Gly

160

Gly Thr Val Thr

Leu Thr Cys Gly 165

Ser Ser Thr Gly 170

Ala Val Thr Thr

175

Ser Asn Tyr Ala

180

Asn Trp Val Gln

Gln Lys Pro Gly 185

Lys Ser Pro Arg 190

Gly Leu Ile Gly

195

Gly Thr Asn Lys

200

Arg Ala Pro Gly

Val Pro Ala Arg 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala

210 215

Leu Thr Ile Ser Gly 220

- 263 044325

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr Ser

235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245 250 <210> 212 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 212

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 213 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide

- 264 044325 <400> 213

Gln Ala Val Val 1

Thr Gln Glu Pro 5

Ser Leu Thr Val

Ser Pro Gly Gly 15

Thr Val Thr Leu

Thr Cys Gly Ser

Ser Thr Gly Ala 25

Val Thr Thr Ser

Asn Tyr Ala Asn

Trp Val Gln Gln 40

Lys Pro Gly Lys

Ser Pro Arg Gly 45

Leu Ile Gly Gly 50

Thr Asn Lys Arg 55

Ala Pro Gly Val 60

Pro Ala Arg Phe

Ser Gly Ser Leu 65

Leu Gly Gly Lys 70

Ala Ala Leu Thr

Ile Ser Gly Ala 80

Gln Pro Glu Asp

Glu Ala Asp Tyr 85

Tyr Cys Ala Leu 90

Trp Tyr Ser Asn 95

His Trp Val

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 100 105 <210> 214 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 214

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

- 265 044325

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250255

His His His

His His His 260 <210> 215 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 215

Glu Val Gln Leu Val Glu Ser Gly Gly 1 5

Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25

Gly Leu Val Gln Pro Gly Gly

15

Gly Phe Thr Phe Ser Thr Tyr 30

- 266 044325

Ala Met Asn Trp Val 35

Arg Gln

Gly Arg Ile Arg Ser 50

Lys Tyr 55

Ser Val Lys Gly Arg 65

Ph Thr 70

Leu Tyr Leu Gln Met 85

Asn Ser

Ala Pro 40

Asn Asn

Ile Ser

Leu Arg

Gly Lys

Tyr Ala

Arg Asp

Ala Glu 90

Gly Leu 45

Thr Tyr 60

Asp Ser

Asp Thr

Glu Trp

Tyr Ala

Lys Asn

Ala Val

Tyr Cys Val Arg His

100

Gly Asn

Phe Gly

105

Asp Ser

Tyr Val

Ser Trp 110

Ala Tyr Trp Gly Gln 115

Gly Thr

Leu Val 120

Thr Val

Ser Ser

125

Gly Lys

Gly Ser Gly Lys Pro 130

Gly Ser

135

Gly Lys

Pro Gly

Ser Gly 140

Lys Pro

Ser Gln Ala Val Val 145

Thr Gln 150

Glu Pro

Ser Leu

155

Thr Val

Ser Pro

Gly Thr Val Thr Leu

165

Thr Cys

Gly Ser

Ser Thr 170

Gly Ala

Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val

Gln Gln

185

Lys Pro

Gly Lys

Ser Pro 190

Gly Leu Ile Gly Gly

195

Thr Asn

Lys Arg 200

Ala Pro

Gly Val

205

Pro Ala

Phe Ser Gly Ser Leu 210

Leu Gly

215

Gly Lys

Ala Ala

Leu Thr

220

Ile Ser

Ala Gln Pro Glu Asp 225

Glu Ala

230

Asp Tyr

Tyr Cys

235

Ala Leu

Trp Tyr

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Asn His Trp Val Phe

245

Gly Gly

Gly Thr

Lys Leu 250

Thr Val

Leu <210> 216 <211> 125 <212> PROTEIN <213> Artificial <220>

subsequence

- 267 044325 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 216

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115120

Ser Ser

125 <210> 217 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 217

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr ThrSer

2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

5560

- 268 044325

Ser Gly Ser Leu 65

Gln Pro Glu Asp

Leu Gly Gly 70

Glu Ala Asp 85

His Trp Val Phe

100

Gly Gly Gly

Lys Ala Ala Leu Thr Ile Ser Gly Ala 75 80

Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 90 95

Thr Lys Leu Thr Val Leu

105 <210> 218 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 218

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu 20

Ser Cys Ala Ala Ser Gly Phe Thr Phe 25

Ser Thr Tyr 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

- 269 044325

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250255

His His His His His

260 <210> 219 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 219

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

- 270 044325

Tyr Cys Val Arg His Gly Asn Phe

100

Gly Asp Ser Tyr Val Ser Trp Phe

105 110

Asp Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

120 125

Gly Ser Gly Lys Pro

130

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

135 140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

150 155 160

Gly Thr Val Thr Leu Thr Cys 165

Gly Ser Ser Thr Gly Ala Val Thr Thr

170 175

Ser Asn Tyr Ala Asn Trp Val 180

Gln Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly Thr Asn 195

Lys Arg Ala Pro Gly Val Pro Ala Arg

200 205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu

250 <210> 220 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 220

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

- 271 044325

Gly Arg Ile Arg Ser Lys Tyr Asn

55

Asn Tyr Ala Thr Tyr Tyr Ala Asp 60

Ser Val Lys Gly Arg Phe Thr Ile 65 70

Ser Arg Asp Asp Ser Lys Asn Thr

80

Leu Tyr Leu Gln Met Asn Ser Leu 85

Arg Ala Glu Asp Thr Ala Val Tyr

95

Tyr Cys Val Arg His Gly Asn Phe

100

Gly Asp Ser Tyr Val Ser Trp Phe

105 110

Asp Tyr Trp Gly Gln Gly Thr Leu

115 120

Val Thr Val Ser Ser

125 <210> 221 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 221

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 222 <211> 262 <212> PROTEIN

- 272 044325 <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 222

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Ser Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Gly Arg Ile Arg 50

Ser Lys Tyr Asn 55

Asn Tyr Ala Thr 60

Tyr Tyr Ala Asp

Ser Val Lys Gly 65

Arg Phe Thr Ile 70

Ser Arg Asp Asp

Ser Lys Asn Thr 80

Leu Tyr Leu Gln

Met Asn Ser Leu 85

Arg Ala Glu Asp 90

Thr Ala Val Tyr 95

Tyr Cys Val Arg

100

His Gly Asn Phe

Gly Asp Ser Tyr 105

Val Ser Trp Phe

110

Ala Tyr Trp Gly

115

Gln Gly Thr Leu

120

Val Thr Val Ser

Ser Gly Lys Pro 125

Gly Ser Gly Lys 130

Pro Gly Ser Gly

135

Lys Pro Gly Ser

140

Gly Lys Pro Gly

Ser Gln Ala Val 145

Val Thr Gln Glu

150

Pro Ser Leu Thr

155

Val Ser Pro Gly

160

Gly Thr Val Thr

Leu Thr Cys Gly 165

Ser Ser Thr Gly 170

Ala Val Thr Thr

175

Ser Asn Tyr Ala

180

Asn Trp Val Gln

Gln Lys Pro Gly 185

Lys Ser Pro Arg 190

Gly Leu Ile Gly

195

Gly Thr Asn Lys

200

Arg Ala Pro Gly

Val Pro Ala Arg 205

Phe Ser Gly Ser Leu Leu Gly Gly

210 215

Lys Ala Ala

Leu Thr Ile Ser Gly

220

- 273 044325

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr Ser

235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250 255

His His His His His

260 <210> 223 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 223

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu 20

Ser Cys Ala Ala Ser Gly Phe Thr Phe 25

Ser Thr Tyr 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

- 274 044325

Gly Thr Val Thr Leu Thr Cys 165

Gly Ser Ser Thr

170

Gly Ala Val Thr Thr

175

Ser Asn Tyr Ala Asn Trp Val 180

Gln Gln Lys Pro

185

Gly Lys Ser Pro Arg 190

Gly Leu Ile Gly Gly Thr Asn 195

Lys Arg Ala Pro 200

Gly Val Pro Ala Arg

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu

250 <210> 224 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 224

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

- 275 044325

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125 <210> 225 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 225

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 226 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 226

Glu Val Gln Leu Val Glu Ser Gly Gly 1 5

Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25

Gly Phe Thr Phe Ser Thr Tyr

- 276 044325

Ala Met Asn

Trp Val Arg

Gln Ala Pro

Gly Lys Gly

Leu Glu Trp 45

Gly Arg Ile 50

Arg Ser Lys

Ala Asn Asn 55

Tyr Ala Thr 60

Tyr Tyr Ala

Ser Val Lys 65

Gly Arg Phe

Thr Ile Ser

Arg Asp Asp 75

Ser Lys Asn

Leu Tyr Leu

Gln Met Asn

Ser Leu Arg

Ala Glu Asp 90

Thr Ala Val

Tyr Cys Val

Arg His Gly 100

Asn Phe Gly

105

Asp Ser Tyr

Val Ser Trp

110

Ala Tyr Trp

115

Gly Gln Gly

Thr Leu Val

120

Thr Val Ser

Ser Gly Lys 125

Gly Ser Gly

130

Lys Pro Gly

Ser Gly Lys 135

Pro Gly Ser

140

Gly Lys Pro

Ser Gln Ala 145

Val Val Thr

150

Gln Glu Pro

Ser Leu Thr

155

Val Ser Pro

Gly Thr Val

Thr Leu Thr

165

Cys Gly Ser

Ser Thr Gly 170

Ala Val Thr

175

Ser Asn Tyr

Ala Asn Trp 180

Val Gln Gln

185

Lys Pro Gly

Lys Ser Pro

190

Gly Leu Ile

195

Gly Gly Thr

Asn Lys Arg

200

Ala Pro Gly

Val Pro Ala 205

Phe Ser Gly 210

Ser Leu Leu

Gly Gly Lys 215

Ala Ala Leu

220

Thr Ile Ser

Ala Gln Pro 225

Glu Asp Glu

230

Ala Asp Tyr

Tyr Cys Ala

235

Leu Trp Tyr

Asn His Trp

Val Phe Gly

245

Gly Gly Thr

Lys Leu Thr 250

Val Leu Gly

255

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Ser

His His His

His His His

260 <210> 227 <211> 254 <212> PROTEIN

- 277 044325 <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 227

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Gly Arg Ile Arg 50

Ser Lys Ala Asn 55

Asn Tyr Ala Thr 60

Tyr Tyr Ala Asp

Ser Val Lys Gly 65

Arg Phe Thr Ile 70

Ser Arg Asp Asp

Ser Lys Asn Thr 80

Leu Tyr Leu Gln

Met Asn Ser Leu 85

Arg Ala Glu Asp 90

Thr Ala Val Tyr 95

Tyr Cys Val Arg

100

His Gly Asn Phe

Gly Asp Ser Tyr 105

Val Ser Trp Phe

110

Ala Tyr Trp Gly

115

Gln Gly Thr Leu

120

Val Thr Val Ser

Ser Gly Lys Pro 125

Gly Ser Gly Lys 130

Pro Gly Ser Gly

135

Lys Pro Gly Ser

140

Gly Lys Pro Gly

Ser Gln Ala Val 145

Val Thr Gln Glu

150

Pro Ser Leu Thr

155

Val Ser Pro Gly

160

Gly Thr Val Thr

Leu Thr Cys Gly 165

Ser Ser Thr Gly 170

Ala Val Thr Thr

175

Ser Asn Tyr Ala

180

Asn Trp Val Gln

Gln Lys Pro Gly 185

Lys Ser Pro Arg 190

Gly Leu Ile Gly

195

Gly Thr Asn Lys

200

Arg Ala Pro Gly

Val Pro Ala Arg 205

Phe Ser Gly Ser Leu Leu Gly Gly

210 215

Lys Ala Ala

Leu Thr Ile Ser Gly

220

- 278 044325

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr Ser

235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245 250 <210> 228 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 228

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 229 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 229

- 279 044325

Gln Ala Val Val 1

Thr Gln 5

Thr Val Thr Leu

Thr Cys

Asn Tyr Ala Asn 35

Trp Val

Glu Pro Ser Leu Thr Val Ser Pro Gly Gly 1015

Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 2530

Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 4045

Leu Ile Gly Gly Thr Asn Lys Arg

55

Ser Gly Ser Leu Leu Gly Gly Lys 65 70

Gln Pro Glu Asp Glu Ala Asp Tyr 85

Ala Pro Gly Val Pro Ala Arg Phe 60

Ala Ala Leu Thr Ile Ser Gly Ala 75 80

Tyr Cys Ala Leu Trp Tyr Ser Asn 90 95

His Trp Val Phe

100

Gly Gly Gly Thr Lys Leu Thr Val Leu 105 <210> 230 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 230

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

- 280 044325

Tyr Cys Val Arg His Gly Asn Phe Gly Pro Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250255

His His His His His

260 <210> 231 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 231

Glu Val Gln Leu Val Glu Ser Gly Gly 1 5

Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25

Gly Phe Thr Phe Ser Thr Tyr

- 281 044325

Ala Met Asn Trp Val 35

Arg Gln

Gly Arg Ile Arg Ser 50

Lys Tyr 55

Ser Val Lys Gly Arg 65

Ph Thr 70

Leu Tyr Leu Gln Met 85

Asn Ser

Ala Pro 40

Asn Asn

Ile Ser

Leu Arg

Gly Lys

Tyr Ala

Arg Asp

Ala Glu 90

Gly Leu 45

Thr Tyr 60

Asp Ser

Asp Thr

Glu Trp

Tyr Ala

Lys Asn

Ala Val

Tyr Cys Val Arg His

100

Gly Asn

Phe Gly

105

Pro Ser

Tyr Val

Ser Trp 110

Ala Tyr Trp Gly Gln 115

Gly Thr

Leu Val 120

Thr Val

Ser Ser

125

Gly Lys

Gly Ser Gly Lys Pro

130

Gly Ser

135

Gly Lys

Pro Gly

Ser Gly 140

Lys Pro

Ser Gln Ala Val Val 145

Thr Gln 150

Glu Pro

Ser Leu

155

Thr Val

Ser Pro

Gly Thr Val Thr Leu

165

Thr Cys

Gly Ser

Ser Thr 170

Gly Ala

Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val

Gln Gln

185

Lys Pro

Gly Lys

Ser Pro 190

Gly Leu Ile Gly Gly

195

Thr Asn

Lys Arg 200

Ala Pro

Gly Val

205

Pro Ala

Phe Ser Gly Ser Leu 210

Leu Gly

215

Gly Lys

Ala Ala

Leu Thr

220

Ile Ser

Ala Gln Pro Glu Asp 225

Glu Ala

230

Asp Tyr

Tyr Cys

235

Ala Leu

Trp Tyr

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Asn His Trp Val Phe

245

Gly Gly

Gly Thr

Lys Leu 250

Thr Val

Leu <210> 232 <211> 125 <212> PROTEIN <213> Artificial <220>

<221> source sequence

- 282 044325 <223> /note=Description of artificial sequence: synthetic polypeptide <400> 232

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Pro Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 233 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 233

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr ThrSer

2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

5560

- 283 044325

Ser Gly Ser Leu 65

Gln Pro Glu Asp

Leu Gly Gly Lys Ala Ala Leu Thr

75

Ile Ser Gly Ala 80

Glu Ala Asp Tyr Tyr Cys Ala Leu 85 90

Trp Tyr Ser Asn 95

His Trp Val Phe

100

Gly Gly Gly Thr Lys Leu Thr Val 105

Leu <210> 234 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 234

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

- 284 044325

Gly Thr Val Thr Leu Thr Cys 165

Gly Ser Ser Thr Gly Ala Val Thr Thr

170 175

Ser Asn Tyr Ala Asn Trp Val 180

Gln Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly Thr Asn 195

Lys Arg Ala Pro Gly Val Pro Ala Arg

200 205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

250 255

His His His His His

260 <210> 235 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 235

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

- 285 044325

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245250 <210> 236 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 236

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

- 286 044325

Gly Arg Ile Arg Ser Lys Tyr Asn

55

Asn Tyr Ala Thr Tyr Tyr Ala Asp 60

Ser Val Lys Gly Arg Phe Thr Ile 65 70

Ser Arg Asp Asp Ser Lys Asn Thr

80

Leu Tyr Leu Gln Met Asn Ser Leu 85

Arg Ala Glu Asp Thr Ala Val Tyr

95

Tyr Cys Val Arg His Gly Asn Phe

100

Gly Asp Glu Tyr Val Ser Trp Phe

105 110

Ala Tyr Trp Gly Gln Gly Thr Leu

115 120

Val Thr Val Ser Ser

125 <210> 237 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 237

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 238 <211> 262 <212> PROTEIN <213> Artificial sequence

- 287 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 238

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Gly Arg Ile Arg 50

Ser Lys Tyr Asn 55

Asn Tyr Ala Thr 60

Tyr Tyr Ala Asp

Ser Val Lys Gly 65

Arg Phe Thr Ile 70

Ser Arg Asp Asp 75

Ser Lys Asn Thr 80

Leu Tyr Leu Gln

Met Asn Ser Leu 85

Arg Ala Glu Asp 90

Thr Ala Val Tyr 95

Tyr Cys Val Arg

100

His Gly Asn Phe

Gly Asp Pro Tyr 105

Val Ser Trp Phe

110

Ala Tyr Trp Gly

115

Gln Gly Thr Leu

120

Val Thr Val Ser

Ser Gly Lys Pro 125

Gly Ser Gly Lys

130

Pro Gly Ser Gly

135

Lys Pro Gly Ser

140

Gly Lys Pro Gly

Ser Gln Ala Val 145

Val Thr Gln Glu

150

Pro Ser Leu Thr

155

Val Ser Pro Gly

160

Gly Thr Val Thr

Leu Thr Cys Gly 165

Ser Ser Thr Gly 170

Ala Val Thr Thr

175

Ser Asn Tyr Ala

180

Asn Trp Val Gln

Gln Lys Pro Gly 185

Lys Ser Pro Arg 190

Gly Leu Ile Gly

195

Gly Thr Asn Lys

200

Arg Ala Pro Gly

Val Pro Ala Arg 205

Phe Ser Gly Ser Leu Leu Gly Gly

210 215

Lys Ala Ala

Leu Thr Ile Ser Gly 220

- 288 044325

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr Ser

235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250 255

His His His His His

260 <210> 239 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 239

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

- 289 044325

Gly Thr Val Thr Leu Thr Cys 165

Gly Ser Ser Thr Gly Ala Val Thr Thr

170 175

Ser Asn Tyr Ala Asn Trp Val 180

Gln Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly Thr Asn 195

Lys Arg Ala Pro Gly Val Pro Ala Arg

200 205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu

250 <210> 240 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 240

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe

100 105 110

- 290 044325

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120 125 <210> 241 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 241

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 242 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 242

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

- 291 044325

Gly Arg Ile Arg Ser 50

Lys Ala

Ser Val Lys Gly Arg 65

Ph Thr 70

Leu Tyr Leu Gln Met 85

Asn Ser

Asn Asn

Ile Ser

Leu Arg

Tyr Ala

Arg Asp

Ala Glu 90

Tyr Cys Val Arg His

100

Gly Asn

Phe Gly

105

Asp Ser

Thr Tyr 60

Asp Ser

Asp Thr

Tyr Val

Tyr Ala

Lys Asn

Ala Val

Ser Trp 110

Ala Tyr Trp Gly Gln 115

Gly Thr

Leu Val 120

Thr Val

Ser Ser

125

Gly Lys

Gly Ser Gly Lys Pro 130

Gly Ser

135

Gly Lys

Pro Gly

Ser Gly 140

Lys Pro

Ser Gln Ala Val Val 145

Thr Gln 150

Glu Pro

Ser Leu

155

Thr Val

Ser Pro

Gly Thr Val Thr Leu

165

Thr Cys

Gly Ser

Ser Thr 170

Gly Ala

Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val

Gln Gln

185

Lys Pro

Gly Lys

Ser Pro 190

Gly Leu Ile Gly Gly

195

Thr Asn

Lys Arg 200

Ala Pro

Gly Val

205

Pro Ala

Phe Ser Gly Ser Leu 210

Leu Gly

215

Gly Lys

Ala Ala

Leu Thr

220

Ile Ser

Ala Gln Pro Glu Asp 225

Glu Ala

230

Asp Tyr

Tyr Cys

235

Ala Leu

Trp Tyr

Asn His Trp Val Phe

245

Gly Gly

Gly Thr

Lys Leu 250

Thr Val

Leu Gly

255

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Ser

His His His His

260

His <210> 243 <211> 254 <212> PROTEIN <213> Artificial sequence

- 292 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 243

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Gly Arg Ile Arg 50

Ser Lys Ala Asn 55

Asn Tyr Ala Thr 60

Tyr Tyr Ala Asp

Ser Val Lys Gly 65

Arg Phe Thr Ile 70

Ser Arg Asp Asp 75

Ser Lys Asn Thr 80

Leu Tyr Leu Gln

Met Asn Ser Leu 85

Arg Ala Glu Asp 90

Thr Ala Val Tyr 95

Tyr Cys Val Arg

100

His Gly Asn Phe

Gly Asp Ser Tyr 105

Val Ser Trp Phe

110

Ala Tyr Trp Gly

115

Gln Gly Thr Leu

120

Val Thr Val Ser

Ser Gly Lys Pro 125

Gly Ser Gly Lys

130

Pro Gly Ser Gly

135

Lys Pro Gly Ser

140

Gly Lys Pro Gly

Ser Gln Ala Val 145

Val Thr Gln Glu

150

Pro Ser Leu Thr

155

Val Ser Pro Gly

160

Gly Thr Val Thr

Leu Thr Cys Gly 165

Ser Ser Thr Gly 170

Ala Val Thr Thr

175

Ser Asn Tyr Ala

180

Asn Trp Val Gln

Gln Lys Pro Gly 185

Lys Ser Pro Arg 190

Gly Leu Ile Gly

195

Gly Thr Asn Lys

200

Arg Ala Pro Gly

Val Pro Ala Arg 205

Phe Ser Gly Ser Leu Leu Gly Gly

210 215

Lys Ala Ala

Leu Thr Ile Ser Gly 220

- 293 044325

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr Ser

235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245 250 <210> 244 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 244

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 245 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 245

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

- 294 044325

Thr Val Thr Leu Thr Cys Gly Ser 20

Ser Thr Gly Ala Val Thr Thr Ser 25 30

Asn Tyr Ala Asn Trp Val Gln Gln

40

Lys Pro Gly Lys Ser Pro Arg Gly 45

Leu Ile Gly Gly Thr Asn Lys Arg

55

Ala Pro Gly Val Pro Ala Arg Phe 60

Ser Gly Ser Leu Leu Gly Gly Lys 65 70

Ala Ala Leu Thr Ile Ser Gly Ala

80

Gln Pro Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Ala Leu Trp Tyr Ser Asn

95

His Trp Val Phe Gly Gly Gly Thr

100

Lys Leu Thr Val Leu 105 <210> 246 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 246

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

- 295 044325

100

105

110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250255

His His His His His

260 <210> 247 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source

<223> /note= polypeptide <400> 247 Glu Val Gln Leu Val 15 Description Glu Ser artificial sequence: synthetic Gly Gly Gly Leu Val Gln Pro Gly Gly 10 15 Ser Leu Arg Leu 20 Ser Cys Ala Ala Ser 25 Gly Phe Thr Phe Ser 30 Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

- 296 044325

Gly

Arg 50

Ile

Arg

Ser

Lys

Tyr 55

Asn

Asn

Tyr

Ala

Thr 60

Ala

Tyr

Ala

Asp

Ser 65

Val

Lys

Gly

Arg

Phe 70

Thr

Ile

Ser

Arg

Asp 75

Asp

Ser

Lys

Asn

Thr 80

Leu

Tyr

Leu

Gln

Met 85

Asn

Ser

Leu

Arg

Ala 90

Glu

Asp

Thr

Ala

Val 95

Tyr

Tyr

Cys

Val

Arg 100

His

Gly

Asn

Phe

Gly 105

Asp

Ser

Tyr

Val

Ser

110

Trp

Phe

Ala

Tyr

Trp

115

Gly

Gln

Gly

Thr

Leu

120

Val

Thr

Val

Ser

Ser

125

Gly

Lys

Pro

Gly

Ser

130

Gly

Lys

Pro

Gly

Ser

135

Gly

Lys

Pro

Gly

Ser

140

Gly

Lys

Pro

Gly

Ser

145

Gln

Ala

Val

Val

Thr

150

Gln

Glu

Pro

Ser

Leu

155

Thr

Val

Ser

Pro

Gly 160

Gly

Thr

Val

Thr

Leu

165

Thr

Cys

Gly

Ser

Ser

170

Thr

Gly

Ala

Val

Thr

175

Thr

Ser

Asn

Tyr

Ala

180

Asn

Trp

Val

Gln

Gln

185

Lys

Pro

Gly

Lys

Ser

190

Pro

Arg

Gly

Leu

Ile

195

Gly

Gly

Thr

Asn

Lys 200

Arg

Ala

Pro

Gly

Val

205

Pro

Ala

Arg

Phe

Ser

210

Gly

Ser

Leu

Leu

Gly

215

Gly

Lys

Ala

Ala

Leu

220

Thr

Ile

Ser

Gly

Ala

225

Gln

Pro

Glu

Asp

Glu 230

Ala

Asp

Tyr

Tyr

Cys 235

Ala

Leu

Trp

Tyr

Ser

240

Asn

His

Trp

Val

Phe

245

Gly

Gly

Gly

Thr

Lys 250

Leu

Thr

Val

Leu <210>

<211>

<212>

<213>

248

125

PROTEIN

Artificial sequence <220>

<221>

<223>

source/note=Description of artificial sequence: synthetic

- 297 044325 polypeptide <400> 248

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu 20

Ser Cys Ala Ala Ser Gly Phe Thr Phe 25

Ser Thr Tyr 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115120

Ser Ser

125 <210> 249 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 249

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr ThrSer

2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe

5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala

- 298 044325

70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 100105 <210> 250 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 250

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Glu Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

- 299 044325

165

170

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

200 205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

250 255

His His His

His His His 260 <210> 251 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 251

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Glu Ser Tyr Val Ser Trp Phe

- 300 044325

100

105

110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115 120

Ser Ser Gly Lys Pro

125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

135 140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

150 155 160

Gly Thr Val Thr Leu Thr Cys 165

Gly Ser Ser Thr Gly Ala Val Thr Thr

170 175

Ser Asn Tyr Ala Asn Trp Val 180

Gln Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly Thr Asn 195

Lys Arg Ala Pro Gly Val Pro Ala Arg

200 205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu

250 <210> 252 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 252

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

- 301 044325

Ser Val Lys Gly Arg Phe Thr Ile 65 70

Ser Arg Asp Asp Ser Lys Asn Thr

80

Leu Tyr Leu Gln Met Asn Ser Leu 85

Arg Ala Glu Asp Thr Ala Val Tyr

95

Tyr Cys Val Arg His Gly Asn Phe

100

Gly Glu Ser Tyr Val Ser Trp Phe

105 110

Ala Tyr Trp Gly Gln Gly Thr Leu

115 120

Val Thr Val Ser Ser

125 <210> 253 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 253

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 254 <211> 262 <212> PROTEIN <213> Artificial sequence

- 302 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 254

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp

Tyr Tyr Cys Ala Leu Trp Tyr Ser

- 303 044325

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250 255

His His His

His His His 260 <210> 255 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 255

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

- 304 044325

165

170

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

200 205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu

250 <210> 256 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 256

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

- 305 044325

115 120 125 <210> 257 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 257

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 258 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 258

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val

- 306 044325

Gly Arg Ile Arg Ser 50

Lys Tyr Asn Asn Tyr 55

Ala Thr Tyr Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Asn Tyr Val Ser Trp

110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Gly

255

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Ser

His His His His

260

His <210> 259 <211> 254 <212> PROTEIN <213> Artificial sequence

- 307 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 259

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Asn Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp

Tyr Tyr Cys Ala Leu Trp Tyr Ser

- 308 044325

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 245 250 <210> 260 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 260

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Asn Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 261 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 261

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 10 15

- 309 044325

Thr Val Thr Leu Thr Cys Gly Ser 20

Ser Thr Gly Ala Val Thr Thr Ser 25 30

Asn Tyr Ala Asn Trp Val Gln Gln

40

Lys Pro Gly Lys Ser Pro Arg Gly 45

Leu Ile Gly Gly Thr Asn Lys Arg

55

Ala Pro Gly Val Pro Ala Arg Phe 60

Ser Gly Ser Leu Leu Gly Gly Lys 65 70

Ala Ala Leu Thr Ile Ser Gly Ala

80

Gln Pro Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Ala Leu Trp Tyr Ser Asn

95

His Trp Val Phe Gly Gly Gly Thr

100

Lys Leu Thr Val Leu 105 <210> 262 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 262

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Gln Tyr Val Ser Trp Phe

100 105110

- 310 044325

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115 120

Ser Ser Gly Lys Pro

125

Gly

Ser

130

Gly

Lys

Pro

Gly

Ser

135

Gly

Lys

Pro

Gly

Ser

140

Gly

Lys

Pro

Gly

Ser

145

Gln

Ala

Val

Val

Thr

150

Gln

Glu

Pro

Ser

Leu

155

Thr

Val

Ser

Pro

Gly 160

Gly

Thr

Val

Thr

Leu

165

Thr

Cys

Gly

Ser

Ser

170

Thr

Gly

Ala

Val

Thr

175

Thr

Ser

Asn

Tyr

Ala

180

Asn

Trp

Val

Gln

Gln

185

Lys

Pro

Gly

Lys

Ser

190

Pro

Arg

Gly

Leu

Ile

195

Gly

Gly

Thr

Asn

Lys 200

Arg

Ala

Pro

Gly

Val

205

Pro

Ala

Arg

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

250 255

His His His

His His His 260 <210> 263 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 263

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val

- 311 044325

Gly Arg Ile Arg Ser Lys Tyr Asn

55

Asn Tyr Ala

Thr Tyr Tyr Ala Asp

Ser Val Lys Gly Arg Phe Thr 65 70

Ile Ser Arg Asp Asp Ser Lys Asn Thr 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Gln Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245250 <210> 264 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide

- 312 044325 <400> 264

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Gln Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 265 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 265

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

- 313 044325

Gln Pro Glu Asp

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105 <210> 266 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 266

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 314 044325

Ser Asn Tyr Ala Asn

180

Gly Leu Ile Gly Gly

195

Trp Val Gln Gln Lys Pro Gly Lys 185

Thr Asn Lys Arg Ala Pro Gly Val 200 205

Ser Pro Arg 190

Pro Ala Arg

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr

215 220

Ile Ser Gly

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu

230 235

Trp Tyr Ser

240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val

250

Leu Gly Ser

255

His His His His His

260 <210> 267 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 267

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

- 315 044325

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245250 <210> 268 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 268

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

5560

- 316 044325

Ser Val Lys Gly Arg Phe Thr Ile 65 70

Ser Arg Asp Asp Ser Lys Asn Thr

80

Leu Tyr Leu Gln Met Asn Ser Leu 85

Arg Ala Glu Asp Thr Ala Val Tyr

95

Tyr Cys Val Arg His Gly Asn Phe

100

Gly Asp Ser Tyr Val Ser Trp Phe

105 110

Asp Tyr Trp Gly Gln Gly Thr Leu

115 120

Val Thr Val Ser Ser

125 <210> 269 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 269

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 270 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

- 317 044325 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 270

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

- 318 044325

Asn His Trp Val

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250 255

His His His His His

260 <210> 271 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 271

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 319 044325

Ser Asn Tyr Ala Asn Trp Val Gln 180

Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly Thr Asn Lys

195200

Phe Ser Gly Ser Leu Leu Gly Gly

210215

Ala Gln Pro Glu Asp Glu Ala Asp

225230

Asn His Trp Val Phe Gly Gly Gly

245

Arg Ala Pro Gly Val Pro Ala Arg 205

Lys Ala Ala Leu Thr Ile Ser Gly 220

Tyr Tyr Cys Ala Leu Trp Tyr Ser 235 240

Thr Lys Leu Thr Val Leu

250 <210> 272 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 272

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125

- 320 044325 <210> 273 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 273

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 274 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 274

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val

- 321 044325

Gly Arg Ile Arg Ser 50

Lys Tyr Asn Asn Tyr 55

Ala Thr Tyr Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Ala

105

Ser Tyr Val Ser Trp

110

Asp Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Gly

255

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Ser

His His His His His

260 <210> 275 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

- 322 044325 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 275

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Ala Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

- 323 044325

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245

250 <210> 276 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 276

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Ala Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 277 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 277

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 10 15

- 324 044325

Thr Val Thr Leu Thr Cys Gly Ser 20

Ser Thr Gly Ala Val Thr Thr Ser 25 30

Asn Tyr Ala Asn Trp Val Gln Gln

40

Lys Pro Gly Lys Ser Pro Arg Gly 45

Leu Ile Gly Gly Thr Asn Lys Arg

55

Ala Pro Gly Val Pro Ala Arg Phe 60

Ser Gly Ser Leu Leu Gly Gly Lys 65 70

Ala Ala Leu Thr Ile Ser Gly Ala

80

Gln Pro Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Ala Leu Trp Tyr Ser Asn

95

His Trp Val Phe Gly Gly Gly Thr

100

Lys Leu Thr Val Leu 105 <210> 278 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 278

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105110

- 325 044325

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250255

His His His His His

260 <210> 279 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 279

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val

- 326 044325

Gly Arg Ile Arg Ser Lys Tyr Asn

55

Asn Tyr Ala

Thr Tyr Tyr Ala Asp

Ser Val Lys Gly Arg Phe Thr 65 70

Ile Ser Arg Asp Asp Ser Lys Asn Thr 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245250 <210> 280 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide

- 327 044325 <400> 280

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115120

Ser Ser

125 <210> 281 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 281

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

- 328 044325

Gln Pro Glu Asp

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105 <210> 282 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 282

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 329 044325

Ser Asn Tyr Ala Asn Trp

180

Val Gln Gln Lys Pro Gly Lys 185

Gly Leu Ile Gly Gly Thr

195

Asn Lys Arg Ala Pro Gly Val

200 205

Ser Pro Arg 190

Pro Ala Arg

Phe Ser Gly Ser Leu Leu

210

Gly Gly Lys Ala Ala Leu Thr

215 220

Ile Ser Gly

Ala Gln Pro Glu Asp Glu

225 230

Ala Asp Tyr Tyr Cys Ala Leu

235

Trp Tyr Ser

240

Asn His Trp Val Phe Gly

245

Gly Gly Thr Lys Leu Thr Val

250

Leu Gly Ser

255

His His His His His

260 <210> 283 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 283

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe

100 105110

- 330 044325

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245250 <210> 284 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 284

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

5560

- 331 044325

Ser Val Lys Gly Arg Phe Thr 65 70

Leu Tyr Leu Gln Met Asn Ser 85

Tyr Cys Val Arg His Gly Asn

100

Ile Ser Arg Asp Asp Ser Lys Asn Thr 7580

Leu Arg Ala Glu Asp Thr Ala Val Tyr 9095

Phe Gly Asp Glu Tyr Val Ser Trp Phe 105110

Asp Tyr Trp Gly Gln Gly Thr 115

Leu Val Thr Val Ser Ser

120 125 <210> 285 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 285

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 286 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source

- 332 044325 <223> /note=Description of artificial sequence: synthetic polypeptide <400> 286

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Asn Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp

225230

Tyr Tyr Cys Ala Leu Trp Tyr Ser

235

240

- 333 044325

Asn His Trp Val

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250 255

His His His His His

260 <210> 287 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 287

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Asn Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 334 044325

Ser Asn Tyr Ala Asn Trp Val Gln 180

Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly Thr Asn Lys

195200

Phe Ser Gly Ser Leu Leu Gly Gly

210215

Ala Gln Pro Glu Asp Glu Ala Asp

225230

Asn His Trp Val Phe Gly Gly Gly

245

Arg Ala Pro Gly Val Pro Ala Arg 205

Lys Ala Ala Leu Thr Ile Ser Gly 220

Tyr Tyr Cys Ala Leu Trp Tyr Ser 235 240

Thr Lys Leu Thr Val Leu

250 <210> 288 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 288

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Asn Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125

- 335 044325 <210> 289 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 289

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 290 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 290

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val

- 336 044325

Gly Arg Ile Arg Ser 50

Lys Tyr Asn Asn Tyr 55

Ala Thr Tyr Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Pro Tyr Val Ser Trp

110

Asp Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Gly

255

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Ser

His His His His

260

His <210> 291 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source

- 337 044325 <223> /note=Description of artificial sequence: synthetic polypeptide <400> 291

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp

225230

Tyr Tyr Cys Ala Leu Trp Tyr Ser

235

240

- 338 044325

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245

250 <210> 292 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 292

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Thr Tyr 25 30

Ala Met Asn Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Gly Arg Ile Arg Ser Lys Tyr Asn

55

Asn Tyr Ala Thr Tyr Tyr Ala Asp 60

Ser Val Lys Gly Arg Phe Thr Ile 65 70

Ser Arg Asp Asp Ser Lys Asn Thr

80

Leu Tyr Leu Gln Met Asn Ser Leu 85

Arg Ala Glu Asp Thr Ala Val Tyr

95

Tyr Cys Val Arg His Gly Asn Phe

100

Gly Asp Pro Tyr Val Ser Trp Phe

105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val

115 120

Ser Ser

125 <210> 293 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 293

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

- 339 044325

Thr Val Thr Leu Thr Cys Gly Ser 20

Ser Thr Gly Ala Val Thr Thr Ser 25 30

Asn Tyr Ala Asn Trp Val Gln Gln

40

Lys Pro Gly Lys Ser Pro Arg Gly 45

Leu Ile Gly Gly Thr Asn Lys Arg

55

Ala Pro Gly Val Pro Ala Arg Phe 60

Ser Gly Ser Leu Leu Gly Gly Lys 65 70

Ala Ala Leu Thr Ile Ser Gly Ala

80

Gln Pro Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Ala Leu Trp Tyr Ser Asn

95

His Trp Val Phe Gly Gly Gly Thr

100

Lys Leu Thr Val Leu 105 <210> 294 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 294

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Gln Tyr Val Ser Trp Phe

100 105110

- 340 044325

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250255

His His His His His

260 < 210> 295 < 211> 254 < 212> PROTEIN < 213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 295

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Phe Ser Thr Tyr 30

Ala Met Asn Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val

- 341 044325

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala

55

Thr Tyr Tyr Ala Asp

Ser Val Lys Gly Arg Phe Thr 65 70

Ile Ser Arg Asp Asp Ser Lys Asn Thr 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Gln Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135 140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155 160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170 175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185 190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200 205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215 220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235 240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245 250 <210> 296 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 296

- 342 044325

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Gln Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 297 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 297

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

- 343 044325

Gln Pro Glu Asp

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 90 95

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105 <210> 298 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 298

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 344 044325

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

200 205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

250 255

His His His His His

260 <210> 299 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 299

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

- 345 044325

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245250 <210> 300 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 300

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp

5560

- 346 044325

Ser Val Lys Gly Arg Phe Thr 65 70

Leu Tyr Leu Gln Met Asn Ser 85

Tyr Cys Val Arg His Gly Asn

100

Ile Ser Arg Asp Asp Ser Lys Asn Thr 7580

Leu Arg Ala Glu Asp Thr Ala Val Tyr 9095

Phe Gly Asp Ser Tyr Val Ser Trp Phe 105110

Ala Tyr Trp Gly Gln Gly Thr 115

Leu Val Thr Val Ser Ser

120 125 <210> 301 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 301

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 302 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic

- 347 044325 polypeptide <400> 302

Glu Val Gln Leu Val 1 5

Glu Ser Gly Gly Gly

Leu Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Thr Phe Ser Thr

Ala Met Asn Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Gly Arg Ile Arg Ser 50

Lys Ala Asn Asn Tyr 55

Ala Thr Ala Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Ala

105

Ser Tyr Val Ser Trp

110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Gly

Tyr

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

- 348 044325

Asn His Trp Val

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250 255

His His His His His

260 <210> 303 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 303

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Ala Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 349 044325

Ser Asn Tyr Ala Asn Trp Val Gln 180

Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly Thr Asn Lys

195 200

Arg Ala Pro Gly Val Pro Ala Arg

205

Phe Ser Gly Ser Leu Leu Gly Gly

210 215

Lys Ala Ala Leu Thr Ile Ser Gly

220

Ala Gln Pro Glu Asp Glu Ala Asp

225 230

Asn His Trp Val Phe Gly Gly Gly

245

Tyr Tyr Cys Ala Leu Trp Tyr Ser

235 240

Thr Lys Leu Thr Val Leu

250 <210> 304 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 304

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Ala Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125

- 350 044325 <210> 305 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 305

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 85 9095

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100105 <210> 306 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 306

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp

- 351 044325

Ser Val Lys Gly Arg Phe Thr 65 70

Ile Ser Arg Asp Asp Ser Lys Asn Thr 75 80

Leu

Tyr Leu Gln Met Asn Ser Leu Arg Ala 85 90

Tyr

Cys Val Arg His Gly Asn Phe Gly Gln

100 105

Glu Asp Thr Ala Val Tyr 95

Ser Tyr Val Ser Trp Phe 110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

120 125

Gly Ser Gly Lys Pro

130

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

135 140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

150 155 160

Gly Thr Val Thr Leu Thr Cys 165

Gly Ser Ser Thr Gly Ala Val Thr Thr

170 175

Ser Asn Tyr Ala Asn Trp Val 180

Gln Gln Lys Pro Gly Lys Ser Pro Arg

185 190

Gly Leu Ile Gly Gly Thr Asn 195

Lys Arg Ala Pro Gly Val Pro Ala Arg

200 205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

215 220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

230 235 240

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

250 255

His His His His His

260 <210> 307 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic

- 352 044325 polypeptide <400> 307

Glu Val Gln Leu Val 1 5

Glu Ser Gly Gly Gly

Leu Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Thr Phe Ser Thr

Ala Met Asn Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Gly Arg Ile Arg Ser 50

Lys Ala Asn Asn Tyr 55

Ala Thr Ala Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Gln

105

Ser Tyr Val Ser Trp

110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Gly

Tyr

Val

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

- 353 044325

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

245

250 <210> 308 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 308

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 309 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 309

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 10 15

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser

- 354 044325

Asn Tyr Ala Asn Trp Val Gln Gln

40

Lys Pro Gly Lys Ser Pro Arg Gly 45

Leu Ile Gly Gly Thr Asn Lys Arg

55

Ala Pro Gly Val Pro Ala Arg Phe 60

Ser Gly Ser Leu Leu Gly Gly Lys 65 70

Ala Ala Leu Thr Ile Ser Gly Ala

80

Gln Pro Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Ala Leu Trp Tyr Ser Asn

95

His Trp Val Phe Gly Gly Gly Thr

100

Lys Leu Thr Val Leu 105 <210> 310 <211> 262 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 310

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

- 355 044325

115

120

125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Ser

245 250255

His His His His His

260 <210> 311 <211> 254 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 311

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp

- 356 044325

Ser 65

Val

Lys

Gly

Arg

Phe 70

Thr

Ile

Ser

Arg

Asp 75

Asp

Ser

Lys

Asn

Thr 80

Leu

Tyr

Leu

Gln

Met 85

Asn

Ser

Leu

Arg

Ala 90

Glu

Asp

Thr

Ala

Val 95

Tyr

Tyr

Cys

Val

Arg 100

His

Gly

Asn

Phe

Gly 105

Asp

Ser

Tyr

Val

Ser

110

Trp

Phe

Asp

Tyr

Trp

115

Gly

Gln

Gly

Thr

Leu

120

Val

Thr

Val

Ser

Ser

125

Gly

Lys

Pro

Gly

Ser

130

Gly

Lys

Pro

Gly

Ser

135

Gly

Lys

Pro

Gly

Ser

140

Gly

Lys

Pro

Gly

Ser

145

Gln

Ala

Val

Val

Thr

150

Gln

Glu

Pro

Ser

Leu

155

Thr

Val

Ser

Pro

Gly 160

Gly

Thr

Val

Thr

Leu

165

Thr

Cys

Gly

Ser

Ser

170

Thr

Gly

Ala

Val

Thr

175

Thr

Ser

Asn

Tyr

Ala

180

Asn

Trp

Val

Gln

Gln

185

Lys

Pro

Gly

Lys

Ser

190

Pro

Arg

Gly

Leu

Ile

195

Gly

Gly

Thr

Asn

Lys 200

Arg

Ala

Pro

Gly

Val

205

Pro

Ala

Arg

Phe

Ser 210

Gly

Ser

Leu

Leu

Gly 215

Gly

Lys

Ala

Ala

Leu

220

Thr

Ile

Ser

Gly

Ala

225

Gln

Pro

Glu

Asp

Glu

230

Ala

Asp

Tyr

Tyr

Cys 235

Ala

Leu

Trp

Tyr

Ser 240

Asn

His

Trp

Val

Phe

245

Gly

Gly

Gly

Thr

Lys 250

Leu

Thr

Val

Leu <210> 312 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 312

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

- 357 044325

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120125 <210> 313 <211> 109 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 313

Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly

5 1015

Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr Ser 20 2530

Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg Gly 35 4045

Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg Phe 50 5560

Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly Ala 65 70 7580

Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn

- 358 044325

His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105 <210> 314 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 314

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

5 1015

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Val Met His Trp Val Arg Gln Ala Pro Gly Gly Gly Leu Glu Trp Ile

4045

Gly Tyr Ile Asn Pro Tyr Asn Asp Gly Thr Lys Tyr Asn Glu Lys Phe 50 5560

Lys Gly Arg Val Thr Ile Ser Ser Asp Lys Ser Lys Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Gly Thr Tyr Tyr Tyr Gly Thr Arg Val Phe Asp Tyr Trp Gly

100 105110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

- 359 044325

180

185

190

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Ser Ser Ser

195

Leu Gly Thr

Gln Thr Tyr 200

Ile Cys Asn

205

Val Asn His

Pro Ser Asp 210

Thr Lys Val

215

Asp Lys Lys

Val Glu Pro

220

Lys Ser Cys

Lys Thr His

Thr Cys Pro

230

Pro Cys Pro

Ala Pro Pro 235

Val Ala Gly

240

Ser Val Phe

Leu Phe Pro 245

Pro Lys Pro

250

Lys Asp Thr

Leu Met Ile

255

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Ser Arg Trp

420

Glu Val Thr

Cys Val Val

265

Val Asp Val

Lys His Glu 270

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Glu Gln Gly

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asp Val Phe

425

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

- 360 044325

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450 <210> 315 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 315

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 361 044325

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Glu Trp

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Glu Ser 420

Trp Val

Thr Asn

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Asn Gly

Gln Gln 185

Lys Arg 200

Gly Lys

Asp Tyr

Gly Thr

Lys Pro

Gly Lys

Ala Pro

Ala Ala

Tyr Cys

235

Lys Leu 250

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Glin Pro

425

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Glu Asn

Gly Val

205

Leu Thr

220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Asn Tyr

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Lys Thr 430

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

- 362 044325

Pro Pro Val Leu Asp Ser Asp Gly Ser

435440

Thr Val Asp Lys Ser Arg Trp Gln Gln

450455

Val Met His Glu Ala Leu His Asn His

465470

Phe Phe Leu Tyr 445 Ser Lys Leu Gly Asn Val 460 Phe Ser Cys Ser Tyr Thr 475 Gln Lys Ser Leu Ser 480

Leu Ser Pro Gly Lys

485 <210> 316 <211> 219 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 316

Asp Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

5 1015

Glu Arg Ala Thr Ile Ser Cys Arg Ser Ser Lys Ser Leu Gln Asn Val 20 2530

Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Gln Gln Lys Pro Gly Gln Ser 35 4045

Pro Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Asn Ser Gly Val Pro 50 5560

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile 65 70 7580

Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln His 85 9095

Leu Glu Tyr Pro Ile Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105110

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

115 120125

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

130 135140

- 363 044325

Tyr Pro Arg Glu Ala Lys Val Gln

145 150

Trp Lys Val Asp Asn Ala Leu Gln

155 160

Ser Gly Asn Ser Gln Glu Ser Val

165

Thr Glu Gln Asp Ser Lys Asp Ser

170 175

Thr Tyr Ser Leu Ser Ser Thr Leu 180

Thr Leu Ser Lys Ala Asp Tyr Glu

185 190

Lys His Lys Val Tyr Ala Cys Glu

195 200

Val Thr His Gln Gly Leu Ser Ser

205

Pro Val Thr Lys Ser Phe Asn Arg

210 215

Gly Glu Cys <210> 317 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 317

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

5 1015

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Val Met His Trp Val Arg Gln Ala Pro Gly Gly Gly Leu Glu Trp Ile

4045

Gly Tyr Ile Asn Pro Tyr Asn Asp Gly Thr Lys Tyr Asn Glu Lys Phe 50 5560

Lys Gly Arg Val Thr Ile Ser Ser Asp Lys Ser Lys Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Gly Thr Tyr Tyr Tyr Gly Thr Arg Val Phe Asp Tyr Trp Gly

100 105110

Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120125

- 364 044325

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Phe Pro 130

Leu Gly

Trp Asn

Leu Gln

Ser Ser

195

Pro Ser 210

Lys Thr

Ser Val

Arg Thr

Pro Glu

275

Ala Lys 290

Val Ser

Tyr Lys

Thr Ile

Leu Pro

355

Cys Asp 370

Leu Ala

Cys Leu

Ser Gly

165

Ser Ser 180

Ser Leu

Asp Thr

His Thr

Phe Leu

245

Pro Glu 260

Val Lys

Thr Lys

Val Leu

Cys Lys

325

Ser Lys 340

Pro Ser

Val Ser

Pro Ser

135

Val Lys 150

Ala Leu

Gly Leu

Gly Thr

Lys Val

215

Cys Pro 230

Phe Pro

Val Thr

Phe Asn

Pro Arg

295

Thr Val 310

Val Ser

Ala Lys

Arg Glu

Gly Phe

375

Ser Lys

Ser Thr

Asp Tyr

Phe Pro

155

Thr Ser

Gly Val 170

Tyr Ser

185

Gln Thr

200

Asp Lys

Pro Cys

Pro Lys

Cys Val

265

Trp Tyr 280

Glu Glu

Leu His

Asn Lys

Gly Gln

345

Glu Met 360

Tyr Pro

Leu Ser

Tyr Ile

Lys Val

Pro Ala

235

Pro Lys 250

Val Val

Val Asp

Glu Tyr

Gln Asp

315

Ala Leu 330

Pro Arg

Thr Lys

Ser Asp

Ser Gly 140

Glu Pro

His Thr

Ser Val

Cys Asn

205

Glu Pro

220

Pro Pro

Asp Thr

Asp Val

Gly Val

285

Asn Ser 300

Trp Leu

Pro Ala

Glu Pro

Asn Gln

365

Ile Ala

380

Gly Thr

Val Thr

Phe Pro

175

Val Thr 190

Val Asn

Lys Ser

Val Ala

Leu Met

255

Lys His 270

Glu Val

Thr Tyr

Asn Gly

Pro Ile

335

Gln Val 350

Val Ser

Val Glu

Ala

Val 160

Ala

Val

His

Cys

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

Leu

Trp

- 365 044325

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

385 390 395

Thr Thr Pro Pro Val

400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

405 410

Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

420 425

Cys Ser Val Met His

430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 318 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 318

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

- 366 044325

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Ser Gly Lys 130

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys

Pro Gly Ser

135

Val Thr Gln

150

Leu Thr Cys 165

Asn Trp Val

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Gly Lys Pro

Glu Pro Ser

Gly Ser Ser 170

Gln Gln Lys 185

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys 250

Thr Cys Pro 265

Leu Phe Pro 280

Glu Val Thr

Gly Ser Gly

140

Leu Thr Val 155

Thr Gly Ala

Pro Gly Lys

Pro Gly Val

205

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Lys Pro Gly

Ser Pro Gly

160

Val Thr Thr

175

Ser Pro Arg 190

Pro Ala Arg

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Pro Glu Val

310

Lys Phe Asn

Trp Tyr Val 315

Asp Gly Val

320

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

Lys Pro Arg

330

Glu Glu Gln

Tyr Asn Ser

335

Leu Thr Val

345

Leu His Gln

Asp Trp Leu 350

Lys Val Ser 360

Lys Ala Lys

Asn Lys Ala

365

Leu Pro Ala

Gly Gln Pro

Arg Glu Pro

- 367 044325

370

375

380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 319 <211> 219 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 319

Asp Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

5 1015

Glu Arg Ala Thr Ile Ser Cys Arg Ser Ser Lys Ser Leu Gln Asn Val 20 2530

Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Gln Gln Lys Pro Gly Gln Ser 35 4045

Pro Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Asn Ser Gly Val Pro 50 5560

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile 65 70 7580

Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln His

- 368 044325

Leu Glu Tyr Pro Ile Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105110

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

115 120125

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

130 135140

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150 155160

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

165 170175

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

180 185190

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

195 200205

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

210215 <210> 320 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 320

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

5 1015

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Tyr Thr Phe Thr SerTyr

2530

Val Met His Trp Val Arg Gln Ala Pro Gly Gly Gly Leu Glu Trp Ile 35 4045

Gly Tyr Ile Asn Pro Tyr Asn Asp Gly Thr Lys Tyr Asn Glu Lys Phe

5560

Lys Gly Arg Val Thr Ile Ser Ser Asp Lys Ser Lys Ser Thr Ala Tyr

- 369 044325

Met

Ala

Gln

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu Leu Ser

Ser Leu Arg 85

Ser Glu Asp

Thr Ala Val

Tyr Tyr Cys 95

Arg Gly Thr

100

Gly Thr Leu 115

Phe Pro Leu 130

Leu Gly Cys

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Tyr Tyr

Gly Thr Arg

105

Val Phe Asp

Tyr Trp Gly 110

Val Thr Val

Ala Pro Ser

135

Leu Val Lys

150

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Ser Ser Ala 120

Ser Thr Lys

125

Gly Pro Ser

Ser Lys Ser

Thr Ser Gly 140

Gly Thr Ala

Asp Tyr Phe

Pro Glu Pro 155

Val Thr Val

160

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Val His Thr

Phe Pro Ala

175

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

- 370 044325

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360365

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His

420 425430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210> 321 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 321

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

5560

- 371 044325

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Ser Tyr Val Ser Trp

110

Asp Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Leu Met Ile Ser Arg

290

Thr Pro Glu Val Thr

295

Cys Val Val Val Asp

300

Lys His Glu Asp Pro 305

Glu Val Lys Phe Asn 310

Trp Tyr Val Asp Gly 315

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

- 372 044325

Glu Val His Asn Ala Lys Thr Lys

325

Pro Arg Glu Glu Gln Tyr Asn Ser

330 335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 322 <211> 219 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 322

Asp Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

5 10 15

Glu Arg Ala Thr Ile Ser Cys Arg Ser 20 25

Ser Lys Ser Leu Gln Asn Val 30

- 373 044325

Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Gln Gln

40

Lys Pro Gly Gln Ser

Pro Lys Leu 50

Leu Ile Tyr Arg Ala Ser Asn Leu Asn 55 60

Ser Gly Val Pro

Asp Arg Phe 65

Ser Gly Ser Gly Ser Gly Thr Glu Phe

75

Thr Leu Thr Ile

Ser Ser Leu

Glu Pro Glu Asp Phe Ala Val Tyr Tyr

90

Cys Met Gln His 95

Leu Glu Tyr

Pro Ile Thr Phe Gly Gly Gly Thr Lys 100 105

Leu Glu Ile Lys 110

Arg Thr Val Ala Ala Pro Ser Val Phe

115 120

Ile Phe Pro Pro Ser Asp Glu

125

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

130 135 140

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150 155 160

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

165 170 175

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

180 185 190

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

195 200 205

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215 <210> 323 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 323

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 10 15

- 374 044325

Ser

Asn

Gly

Gln 65

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Val Lys Val

Met His Trp 35

Ala Ile Tyr 50

Gly Arg Val

Glu Leu Ser

Arg Ser Thr

100

Gly Thr Leu

115

Phe Pro Leu 130

Leu Gly Cys

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Ser Cys Lys

Val Arg Gln

Pro Gly Asn

Thr Ile Thr

Ser Leu Arg 85

Tyr Tyr Gly

Val Thr Val

Ala Pro Ser

135

Leu Val Lys

150

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Ala Ser Gly 25

Ala Pro Gly 40

Gly Asp Thr

Ala Asp Lys

Ser Glu Asp

Gly Asp Trp

105

Ser Ser Ala 120

Ser Lys Ser

Asp Tyr Phe

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Tyr Thr Phe

Gln Gly Leu 45

Ser Tyr Asn 60

Ser Ile Ser 75

Thr Ala Val

Tyr Phe Asn

Ser Thr Lys

125

Thr Ser Gly 140

Pro Glu Pro 155

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Thr Ser Tyr 30

Glu Trp Met

Gln Lys Phe

Thr Ala Tyr

Tyr Tyr Cys 95

Val Trp Gly 110

Gly Pro Ser

Gly Thr Ala

Val Thr Val

160

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

- 375 044325

Asp Pro Glu Val Lys Phe Asn Trp

275 280

Tyr Val Asp Gly Val Glu Val His

285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr

385 390

Lys Thr Thr Pro Pro Val

395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

405 410

Ser Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe

420 425

Ser Cys Ser Val Met His

430

Glu Ala Leu His Asn His Tyr Thr Gln Lys

435 440

Ser Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 324 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 324

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

- 376 044325

Ser

Ala

Gly

Ser 65

Leu

Tyr

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Leu Arg Leu Ser Cys 20

Met Asn Trp Val Arg 35

Arg Ile Arg Ser Lys 50

Val Lys Gly Arg Phe 70

Tyr Leu Gln Met Asn 85

Cys Val Arg His Gly 100

Tyr Trp Gly Gln Gly 115

Ser Gly Lys Pro Gly 130

Gln Ala Val Val Thr

150

Thr Val Thr Leu Thr

165

Asn Tyr Ala Asn Trp 180

Leu Ile Gly Gly Thr

195

Ser Gly Ser Leu Leu 210

Gln Pro Glu Asp Glu

230

His Trp Val Phe Gly

245

Ser Ser Asp Lys Thr

Ala Ala Ser Gly Phe 25

Gln Ala Pro Gly Lys 40

Tyr Asn Asn Tyr Ala 55

Thr Ile Ser Arg Asp

Ser Leu Arg Ala Glu 90

Asn Phe Gly Asp Ser 105

Thr Leu Val Thr Val

120

Ser Gly Lys Pro Gly 135

Gln Glu Pro Ser Leu

155

Cys Gly Ser Ser Thr

170

Val Gln Gln Lys Pro 185

Asn Lys Arg Ala Pro 200

Gly Gly Lys Ala Ala 215

Ala Asp Tyr Tyr Cys

235

Gly Gly Thr Lys Leu

250

His Thr Cys Pro Pro

Thr Phe Ser Thr Tyr 30

Gly Leu Glu Trp Val 45

Thr Tyr Tyr Ala Asp 60

Asp Ser Lys Asn Thr 80

Asp Thr Ala Val Tyr 95

Tyr Val Ser Trp Phe

110

Ser Ser Gly Lys Pro

125

Ser Gly Lys Pro Gly 140

Thr Val Ser Pro Gly

160

Gly Ala Val Thr Thr

175

Gly Lys Ser Pro Arg 190

Gly Val Pro Ala Arg

205

Leu Thr Ile Ser Gly 220

Ala Leu Trp Tyr Ser

240

Thr Val Leu Glu Pro

255

Cys Pro Ala Pro Pro

- 377 044325

260

265

270

Val

Ala

Gly 275

Pro

Ser

Val

Phe

Leu

280

Phe

Pro

Pro

Lys

Pro

285

Lys

Asp

Leu

Met

290

Ile

Ser

Arg

Thr

Pro

295

Glu

Val

Thr

Cys

Val

300

Val

Val

Asp

Lys 305

His

Glu

Asp

Pro

Glu

310

Val

Lys

Phe

Asn

Trp 315

Tyr

Val

Asp

Gly

Glu

Val

His

Asn

Ala

325

Lys

Thr

Lys

Pro

Arg 330

Glu

Glu

Gln

Tyr

Asn

335

Thr

Tyr

Arg

Val

340

Val

Ser

Val

Leu

Thr

345

Val

Leu

His

Gln

Asp 350

Trp

Asn

Gly

Lys

355

Glu

Tyr

Lys

Cys

Lys 360

Val

Ser

Asn

Lys

Ala

365

Leu

Pro

Pro

Ile

370

Glu

Lys

Thr

Ile

Ser

375

Lys

Ala

Lys

Gly

Gln

380

Pro

Arg

Glu

Gln

385

Val

Tyr

Thr

Leu

Pro

390

Pro

Ser

Arg

Glu

Gln

395

Met

Thr

Lys

Asn

Val

Lys

Leu

Thr

Cys 405

Leu

Val

Lys

Gly

Phe

410

Tyr

Pro

Ser

Asp

Ile

415

Val

Glu

Trp

Glu

420

Ser

Asn

Gly

Gln

Pro

425

Glu

Asn

Asn

Tyr

Lys 430

Thr

Pro

Pro

Val

435

Leu

Asp

Ser

Asp

Gly 440

Ser

Phe

Phe

Leu

Tyr 445

Ser

Lys

Thr

Val

450

Asp

Lys

Ser

Arg

Trp

455

Gln

Gln

Gly

Asn

Val

460

Phe

Ser

Cys

Val

465

Met

His

Glu

Ala

Leu

470

His

Asn

His

Tyr

Thr

475

Gln

Lys

Ser

Leu

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

Leu

Ser

Ser 480

Leu Ser Pro Gly Lys

485 <210> 325 <211> 213 <212> PROTEIN <213> Artificial sequence

- 378 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 325

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Ser Ser 25

Val Ser Tyr Ile 30

His Trp Phe Gln 35

Gln Lys Pro Gly 40

Lys Ser Pro Lys

Pro Leu Ile Tyr 45

Ala Thr Ser Asn

Leu Ala Ser Gly 55

Val Pro Val Arg 60

Phe Ser Gly Ser

Gly Ser Gly Thr 65

Asp Tyr Thr Leu 70

Thr Ile Ser Ser

Leu Gln Pro Glu

Asp Phe Ala Thr

Tyr Tyr Cys Gln 85

Gln Trp Thr Ser 90

Asn Pro Pro Thr

Phe Gly Gly Gly

100

Thr Lys Val Glu

Ile Lys Arg Thr 105

Val Ala Ala Pro

110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

115 120

Gln Leu Lys Ser Gly Thr

125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe

130 135

Tyr Pro Arg Glu Ala Lys

140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150

Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu

Gln Asp Ser Lys 165

Asp Ser Thr Tyr 170

Ser Leu Ser Ser

175

Thr Leu Thr Leu

180

Ser Lys Ala Asp

Tyr Glu Lys His 185

Lys Val Tyr Ala 190

Cys Glu Val Thr

195

His Gln Gly Leu

200

Ser Ser Pro Val

Thr Lys Ser Phe 205

Asn Arg Gly Glu Cys

210

- 379 044325 <210> 326 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 326

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 7580

Met Glu Leu

Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

8590

Tyr Tyr Cys 95

Ala Arg

Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val

100 105110

Trp Gly

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135140

Ala Leu Gly Cys 145

Leu Val Lys Asp 150

Tyr Phe Pro Glu

155

Pro Val Thr Val

160

Ser Trp Asn Ser

Gly Ala Leu Thr 165

Ser Gly Val His 170

Thr Phe Pro Ala

175

Val Leu Gln Ser

180

Ser Gly Leu Tyr

Ser Leu Ser Ser 185

Val Val Thr Val

190

Pro Ser Ser Ser

195

Leu Gly Thr Gln

200

Thr Tyr Ile Cys

Asn Val Asn His 205

- 380 044325

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Glu

Gly

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Ser Arg Trp

420

Ala Leu His

435

Lys 450

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Glu Gln Gly

Asn His Tyr

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asp Val Phe

425

Thr Gln Lys 440

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

445

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

Leu Ser Pro

- 381 044325 <210> 327 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 327

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

- 382 044325

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Glu Trp

Pro Val

435

Val Asp 450

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Glu Ser 420

Leu Asp

Lys Ser

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Asn Gly

Ser Asp

Arg Trp

455

Gly Lys

Asp Tyr

Gly Thr

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Glin Pro

425

Gly Ser 440

Gln Gln

Ala Ala

Tyr Cys

235

Lys Leu 250

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Glu Asn

Phe Phe

Gly Asn

Leu Thr 220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Asn Tyr

Leu Tyr

445

Val Phe 460

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Lys Thr 430

Ser Lys

Ser Cys

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

Leu

Ser

- 383 044325

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485 <210> 328 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 328

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

- 384 044325

Thr Leu Thr Leu

180

Ser Lys Ala Asp

Tyr Glu Lys His Lys Val Tyr Ala

185 190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200 205

Asn Arg Gly Glu Cys

210 <210> 329 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 329

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly

100 105110

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155160

- 385 044325

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala 330

Gly Gln Pro 345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

- 386 044325

405 410415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His

420 425430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210> 330 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 330

Glu 1 Val Gln Leu Val 5 Glu Ser Gly Gly Gly 10 Leu Val Gln Pro Gly 15 Gly Ser Leu Arg Leu 20 Ser Cys Ala Ala Ser 25 Gly Phe Thr Phe Ser 30 Thr Tyr Ala Met Asn 35 Trp Val Arg Gln Ala 40 Pro Gly Lys Gly Leu 45 Glu Trp Val Gly Arg 50 Ile Arg Ser Lys Ala 55 Asn Asn Tyr Ala Thr 60 Tyr Tyr Ala Asp Ser 65 Val Lys Gly Arg Phe 70 Thr Ile Ser Arg Asp 75 Asp Ser Lys Asn Thr 80 Leu Tyr Leu Gln Met 85 Asn Ser Leu Arg Ala 90 Glu Asp Thr Ala Val 95 Tyr Tyr Cys Val Arg 100 His Gly Asn Phe Gly 105 Asp Ser Tyr Val Ser 110 Trp Phe Ala Tyr Trp 115 Gly Gln Gly Thr Leu 120 Val Thr Val Ser Ser 125 Gly Lys Pro Gly Ser 130 Gly Lys Pro Gly Ser 135 Gly Lys Pro Gly Ser 140 Gly Lys Pro Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

- 387 044325

145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Thr Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

150

155

Thr Leu

165

Thr Cys

Gly Ser

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Trp Val

Gln Gln

185

Thr Asn

Leu Gly 215

Glu Ala 230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Lys Arg 200

Gly Lys

Ser Thr 170

Lys Pro

Ala Pro

Ala Ala

Gly Ala

Val Thr

175

Asp Tyr

Tyr Cys

235

Gly Thr

Lys Leu 250

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Gly Lys

Gly Val 205

Leu Thr 220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

- 388 044325

Val Lys Leu

Thr Cys Leu Val Lys Gly Phe Tyr Pro

405 410

Ser Asp Ile Ala

415

Val Glu Trp

Glu Ser Asn Gly Gln Pro Glu Asn Asn 420 425

Tyr Lys Thr Thr 430

Pro Pro Val

435

Leu Asp Ser Asp Gly Ser Phe Phe Leu

440

Tyr Ser Lys Leu 445

Thr Val Asp

450

Lys Ser Arg Trp Gln Gln Gly Asn Val

455 460

Phe Ser Cys Ser

Val Met His 465

Glu Ala Leu His Asn His Tyr Thr Gln

470 475

Lys Ser Leu Ser

480

Leu Ser Pro Gly Lys

485 <210> 331 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 331

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile 20 25 30

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 40 45

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 55 60

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr 85 90 95

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105 110

- 389 044325

Ser Val Phe Ile Phe Pro Pro Ser

115 120

Asp Glu Gln Leu Lys Ser Gly Thr

125

Ala Ser Val Val Cys Leu Leu Asn

130 135

Asn Phe Tyr Pro Arg Glu Ala Lys

140

Val Gln Trp Lys Val Asp Asn Ala

145 150

Leu Gln Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu Gln Asp Ser Lys

165

Asp Ser Thr Tyr Ser Leu Ser Ser

170 175

Thr Leu Thr Leu Ser Lys Ala Asp 180

Tyr Glu Lys His Lys Val Tyr Ala

185 190

Cys Glu Val Thr His Gln Gly Leu

195 200

Ser Ser Pro Val Thr Lys Ser Phe

205

Asn Arg Gly Glu Cys

210 <210> 332 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 332

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

- 390 044325

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Arg Ser

Gly Thr

115

Phe Pro 130

Leu Gly

Trp Asn

Leu Gln

Ser Ser

195

Pro Ser 210

Lys Thr

Ser Val

Arg Thr

Pro Glu

275

Ala Lys 290

Val Ser

Tyr Lys

Thr Ile

Thr Tyr 100

Leu Val

Leu Ala

Cys Leu

Tyr Gly

Thr Val

Pro Ser

135

Val Lys 150

Ser Gly

165

Ser Ser 180

Ser Leu

Asp Thr

His Thr

Phe Leu

245

Pro Glu 260

Val Lys

Thr Lys

Val Leu

Cys Lys

325

Ser Lys 340

Ala Leu

Gly Leu

Gly Thr

Lys Val

215

Cys Pro 230

Phe Pro

Val Thr

Phe Asn

Pro Arg

295

Thr Val 310

Val Ser

Ala Lys

Gly Asp

105

Trp Tyr

Phe Asn

Ser Ser 120

Ser Lys

Asp Tyr

Thr Ser

Tyr Ser

185

Gln Thr

200

Asp Lys

Pro Cys

Pro Lys

Cys Val

265

Trp Tyr 280

Glu Glu

Leu His

Asn Lys

Gly Gln

345

Ala Ser

Thr Lys

125

Ser Thr

Ser Gly 140

Phe Pro

155

Gly Val 170

Leu Ser

Tyr Ile

Lys Val

Pro Ala

235

Pro Lys 250

Val Val

Val Asp

Glu Tyr

Gln Asp

315

Ala Leu 330

Pro Arg

Glu Pro

His Thr

Ser Val

Cys Asn

205

Glu Pro

220

Pro Pro

Asp Thr

Asp Val

Gly Val

285

Asn Ser 300

Trp Leu

Pro Ala

Glu Pro

Val Trp 110

Gly Pro

Gly Thr

Val Thr

Phe Pro

175

Val Thr 190

Val Asn

Lys Ser

Val Ala

Leu Met

255

Lys His 270

Glu Val

Thr Tyr

Asn Gly

Pro Ile

335

Gln Val 350

Gly

Ser

Ala

Val 160

Ala

Val

His

Cys

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

- 391 044325

Thr

Leu

Pro

355

Pro

Ser

Arg

Glu

Glu

360

Met

Thr

Lys

Asn

Gln

365

Val

Ser

Leu

Thr

Cys 370

Asp

Val

Ser

Gly

Phe

375

Tyr

Pro

Ser

Asp

Ile

380

Ala

Val

Glu

Trp

Glu

385

Ser

Asp

Gly

Gln

Pro

390

Glu

Asn

Asn

Tyr

Lys

395

Thr

Thr

Pro

Pro

Val

400

Leu

Asp

Ser

Asp

Gly 405

Ser

Phe

Phe

Leu

Tyr 410

Ser

Lys

Leu

Thr

Val

415

Asp

Lys

Ser

Arg

Trp 420

Glu

Gln

Gly

Asp

Val

425

Phe

Ser

Cys

Ser

Val

430

Met

His

Glu

Ala

Leu

435

His

Asn

His

Tyr

Thr

440

Gln

Lys

Ser

Leu

Ser

445

Leu

Ser

Pro

Gly Lys

450 <210> 333 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 333

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

- 392 044325

Tyr

Asp

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Cys Val

Tyr Trp

115

Ser Gly 130

Gln Ala

Thr Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Arg His 100

Gly Gln

Lys Pro

Val Val

Thr Leu

165

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Gly Asn

Gly Thr

Gly Ser

135

Thr Gln 150

Thr Cys

Trp Val

Thr Asn

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Phe Gly

105

Asp Ser

Tyr Val

Leu Val 120

Gly Lys

Glu Pro

Gly Ser

Gln Gln

185

Lys Arg 200

Gly Lys

Asp Tyr

Gly Thr

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Thr Val

Ser Ser

125

Pro Gly

Ser Gly 140

Ser Leu

155

Ser Thr 170

Lys Pro

Ala Pro

Ala Ala

Tyr Cys

235

Lys Leu 250

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Thr Val

Gly Ala

Gly Lys

Gly Val

205

Leu Thr

220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Ser Trp 110

Gly Lys

Lys Pro

Ser Pro

Val Thr

175

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

- 393 044325

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 334 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 334

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser TyrIle

2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser

5560

- 394 044325

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys 210 <210> 335 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 335

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

- 395 044325

Gly

Gln 65

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Ala Ile Tyr Pro Gly 50

Asn Gly Asp Thr Ser 55

Tyr Asn Gln Lys Phe 60

Gly Arg Val Thr Ile 70

Thr Ala Asp Lys Ser

Ile Ser Thr Ala Tyr 80

Glu Leu Ser Ser Leu

Arg Ser Thr Tyr Tyr 100

Gly Thr Leu Val Thr 115

Phe Pro Leu Ala Pro 130

Leu Gly Cys Leu Val

150

Trp Asn Ser Gly Ala

165

Leu Gln Ser Ser Gly 180

Ser Ser Ser Leu Gly

195

Pro Ser Asp Thr Lys 210

Lys Thr His Thr Cys

230

Ser Val Phe Leu Phe

245

Arg Thr Pro Glu Val 260

Pro Glu Val Lys Phe

275

Ala Lys Thr Lys Pro

Arg Ser Glu Asp Thr

Ala Val Tyr Tyr Cys 95

Gly Gly Asp Trp Tyr

105

Phe Asn Val Trp Gly

110

Val Ser Ser Ala Ser

120

Thr Lys Gly Pro Ser

125

Ser Ser Lys Ser Thr 135

Ser Gly Gly Thr Ala 140

Lys Asp Tyr Phe Pro

155

Glu Pro Val Thr Val

160

Leu Thr Ser Gly Val

170

Leu Tyr Ser Leu Ser

185

Thr Gln Thr Tyr Ile 200

Val Asp Lys Lys Val 215

Pro Pro Cys Pro Ala

235

Pro Pro Lys Pro Lys

250

Thr Cys Val Val Val

265

Asn Trp Tyr Val Asp

280

Arg Glu Glu Glu Tyr

His Thr Phe Pro Ala

175

Ser Val Val Thr Val

190

Cys Asn Val Asn His

205

Glu Pro Lys Ser Cys 220

Pro Pro Val Ala Gly

240

Asp Thr Leu Met Ile

255

Asp Val Lys His Glu

270

Gly Val Glu Val His

285

Asn Ser Thr Tyr Arg

- 396 044325

290

295

300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val

325

Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

330 335

Lys Thr

Ile Ser Lys Ala Lys

340

Gly Gln Pro Arg Glu Pro Gln Val Tyr

345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val

355 360 365

Ser Leu

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp

370 375

Ile Ala Val Glu Trp 380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

385 390 395

Thr Thr Pro Pro Val

400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

405 410

Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

420 425

Cys Ser Val Met His 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 336 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 336

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

- 397 044325

Gly Arg Ile Arg Ser 50

Lys Tyr Asn Asn Tyr 55

Ala Thr Tyr Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Pro

105

Ser Tyr Val Ser Trp

110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys

125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala

200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

- 398 044325

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 337 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 337

- 399 044325

Gln Ile Val Leu Thr

5

Gln

Ser

Pro

Ser

Ser 10

Leu

Ser

Ala

Ser

Val 15

Asp Arg Val Thr Ile

Thr

Cys

Arg

Ala 25

Ser

Ser

Ser

Val

Ser 30

Tyr

His Trp Phe Gln Gln 35

Lys

Pro

Gly 40

Lys

Ser

Pro

Lys

Pro 45

Leu

Ile

Ala Thr Ser Asn Leu 50

Ala

Ser 55

Gly

Val

Pro

Val

Arg 60

Phe

Ser

Gly

Gly Ser Gly Thr Asp 65

Tyr 70

Thr

Leu

Thr

Ile

Ser 75

Ser

Leu

Gln

Pro

Asp Phe Ala Thr Tyr 85

Tyr

Cys

Gln

Gln

Trp 90

Thr

Ser

Asn

Pro

Pro 95

Phe Gly Gly Gly Thr

100

Lys

Val

Glu

Ile

105

Lys

Arg

Thr

Val

Ala

110

Ala

Ser Val Phe Ile Phe

115

Pro

Pro

Ser

120

Asp

Glu

Gln

Leu

Lys 125

Ser

Gly

Ala Ser Val Val Cys 130

Leu

Leu

135

Asn

Asn

Phe

Tyr

Pro

140

Arg

Glu

Ala

Val Gln Trp Lys Val 145

Asp

150

Asn

Ala

Leu

Gln

Ser

155

Gly

Asn

Ser

Gln

Ser Val Thr Glu Gln

165

Asp

Ser

Lys

Asp

Ser

170

Thr

Tyr

Ser

Leu

Ser

175

Thr Leu Thr Leu Ser

180

Lys

Ala

Asp

Tyr 185

Glu

Lys

His

Lys

Val

190

Tyr

Cys Glu Val Thr His 195

Gln

Gly

Leu 200

Ser

Ser

Pro

Val

Thr

205

Lys

Ser

Gly

Ile

Tyr

Ser

Glu 80

Thr

Pro

Thr

Lys

Glu 160

Ser

Ala

Phe

Asn Arg Gly Glu Cys 210 <210> 338 <211> 450 <212> PROTEIN <213> Artificial <220>

<221> source sequence

- 400 044325 <223> /note=Description of artificial sequence: synthetic polypeptide <400> 338

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly

100 105110

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200205

Lys Pro Ser Asp Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys

210 215220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly

225 230 235240

- 401 044325

Pro Ser Val

Phe Leu Phe

245

Pro Pro Lys

Pro Lys Asp 250

Thr Leu Met

255

Ser Arg Thr

Pro Glu Val 260

Thr Cys Val

265

Val Val Asp

Val Lys His

270

Asp Pro Glu

275

Val Lys Phe

Asn Trp Tyr

280

Val Asp Gly

Val Glu Val 285

Asn Ala Lys

290

Thr Lys Pro

Arg Glu Glu 295

Glu Tyr Asn

300

Ser Thr Tyr

Val Val Ser 305

Val Leu Thr

310

Val Leu His

Gln Asp Trp

315

Leu Asn Gly

Glu Tyr Lys

Cys Lys Val

325

Ser Asn Lys

Ala Leu Pro 330

Ala Pro Ile

335

Lys Thr Ile

Ser Lys Ala 340

Lys Gly Gln

345

Pro Arg Glu

Pro Gln Val

350

Thr Leu Pro

355

Pro Ser Arg

Glu Glu Met

360

Thr Lys Asn

Gln Val Ser 365

Thr Cys Asp

370

Val Ser Gly

Phe Tyr Pro 375

Ser Asp Ile

380

Ala Val Glu

Glu Ser Asp 385

Gly Gln Pro

390

Glu Asn Asn

Tyr Lys Thr

395

Thr Pro Pro

Leu Asp Ser

Asp Gly Ser

405

Phe Phe Leu

Tyr Ser Lys 410

Leu Thr Val

415

Lys Ser Arg

Trp Glu Gln 420

Gly Asp Val

425

Phe Ser Cys

Ser Val Met

430

Glu Ala Leu

435

His Asn His

Tyr Thr Gln

440

Lys Ser Leu

Ser Leu Ser 445

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

Leu

Trp

Val 400

Asp

His

Pro

Gly Lys

450 <210> 339 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

- 402 044325 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 339

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

- 403 044325

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Val 465

Leu

His Trp Val

Phe Gly Gly 245

Gly Thr Lys

250

Leu Thr Val

Leu Glu Pro

255

Ser Ser Asp

260

Lys Thr His

Thr Cys Pro

265

Pro Cys Pro

Ala Pro Pro 270

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys 370

Val Tyr Thr

Lys Leu Thr

Glu Trp Glu

420

Pro Val Leu

435

Val Asp Lys 450

Met His Glu

Ser Val Phe

Leu Phe Pro 280

Pro Lys Pro

285

Lys Asp Thr

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

375

Leu Pro Pro

390

Cys Leu Val 405

Ser Asn Gly

Asp Ser Asp

Ser Arg Trp

455

Ala Leu His

470

Glu Val Thr

Cys Val Val

300

Val Asp Val

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Lys Ala Lys

Ser Arg Glu

Lys Gly Phe

410

Gln Pro Glu

425

Gly Ser Phe 440

Gln Gln Gly

Asn His Tyr

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Asn Lys Ala

365

Gly Gln Pro

380

Gln Met Thr 395

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

445

Asn Val Phe

460

Thr Gln Lys 475

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

400

Asp Ile Ala 415

Lys Thr Thr 430

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

480

Ser Pro Gly Lys

- 404 044325

485 <210> 340 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 340

Gln Ile Val Leu Thr Gln Ser Pro

5

Ser Ser Leu Ser Ala Ser Val Gly

15

Asp Arg Val Thr Ile Thr Cys Arg 20

Ala Ser Ser Ser Val Ser Tyr Ile 25 30

His Trp Phe Gln Gln Lys Pro Gly

40

Lys Ser Pro Lys Pro Leu Ile Tyr 45

Ala Thr Ser Asn Leu Ala Ser Gly

55

Val Pro Val Arg Phe Ser Gly Ser 60

Gly Ser Gly Thr Asp Tyr Thr Leu 65 70

Thr Ile Ser Ser Leu Gln Pro Glu

80

Asp Phe Ala Thr Tyr Tyr Cys Gln 85

Gln Trp Thr Ser Asn Pro Pro Thr

95

Phe Gly Gly Gly Thr Lys Val Glu

100

Ile Lys Arg Thr Val Ala Ala Pro

105 110

Ser Val Phe Ile Phe Pro Pro Ser

115 120

Asp Glu Gln Leu Lys Ser Gly Thr

125

Ala Ser Val Val Cys Leu Leu Asn

130 135

Asn Phe Tyr Pro Arg Glu Ala Lys

140

Val Gln Trp Lys Val Asp Asn Ala

145 150

Leu Gln Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu Gln Asp Ser Lys

165

Asp Ser Thr Tyr Ser Leu Ser Ser

170 175

Thr Leu Thr Leu Ser Lys Ala Asp 180

Tyr Glu Lys His Lys Val Tyr Ala

185 190

Cys Glu Val Thr His Gln Gly Leu

Ser Ser Pro Val Thr Lys Ser Phe

- 405 044325

195

200

205

Asn Arg Gly Glu Cys 210 <210> 341 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 341

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 7580

Met Glu Leu

Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

9095

Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly

100 105110

Ala Gly

Val Phe

130

Ala Leu 145

Ser Trp

Thr Leu 115

ProLeu

Gly Cys

Asn Ser

Val Thr

Ala Pro

Leu Val

150

Gly Ala 165

Val Ser

120

Ser Ser 135

Lys Asp

Leu Thr

Ser Ala

Lys Ser

Tyr Phe

Ser Gly

170

Ser Thr

Thr Ser

140

Pro Glu 155

Val His

Lys Gly 125

Gly Gly

Pro Val

Thr Phe

Pro Ser

Thr Ala

Thr Val

160

Pro Ala 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

- 406 044325

180

185

190

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Ser Ser Ser

195

Leu Gly Thr

Gln Thr Tyr 200

Ile Cys Asn

205

Val Asn His

Pro Ser Asp 210

Thr Lys Val

215

Asp Lys Lys

Val Glu Pro

220

Lys Ser Cys

Lys Thr His

Thr Cys Pro

230

Pro Cys Pro

Ala Pro Pro 235

Val Ala Gly

240

Ser Val Phe

Leu Phe Pro 245

Pro Lys Pro

250

Lys Asp Thr

Leu Met Ile

255

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Ser Arg Trp

420

Glu Val Thr

Cys Val Val

265

Val Asp Val

Lys His Glu 270

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Glu Gln Gly

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asp Val Phe

425

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

- 407 044325

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450 <210> 342 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 342

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 408 044325

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Glu Trp

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Glu Ser 420

Trp Val

Thr Asn

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Asn Gly

Gln Gln 185

Lys Arg 200

Gly Lys

Asp Tyr

Gly Thr

Lys Pro

Gly Lys

Ala Pro

Ala Ala

Tyr Cys

235

Lys Leu 250

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Glin Pro

425

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Glu Asn

Gly Val

205

Leu Thr

220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Asn Tyr

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Lys Thr 430

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

- 409 044325

Pro Pro Val Leu Asp Ser Asp Gly Ser

435 440

Phe Phe Leu Tyr Ser Lys Leu 445

Thr Val Asp Lys Ser Arg Trp Gln Gln

450 455

Val Met His Glu Ala Leu His Asn His

465 470

Gly Asn Val Phe Ser Cys Ser 460

Tyr Thr Gln Lys Ser Leu Ser

475 480

Leu Ser Pro Gly Lys

485 <210> 343 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 343

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

- 410 044325

Val Gln Trp Lys Val Asp Asn Ala Leu

145 150

Gln Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu Gln Asp Ser Lys Asp

165

Ser Thr Tyr Ser Leu Ser Ser

170 175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185

Glu Lys His Lys Val Tyr Ala 190

Cys Glu Val Thr His Gln Gly Leu Ser

195 200

Ser Pro Val Thr Lys Ser Phe

205

Asn Arg Gly Glu Cys

210 <210> 344 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 344

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys 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 Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly

100 105 110

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

- 411 044325

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Phe Pro Leu 130

Leu Gly Cys

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ala Pro Ser

135

Leu Val Lys

150

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Ser Lys Ser

Asp Tyr Phe

Thr Ser Gly 170

Tyr Ser Leu 185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Thr Ser Gly 140

Pro Glu Pro 155

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Gly Thr Ala

Val Thr Val

160

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

- 412 044325

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

385 390 395

Thr Thr Pro Pro Val

400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

405 410

Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

420 425

Cys Ser Val Met His

430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 345 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 345

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

- 413 044325

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Ser Gly Lys 130

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys

Pro Gly Ser

135

Val Thr Gln

150

Leu Thr Cys 165

Asn Trp Val

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Gly Lys Pro

Glu Pro Ser

Gly Ser Ser 170

Gln Gln Lys 185

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys 250

Thr Cys Pro 265

Leu Phe Pro 280

Glu Val Thr

Gly Ser Gly

140

Leu Thr Val 155

Thr Gly Ala

Pro Gly Lys

Pro Gly Val

205

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Lys Pro Gly

Ser Pro Gly

160

Val Thr Thr

175

Ser Pro Arg 190

Pro Ala Arg

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Pro Glu Val

310

Lys Phe Asn

Trp Tyr Val 315

Asp Gly Val

320

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

Lys Pro Arg

330

Glu Glu Gln

Tyr Asn Ser

335

Leu Thr Val

345

Leu His Gln

Asp Trp Leu 350

Lys Val Ser 360

Lys Ala Lys

Asn Lys Ala

365

Leu Pro Ala

Gly Gln Pro

Arg Glu Pro

- 414 044325

370

375

380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 346 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 346

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr

- 415 044325

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys

210 <210> 347 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 347

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr SerTyr

2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe

5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr

- 416 044325

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu Leu Ser Ser Leu

Arg Ser Glu Asp Thr

Ala Val Tyr Tyr Cys 95

Arg Ser Thr Tyr Tyr 100

Gly Gly Asp Trp Tyr 105

Phe Asn Val Trp Gly

110

Gly Thr Leu Val Thr 115

Phe Pro Leu Ala Pro 130

Leu Gly Cys Leu Val

150

Trp Asn Ser Gly Ala

165

Leu Gln Ser Ser Gly 180

Ser Ser Ser Leu Gly 195

Pro Ser Asp Thr Lys 210

Lys Thr His Thr Cys

230

Ser Val Phe Leu Phe

245

Arg Thr Pro Glu Val 260

Pro Glu Val Lys Phe

275

Ala Lys Thr Lys Pro 290

Val Ser Val Leu Thr

310

Val Ser Ser Ala Ser

120

Thr Lys Gly Pro Ser

125

Ser Ser Lys Ser Thr 135

Ser Gly Gly Thr Ala 140

Lys Asp Tyr Phe Pro

155

Glu Pro Val Thr Val

160

Leu Thr Ser Gly Val

170

Leu Tyr Ser Leu Ser 185

Thr Gln Thr Tyr Ile 200

Val Asp Lys Lys Val 215

Pro Pro Cys Pro Ala

235

Pro Pro Lys Pro Lys

250

Thr Cys Val Val Val

265

Asn Trp Tyr Val Asp

280

Arg Glu Glu Glu Tyr 295

Val Leu His Gln Asp

315

His Thr Phe Pro Ala

175

Ser Val Val Thr Val

190

Cys Asn Val Asn His

205

Glu Pro Lys Ser Cys 220

Pro Pro Val Ala Gly

240

Asp Thr Leu Met Ile

255

Asp Val Lys His Glu

270

Gly Val Glu Val His

285

Asn Ser Thr Tyr Arg 300

Trp Leu Asn Gly Lys

320

- 417 044325

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360365

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His

420 425430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210> 348 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 348

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp

5560

- 418 044325

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Ser Tyr Val Ser Trp

110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Leu Met Ile Ser Arg

290

Thr Pro Glu Val Thr

295

Cys Val Val Val Asp

300

Lys His Glu Asp Pro 305

Glu Val Lys Phe Asn 310

Trp Tyr Val Asp Gly 315

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

- 419 044325

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 349 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 349

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala 20 25

Ser Ser Ser Val Ser Tyr Ile 30

- 420 044325

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro

3540

Lys Pro Leu Ile Tyr

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys

210 <210> 350 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 350

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 10 15

- 421 044325

Ser

Asn

Gly

Gln 65

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Val Lys Val

Met His Trp 35

Ala Ile Tyr 50

Gly Arg Val

Glu Leu Ser

Arg Ser Thr

100

Gly Thr Leu

115

Phe Pro Leu 130

Leu Gly Cys

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Ser Cys Lys

Val Arg Gln

Pro Gly Asn

Thr Ile Thr

Ser Leu Arg 85

Tyr Tyr Gly

Val Thr Val

Ala Pro Ser

135

Leu Val Lys

150

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Ala Ser Gly 25

Ala Pro Gly 40

Gly Asp Thr

Ala Asp Lys

Ser Glu Asp

Gly Asp Trp

105

Ser Ser Ala 120

Ser Lys Ser

Asp Tyr Phe

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Tyr Thr Phe

Gln Gly Leu 45

Ser Tyr Asn 60

Ser Ile Ser 75

Thr Ala Val

Tyr Phe Asn

Ser Thr Lys

125

Thr Ser Gly 140

Pro Glu Pro 155

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Thr Ser Tyr 30

Glu Trp Met

Gln Lys Phe

Thr Ala Tyr

Tyr Tyr Cys 95

Val Trp Gly 110

Gly Pro Ser

Gly Thr Ala

Val Thr Val

160

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

- 422 044325

Asp Pro Glu Val Lys Phe Asn Trp

275 280

Tyr Val Asp Gly Val Glu Val His

285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr

385 390

Lys Thr Thr Pro Pro Val

395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

405 410

Ser Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe

420 425

Ser Cys Ser Val Met His

430

Glu Ala Leu His Asn His Tyr Thr Gln Lys

435 440

Ser Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 351 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 351

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

- 423 044325

Ser

Ala

Gly

Ser 65

Leu

Tyr

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Leu Arg Leu Ser Cys 20

Met Asn Trp Val Arg 35

Arg Ile Arg Ser Lys 50

Val Lys Gly Arg Phe 70

Tyr Leu Gln Met Asn 85

Cys Val Arg His Gly 100

Tyr Trp Gly Gln Gly 115

Ser Gly Lys Pro Gly 130

Gln Ala Val Val Thr

150

Thr Val Thr Leu Thr

165

Asn Tyr Ala Asn Trp 180

Leu Ile Gly Gly Thr

195

Ser Gly Ser Leu Leu 210

Gln Pro Glu Asp Glu

230

His Trp Val Phe Gly

245

Ser Ser Asp Lys Thr

Ala Ala Ser Gly Phe 25

Gln Ala Pro Gly Lys 40

Tyr Asn Asn Tyr Ala 55

Thr Ile Ser Arg Asp

Ser Leu Arg Ala Glu 90

Asn Phe Gly Glu Ser 105

Thr Leu Val Thr Val

120

Ser Gly Lys Pro Gly 135

Gln Glu Pro Ser Leu

155

Cys Gly Ser Ser Thr

170

Val Gln Gln Lys Pro 185

Asn Lys Arg Ala Pro 200

Gly Gly Lys Ala Ala 215

Ala Asp Tyr Tyr Cys

235

Gly Gly Thr Lys Leu

250

His Thr Cys Pro Pro

Thr Phe Ser Thr Tyr 30

Gly Leu Glu Trp Val 45

Thr Tyr Tyr Ala Asp 60

Asp Ser Lys Asn Thr 80

Asp Thr Ala Val Tyr 95

Tyr Val Ser Trp Phe

110

Ser Ser Gly Lys Pro

125

Ser Gly Lys Pro Gly 140

Thr Val Ser Pro Gly

160

Gly Ala Val Thr Thr

175

Gly Lys Ser Pro Arg 190

Gly Val Pro Ala Arg

205

Leu Thr Ile Ser Gly 220

Ala Leu Trp Tyr Ser

240

Thr Val Leu Glu Pro

255

Cys Pro Ala Pro Pro

- 424 044325

260

265

270

Val

Ala

Gly 275

Pro

Ser

Val

Phe

Leu

280

Phe

Pro

Pro

Lys

Pro

285

Lys

Asp

Leu

Met

290

Ile

Ser

Arg

Thr

Pro

295

Glu

Val

Thr

Cys

Val

300

Val

Val

Asp

Lys 305

His

Glu

Asp

Pro

Glu

310

Val

Lys

Phe

Asn

Trp 315

Tyr

Val

Asp

Gly

Glu

Val

His

Asn

Ala

325

Lys

Thr

Lys

Pro

Arg 330

Glu

Glu

Gln

Tyr

Asn

335

Thr

Tyr

Arg

Val

340

Val

Ser

Val

Leu

Thr

345

Val

Leu

His

Gln

Asp 350

Trp

Asn

Gly

Lys

355

Glu

Tyr

Lys

Cys

Lys 360

Val

Ser

Asn

Lys

Ala

365

Leu

Pro

Pro

Ile

370

Glu

Lys

Thr

Ile

Ser

375

Lys

Ala

Lys

Gly

Gln

380

Pro

Arg

Glu

Gln

385

Val

Tyr

Thr

Leu

Pro

390

Pro

Ser

Arg

Glu

Gln

395

Met

Thr

Lys

Asn

Val

Lys

Leu

Thr

Cys 405

Leu

Val

Lys

Gly

Phe

410

Tyr

Pro

Ser

Asp

Ile

415

Val

Glu

Trp

Glu

420

Ser

Asn

Gly

Gln

Pro

425

Glu

Asn

Asn

Tyr

Lys 430

Thr

Pro

Pro

Val

435

Leu

Asp

Ser

Asp

Gly 440

Ser

Phe

Phe

Leu

Tyr 445

Ser

Lys

Thr

Val

450

Asp

Lys

Ser

Arg

Trp

455

Gln

Gln

Gly

Asn

Val

460

Phe

Ser

Cys

Val

465

Met

His

Glu

Ala

Leu

470

His

Asn

His

Tyr

Thr

475

Gln

Lys

Ser

Leu

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

Leu

Ser

Ser 480

Leu Ser Pro Gly Lys

485 <210> 352 <211> 213 <212> PROTEIN <213> Artificial sequence

- 425 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 352

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Ser Ser 25

Val Ser Tyr Ile 30

His Trp Phe Gln 35

Gln Lys Pro Gly 40

Lys Ser Pro Lys

Pro Leu Ile Tyr 45

Ala Thr Ser Asn

Leu Ala Ser Gly 55

Val Pro Val Arg 60

Phe Ser Gly Ser

Gly Ser Gly Thr 65

Asp Tyr Thr Leu 70

Thr Ile Ser Ser

Leu Gln Pro Glu

Asp Phe Ala Thr

Tyr Tyr Cys Gln 85

Gln Trp Thr Ser 90

Asn Pro Pro Thr

Phe Gly Gly Gly

100

Thr Lys Val Glu

Ile Lys Arg Thr 105

Val Ala Ala Pro

110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

115 120

Gln Leu Lys Ser Gly Thr

125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe

130 135

Tyr Pro Arg Glu Ala Lys

140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150

Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu

Gln Asp Ser Lys 165

Asp Ser Thr Tyr 170

Ser Leu Ser Ser

175

Thr Leu Thr Leu

180

Ser Lys Ala Asp

Tyr Glu Lys His 185

Lys Val Tyr Ala 190

Cys Glu Val Thr

195

His Gln Gly Leu

200

Ser Ser Pro Val

Thr Lys Ser Phe 205

Asn Arg Gly Glu Cys

210

- 426 044325 <210> 353 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 353

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 7580

Met Glu Leu

Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

8590

Tyr Tyr Cys 95

Ala Arg

Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val

100 105110

Trp Gly

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135140

Ala Leu Gly Cys 145

Leu Val Lys Asp 150

Tyr Phe Pro Glu

155

Pro Val Thr Val

160

Ser Trp Asn Ser

Gly Ala Leu Thr 165

Ser Gly Val His 170

Thr Phe Pro Ala

175

Val Leu Gln Ser

180

Ser Gly Leu Tyr

Ser Leu Ser Ser 185

Val Val Thr Val

190

Pro Ser Ser Ser

195

Leu Gly Thr Gln

200

Thr Tyr Ile Cys

Asn Val Asn His 205

- 427 044325

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Glu

Gly

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Ser Arg Trp

420

Ala Leu His

435

Lys 450

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Glu Gln Gly

Asn His Tyr

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asp Val Phe

425

Thr Gln Lys 440

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

445

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

Leu Ser Pro

- 428 044325 <210> 354 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 354

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

- 429 044325

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Glu Trp

Pro Val

435

Val Asp 450

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Glu Ser 420

Leu Asp

Lys Ser

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Asn Gly

Ser Asp

Arg Trp

455

Gly Lys

Asp Tyr

Gly Thr

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Glin Pro

425

Gly Ser 440

Gln Gln

Ala Ala

Tyr Cys

235

Lys Leu 250

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Glu Asn

Phe Phe

Gly Asn

Leu Thr 220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Asn Tyr

Leu Tyr

445

Val Phe 460

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Lys Thr 430

Ser Lys

Ser Cys

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

Leu

Ser

- 430 044325

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485 <210> 355 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 355

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

- 431 044325

Thr Leu Thr Leu

180

Ser Lys Ala Asp

Tyr Glu Lys His Lys Val Tyr Ala

185 190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200 205

Asn Arg Gly Glu Cys

210 <210> 356 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 356

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly

100 105110

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155160

- 432 044325

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala 330

Gly Gln Pro 345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

- 433 044325

405 410415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His

420 425430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210> 357 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 357

Glu 1 Val Gln Leu Val 5 Glu Ser Gly Gly Gly 10 Leu Val Gln Pro Gly 15 Gly Ser Leu Arg Leu 20 Ser Cys Ala Ala Ser 25 Gly Phe Thr Phe Ser 30 Thr Tyr Ala Met Asn 35 Trp Val Arg Gln Ala 40 Pro Gly Lys Gly Leu 45 Glu Trp Val Gly Arg 50 Ile Arg Ser Lys Tyr 55 Asn Asn Tyr Ala Thr 60 Tyr Tyr Ala Asp Ser 65 Val Lys Gly Arg Phe 70 Thr Ile Ser Arg Asp 75 Asp Ser Lys Asn Thr 80 Leu Tyr Leu Gln Met 85 Asn Ser Leu Arg Ala 90 Glu Asp Thr Ala Val 95 Tyr Tyr Cys Val Arg 100 His Gly Asn Phe Gly 105 Asp Glu Tyr Val Ser 110 Trp Phe Ala Tyr Trp 115 Gly Gln Gly Thr Leu 120 Val Thr Val Ser Ser 125 Gly Lys Pro Gly Ser 130 Gly Lys Pro Gly Ser 135 Gly Lys Pro Gly Ser 140 Gly Lys Pro Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

- 434 044325

145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Thr Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

150

155

Thr Leu

165

Thr Cys

Gly Ser

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Trp Val

Gln Gln

185

Thr Asn

Leu Gly 215

Glu Ala 230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Lys Arg 200

Gly Lys

Ser Thr 170

Lys Pro

Ala Pro

Ala Ala

Gly Ala

Val Thr

175

Asp Tyr

Tyr Cys

235

Gly Thr

Lys Leu 250

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Gly Lys

Gly Val 205

Leu Thr 220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

- 435 044325

Val Lys Leu

Thr Cys Leu Val Lys Gly Phe Tyr Pro

405 410

Ser Asp Ile Ala

415

Val Glu Trp

Glu Ser Asn Gly Gln Pro Glu Asn Asn 420 425

Tyr Lys Thr Thr 430

Pro Pro Val

435

Leu Asp Ser Asp Gly Ser Phe Phe Leu

440

Tyr Ser Lys Leu 445

Thr Val Asp

450

Lys Ser Arg Trp Gln Gln Gly Asn Val

455 460

Phe Ser Cys Ser

Val Met His 465

Glu Ala Leu His Asn His Tyr Thr Gln

470 475

Lys Ser Leu Ser

480

Leu Ser Pro Gly Lys

485 <210> 358 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 358

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile 20 25 30

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 40 45

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 55 60

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr 85 90 95

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105 110

- 436 044325

Ser Val Phe Ile Phe Pro Pro Ser

115 120

Asp Glu Gln Leu Lys Ser Gly Thr

125

Ala Ser Val Val Cys Leu Leu Asn

130 135

Asn Phe Tyr Pro Arg Glu Ala Lys

140

Val Gln Trp Lys Val Asp Asn Ala

145 150

Leu Gln Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu Gln Asp Ser Lys

165

Asp Ser Thr Tyr Ser Leu Ser Ser

170 175

Thr Leu Thr Leu Ser Lys Ala Asp 180

Tyr Glu Lys His Lys Val Tyr Ala

185 190

Cys Glu Val Thr His Gln Gly Leu

195 200

Ser Ser Pro Val Thr Lys Ser Phe

205

Asn Arg Gly Glu Cys

210 <210> 359 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 359

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

- 437 044325

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Arg Ser

Gly Thr

115

Phe Pro 130

Leu Gly

Trp Asn

Leu Gln

Ser Ser

195

Pro Ser 210

Lys Thr

Ser Val

Arg Thr

Pro Glu

275

Ala Lys 290

Val Ser

Tyr Lys

Thr Ile

Thr Tyr 100

Leu Val

Leu Ala

Cys Leu

Tyr Gly

Thr Val

Pro Ser

135

Val Lys 150

Ser Gly

165

Ser Ser 180

Ser Leu

Asp Thr

His Thr

Phe Leu

245

Pro Glu 260

Val Lys

Thr Lys

Val Leu

Cys Lys

325

Ser Lys 340

Ala Leu

Gly Leu

Gly Thr

Lys Val

215

Cys Pro 230

Phe Pro

Val Thr

Phe Asn

Pro Arg

295

Thr Val 310

Val Ser

Ala Lys

Gly Asp

105

Trp Tyr

Phe Asn

Ser Ser 120

Ser Lys

Asp Tyr

Thr Ser

Tyr Ser

185

Gln Thr

200

Asp Lys

Pro Cys

Pro Lys

Cys Val

265

Trp Tyr 280

Glu Glu

Leu His

Asn Lys

Gly Gln

345

Ala Ser

Thr Lys

125

Ser Thr

Ser Gly 140

Phe Pro

155

Gly Val 170

Leu Ser

Tyr Ile

Lys Val

Pro Ala

235

Pro Lys 250

Val Val

Val Asp

Glu Tyr

Gln Asp

315

Ala Leu 330

Pro Arg

Glu Pro

His Thr

Ser Val

Cys Asn

205

Glu Pro

220

Pro Pro

Asp Thr

Asp Val

Gly Val

285

Asn Ser 300

Trp Leu

Pro Ala

Glu Pro

Val Trp 110

Gly Pro

Gly Thr

Val Thr

Phe Pro

175

Val Thr 190

Val Asn

Lys Ser

Val Ala

Leu Met

255

Lys His 270

Glu Val

Thr Tyr

Asn Gly

Pro Ile

335

Gln Val 350

Gly

Ser

Ala

Val 160

Ala

Val

His

Cys

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

- 438 044325

Thr

Leu

Pro

355

Pro

Ser

Arg

Glu

Glu

360

Met

Thr

Lys

Asn

Gln

365

Val

Ser

Leu

Thr

Cys 370

Asp

Val

Ser

Gly

Phe

375

Tyr

Pro

Ser

Asp

Ile

380

Ala

Val

Glu

Trp

Glu

385

Ser

Asp

Gly

Gln

Pro

390

Glu

Asn

Asn

Tyr

Lys

395

Thr

Thr

Pro

Pro

Val

400

Leu

Asp

Ser

Asp

Gly 405

Ser

Phe

Phe

Leu

Tyr 410

Ser

Lys

Leu

Thr

Val

415

Asp

Lys

Ser

Arg

Trp 420

Glu

Gln

Gly

Asp

Val

425

Phe

Ser

Cys

Ser

Val

430

Met

His

Glu

Ala

Leu

435

His

Asn

His

Tyr

Thr

440

Gln

Lys

Ser

Leu

Ser

445

Leu

Ser

Pro

Gly Lys

450 <210> 360 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 360

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

- 439 044325

Tyr

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Cys Val Arg

100

Tyr Trp Gly

115

Ser Gly Lys 130

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

His Gly Asn

Gln Gly Thr

Pro Gly Ser

135

Val Thr Gln

150

Leu Thr Cys 165

Asn Trp Val

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Phe Gly Asp

105

Leu Val Thr 120

Gly Lys Pro

Glu Pro Ser

Gly Ser Ser

170

Gln Gln Lys

185

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys

250

Thr Cys Pro

265

Leu Phe Pro 280

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Gln Tyr Val

Ser Trp Phe 110

Val Ser Ser

125

Gly Ser Gly

140

Leu Thr Val 155

Thr Gly Ala

Pro Gly Lys

Pro Gly Val

205

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Gly Lys Pro

Lys Pro Gly

Ser Pro Gly

160

Val Thr Thr

175

Ser Pro Arg 190

Pro Ala Arg

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

- 440 044325

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 361 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 361

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser TyrIle

2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser

5560

- 441 044325

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys 210 <210> 362 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 362

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

- 442 044325

Gly

Gln 65

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Ala Ile Tyr Pro Gly 50

Asn Gly Ala Thr Ser 55

Tyr Ser Gln Lys Phe 60

Gly Arg Val Thr Ile 70

Glu Leu Ser Ser Leu

Arg Ser Tyr Tyr Met 100

Gly Thr Leu Val Thr 115

Phe Pro Leu Ala Pro 130

Leu Gly Cys Leu Val

150

Trp Asn Ser Gly Ala

165

Leu Gln Ser Ser Gly 180

Ser Ser Ser Leu Gly

195

Pro Ser Asp Thr Lys 210

Lys Thr His Thr Cys

230

Ser Val Phe Leu Phe

245

Arg Thr Pro Glu Val 260

Pro Glu Val Lys Phe

275

Ala Lys Thr Lys Pro

Thr Ala Asp Thr Ser 75

Arg Ser Glu Asp Thr

Gly Gly Asp Trp Tyr

105

Val Ser Ser Ala Ser

120

Ser Ser Lys Ser Thr 135

Lys Asp Tyr Phe Pro

155

Leu Thr Ser Gly Val

170

Leu Tyr Ser Leu Ser

185

Thr Gln Thr Tyr Ile 200

Val Asp Lys Lys Val 215

Pro Pro Cys Pro Ala

235

Pro Pro Lys Pro Lys

250

Thr Cys Val Val Val

265

Asn Trp Tyr Val Asp

280

Arg Glu Glu Glu Tyr

Ala Ser Thr Ala Tyr 80

Ala Val Tyr Tyr Cys 95

Phe Asp Val Trp Gly

110

Thr Lys Gly Pro Ser

125

Ser Gly Gly Thr Ala 140

Glu Pro Val Thr Val

160

His Thr Phe Pro Ala

175

Ser Val Val Thr Val

190

Cys Asn Val Asn His

205

Glu Pro Lys Ser Cys 220

Pro Pro Val Ala Gly

240

Asp Thr Leu Met Ile

255

Asp Val Lys His Glu

270

Gly Val Glu Val His

285

Asn Ser Thr Tyr Arg

- 443 044325

290

295

300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val

325

Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

330 335

Lys Thr

Ile Ser Lys Ala Lys

340

Gly Gln Pro Arg Glu Pro Gln Val Tyr

345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val

355 360 365

Ser Leu

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp

370 375

Ile Ala Val Glu Trp 380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

385 390 395

Thr Thr Pro Pro Val

400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

405 410

Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

420 425

Cys Ser Val Met His 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 363 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 363

Glu 1 Val Gln Leu Val 5 Glu Ser Gly Gly Gly 10 Leu Val Gln Pro Gly 15 Gly Ser Leu Arg Leu 20 Ser Cys Ala Ala Ser 25 Gly Phe Thr Phe Ser 30 Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

- 444 044325

Gly Arg Ile Arg Ser 50

Lys Tyr Asn Asn Tyr 55

Ala Thr Tyr Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Ser Tyr Val Ser Trp

110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys

125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

- 445 044325

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 364 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 364

- 446 044325

Gln Ile Val 1

Leu Thr Gln

Ser Pro Ser

Ser Leu Ser 10

Ala Ser Val

Asp Arg Val

Thr Ile Thr 20

Cys Arg Ala

Ser Trp Ser

Val Ser Tyr 30

His Trp Phe

Gln Gln Lys

Pro Gly Lys 40

Ser Pro Lys

Pro Leu Ile 45

Ala Thr Ser

Asn Leu Ala

Ser Gly Val 55

Pro Val Arg 60

Phe Ser Gly

Gly Ser Gly 65

Thr Asp Tyr

Thr Leu Thr

Ile Ser Ser

Leu Gln Pro

Asp Phe Ala

Thr Tyr Tyr

Cys Gln Gln

Trp Thr His 90

Asn Pro Pro

Phe Gly Gly

Gly Thr Lys 100

Val Glu Ile

105

Lys Arg Thr

Val Ala Ala

110

Ser Val Phe

115

Ile Phe Pro

Pro Ser Asp

120

Glu Gln Leu

Lys Ser Gly 125

Ala Ser Val

130

Val Cys Leu

Leu Asn Asn 135

Phe Tyr Pro

140

Arg Glu Ala

Val Gln Trp 145

Lys Val Asp

150

Asn Ala Leu

Gln Ser Gly

155

Asn Ser Gln

Ser Val Thr

Glu Gln Asp

165

Ser Lys Asp

Ser Thr Tyr 170

Ser Leu Ser

175

Thr Leu Thr

Leu Ser Lys 180

Ala Asp Tyr

185

Glu Lys His

Lys Val Tyr

190

Cys Glu Val

195

Thr His Gln

Gly Leu Ser

200

Ser Pro Val

Thr Lys Ser 205

Gly

Ile

Tyr

Ser

Glu 80

Thr

Pro

Thr

Lys

Glu 160

Ser

Ala

Phe

Asn Arg Gly Glu Cys

210 <210> 365 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source

- 447 044325 <223> /note=Description of artificial sequence: synthetic polypeptide <400> 365

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Ser Tyr Tyr Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

100 105110

Ala Gly Thr Leu Val Thr Val Ser

115 120

Ser Ala Ser Thr Lys Gly Pro Ser

125

Val Phe Pro Leu Ala Pro Ser Ser

130 135

Lys Ser Thr Ser Gly Gly Thr Ala

140

Ala Leu Gly Cys Leu Val Lys Asp

145 150

Tyr Phe Pro Glu Pro Val Thr Val

155 160

Ser Trp Asn Ser Gly Ala Leu Thr

165

Ser Gly Val His Thr Phe Pro Ala

170 175

Val Leu Gln Ser Ser Gly Leu Tyr

180

Ser Leu Ser Ser Val Val Thr Val

185 190

Pro Ser Ser Ser Leu Gly Thr Gln

195 200

Thr Tyr Ile Cys Asn Val Asn His

205

Lys Pro Ser Asp Thr Lys Val Asp

210 215

Lys Lys Val Glu Pro Lys Ser Cys

220

Asp Lys Thr His Thr Cys Pro Pro

225 230

Cys Pro Ala Pro Pro Val Ala Gly

235 240

- 448 044325

Pro Ser Val

Phe Leu Phe

245

Pro Pro Lys

Pro Lys Asp 250

Thr Leu Met

255

Ser Arg Thr

Pro Glu Val 260

Thr Cys Val

265

Val Val Asp

Val Lys His

270

Asp Pro Glu

275

Val Lys Phe

Asn Trp Tyr

280

Val Asp Gly

Val Glu Val 285

Asn Ala Lys

290

Thr Lys Pro

Arg Glu Glu 295

Glu Tyr Asn

300

Ser Thr Tyr

Val Val Ser 305

Val Leu Thr

310

Val Leu His

Gln Asp Trp

315

Leu Asn Gly

Glu Tyr Lys

Cys Lys Val

325

Ser Asn Lys

Ala Leu Pro 330

Ala Pro Ile

335

Lys Thr Ile

Ser Lys Ala 340

Lys Gly Gln

345

Pro Arg Glu

Pro Gln Val

350

Thr Leu Pro

355

Pro Ser Arg

Glu Glu Met

360

Thr Lys Asn

Gln Val Ser 365

Thr Cys Asp

370

Val Ser Gly

Phe Tyr Pro 375

Ser Asp Ile

380

Ala Val Glu

Glu Ser Asp 385

Gly Gln Pro

390

Glu Asn Asn

Tyr Lys Thr

395

Thr Pro Pro

Leu Asp Ser

Asp Gly Ser

405

Phe Phe Leu

Tyr Ser Lys 410

Leu Thr Val

415

Lys Ser Arg

Trp Glu Gln 420

Gly Asp Val

425

Phe Ser Cys

Ser Val Met

430

Glu Ala Leu

435

His Asn His

Tyr Thr Gln

440

Lys Ser Leu

Ser Leu Ser 445

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

Leu

Trp

Val 400

Asp

His

Pro

Gly Lys

450 <210> 366 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

- 449 044325 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 366

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

- 450 044325

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Val 465

Leu

His Trp Val

Phe Gly Gly 245

Gly Thr Lys

250

Leu Thr Val

Leu Glu Pro

255

Ser Ser Asp

260

Lys Thr His

Thr Cys Pro

265

Pro Cys Pro

Ala Pro Pro 270

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys 370

Val Tyr Thr

Lys Leu Thr

Glu Trp Glu

420

Pro Val Leu

435

Val Asp Lys 450

Met His Glu

Ser Val Phe

Leu Phe Pro 280

Pro Lys Pro

285

Lys Asp Thr

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

375

Leu Pro Pro

390

Cys Leu Val 405

Ser Asn Gly

Asp Ser Asp

Ser Arg Trp

455

Ala Leu His

470

Glu Val Thr

Cys Val Val

300

Val Asp Val

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Lys Ala Lys

Ser Arg Glu

Lys Gly Phe

410

Gln Pro Glu

425

Gly Ser Phe 440

Gln Gln Gly

Asn His Tyr

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Asn Lys Ala

365

Gly Gln Pro

380

Gln Met Thr 395

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

445

Asn Val Phe

460

Thr Gln Lys 475

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

400

Asp Ile Ala 415

Lys Thr Thr 430

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

480

Ser Pro Gly Lys

- 451 044325

485 <210> 367 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 367

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

- 452 044325

195

200

205

Asn Arg Gly Glu Cys 210 <210> 368 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 368

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 7580

Met Glu Leu

Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

9095

Ala Arg Ser Tyr Tyr Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

100 105110

Ala Gly

Val Phe

130

Ala Leu 145

Ser Trp

Thr Leu 115

ProLeu

Gly Cys

Asn Ser

Val Thr

Ala Pro

Leu Val

150

Gly Ala 165

Val Ser

120

Ser Ser 135

Lys Asp

Leu Thr

Ser Ala

Lys Ser

Tyr Phe

Ser Gly

170

Ser Thr

Thr Ser

140

Pro Glu 155

Val His

Lys Gly 125

Gly Gly

Pro Val

Thr Phe

Pro Ser

Thr Ala

Thr Val

160

Pro Ala 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

- 453 044325

180

185

190

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Ser Ser Ser

195

Leu Gly Thr

Gln Thr Tyr 200

Ile Cys Asn

205

Val Asn His

Pro Ser Asp 210

Thr Lys Val

215

Asp Lys Lys

Val Glu Pro

220

Lys Ser Cys

Lys Thr His

Thr Cys Pro

230

Pro Cys Pro

Ala Pro Pro 235

Val Ala Gly

240

Ser Val Phe

Leu Phe Pro 245

Pro Lys Pro

250

Lys Asp Thr

Leu Met Ile

255

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Ser Arg Trp

420

Glu Val Thr

Cys Val Val

265

Val Asp Val

Lys His Glu 270

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Glu Gln Gly

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asp Val Phe

425

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

- 454 044325

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450 <210> 369 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 369

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 455 044325

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Glu Trp

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Glu Ser 420

Trp Val

Thr Asn

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Asn Gly

Gln Gln 185

Lys Arg 200

Gly Lys

Asp Tyr

Gly Thr

Lys Pro

Gly Lys

Ala Pro

Ala Ala

Tyr Cys

235

Lys Leu 250

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Glin Pro

425

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Glu Asn

Gly Val

205

Leu Thr

220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Asn Tyr

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Lys Thr 430

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

- 456 044325

Pro Pro Val 435 Leu Asp Ser Asp Gly 440 Ser Phe Phe Leu Tyr 445 Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 450 455 460 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 465 470 475 480

Leu Ser Pro Gly Lys

485 <210> 370 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 370

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

- 457 044325

Val Gln Trp Lys Val Asp Asn Ala Leu

145 150

Gln Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu Gln Asp Ser Lys Asp

165

Ser Thr Tyr Ser Leu Ser Ser

170 175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185

Glu Lys His Lys Val Tyr Ala 190

Cys Glu Val Thr His Gln Gly Leu Ser

195 200

Ser Pro Val Thr Lys Ser Phe

205

Asn Arg Gly Glu Cys

210 <210> 371 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 371

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 40 45

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala 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 Ser Tyr Tyr Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

100 105 110

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

- 458 044325

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Phe Pro Leu 130

Leu Gly Cys

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ala Pro Ser

135

Leu Val Lys

150

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Ser Lys Ser

Asp Tyr Phe

Thr Ser Gly 170

Tyr Ser Leu 185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Thr Ser Gly 140

Pro Glu Pro 155

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Gly Thr Ala

Val Thr Val

160

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

- 459 044325

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

385 390 395

Thr Thr Pro Pro Val

400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

405 410

Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

420 425

Cys Ser Val Met His

430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 372 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 372

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

- 460 044325

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Ser Gly Lys 130

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys

Pro Gly Ser

135

Val Thr Gln

150

Leu Thr Cys 165

Asn Trp Val

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Gly Lys Pro

Glu Pro Ser

Gly Ser Ser 170

Gln Gln Lys 185

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys 250

Thr Cys Pro 265

Leu Phe Pro 280

Glu Val Thr

Gly Ser Gly

140

Leu Thr Val 155

Thr Gly Ala

Pro Gly Lys

Pro Gly Val

205

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Lys Pro Gly

Ser Pro Gly

160

Val Thr Thr

175

Ser Pro Arg 190

Pro Ala Arg

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Pro Glu Val

310

Lys Phe Asn

Trp Tyr Val 315

Asp Gly Val

320

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

Lys Pro Arg

330

Glu Glu Gln

Tyr Asn Ser

335

Leu Thr Val

345

Leu His Gln

Asp Trp Leu 350

Lys Val Ser 360

Lys Ala Lys

Asn Lys Ala

365

Leu Pro Ala

Gly Gln Pro

Arg Glu Pro

- 461 044325

370

375

380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 373 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 373

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr

- 462 044325

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys

210 <210> 374 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 374

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr SerTyr

2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe

5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr

- 463 044325

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu Leu Ser

Ser Leu Arg 85

Ser Glu Asp

Thr Ala Val

Tyr Tyr Cys 95

Arg Ser Tyr

100

Gly Thr Leu 115

Phe Pro Leu 130

Leu Gly Cys

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Met Gly

Gly Asp Trp

105

Tyr Phe Asp

Val Trp Gly 110

Val Thr Val

Ala Pro Ser

135

Leu Val Lys

150

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Ser Ser Ala 120

Ser Thr Lys

125

Gly Pro Ser

Ser Lys Ser

Thr Ser Gly 140

Gly Thr Ala

Asp Tyr Phe

Pro Glu Pro 155

Val Thr Val

160

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Val His Thr

Phe Pro Ala

175

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

- 464 044325

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360365

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His

420 425430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210> 375 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 375

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

5560

- 465 044325

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Pro

105

Ser Tyr Val Ser Trp

110

Ala Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Leu Met Ile Ser Arg

290

Thr Pro Glu Val Thr

295

Cys Val Val Val Asp

300

Lys His Glu Asp Pro 305

Glu Val Lys Phe Asn 310

Trp Tyr Val Asp Gly 315

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

- 466 044325

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 376 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 376

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala 20 25

Ser Trp Ser Val Ser Tyr Ile

- 467 044325

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro

3540

Lys Pro Leu Ile Tyr

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys

210 <210> 377 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 377

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 10 15

- 468 044325

Ser

Asn

Gly

Gln 65

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Val Lys Val

Met His Trp 35

Ala Ile Tyr 50

Gly Arg Val

Glu Leu Ser

Arg Ser Tyr

100

Gly Thr Leu

115

Phe Pro Leu 130

Leu Gly Cys

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Ser Cys Lys

Val Arg Gln

Pro Gly Asn

Thr Ile Thr

Ser Leu Arg 85

Tyr Met Gly

Val Thr Val

Ala Pro Ser

135

Leu Val Lys

150

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Ala Ser Gly 25

Ala Pro Gly 40

Gly Ala Thr

Ala Asp Thr

Ser Glu Asp

Gly Asp Trp

105

Ser Ser Ala 120

Ser Lys Ser

Asp Tyr Phe

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Tyr Thr Phe

Gln Arg Leu

Ser Tyr Ser 60

Ser Ala Ser 75

Thr Ala Val

Tyr Phe Asp

Ser Thr Lys

125

Thr Ser Gly 140

Pro Glu Pro 155

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Thr Ser Tyr 30

Glu Trp Met

Gln Lys Phe

Thr Ala Tyr

Tyr Tyr Cys 95

Val Trp Gly 110

Gly Pro Ser

Gly Thr Ala

Val Thr Val

160

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

- 469 044325

Asp Pro Glu Val Lys Phe Asn Trp

275 280

Tyr Val Asp Gly Val Glu Val His

285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr

385 390

Lys Thr Thr Pro Pro Val

395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

405 410

Ser Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe

420 425

Ser Cys Ser Val Met His

430

Glu Ala Leu His Asn His Tyr Thr Gln Lys

435 440

Ser Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 378 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 378

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

- 470 044325

Ser

Ala

Gly

Ser 65

Leu

Tyr

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Leu Arg Leu Ser Cys 20

Met Asn Trp Val Arg 35

Arg Ile Arg Ser Lys 50

Val Lys Gly Arg Phe 70

Tyr Leu Gln Met Asn 85

Cys Val Arg His Gly 100

Tyr Trp Gly Gln Gly 115

Ser Gly Lys Pro Gly 130

Gln Ala Val Val Thr

150

Thr Val Thr Leu Thr

165

Asn Tyr Ala Asn Trp 180

Leu Ile Gly Gly Thr

195

Ser Gly Ser Leu Leu 210

Gln Pro Glu Asp Glu

230

His Trp Val Phe Gly

245

Ser Ser Asp Lys Thr

Ala Ala Ser Gly Phe 25

Gln Ala Pro Gly Lys 40

Tyr Asn Asn Tyr Ala 55

Thr Ile Ser Arg Asp

Ser Leu Arg Ala Glu 90

Asn Phe Gly Asp Glu 105

Thr Leu Val Thr Val

120

Ser Gly Lys Pro Gly 135

Gln Glu Pro Ser Leu

155

Cys Gly Ser Ser Thr

170

Val Gln Gln Lys Pro 185

Asn Lys Arg Ala Pro 200

Gly Gly Lys Ala Ala 215

Ala Asp Tyr Tyr Cys

235

Gly Gly Thr Lys Leu

250

His Thr Cys Pro Pro

Thr Phe Ser Thr Tyr 30

Gly Leu Glu Trp Val 45

Thr Tyr Tyr Ala Asp 60

Asp Ser Lys Asn Thr 80

Asp Thr Ala Val Tyr 95

Tyr Val Ser Trp Phe

110

Ser Ser Gly Lys Pro

125

Ser Gly Lys Pro Gly 140

Thr Val Ser Pro Gly

160

Gly Ala Val Thr Thr

175

Gly Lys Ser Pro Arg 190

Gly Val Pro Ala Arg

205

Leu Thr Ile Ser Gly 220

Ala Leu Trp Tyr Ser

240

Thr Val Leu Glu Pro

255

Cys Pro Ala Pro Pro

- 471 044325

260

265

270

Val

Ala

Gly 275

Pro

Ser

Val

Phe

Leu

280

Phe

Pro

Pro

Lys

Pro

285

Lys

Asp

Leu

Met

290

Ile

Ser

Arg

Thr

Pro

295

Glu

Val

Thr

Cys

Val

300

Val

Val

Asp

Lys 305

His

Glu

Asp

Pro

Glu

310

Val

Lys

Phe

Asn

Trp 315

Tyr

Val

Asp

Gly

Glu

Val

His

Asn

Ala

325

Lys

Thr

Lys

Pro

Arg 330

Glu

Glu

Gln

Tyr

Asn

335

Thr

Tyr

Arg

Val

340

Val

Ser

Val

Leu

Thr

345

Val

Leu

His

Gln

Asp 350

Trp

Asn

Gly

Lys

355

Glu

Tyr

Lys

Cys

Lys 360

Val

Ser

Asn

Lys

Ala

365

Leu

Pro

Pro

Ile

370

Glu

Lys

Thr

Ile

Ser

375

Lys

Ala

Lys

Gly

Gln

380

Pro

Arg

Glu

Gln

385

Val

Tyr

Thr

Leu

Pro

390

Pro

Ser

Arg

Glu

Gln

395

Met

Thr

Lys

Asn

Val

Lys

Leu

Thr

Cys 405

Leu

Val

Lys

Gly

Phe

410

Tyr

Pro

Ser

Asp

Ile

415

Val

Glu

Trp

Glu

420

Ser

Asn

Gly

Gln

Pro

425

Glu

Asn

Asn

Tyr

Lys 430

Thr

Pro

Pro

Val

435

Leu

Asp

Ser

Asp

Gly 440

Ser

Phe

Phe

Leu

Tyr 445

Ser

Lys

Thr

Val

450

Asp

Lys

Ser

Arg

Trp

455

Gln

Gln

Gly

Asn

Val

460

Phe

Ser

Cys

Val

465

Met

His

Glu

Ala

Leu

470

His

Asn

His

Tyr

Thr

475

Gln

Lys

Ser

Leu

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

Leu

Ser

Ser 480

Leu Ser Pro Gly Lys

485 <210> 379 <211> 213 <212> PROTEIN <213> Artificial sequence

- 472 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 379

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Trp Ser 25

Val Ser Tyr Ile 30

His Trp Phe Gln 35

Gln Lys Pro Gly 40

Lys Ser Pro Lys

Pro Leu Ile Tyr 45

Ala Thr Ser Asn

Leu Ala Ser Gly 55

Val Pro Val Arg 60

Phe Ser Gly Ser

Gly Ser Gly Thr 65

Asp Tyr Thr Leu 70

Thr Ile Ser Ser

Leu Gln Pro Glu

Asp Phe Ala Thr

Tyr Tyr Cys Gln 85

Gln Trp Thr His 90

Asn Pro Pro Thr

Phe Gly Gly Gly

100

Thr Lys Val Glu

Ile Lys Arg Thr 105

Val Ala Ala Pro

110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

115 120

Gln Leu Lys Ser Gly Thr

125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe

130 135

Tyr Pro Arg Glu Ala Lys

140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150

Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu

Gln Asp Ser Lys 165

Asp Ser Thr Tyr 170

Ser Leu Ser Ser

175

Thr Leu Thr Leu

180

Ser Lys Ala Asp

Tyr Glu Lys His 185

Lys Val Tyr Ala 190

Cys Glu Val Thr

195

His Gln Gly Leu

200

Ser Ser Pro Val

Thr Lys Ser Phe 205

Asn Arg Gly Glu Cys

210

- 473 044325 <210> 380 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 380

Gln Val Gln Leu 1

Val Gln Ser Gly 5

Ala Glu Val Lys 10

Lys Pro Gly Ala 15

Ser Val Lys Val 20

Ser Cys Lys Ala

Ser Gly Tyr Thr 25

Phe Thr Ser Tyr 30

Asn Met His Trp 35

Val Arg Gln Ala 40

Pro Gly Gln Arg

Leu Glu Trp Met 45

Gly Ala Ile Tyr 50

Pro Gly Asn Gly

Ala Thr Ser Tyr 60

Ser Gln Lys Phe

Gln Gly Arg Val 65

Thr Ile Thr Ala

Asp Thr Ser Ala 75

Ser Thr Ala Tyr 80

Met Glu Leu

Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

90

Tyr Tyr Cys 95

Ala Arg Ser Tyr Tyr Met

100

Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

105 110

Ala Gly Thr Leu Val Thr Val 115

Val Phe Pro Leu Ala Pro Ser

130 135

Ser Ser Ala Ser Thr Lys Gly Pro Ser 120 125

Ser Lys Ser Thr Ser Gly Gly Thr Ala

140

Ala Leu Gly Cys 145

Leu Val Lys Asp 150

Tyr Phe Pro Glu

155

Pro Val Thr Val

160

Ser Trp Asn Ser

Gly Ala Leu Thr 165

Ser Gly Val His 170

Thr Phe Pro Ala

175

Val Leu Gln Ser

180

Ser Gly Leu Tyr

Ser Leu Ser Ser 185

Val Val Thr Val

190

Pro Ser Ser Ser

195

Leu Gly Thr Gln

200

Thr Tyr Ile Cys

Asn Val Asn His 205

- 474 044325

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Glu

Gly

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Ser Arg Trp

420

Ala Leu His

435

Lys 450

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Glu Gln Gly

Asn His Tyr

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asp Val Phe

425

Thr Gln Lys 440

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

445

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

Leu Ser Pro

- 475 044325 <210> 381 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 381

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Pro Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

- 476 044325

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Glu Trp

Pro Val

435

Val Asp 450

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Glu Ser 420

Leu Asp

Lys Ser

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Asn Gly

Ser Asp

Arg Trp

455

Gly Lys

Asp Tyr

Gly Thr

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Glin Pro

425

Gly Ser 440

Gln Gln

Ala Ala

Tyr Cys

235

Lys Leu 250

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Glu Asn

Phe Phe

Gly Asn

Leu Thr 220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Asn Tyr

Leu Tyr

445

Val Phe 460

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Lys Thr 430

Ser Lys

Ser Cys

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

Leu

Ser

- 477 044325

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485 <210> 382 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 382

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

- 478 044325

Thr Leu Thr Leu Ser Lys Ala Asp 180

Tyr Glu Lys His Lys Val Tyr Ala

185 190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200 205

Asn Arg Gly Glu Cys

210 <210> 383 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 383

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Ser Tyr Tyr Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

100 105110

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155160

- 479 044325

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala 330

Gly Gln Pro 345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

- 480 044325

405 410415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His

420 425430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210> 384 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 384

Glu 1 Val Gln Leu Val 5 Glu Ser Gly Gly Gly 10 Leu Val Gln Pro Gly 15 Gly Ser Leu Arg Leu 20 Ser Cys Ala Ala Ser 25 Gly Phe Thr Phe Ser 30 Thr Tyr Ala Met Asn 35 Trp Val Arg Gln Ala 40 Pro Gly Lys Gly Leu 45 Glu Trp Val Gly Arg 50 Ile Arg Ser Lys Ala 55 Asn Asn Tyr Ala Thr 60 Tyr Tyr Ala Asp Ser 65 Val Lys Gly Arg Phe 70 Thr Ile Ser Arg Asp 75 Asp Ser Lys Asn Thr 80 Leu Tyr Leu Gln Met 85 Asn Ser Leu Arg Ala 90 Glu Asp Thr Ala Val 95 Tyr Tyr Cys Val Arg 100 His Gly Asn Phe Gly 105 Asp Ser Tyr Val Ser 110 Trp Phe Asp Tyr Trp 115 Gly Gln Gly Thr Leu 120 Val Thr Val Ser Ser 125 Gly Lys Pro Gly Ser 130 Gly Lys Pro Gly Ser 135 Gly Lys Pro Gly Ser 140 Gly Lys Pro Gly Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

- 481 044325

145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Thr Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

150

155

Thr Leu

165

Thr Cys

Gly Ser

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Trp Val

Gln Gln

185

Thr Asn

Leu Gly 215

Glu Ala 230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Lys Arg 200

Gly Lys

Ser Thr 170

Lys Pro

Ala Pro

Ala Ala

Gly Ala

Val Thr

175

Asp Tyr

Tyr Cys

235

Gly Thr

Lys Leu 250

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Gly Lys

Gly Val 205

Leu Thr 220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

- 482 044325

Val Lys Leu

Thr Cys Leu Val Lys Gly Phe Tyr Pro

405 410

Ser Asp Ile Ala

415

Val Glu Trp

Glu Ser Asn Gly Gln Pro Glu Asn Asn 420 425

Tyr Lys Thr Thr 430

Pro Pro Val

435

Leu Asp Ser Asp Gly Ser Phe Phe Leu

440

Tyr Ser Lys Leu 445

Thr Val Asp

450

Lys Ser Arg Trp Gln Gln Gly Asn Val

455 460

Phe Ser Cys Ser

Val Met His 465

Glu Ala Leu His Asn His Tyr Thr Gln

470 475

Lys Ser Leu Ser

480

Leu Ser Pro Gly Lys

485 <210> 385 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 385

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 25 30

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 40 45

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 55 60

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 90 95

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105 110

- 483 044325

Ser Val Phe Ile Phe Pro Pro Ser

115 120

Asp Glu Gln Leu Lys Ser Gly Thr

125

Ala Ser Val Val Cys Leu Leu Asn

130 135

Asn Phe Tyr Pro Arg Glu Ala Lys

140

Val Gln Trp Lys Val Asp Asn Ala

145 150

Leu Gln Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu Gln Asp Ser Lys

165

Asp Ser Thr Tyr Ser Leu Ser Ser

170 175

Thr Leu Thr Leu Ser Lys Ala Asp 180

Tyr Glu Lys His Lys Val Tyr Ala

185 190

Cys Glu Val Thr His Gln Gly Leu

195 200

Ser Ser Pro Val Thr Lys Ser Phe

205

Asn Arg Gly Glu Cys

210 <210> 386 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 386

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

- 484 044325

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Arg Ser

Gly Thr

115

Phe Pro 130

Leu Gly

Trp Asn

Leu Gln

Ser Ser

195

Pro Ser 210

Lys Thr

Ser Val

Arg Thr

Pro Glu

275

Ala Lys 290

Val Ser

Tyr Lys

Thr Ile

Tyr Tyr 100

Leu Val

Leu Ala

Cys Leu

Ser Gly

165

Ser Ser 180

Ser Leu

Asp Thr

His Thr

Phe Leu

245

Pro Glu 260

Val Lys

Thr Lys

Val Leu

Cys Lys

325

Ser Lys 340

Met Gly

Thr Val

Pro Ser

135

Val Lys 150

Ala Leu

Gly Leu

Gly Thr

Lys Val

215

Cys Pro 230

Phe Pro

Val Thr

Phe Asn

Pro Arg

295

Thr Val 310

Val Ser

Ala Lys

Gly Asp

105

Trp Tyr

Phe Asp

Ser Ser 120

Ser Lys

Asp Tyr

Thr Ser

Tyr Ser

185

Gln Thr

200

Asp Lys

Pro Cys

Pro Lys

Cys Val

265

Trp Tyr 280

Glu Glu

Leu His

Asn Lys

Gly Gln

345

Ala Ser

Thr Lys

125

Ser Thr

Ser Gly 140

Phe Pro

155

Gly Val 170

Leu Ser

Tyr Ile

Lys Val

Pro Ala

235

Pro Lys 250

Val Val

Val Asp

Glu Tyr

Gln Asp

315

Ala Leu 330

Pro Arg

Glu Pro

His Thr

Ser Val

Cys Asn

205

Glu Pro

220

Pro Pro

Asp Thr

Asp Val

Gly Val

285

Asn Ser 300

Trp Leu

Pro Ala

Glu Pro

Val Trp 110

Gly Pro

Gly Thr

Val Thr

Phe Pro

175

Val Thr 190

Val Asn

Lys Ser

Val Ala

Leu Met

255

Lys His 270

Glu Val

Thr Tyr

Asn Gly

Pro Ile

335

Gln Val 350

Gly

Ser

Ala

Val 160

Ala

Val

His

Cys

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

- 485 044325

Thr

Leu

Pro

355

Pro

Ser

Arg

Glu

Glu

360

Met

Thr

Lys

Asn

Gln

365

Val

Ser

Leu

Thr

Cys 370

Asp

Val

Ser

Gly

Phe

375

Tyr

Pro

Ser

Asp

Ile

380

Ala

Val

Glu

Trp

Glu

385

Ser

Asp

Gly

Gln

Pro

390

Glu

Asn

Asn

Tyr

Lys

395

Thr

Thr

Pro

Pro

Val

400

Leu

Asp

Ser

Asp

Gly 405

Ser

Phe

Phe

Leu

Tyr 410

Ser

Lys

Leu

Thr

Val

415

Asp

Lys

Ser

Arg

Trp 420

Glu

Gln

Gly

Asp

Val

425

Phe

Ser

Cys

Ser

Val

430

Met

His

Glu

Ala

Leu

435

His

Asn

His

Tyr

Thr

440

Gln

Lys

Ser

Leu

Ser

445

Leu

Ser

Pro

Gly Lys

450 <210> 387 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 387

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

- 486 044325

Tyr

Asp

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Cys Val

Tyr Trp

115

Ser Gly 130

Gln Ala

Thr Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Arg His 100

Gly Gln

Lys Pro

Val Val

Thr Leu

165

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Gly Asn

Gly Thr

Gly Ser

135

Thr Gln 150

Thr Cys

Trp Val

Thr Asn

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Phe Gly

105

Asp Ser

Tyr Val

Leu Val 120

Gly Lys

Glu Pro

Gly Ser

Gln Gln

185

Lys Arg 200

Gly Lys

Asp Tyr

Gly Thr

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Thr Val

Ser Ser

125

Pro Gly

Ser Gly 140

Ser Leu

155

Ser Thr 170

Lys Pro

Ala Pro

Ala Ala

Tyr Cys

235

Lys Leu 250

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Thr Val

Gly Ala

Gly Lys

Gly Val

205

Leu Thr

220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Ser Trp 110

Gly Lys

Lys Pro

Ser Pro

Val Thr

175

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

- 487 044325

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 388 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 388

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser TyrIle

2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser

5560

- 488 044325

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys 210 <210> 389 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 389

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

- 489 044325

Gly

Gln 65

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Ala Ile Tyr Pro Gly 50

Asn Gly Ala Thr Ser 55

Tyr Ser Gln Lys Phe 60

Gly Arg Val Thr Ile 70

Glu Leu Ser Ser Leu

Arg Ser Tyr Tyr Met 100

Gly Thr Leu Val Thr 115

Phe Pro Leu Ala Pro 130

Leu Gly Cys Leu Val

150

Trp Asn Ser Gly Ala

165

Leu Gln Ser Ser Gly 180

Ser Ser Ser Leu Gly

195

Pro Ser Asp Thr Lys 210

Lys Thr His Thr Cys

230

Ser Val Phe Leu Phe

245

Arg Thr Pro Glu Val 260

Pro Glu Val Lys Phe

275

Ala Lys Thr Lys Pro

Thr Ala Asp Thr Ser 75

Arg Ser Glu Asp Thr

Gly Gly Asp Trp Tyr

105

Val Ser Ser Ala Ser

120

Ser Ser Lys Ser Thr 135

Lys Asp Tyr Phe Pro

155

Leu Thr Ser Gly Val

170

Leu Tyr Ser Leu Ser

185

Thr Gln Thr Tyr Ile 200

Val Asp Lys Lys Val 215

Pro Pro Cys Pro Ala

235

Pro Pro Lys Pro Lys

250

Thr Cys Val Val Val

265

Asn Trp Tyr Val Asp

280

Arg Glu Glu Glu Tyr

Ala Ser Thr Ala Tyr 80

Ala Val Tyr Tyr Cys 95

Phe Asp Val Trp Gly

110

Thr Lys Gly Pro Ser

125

Ser Gly Gly Thr Ala 140

Glu Pro Val Thr Val

160

His Thr Phe Pro Ala

175

Ser Val Val Thr Val

190

Cys Asn Val Asn His

205

Glu Pro Lys Ser Cys 220

Pro Pro Val Ala Gly

240

Asp Thr Leu Met Ile

255

Asp Val Lys His Glu

270

Gly Val Glu Val His

285

Asn Ser Thr Tyr Arg

- 490 044325

290

295

300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val

325

Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

330 335

Lys Thr

Ile Ser Lys Ala Lys

340

Gly Gln Pro Arg Glu Pro Gln Val Tyr

345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val

355 360 365

Ser Leu

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp

370 375

Ile Ala Val Glu Trp 380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

385 390 395

Thr Thr Pro Pro Val

400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

405 410

Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

420 425

Cys Ser Val Met His 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 390 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 390

Glu 1 Val Gln Leu Val 5 Glu Ser Gly Gly Gly 10 Leu Val Gln Pro Gly 15 Gly Ser Leu Arg Leu 20 Ser Cys Ala Ala Ser 25 Gly Phe Thr Phe Ser 30 Thr Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

- 491 044325

Gly Arg Ile Arg Ser 50

Lys Tyr Asn Asn Tyr 55

Ala Thr Tyr Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Ala

105

Ser Tyr Val Ser Trp

110

Asp Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys

125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

- 492 044325

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 391 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 391

- 493 044325

Gln Ile Val 1

Leu Thr Gln

Ser Pro Ser

Ser Leu Ser 10

Ala Ser Val

Asp Arg Val

Thr Ile Thr 20

Cys Arg Ala

Ser Trp Ser

Val Ser Tyr 30

His Trp Phe

Gln Gln Lys

Pro Gly Lys 40

Ser Pro Lys

Pro Leu Ile 45

Ala Thr Ser

Asn Leu Ala

Ser Gly Val 55

Pro Val Arg 60

Phe Ser Gly

Gly Ser Gly 65

Thr Asp Tyr

Thr Leu Thr

Ile Ser Ser

Leu Gln Pro

Asp Phe Ala

Thr Tyr Tyr

Cys Gln Gln

Trp Thr His 90

Asn Pro Pro

Phe Gly Gly

Gly Thr Lys 100

Val Glu Ile

105

Lys Arg Thr

Val Ala Ala

110

Ser Val Phe

115

Ile Phe Pro

Pro Ser Asp

120

Glu Gln Leu

Lys Ser Gly 125

Ala Ser Val

130

Val Cys Leu

Leu Asn Asn 135

Phe Tyr Pro

140

Arg Glu Ala

Val Gln Trp 145

Lys Val Asp

150

Asn Ala Leu

Gln Ser Gly

155

Asn Ser Gln

Ser Val Thr

Glu Gln Asp

165

Ser Lys Asp

Ser Thr Tyr 170

Ser Leu Ser

175

Thr Leu Thr

Leu Ser Lys 180

Ala Asp Tyr

185

Glu Lys His

Lys Val Tyr

190

Cys Glu Val

195

Thr His Gln

Gly Leu Ser

200

Ser Pro Val

Thr Lys Ser 205

Gly

Ile

Tyr

Ser

Glu 80

Thr

Pro

Thr

Lys

Glu 160

Ser

Ala

Phe

Asn Arg Gly Glu Cys

210 <210> 392 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source

- 494 044325 <223> /note=Description of artificial sequence: synthetic polypeptide <400> 392

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Ser Tyr Tyr Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

100 105110

Ala Gly Thr Leu Val Thr Val Ser

115 120

Ser Ala Ser Thr Lys Gly Pro Ser

125

Val Phe Pro Leu Ala Pro Ser Ser

130 135

Lys Ser Thr Ser Gly Gly Thr Ala

140

Ala Leu Gly Cys Leu Val Lys Asp

145 150

Tyr Phe Pro Glu Pro Val Thr Val

155 160

Ser Trp Asn Ser Gly Ala Leu Thr

165

Ser Gly Val His Thr Phe Pro Ala

170 175

Val Leu Gln Ser Ser Gly Leu Tyr

180

Ser Leu Ser Ser Val Val Thr Val

185 190

Pro Ser Ser Ser Leu Gly Thr Gln

195 200

Thr Tyr Ile Cys Asn Val Asn His

205

Lys Pro Ser Asp Thr Lys Val Asp

210 215

Lys Lys Val Glu Pro Lys Ser Cys

220

Asp Lys Thr His Thr Cys Pro Pro

225 230

Cys Pro Ala Pro Pro Val Ala Gly

235 240

- 495 044325

Pro Ser Val

Phe Leu Phe

245

Pro Pro Lys

Pro Lys Asp 250

Thr Leu Met

255

Ser Arg Thr

Pro Glu Val 260

Thr Cys Val

265

Val Val Asp

Val Lys His

270

Asp Pro Glu

275

Val Lys Phe

Asn Trp Tyr

280

Val Asp Gly

Val Glu Val 285

Asn Ala Lys

290

Thr Lys Pro

Arg Glu Glu 295

Glu Tyr Asn

300

Ser Thr Tyr

Val Val Ser 305

Val Leu Thr

310

Val Leu His

Gln Asp Trp

315

Leu Asn Gly

Glu Tyr Lys

Cys Lys Val

325

Ser Asn Lys

Ala Leu Pro 330

Ala Pro Ile

335

Lys Thr Ile

Ser Lys Ala 340

Lys Gly Gln

345

Pro Arg Glu

Pro Gln Val

350

Thr Leu Pro

355

Pro Ser Arg

Glu Glu Met

360

Thr Lys Asn

Gln Val Ser 365

Thr Cys Asp

370

Val Ser Gly

Phe Tyr Pro 375

Ser Asp Ile

380

Ala Val Glu

Glu Ser Asp 385

Gly Gln Pro

390

Glu Asn Asn

Tyr Lys Thr

395

Thr Pro Pro

Leu Asp Ser

Asp Gly Ser

405

Phe Phe Leu

Tyr Ser Lys 410

Leu Thr Val

415

Lys Ser Arg

Trp Glu Gln 420

Gly Asp Val

425

Phe Ser Cys

Ser Val Met

430

Glu Ala Leu

435

His Asn His

Tyr Thr Gln

440

Lys Ser Leu

Ser Leu Ser 445

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

Leu

Trp

Val 400

Asp

His

Pro

Gly Lys

450 <210> 393 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

- 496 044325 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 393

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Gln Ser Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Ile Ser Gly

210 215220

Ala Gln Pro Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Leu Trp Tyr Ser

225 230 235240

- 497 044325

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Val 465

Leu

His Trp Val

Phe Gly Gly 245

Gly Thr Lys

250

Leu Thr Val

Leu Glu Pro

255

Ser Ser Asp

260

Lys Thr His

Thr Cys Pro

265

Pro Cys Pro

Ala Pro Pro 270

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys 370

Val Tyr Thr

Lys Leu Thr

Glu Trp Glu

420

Pro Val Leu

435

Val Asp Lys 450

Met His Glu

Ser Val Phe

Leu Phe Pro 280

Pro Lys Pro

285

Lys Asp Thr

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

375

Leu Pro Pro

390

Cys Leu Val 405

Ser Asn Gly

Asp Ser Asp

Ser Arg Trp

455

Ala Leu His

470

Glu Val Thr

Cys Val Val

300

Val Asp Val

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Lys Val Ser 360

Lys Ala Lys

Ser Arg Glu

Lys Gly Phe

410

Gln Pro Glu

425

Gly Ser Phe 440

Gln Gln Gly

Asn His Tyr

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Asn Lys Ala

365

Gly Gln Pro

380

Gln Met Thr 395

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

445

Asn Val Phe

460

Thr Gln Lys 475

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

400

Asp Ile Ala 415

Lys Thr Thr 430

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

480

Ser Pro Gly Lys

- 498 044325

485 <210> 394 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 394

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

- 499 044325

195

200

205

Asn Arg Gly Glu Cys 210 <210> 395 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 395

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 7580

Met Glu Leu

Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

9095

Ala Arg Ser Tyr Tyr Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

100 105110

Ala Gly

Val Phe

130

Ala Leu 145

Ser Trp

Thr Leu 115

ProLeu

Gly Cys

Asn Ser

Val Thr

Ala Pro

Leu Val

150

Gly Ala 165

Val Ser

120

Ser Ser 135

Lys Asp

Leu Thr

Ser Ala

Lys Ser

Tyr Phe

Ser Gly

170

Ser Thr

Thr Ser

140

Pro Glu 155

Val His

Lys Gly 125

Gly Gly

Pro Val

Thr Phe

Pro Ser

Thr Ala

Thr Val

160

Pro Ala 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

- 500 044325

180

185

190

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Ser Ser Ser

195

Leu Gly Thr

Gln Thr Tyr 200

Ile Cys Asn

205

Val Asn His

Pro Ser Asp 210

Thr Lys Val

215

Asp Lys Lys

Val Glu Pro

220

Lys Ser Cys

Lys Thr His

Thr Cys Pro

230

Pro Cys Pro

Ala Pro Pro 235

Val Ala Gly

240

Ser Val Phe

Leu Phe Pro 245

Pro Lys Pro

250

Lys Asp Thr

Leu Met Ile

255

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Ser Arg Trp

420

Glu Val Thr

Cys Val Val

265

Val Asp Val

Lys His Glu 270

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Glu Gln Gly

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asp Val Phe

425

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

- 501 044325

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450 <210> 396 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 396

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Glu Tyr Val Ser Trp Phe

100 105110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

- 502 044325

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Glu Trp

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Glu Ser 420

Trp Val

Thr Asn

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Asn Gly

Gln Gln 185

Lys Arg 200

Gly Lys

Asp Tyr

Gly Thr

Lys Pro

Gly Lys

Ala Pro

Ala Ala

Tyr Cys

235

Lys Leu 250

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Glin Pro

425

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Glu Asn

Gly Val

205

Leu Thr

220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Asn Tyr

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Lys Thr 430

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

- 503 044325

Pro Pro Val Leu Asp Ser Asp Gly Ser

435440

Thr Val Asp Lys Ser Arg Trp Gln Gln

450455

Val Met His Glu Ala Leu His Asn His

465470

Phe Phe Leu Tyr 445 Ser Lys Leu Gly Asn Val 460 Phe Ser Cys Ser Tyr Thr 475 Gln Lys Ser Leu Ser 480

Leu Ser Pro Gly Lys

485 <210> 397 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 397

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

- 504 044325

Val Gln Trp Lys Val Asp Asn Ala Leu

145 150

Gln Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu Gln Asp Ser Lys Asp

165

Ser Thr Tyr Ser Leu Ser Ser

170 175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185

Glu Lys His Lys Val Tyr Ala 190

Cys Glu Val Thr His Gln Gly Leu Ser

195 200

Ser Pro Val Thr Lys Ser Phe

205

Asn Arg Gly Glu Cys

210 <210> 398 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 398

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 40 45

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala 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 Ser Tyr Tyr Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

100 105 110

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

- 505 044325

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Phe Pro 130

Leu Gly

Trp Asn

Leu Gln

Ser Ser

195

Pro Ser 210

Lys Thr

Ser Val

Arg Thr

Pro Glu

275

Ala Lys 290

Val Ser

Tyr Lys

Thr Ile

Leu Pro

355

Cys Asp 370

Leu Ala

Cys Leu

Ser Gly

165

Ser Ser 180

Ser Leu

Asp Thr

His Thr

Phe Leu

245

Pro Glu 260

Val Lys

Thr Lys

Val Leu

Cys Lys

325

Ser Lys 340

Pro Ser

Val Ser

Pro Ser

135

Val Lys 150

Ala Leu

Gly Leu

Gly Thr

Lys Val

215

Cys Pro 230

Phe Pro

Val Thr

Phe Asn

Pro Arg

295

Thr Val 310

Val Ser

Ala Lys

Arg Glu

Gly Phe

375

Ser Lys

Ser Thr

Asp Tyr

Phe Pro

155

Thr Ser

Gly Val 170

Tyr Ser

185

Gln Thr

200

Asp Lys

Pro Cys

Pro Lys

Cys Val

265

Trp Tyr 280

Glu Glu

Leu His

Asn Lys

Gly Gln

345

Glu Met 360

Tyr Pro

Leu Ser

Tyr Ile

Lys Val

Pro Ala

235

Pro Lys 250

Val Val

Val Asp

Glu Tyr

Gln Asp

315

Ala Leu 330

Pro Arg

Thr Lys

Ser Asp

Ser Gly 140

Glu Pro

His Thr

Ser Val

Cys Asn

205

Glu Pro

220

Pro Pro

Asp Thr

Asp Val

Gly Val

285

Asn Ser 300

Trp Leu

Pro Ala

Glu Pro

Asn Gln

365

Ile Ala

380

Gly Thr

Val Thr

Phe Pro

175

Val Thr 190

Val Asn

Lys Ser

Val Ala

Leu Met

255

Lys His 270

Glu Val

Thr Tyr

Asn Gly

Pro Ile

335

Gln Val 350

Val Ser

Val Glu

Ala

Val 160

Ala

Val

His

Cys

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

Leu

Trp

- 506 044325

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

385 390 395

Thr Thr Pro Pro Val

400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

405 410

Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

420 425

Cys Ser Val Met His

430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 399 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 399

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 50 55 60

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 75 80

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 90 95

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Asn Tyr Val Ser Trp Phe

100 105 110

Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120 125

- 507 044325

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Ser Gly Lys 130

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

Gly Lys Glu

355

Ile Glu Lys

Pro Gly Ser

135

Val Thr Gln

150

Leu Thr Cys 165

Asn Trp Val

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Gly Lys Pro

Glu Pro Ser

Gly Ser Ser 170

Gln Gln Lys 185

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys 250

Thr Cys Pro 265

Leu Phe Pro 280

Glu Val Thr

Gly Ser Gly

140

Leu Thr Val 155

Thr Gly Ala

Pro Gly Lys

Pro Gly Val

205

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Lys Pro Gly

Ser Pro Gly

160

Val Thr Thr

175

Ser Pro Arg 190

Pro Ala Arg

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Pro Glu Val

310

Lys Phe Asn

Trp Tyr Val 315

Asp Gly Val

320

Ala Lys Thr 325

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

Lys Pro Arg

330

Glu Glu Gln

Tyr Asn Ser

335

Leu Thr Val

345

Leu His Gln

Asp Trp Leu 350

Lys Val Ser 360

Lys Ala Lys

Asn Lys Ala

365

Leu Pro Ala

Gly Gln Pro

Arg Glu Pro

- 508 044325

370

375

380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 400 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 400

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr

- 509 044325

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys

210 <210> 401 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 401

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr SerTyr

2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe

5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr

- 510 044325

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu Leu Ser Ser Leu

Arg Ser Glu Asp Thr

Ala Val Tyr Tyr Cys 95

Arg Ser Tyr Tyr Met 100

Gly Gly Asp Trp Tyr 105

Phe Asp Val Trp Gly

110

Gly Thr Leu Val Thr 115

Phe Pro Leu Ala Pro 130

Leu Gly Cys Leu Val

150

Trp Asn Ser Gly Ala

165

Leu Gln Ser Ser Gly 180

Ser Ser Ser Leu Gly 195

Pro Ser Asp Thr Lys 210

Lys Thr His Thr Cys

230

Ser Val Phe Leu Phe

245

Arg Thr Pro Glu Val 260

Pro Glu Val Lys Phe

275

Ala Lys Thr Lys Pro 290

Val Ser Val Leu Thr

310

Val Ser Ser Ala Ser

120

Thr Lys Gly Pro Ser

125

Ser Ser Lys Ser Thr 135

Ser Gly Gly Thr Ala 140

Lys Asp Tyr Phe Pro

155

Glu Pro Val Thr Val

160

Leu Thr Ser Gly Val

170

Leu Tyr Ser Leu Ser 185

Thr Gln Thr Tyr Ile 200

Val Asp Lys Lys Val 215

Pro Pro Cys Pro Ala

235

Pro Pro Lys Pro Lys

250

Thr Cys Val Val Val

265

Asn Trp Tyr Val Asp

280

Arg Glu Glu Glu Tyr 295

Val Leu His Gln Asp

315

His Thr Phe Pro Ala

175

Ser Val Val Thr Val

190

Cys Asn Val Asn His

205

Glu Pro Lys Ser Cys 220

Pro Pro Val Ala Gly

240

Asp Thr Leu Met Ile

255

Asp Val Lys His Glu

270

Gly Val Glu Val His

285

Asn Ser Thr Tyr Arg 300

Trp Leu Asn Gly Lys

320

- 511 044325

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360365

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His

420 425430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210> 402 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 402

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp

5560

- 512 044325

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Pro Tyr Val Ser Trp

110

Asp Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys 125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Leu Met Ile Ser Arg

290

Thr Pro Glu Val Thr

295

Cys Val Val Val Asp

300

Lys His Glu Asp Pro 305

Glu Val Lys Phe Asn 310

Trp Tyr Val Asp Gly 315

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

- 513 044325

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 403 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 403

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala 20 25

Ser Trp Ser Val Ser Tyr Ile

- 514 044325

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro

3540

Lys Pro Leu Ile Tyr

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys

210 <210> 404 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 404

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 10 15

- 515 044325

Ser

Asn

Gly

Gln 65

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Val Lys Val

Met His Trp 35

Ala Ile Tyr 50

Gly Arg Val

Glu Leu Ser

Arg Ser Tyr

100

Gly Thr Leu

115

Phe Pro Leu 130

Leu Gly Cys

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Ser Cys Lys

Val Arg Gln

Pro Gly Asn

Thr Ile Thr

Ser Leu Arg 85

Tyr Met Gly

Val Thr Val

Ala Pro Ser

135

Leu Val Lys

150

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Ala Ser Gly 25

Ala Pro Gly 40

Gly Ala Thr

Ala Asp Thr

Ser Glu Asp

Gly Asp Trp

105

Ser Ser Ala 120

Ser Lys Ser

Asp Tyr Phe

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Tyr Thr Phe

Gln Arg Leu

Ser Tyr Ser 60

Ser Ala Ser 75

Thr Ala Val

Tyr Phe Asp

Ser Thr Lys

125

Thr Ser Gly 140

Pro Glu Pro 155

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Thr Ser Tyr 30

Glu Trp Met

Gln Lys Phe

Thr Ala Tyr

Tyr Tyr Cys 95

Val Trp Gly 110

Gly Pro Ser

Gly Thr Ala

Val Thr Val

160

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

- 516 044325

Asp Pro Glu Val Lys Phe Asn Trp

275 280

Tyr Val Asp Gly Val Glu Val His

285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Glu Tyr Asn Ser Thr Tyr Arg

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr

385 390

Lys Thr Thr Pro Pro Val

395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

405 410

Ser Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe

420 425

Ser Cys Ser Val Met His

430

Glu Ala Leu His Asn His Tyr Thr Gln Lys

435 440

Ser Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 405 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 405

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

- 517 044325

Ser

Ala

Gly

Ser 65

Leu

Tyr

Asp

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Leu Arg Leu Ser Cys 20

Met Asn Trp Val Arg 35

Arg Ile Arg Ser Lys 50

Val Lys Gly Arg Phe 70

Tyr Leu Gln Met Asn 85

Cys Val Arg His Gly 100

Tyr Trp Gly Gln Gly 115

Ser Gly Lys Pro Gly 130

Gln Ala Val Val Thr

150

Thr Val Thr Leu Thr

165

Asn Tyr Ala Asn Trp 180

Leu Ile Gly Gly Thr

195

Ser Gly Ser Leu Leu 210

Gln Pro Glu Asp Glu

230

His Trp Val Phe Gly

245

Ser Ser Asp Lys Thr

Ala Ala Ser Gly Phe 25

Gln Ala Pro Gly Lys 40

Tyr Asn Asn Tyr Ala 55

Thr Ile Ser Arg Asp

Ser Leu Arg Ala Glu 90

Asn Phe Gly Asp Gln 105

Thr Leu Val Thr Val

120

Ser Gly Lys Pro Gly 135

Gln Glu Pro Ser Leu

155

Cys Gly Ser Ser Thr

170

Val Gln Gln Lys Pro 185

Asn Lys Arg Ala Pro 200

Gly Gly Lys Ala Ala 215

Ala Asp Tyr Tyr Cys

235

Gly Gly Thr Lys Leu

250

His Thr Cys Pro Pro

Thr Phe Ser Thr Tyr 30

Gly Leu Glu Trp Val 45

Thr Tyr Tyr Ala Asp 60

Asp Ser Lys Asn Thr 80

Asp Thr Ala Val Tyr 95

Tyr Val Ser Trp Phe

110

Ser Ser Gly Lys Pro

125

Ser Gly Lys Pro Gly 140

Thr Val Ser Pro Gly

160

Gly Ala Val Thr Thr

175

Gly Lys Ser Pro Arg 190

Gly Val Pro Ala Arg

205

Leu Thr Ile Ser Gly 220

Ala Leu Trp Tyr Ser

240

Thr Val Leu Glu Pro

255

Cys Pro Ala Pro Pro

- 518 044325

260

265 270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

280 285

Leu Met Ile Ser Arg

290

Thr Pro Glu Val Thr Cys Val Val Val Asp

295 300

Lys His Glu Asp Pro 305

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

310 315

Glu Val His Asn Ala

325

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

330 335

Thr Tyr Arg Val Val

340

Ser Val Leu Thr Val Leu His Gln Asp Trp

345 350

Asn Gly Lys Glu Tyr

355

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

360 365

Pro Ile Glu Lys Thr 370

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

375 380

Gln Val Tyr Thr Leu 385

Pro Pro Ser Arg Glu Gln Met Thr Lys Asn 390 395

Val Lys Leu Thr Cys

405

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

410 415

Val Glu Trp Glu Ser

420

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

425 430

Pro Pro Val Leu Asp

435

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

440 445

Thr Val Asp Lys Ser 450

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

455 460

Val Met His Glu Ala 465

Leu His Asn His Tyr Thr Gln Lys Ser Leu 470 475

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

Leu

Ser

Ser 480

Leu Ser Pro Gly Lys

485 <210> 406 <211> 213 <212> PROTEIN <213> Artificial sequence

- 519 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 406

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Trp Ser 25

Val Ser Tyr Ile 30

His Trp Phe Gln 35

Gln Lys Pro Gly 40

Lys Ser Pro Lys

Pro Leu Ile Tyr 45

Ala Thr Ser Asn

Leu Ala Ser Gly 55

Val Pro Val Arg 60

Phe Ser Gly Ser

Gly Ser Gly Thr 65

Asp Tyr Thr Leu 70

Thr Ile Ser Ser

Leu Gln Pro Glu

Asp Phe Ala Thr

Tyr Tyr Cys Gln 85

Gln Trp Thr His 90

Asn Pro Pro Thr

Phe Gly Gly Gly

100

Thr Lys Val Glu

Ile Lys Arg Thr 105

Val Ala Ala Pro

110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

115 120

Gln Leu Lys Ser Gly Thr

125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe

130 135

Tyr Pro Arg Glu Ala Lys

140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150

Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu

Gln Asp Ser Lys 165

Asp Ser Thr Tyr 170

Ser Leu Ser Ser

175

Thr Leu Thr Leu

180

Ser Lys Ala Asp

Tyr Glu Lys His 185

Lys Val Tyr Ala 190

Cys Glu Val Thr

195

His Gln Gly Leu

200

Ser Ser Pro Val

Thr Lys Ser Phe 205

Asn Arg Gly Glu Cys

210

- 520 044325 <210> 407 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 407

Gln Val Gln Leu 1

Val Gln Ser Gly 5

Ala Glu Val Lys 10

Lys Pro Gly Ala 15

Ser Val Lys Val 20

Ser Cys Lys Ala

Ser Gly Tyr Thr 25

Phe Thr Ser Tyr 30

Asn Met His Trp 35

Val Arg Gln Ala 40

Pro Gly Gln Arg

Leu Glu Trp Met 45

Gly Ala Ile Tyr 50

Pro Gly Asn Gly

Ala Thr Ser Tyr 60

Ser Gln Lys Phe

Gln Gly Arg Val 65

Thr Ile Thr Ala

Asp Thr Ser Ala 75

Ser Thr Ala Tyr 80

Met Glu Leu

Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

90

Tyr Tyr Cys 95

Ala Arg Ser Tyr Tyr Met

100

Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

105 110

Ala Gly Thr Leu Val Thr Val 115

Val Phe Pro Leu Ala Pro Ser

130 135

Ser Ser Ala Ser Thr Lys Gly Pro Ser 120 125

Ser Lys Ser Thr Ser Gly Gly Thr Ala

140

Ala Leu Gly Cys 145

Leu Val Lys Asp 150

Tyr Phe Pro Glu

155

Pro Val Thr Val

160

Ser Trp Asn Ser

Gly Ala Leu Thr 165

Ser Gly Val His 170

Thr Phe Pro Ala

175

Val Leu Gln Ser

180

Ser Gly Leu Tyr

Ser Leu Ser Ser 185

Val Val Thr Val

190

Pro Ser Ser Ser

195

Leu Gly Thr Gln

200

Thr Tyr Ile Cys

Asn Val Asn His 205

- 521 044325

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Glu

Gly

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Ser Arg Trp

420

Ala Leu His

435

Lys 450

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Glu Gln Gly

Asn His Tyr

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asp Val Phe

425

Thr Gln Lys 440

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

445

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

Leu Ser Pro

- 522 044325 <210> 408 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 408

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Asp Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

145 150 155160

Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Thr

165 170175

Ser Asn Tyr Ala Asn Trp Val Gln Gln Lys Pro Gly Lys Ser Pro Arg

180 185190

Gly Leu Ile Gly Gly Thr Asn Lys Arg Ala Pro Gly Val Pro Ala Arg

195 200205

- 523 044325

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Val

Val

Pro

Thr

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

Lys Leu

Glu Trp

Pro Val

435

Val Asp 450

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Thr Cys

405

Glu Ser 420

Leu Asp

Lys Ser

Leu Gly

215

Glu Ala

230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Leu Val

Asn Gly

Ser Asp

Arg Trp

455

Gly Lys

Asp Tyr

Gly Thr

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Lys Gly

Glin Pro

425

Gly Ser 440

Gln Gln

Ala Ala

Tyr Cys

235

Lys Leu 250

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Phe Tyr 410

Glu Asn

Phe Phe

Gly Asn

Leu Thr 220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Pro Ser

Asn Tyr

Leu Tyr

445

Val Phe 460

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

Asp Ile

415

Lys Thr 430

Ser Lys

Ser Cys

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

Ala

Thr

Leu

Ser

- 524 044325

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475 480

Leu Ser Pro Gly Lys

485 <210> 409 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 409

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

- 525 044325

Thr Leu Thr Leu Ser Lys Ala Asp 180

Tyr Glu Lys His Lys Val Tyr Ala

185 190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200 205

Asn Arg Gly Glu Cys

210 <210> 410 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 410

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr SerTyr

2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Ser Tyr Tyr Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly

100 105110

Ala Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155160

- 526 044325

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asp 210

Lys Thr His

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Asp Val 370

Ser Asp Gly

Asp Ser Asp

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Thr Cys Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Glu

Ser Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe

Thr Ser Gly

170

Tyr Ser Leu

185

Gln Thr Tyr 200

Asp Lys Lys

Pro Cys Pro

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Glu

Leu His Gln

Asn Lys Ala 330

Gly Gln Pro 345

Glu Met Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

Val His Thr

Ser Ser Val

Ile Cys Asn

205

Val Glu Pro

220

Ala Pro Pro 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Phe Pro Ala

175

Val Thr Val 190

Val Asn His

Lys Ser Cys

Val Ala Gly

240

Leu Met Ile

255

Lys His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

- 527 044325

405 410415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser Cys Ser Val Met His

420 425430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210> 411 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 411

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp 50 5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 65 70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr 85 9095

Tyr Cys Val Arg His Gly Asn Phe Gly Ala Ser Tyr Val Ser Trp Phe

100 105110

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Lys Pro

115 120125

Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly

130 135140

Ser Gln Ala Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly

- 528 044325

145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Asn

Pro

Gln 385

Thr Val

Asn Tyr

Leu Ile

195

Ser Gly 210

Glin Pro

His Trp

Ser Ser

Ala Gly

275

Met Ile 290

His Glu

Val His

Tyr Arg

Gly Lys

355

Ile Glu

370

Val Tyr

150

155

Thr Leu

165

Thr Cys

Gly Ser

Ala Asn 180

Gly Gly

Ser Leu

Glu Asp

Val Phe

245

Asp Lys 260

Pro Ser

Ser Arg

Asp Pro

Asn Ala

325

Val Val 340

Glu Tyr

Lys Thr

Thr Leu

Trp Val

Gln Gln

185

Thr Asn

Leu Gly 215

Glu Ala 230

Gly Gly

Thr His

Val Phe

Thr Pro

295

Glu Val 310

Lys Thr

Ser Val

Lys Cys

Ile Ser

375

Pro Pro 390

Lys Arg 200

Gly Lys

Ser Thr 170

Lys Pro

Ala Pro

Ala Ala

Gly Ala

Val Thr

175

Asp Tyr

Tyr Cys

235

Gly Thr

Lys Leu 250

Thr Cys

265

Leu Phe

280

Glu Val

Lys Phe

Lys Pro

Leu Thr

345

Lys Val 360

Lys Ala

Ser Arg

Pro Pro

Pro Pro

Thr Cys

Asn Trp

315

Arg Glu 330

Val Leu

Ser Asn

Lys Gly

Glu Gln

395

Gly Lys

Gly Val 205

Leu Thr 220

Ala Leu

Thr Val

Cys Pro

Lys Pro

285

Val Val 300

Tyr Val

Glu Gln

His Gln

Lys Ala

365

Glin Pro 380

Met Thr

Ser Pro 190

Pro Ala

Ile Ser

Trp Tyr

Leu Glu

255

Ala Pro 270

Lys Asp

Val Asp

Asp Gly

Tyr Asn

335

Asp Trp 350

Leu Pro

Arg Glu

Lys Asn

160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

Val

Val 320

Ser

Leu

Ala

Pro

Gln 400

- 529 044325

Val Lys Leu

Thr Cys Leu Val Lys Gly Phe Tyr Pro

405 410

Ser Asp Ile Ala

415

Val Glu Trp

Glu Ser Asn Gly Gln Pro Glu Asn Asn 420 425

Tyr Lys Thr Thr 430

Pro Pro Val

435

Leu Asp Ser Asp Gly Ser Phe Phe Leu

440

Tyr Ser Lys Leu 445

Thr Val Asp

450

Lys Ser Arg Trp Gln Gln Gly Asn Val

455 460

Phe Ser Cys Ser

Val Met His 465

Glu Ala Leu His Asn His Tyr Thr Gln

470 475

Lys Ser Leu Ser

480

Leu Ser Pro Gly Lys

485 <210> 412 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic polypeptide <400> 412

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 25 30

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 40 45

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 55 60

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 90 95

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105 110

- 530 044325

Ser Val Phe Ile Phe Pro Pro Ser

115 120

Asp Glu Gln Leu Lys Ser Gly Thr

125

Ala Ser Val Val Cys Leu Leu Asn

130 135

Asn Phe Tyr Pro Arg Glu Ala Lys

140

Val Gln Trp Lys Val Asp Asn Ala

145 150

Leu Gln Ser Gly Asn Ser Gln Glu

155 160

Ser Val Thr Glu Gln Asp Ser Lys

165

Asp Ser Thr Tyr Ser Leu Ser Ser

170 175

Thr Leu Thr Leu Ser Lys Ala Asp 180

Tyr Glu Lys His Lys Val Tyr Ala

185 190

Cys Glu Val Thr His Gln Gly Leu

195 200

Ser Ser Pro Val Thr Lys Ser Phe

205

Asn Arg Gly Glu Cys

210 <210> 413 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 413

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe 50 5560

Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr 65 70 7580

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

- 531 044325

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Arg Ser

Gly Thr

115

Phe Pro 130

Leu Gly

Trp Asn

Leu Gln

Ser Ser

195

Pro Ser 210

Lys Thr

Ser Val

Arg Thr

Pro Glu

275

Ala Lys 290

Val Ser

Tyr Lys

Thr Ile

Tyr Tyr 100

Leu Val

Leu Ala

Cys Leu

Ser Gly

165

Ser Ser 180

Ser Leu

Asp Thr

His Thr

Phe Leu

245

Pro Glu 260

Val Lys

Thr Lys

Val Leu

Cys Lys

325

Ser Lys 340

Met Gly

Thr Val

Pro Ser

135

Val Lys 150

Ala Leu

Gly Leu

Gly Thr

Lys Val

215

Cys Pro 230

Phe Pro

Val Thr

Phe Asn

Pro Arg

295

Thr Val 310

Val Ser

Ala Lys

Gly Asp

105

Trp Tyr

Phe Asp

Ser Ser 120

Ser Lys

Asp Tyr

Thr Ser

Tyr Ser

185

Gln Thr

200

Asp Lys

Pro Cys

Pro Lys

Cys Val

265

Trp Tyr 280

Glu Glu

Leu His

Asn Lys

Gly Gln

345

Ala Ser

Thr Lys

125

Ser Thr

Ser Gly 140

Phe Pro

155

Gly Val 170

Leu Ser

Tyr Ile

Lys Val

Pro Ala

235

Pro Lys 250

Val Val

Val Asp

Glu Tyr

Gln Asp

315

Ala Leu 330

Pro Arg

Glu Pro

His Thr

Ser Val

Cys Asn

205

Glu Pro

220

Pro Pro

Asp Thr

Asp Val

Gly Val

285

Asn Ser 300

Trp Leu

Pro Ala

Glu Pro

Val Trp 110

Gly Pro

Gly Thr

Val Thr

Phe Pro

175

Val Thr 190

Val Asn

Lys Ser

Val Ala

Leu Met

255

Lys His 270

Glu Val

Thr Tyr

Asn Gly

Pro Ile

335

Gln Val 350

Gly

Ser

Ala

Val 160

Ala

Val

His

Cys

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

- 532 044325

Thr

Leu

Pro

355

Pro

Ser

Arg

Glu

Glu

360

Met

Thr

Lys

Asn

Gln

365

Val

Ser

Leu

Thr

Cys 370

Asp

Val

Ser

Gly

Phe

375

Tyr

Pro

Ser

Asp

Ile

380

Ala

Val

Glu

Trp

Glu

385

Ser

Asp

Gly

Gln

Pro

390

Glu

Asn

Asn

Tyr

Lys

395

Thr

Thr

Pro

Pro

Val

400

Leu

Asp

Ser

Asp

Gly 405

Ser

Phe

Phe

Leu

Tyr 410

Ser

Lys

Leu

Thr

Val

415

Asp

Lys

Ser

Arg

Trp 420

Glu

Gln

Gly

Asp

Val

425

Phe

Ser

Cys

Ser

Val

430

Met

His

Glu

Ala

Leu

435

His

Asn

His

Tyr

Thr

440

Gln

Lys

Ser

Leu

Ser

445

Leu

Ser

Pro

Gly Lys

450 <210> 414 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 414

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser ThrTyr

2530

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Gly Arg Ile Arg Ser Lys Ala Asn Asn Tyr Ala Thr Ala Tyr Ala Asp

5560

Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys AsnThr

70 7580

Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala ValTyr

9095

- 533 044325

Tyr

Ala

Gly

Ser 145

Gly

Ser

Gly

Phe

Ala 225

Asn

Lys

Val

Leu

Lys 305

Glu

Thr

Cys Val Arg

100

Tyr Trp Gly

115

Ser Gly Lys 130

Gln Ala Val

Thr Val Thr

Asn Tyr Ala

180

Leu Ile Gly

195

Ser Gly Ser 210

Gln Pro Glu

His Trp Val

Ser Ser Asp

260

Ala Gly Pro

275

Met Ile Ser 290

His Glu Asp

Val His Asn

Tyr Arg Val

340

His Gly Asn

Gln Gly Thr

Pro Gly Ser

135

Val Thr Gln

150

Leu Thr Cys 165

Asn Trp Val

Gly Thr Asn

Leu Leu Gly

215

Asp Glu Ala

230

Phe Gly Gly 245

Lys Thr His

Ser Val Phe

Arg Thr Pro

295

Pro Glu Val

310

Ala Lys Thr 325

Val Ser Val

Phe Gly Gln

105

Leu Val Thr 120

Gly Lys Pro

Glu Pro Ser

Gly Ser Ser

170

Gln Gln Lys

185

Lys Arg Ala 200

Gly Lys Ala

Asp Tyr Tyr

Gly Thr Lys

250

Thr Cys Pro

265

Leu Phe Pro 280

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

330

Leu Thr Val

345

Ser Tyr Val

Ser Trp Phe 110

Val Ser Ser

125

Gly Ser Gly

140

Leu Thr Val 155

Thr Gly Ala

Pro Gly Lys

Pro Gly Val

205

Ala Leu Thr

220

Cys Ala Leu 235

Leu Thr Val

Pro Cys Pro

Pro Lys Pro

285

Cys Val Val

300

Trp Tyr Val 315

Glu Glu Gln

Leu His Gln

Gly Lys Pro

Lys Pro Gly

Ser Pro Gly

160

Val Thr Thr

175

Ser Pro Arg 190

Pro Ala Arg

Ile Ser Gly

Trp Tyr Ser

240

Leu Glu Pro

255

Ala Pro Pro 270

Lys Asp Thr

Val Asp Val

Asp Gly Val

320

Tyr Asn Ser

335

Asp Trp Leu 350

- 534 044325

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 415 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 415

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser TyrIle

2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser

5560

- 535 044325

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105110

Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr

115 120125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155160

Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser

165 170175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185190

Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe

195 200205

Asn Arg Gly Glu Cys 210 <210> 416 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 416

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 35 4045

- 536 044325

Gly

Gln 65

Met

Ala

Ala

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Pro

Ser

Asp

Asn

Ala Ile Tyr Pro Gly 50

Asn Gly Ala Thr Ser 55

Tyr Ser Gln Lys Phe 60

Gly Arg Val Thr Ile 70

Glu Leu Ser Ser Leu

Arg Ser Tyr Tyr Met 100

Gly Thr Leu Val Thr 115

Phe Pro Leu Ala Pro 130

Leu Gly Cys Leu Val

150

Trp Asn Ser Gly Ala

165

Leu Gln Ser Ser Gly 180

Ser Ser Ser Leu Gly

195

Pro Ser Asp Thr Lys 210

Lys Thr His Thr Cys

230

Ser Val Phe Leu Phe

245

Arg Thr Pro Glu Val 260

Pro Glu Val Lys Phe

275

Ala Lys Thr Lys Pro

Thr Ala Asp Thr Ser 75

Arg Ser Glu Asp Thr

Gly Gly Asp Trp Tyr

105

Val Ser Ser Ala Ser

120

Ser Ser Lys Ser Thr 135

Lys Asp Tyr Phe Pro

155

Leu Thr Ser Gly Val

170

Leu Tyr Ser Leu Ser

185

Thr Gln Thr Tyr Ile 200

Val Asp Lys Lys Val 215

Pro Pro Cys Pro Ala

235

Pro Pro Lys Pro Lys

250

Thr Cys Val Val Val

265

Asn Trp Tyr Val Asp

280

Arg Glu Glu Glu Tyr

Ala Ser Thr Ala Tyr 80

Ala Val Tyr Tyr Cys 95

Phe Asp Val Trp Gly

110

Thr Lys Gly Pro Ser

125

Ser Gly Gly Thr Ala 140

Glu Pro Val Thr Val

160

His Thr Phe Pro Ala

175

Ser Val Val Thr Val

190

Cys Asn Val Asn His

205

Glu Pro Lys Ser Cys 220

Pro Pro Val Ala Gly

240

Asp Thr Leu Met Ile

255

Asp Val Lys His Glu

270

Gly Val Glu Val His

285

Asn Ser Thr Tyr Arg

- 537 044325

290

295

300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val

325

Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

330 335

Lys Thr

Ile Ser Lys Ala Lys

340

Gly Gln Pro Arg Glu Pro Gln Val Tyr

345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val

355 360 365

Ser Leu

Thr Cys Asp Val Ser Gly Phe Tyr Pro Ser Asp

370 375

Ile Ala Val Glu Trp 380

Glu Ser Asp Gly Gln Pro Glu Asn Asn Tyr Lys

385 390 395

Thr Thr Pro Pro Val

400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

405 410

Lys Leu Thr Val Asp

415

Lys Ser Arg Trp Glu Gln Gly Asp Val Phe Ser

420 425

Cys Ser Val Met His 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 417 <211> 485 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 417

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 20 25 30

Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

- 538 044325

Gly Arg Ile Arg Ser 50

Lys Ala Asn Asn Tyr 55

Ala Thr Ala Tyr Ala 60

Ser Val Lys Gly Arg 65

Phe Thr Ile Ser Arg 70

Asp Asp Ser Lys Asn 75

Leu Tyr Leu Gln Met 85

Asn Ser Leu Arg Ala 90

Glu Asp Thr Ala Val 95

Tyr Cys Val Arg His

100

Gly Asn Phe Gly Asp

105

Ser Tyr Val Ser Trp

110

Asp Tyr Trp Gly Gln 115

Gly Thr Leu Val Thr

120

Val Ser Ser Gly Lys

125

Gly Ser Gly Lys Pro 130

Gly Ser Gly Lys Pro

135

Gly Ser Gly Lys Pro

140

Ser Gln Ala Val Val 145

Thr Gln Glu Pro Ser 150

Leu Thr Val Ser Pro 155

Gly Thr Val Thr Leu

165

Thr Cys Gly Ser Ser

170

Thr Gly Ala Val Thr

175

Ser Asn Tyr Ala Asn

180

Trp Val Gln Gln Lys

185

Pro Gly Lys Ser Pro

190

Gly Leu Ile Gly Gly

195

Thr Asn Lys Arg Ala 200

Pro Gly Val Pro Ala

205

Phe Ser Gly Ser Leu 210

Leu Gly Gly Lys Ala

215

Ala Leu Thr Ile Ser

220

Ala Gln Pro Glu Asp 225

Glu Ala Asp Tyr Tyr 230

Cys Ala Leu Trp Tyr 235

Asn His Trp Val Phe

245

Gly Gly Gly Thr Lys

250

Leu Thr Val Leu Glu

255

Lys Ser Ser Asp Lys

260

Thr His Thr Cys Pro

265

Pro Cys Pro Ala Pro

270

Val Ala Gly Pro Ser

275

Val Phe Leu Phe Pro

280

Pro Lys Pro Lys Asp

285

Asp

Thr 80

Tyr

Phe

Pro

Gly

Gly 160

Thr

Arg

Arg

Gly

Ser 240

Pro

Pro

Thr

- 539 044325

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

290 295300

Lys His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

305 310 315320

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

325 330335

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

340 345350

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

355 360365

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

370 375380

Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Gln Met Thr Lys Asn Gln

385 390 395400

Val Lys Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

405 410415

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

420 425430

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

435 440445

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

450 455460

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

465 470 475480

Leu Ser Pro Gly Lys

485 <210> 418 <211> 213 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 418

- 540 044325

Gln Ile Val Leu Thr

5

Gln Ser

Pro Ser

Asp Arg Val Thr Ile

Thr Cys

Arg Ala 25

His Trp Phe Gln Gln 35

Lys Pro

Gly Lys 40

Ala Thr Ser Asn Leu 50

Ala Ser

Gly Val

Ser Leu 10

Ser Trp

Ser Pro

Pro Val

Ser Ala

Ser Val

Lys Pro 45

Arg Phe 60

Ser Val

Ser Tyr 30

Leu Ile

Ser Gly

Gly Ser Gly Thr Asp 65

Tyr Thr 70

Leu Thr

Ile Ser

Ser Leu

Glin Pro

Asp Phe Ala Thr Tyr 85

Tyr Cys

Gln Gln

Trp Thr 90

His Asn

Pro Pro

Phe Gly Gly Gly Thr

100

Lys Val

Glu Ile

105

Lys Arg

Thr Val

Ala Ala

110

Ser Val Phe Ile Phe

115

Pro Pro

Ser Asp 120

Glu Gln

Leu Lys

125

Ser Gly

Ala Ser Val Val Cys 130

Leu Leu

135

Asn Asn

Phe Tyr

Pro Arg 140

Glu Ala

Val Gln Trp Lys Val 145

Asp Asn 150

Ala Leu

Gln Ser

155

Gly Asn

Ser Gln

Ser Val Thr Glu Gln

165

Asp Ser

Lys Asp

Ser Thr 170

Tyr Ser

Leu Ser

175

Thr Leu Thr Leu Ser

180

Lys Ala

Asp Tyr

185

Glu Lys

His Lys

Val Tyr 190

Cys Glu Val Thr His 195

Gln Gly

Leu Ser 200

Ser Pro

Val Thr

205

Lys Ser

Gly

Ile

Tyr

Ser

Glu 80

Thr

Pro

Thr

Lys

Glu 160

Ser

Ala

Phe

Asn Arg Gly Glu Cys 210 <210> 419 <211> 297 <212> PROTEIN <213> Homo sapiens <400> 419

Met Thr Thr Pro Arg

Asn Ser

Val Asn

Gly Thr

Phe Pro

Ala Glu

Pro

- 541 044325

15

Met Lys Gly Pro Ile 20

Ala Met Gln Ser Gly

Pro Lys Pro Leu Phe 30

Arg Met Ser Ser Leu 35

Val Gly Pro Thr Gln 40

Ser Phe Phe Met Arg 45

Ser Lys Thr Leu Gly 50

Ala Val Gln Ile Met

Asn Gly Leu Phe His 60

Ala Leu Gly Gly Leu 65

Leu Met Ile Pro Ala 70

Gly Ile Tyr Ala Pro 75

Cys Val Thr Val Trp 85

Tyr Pro Leu Trp Gly 90

Gly Ile Met Tyr Ile 95

Ser Gly Ser Leu Leu

100

Ala Ala Thr Glu Lys

105

Asn Ser Arg Lys Cys

110

Val Lys Gly Lys Met 115

Ile Met Asn Ser Leu

120

Ser Leu Phe Ala Ala

125

Ser Gly Met Ile Leu 130

Ser Ile Met Asp Ile

135

Leu Asn Ile Lys Ile 140

His Phe Leu Lys Met 145

Glu Ser Leu Asn Phe 150

Ile Arg Ala His Thr 155

Tyr Ile Asn Ile Tyr

165

Asn Cys Glu Pro Ala

170

Asn Pro Ser Glu Lys

175

Ser Pro Ser Thr Gln

180

Tyr Cys Tyr Ser Ile

185

Gln Ser Leu Phe Leu

190

Ile Leu Ser Val Met

195

Leu Ile Phe Ala Phe

200

Phe Gln Glu Leu Val

205

Ala Gly Ile Val Glu

210

Asn Glu Trp Lys Arg

215

Thr Cys Ser Arg Pro

220

Ser Asn Ile Val Leu 225

Leu Ser Ala Glu Glu 230

Lys Lys Glu Gln Thr 235

Glu Ile Lys Glu Glu

245

Val Val Gly Leu Thr

250

Glu Thr Ser Ser Gln

255

Arg

Glu

Ile

Ile 80

Ile

Leu

Ile

Ser

Pro 160

Asn

Gly

Ile

Lys

Ile 240

Pro

- 542 044325

Lys Asn Glu Glu Asp

260

Ile Glu

Ile Ile

265

Pro Ile

Gln Glu

Glu Glu Thr Glu Thr

275

Asn Phe

Pro Glu 280

Pro Pro

Gln Asp

285

Glu Glu

270

Gln Glu

Glu

Ser

Ser Pro Ile Glu Asn

290

Asp Ser

295

Ser Pro <210> 420 <211> 378 <212> PROTEIN <213> Homo sapiens <400> 420

Met Val Leu Leu Trp 1 5

Leu Thr

Leu Leu

Leu Gln Thr Lys Glu 20

Asp Pro

Asn Pro

Lys Ala Lys Ala Gln 35

Gln Leu

Thr Trp 40

Asp Ile Glu Cys Val 50

Lys Asp 55

Ala Asp

Leu Ile 10

Pro Ile

Asp Leu

Tyr Ser

Ala Leu

Thr Asn

Asn Arg

Met Pro 60

Asn Ser Tyr Cys Gln 65

Phe Gly 70

Ala Ile

Ser Leu

Cys Glu

Tyr Thr Val Arg Val 85

Ala Asn

Pro Pro

Phe Ser 90

Thr Trp

Pro Glu Asn Ser Gly

100

Lys Pro

Trp Ala

105

Gly Ala

Glu Asn

Trp Ile His Asp Val 115

Asp Phe

Leu Ser 120

Cys Ser

Trp Ala

125

Gly Ala Pro Ala Asp 130

Val Gln

135

Tyr Asp

Leu Tyr

Leu Asn 140

Arg Arg Gln Gln Tyr 145

Glu Cys 150

Leu His

Tyr Lys

155

Thr Asp

Thr Arg Ile Gly Cys

165

Arg Phe

Asp Asp

Ile Ser

170

Arg Leu

Ser Gln Ser Ser His

Ile Leu

Val Arg

Gly Arg

Ser Ala

Pro Cys 15

Leu Arg 30

Asn Val

Ala Val

Val Thr

Ile Leu 95

Leu Thr

110

Val Gly

Val Ala

Ala Gln

Ser Ser

175

Ala Phe

Leu

Met

Thr

Asn

Asn 80

Phe

Cys

Pro

Asn

Gly 160

Gly

Gly

- 543 044325

180

185

190

Ile Pro Cys Thr Asp Lys Phe Val Val Phe Ser Gln Ile Glu Ile Leu

195 200205

Thr Pro Pro Asn Met Thr Ala Lys Cys Asn Lys Thr His Ser Phe Met

210 215220

His Trp Lys Met Arg Ser His Phe Asn Arg Lys Phe Arg Tyr Glu Leu

225 230 235240

Gln Ile Gln Lys Arg Met Gln Pro Val Ile Thr Glu Gln Val Arg Asp

245 250255

Arg Thr Ser Phe Gln Leu Leu Asn Pro Gly Thr Tyr Thr Val Gln Ile

260 265270

Arg Ala Arg Glu Arg Val Tyr Glu Phe Leu Ser Ala Trp Ser Thr Pro

275 280285

Gln Arg Phe Glu Cys Asp Gln Glu Glu Gly Ala Asn Thr Arg Ala Trp

290 295300

Arg Thr Ser Leu Leu Ile Ala Leu Gly Thr Leu Leu Ala Leu Val Cys

305 310 315320

Val Phe Val Ile Cys Arg Arg Tyr Leu Val Met Gln Arg Leu Phe Pro

325 330335

Arg Ile Pro His Met Lys Asp Pro Ile Gly Asp Ser Phe Gln Asn Asp

340 345350

Lys Leu Val Val Trp Glu Ala Gly Lys Ala Gly Leu Glu Glu Cys Leu

355 360365

Val Thr Glu Val Gln Val Val Gln Lys Thr

370375 <210> 421 <211> 116 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 421

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

- 544 044325

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Trp Val 20 2530

Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met Gly Ala Ile Tyr Pro 35 4045

Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe Gln Gly Arg Val Thr 50 5560

Ile Thr Ala Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser 65 70 7580

Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Tyr Tyr 85 9095

Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly Ala Gly Thr Leu Val

100 105110

Thr Val Ser Ser

115 <210> 422 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 422

Ser Tyr Asn Met His 1 5 <210> 423 <211> 17 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 423

Ala Ile Tyr Pro Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe Gln

5 10 15

Gly

- 545 044325 <210> 424 <211> 12 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 424

Ser Tyr Tyr Met Gly Gly Asp Trp Tyr Phe Asp Val

5 10 <210> 425 <211> 106 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 425

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Trp Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr His Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100105 <210> 426 <211> 10 <212> PROTEIN <213> Artificial sequence <220>

<221> source

- 546 044325 <223> /note=Description of artificial sequence: synthetic peptide <400> 426

Arg Ala Ser Trp Ser Val Ser Tyr Ile His <210> 427 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 427

Ala Thr Ser Asn Leu Ala Ser

5 <210> 428 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 428

Gln Gln Trp Thr His Asn Pro Pro Thr

5 <210> 429 <211> 242 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 429

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Trp Val

Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met Gly Ala Ile Tyr Pro

Gly Asn Gly Ala Thr Ser Tyr Ser Gln Lys Phe Gln Gly Arg Val Thr

- 547 044325

Ile Thr Ala Asp Thr Ser Ala Ser 65 70

Thr Ala Tyr Met Glu Leu Ser Ser

80

Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ser Tyr Tyr 85 9095

Met Gly Gly Asp Trp Tyr Phe Asp Val Trp Gly Ala Gly Thr Leu Val

100 105110

Thr Val Ser Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys

115 120125

Pro Gly Ser Gly Lys Pro Gly Ser Gln Ile Val Leu Thr Gln Ser Pro

130 135140

Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg

145 150 155160

Ala Ser Trp Ser Val Ser Tyr Ile His Trp Phe Gln Gln Lys Pro Gly

165 170175

Lys Ser Pro Lys Pro Leu Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly

180 185190

Val Pro Val Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu

195 200205

Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln

210 215220

Gln Trp Thr His Asn Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu

225 230 235240

Ile Lys <210> 430 <211> 121 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 430

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 10 15

- 548 044325

Ser Val Lys Val Ser Cys Lys Ala 20

Ser Gly Tyr Thr Phe Thr Ser Tyr

thirty

Asn Met His Trp Val Arg Gln Ala

40

Pro Gly Gln Gly Leu Glu Trp Met 45

Gly Ala Ile Tyr Pro Gly Asn Gly

55

Asp Thr Ser Tyr Asn Gln Lys Phe 60

Gln Gly Arg Val Thr Ile Thr Ala 65 70

Asp Lys Ser Ile Ser Thr Ala Tyr

80

Met Glu Leu Ser Ser Leu Arg Ser 85

Glu Asp Thr Ala Val Tyr Tyr Cys

95

Ala Arg Ser Thr Tyr Tyr Gly Gly

100

Asp Trp Tyr Phe Asn Val Trp Gly

105 110

Ala Gly Thr Leu Val Thr Val Ser

115 120

Ser <210> 431 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 431

Ser Tyr Asn Met His 1 5 <210> 432 <211> 17 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 432

Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe Gln

5 10 15

Gly

- 549 044325 <210> 433 <211> 12 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 433

Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val

5 10 <210> 434 <211> 106 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 434

Gln Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile 20 2530

His Trp Phe Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr 35 4045

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 50 5560

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 65 70 7580

Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr 85 9095

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100105 <210> 435 <211> 10 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic

- 550 044325 peptide <400> 435

Arg Ala Ser Ser Ser Val Ser Tyr Ile His

5 10 <210> 436 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 436

Ala Thr Ser Asn Leu Ala Ser

5 <210> 437 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 437

Gln Gln Trp Thr Ser Asn Pro Pro Thr

5 <210> 438 <211> 247 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 438

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 2530

Asn Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe 50 5560

- 551 044325

Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser 65 70 75

Ile Ser Thr Ala Tyr 80

Met Glu Leu

Ser Ser

Ala Arg Ser

Thr Tyr 100

Ala Gly Thr

115

Leu Val

Leu Arg Ser Glu Asp Thr Ala Val Tyr 90

Tyr Gly Gly Asp Trp Tyr Phe Asn Val 105 110

Thr Val Ser Ser Gly Lys Pro Gly Ser 120 125

Tyr Cys 95

Trp Gly

Gly Lys

Pro Gly Ser Gly Lys Pro Gly Ser Gly Lys Pro Gly Ser Gln Ile Val

130 135140

Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val

145 150 155160

Thr Ile Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile His Trp Phe

165 170175

Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr Ala Thr Ser

180 185190

Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser Gly Ser Gly

195 200205

Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala

210 215220

Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr Phe Gly Gly

225 230 235240

Gly Thr Lys Val Glu Ile Lys

245 <210> 439 <211> 120 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 439

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 10 15

- 552 044325

Ser Val Lys Val Ser

Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr

thirty

Tyr Met Lys Trp Val 35

Lys Gln Ser His Gly Lys Ser Leu Glu Trp Met

45

Gly Asp Ile Ile Pro 50

Ser Asn Gly Ala Thr Phe Tyr Asn Gln Lys Phe

60

Lys Gly Lys Ala Thr 65

Leu Thr Val Asp Arg Ser Thr Ser Thr Ala Tyr 70 75 80

Met Glu Leu Ser

Ala Arg Ser His

100

Ser Leu Arg Ser 85

Leu Leu Arg Ala

Glu Asp Thr Ala Val Tyr Tyr Cys

95

Ser Trp Phe Ala Tyr Trp Gly Gln

105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120 <210> 440 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 440

Asp Tyr Tyr Met Lys 1 5 <210> 441 <211> 17 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 441

Asp Ile Ile Pro Ser Asn Gly Ala Thr Phe Tyr Asn Gln Lys Phe Lys

5 10 15

Gly

- 553 044325 <210> 442 <211> 11 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 442

Ser His Leu Leu Arg Ala Ser Trp Phe Ala Tyr

5 10 <210> 443 <211> 113 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 443

Asp 1 Phe Val Met Thr 5 Gln Ser Pro Asp Ser 10 Leu Ala Val Ser Leu 15 Gly Glu Arg Ala Thr 20 Ile Asn Cys Lys Ser 25 Ser Gln Ser Leu Leu 30 Asn Thr Gly Asn Gln 35 Lys Asn Tyr Leu Thr 40 Trp Tyr Gln Gln Lys 45 Pro Gly Gln Pro Pro 50 Lys Leu Leu Ile Tyr 55 Trp Ala Ser Thr Arg 60 Glu Ser Gly Val Pro 65 Asp Arg Phe Thr Gly 70 Ser Gly Ser Gly Thr 75 Asp Phe Thr Leu Thr 80 Ile Ser Ser Leu Gln 85 Ala Glu Asp Val Ala 90 Val Tyr Tyr Cys Gln 95 Asn Asp Tyr Ser Tyr 100 Pro Tyr Thr Phe Gly 105 Gly Gly Thr Lys Leu 110 Glu Ile

Lys <210> 444 <211> 17 <212> PROTEIN <213> Artificial sequence

- 554 044325 <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 444

Lys Ser Ser Gln Ser Leu Leu Asn Thr Gly Asn Gln Lys Asn Tyr Leu

5 10 15

Thr <210> 445 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 445 Trp Ala Ser Thr Arg Glu Ser 1 5 <210> 446 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 446 Gln Asn Asp Tyr Ser Tyr Pro Tyr Thr 1 5 <210> 447 <211> 253 <212> PROTEIN <213> Artificial sequence <220 >

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 447

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 20 25

Gly Tyr Thr Phe Thr Asp Tyr 30

- 555 044325

Tyr Met Lys Trp Val 35

Lys Gln

Gly Asp Ile Ile Pro 50

Ser Asn

Lys Gly Lys Ala Thr 65

Leu Thr 70

Met Glu Leu Ser Ser

Leu Arg

Ser His 40

Gly Ala

Val Asp

Ser Glu

Gly Lys

Thr Phe

Arg Ser

Asp Thr 90

Ser Leu

Tyr Asn 60

Thr Ser

Ala Val

Glu Trp

Gln Lys

Thr Ala

Tyr Tyr

Ala Arg Ser His Leu

100

Leu Arg

Ala Ser

105

Trp Phe

Ala Tyr

Trp Gly

110

Gly Thr Leu Val Thr 115

Val Ser

Ser Gly

120

Lys Pro

Gly Ser

125

Gly Lys

Gly Ser Gly Lys Pro

130

Gly Ser

135

Gly Lys

Pro Gly

Ser Asp 140

PheVal

Thr Gln Ser Pro Asp 145

Ser Leu 150

Ala Val

Ser Leu

155

Gly Glu

Arg Ala

Ile Asn Cys Lys Ser

165

Ser Gln

Ser Leu

Leu Asn 170

Thr Gly

Asn Gln

175

Asn Tyr Leu Thr Trp

180

Tyr Gln

Gln Lys

185

Pro Gly

Glin Pro

Pro Lys 190

Leu Ile Tyr Trp Ala

195

Ser Thr

Arg Glu 200

Ser Gly

Val Pro

205

Asp Arg

Thr Gly Ser Gly Ser

210

Gly Thr

215

Asp Phe

Thr Leu

Thr Ile

220

Ser Ser

Gln Ala Glu Asp Val 225

Ala Val 230

Tyr Tyr

Cys Gln

235

Asn Asp

Tyr Ser

Met

Phe

Tyr 80

Cys

Gln

Pro

Met

Thr 160

Lys

Leu

Phe

Leu

Tyr 240

Pro Tyr Thr Phe Gly

245

Gly Gly

Thr Lys

Leu Glu

250

Ile Lys <210> 448 <211> 6 <212> PROTEIN <213> Artificial <220>

<221> source sequence

- 556 044325 <223> /note=Description of artificial sequence: Synthetic tag 6xHis <400> 448

His His His His His His <210> 449 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 449

Gly Ser Gly Gly Ser

5 <210> 450 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 450

Gly Gly Gly Gly Ser

5 <210> 451 <211> 4 <212> PROTEIN <213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide <400> 451

Gly Gly Gly Ser < 210> 452 < 211> 4 < 212> PROTEIN < 213> Artificial sequence <220>

< 221> source < 223> /note=Description of artificial sequence: synthetic peptide

- 557 044325 <400> 452

Asp Glu Asp Glu 1

Claims (6)

1. Heterodimeric aHmu-CD3xCD20 antibody containing: a) a first monomer containing VH1-CH1-hinge-CH2-CH3 having the amino acid sequence SEQ ID NO: 323; b) a second monomer comprising VH2-scFv-linker-VL2-linker-CH2-CH3 having the amino acid sequence of SEQ ID NO: 324; And c) a light chain comprising VL1-CL having the amino acid sequence of SEQ ID NO: 325, where VH1 is a first heavy chain variable domain, VL1 is a first light chain variable domain, VH2 is a second heavy chain variable domain, and VL2 is the second light chain variable domain, where VH1 and VL1 form the CD20 binding domain, and VH2-scFv-linker-VL2 is an anti-CD3 scFv. 2. A nucleic acid composition encoding a heterodimeric anti-CD3xCD20 antibody according to claim 1, containing: a) a first nucleic acid sequence encoding SEQ ID NO: 323; b) a second nucleic acid sequence encoding SEQ ID NO: 324; And c) a third nucleic acid sequence encoding SEQ ID NO: 325. 3. The composition of expression vectors for the expression of a heterodimeric anti-CD3xCD20 antibody according to claim 1, containing: a) a first expression vector containing a first nucleic acid sequence encoding SEQ ID NO: 323; b) a second expression vector containing a second nucleic acid sequence encoding SEQ ID NO: 324; And c) a third expression vector containing a third nucleic acid sequence encoding SEQ ID NO: 325. 4. A host cell for producing a heterodimeric antibody according to claim 1, containing a composition of expression vectors according to claim 3. 5. Use of a heterodimeric antibody according to claim 1 for the treatment of CD20-associated malignancy. 6. Use of a heterodimeric antibody according to claim 5, wherein the malignancy is B-cell lymphoma or leukemia.