KR20210149796A - Trispecific and/or trivalent binding proteins using crossed double variable domain (CODV) conformations for the treatment of HIV infection - Google Patents

Abstract

Using the crossed double variable domain (CODV) form, the present invention provides trispecific and/or trivalent binding comprising four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins. A composition comprising a protein, wherein a first pair of polypeptides forming a binding protein has dual variable domains with cross orientation and a second pair of polypeptides forming a binding protein has a single variable domain. Also provided herein are methods of making trispecific and/or trivalent binding proteins and the use of such binding proteins for the treatment and/or prophylaxis of HIV/AIDS.

Description

Trispecific and/or trivalent binding proteins using crossed double variable domain (CODV) conformations for the treatment of HIV infection

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No. 62/831,415, filed on April 9, 2019, and to European Application, EP19306312.0, filed on October 8, 2019, the disclosures of each of which are incorporated herein by reference in their entirety. is incorporated by reference.

Submission of an ASCII text file sequence listing

The following submissions in ASCII text files are hereby incorporated by reference in their entirety: Sequence Listing in Computer-readable Format (CRF) (filename: 183952031940SEQLIST.TXT, archived: March 25, 2020, size: 580 KB).

technical field

The present invention relates to trispecific and/or trivalent binding proteins comprising four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first Polypeptide pairs have dual variable domains with cross-orientation. The present invention also relates to a process for the preparation of trispecific and/or trivalent binding proteins and to the use of such binding proteins for the treatment and/or prophylaxis of HIV/AIDS.

Antiretroviral therapy (ART) has been the standard of care for HIV/AIDS patients for decades. ART drugs inhibit reverse transcriptase (RT), integrase (IN), and viral proteases ( internal proteins such as PI). Treatment with ART or a combination of other classes of ART results in inhibition of HIV-1 replication and subsequent reduction of viremia to usually undetectable levels (aviremia state). Although ART greatly helps people with HIV in controlling disease progression and in the containment of the global HIV epidemic, it usually requires patients to take their medication daily on a strict prescription. About 10% of patients fail treatment each year due to drug toxicity, non-adherence to therapy, and new drug resistance. As more HIV patients are able to live normal lifespans (over 80 years old), aging and chronic complications such as drug-drug interactions, and cardiovascular/renal/bone toxicity are of particular concern. The economic burden of HIV/AIDS treatment has not yet diminished.

HIV latentally infects long-term resting memory CD4+ T cells in the form of proviral DNA integrated into the host genome. Latent infected cells survive for decades and, like stem cells, self-renew through homeostatic proliferation, which is considered an HIV-1 reservoir. Because HIV-1 reservoirs do not express viral proteins, they are not affected by ART nor by the host immune system. However, a small percentage of cells in the reservoir are randomly reactivated by an unknown mechanism, which causes relapse of viremia when ART is discontinued.

Therefore, there is a need to develop HIV/AIDS therapeutics to target the HIV-1 reservoir(s) and ultimately to completely eliminate them to achieve cure or long-term remission of HIV without further treatment. Any therapeutic strategy to clear the HIV-1 reservoir requires first activating the reservoir and then removing the activated HIV-1 reservoir cells.

All references cited herein, including patent applications, patent publications, and UniProtKB/Swiss-Prot accession numbers, are hereby incorporated by reference in their entirety as if each individual reference were specifically and individually indicated to be incorporated by reference.

To meet these and other needs, provided herein are multispecific binding proteins (eg, antibodies) that form three antigen binding sites. In some embodiments, the binding protein binds one or more HIV target proteins and a CD3 polypeptide. In some embodiments, the binding protein binds an HIV target protein, a CD28 polypeptide, and a CD3 polypeptide. The trispecific anti-HIV/CD28xCD3 T cell engager (TCE) concept disclosed herein combines anti-HIV/anti-activation by anti-CD3, co-activation by anti-CD28, and binding to activated CD8 T cells. It is thought to be an effective scavenger of HIV-1 depots through subsequent killing of activated HIV-1 depot cells via CD28, which provides a potential strategy for attacking HIV-1 depots. In addition, anti-CD3 binding sites are described as exhibiting high affinity binding to human CD3 polypeptides and eliminating potential manufacturing burdens (eg, deamidation sites).

In some embodiments, provided herein is a binding protein comprising four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain has a structure represented by including,

V _L2 -L ₁ -V _L1 -L ₂ -C _L [I]

The second polypeptide chain comprises a structure represented by the formula

V _H1 -L ₃ -V _H2 -L ₄ -C _{H1 -Hinge} -C _H2 -C _H3 [II]

The third polypeptide chain comprises a structure represented by the formula

V _H3 -C _{H1 -Hinge} -C _H2 -C _H3 [III]

The fourth polypeptide chain comprises a structure represented by the formula

V _L3 -C _L [IV]

during the meal,

V _L1 is a first immunoglobulin light chain variable domain;

V _L2 is a second immunoglobulin light chain variable domain;

V _L3 is a third immunoglobulin light chain variable domain;

V _H1 is a first immunoglobulin heavy chain variable domain;

V _H2 is a second immunoglobulin heavy chain variable domain;

V _H3 is a third immunoglobulin heavy chain variable domain;

_CL is an immunoglobulin light chain constant domain;

C _H1 is an immunoglobulin C _H1 heavy chain constant domain;

C _H2 is an immunoglobulin C _H2 heavy chain constant domain;

C _H3 is an immunoglobulin C _H3 heavy chain constant domain;

The hinge is an immunoglobulin hinge region that connects the _{C H1} domain and the C _{H2 domain;}

L ₁ , L ₂ , L ₃ , and L ₄ are amino acid linkers;

the polypeptide of formula I and the polypeptide of formula II form a cross light chain-heavy chain pair;

V _H1 and V _L1 form a first antigen binding site;

V _H2 and V _L2 form a second antigen binding site that binds to the CD3 polypeptide, and the V _H2 domain is a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21) and a CDR-H3 sequence comprising the amino acid sequence of RGVYYALSPFDY (SEQ ID NO: 22), wherein the V _L2 domain is QSLVHX ₁ NX ₂ X ₃ TY (X ₁ is E or Q, and X ₂ is A or L, and X ₃ is Q, R, or F) a CDR-L1 sequence comprising the amino acid sequence of (SEQ ID NO: 293), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29) , and a CDR-L3 sequence comprising the amino acid sequence of GQGTQYPFT (SEQ ID NO: 30);

V _H3 and V _L3 form a third antigen binding site that binds to the HIV target protein.

In some embodiments, the first binding site binds a CD28 polypeptide (eg, a human CD28 polypeptide). In some embodiments, the V _H1 domain comprises a CDR-H1 sequence comprising the amino acid sequence of GYTFTSYY (SEQ ID NO: 31), a CDR-H2 sequence comprising the amino acid sequence of IYPGNVNT (SEQ ID NO: 32), and TRSHYGLDWNFDV (SEQ ID NO: 33) in comprises a CDR-H3 sequence comprising the amino acid sequence, V _L1 domain is CDR-L2 comprising the amino acid sequence of CDR-L1 sequence, KAS (SEQ ID NO: 35) comprising the amino acid sequence of QNIYVW (SEQ ID NO: 34) sequence, and a CDR-L3 sequence comprising the amino acid sequence of QQGQTYPY (SEQ ID NO: 36). In some embodiments, V is _H1 domain comprises the amino acid sequence and / or, V _L1 domain of QVQLVQSGAEVVKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWIGSIYPGNVNTNYAQKFQGRATLTVDTSISTAYMELSRLRSDDTAVYYCTRSHYGLDWNFDVWGKGTTVTVSS (SEQ ID NO: 59) comprises the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCQASQNIYVWLNWYQQKPGKAPKLLIYKASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDIATYYCQQGQTYPYTFGQGTKLEIK (SEQ ID NO: 60).

In some embodiments, _{the CDR-L1 sequence of the V L2} domain is an amino acid sequence selected from the group consisting of QSLVHQNAQTY (SEQ ID NO: 24), QSLVHENLQTY (SEQ ID NO: 25), QSLVHENLFTY (SEQ ID NO: 26), and QSLVHENLRTY (SEQ ID NO: 27) includes In some embodiments, the V _H2 domain comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of The V _L2 domain comprises a CDR-L1 sequence comprising the amino acid sequence of QSLVHQNAQTY (SEQ ID NO: 24), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and an amino acid sequence of GQGTQYPFT (SEQ ID NO: 30) CDR-L3 sequence. In some embodiments, the V _H2 domain comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 22) in comprises a CDR-H3 sequence comprising the amino acid sequence, V _L2 domain is CDR-L2 comprising the amino acid sequence of CDR-L1 sequence, KVS (SEQ ID NO: 29) comprising the amino acid sequence of QSLVHENLQTY (SEQ ID NO: 25) sequence, and a CDR-L3 sequence comprising the amino acid sequence of GQGTQYPFT (SEQ ID NO: 30). In some embodiments, the V _H2 domain comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 22) in comprises a CDR-H3 sequence comprising the amino acid sequence, V _L2 domain is CDR-L2 comprising the amino acid sequence of CDR-L1 sequence, KVS (SEQ ID NO: 29) comprising the amino acid sequence of QSLVHENLFTY (SEQ ID NO: 26) sequence, and a CDR-L3 sequence comprising the amino acid sequence of GQGTQYPFT (SEQ ID NO: 30). In some embodiments, the V _H2 domain comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 22) a CDR-H3 sequence comprising the amino acid sequence of The V _L2 domain comprises a CDR-L1 sequence comprising the amino acid sequence of QSLVHENLRTY (SEQ ID NO: 27), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and an amino acid sequence of GQGTQYPFT (SEQ ID NO: 30) CDR-L3 sequence. In some embodiments, V _H2 domain QVQLVESGGGVVQPGRSLRLSCAASGFTFTKAWMHWVRQAPGKQLEWVAQIKDKSNSYATYYADSVKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCRGVYYALSPFDYWGQGTLVTVSS comprises the amino acid sequence of (SEQ ID NO: 52) and / or, V _L2 domain DIVMTQTPLSLSVTPGQPASISCKSSQSLVHQNAQTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 54), DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLQTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 55), DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLFTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 56), and DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLRTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 57). In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 54 an antigen binding site. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 55 an antigen binding site. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 56 an antigen binding site. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 57 an antigen binding site.

In some embodiments, the third antigen binding site binds an HIV target protein selected from the group consisting of glycoprotein 120, glycoprotein 41, and glycoprotein 160. In some embodiments, the V _H3 domain comprises a CDR-H1 sequence comprising the amino acid sequence of NCPIN (SEQ ID NO: 1), a CDR-H2 sequence comprising the amino acid sequence of WMKPRHGAVSYARQLQG (SEQ ID NO: 2), and GKYCTARDYYNWDFEH (SEQ ID NO: 3) in comprises a CDR-H3 sequence comprising the amino acid sequence, V _L3 domain is CDR-L2 comprising the amino acid sequence of CDR-L1 sequence, SGSTRAA (SEQ ID NO: 5) comprising the amino acid sequence of RTSQYGSLA (SEQ ID NO: 4) sequence, and a CDR-L3 sequence comprising the amino acid sequence of QQYEF (SEQ ID NO: 6). In some embodiments, the V _H3 domain comprises a CDR-H1 sequence comprising the amino acid sequence of GYTFTAHI (SEQ ID NO: 7), a CDR-H2 sequence comprising the amino acid sequence of IKPQYGAV (SEQ ID NO: 8) or IKPQYGAT (SEQ ID NO: 9), and a CDR-H3 sequence comprising the amino acid sequence of DRSYGDSSWALDA (SEQ ID NO: 10), wherein the V _L3 domain comprises a CDR-L1 sequence comprising the amino acid sequence of QGVGSD (SEQ ID NO: 11), amino acids of HTS (SEQ ID NO: 12) a CDR-L2 sequence comprising the sequence, and a CDR-L3 sequence comprising the amino acid sequence of CQVLQF (SEQ ID NO: 13). In some embodiments, the V _H3 domain comprises a CDR-H1 sequence comprising the amino acid sequence of DCTLN (SEQ ID NO: 14), a CDR-H2 sequence comprising the amino acid sequence of WLKPRWGAVNYARPLQG (SEQ ID NO: 15), and GKNCDYNWDFEH (SEQ ID NO: 16) in comprises a CDR-H3 sequence comprising the amino acid sequence, V _L3 domain is CDR-L2 comprising the amino acid sequence of CDR-L1 sequence, SGSTRAA (SEQ ID NO: 18) comprising the amino acid sequence of RTSQYGSLA (SEQ ID NO: 17) sequence, and a CDR-L3 sequence comprising the amino acid sequence of QQYEF (SEQ ID NO: 19). In some embodiments, V is _H3 domain comprises the amino acid sequence and / or, V _L3 of QVRLSQSGGQMKKPGDSMRISCRASGYEFINCPINWIRLAPGKRPEWMGWMKPRHGAVSYARQLQGRVTMTRDMYSETAFLELRSLTSDDTAVYFCTRGKYCTARDYYNWDFEHWGQGTPVTVSS domain (SEQ ID NO: 43) comprises the amino acid sequence of SLTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQRPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNLTISNLESGDFGVYYCQQYEFFGQGTKVQVDIK (SEQ ID NO: 45). In some embodiments, V is _H3 domain comprises the amino acid sequence and / or, V _L3 of QVRLSQSGGQMKKPGDSMRISCRASGYEFINCPINWIRLAPGKRPEWMGWMKPRHGAVSYARQLQGRVTMTRQLSQDPDDPDWGTAFLELRSLTSDDTAVYFCTRGKYCTARDYYNWDFEHWGQGTPVTVSS domain (SEQ ID NO: 44) comprises the amino acid sequence of SLTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQRPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNLTISNLESGDFGVYYCQQYEFFGQGTKVQVDIK (SEQ ID NO: 45). In some embodiments, V is _H3 domain comprises the amino acid sequence and / or, V _L3 of RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA domain (SEQ ID NO: 46) comprises the amino acid sequence of YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK (SEQ ID NO: 49). In some embodiments, V is _H3 domain comprises the amino acid sequence and / or, V _L3 of RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGATNFGGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA domain (SEQ ID NO: 47) comprises the amino acid sequence of YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK (SEQ ID NO: 49). In some embodiments, V is _H3 domain comprises the amino acid sequence and / or, V _L3 of RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRQLSQDPDDPDWGIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA domain (SEQ ID NO: 48) comprises the amino acid sequence of YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK (SEQ ID NO: 49). In some embodiments, V is _H3 domain comprises the amino acid sequence and / or, V _L3 of QVQLVQSGGQMKKPGESMRISCRASGYEFIDCTLNWIRLAPGKRPEWMGWLKPRWGAVNYARPLQGRVTMTRQLSQDPDDPDWGTAFLELRSLTVDDTAVYFCTRGKNCDYNWDFEHWGRGTPVIVSS domain (SEQ ID NO: 50) comprises the amino acid sequence of LTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQRPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNLTISNLESGDFGVYYCQQYEFFGQGTKVQVDIK (SEQ ID NO: 51).

In some embodiments that may be combined with any other embodiments described herein, _{at least one of L 1} , L ₂ , L ₃ , or L ₄ is independently 0 amino acids in length. In some embodiments, L ₁ , L ₂ , L ₃ , and L ₄ are each independently 0 amino acids in length or GGGGSGGGGS (SEQ ID NO: 40), GGGGSGGGGSGGGGS (SEQ ID NO: 41), S, RT, TKGPS (SEQ ID NO: 39) , GQPKAAP (SEQ ID NO: 38), and GGSGSSGSGG (SEQ ID NO: 42). In some embodiments, L ₁ , L ₂ , L ₃ , and L ₄ are each independently GGGGSGGGGS (SEQ ID NO: 40), GGGGSGGGGSGGGGS (SEQ ID NO: 41), S, RT, TKGPS (SEQ ID NO: 39), GQPKAAP (SEQ ID NO: 40) 38), and GGSGSSGSGG (SEQ ID NO: 42). In some embodiments, L ₁ comprises the sequence GQPKAAP (SEQ ID NO: 38), L ₂ comprises the sequence TKGPS (SEQ ID NO: 39), L ₃ comprises the sequence S, and L ₄ comprises the sequence RT . In some embodiments _{, at least one of L 1} , L ₂ , L ₃ , or L ₄ comprises the sequence DKTHT (SEQ ID NO: 37). In some embodiments, L ₁ , L ₂ , L ₃ , and L ₄ comprise the sequence DKTHT (SEQ ID NO: 37).

In some embodiments that may be combined with any other embodiments described herein, the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG4 hinge-C _H2 -C _H3 domains, and the hinge-C _{The H2-} C _H3 domain contains amino acid substitutions at positions corresponding to positions 234 and 235 of human IgG4 according to the EU index, respectively, and the amino acid substitutions are F234A and L235A. In some embodiments, the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG4 hinge-C _H2 -C _H3 domains, and the hinge-C _H2 -C _H3 domains are each human IgG4 according to the EU index. and an amino acid substitution at a position corresponding to positions 233 to 236 of In some embodiments, the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG4 hinge-C _H2 -C _H3 domains, and the hinge-C _H2 -C _H3 domains are each human IgG4 according to the EU index. and amino acid substitutions at positions corresponding to positions 228 and 409 of , and the amino acid substitutions are S228P and R409K. In some embodiments, the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG1 hinge-C _H2 -C _H3 domains, and the hinge-C _H2 -C _H3 domains are each human IgG1 according to the EU index. amino acid substitutions at positions corresponding to positions 234, 235, and 329 of In some embodiments, the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG1 hinge-C _H2 -C _H3 domains, and the hinge-C _H2 -C _H3 domains are each human IgG1 according to the EU index. and amino acid substitutions at positions corresponding to positions 298, 299, and 300 of , and the amino acid substitutions are S298N, T299A, and Y300S. In some embodiments, the hinge-C _H2- C _H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 or IgG4 according to the EU index, substitutions are Y349C, T366S, L368A, and Y407V; The hinge-C _H2- C _H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 or IgG4 according to the EU index, the amino acid substitutions being S354C and T366W. In some embodiments, the hinge-C _H2- C _H3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 or IgG4 according to the EU index, wherein the amino acid substitutions are S354C and T366W ego; the hinge-C _H2- C _H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 or IgG4 according to the EU index, wherein the amino acid substitutions are Y349C, T366S , L368A, and Y407V.

In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 61 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 61; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 62 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 62; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 63; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 64 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 64. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 69 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 69; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 70 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 70; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 71 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 71; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 72 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 72. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 73; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 74; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 75 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 75; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 76 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 77 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 77; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 78 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 78; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 79 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 79; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:80 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:80. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 81 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 81; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 82 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 82; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 83 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 83; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:84 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:84. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 85 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 85; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:86 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:86; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 87 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 87; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:88 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:88. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 89 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 89; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 90 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 90; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 91 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 91; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 92 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 92. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 93 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 93; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 94 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 94; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 95 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 95; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 96 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 96. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 97 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 97; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 98 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 98; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 99 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 99; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 100 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 101 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 101; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 102 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 102; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 103 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 104 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 104. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 105 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 106 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 106; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 107 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 107; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 108 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 109 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 109; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 110 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 110; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 111 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 111; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 112 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 112. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 113 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 114 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 114; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 115 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 115; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 116 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 117 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 117; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 118 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 119 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 119; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 120 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 120. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 121 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 121; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 122 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 122; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 123 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 124 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 124. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 129 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 129; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 130 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 130; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 131 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 131; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 132 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 132. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 133 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 134 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 134; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 135 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 135; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 136 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 136. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 137 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 137; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 138 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 139 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 139; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 140 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 141 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 141; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 142 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 142; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 143 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 144 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 145 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 145; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 146 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 146; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 147 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 147; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 148 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 149 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 149; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 150 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 150; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 151 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 151; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 152 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 152. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 153 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 154 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 154; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 155 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 155; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 156 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 156. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 157 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 157; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 158 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 159 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 159; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 160 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 160. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 161 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 161; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 162 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 162; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO:163 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:163; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 164 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 164. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 165 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 165; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 166 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 166; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 167 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 167; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 168 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 169 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 169; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 170 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 170; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 171 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 171; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 172 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 172. In some embodiments, the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 173 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 174 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 174; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 175 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 175; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 176 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 176.

In some embodiments, provided herein is an isolated nucleic acid molecule comprising a nucleotide sequence encoding a binding protein of any one of the above embodiments. In some embodiments, provided herein are expression vectors comprising a nucleic acid molecule of any one of the preceding embodiments. In some embodiments, provided herein is an isolated host cell comprising a nucleic acid molecule of any one of the above embodiments or an expression vector of any one of the above embodiments. In some embodiments, the host cell is a mammalian or insect cell.

In some embodiments, provided herein is a pharmaceutical composition comprising the binding protein of any one of the preceding embodiments and a pharmaceutically acceptable carrier.

In some embodiments, there is provided a method of preventing and/or treating HIV infection in a patient, comprising administering to the patient a therapeutically effective amount of at least one binding protein of any one of the above embodiments or a pharmaceutical composition of any one of the above embodiments. Provided herein are methods comprising administering. In some embodiments, the binding protein is co-administered with standard antiretroviral therapy. In some embodiments, administration of the at least one binding protein results in clearance of one or more latent and/or chronic HIV-infected cells in the patient. In some embodiments, the patient is a human.

In some embodiments, the binding protein or pharmaceutical composition of any one of the above embodiments is provided for the prevention and/or treatment of HIV infection in a patient. In some embodiments, the binding protein is co-administered with standard antiretroviral therapy. In some embodiments, the binding protein results in clearance of one or more latent and/or chronic HIV-infected cells in the patient. In some embodiments, the patient is a human.

In some embodiments, the binding protein or pharmaceutical composition of any one of the above embodiments is provided for use in the manufacture of a medicament for the prevention and/or treatment of HIV infection in a patient. In some embodiments, the binding protein is co-administered with standard antiretroviral therapy. In some embodiments, the binding protein results in clearance of one or more latent and/or chronic HIV-infected cells in the patient. In some embodiments, the patient is a human.

In some embodiments, provided herein is a vector system comprising one or more vectors encoding the first, second, third, and fourth polypeptide chains of a binding protein of any one of the above embodiments. In some embodiments, the vector system comprises a first vector encoding a first polypeptide chain of a binding protein, a second vector encoding a second polypeptide chain of a binding protein, a third vector encoding a third polypeptide chain of a binding protein, and a fourth vector encoding a fourth polypeptide chain of the binding protein.

In some embodiments, provided herein is a kit comprising 1, 2, 3, or 4 polypeptide chains of a binding protein according to any one of the above embodiments. In some embodiments, the kit further comprises instructions for using the polypeptide chain or binding protein according to any of the methods or uses described herein, eg, described above.

In some embodiments, provided herein is a kit comprising 1, 2, 3, or 4 polynucleotides according to any one of the above embodiments. In some embodiments, provided herein is a polynucleotide kit comprising 1, 2, 3, or 4 polynucleotides of a polynucleotide kit comprising: (a) the polynucleotide sequence of SEQ ID NO: 177; A first polynucleotide comprising a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 178, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 179, and a fourth polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 180 polynucleotides; (b) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 181, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 182, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 183, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 184; (c) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 185, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 186, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 187, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 188; (d) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 189, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 190, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 191, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 192; (e) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 193, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 194, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 195, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 196; (f) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 197, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 198, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 199, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 200; (g) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 201, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 202, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 203, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 204; (h) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 205, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 206, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 207, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 208; (i) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 209, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 210, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 211, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 212; (j) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 213, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 214, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 215, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 216; (k) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 217, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 218, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 219, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 220; (l) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 221, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 222, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 223, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 224; (m) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 225, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 226, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 227, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 228; (n) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 229, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 230, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 231, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 232; (o) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 233, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 234, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 235, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 236; (p) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 237, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 238, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 239, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 240; (q) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 241, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 242, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 243, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 244; (r) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 245, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 246, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 247, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 248; (s) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 249, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 250, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 251, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 252; (t) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 253, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 254, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 255, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 256; (u) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 257, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 258, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 259, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 260; (v) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 261, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 262, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 263, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 264; (w) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 265, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 266, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 267, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 268; (x) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 269, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 270, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 271, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 272; (y) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 273, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 274, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 275, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 276; (z) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 277, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 278, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 279, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 280; (aa) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 281, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 282, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 283, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 284; (bb) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 285, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 286, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 287, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 288; or (cc) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 289, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 290, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 291, and A fourth polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 292. In some embodiments, the first, second, third, and fourth polynucleotides are present in one or more expression vectors, eg, one, two, three, or four expression vectors.

It should be understood that one, some, or all of the properties of the various embodiments described herein may be combined to form other embodiments of the invention. These and other aspects of the present invention will become apparent to those skilled in the art.

1 provides a schematic diagram of a trispecific binding protein comprising four polypeptide chains forming three antigen binding sites that bind to three target proteins, CD28, CD3, and HIV Env. The first pair of polypeptides has dual variable domains (VH1-VH2 and VL2-VL1) with cross orientation forming two antigen binding sites (VH1 and VL1; VH2 and VL2) that recognize CD28 and CD3, respectively, and The two polypeptide pairs have a single variable domain (VH3 and VL3) that forms a single antigen binding site that recognizes HIV Env. The trispecific binding protein depicted in Figure 1 uses constant regions comprising "knobs-into-holes" mutations, wherein the knob is in a second pair of polypeptides with a single variable domain.
Figure 2 shows a schematic view of a triple-specific T cells actor (TCE) strategy for targeting and removing the anti-HIV -HIV store using the triple-specific binding protein of FIG.

The present invention relates to a trispecific and/or trispecific comprising four polypeptide chains forming three antigen binding sites that specifically bind to at least one human immunodeficiency virus (HIV) target protein and/or to at least one T cell receptor target protein. or a trivalent binding protein, wherein a first pair of polypeptides forming the binding protein has dual variable domains with cross orientation and a second pair of polypeptides has a single variable domain.

The following description presents exemplary methods, parameters, and the like. It should be understood, however, that this description is provided as a description of exemplary embodiments and not for the purpose of limiting the scope of the invention.

Justice

As used in accordance with the present invention, the following terms are understood to have the following meanings, unless otherwise specified. Unless the context requires otherwise, singular terms include the plural and plural terms include the singular.

Aspects and embodiments of the invention described herein are understood to include "comprising", "consisting of", and "consisting essentially of" the aspects and embodiments.

As used herein, the term “polynucleotide” refers to a single-stranded or double-stranded nucleic acid polymer of at least 10 nucleotides in length. In certain embodiments, nucleotides comprising polynucleotides may be ribonucleotides or deoxyribonucleotides, or modified forms of either type of nucleotide. These modifications include base modifications such as bromouridine, ribose modifications such as arabinoside and 2',3'-dideoxyribose, and phosphorothioates, phosphorodithioates, phosphoroselenoates, phosphoros. internucleotide linkage modifications such as diselenoate, phosphoroanilothioate, phosphoraniladate, and phosphoroamidate. The term "polynucleotide" specifically includes single-stranded and double-stranded forms of DNA.

An "isolated polynucleotide" is a polynucleotide of genomic, cDNA, or synthetic origin, or some combination thereof, which (1) is not associated with all or part of a polynucleotide in which an isolated polynucleotide is found in nature, or (2) ) linked to a polynucleotide that is not linked in nature, or (3) does not exist as part of a larger sequence in nature.

An "isolated polypeptide" is defined as (1) essentially free of at least some other polypeptides with which it is normally found, (2) essentially free of other polypeptides from the same source (eg, the same species), (3) different expressed by the cells of the species, (4) separated from at least about 50% of the polynucleotide, lipid, carbohydrate, or other substance with which it in nature binds, (5) that in nature is associated with an “isolated polypeptide” not bound (by covalent or non-covalent interactions) to a portion of the polypeptide, (6) operably linked (by covalent or non-covalent interactions) to a polypeptide not associated with it in nature, or (7) in nature does not exist in Such isolated polypeptides may be encoded by genomic DNA, cDNA, mRNA or other RNA of synthetic origin, or any combination thereof. Preferably, the isolated polypeptide is substantially free of polypeptides or other contaminants found in its natural environment that could interfere with its use (therapeutic, diagnostic, prophylactic, research, etc.).

Naturally occurring antibodies generally comprise tetramers. Each of these tetramers is usually composed of two identical pairs of polypeptide chains, each pair having one full-length "light" chain (typically having a molecular weight of about 25 kDa) and a molecular weight (typically of about 50-70 kDa). having one full-length "heavy chain". As used herein, the terms “heavy chain” and “light chain” refer to any immunoglobulin polypeptide having sufficient variable domain sequence to confer specificity for a target antigen. In general, the amino-terminal portion of each light and heavy chain comprises a variable domain of about 100 to 110 or more amino acids, which is generally responsible for antigen recognition. In general, the carboxy-terminal portion of each chain defines a constant domain responsible for effector functions. Thus, in a naturally occurring antibody, a full-length heavy chain immunoglobulin polypeptide comprises one variable domain (V _H ) and three constant domains ( _CH1 , C _H2 , and C _H3 ), wherein the V _H domain is the amino-terminus of the polypeptide. a and C _H3 domains are carboxy- and at the terminal, full-length light chain immunoglobulin polypeptide comprises a variable domain (V _L) and a constant domain (C _L) and, V _L domain has the amino of the polypeptide - and the terminal The C _L domain is at the carboxy-terminus.

Human light chains are generally classified as kappa and lambda light chains, human heavy chains are generally classified as mu, delta, gamma, alpha, or epsilon, defining the isotypes of antibodies as IgM, IgD, IgG, IgA, and IgE, respectively do. There are several subclasses of IgG including, but not limited to, IgG1, IgG2, IgG3, and IgG4. There are subclasses of IgM including, but not limited to, IgM1 and IgM2. Similarly, IgA is subdivided into subclasses including, but not limited to, IgA1 and IgA2. Within full-length light and heavy chains, generally the variable and constant domains are joined by a “J” region of at least about 12 amino acids, and the heavy chain also includes a “D” region of greater than about 10 amino acids. See, eg, Fundamental Immunology (Paul, W., ed., Raven Press, 2nd ed., 1989), which is incorporated by reference in its entirety for all purposes. The variable regions of each light/heavy chain pair generally form an antigen binding site. In general, the variable domains of naturally occurring antibodies exhibit the same general structure of relatively conserved framework regions (FRs) joined by three hypervariable regions, also referred to as complementarity determining regions or CDRs. The CDRs from both chains of each pair are generally aligned by framework regions, which may allow binding to specific epitopes. From amino-terminus to carboxy-terminus, both light and heavy chain variable domains generally comprise domains FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4.

The term “CDR set” refers to a group of three CDRs present in a single variable region capable of binding antigen. The exact boundaries of these CDRs were defined differently depending on the system. The system described by Kabat (Kabat et al ., Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987) and (1991)) provides unambiguous residue numbering applicable to all variable regions of antibodies. Not only provides a system, but also provides precise residue boundaries defining three CDRs.These CDRs can be referred to as Kabat CDRs.Chothia and Lesk, 1987, J. Mol. Biol . 196: 901 -17; Chothia et al ., 1989, Nature 342: 877-83) found that certain sub-portions within the Kabat CDRs adopt nearly identical peptide framework structures despite great diversity at the amino acid sequence level. The parts are designated as L1, L2, and L3 or H1, H2, and H3, where "L" and "H" represent the light chain region and heavy chain region, respectively. This region has a border that overlaps with the Kabat CDR, Chothia Can be referred to as CDR.Other boundaries defining the CDR overlapping Kabat CDR are described in Padlan, 1995, FASEB J. 9: 133-39; MacCallum, 1996, J. Mol. Biol . 262(5): 732 -45; and Lefranc, 2003, Dev Comp Immunol 27 :.... 55-77] have been described in other CDR boundary definitions may not strictly follow this one system, and despite the specific residue or residue group Or even the whole CDR can be shortened or lengthened according to the prediction or experimental result that does not significantly affect antigen binding but overlaps with Kabat CDR.In certain embodiments, Kabat or Chothia defined CDR is used, but the method used herein is these cis CDRs defined according to any of the above systems may be used. Identification of predicted CDRs using amino acid sequences is described in Martin, AC "Protein sequence and structure analysis of antibody variable domains," In Antibody Engineering , Vol. 2. Kontermann R., Duebel S., eds. Springer-Verlag, Berlin, p. 33-51 (2010)] is well known in the art. The amino acid sequences of heavy and/or light chain variable domains are determined by other conventional methods to determine sequence hypervariable regions by confirming the sequence of the CDRs by, for example, comparison with the known amino acid sequences of other heavy and light chain variable regions. may be inspected. Numbered sequences can be obtained visually, or as described in Thompson, 1994, Nucleic Acids Res . 22: 4673-80]. Molecular models are typically used to accurately describe the framework and CDR regions, modifying sequence-based assignments accordingly.

The term “Fc,” as used herein, refers to a molecule comprising the sequence of a non-antigen-binding fragment generated from degradation of an antibody or by other means, whether in monomeric or multimeric form, and may include a hinge region. The original immunoglobulin source of the native Fc is preferably of human origin, preferably IgG1 and IgG2, but may be any immunoglobulin. Fc molecules consist of monomeric polypeptides that can be linked in dimeric or multimeric form by covalent (ie, disulfide bonds) and non-covalent bonds. The number of intermolecular disulfide bonds between monomeric subunits of native Fc molecules ranges from 1 to 4 depending on the class (eg, IgG, IgA, and IgE) or subclass (eg, IgG1, IgG2, IgG3, IgA1, and IgGA2). is the range An example of an Fc is a disulfide linked dimer resulting from papain degradation of IgG. As used herein, the term “Fc” is a generic term for monomeric, dimeric, and multimeric forms.

F(ab) fragments generally comprise one light chain and the V _H and C _{H1 domains of one heavy chain, wherein the V H} -C _H1 heavy chain portion of the F(ab) fragment forms a disulfide bond with another heavy chain polypeptide. Can not. As used herein, an F(ab) fragment is also defined as one light chain comprising two variable domains separated by an amino acid linker, and one comprising two variable domains and a C _H1 domain separated by an amino acid linker. may contain a heavy chain of

F(ab') fragments are generally constant (between the _{C H1} and C _H2 domains) such that an interchain disulfide bond is formed between one light chain and two heavy chains to form an F(ab') ₂ molecule. a portion of one heavy chain that further comprises a region.

As used herein, the term “binding protein” refers to a molecule that is not naturally occurring (or recombines or engineered) that specifically binds to at least one target antigen. Unless otherwise specified, trispecific binding proteins of the invention typically comprise four polypeptide chains forming three antigen binding sites, the first polypeptide chain having a structure represented by the formula

V _L2 -L ₁ -V _L1 -L ₂ -C _L [I]

The second polypeptide chain has a structure represented by the formula

V _H1 -L ₃ -V _H2 -L ₄ -C _{H1 -Hinge} -C _H2 -C _H3 [II]

The third polypeptide chain has a structure represented by the formula

V _H3 -C _H1 [III]

The fourth polypeptide chain has a structure represented by the following formula,

V_L3-C_L [IV]

during the meal,

V _L1 is a first immunoglobulin light chain variable domain;

V _L2 is a second immunoglobulin light chain variable domain;

V _L3 is a third immunoglobulin light chain variable domain;

V _H1 is a first immunoglobulin heavy chain variable domain;

V _H2 is a second immunoglobulin heavy chain variable domain;

V _H3 is a third immunoglobulin heavy chain variable domain;

_CL is an immunoglobulin light chain constant domain;

C _H1 is an immunoglobulin C _H1 heavy chain constant domain;

The hinge is an immunoglobulin hinge region that connects the _{C H1} domain and the C _{H2 domain;}

L ₁ , L ₂ , L ₃ , and L ₄ are amino acid linkers;

The polypeptide of formula I and the polypeptide of formula II form a cross light chain-heavy chain pair.

A “recombinant” molecule is one made, expressed, produced, or isolated by recombinant means.

One embodiment of the present invention provides binding proteins having biological and immunological specificity for 1 to 3 target antigens. Another embodiment of the invention provides a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide chain forming such a binding protein. Another embodiment of the invention provides an expression vector comprising a nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide chain forming such a binding protein. Another embodiment of the invention provides a host cell expressing such a binding protein (ie, comprising a nucleic acid molecule or vector encoding a polypeptide chain forming such a binding protein).

As used herein, the term “swapability” refers to the interchangeability of variable domains in the form of a binding protein while maintaining folding and ultimate binding affinity. "Fully swappable" refers to reversing the order of the V _H1 and V _H2 domains in a polypeptide chain of Formula I or a polypeptide chain of Formula II, while maintaining the overall function of the binding protein, as evidenced by maintenance of binding affinity, resulting in _{V L1} and V _{refers to the ability to change the order of the L2} domains (ie, the ability to reverse the order). It is also noted that the notations V _H and V _L indicate only the position of the domain in a particular protein chain in the final form. For example, V _H1 and V _{H2 may be derived from the V L1} and V _L2 domains of a parent antibody and may be located at the V _H1 and V _H2 positions of the binding protein. Similarly, V _L1 and V _{L2 may be derived from the V H1} and V _H2 domains of the parent antibody and may be located at the V _H1 and V _H2 positions of the binding protein. Thus, the V _H and V _L notations refer to the current position and not the original position in the parent antibody. Thus, the V _H and V _L domains are “swappable”.

As used herein, the term “antigen” or “target antigen” or “antigen target” refers to a molecule capable of being bound by a binding protein and further used in an animal to generate an antibody capable of binding to an epitope of that antigen or Refers to a part of a molecule. A target antigen may have more than one epitope. For each target antigen recognized by the binding protein, the binding protein can compete with an intact antibody that recognizes the target antigen.

As used herein, the term “HIV” refers to human immunodeficiency virus. As used herein, the term "HIV infection" generally includes retroviruses of the human immunodeficiency virus (HIV) family (HIV I, HIV II, HIV III (also known as HTLV-II, LAV-1, LAV-2), but infection of a host, particularly a human host, by HIV may be used herein to refer to any strain, form, subtype, clade, and variant of the HIV family. Accordingly, treatment of HIV infection will include treatment of persons who are carriers of the HIV family of retroviruses or who have been diagnosed with active AIDS, as well as treatment or prevention of AIDS-related conditions in such persons.

As used herein, the term “AIDS” refers to acquired immunodeficiency syndrome. AIDS is caused by HIV.

The term "CD4bs" or "CD4 binding site" refers to the binding site for CD4 (Cluster of Differentiation 4), a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells.

The term “CD3” is a differentiation factor cluster 3 polypeptide, a T cell surface protein that is generally part of the T cell receptor (TCR) complex.

"CD28" is a differentiation cluster 28 polypeptide, a T cell surface protein that provides a costimulatory signal for T cell activation and survival.

The term “glycoprotein 160” or “gp160 protein” refers to the envelope glycoprotein complex of HIV, which is a homotrimer that is cleaved into gp120 and gp41 subunits.

The term “MPER” refers to the proximal outer region of glycoprotein 41 (gp41), a subunit of the envelope protein complex of retroviruses, including HIV.

The term “glycan” refers to the carbohydrate portion of a glycoconjugate, such as a glycoprotein, glycolipid, or proteoglycan. In the disclosed binding proteins, the glycan refers to HIV-1, the envelope glycoprotein gp120.

The term "T-cell engager" refers to a binding protein directed against an HIV target protein as well as a binding protein directed against the cytotoxic activity of the host's immune system, more specifically T cells.

The term “trimer apex” refers to the apex of the HIV-1 envelope glycoprotein gp120.

The term “monospecific binding protein” refers to a binding protein that specifically binds to one antigenic target.

The term “monovalent binding protein” refers to a binding protein having one antigen binding site.

The term “bispecific binding protein” refers to a binding protein that specifically binds to two different antigenic targets.

The term “bivalent binding protein” refers to a binding protein having two binding sites.

The term “trispecific binding protein” refers to a binding protein that specifically binds to three different antigenic targets.

The term “trivalent binding protein” refers to a binding protein having three binding sites. In certain embodiments, a trivalent binding protein is capable of binding one antigen target. In other embodiments, the trivalent binding protein is capable of binding two antigenic targets. In other embodiments, the trivalent binding protein is capable of binding three antigen targets.

An “isolated” binding protein is one that has been identified, separated and/or recovered from a component of its natural environment. Contaminant components of the natural environment are substances that would interfere with diagnostic or therapeutic uses of the binding protein, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In some embodiments, the binding protein contains (1) greater than 95%, most preferably greater than 99% by weight of antibody as determined by the Lowry method, (2) N-terminal or internal amino acids using a spinning cup sequencer will be purified to homogeneity by SDS-PAGE in reducing or non-reducing conditions to a sufficient extent to obtain at least 15 residues of the sequence, or (3) using Coomassie blue or preferably silver staining. An isolated binding protein comprises the binding protein in situ within the recombinant cell since at least one component of the binding protein's natural environment will not be present.

As used herein, the term "substantially pure" or "substantially purified" refers to a species or compound that is the predominant species present (ie, more abundant than any other individual species in the composition on a molar basis). In some embodiments, the substantially purified fraction is a composition comprising at least about 50% (on a molar basis) of all macromolecular species present. In other embodiments, a substantially pure composition will comprise greater than about 80%, 85%, 90%, 95%, or 99% of all macromolecular species present in the composition. In another embodiment, purified to essentially homogeneity (contaminant species cannot be detected in the composition by conventional detection methods), and the composition consists essentially of a single macromolecular species.

A “neutralizing” binding protein, as used herein, refers to a molecule capable of blocking or substantially reducing the effector function of a target antigen to which it binds. As used herein, “substantially reduced” means at least about 60%, preferably at least about 70%, more preferably at least about 75%, even more preferably at least about 80% of the effector function of the target antigen. , even more preferably at least about 85%, most preferably at least about 90% reduction.

The term "epitope" includes any determinant, preferably a polypeptide determinant, capable of specifically binding to an immunoglobulin or T cell receptor. In certain embodiments, epitope determinants include chemically active surface groups of molecules such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, which in certain embodiments will have specific three-dimensional structural properties and/or specific charge properties. can An epitope is a region of an antigen to which an antibody or binding protein binds. In certain embodiments, a binding protein is said to specifically bind an antigen when the binding protein preferentially recognizes a target antigen in a complex mixture of proteins and/or macromolecules. In some embodiments, the binding protein is antigen specific when the equilibrium dissociation constant is 10 ^-8 M or less, more preferably the equilibrium dissociation constant is 10 ^-9 M or less, and most preferably the dissociation constant is 10 ^{-10 M or less.} is said to be combined with

The dissociation constant (K _D ) of a binding protein can be determined, for example, by surface plasmon resonance. In general, surface plasmon resonance assays involve the use of a BIAcore system (Pharmacia Biosensor; Piscataway, NJ) between a ligand (target antigen on a biosensor matrix) and analyte (binding protein in solution) via surface plasmon resonance (SPR). Real-time binding interactions are measured. Surface plasmon analysis can also be performed by immobilization of an analyte (binding protein on a biosensor matrix) and presentation of a ligand (target antigen). As used herein, the term “K _D ” refers to the dissociation constant of an interaction between a particular binding protein and a target antigen.

As used herein, the term "specifically binding" refers to at least about 1 x 10 ^-6 M, 1 x 10 ^-7 M, 1 x 10 ^-8 M, 1 x 10 ^-9 M, 1 x 10 ^-10 M, of a binding protein or antigen-binding fragment thereof that binds to an epitope-containing antigen with a Kd of 1 x 10 ^-11 M, 1 x 10 ^-12 M or greater and/or binds to an epitope with an affinity that is at least 2-fold greater than the degree of substitution for a non-specific antigen indicates ability.

As used herein, the term “linker” refers to one or more amino acid residues inserted between the immunoglobulin domains to provide the domains of the light and heavy chains with sufficient mobility to fold into a crossed double variable region immunoglobulin. A linker is inserted at the sequence level at the transition between the variable domains or between the variable domain and the constant domain, respectively. Transitions between domains can be identified because the approximate size of the immunoglobulin domains is well known. The exact location of the domain transition site is a region of peptide stretch that does not form secondary structural elements such as beta sheets or alpha helices, as evidenced by experimental data or can be estimated by modeling or secondary structure prediction techniques. can be found and determined. The linkers described herein include _{L 1} located in the light chain between the _{C-terminus of V L2} and the N-terminus of the V _L1 domain; and _{L 2} located in the light chain between the _{C-terminus of V L1} and the N-terminus of the C _L domain. The heavy chain linker is _{L 3} located between _{the C-terminus of V H1} and the N-terminus of the V _H2 domain; and _{L 4} located between the _{C-terminus of V H2} and the N-terminus of the C _H1 domain.

As used herein, the term “vector” refers to any molecule (eg, nucleic acid, plasmid, or virus) used to transfer coding information to a host cell. The term “vector” includes a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid", which represents a circular double-stranded DNA molecule into which additional DNA segments can be inserted. Another type of vector is a viral vector into which additional DNA segments can be inserted within the viral genome. Certain vectors (eg, bacterial vectors with a bacterial origin of replication and episomal mammalian vectors) are capable of autonomous replication in the host cell into which they are introduced. Other vectors (eg, non-episomal mammalian vectors) can integrate into the genome of a host cell upon introduction into the host cell and replicate along with the host genome. In addition, certain vectors are capable of directing the expression of operably linked genes. Such vectors are referred to herein as “recombinant expression vectors” (or simply “expression vectors”). In general, expression vectors useful in recombinant DNA technology are usually in the form of plasmids. Since a plasmid is the most commonly used form of vector, the terms "plasmid" and "vector" may be used interchangeably herein. However, the present invention is intended to include other forms of expression vectors, such as viral vectors (eg, replication defective retroviruses, adenoviruses, and adeno-associated viruses), which serve equivalent functions.

As used herein, the phrase “recombinant host cell” (or “host cell”) refers to a cell into which a recombinant expression vector has been introduced. Recombinant host cell or host cell is intended to refer to the particular subject cell as well as the progeny of such cell. Because certain modifications may occur in subsequent generations due to mutations or environmental influences, such progeny may not in fact be identical to the parental cells, but such cells are still included within the scope of the term "host cell" as used herein. A wide variety of host cell expression systems can be used to express the binding protein, including bacterial, yeast, baculovirus, and mammalian expression systems (as well as phage display expression systems). An example of a suitable bacterial expression vector is pUC19. For recombinant expression of the binding protein, the host cell is transformed or transfected with one or more recombinant expression vectors carrying a DNA fragment encoding the polypeptide chain of the binding protein, whereby the polypeptide chain is expressed in the host cell, preferably is secreted into the medium in which the host cells are cultured, and the binding protein can be recovered from the medium.

As used herein, the term “transformation” refers to a change in the genetic properties of a cell, wherein a cell has been transformed when it has been modified to contain new DNA. For example, a cell is transformed when it is genetically modified from its native state. After transformation, the transforming DNA can be physically integrated into the cell's chromosome and recombined with the cell's DNA, can be temporarily maintained as an episomal element without replication, or replicated independently as a plasmid. A cell is considered to be stably transformed when DNA replicates with cell division. As used herein, the term “transfection” refers to the uptake of foreign or exogenous DNA by a cell, and a cell is “transfected” when the exogenous DNA has been introduced inside the cell membrane. A number of transfection techniques are well known in the art. Such techniques can be used to introduce one or more exogenous DNA molecules into a suitable host cell.

The term "naturally occurring" as used herein and applied to a subject refers to the fact that the subject can be found in nature and has not been manipulated by humans. For example, a polynucleotide or polypeptide present in an organism (including viruses) that can be isolated from a source in nature and has not been intentionally modified by humans is naturally occurring. Similarly, "non-naturally occurring" as used herein refers to an object not found in nature or structurally modified or synthesized by humans.

As used herein, the twenty common amino acids and their abbreviations follow conventional usage. stereoisomers of the 20 common amino acids (eg, d-amino acids); Unnatural amino acids and analogs such as α-, α-disubstituted amino acids, N-alkyl amino acids, lactic acid, and other unconventional amino acids may also be suitable components of the polypeptide chain of a binding protein. Examples of unconventional amino acids include 4-hydroxyproline, γ-carboxyglutamate, ε-N,N,N-trimethyllysine, ε-N-acetyllysine, O-phosphoserine, N-acetylserine, N-formyl methionine, 3-methylhistidine, 5-hydroxylysine, σ-N-methylarginine, and other similar amino acids and imino acids (eg, 4-hydroxyproline). In polypeptide notation as used herein, the left direction is the amino-terminal direction and the right direction is the carboxy-terminal direction according to standard usage and conventions.

Naturally occurring residues can be classified into the following classes according to their common side chain properties.

(1) hydrophobic: Met, Ala, Val, Leu, Ile, Phe, Trp, Tyr, Pro;

(2) polar hydrophilicity: Arg, Asn, Asp, Gin, Glu, His, Lys, Ser, Thr;

(3) aliphatic: Ala, Gly, Ile, Leu, Val, Pro;

(4) aliphatic hydrophobic: Ala, Ile, Leu, Val, Pro;

(5) neutral hydrophilicity: Cys, Ser, Thr, Asn, Gin;

(6) acidic: Asp, Glu;

(7) Basic: His, Lys, Arg;

(8) residues affecting chain orientation: Gly, Pro;

(9) aromatic: His, Trp, Tyr, Phe; and

(10) Aromatic hydrophobicity: Phe, Trp, Tyr.

Conservative amino acid substitutions may involve exchanging a member of one of these classes for another member of the same class. Non-conservative substitutions may include exchanging members of one of these classes for members of another class.

Those skilled in the art will be able to determine suitable variants of the polypeptide chain of the binding protein using well-known techniques. For example, one of ordinary skill in the art can identify suitable regions of a polypeptide chain that can be changed without disrupting activity by targeting regions that are not considered to be critical for activity. Alternatively, one of ordinary skill in the art can identify residues and portions of molecules that are conserved among similar polypeptides. Conservative amino acid substitutions can also be made without disrupting biological activity or adversely affecting polypeptide structure, even in regions that may be important for biological activity or structure.

As used herein, the term “patient” includes human and animal subjects.

As used herein, the term “treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those with the disorder as well as those prone to develop the disorder or those in which the disorder is to be prevented. In certain embodiments, the binding protein may be used to treat a human infected with or susceptible to HIV infection, or used to ameliorate HIV infection in a human subject infected with HIV. The binding protein can also be used to prevent HIV in human patients.

Treatment of HIV-infected humans includes, for example, acute primary infection syndrome (which may be asymptomatic or associated with influenza-like illness with neurological symptoms such as fever, malaise, diarrhea, and headache), asymptomatic infection (circulatory) HIV, including a long latency period in which the CD4 ⁺ T cell number gradually decreases), and AIDS (defined as a more severe AIDS-defining disease and/or a decrease in the number of circulating CD4 cells below a level compatible with effective immune function) It should be understood to include subjects at any one of several stages of the infection progression. Also, treatment or prevention of HIV infection includes, for example, contact with HIV-contaminated blood, transfusions, exchange of bodily fluids, "unsafe" sex with an infected person, accidental needle puncture, tattooing or It will also include treatment of suspected HIV infection following a suspected past exposure to HIV by transmission of the virus from mother to baby during or shortly after undergoing acupuncture procedures, pregnancy, and delivery.

As used herein, the term "pharmaceutical composition" or "therapeutic composition" refers to a compound or composition capable of inducing a desired therapeutic effect when properly administered to a patient.

As used herein, the term “pharmaceutically acceptable carrier” or “physiologically acceptable carrier” refers to one or more formulation materials suitable for effectuating or enhancing delivery of a binding protein.

The terms “effective amount” and “therapeutically effective amount” when used in reference to a pharmaceutical composition comprising one or more binding proteins refer to an amount or dosage sufficient to produce the desired therapeutic result. More specifically, a therapeutically effective amount is an amount of a binding protein sufficient to inhibit for a period of time one or more of the clinically defined pathological processes associated with the condition being treated. The effective amount will vary depending on the particular binding protein used, and will also depend on various factors associated with the patient being treated and the severity of the condition and disorder. For example, if the binding protein is to be administered in vivo, factors such as the age, weight, and health of the patient, as well as dose response curves and toxicity data obtained from preclinical animal studies, will be among the factors considered. Determination of an effective or therapeutically effective amount of a given pharmaceutical composition is within the ability of one of ordinary skill in the art.

One embodiment of the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a binding protein.

trispecific and/or trivalent binding proteins

Certain aspects of the invention relate to trispecific and/or trivalent binding proteins. Any CDR or variable domain of any antigen binding protein described herein can be used in the trispecific binding protein of the invention. Various types of trispecific binding proteins are contemplated. In some embodiments, a binding protein of the invention is a trispecific and/or trivalent binding protein comprising four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, 1 polypeptide chain comprises a structure represented by the following formula,

V _L2 -L ₁ -V _L1 -L ₂ -C _L [I]

The second polypeptide chain comprises a structure represented by the formula

V _H1 - L ₃ -V _H2 -L ₄ -C _{H1 -Hinge} -C _H2 -C _H3 [II]

The third polypeptide chain comprises a structure represented by the formula

V _H3 -C _{H1 -Hinge} -C _H2 -C _H3 [III]

The fourth polypeptide chain comprises a structure represented by the formula

V _L3 -C _L [IV]

during the meal,

V _L1 is a first immunoglobulin light chain variable domain;

V _L2 is a second immunoglobulin light chain variable domain;

V _L3 is a third immunoglobulin light chain variable domain;

V _H1 is a first immunoglobulin heavy chain variable domain;

V _H2 is a second immunoglobulin heavy chain variable domain;

V _H3 is a third immunoglobulin heavy chain variable domain;

_CL is an immunoglobulin light chain constant domain;

C _H1 is an immunoglobulin C _H1 heavy chain constant domain;

C _H2 is an immunoglobulin C _H2 heavy chain constant domain;

C _H3 is an immunoglobulin C _H3 heavy chain constant domain;

The hinge is an immunoglobulin hinge region that connects the _{C H1} domain and the C _{H2 domain;}

L ₁ , L ₂ , L ₃ , and L ₄ are amino acid linkers;

The polypeptide of formula I and the polypeptide of formula II form a cross light chain-heavy chain pair.

In some embodiments, the first polypeptide chain and the second polypeptide chain have a cross orientation that forms two distinct antigen binding sites. In some embodiments, V _H1 and V _L1 form a binding pair and form a first antigen binding site. In some embodiments, V _H2 and V _L2 form a binding pair and form a second antigen binding site. In some embodiments, the third and fourth polypeptides form a third antigen binding site. In some embodiments, V _H3 and V _L3 form a binding pair and form a third antigen binding site.

In some embodiments, one or more of the antigen binding sites bind an HIV target protein. In some embodiments, V _H3 and V _L3 form a third antigen binding site that binds to an HIV target protein. In some embodiments, V _H1 and V _L1 form a first antigen binding site that binds to a T cell target protein, V _H2 and V _L2 form a second antigen binding site that binds to a T cell target protein, and V _H3 and V _L3 form a third antigen binding site that binds to the HIV target protein. In some embodiments, V _H1 and V _L1 form a first antigen binding site that binds to a T cell target protein, V _H2 and V _L2 form a second antigen binding site that binds a CD3 polypeptide, and V _H3 and V _L3 forms a third antigen binding site that binds to the HIV target protein. In some embodiments, V _H1 and V _L1 form a first antigen binding site that binds a CD28 polypeptide, V _H2 and V _L2 form a second antigen binding site that binds a CD3 polypeptide, and V _H3 and V _L3 forms a third antigen binding site that binds to the HIV target protein.

In some embodiments, the binding protein specifically binds one or more HIV target proteins (eg, as described below), and one or more target proteins on a T cell comprising a T cell receptor complex. These T cell-involving binding proteins can temporarily replenish target cells with T cells, and at the same time activate the cytolytic activity of T cells. T-cell actor trispecific antibodies can be used to activate HIV-1 reservoirs and redirect/activate T cells to lyse ^{latent infected HIV-1 + T cells.} Examples of target proteins on T cells include, but are not limited to, particularly CD3 and CD28. In some embodiments, trispecific binding proteins can be generated by binding the antigen binding domains of two or more monospecific antibodies (parent antibodies) into one antibody. See International Publications WO 2011/038290 A2, WO 2013/086533 A1, WO 2013/070776 A1, WO 2012/154312 A1, and WO 2013/163427 A1. Binding proteins of the invention can be prepared using domains or sequences obtained or derived from any human or non-human antibody, including, for example, human, murine, or humanized antibodies.

In some embodiments of the invention, a trivalent binding protein is capable of binding three different antigenic targets. In one embodiment, the binding protein is trispecific, one light chain-heavy chain pair is capable of binding two different antigen targets or epitopes, and one light chain-heavy chain pair is capable of binding one antigen target or epitope. .

In some embodiments, a binding protein of the invention binds one or more HIV target proteins and one or more T cell target proteins. In some embodiments, a binding protein is capable of specifically binding one HIV target protein and two different epitopes on a single T cell target protein. In some embodiments, the binding protein is capable of specifically binding one HIV target protein and two different T cell target proteins (eg, CD28 and CD3). In some embodiments, the first and second polypeptide chains of the binding protein form two antigen binding sites that specifically target two T cell target proteins, and the third and fourth polypeptide chains of the binding protein are HIV targets Forms an antigen binding site that specifically binds to a protein. In some embodiments, the one or more HIV target proteins are one or more of glycoprotein 120, glycoprotein 41, and glycoprotein 160. In some embodiments, the one or more T cell target proteins are one or more of CD3 and CD28.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 61 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:61; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 62 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 62; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 63; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 64 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 64.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 65 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO: 69 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 69; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 70 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 70; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 71 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 71; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 72 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 72.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 73 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:73; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 74; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 75 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 75; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 76 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 76.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 77 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 77; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 78 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 78; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 79 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 79; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:80 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:80.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:81 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:81; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 82 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 82; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 83 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 83; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:84 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:84.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 85 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 85; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:86 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:86; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 87 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 87; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO:88 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:88.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO:89 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:89; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 90 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 90; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 91 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 91; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 92 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 92.

In some embodiments, a binding protein of the present invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:93 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:93; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 94 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 94; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 95 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 95; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 96 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 96.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO: 97 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:97; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 98 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 98; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 99 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 99; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 100 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 100.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO: 101 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 101; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 102 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 102; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 103 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 104 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 104.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:105 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 106 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 106; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 107 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 107; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 108 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO: 109 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 109; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 110 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 110; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 111 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 111; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 112 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 112.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 113 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:113; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 114 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 114; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 115 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 115; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 116 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 116.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO: 117 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 117; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 118 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 119 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 119; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 120 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 120.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:121 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:121; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 122 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 122; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 123 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 124 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 124.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 129 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 129; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 130 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 130; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 131 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 131; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 132 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 132.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 133 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:133; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 134 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 134; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 135 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 135; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 136 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 136.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 137 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:137; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 138 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 139 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 139; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 140 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 140.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 141 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 141; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 142 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 142; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 143 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 144 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 144.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 145 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:145; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 146 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 146; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 147 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 147; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 148 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO: 149 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 149; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 150 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 150; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 151 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 151; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 152 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 152.

In some embodiments, a binding protein of the present invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 153 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:153; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 154 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 154; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 155 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 155; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 156 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 156.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 157 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 157; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 158 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 159 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 159; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 160 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 160.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO: 161 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 161; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 162 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 162; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO:163 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:163; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 164 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 164.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 165 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 165; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 166 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 166; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 167 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 167; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 168 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO: 169 or comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 169; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 170 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 170; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 171 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 171; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 172 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 172.

In some embodiments, a binding protein of the invention comprises four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, the first polypeptide chain having the amino acid sequence of SEQ ID NO: 173 or comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 174 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 174; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 175 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 175; The fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 176 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 176.

Exemplary, non-limiting polypeptides that can be used in any of the trispecific binding proteins described herein are provided in Table 4.

anti-HIV binding site

Certain aspects of the invention relate to binding proteins comprising an antigen binding site that binds to an HIV target protein or polypeptide.

In some embodiments, the HIV target protein is glycoprotein 120, glycoprotein 41, or glycoprotein 160. In some embodiments, the binding protein binds to one or more of glycoprotein 120, glycoprotein 41, and glycoprotein 160. Exemplary HIV target proteins restrict the MPER of HIV-1 gp41 protein, the CD4 binding site of HIV-1 gp120 protein, glycans in the V3 loop of HIV-1 gp120 protein, or the trimeric apex of HIV-1 gp120 protein or gp160 include without For example, in some embodiments, a binding protein of the invention comprises an antigen binding site that binds to the CD4 binding site of an HIV-1 gp120 protein. Exemplary antigen binding sites that bind HIV target proteins contemplated for use herein include those described in International Publication No. WO2017/074878, such as antibodies CD4BS “a”, CD4BS “b”, MPER, MPER_100W, V1/V2 “a” , V1/V2 “b”, or those derived from V3.

In some embodiments, a binding protein comprising an antigen binding site that binds an HIV target protein is monospecific and/or monovalent, bispecific and/or bivalent, trispecific and/or trivalent, or multispecific enemy and/or multivalent. In some embodiments, a binding protein comprising an antigen binding site that binds an HIV target protein is a trispecific binding protein comprising four polypeptides that form three antigen binding sites.

In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of NCPIN (SEQ ID NO: 1), a CDR-H2 sequence comprising the amino acid sequence of WMKPRHGAVSYARQLQG (SEQ ID NO: 2), and GKYCTARDYYNWDFEH (SEQ ID NO: 2) 3) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and/or a CDR-L1 sequence comprising the amino acid sequence of RTSQYGSLA (SEQ ID NO: 4), a CDR-L2 sequence comprising the amino acid sequence of SGSTRAA (SEQ ID NO: 5), and an amino acid sequence of QQYEF (SEQ ID NO: 6) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of NCPIN (SEQ ID NO: 1), a CDR-H2 sequence comprising the amino acid sequence of WMKPRHGAVSYARQLQG (SEQ ID NO: 2), and GKYCTARDYYNWDFEH (SEQ ID NO: 2) 3) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and a CDR-L1 sequence comprising the amino acid sequence of RTSQYGSLA (SEQ ID NO: 4), a CDR-L2 sequence comprising the amino acid sequence of SGSTRAA (SEQ ID NO: 5), and a CDR- comprising the amino acid sequence of QQYEF (SEQ ID NO: 6)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence.

In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GYTFTAHI (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence of IKPQYGAV (SEQ ID NO: 8) or IKPQYGAT (SEQ ID NO: 9) an antibody heavy chain variable (VH) domain comprising the sequence; and/or a CDR-L1 sequence comprising the amino acid sequence of QGVGSD (SEQ ID NO: 11), a CDR-L2 sequence comprising the amino acid sequence of HTS (SEQ ID NO: 12), and an amino acid sequence of CQVLQF (SEQ ID NO: 13) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GYTFTAHI (SEQ ID NO: 7), a CDR-H2 comprising the amino acid sequence of IKPQYGAV (SEQ ID NO: 8) or IKPQYGAT (SEQ ID NO: 9) an antibody heavy chain variable (VH) domain comprising the sequence; and a CDR-L1 sequence comprising the amino acid sequence of QGVGSD (SEQ ID NO: 11), a CDR-L2 sequence comprising the amino acid sequence of HTS (SEQ ID NO: 12), and a CDR- comprising the amino acid sequence of CQVLQF (SEQ ID NO: 13)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable comprising a CDR-H1 sequence comprising the amino acid sequence of GYTFTAHI (SEQ ID NO: 7), a CDR-H2 sequence comprising the amino acid sequence of IKPQYGAV (SEQ ID NO: 8) (VH) domains; and/or a CDR-L1 sequence comprising the amino acid sequence of QGVGSD (SEQ ID NO: 11), a CDR-L2 sequence comprising the amino acid sequence of HTS (SEQ ID NO: 12), and an amino acid sequence of CQVLQF (SEQ ID NO: 13) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable comprising a CDR-H1 sequence comprising the amino acid sequence of GYTFTAHI (SEQ ID NO: 7), a CDR-H2 sequence comprising the amino acid sequence of IKPQYGAV (SEQ ID NO: 8) (VH) domains; and a CDR-L1 sequence comprising the amino acid sequence of QGVGSD (SEQ ID NO: 11), a CDR-L2 sequence comprising the amino acid sequence of HTS (SEQ ID NO: 12), and a CDR- comprising the amino acid sequence of CQVLQF (SEQ ID NO: 13)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable comprising a CDR-H1 sequence comprising the amino acid sequence of GYTFTAHI (SEQ ID NO: 7), a CDR-H2 sequence comprising the amino acid sequence of IKPQYGAT (SEQ ID NO: 9) (VH) domains; and/or a CDR-L1 sequence comprising the amino acid sequence of QGVGSD (SEQ ID NO: 11), a CDR-L2 sequence comprising the amino acid sequence of HTS (SEQ ID NO: 12), and an amino acid sequence of CQVLQF (SEQ ID NO: 13) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable comprising a CDR-H1 sequence comprising the amino acid sequence of GYTFTAHI (SEQ ID NO: 7), a CDR-H2 sequence comprising the amino acid sequence of IKPQYGAT (SEQ ID NO: 9) (VH) domains; and a CDR-L1 sequence comprising the amino acid sequence of QGVGSD (SEQ ID NO: 11), a CDR-L2 sequence comprising the amino acid sequence of HTS (SEQ ID NO: 12), and a CDR- comprising the amino acid sequence of CQVLQF (SEQ ID NO: 13)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence.

In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of DCTLN (SEQ ID NO: 14), a CDR-H2 sequence comprising the amino acid sequence of WLKPRWGAVNYARPLQG (SEQ ID NO: 15), and GKNCDYNWDFEH (SEQ ID NO: 15) 16) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and/or a CDR-L1 sequence comprising the amino acid sequence of RTSQYGSLA (SEQ ID NO: 17), a CDR-L2 sequence comprising the amino acid sequence of SGSTRAA (SEQ ID NO: 18), and an amino acid sequence of QQYEF (SEQ ID NO: 19) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of DCTLN (SEQ ID NO: 14), a CDR-H2 sequence comprising the amino acid sequence of WLKPRWGAVNYARPLQG (SEQ ID NO: 15), and GKNCDYNWDFEH (SEQ ID NO: 15) 16) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and a CDR-L1 sequence comprising the amino acid sequence of RTSQYGSLA (SEQ ID NO: 17), a CDR-L2 sequence comprising the amino acid sequence of SGSTRAA (SEQ ID NO: 18), and a CDR- comprising the amino acid sequence of QQYEF (SEQ ID NO: 19)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence.

In some embodiments, binding proteins of the invention are described, for example, in Liu, Q. et al. (2019) Nat. Commun. 10:721], comprising an antigen binding site having a VH domain comprising an extended heavy chain FR3 loop of antibody VRC03.

In some embodiments, a binding protein of the invention comprises an amino acid sequence of at least 90%, at least 85%, at least 89%, at least 86%, at least 85%, at least 89%, at least 86%, at least QVRLSQSGGQMKKPGDSMRISCRASGYEFINCPINWIRLAPGKRPEWMGWMKPRHGAVSYARQLQGRVTMTRDMYSETAFLELRSLTSDDTAVYFCTRGKYCTARDYYNWDFEHWGQGTPVTVSS (SEQ ID NO: 43). an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or an amino acid sequence of SLTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQRPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNLTISNLESGDFGVYYCQQYEFFGQGTKVQVDIK (SEQ ID NO: 45) and at least 85%, at least 86%, at least 87%, at least 92%, at least 89%, at least 93%, at least 92%, at least 94% , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 43, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 45 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 43, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 45 includes parts.

In some embodiments, a binding protein of the present invention comprises at least 90%, at least 89%, at least 88%, at least 89%, at least 89%, at least 89%, at least 89% of QVRLSQSGGQMKKPGDSMRISCRASGYEFINCPINWIRLAPGKRPEWMGWMKPRHGAVSYARQLQLQGRVTMTRQLSQDPDDPDWGTAFLELRSLTSDDTAVYFCTRGKYCTARDYYNWDFEHWGQGTPVTVSS (SEQ ID NO: 44) amino acids an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or an amino acid sequence of SLTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQRPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNLTISNLESGDFGVYYCQQYEFFGQGTKVQVDIK (SEQ ID NO: 45) and at least 85%, at least 86%, at least 87%, at least 92%, at least 89%, at least 93%, at least 92%, at least 94% , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 44, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 45 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 44, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 45 includes parts.

In some embodiments, a binding protein of the invention comprises at least 88%, at least 87%, at least 85%, at least 86%, at least 87%, 89%, at least 86%, at least 87%, 89%, at least 86%, at least 87%, 91%, at least amino acid sequence of RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA (SEQ ID NO: 46) an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or the amino acid sequence of YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK (SEQ ID NO: 49) and at least 85%, at least 86%, at least 87%, at least 93%, at least 90%, at least 89%, at least 92%, at least 89% , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 46, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 49 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 46, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 49 includes parts.

In some embodiments, a binding protein of the invention comprises an amino acid sequence of RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGATNFGGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA (SEQ ID NO: 47), at least 86%, at least 86%, at least 85%, at least 89%, at least 86%, at least 87%, 89%, at least 91 an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or the amino acid sequence of YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK (SEQ ID NO: 49) and at least 85%, at least 86%, at least 87%, at least 93%, at least 90%, at least 89%, at least 92%, at least 89% , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 47, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 49 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 47, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 49 includes parts.

In some embodiments, a binding protein of the present invention comprises at least 89%, at least 89%, 89%, at least 89%, at least 89%, at least 89%, 89%, at least 88%, SEQ ID NO: 48, at least 88%, SEQ ID NO: 48, RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRQLSQDPDDPDWGIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA of an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or the amino acid sequence of YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK (SEQ ID NO: 49) and at least 85%, at least 86%, at least 87%, at least 93%, at least 90%, at least 89%, at least 92%, at least 89% , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 48, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 49 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 48, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 49 includes parts.

In some embodiments, a binding protein of the present invention comprises at least 90%, at least 88%, at least 89%, at least 88%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89% amino acid sequence of QVQLVQSGGQMKKPGESMRISCRASGYEFIDCTLNWIRLAPGKRPEWMGWLKPRWGAVNYARPLQGRVTMTRQLSQDPDDPDWGTAFLELRSLTVDDTAVYFCTRGKNCDYNWDFEHWGRGTPVIVSS sequence. an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or an amino acid sequence of LTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQRPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNLTISNLESGDFGVYYCQQYEFFGQGTKVQVDIK (SEQ ID NO: 51) and at least 85%, at least 86%, at least 87%, at least 89%, at least 92%, at least 89% , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 50, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 51 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 50, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 51 includes parts.

In some embodiments of any of the above embodiments, the binding protein is a trispecific binding protein. In some embodiments, the trispecific binding protein comprises an antigen binding site that binds an HIV target protein, an antigen binding site that binds a CD28 polypeptide, and an antigen binding site that binds a CD3 polypeptide. In some embodiments, the binding protein is a trispecific binding protein comprising four polypeptides comprising three antigen binding sites, wherein the polypeptide of formula I and the polypeptide of formula II are (eg, as described herein) form cross-light chain-heavy chain pairs. In some embodiments, the VH and VL domains of any of the anti-CD38 antigen binding sites described above represent V _H3 and V _L3 and form a third antigen binding site that binds an HIV target protein. In some embodiments, V _H1 and V _L1 form a first antigen binding site that binds to a CD28 polypeptide, and V _H2 and V _L2 form a second antigen binding site that binds a CD3 polypeptide, The VH and VL domains of any of the anti-HIV antigen binding sites described in 1 represent V _H3 and V _L3 and form a third antigen binding site that binds to the HIV target protein.

The sequences of exemplary anti-HIV antigen binding sites are provided in Table 1. In some embodiments, a binding protein comprising an anti-HIV antigen binding site of the invention comprises one, two, three, four, five or all six CDR sequences of an anti-HIV antibody set forth in Table 1. includes In some embodiments, a binding protein comprising an anti-HIV antigen binding site of the invention comprises a VH domain sequence and/or a VL domain sequence of an anti-HIV antibody set forth in Table 1.

[Table 1]

Anti-HIV binding protein sequence

anti-CD28 binding site

Certain aspects of the invention relate to binding proteins comprising an antigen binding site that binds to a CD28 polypeptide. In some embodiments, the CD28 polypeptide is a human CD28 polypeptide, also known as Tp44. Human CD28 polypeptides are known in the art and are produced from NCBI accession numbers XP_011510499.1, XP_011510497.1, XP_011510496.1, NP_001230007.1, NP_001230006.1, or NP_006130.1, or produced from NCBI gene ID number 940. Polypeptides are included without limitation. In some embodiments, a binding protein comprising an antigen binding site that binds to a CD28 polypeptide is monospecific and/or monovalent, bispecific and/or bivalent, trispecific and/or trivalent, or multispecific and/or polyvalent. In some embodiments, a binding protein comprising an antigen binding site that binds to a CD28 polypeptide is a trispecific binding protein comprising four polypeptides that form three antigen binding sites. In some embodiments, a binding protein comprising an antigen binding site that binds to a CD28 polypeptide comprises four polypeptides that form three antigen binding sites, one of which binds a CD28 polypeptide and one of which binds a CD3 polypeptide. It is a trispecific binding protein comprising In some embodiments, a binding protein comprising an antigen binding site that binds to a CD28 polypeptide has three antigen binding sites, one of which binds a CD28 polypeptide, one of which binds a CD3 polypeptide, and one that binds an HIV target protein. It is a trispecific binding protein comprising four polypeptides that form

In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GYTFTSYY (SEQ ID NO: 31), a CDR-H2 sequence comprising the amino acid sequence of IYPGNVNT (SEQ ID NO: 32), and TRSHYGLDWNFDV (SEQ ID NO: 32) 33) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and/or a CDR-L1 sequence comprising the amino acid sequence of QNIYVW (SEQ ID NO: 34), a CDR-L2 sequence comprising the amino acid sequence of KAS (SEQ ID NO: 35), and an amino acid sequence of QQGQTYPY (SEQ ID NO: 36) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GYTFTSYY (SEQ ID NO: 31), a CDR-H2 sequence comprising the amino acid sequence of IYPGNVNT (SEQ ID NO: 32), and TRSHYGLDWNFDV (SEQ ID NO: 32) 33) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and a CDR-L1 sequence comprising the amino acid sequence of QNIYVW (SEQ ID NO: 34), a CDR-L2 sequence comprising the amino acid sequence of KAS (SEQ ID NO: 35), and a CDR- comprising the amino acid sequence of QQGQTYPY (SEQ ID NO: 36)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence.

In some embodiments, a binding protein of the present invention comprises at least 88%, at least 88%, at least 88%, at least 87%, 89%, at least 88% of an amino acid sequence of QVQLVQSGAEVVKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWIGSIYPGNVNTNYAQKFQGRATLTVDTSISTAYMELSRLRSDDTAVYYCTRSHYGLDWNFDVWGKGTTVTVSS (SEQ ID NO:59) an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or an amino acid sequence of DIQMTQSPSSLSASVGDRVTITCQASQNIYVWLNWYQQKPGKAPKLLIYKASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDIATYYCQQGQTYPYTFGQGTKLEIK (SEQ ID NO: 60) and at least 85%, at least 86%, at least 92%, at least 89%, at least 90%, at least 86%, at least 92%, at least 89%, at least 93% , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 59, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 60 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 59, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 60 includes parts.

In some embodiments of any of the above embodiments, the binding protein is a trispecific binding protein. In some embodiments, the trispecific binding protein comprises an antigen binding site that binds an HIV target protein, an antigen binding site that binds a CD28 polypeptide, and an antigen binding site that binds a CD3 polypeptide. In some embodiments, the binding protein is a trispecific binding protein comprising four polypeptides comprising three antigen binding sites, wherein the polypeptide of formula I and the polypeptide of formula II are (eg, as described herein) form cross-light chain-heavy chain pairs. In some embodiments, the VH and VL domains of any of the anti-CD28 antigen binding sites described above represent V _H1 and V _L1 and form a first antigen binding site that binds a CD28 polypeptide. In some embodiments, the VH and VL domains of any of the anti-CD28 antigen binding sites described above represent V _H1 and V _L1 and form a first antigen binding site that binds to the CD28 polypeptide, and V _H2 and V _L2 are CD3 form a second antigen binding site that binds to the polypeptide, and V _H3 and V _L3 form a third antigen binding site that binds the HIV target protein.

The sequences of exemplary anti-CD28 antigen binding sites are provided in Table 2. In some embodiments, a binding protein comprising an anti-CD28 antigen binding site of the invention comprises one, two, three, four, five or all six CDR sequences of an anti-CD28 antibody set forth in Table 2 includes In some embodiments, a binding protein comprising an anti-CD28 antigen binding site of the invention comprises a VH domain sequence and/or a VL domain sequence of an anti-CD28 antibody set forth in Table 2.

[Table 2]

Anti-CD28 binding protein sequence

anti-CD3 binding site

Certain aspects of the invention relate to binding proteins comprising an antigen binding site that binds to a CD3 polypeptide. In some embodiments, the CD3 polypeptide is CD3-delta (also known as T3D, IMD19, and CD3-DELTA), CD3-epsilon (also known as T3E, IMD18, and TCRE), and CD3-gamma (T3G, IMD17, and CD3- also known as GAMMA). Human CD3 polypeptides are known in the art and include, but are not limited to, a polypeptide designated by NCBI Accession No. XP_006510029.1 or NP_031674.1, or a polypeptide produced from NCBI Gene ID Nos. 915, 916, or 917. In some embodiments, the binding protein comprising an antigen binding site that binds to a CD3 polypeptide is monospecific and/or monovalent, bispecific and/or bivalent, trispecific and/or trivalent, or multispecific and/or polyvalent. In some embodiments, a binding protein comprising an antigen binding site that binds to a CD3 polypeptide is a trispecific binding protein comprising four polypeptides that form three antigen binding sites. In some embodiments, a binding protein comprising an antigen binding site that binds to a CD3 polypeptide comprises four polypeptides that form three antigen binding sites, one of which binds a CD28 polypeptide and one of which binds a CD3 polypeptide. It is a trispecific binding protein comprising In some embodiments, a binding protein comprising an antigen binding site that binds to a CD3 polypeptide has three antigen binding sites, one of which binds a CD28 polypeptide, one of which binds a CD3 polypeptide, and one that binds an HIV target protein. It is a trispecific binding protein comprising four polypeptides that form

In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 21) 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and/or _{a CDR comprising the amino acid sequence of QSLVHX 1} NX ₂ X ₃ TY, wherein X ₁ is E or Q, X ₂ is A or L, and X ₃ is Q, R, or F (SEQ ID NO: 293). - an antibody light chain variable (VL) domain comprising a L1 sequence, a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and a CDR-L3 sequence comprising the amino acid sequence of GQGTQYPFT (SEQ ID NO: 30) and an antigen-binding site. In some embodiments, _{the CDR-L1 sequence of the V L2} domain is an amino acid sequence selected from the group consisting of QSLVHQNAQTY (SEQ ID NO: 24), QSLVHENLQTY (SEQ ID NO: 25), QSLVHENLFTY (SEQ ID NO: 26), and QSLVHENLRTY (SEQ ID NO: 27) includes

In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 21) 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and/or a CDR-L1 sequence comprising the amino acid sequence of QSLVHQNAQTY (SEQ ID NO: 24), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and an amino acid sequence of GQGTQYPFT (SEQ ID NO: 30) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 21) 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and a CDR-L1 sequence comprising the amino acid sequence of QSLVHQNAQTY (SEQ ID NO: 24), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and a CDR- comprising the amino acid sequence of GQGTQYPFT (SEQ ID NO: 30)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence.

In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 21) 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and/or a CDR-L1 sequence comprising the amino acid sequence of QSLVHENLQTY (SEQ ID NO: 25), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and an amino acid sequence of GQGTQYPFT (SEQ ID NO: 30) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 21) 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and a CDR-L1 sequence comprising the amino acid sequence of QSLVHENLQTY (SEQ ID NO: 25), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and a CDR- comprising the amino acid sequence of GQGTQYPFT (SEQ ID NO: 30)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence.

In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 21) 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and/or a CDR-L1 sequence comprising the amino acid sequence of QSLVHENLFTY (SEQ ID NO: 26), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and an amino acid sequence of GQGTQYPFT (SEQ ID NO: 30) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 21) 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and a CDR-L1 sequence comprising the amino acid sequence of QSLVHENLFTY (SEQ ID NO: 26), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and a CDR- comprising the amino acid sequence of GQGTQYPFT (SEQ ID NO: 30)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence.

In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 21) 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and/or a CDR-L1 sequence comprising the amino acid sequence of QSLVHENLRTY (SEQ ID NO: 27), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and an amino acid sequence of GQGTQYPFT (SEQ ID NO: 30) and an antigen binding site comprising an antibody light chain variable (VL) domain comprising a CDR-L3 sequence. In some embodiments, a binding protein of the invention comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and RGVYYALSPFDY (SEQ ID NO: 21) 22) an antibody heavy chain variable (VH) domain comprising a CDR-H3 sequence comprising the amino acid sequence of; and a CDR-L1 sequence comprising the amino acid sequence of QSLVHENLRTY (SEQ ID NO: 27), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and a CDR- comprising the amino acid sequence of GQGTQYPFT (SEQ ID NO: 30)- and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an L3 sequence.

In some embodiments, a binding protein of the invention comprises an amino acid sequence of at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 86%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or DIVMTQTPLSLSVTPGQPASISCKSSQSLVHQNAQTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 54), DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLQTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 55), DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLFTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 56), and DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLRTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 57), at least 85% to the amino acid sequence selected from the group consisting of, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99 an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is %, or 100% identical. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52; and/or an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52; and an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, and SEQ ID NO: 57.

In some embodiments, a binding protein of the invention comprises an amino acid sequence of at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 86%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or at least 85%, at least 86%, at least 92%, at least 87%, at least 89%, at least 94%, at least 86%, at least 92%, at least 87%, at least 89% of an amino acid sequence of DIVMTQTPLSLSVTPGQPASISCKSSQSLVHQNAQTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 54) , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 54 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 54 includes parts.

In some embodiments, a binding protein of the invention comprises an amino acid sequence of at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 86%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLQTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 55) with at least 85%, at least 86%, at least 92%, at least 89%, at least 89%, at least 89%, , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 55 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 55 includes parts.

In some embodiments, a binding protein of the invention comprises an amino acid sequence of at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 86%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or at least 85%, at least 86%, at least 92%, at least 89%, at least 89%, at least 94%, at least 86%, at least 92%, at least 89%, at least 89% and , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 56 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 56 includes parts.

In some embodiments, a binding protein of the invention comprises an amino acid sequence of at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 86%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, at least 89%, an antibody heavy chain variable (VH) domain comprising an amino acid sequence that is 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to, and/ or DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLRTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 57) and at least 85%, at least 86%, at least 92%, at least 89%, at least 89%, , an antigen binding site comprising an antibody light chain variable (VL) domain comprising an amino acid sequence that is at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to. In some embodiments, a binding protein of the invention comprises an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and/or an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 57 an antigen binding site. In some embodiments, a binding protein of the invention is an antigen binding comprising an antibody heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 52, and an antibody light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 57 includes parts.

Advantageously, anti-CD3 binding sites are described herein as exhibiting high affinity binding to human CD3 polypeptides and eliminating potential manufacturing burdens (eg, deamidation sites).

In some embodiments of any of the above embodiments, the binding protein is a trispecific binding protein. In some embodiments, the trispecific binding protein comprises an antigen binding site that binds an HIV target protein, an antigen binding site that binds a CD28 polypeptide, and an antigen binding site that binds a CD3 polypeptide. In some embodiments, the binding protein is a trispecific binding protein comprising four polypeptides comprising three antigen binding sites, wherein the polypeptide of formula I and the polypeptide of formula II are (eg, as described herein) form cross-light chain-heavy chain pairs. In some embodiments, the VH and VL domains of any of the anti-CD3 antigen binding sites described above represent V _H2 and V _L2 and form a second antigen binding site that binds a CD3 polypeptide. In some embodiments, V _H1 and V _L1 form a first antigen binding site that binds to a CD28 polypeptide, and the VH and VL domains of any anti-CD3 antigen binding site described above and/or in Table 3 are V _H2 and represents V _L2 and forms a second antigen binding site that binds to a CD3 polypeptide, and V _H3 and V _L3 form a third antigen binding site that binds to an HIV target protein.

The sequences of exemplary anti-CD3 antigen binding sites are provided in Table 3. In some embodiments, a binding protein comprising an anti-CD3 antigen binding site of the invention comprises one, two, three, four, five or all six CDR sequences of an anti-CD3 antibody set forth in Table 3 includes In some embodiments, a binding protein comprising an anti-CD3 antigen binding site of the invention comprises a VH domain sequence and/or a VL domain sequence of an anti-CD3 antibody set forth in Table 3.

[Table 3]

Anti-CD3 binding protein sequence

linker

In some embodiments, the linkers L ₁ , L ₂ , L ₃ , and L ₄ are 0 amino acids (length=0) to about 100 amino acids in length, or 100, 50, 40, 30, 20, or 15 or less amino acids in length. The linker may be 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid in length. In one binding protein, L ₁ , L ₂ , L ₃ , and L ₄ may all have the same amino acid sequence, or they may all have different amino acid sequences.

Examples of suitable linkers include, for example, GGGGSGGGGS (SEQ ID NO: 40), GGGGSGGGGSGGGGS (SEQ ID NO: 41), S, RT, TKGPS (SEQ ID NO: 39), GQPKAAP (SEQ ID NO: 38), GGSGSSGSGG (SEQ ID NO: 42), and DKTHT ( SEQ ID NO: 37), as well as those disclosed in International Publications WO2017/074878 and WO2017/180913. The above-listed examples are not intended to limit the scope of the invention in any way, and are not intended to limit the scope of the invention to valine, leucine, isoleucine, serine, threonine, lysine, arginine, histidine, aspartate, glutamate, asparagine, glutamine, glycine, and proline. Linkers comprising randomly selected amino acids selected from the group consisting of

The identity and sequence of amino acid residues in the linker may vary depending on the type of secondary structural element that needs to be achieved in the linker. For example, glycine, serine, and alanine are best suited for linkers with maximum flexibility. When a stiffer extended linker is desired, some combinations of glycine, proline, threonine, and serine are useful. Any amino acid residue can be combined with other amino acid residues to form a larger peptide linker, if necessary depending on the desired properties, to be considered a linker.

In some embodiments, _{the length of L 1} is at least twice the length of L _{3 .} In some implementations, the length L ₂ is at least twice the length L _4. In some embodiments, _{the length of L 1} is at least twice the length of L _{3 and the length of L 2} is at least twice the length of L ₄ . In some embodiments, L ₁ is 3 to 12 amino acid residues in length, L ₂ is 3 to 14 amino acid residues in length, L ₃ is 1 to 8 amino acid residues in length, and L ₄ is 1 to 8 amino acid residues in length. It is three amino acid residues long. In some embodiments, L ₁ is 5 to 10 amino acid residues in length, L ₂ is 5 to 8 amino acid residues in length, L ₃ is 1 to 5 amino acid residues in length, and L ₄ is 1 to 5 amino acid residues in length. It is two amino acid residues long. In some embodiments, L ₁ is 7 amino acid residues long, L ₂ is 5 amino acid residues long, L ₃ is 1 amino acid residue long, and L ₄ is 2 amino acid residues long.

In some embodiments, L ₁ , L ₂ , L ₃ , and L ₄ are each independently 0 amino acids in length or GGGGSGGGGS (SEQ ID NO: 40), GGGGSGGGGSGGGGS (SEQ ID NO: 41), S, RT, TKGPS (SEQ ID NO: 39) , GQPKAAP (SEQ ID NO: 38), and GGSGSSGSGG (SEQ ID NO: 42). In some embodiments, L ₁ , L ₂ , L ₃ , and L ₄ are each independently GGGGSGGGGS (SEQ ID NO: 40), GGGGSGGGGSGGGGS (SEQ ID NO: 41), S, RT, TKGPS (SEQ ID NO: 39), GQPKAAP (SEQ ID NO: 40) 38), and GGSGSSGSGG (SEQ ID NO: 42). In some embodiments, L ₁ comprises the sequence GQPKAAP (SEQ ID NO: 38), L ₂ comprises the sequence TKGPS (SEQ ID NO: 39), L ₃ comprises the sequence S, and L ₄ comprises the sequence RT .

In some embodiments _{, at least one of L 1} , L ₂ , L ₃ , or L ₄ comprises the sequence DKTHT (SEQ ID NO: 37). In some embodiments, L ₁ , L ₂ , L ₃ , and L ₄ comprise the sequence DKTHT (SEQ ID NO: 37).

Fc region and constant domain

In some embodiments, a binding protein of the invention _{comprises a second polypeptide chain further comprising an Fc region linked to C H1} , wherein the Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains. do. In some embodiments, the binding protein of the present invention _{comprises a third polypeptide chain further comprising an Fc region linked to C H1} , wherein the Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains. do. In some embodiments, a binding protein of the invention _{comprises a second polypeptide chain further comprising an Fc region linked to C H1} , wherein the Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains; and _{a third polypeptide chain further comprising an Fc region linked to C H1} , wherein the Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains.

In some embodiments, a binding protein of the invention comprises a polypeptide chain comprising an Fc region or a full length antibody heavy chain. In some embodiments, the Fc region is a human Fc region, eg, a human IgG1, IgG2, IgG3, or IgG4 Fc region. In some embodiments, the Fc region comprises an antibody hinge, C _H1 , C _H2 , C _H3 , and optionally C _H4 domains. In some embodiments, the Fc region is a human IgG1 Fc region. In some embodiments, the Fc region is a human IgG4 Fc region. In some embodiments, the Fc region comprises one or more of the mutations described below. In some embodiments, the Fc region is the Fc region of one of the heavy chain polypeptides (eg, polypeptides 2 or 3) of the binding proteins shown in Table 4. In some embodiments, the heavy chain constant region is the constant region of one of the heavy chain polypeptides (eg, Polypeptide 2 or 3) of the binding protein shown in Table 4. In some embodiments, the light chain constant region is the constant region of one of the light chain polypeptides (eg, polypeptides 1 or 4) of the binding proteins shown in Table 4.

In some embodiments, a binding protein of the invention comprises one or two Fc variants. As used herein, the term “Fc variant” refers to a molecule or sequence that has been modified from a native Fc but still comprises a binding site for the repair receptor, FcRn (a neonatal Fc receptor). Exemplary Fc variants, and their interactions with repair receptors, are known in the art. Accordingly, the term “Fc variant” may include a humanized molecule or sequence from a non-human native Fc. In addition, native Fc comprises regions that can be removed because they provide structural features or biological activities that are not required for the antibody-like binding proteins of the invention. Thus, the term "Fc variant" refers to (1) disulfide bond formation, (2) incompatibility with the selected host cell, (3) N-terminal heterogeneity upon expression in the selected host cell, (4) glycosylation, (5) complement lacks one or more native Fc regions or residues that affect or are involved in interaction with, (6) binding to Fc receptors other than repair receptors, or (7) antibody-dependent cytotoxicity (ADCC); and a molecule or sequence in which one or more Fc moieties or residues have been modified.

In some embodiments, a binding protein (eg, a trispecific binding protein) of the invention comprises a "knob" mutation on a second polypeptide chain and a "hole" mutation on a third polypeptide chain. In some embodiments, a binding protein of the invention comprises a “knob” mutation on a third polypeptide chain and a “hole” mutation on a second polypeptide chain. In some embodiments, the "knob" mutation comprises a substitution at a position corresponding to positions 354 and/or 366 of a human IgG1 or IgG4 according to the EU index. In some embodiments, the amino acid substitutions are S354C, T366W, T366Y, S354C, and T366W, or S354C and T366Y. In some embodiments, the "knob" mutation comprises a substitution at positions corresponding to positions 354 and 366 of human IgG1 or IgG4 according to the EU index. In some embodiments, the amino acid substitutions are S354C and T366W. In some embodiments, a “hole” mutation comprises a substitution at a position corresponding to 407 and optionally positions 349, 366, and/or 368 of human IgG1 or IgG4 according to the EU index. In some embodiments, the amino acid substitutions are Y407V or Y407T and optionally Y349C, T366S, and/or L368A. In some embodiments, a “hole” mutation comprises a substitution at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 or IgG4 according to the EU index. In some embodiments, the amino acid substitutions are Y349C, T366S, L368A, and Y407V.

In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region comprises an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises: an amino acid substitution at a position corresponding to position 366 and optionally position 354 of human IgG1 or IgG4 according to the EU index, wherein the amino acid substitution is T366W or T366Y and optionally S354C; the third polypeptide chain further comprises a second Fc region linked to CH1, the second Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising a human according to EU index and amino acid substitutions at positions corresponding to positions 407 and optionally positions 349, 366, and/or 368 of IgGl or IgG4, wherein the amino acid substitutions are Y407V or Y407T and optionally Y349C, T366S, and/or L368A.

In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region comprises an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises: an amino acid substitution at a position corresponding to position 407 and optionally positions 349, 366, and/or 368 of human IgG1 or IgG4 according to the EU index, wherein the amino acid substitution is Y407V or Y407T and optionally Y349C, T366S, and/or L368A; the third polypeptide chain further comprises a second Fc region linked to CH1, the second Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising a human according to EU index and amino acid substitutions at positions corresponding to positions 366 and optionally 354 of IgG1 or IgG4, wherein the amino acid substitutions are T366W or T366Y and optionally S354C.

In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region comprises an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises: comprising an amino acid substitution at the position corresponding to position 366 of human IgG1 or IgG4 according to the EU index, wherein the amino acid substitution is T366W; the third polypeptide chain further comprises a second Fc region linked to CH1, the second Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising a human according to EU index and an amino acid substitution at positions corresponding to positions 366, 368, and/or 407 of IgG1 or IgG4, wherein the amino acid substitutions are T366S, L368A, and/or Y407V.

In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region comprises an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises: comprising an amino acid substitution at positions corresponding to positions 366, 368, and/or 407 of human IgG1 or IgG4 according to the EU index, wherein the amino acid substitutions are T366S, L368A, and/or Y407V; the third polypeptide chain further comprises a second Fc region linked to CH1, the second Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising a human according to EU index and an amino acid substitution at the position corresponding to position 366 of IgG1 or IgG4, wherein the amino acid substitution is T366W.

In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region comprises an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises: amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 or IgG4 according to the EU index, wherein the amino acid substitutions are S354C and T366W; the third polypeptide chain further comprises a second Fc region linked to CH1, the second Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising a human according to EU index and amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of IgG1 or IgG4, wherein the amino acid substitutions are Y407V or Y349C and optionally Y349C, T366S, L368A, and Y407V. In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region comprises an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, wherein the first Fc region comprises: amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 or IgG4 according to the EU index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; the third polypeptide chain further comprises a second Fc region linked to CH1, the second Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising a human according to EU index and amino acid substitutions at positions corresponding to positions 354 and 366 of IgG1 or IgG4, the amino acid substitutions being S354C and T366W. In some embodiments, the first and/or second Fc region is a human IgG1 Fc region. In some embodiments, the first and/or second Fc region is a human IgG4 Fc region.

In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the first Fc region comprises amino acid substitutions at positions corresponding to positions 228, 354, 366, and 409 of human IgG4 according to the EU index, the amino acid substitutions being S228P, S354C, T366W, and R409K; the third polypeptide chain further comprises a second Fc region linked to CH1, wherein the second Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising amino acid substitutions at positions corresponding to positions 228, 349, 366, 368, 407, and 409 of human IgG4 according to the EU index, the amino acid substitutions being S228P, Y349C, T366S, L368A, Y407V, and R409K. In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, The first Fc region comprises amino acid substitutions at positions corresponding to positions 228, 349, 366, 368, 407, and 409 of human IgG4 according to the EU index, wherein the amino acid substitutions are S228P, Y349C, T366S, L368A, Y407V, and R409K; the third polypeptide chain further comprises a second Fc region linked to CH1, wherein the second Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising and amino acid substitutions at positions corresponding to positions 228, 354, 366, and 409 of human IgG4 according to the EU index, the amino acid substitutions being S228P, S354C, T366W, and R409K.

In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the first Fc region comprises amino acid substitutions at positions corresponding to positions 234, 235, 354, and 366 of human IgG4 according to the EU index, the amino acid substitutions being F234A, L235A, S354C, and T366W; the third polypeptide chain further comprises a second Fc region linked to CH1, wherein the second Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising amino acid substitutions at positions corresponding to positions 234, 235, 349, 366, 368, and 407 of human IgG4 according to the EU index, the amino acid substitutions being F234A, L235A, Y349C, T366S, L368A, and Y407V. In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, The first Fc region comprises amino acid substitutions at positions corresponding to positions 234, 235, 349, 366, 368, and 407 of human IgG4 according to the EU index, wherein the amino acid substitutions are F234A, L235A, Y349C, T366S, L368A, and Y407V; the third polypeptide chain further comprises a second Fc region linked to CH1, wherein the second Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising amino acid substitutions at positions corresponding to positions 234, 235, 354, and 366 of human IgG4 according to the EU index, the amino acid substitutions being F234A, L235A, S354C, and T366W.

In some embodiments, the binding proteins of the invention have effector functions, e.g., Fc receptor-mediated antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and/or antibody-dependent cytotoxicity (ADCC). ) and one or more mutations that reduce In some embodiments, the second polypeptide chain further comprises _{a first Fc region linked to C H1} , wherein the first Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains; the third polypeptide chain further comprises _{a second Fc region linked to C H1} , wherein the second Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains; the first and second Fc regions are human IgG1 Fc regions; The first and second Fc regions contain amino acid substitutions at positions corresponding to positions 234 and 235 of human IgG1 according to the EU index, respectively, and the amino acid substitutions are L234A and L235A. In some embodiments, the Fc region of the second and third polypeptide chains is a human IgG1 Fc region, the Fc region comprising amino acid substitutions at positions corresponding to positions 234 and 235 of human IgG1 according to the EU index, respectively, an amino acid Substitutions are L234A and L235A. In some embodiments, the second polypeptide chain further comprises _{a first Fc region linked to C H1} , wherein the first Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains; the third polypeptide chain further comprises _{a second Fc region linked to C H1} , wherein the second Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains; the first and second Fc regions are human IgG1 Fc regions; The first and second Fc regions contain amino acid substitutions at positions corresponding to positions 234, 235, and 329 of human IgG1 according to the EU index, respectively, and the amino acid substitutions are L234A, L235A, and P329A. In some embodiments, the Fc region of the second and third polypeptide chains is a human IgG1 Fc region, wherein the Fc region comprises amino acid substitutions at positions corresponding to positions 234, 235, and 329 of human IgG1 according to the EU index, respectively and the amino acid substitutions are L234A, L235A, and P329A. In some embodiments, the Fc region of the second and third polypeptide chains is a human IgG4 Fc region, the Fc region comprising amino acid substitutions at positions corresponding to positions 234 and 235 of human IgG4 according to the EU index, respectively, and amino acid Substitutions are F234A and L235A. In some embodiments, the binding protein is _{a second polypeptide chain further comprising a first Fc region linked to C H1} , wherein the first Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains. and _{a third polypeptide chain further comprising a second Fc region linked to C H1} , wherein the second Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains; The first and second Fc regions contain amino acid substitutions at positions corresponding to positions 234 and 235 of human IgG4 according to the EU index, respectively, and the amino acid substitutions are F234A and L235A.

In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, The first Fc region comprises amino acid substitutions at positions corresponding to positions 228, 234, 235, 354, 366, and 409 of human IgG4 according to the EU index, wherein the amino acid substitutions are S228P, F234A, L235A, S354C, T366W, and R409K; the third polypeptide chain further comprises a second Fc region linked to CH1, wherein the second Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising and amino acid substitutions at positions corresponding to positions 228, 234, 235, 349, 366, 368, 407, and 409 of human IgG4 according to the EU index, wherein the amino acid substitutions are S228P, F234A, L235A, Y349C, T366S, L368A , Y407V, and R409K. In some embodiments, the second polypeptide chain further comprises a first Fc region linked to CH1, wherein the first Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, The first Fc region comprises amino acid substitutions at positions corresponding to positions 228, 234, 235, 349, 366, 368, 407, and 409 of human IgG4 according to the EU index, wherein the amino acid substitutions are S228P, F234A, L235A, Y349C, T366S, L368A, Y407V, and R409K; the third polypeptide chain further comprises a second Fc region linked to CH1, wherein the second Fc region is a human IgG4 Fc region comprising an immunoglobulin hinge region and CH2 and CH3 immunoglobulin heavy chain constant domains, the second Fc region comprising and amino acid substitutions at positions corresponding to positions 228, 234, 235, 354, 366, and 409 of human IgG4 according to the EU index, the amino acid substitutions being S228P, F234A, L235A, S354C, T366W, and R409K.

In some embodiments, the Fc region is a human IgG4 Fc region comprising one or more mutations that reduce or eliminate FcγI and/or FcγII binding. In some embodiments, the Fc region is a human IgG4 Fc region comprising one or more mutations that reduce or eliminate FcγI and/or FcγII binding but do not affect FcRn binding. In some embodiments, the Fc region is a human IgG4 Fc region comprising an amino acid substitution at a position corresponding to positions 228 and/or 409 of a human IgG4 according to the EU index. In some embodiments, the amino acid substitution is S228P and/or R409K. In some embodiments, the Fc region is a human IgG4 Fc region comprising an amino acid substitution at a position corresponding to positions 234 and/or 235 of a human IgG4 according to the EU index. In some embodiments, the amino acid substitution is F234A and/or L235A. In some embodiments, the Fc region is a human IgG4 Fc region comprising an amino acid substitution at positions corresponding to positions 228, 234, 235, and/or 409 of human IgG4 according to the EU index. In some embodiments, the amino acid substitution is S228P, F234A, L235A, and/or R409K. In some embodiments, the Fc region is a human IgG4 Fc region comprising an amino acid substitution at a position corresponding to positions 233 to 236 of a human IgG4 according to the EU index. In some embodiments, the amino acid substitution is a deletion at E233P, F234V, L235A, and 236. In some embodiments, the Fc region is a human IgG4 Fc region comprising an amino acid mutation in the substitution corresponding to positions 228, 233 to 236, and/or 409 of a human IgG4 according to the EU index. In some embodiments, the amino acid mutation is S228P; deletions at E233P, F234V, L235A, and 236; and/or R409K.

In some embodiments, the Fc region comprises Fc receptor binding and/or effector function of the Fc region (eg, Fc receptor-mediated antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and/or and one or more mutations that reduce or eliminate antibody-dependent cytotoxicity (ADCC).

In some embodiments, the Fc region is a human IgG1 Fc region comprising one or more amino acid substitutions at positions corresponding to positions 234, 235, and/or 329 of human IgG1 according to the EU index. In some embodiments, the amino acid substitution is L234A, L235A, and/or P329A. In some embodiments, the Fc region is a human IgG1 Fc region comprising an amino acid substitution at positions corresponding to positions 298, 299, and/or 300 of human IgG1 according to the EU index. In some embodiments, the amino acid substitutions are S298N, T299A, and/or Y300S.

In some embodiments, a binding protein of the invention comprises one or more mutations, e.g., to improve the stability of the hinge region and/or the dimer interface of IgG4 (e.g., Spiess, C. et al. Referring 26583-26593]): (2013) J. Biol Chem 288... In some embodiments, the mutation comprises a substitution at positions corresponding to positions 228 and 409 of human IgG4 according to the EU index, and the amino acid substitutions are S228P and R409K. In some embodiments, the binding protein is _{a second polypeptide chain further comprising a first Fc region linked to C H1} , wherein the first Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains. and _{a third polypeptide chain further comprising a second Fc region linked to C H1} , wherein the second Fc region comprises an immunoglobulin hinge region and C _H2 and C _H3 immunoglobulin heavy chain constant domains; the first and second Fc regions are human IgG4 Fc regions; The first and second Fc regions contain amino acid substitutions at positions corresponding to positions 228 and 409 of human IgG4 according to the EU index, respectively, and the amino acid substitutions are S228P and R409K. In some embodiments, the binding proteins of the invention comprise knob and hole mutations and one or more mutations to improve stability. In some embodiments, the first and/or second Fc region is a human IgG4 Fc region.

In some embodiments, the Fc region is a human IgG1 Fc region comprising one or more amino acid substitutions at positions corresponding to positions 234, 235, and/or 329 of human IgG1 according to the EU index. In some embodiments, the amino acid substitution is L234A, L235A, and/or P329A. In some embodiments, the Fc region is a human IgG1 Fc region comprising an amino acid substitution at positions corresponding to positions 298, 299, and/or 300 of human IgG1 according to the EU index. In some embodiments, the amino acid substitutions are S298N, T299A, and/or Y300S.

nucleic acid

Another aspect of the invention relates to an isolated nucleic acid molecule comprising a nucleotide sequence encoding any of the binding proteins described herein. Exemplary and non-limiting nucleic acid sequences are provided in Table 5.

Another aspect of the invention relates to a kit of polynucleotides encoding one or more polypeptides of a binding protein, for example as described herein. In some embodiments, a polynucleotide kit of the present invention comprises 1, 2, 3, or 4 polynucleotides of a polynucleotide kit comprising: (a) comprising the polynucleotide sequence of SEQ ID NO: 177 a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 178, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 179, and a fourth polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 180 nucleotides; (b) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 181, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 182, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 183, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 184; (c) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 185, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 186, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 187, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 188; (d) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 189, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 190, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 191, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 192; (e) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 193, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 194, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 195, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 196; (f) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 197, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 198, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 199, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 200; (g) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 201, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 202, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 203, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 204; (h) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 205, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 206, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 207, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 208; (i) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 209, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 210, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 211, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 212; (j) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 213, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 214, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 215, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 216; (k) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 217, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 218, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 219, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 220; (l) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 221, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 222, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 223, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 224; (m) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 225, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 226, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 227, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 228; (n) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 229, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 230, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 231, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 232; (o) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 233, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 234, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 235, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 236; (p) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 237, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 238, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 239, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 240; (q) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 241, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 242, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 243, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 244; (r) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 245, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 246, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 247, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 248; (s) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 249, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 250, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 251, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 252; (t) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 253, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 254, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 255, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 256; (u) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 257, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 258, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 259, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 260; (v) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 261, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 262, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 263, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 264; (w) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 265, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 266, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 267, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 268; (x) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 269, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 270, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 271, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 272; (y) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 273, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 274, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 275, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 276; (z) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 277, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 278, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 279, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 280; (aa) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 281, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 282, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 283, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 284; (bb) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 285, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 286, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 287, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 288; or (cc) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 289, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 290, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 291, and A fourth polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 292.

Another aspect of the invention relates to a vector system comprising one or more vectors encoding the first, second, third, and fourth polypeptide chains of any of the binding proteins described herein. In some embodiments, the vector system comprises a first vector encoding a first polypeptide chain of a binding protein, a second vector encoding a second polypeptide chain of a binding protein, e.g., as shown in the polynucleotides of Table 5, binding a third vector encoding a third polypeptide chain of the protein, and a fourth vector encoding a fourth polypeptide chain of the binding protein. In some embodiments, the vector system comprises a first vector encoding first and second polypeptide chains of a binding protein, and a second vector encoding a third and fourth polypeptide chain of a binding protein. In some embodiments, the vector system comprises a first vector encoding a first and a third polypeptide chain of a binding protein, and a second vector encoding a second and a fourth polypeptide chain of a binding protein. In some embodiments, the vector system comprises a first vector encoding a first and a fourth polypeptide chain of a binding protein, and a second vector encoding a second and third polypeptide chain of a binding protein. In some embodiments, the vector system comprises a first vector encoding a first, second, third, and fourth polypeptide chain of a binding protein. One or more vectors in the vector system may be any of the vectors described herein. In some embodiments, the one or more vectors are expression vectors. In some embodiments, the first, second, third, and fourth polynucleotides are present in one or more expression vectors, eg, one, two, three, or four expression vectors.

Standard recombinant DNA methodologies are used to construct polynucleotides encoding the polypeptides forming the binding protein, incorporate such polynucleotides into recombinant expression vectors, and introduce such vectors into host cells. See, eg, Sambrook et al. , 2001, Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 3rd ed.)]. Enzymatic reactions and purification techniques may be performed according to the manufacturer's specifications, as commonly accomplished in the art, or as described herein. Unless specific definitions are provided, the nomenclature used in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well known and commonly used in the art. Similarly, conventional techniques may be used for chemical synthesis, chemical analysis, pharmaceutical preparation, formulation, delivery, and patient treatment.

In some embodiments, the isolated nucleic acid is operably linked to a heterologous promoter to direct transcription of the binding protein-encoding nucleic acid sequence. A promoter may refer to a nucleic acid control sequence that directs the transcription of a nucleic acid. A first nucleic acid sequence is operably linked to a second nucleic acid sequence when the first nucleic acid sequence is placed in functional association with the second nucleic acid sequence. For example, a promoter is operably linked to that coding sequence if it affects the transcription or expression of the coding sequence of the binding protein. Examples of promoters include viruses (eg, polyoma virus, fowlpox virus, adenovirus (eg, adenovirus 2), bovine papillomavirus, avian sarcoma virus, cytomegalovirus, retrovirus, hepatitis B virus, simian virus 40 ( SV40), etc.), heterologous eukaryotic promoters (eg, actin promoter, immunoglobulin promoter, heat shock promoter, etc.), CAG-promoter (Niwa et al., Gene 108(2):193-9, 1991) , phosphoglycerate kinase (PGK)-promoter, tetracycline-inducible promoter (Masui et al., Nucleic Acids Res. 33:e43, 2005), lac system, trp system, tac system, trc system, of phage lambda key operator and promoter regions, promoters for 3-phosphoglycerate kinase, promoters of yeast acid phosphatase, and promoters of yeast alpha-mating factors. A polynucleotide encoding a binding protein of the invention may be under the control of a constitutive promoter, an inducible promoter, or any other suitable promoter described herein or other suitable promoter readily recognized by one of ordinary skill in the art.

In some embodiments, the isolated nucleic acid is integrated into a vector. In some embodiments, the vector is an expression vector. An expression vector may comprise one or more regulatory sequences operably linked to the polynucleotide to be expressed. The term “regulatory sequences” includes promoters, enhancers, and other expression control elements (eg, polyadenylation signals). Examples of suitable enhancers include enhancer sequences from mammalian genes (eg, globin, elastase, albumin, α-fetoprotein, insulin, etc.), and enhancer sequences from eukaryotic viruses (eg, origin of replication late SV40 enhancer (bp 100) 270), cytomegalovirus early promoter enhancer, origin of replication late polyoma enhancer, adenovirus enhancer, etc.). Examples of suitable vectors include, for example, plasmids, cosmids, episomes, transposons, and viral vectors (eg, adenovirus, vaccinia virus, sindbis virus, measles virus, herpes virus, lentivirus, retrovirus, adenovirus). related viral vectors, etc.). Expression vectors can be used to transfect host cells such as, for example, bacterial cells, yeast cells, insect cells, and mammalian cells. Biologically functional viral and plasmid DNA vectors capable of expression and replication in a host are known in the art and can be used to transfect any cell of interest.

host cell

Another aspect of the invention relates to a host cell (eg, an isolated host cell) comprising one or more isolated polynucleotides, vectors, and/or vector systems described herein. In some embodiments, an isolated host cell of the invention is cultured in vitro. In some embodiments, the host cell is a bacterial cell (eg, an E. coli cell). In some embodiments, the host cell is a yeast cell (eg, S. cerevisiae cell). In some embodiments, the host cell is an insect cell. Examples of insect host cells include, for example, Drosophila cells (eg, S2 cells), Trichoplusia ni cells (eg, High Five ^™ cells), and Spodoptera frugiperda cells (eg, Sf21 or Sf9 cells). can do. In some embodiments, the host cell is a mammalian cell. Examples of mammalian host cells include, for example, human embryonic kidney cells (eg, 293 or 293 cells subcloned for growth in suspension culture), Expi293 ^™ cells, CHO cells, baby hamster kidney cells (eg, BHK). , ATCC CCL 10), mouse Sertoli cells (eg TM4 cells), monkey kidney cells (eg CV1 ATCC CCL 70), African green monkey kidney cells (eg VERO-76, ATCC CRL- 1587), human cervical carcinoma cells (eg HELA, ATCC CCL 2), canine kidney cells (eg MDCK, ATCC CCL 34), buffalo rat liver cells (eg BRL 3A, ATCC CRL 1442) ), human lung cells (eg W138, ATCC CCL 75), human liver cells (eg Hep G2, HB 8065), mouse mammary tumor cells (eg MMT 060562, ATCC CCL51), TRI cells , MRC 5 cells, FS4 cells, human liver cancer cell lines (eg, Hep G2), and myeloma cells (eg, NS0 and Sp2/0 cells).

Another aspect of the invention relates to a method of producing any of the binding proteins described herein. In some embodiments, the method comprises a) a host cell (eg, a host cell) comprising an isolated nucleic acid, vector, and/or vector system (eg, any isolated nucleic acid, vector, and/or vector system described herein). culturing the host cell (eg, any host cell described herein) under conditions such that the host cell expresses the binding protein; and b) isolating the binding protein from the host cell. Methods of culturing host cells under conditions to express a protein are well known to those skilled in the art. Methods for isolating proteins from cultured host cells are well known to those skilled in the art, including, for example, affinity chromatography (eg, protein A affinity chromatography followed by two-step affinity chromatography comprising size exclusion chromatography). is known

pharmaceutical composition

A therapeutic or pharmaceutical composition comprising a binding protein is within the scope of the present invention. Such therapeutic or pharmaceutical compositions may comprise a therapeutically effective amount of a binding protein, or binding protein-drug conjugate, admixed with a pharmaceutically or physiologically acceptable formulation agent selected to be suitable for the mode of administration.

Acceptable formulation materials are nontoxic to recipients at the dosages and concentrations employed.

A pharmaceutical composition is a formulation material for altering, maintaining, or preserving, for example, the pH, osmolality, viscosity, clarity, color, isotonicity, odor, sterility, stability, dissolution or release rate, adsorption or permeability of the composition may contain. Suitable formulating materials include amino acids (eg, glycine, glutamine, asparagine, arginine, or lysine), antibacterial agents, antioxidants (eg, ascorbic acid, sodium sulfite, or sodium hydrogen sulfite), buffers (eg, borate, bicarbonate, tris- HCl, citrate, phosphate, or other organic acids), bulking agents (such as mannitol or glycine), chelating agents (such as ethylenediamine tetraacetic acid (EDTA)), complexing agents (such as caffeine, polyvinylpyrrolidone, beta- cyclodextrin, or hydroxypropyl-beta-cyclodextrin), fillers, monosaccharides, disaccharides, and other carbohydrates (such as glucose, mannose, or dextrin), proteins (such as serum albumin, gelatin, or immunoglobulin), colorants, Flavoring and diluents, emulsifying agents, hydrophilic polymers (such as polyvinylpyrrolidone), low molecular weight polypeptides, salt-forming counterions (such as sodium), preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenol ethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid, or hydrogen peroxide), a solvent (such as glycerin, propylene glycol, or polyethylene glycol), a sugar alcohol (such as mannitol or sorbitol), a suspending agent, a surfactant or wetting agent ( For example, pluronic; PEG; sorbitan esters; polysorbates such as polysorbate 20 or polysorbate 80; triton; tromethamine; lecithin; cholesterol or tyloxapol), stability enhancing agents such as sucrose or sorbitol ), tonicity enhancing agents (e.g., alkali metal halides (e.g., sodium or potassium chloride) or mannitol sorbitol), delivery vehicles, diluents, excipients and/or pharmaceutical adjuvants (e.g., See Remington's Pharmaceutical Sciences (18th Ed., AR Gennaro, ed., Mack Publishing Company 1990), and subsequent editions thereof, which are incorporated herein by reference for all purposes.

The optimal pharmaceutical composition will be determined by one of ordinary skill in the art depending on, for example, the intended route of administration, mode of delivery, and desired dosage. Such compositions can affect the physical state, stability, rate of release in vivo, and rate of clearance in vivo of the binding protein.

The primary vehicle or carrier in the pharmaceutical composition may be aqueous or non-aqueous in nature. For example, a vehicle or carrier suitable for injection may be water, physiological saline solution, or artificial cerebrospinal fluid, supplemented with other substances commonly used in compositions for parenteral administration. Neutral buffered saline or saline mixed with serum albumin are additional exemplary vehicles. Another exemplary pharmaceutical composition comprises a Tris buffer of about pH 7.0-8.5, or an acetate buffer of about pH 4.0-5.5, which may further comprise sorbitol or a suitable substitute. In one embodiment of the invention, a binding protein composition can be prepared for storage by mixing a selected composition having a desired degree of purity with an optional formulator in the form of a lyophilized cake or aqueous solution. In addition, the binding protein may be formulated as a lyophilisate using an appropriate excipient such as sucrose.

The pharmaceutical composition of the present invention may be selected for parenteral or subcutaneous delivery. Alternatively, the composition may be selected for inhalation or for delivery through the digestive tract, such as oral. The preparation of such pharmaceutically acceptable compositions is within the skill of the art.

The formulation components are present in concentrations that are acceptable at the site of administration. For example, a buffer is used to maintain the composition at a physiological pH or slightly lower pH, typically within a pH range of about 5 to about 8.

When parenteral administration is contemplated, therapeutic compositions for use may be in the form of a pyrogen-free, parenterally acceptable aqueous solution comprising the binding protein of interest in a pharmaceutically acceptable vehicle. A particularly suitable vehicle for parenteral injection is properly preserved sterile distilled water in which the binding protein is formulated as a sterile isotonic solution. Another formulation is an injectable microsphere, biodegradable particle, polymer compound (eg, polylactic or polyglycolic acid), bead, or formulation of the molecule of interest using agents such as liposomes. Hyaluronic acid may also be used, which may have the effect of promoting the continuation of the duration of circulation. Other suitable means for introducing a molecule of interest include implantable drug delivery devices.

In one embodiment, the pharmaceutical composition may be formulated for inhalation. For example, the binding protein may be formulated as a dry powder for inhalation. Binding protein inhalation solutions may also be formulated with propellants for aerosol delivery. In another embodiment, the solution may be nebulized.

It is also contemplated that certain formulations may be administered orally. In one embodiment of the invention, binding proteins administered in this manner may be formulated with or without carriers conventionally used in the formulation of solid dosage forms such as tablets and capsules. For example, the capsule may be designed to release the active portion of the formulation at a point in the gastrointestinal tract where bioavailability is maximized and systemic degradation is minimized. Additional agents may be included to facilitate absorption of the binding protein. Diluents, flavoring agents, low melting point waxes, vegetable oils, glidants, suspending agents, tablet disintegrating agents, and binders may also be used.

Other pharmaceutical compositions may include an effective amount of the binding protein in admixture with a non-toxic excipient suitable for the manufacture of tablets. Solutions can be prepared in unit dose form by dissolving the tablets in sterile water or other suitable vehicle. Suitable excipients include inert diluents such as calcium carbonate, sodium carbonate or sodium bicarbonate, lactose, or calcium phosphate; or a binder such as starch, gelatin, or acacia; or glidants such as magnesium stearate, stearic acid, or talc.

Additional pharmaceutical compositions of the present invention, including formulations comprising the binding protein in sustained delivery or controlled delivery formulations, will be apparent to those skilled in the art. Techniques for formulating various other sustained or controlled delivery means such as liposomal carriers, biodegradable microparticles or porous beads and depot injections are also known to those skilled in the art. Further examples of sustained release formulations include semipermeable polymer matrices in the form of molded articles, for example films or microcapsules. The sustained release matrix may be polyester, hydrogel, polylactide, a copolymer of L-glutamic acid and gamma ethyl-L-glutamate, poly(2-hydroxyethyl-methacrylate), ethylene vinyl acetate, or poly-D (-)-3-hydroxybutyric acid. Sustained release compositions may also include liposomes, which may be prepared by any of a number of methods known in the art.

Pharmaceutical compositions used for in vivo administration must generally be sterile. This may be accomplished by filtration through a sterile filtration membrane. Where the composition is lyophilized, sterilization using this method may be performed before or after lyophilization and reconstitution. The composition for parenteral administration may be stored in a lyophilized form or as a solution. In addition, parenteral compositions are generally placed in a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.

Once formulated, the pharmaceutical composition may be stored in sterile vials as a solution, suspension, gel, emulsion, solid, or dehydrated or lyophilized powder. Such formulations may be stored in ready-to-use form or in a form requiring reconstitution prior to administration (lyophilized form).

The present invention also includes kits for producing single-dose dosage units. The kits may each include both a first container with a dry protein and a second container with an aqueous formulation. Kits comprising single and multi-chamber prefilled syringes (eg, liquid syringes and lyosyringes) are also included within the scope of the present invention.

The effective amount of the binding protein pharmaceutical composition to be used therapeutically will depend, for example, on the therapeutic context and purpose. Thus, those skilled in the art will know how to determine, in part, the appropriate dosage level for treatment, the molecule delivered, the indication for which the binding protein is used, the route of administration, and the patient's physique (weight, body surface area, or organ size) and condition (age and general health). will understand that it will depend on Therefore, the clinician can titrate the dosage and modify the route of administration to obtain the optimal therapeutic effect.

Dosing frequency will depend on the pharmacokinetic parameters of the binding protein in the formulation used. In general, the clinician will administer the composition until a dosage is reached that achieves the desired effect. Thus, the composition may be administered as a single dose, in two or more doses over time (which may or may not contain the same amount of the molecule of interest), or as continuous infusion through an implantation device or catheter. . Further refinements of appropriate dosages are routinely made by those skilled in the art and are within the scope of work routinely performed by those skilled in the art. Appropriate dosages can be ascertained using appropriate dose-response data.

The route of administration of the pharmaceutical composition is according to known methods (eg, orally; intravenously, intraperitoneally, intracerebral (intraventricular), intraventricular, intramuscular, intraocular, intraarterial, intraportal, or intralesional. via injection by route; by a sustained release system; or by an implantable device). If desired, the composition may be administered by bolus injection, administered continuously by infusion, or administered by an implantable device.

The composition may also be administered topically via implantation of a membrane, sponge, or other suitable material in which the molecule of interest is absorbed or encapsulated. When an implantable device is used, the device may be implanted in any suitable tissue or organ, and the molecule of interest may be delivered via diffusion, timed release bolus, or continuous administration.

The pharmaceutical composition may be used for the prevention and/or treatment of HIV infection. The pharmaceutical composition may be used as a sole therapy or in combination with standard antiretroviral therapy.

The present invention also relates to kits comprising binding proteins and other reagents useful for detecting the level of a target antigen in a biological sample. Such reagents may include detectable labels, blocking sera, positive and negative control samples, and detection reagents. In some embodiments, a kit comprises a composition comprising any of the binding proteins, polynucleotides, vectors, vector systems, and/or host cells described herein. In some embodiments, a kit comprises a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, IV solution bags, and the like. The container may be formed from a variety of materials, such as glass or plastic. The container contains a composition, alone or in combination with other compositions effective for the treatment, prevention, and/or diagnosis of a condition (eg, HIV infection), and may have a sterile access port (eg, the container may have a subcutaneous may be an intravenous solution bag or vial with a stopper pierceable by a needle). In some embodiments, the label or package insert indicates that the composition is for use in the prevention, diagnosis, and/or treatment of a condition of choice. Alternatively or additionally, the article of manufacture or kit further comprises a second (or third) container comprising a pharmaceutically acceptable buffer such as bacteriostatic water for injection (BWFI), phosphate buffered saline, Ringer's solution, and dextrose solution. may include It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes.

Methods and uses for binding proteins

Certain aspects of the invention provide methods for preventing HIV infection in a patient, treating HIV infection in a patient, preventing AIDS in a patient, and treating AIDS in a patient using any of the binding proteins or pharmaceutical compositions disclosed herein. is about Any binding protein or pharmaceutical composition disclosed herein can be used in a method of the invention, e.g., a method of preventing an HIV infection in a patient, treating an HIV infection in a patient, preventing AIDS in a patient, and treating AIDS in a patient. can be used for

1 illustrates exemplary, non-limiting forms for trispecific binding proteins that may be used in the methods and uses described herein. As shown in FIG . 2 , the proposed mechanisms by which the binding protein shown in FIG. 1 may cause clearance of HIV reservoir cells in a patient include: (1) anti-CD28 and activation of latent infected CD4+ T cells via anti-CD3 arms; (2) CD8+ T cell recruitment with activated latent infected CD4+ T cells via anti-Env and anti-CD3 arms; (3) activation of bound CD8+ T cells via anti-CD28 and anti-CD3 arms; and (4) killing of latent infected CD4+ T cells via a perforin/granzyme mechanism. Advantageously, this mechanism is thought to activate and subsequently kill HIV-1 depot cells, providing a novel strategy to attack HIV-1 depots in patients.

In some embodiments, the methods of the invention comprise administering to a patient a therapeutically effective amount of at least one of the binding proteins described herein or a pharmaceutical composition.

In some embodiments, the at least one binding protein is administered in combination with an antiretroviral therapy (eg, an anti-HIV therapy). In some embodiments, at least one binding protein is administered prior to antiretroviral therapy. In some embodiments, the at least one binding protein is administered concurrently with antiretroviral therapy. In some embodiments, the binding protein is administered following standard antiretroviral therapy. In some embodiments, the at least one binding protein is co-administered with any standard antiretroviral therapy known in the art.

In some embodiments, administration of the at least one binding protein or pharmaceutical composition results in clearance of one or more latent and/or chronic HIV-infected cells in the patient. In some embodiments, administration of the at least one binding protein results in neutralization of one or more HIV virions and clearance of one or more latent and/or chronic HIV-infected cells in the patient. In some embodiments, the patient is a human.

[Table 4]

Trispecific Binding Protein Polypeptide Sequence

[Table 5]

Trispecific binding protein polynucleotide sequence

SEQUENCE LISTING <110> Sanofi Department of Health and Human Services The United States of America as Represented by the Secretary <120> TRISPECIFIC AND/OR TRIVALENT BINDING PROTEINS FOR TREATMENT OF HIV INFECTION <130> 18395-20319.40 <140> Not Yet Assigned <141> Concurrently Herewith <150> EP 19306312.0 <151> 2019-10-08 <150> US 62/831,415 <151> 2019-04-09 <160> 293 <170> FastSEQ for Windows Version 4.0 <210> 1 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 1 Asn Cys Pro Ile Asn 1 5 <210> 2 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 2 Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu Gln 1 5 10 15 Gly <210> 3 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 3 Gly Lys Tyr Cys Thr Ala Arg Asp Tyr Tyr Asn Trp Asp Phe Glu His 1 5 10 15 <210> 4 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 4 Arg Thr Ser Gln Tyr Gly Ser Leu Ala 1 5 <210> 5 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 5 Ser Gly Ser Thr Arg Ala Ala 1 5 <210> 6 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 6 Gln Gln Tyr Glu Phe 1 5 <210> 7 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 7 Gly Tyr Thr Phe Thr Ala His Ile 1 5 <210> 8 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 8 Ile Lys Pro Gln Tyr Gly Ala Val 1 5 <210> 9 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 9 Ile Lys Pro Gln Tyr Gly Ala Thr 1 5 <210> 10 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 10 Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala 1 5 10 <210> 11 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 11 Gln Gly Val Gly Ser Asp 1 5 <210> 12 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 12 His Thr Ser One <210> 13 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 13 Cys Gln Val Leu Gln Phe 1 5 <210> 14 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 14 Asp Cys Thr Leu Asn 1 5 <210> 15 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 15 Trp Leu Lys Pro Arg Trp Gly Ala Val Asn Tyr Ala Arg Pro Leu Gln 1 5 10 15 Gly <210> 16 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 16 Gly Lys Asn Cys Asp Tyr Asn Trp Asp Phe Glu His 1 5 10 <210> 17 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 17 Arg Thr Ser Gln Tyr Gly Ser Leu Ala 1 5 <210> 18 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 18 Ser Gly Ser Thr Arg Ala Ala 1 5 <210> 19 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 19 Gln Gln Tyr Glu Phe 1 5 <210> 20 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 20 Gly Phe Thr Phe Thr Lys Ala Trp 1 5 <210> 21 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 21 Ile Lys Asp Lys Ser Asn Ser Tyr Ala Thr 1 5 10 <210> 22 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 22 Arg Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr 1 5 10 <210> 23 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 23 Gln Ser Leu Val His Asn Asn Ala Asn Thr Tyr 1 5 10 <210> 24 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 24 Gln Ser Leu Val His Gln Asn Ala Gln Thr Tyr 1 5 10 <210> 25 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 25 Gln Ser Leu Val His Glu Asn Leu Gln Thr Tyr 1 5 10 <210> 26 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 26 Gln Ser Leu Val His Glu Asn Leu Phe Thr Tyr 1 5 10 <210> 27 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 27 Gln Ser Leu Val His Glu Asn Leu Arg Thr Tyr 1 5 10 <210> 28 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 28 Gln Ser Leu Val His Asp Asn Ala Gln Thr Tyr 1 5 10 <210> 29 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 29 Lys Val Ser One <210> 30 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 30 Gly Gln Gly Thr Gln Tyr Pro Phe Thr 1 5 <210> 31 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 31 Gly Tyr Thr Phe Thr Ser Tyr Tyr 1 5 <210> 32 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 32 Ile Tyr Pro Gly Asn Val Asn Thr 1 5 <210> 33 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 33 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val 1 5 10 <210> 34 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 34 Gln Asn Ile Tyr Val Trp 1 5 <210> 35 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 35 Lys Ala Ser One <210> 36 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 36 Gln Gln Gly Gln Thr Tyr Pro Tyr 1 5 <210> 37 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 37 Asp Lys Thr His Thr 1 5 <210> 38 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 38 Gly Gln Pro Lys Ala Ala Pro 1 5 <210> 39 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 39 Thr Lys Gly Pro Ser 1 5 <210> 40 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 40 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 <210> 41 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 41 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15 <210> 42 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 42 Gly Gly Ser Gly Ser Ser Gly Ser Gly Gly 1 5 10 <210> 43 <211> 125 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 43 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Met Tyr Ser Glu Thr Ala Phe 65 70 75 80 Leu Glu Leu Arg Ser Leu Thr Ser Asp Asp Thr Ala Val Tyr Phe Cys 85 90 95 Thr Arg Gly Lys Tyr Cys Thr Ala Arg Asp Tyr Tyr Asn Trp Asp Phe 100 105 110 Glu His Trp Gly Gin Gly Thr Pro Val Thr Val Ser Ser 115 120 125 <210> 44 <211> 132 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 44 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Thr Ala Phe Leu Glu Leu Arg Ser Leu Thr Ser Asp 85 90 95 Asp Thr Ala Val Tyr Phe Cys Thr Arg Gly Lys Tyr Cys Thr Ala Arg 100 105 110 Asp Tyr Tyr Asn Trp Asp Phe Glu His Trp Gly Gln Gly Thr Pro Val 115 120 125 Thr Val Ser Ser 130 <210> 45 <211> 101 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 45 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys 100 <210> 46 <211> 122 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 46 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala 115 120 <210> 47 <211> 122 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 47 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Thr Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala 115 120 <210> 48 <211> 129 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 48 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Ile Ala Tyr Met Asp Ile Arg Gly Leu Lys Pro Asp 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Ser Tyr Gly Asp Ser 100 105 110 Ser Trp Ala Leu Asp Ala Trp Gly Gin Gly Thr Thr Val Val Val Ser 115 120 125 Ala <210> 49 <211> 103 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 49 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys 100 <210> 50 <211> 128 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 50 Gln Val Gln Leu Val Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Glu 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asp Cys 20 25 30 Thr Leu Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Leu Lys Pro Arg Trp Gly Ala Val Asn Tyr Ala Arg Pro Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Thr Ala Phe Leu Glu Leu Arg Ser Leu Thr Val Asp 85 90 95 Asp Thr Ala Val Tyr Phe Cys Thr Arg Gly Lys Asn Cys Asp Tyr Asn 100 105 110 Trp Asp Phe Glu His Trp Gly Arg Gly Thr Pro Val Ile Val Ser Ser 115 120 125 <210> 51 <211> 100 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 51 Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr Ala 1 5 10 15 Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr Gln 20 25 30 Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser Thr 35 40 45 Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly Pro 50 55 60 Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly Val 65 70 75 80 Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val Gln 85 90 95 Val Asp Ile Lys 100 <210> 52 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 52 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala 20 25 30 Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val 35 40 45 Ala Gln Ile Lys Asp Lys Ser Asn Ser 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 Arg Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly 100 105 110 Gln Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 53 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 53 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Asn 20 25 30 Asn Ala Asn Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 54 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 54 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Gln 20 25 30 Asn Ala Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 55 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 55 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 56 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 56 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Phe Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 57 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 57 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Arg Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 58 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 58 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Asp 20 25 30 Asn Ala Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 59 <211> 120 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 59 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser 115 120 <210> 60 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 60 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asn Ile Tyr Val Trp 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 40 45 Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 75 80 Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly Gln Thr Tyr Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 100 105 <210> 61 <211> 338 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 61 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Asn 20 25 30 Asn Ala Asn Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Gly Gln Pro Lys Ala Ala Pro Asp Ile Gln Met Thr Gln Ser Pro Ser 115 120 125 Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala 130 135 140 Ser Gln Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly 145 150 155 160 Lys Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly 165 170 175 Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 180 185 190 Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln 195 200 205 Gln Gly Gln Thr Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu 210 215 220 Ile Lys Thr Lys Gly Pro Ser Arg Thr Val Ala Ala Pro Ser Val Phe 225 230 235 240 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 245 250 255 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 260 265 270 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 275 280 285 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 290 295 300 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 305 310 315 320 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 325 330 335 Glu Cys <210> 62 <211> 573 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 62 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 340 345 350 Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe 355 360 365 Leu Phe Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 370 375 380 Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 385 390 395 400 Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 405 410 415 Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 420 425 430 Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 435 440 445 Lys Val Ser Asn Lys Ala Leu Ala Ala Pro Ile Glu Lys Thr Ile Ser 450 455 460 Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro 465 470 475 480 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val 485 490 495 Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 500 505 510 Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Val Leu Asp Ser Asp 515 520 525 Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 530 535 540 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 545 550 555 560 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 565 570 <210> 63 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 63 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Met Tyr Ser Glu Thr Ala Phe 65 70 75 80 Leu Glu Leu Arg Ser Leu Thr Ser Asp Asp Thr Ala Val Tyr Phe Cys 85 90 95 Thr Arg Gly Lys Tyr Cys Thr Ala Arg Asp Tyr Tyr Asn Trp Asp Phe 100 105 110 Glu His Trp Gly Gin Gly Thr Pro Val Thr Val Ser Ser Ala Ser Thr 115 120 125 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 130 135 140 Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 145 150 155 160 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 165 170 175 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 180 185 190 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 195 200 205 Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 210 215 220 Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 225 230 235 240 Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 245 250 255 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 260 265 270 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 275 280 285 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 290 295 300 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 305 310 315 320 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 325 330 335 Ala Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 340 345 350 Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys 355 360 365 Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 370 375 380 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 385 390 395 400 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 405 410 415 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 420 425 430 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 435 440 445 Leu Ser Leu Ser Pro Gly 450 <210> 64 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 64 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 65 <211> 338 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 65 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Asn 20 25 30 Asn Ala Asn Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Gly Gln Pro Lys Ala Ala Pro Asp Ile Gln Met Thr Gln Ser Pro Ser 115 120 125 Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala 130 135 140 Ser Gln Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly 145 150 155 160 Lys Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly 165 170 175 Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 180 185 190 Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln 195 200 205 Gln Gly Gln Thr Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu 210 215 220 Ile Lys Thr Lys Gly Pro Ser Arg Thr Val Ala Ala Pro Ser Val Phe 225 230 235 240 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 245 250 255 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 260 265 270 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 275 280 285 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 290 295 300 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 305 310 315 320 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 325 330 335 Glu Cys <210> 66 <211> 573 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 66 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 340 345 350 Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 355 360 365 Leu Phe Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 370 375 380 Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 385 390 395 400 Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 405 410 415 Lys Pro Arg Glu Glu Gln Tyr Asn Asn Ala Ser Arg Val Val Ser Val 420 425 430 Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 435 440 445 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 450 455 460 Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro 465 470 475 480 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val 485 490 495 Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 500 505 510 Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Val Leu Asp Ser Asp 515 520 525 Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 530 535 540 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 545 550 555 560 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 565 570 <210> 67 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 67 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Met Tyr Ser Glu Thr Ala Phe 65 70 75 80 Leu Glu Leu Arg Ser Leu Thr Ser Asp Asp Thr Ala Val Tyr Phe Cys 85 90 95 Thr Arg Gly Lys Tyr Cys Thr Ala Arg Asp Tyr Tyr Asn Trp Asp Phe 100 105 110 Glu His Trp Gly Gin Gly Thr Pro Val Thr Val Ser Ser Ala Ser Thr 115 120 125 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 130 135 140 Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 145 150 155 160 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 165 170 175 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 180 185 190 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 195 200 205 Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 210 215 220 Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 225 230 235 240 Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Lys Pro Lys 245 250 255 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 260 265 270 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 275 280 285 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 290 295 300 Asn Asn Ala Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 305 310 315 320 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 325 330 335 Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 340 345 350 Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys 355 360 365 Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 370 375 380 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 385 390 395 400 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 405 410 415 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 420 425 430 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 435 440 445 Leu Ser Leu Ser Pro Gly 450 <210> 68 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 68 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 69 <211> 338 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 69 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Asn 20 25 30 Asn Ala Asn Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Gly Gln Pro Lys Ala Ala Pro Asp Ile Gln Met Thr Gln Ser Pro Ser 115 120 125 Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala 130 135 140 Ser Gln Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly 145 150 155 160 Lys Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly 165 170 175 Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 180 185 190 Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln 195 200 205 Gln Gly Gln Thr Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu 210 215 220 Ile Lys Thr Lys Gly Pro Ser Arg Thr Val Ala Ala Pro Ser Val Phe 225 230 235 240 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 245 250 255 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 260 265 270 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 275 280 285 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 290 295 300 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 305 310 315 320 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 325 330 335 Glu Cys <210> 70 <211> 570 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 70 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 340 345 350 Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro 355 360 365 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 370 375 380 Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 385 390 395 400 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 405 410 415 Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 420 425 430 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 435 440 445 Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 450 455 460 Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Gln Glu 465 470 475 480 Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 485 490 495 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 500 505 510 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 515 520 525 Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 530 535 540 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 545 550 555 560 Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 565 570 <210> 71 <211> 451 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 71 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Met Tyr Ser Glu Thr Ala Phe 65 70 75 80 Leu Glu Leu Arg Ser Leu Thr Ser Asp Asp Thr Ala Val Tyr Phe Cys 85 90 95 Thr Arg Gly Lys Tyr Cys Thr Ala Arg Asp Tyr Tyr Asn Trp Asp Phe 100 105 110 Glu His Trp Gly Gin Gly Thr Pro Val Thr Val Ser Ser Ala Ser Thr 115 120 125 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser 130 135 140 Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 145 150 155 160 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 165 170 175 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 180 185 190 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys 195 200 205 Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 210 215 220 Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 225 230 235 240 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 245 250 255 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 260 265 270 Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 275 280 285 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 290 295 300 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 305 310 315 320 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 325 330 335 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 340 345 350 Val Tyr Thr Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val 355 360 365 Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 370 375 380 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 385 390 395 400 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 405 410 415 Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 420 425 430 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 435 440 445 Ser Leu Gly 450 <210> 72 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 72 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 73 <211> 338 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 73 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Gln 20 25 30 Asn Ala Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Gly Gln Pro Lys Ala Ala Pro Asp Ile Gln Met Thr Gln Ser Pro Ser 115 120 125 Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala 130 135 140 Ser Gln Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly 145 150 155 160 Lys Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly 165 170 175 Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 180 185 190 Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln 195 200 205 Gln Gly Gln Thr Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu 210 215 220 Ile Lys Thr Lys Gly Pro Ser Arg Thr Val Ala Ala Pro Ser Val Phe 225 230 235 240 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 245 250 255 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 260 265 270 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 275 280 285 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 290 295 300 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 305 310 315 320 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 325 330 335 Glu Cys <210> 74 <211> 570 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 74 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 340 345 350 Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro 355 360 365 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 370 375 380 Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 385 390 395 400 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 405 410 415 Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 420 425 430 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 435 440 445 Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 450 455 460 Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Gln Glu 465 470 475 480 Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 485 490 495 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 500 505 510 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 515 520 525 Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 530 535 540 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 545 550 555 560 Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 565 570 <210> 75 <211> 451 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 75 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Met Tyr Ser Glu Thr Ala Phe 65 70 75 80 Leu Glu Leu Arg Ser Leu Thr Ser Asp Asp Thr Ala Val Tyr Phe Cys 85 90 95 Thr Arg Gly Lys Tyr Cys Thr Ala Arg Asp Tyr Tyr Asn Trp Asp Phe 100 105 110 Glu His Trp Gly Gin Gly Thr Pro Val Thr Val Ser Ser Ala Ser Thr 115 120 125 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser 130 135 140 Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 145 150 155 160 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 165 170 175 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 180 185 190 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys 195 200 205 Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 210 215 220 Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 225 230 235 240 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 245 250 255 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 260 265 270 Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 275 280 285 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 290 295 300 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 305 310 315 320 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 325 330 335 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 340 345 350 Val Tyr Thr Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val 355 360 365 Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 370 375 380 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 385 390 395 400 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 405 410 415 Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 420 425 430 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 435 440 445 Ser Leu Gly 450 <210> 76 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 76 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 77 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 77 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Gln 20 25 30 Asn Ala Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 78 <211> 570 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 78 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 340 345 350 Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro 355 360 365 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 370 375 380 Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 385 390 395 400 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 405 410 415 Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 420 425 430 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 435 440 445 Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 450 455 460 Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Gln Glu 465 470 475 480 Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 485 490 495 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 500 505 510 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 515 520 525 Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 530 535 540 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 545 550 555 560 Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 565 570 <210> 79 <211> 451 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 79 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Met Tyr Ser Glu Thr Ala Phe 65 70 75 80 Leu Glu Leu Arg Ser Leu Thr Ser Asp Asp Thr Ala Val Tyr Phe Cys 85 90 95 Thr Arg Gly Lys Tyr Cys Thr Ala Arg Asp Tyr Tyr Asn Trp Asp Phe 100 105 110 Glu His Trp Gly Gin Gly Thr Pro Val Thr Val Ser Ser Ala Ser Thr 115 120 125 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser 130 135 140 Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 145 150 155 160 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 165 170 175 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 180 185 190 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys 195 200 205 Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu 210 215 220 Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 225 230 235 240 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 245 250 255 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 260 265 270 Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu 275 280 285 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr 290 295 300 Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 305 310 315 320 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser 325 330 335 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 340 345 350 Val Tyr Thr Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val 355 360 365 Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 370 375 380 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 385 390 395 400 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 405 410 415 Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val 420 425 430 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 435 440 445 Ser Leu Gly 450 <210> 80 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 80 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 81 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 81 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Gln 20 25 30 Asn Ala Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 82 <211> 580 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 82 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 325 330 335 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 340 345 350 Ser Cys Asp Lys Thr His Thr Cys Pro Cys Pro Ala Pro Glu Leu 355 360 365 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 370 375 380 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 385 390 395 400 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 405 410 415 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Asn 420 425 430 Ala Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 435 440 445 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 450 455 460 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 465 470 475 480 Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 485 490 495 Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 500 505 510 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 515 520 525 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 530 535 540 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 545 550 555 560 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 565 570 575 Leu Ser Pro Gly 580 <210> 83 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 83 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Asp Met Tyr Ser Glu Thr Ala Phe 65 70 75 80 Leu Glu Leu Arg Ser Leu Thr Ser Asp Asp Thr Ala Val Tyr Phe Cys 85 90 95 Thr Arg Gly Lys Tyr Cys Thr Ala Arg Asp Tyr Tyr Asn Trp Asp Phe 100 105 110 Glu His Trp Gly Gin Gly Thr Pro Val Thr Val Ser Ser Ala Ser Thr 115 120 125 Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 130 135 140 Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 145 150 155 160 Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 165 170 175 Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 180 185 190 Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 195 200 205 Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 210 215 220 Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 225 230 235 240 Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Lys Pro Lys 245 250 255 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 260 265 270 Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 275 280 285 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 290 295 300 Asn Asn Ala Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 305 310 315 320 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 325 330 335 Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 340 345 350 Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys 355 360 365 Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 370 375 380 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 385 390 395 400 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 405 410 415 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 420 425 430 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 435 440 445 Leu Ser Leu Ser Pro Gly 450 <210> 84 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 84 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 85 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 85 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 86 <211> 570 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 86 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 340 345 350 Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro 355 360 365 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 370 375 380 Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 385 390 395 400 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 405 410 415 Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 420 425 430 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 435 440 445 Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 450 455 460 Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Gln Glu 465 470 475 480 Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 485 490 495 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 500 505 510 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 515 520 525 Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 530 535 540 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 545 550 555 560 Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 565 570 <210> 87 <211> 458 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 87 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Thr Ala Phe Leu Glu Leu Arg Ser Leu Thr Ser Asp 85 90 95 Asp Thr Ala Val Tyr Phe Cys Thr Arg Gly Lys Tyr Cys Thr Ala Arg 100 105 110 Asp Tyr Tyr Asn Trp Asp Phe Glu His Trp Gly Gln Gly Thr Pro Val 115 120 125 Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 130 135 140 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 145 150 155 160 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 165 170 175 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 180 185 190 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 195 200 205 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 210 215 220 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 225 230 235 240 Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro 245 250 255 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 260 265 270 Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 275 280 285 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 290 295 300 Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 305 310 315 320 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 325 330 335 Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 340 345 350 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Gln Glu 355 360 365 Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe 370 375 380 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 385 390 395 400 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 405 410 415 Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 420 425 430 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 435 440 445 Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 450 455 <210> 88 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 88 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 89 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 89 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Phe Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 90 <211> 570 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 90 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 340 345 350 Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro 355 360 365 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 370 375 380 Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 385 390 395 400 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 405 410 415 Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 420 425 430 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 435 440 445 Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 450 455 460 Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Gln Glu 465 470 475 480 Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 485 490 495 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 500 505 510 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 515 520 525 Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 530 535 540 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 545 550 555 560 Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 565 570 <210> 91 <211> 458 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 91 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Thr Ala Phe Leu Glu Leu Arg Ser Leu Thr Ser Asp 85 90 95 Asp Thr Ala Val Tyr Phe Cys Thr Arg Gly Lys Tyr Cys Thr Ala Arg 100 105 110 Asp Tyr Tyr Asn Trp Asp Phe Glu His Trp Gly Gln Gly Thr Pro Val 115 120 125 Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 130 135 140 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 145 150 155 160 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 165 170 175 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 180 185 190 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 195 200 205 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 210 215 220 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 225 230 235 240 Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro 245 250 255 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 260 265 270 Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 275 280 285 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 290 295 300 Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 305 310 315 320 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 325 330 335 Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 340 345 350 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Gln Glu 355 360 365 Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe 370 375 380 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 385 390 395 400 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 405 410 415 Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 420 425 430 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 435 440 445 Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 450 455 <210> 92 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 92 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 93 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 93 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 94 <211> 580 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 94 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 325 330 335 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 340 345 350 Ser Cys Asp Lys Thr His Thr Cys Pro Cys Pro Ala Pro Glu Leu 355 360 365 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 370 375 380 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 385 390 395 400 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 405 410 415 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Asn 420 425 430 Ala Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 435 440 445 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 450 455 460 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 465 470 475 480 Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 485 490 495 Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 500 505 510 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 515 520 525 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 530 535 540 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 545 550 555 560 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 565 570 575 Leu Ser Pro Gly 580 <210> 95 <211> 461 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 95 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Thr Ala Phe Leu Glu Leu Arg Ser Leu Thr Ser Asp 85 90 95 Asp Thr Ala Val Tyr Phe Cys Thr Arg Gly Lys Tyr Cys Thr Ala Arg 100 105 110 Asp Tyr Tyr Asn Trp Asp Phe Glu His Trp Gly Gln Gly Thr Pro Val 115 120 125 Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 130 135 140 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 145 150 155 160 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 165 170 175 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 180 185 190 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 195 200 205 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 210 215 220 Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 225 230 235 240 Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 245 250 255 Leu Phe Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 260 265 270 Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 275 280 285 Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 290 295 300 Lys Pro Arg Glu Glu Gln Tyr Asn Asn Ala Ser Arg Val Val Ser Val 305 310 315 320 Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 325 330 335 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 340 345 350 Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 355 360 365 Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val 370 375 380 Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 385 390 395 400 Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Val Leu Asp Ser Asp 405 410 415 Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 420 425 430 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 435 440 445 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 450 455 460 <210> 96 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 96 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 97 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 97 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Phe Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 98 <211> 580 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 98 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 325 330 335 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 340 345 350 Ser Cys Asp Lys Thr His Thr Cys Pro Cys Pro Ala Pro Glu Leu 355 360 365 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 370 375 380 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 385 390 395 400 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 405 410 415 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Asn 420 425 430 Ala Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 435 440 445 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 450 455 460 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 465 470 475 480 Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 485 490 495 Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 500 505 510 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 515 520 525 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 530 535 540 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 545 550 555 560 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 565 570 575 Leu Ser Pro Gly 580 <210> 99 <211> 461 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 99 Gln Val Arg Leu Ser Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Asp 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asn Cys 20 25 30 Pro Ile Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Met Lys Pro Arg His Gly Ala Val Ser Tyr Ala Arg Gln Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Thr Ala Phe Leu Glu Leu Arg Ser Leu Thr Ser Asp 85 90 95 Asp Thr Ala Val Tyr Phe Cys Thr Arg Gly Lys Tyr Cys Thr Ala Arg 100 105 110 Asp Tyr Tyr Asn Trp Asp Phe Glu His Trp Gly Gln Gly Thr Pro Val 115 120 125 Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 130 135 140 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 145 150 155 160 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 165 170 175 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 180 185 190 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 195 200 205 Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 210 215 220 Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 225 230 235 240 Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 245 250 255 Leu Phe Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 260 265 270 Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 275 280 285 Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 290 295 300 Lys Pro Arg Glu Glu Gln Tyr Asn Asn Ala Ser Arg Val Val Ser Val 305 310 315 320 Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 325 330 335 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 340 345 350 Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 355 360 365 Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val 370 375 380 Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 385 390 395 400 Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Val Leu Asp Ser Asp 405 410 415 Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 420 425 430 Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 435 440 445 Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 450 455 460 <210> 100 <211> 208 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 100 Ser Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr 1 5 10 15 Ala Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr 20 25 30 Gln Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser 35 40 45 Thr Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly 50 55 60 Pro Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly 65 70 75 80 Val Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val 85 90 95 Gln Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 100 105 110 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 115 120 125 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 130 135 140 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 145 150 155 160 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 165 170 175 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 180 185 190 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 101 <211> 338 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 101 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Asn 20 25 30 Asn Ala Asn Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Gly Gln Pro Lys Ala Ala Pro Asp Ile Gln Met Thr Gln Ser Pro Ser 115 120 125 Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala 130 135 140 Ser Gln Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly 145 150 155 160 Lys Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly 165 170 175 Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 180 185 190 Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln 195 200 205 Gln Gly Gln Thr Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu 210 215 220 Ile Lys Thr Lys Gly Pro Ser Arg Thr Val Ala Ala Pro Ser Val Phe 225 230 235 240 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 245 250 255 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 260 265 270 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 275 280 285 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 290 295 300 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 305 310 315 320 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 325 330 335 Glu Cys <210> 102 <211> 569 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 102 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 340 345 350 Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro 355 360 365 Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 370 375 380 Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp 385 390 395 400 Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 405 410 415 Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 420 425 430 His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 435 440 445 Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 450 455 460 Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Gln Glu Glu 465 470 475 480 Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 485 490 495 Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 500 505 510 Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 515 520 525 Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn 530 535 540 Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 545 550 555 560 Gln Lys Ser Leu Ser Leu Ser Leu Gly 565 <210> 103 <211> 447 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 103 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser 225 230 235 240 Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 245 250 255 Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 260 265 270 Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 275 280 285 Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 290 295 300 Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 305 310 315 320 Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 325 330 335 Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 340 345 350 Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 355 360 365 Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 370 375 380 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 385 390 395 400 Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 405 410 415 Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 420 425 430 Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 104 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 104 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 105 <211> 338 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 105 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Asn 20 25 30 Asn Ala Asn Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Gly Gln Pro Lys Ala Ala Pro Asp Ile Gln Met Thr Gln Ser Pro Ser 115 120 125 Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala 130 135 140 Ser Gln Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly 145 150 155 160 Lys Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly 165 170 175 Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 180 185 190 Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln 195 200 205 Gln Gly Gln Thr Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu 210 215 220 Ile Lys Thr Lys Gly Pro Ser Arg Thr Val Ala Ala Pro Ser Val Phe 225 230 235 240 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 245 250 255 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 260 265 270 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 275 280 285 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 290 295 300 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 305 310 315 320 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 325 330 335 Glu Cys <210> 106 <211> 570 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 106 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 340 345 350 Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro 355 360 365 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 370 375 380 Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 385 390 395 400 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 405 410 415 Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 420 425 430 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 435 440 445 Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 450 455 460 Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Gln Glu 465 470 475 480 Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 485 490 495 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 500 505 510 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 515 520 525 Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 530 535 540 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 545 550 555 560 Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 565 570 <210> 107 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 107 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 108 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 108 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 109 <211> 338 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 109 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Gln 20 25 30 Asn Ala Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Gly Gln Pro Lys Ala Ala Pro Asp Ile Gln Met Thr Gln Ser Pro Ser 115 120 125 Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala 130 135 140 Ser Gln Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly 145 150 155 160 Lys Ala Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly 165 170 175 Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 180 185 190 Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln 195 200 205 Gln Gly Gln Thr Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu 210 215 220 Ile Lys Thr Lys Gly Pro Ser Arg Thr Val Ala Ala Pro Ser Val Phe 225 230 235 240 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 245 250 255 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 260 265 270 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 275 280 285 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 290 295 300 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 305 310 315 320 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 325 330 335 Glu Cys <210> 110 <211> 570 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 110 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Ser Gln Val Gln Leu Val Glu Ser 115 120 125 Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala 130 135 140 Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His Trp Val Arg Gln 145 150 155 160 Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile Lys Asp Lys Ser 165 170 175 Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 180 185 190 Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 195 200 205 Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg Gly Val Tyr Tyr 210 215 220 Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 225 230 235 240 Ser Ser Arg Thr Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 245 250 255 Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu 260 265 270 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 275 280 285 Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 290 295 300 Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 305 310 315 320 Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr 325 330 335 Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro 340 345 350 Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro 355 360 365 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 370 375 380 Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn 385 390 395 400 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 405 410 415 Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 420 425 430 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 435 440 445 Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys 450 455 460 Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Gln Glu 465 470 475 480 Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe 485 490 495 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 500 505 510 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 515 520 525 Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly 530 535 540 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 545 550 555 560 Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 565 570 <210> 111 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 111 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 112 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 112 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 113 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 113 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Gln 20 25 30 Asn Ala Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 114 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 114 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 115 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 115 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 116 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 116 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 117 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 117 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Asn 20 25 30 Asn Ala Asn Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 118 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 118 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 119 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 119 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 120 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 120 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 121 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 121 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Gln 20 25 30 Asn Ala Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 122 <211> 580 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 122 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 325 330 335 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 340 345 350 Ser Cys Asp Lys Thr His Thr Cys Pro Cys Pro Ala Pro Glu Leu 355 360 365 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 370 375 380 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 385 390 395 400 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 405 410 415 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Asn 420 425 430 Ala Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 435 440 445 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 450 455 460 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 465 470 475 480 Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 485 490 495 Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 500 505 510 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 515 520 525 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 530 535 540 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 545 550 555 560 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 565 570 575 Leu Ser Pro Gly 580 <210> 123 <211> 451 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 123 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser 210 215 220 Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 225 230 235 240 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 245 250 255 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 260 265 270 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 275 280 285 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Asn Ala 290 295 300 Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 305 310 315 320 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 325 330 335 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 340 345 350 Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val 355 360 365 Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 370 375 380 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 385 390 395 400 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 405 410 415 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 420 425 430 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 435 440 445 Ser Pro Gly 450 <210> 124 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 124 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 125 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 125 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Asp 20 25 30 Asn Ala Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 126 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 126 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 127 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 127 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 128 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 128 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 129 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 129 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 130 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 130 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 131 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 131 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 132 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 132 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 133 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 133 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Arg Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 134 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 134 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 135 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 135 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 136 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 136 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 137 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 137 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Phe Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 138 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 138 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 139 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 139 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 140 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 140 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 141 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 141 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 142 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 142 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 143 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 143 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Thr Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 144 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 144 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Ser Glu Glu Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 145 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 145 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Phe Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 146 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 146 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 147 <211> 448 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 147 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Thr Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 210 215 220 Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro 225 230 235 240 Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 245 250 255 Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 260 265 270 Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 275 280 285 Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 290 295 300 Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 305 310 315 320 Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 325 330 335 Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 340 345 350 Leu Pro Pro Cys Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp 355 360 365 Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 370 375 380 Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 385 390 395 400 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys 405 410 415 Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 420 425 430 Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 435 440 445 <210> 148 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 148 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Ser Glu Glu Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 149 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 149 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Phe Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 150 <211> 580 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 150 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 325 330 335 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 340 345 350 Ser Cys Asp Lys Thr His Thr Cys Pro Cys Pro Ala Pro Glu Leu 355 360 365 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 370 375 380 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 385 390 395 400 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 405 410 415 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Asn 420 425 430 Ala Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 435 440 445 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 450 455 460 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 465 470 475 480 Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 485 490 495 Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 500 505 510 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 515 520 525 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 530 535 540 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 545 550 555 560 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 565 570 575 Leu Ser Pro Gly 580 <210> 151 <211> 451 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 151 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Thr Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Asp Val Tyr Arg Glu Ile Ala Tyr 65 70 75 80 Met Asp Ile Arg Gly Leu Lys Pro Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Arg Ser Tyr Gly Asp Ser Ser Trp Ala Leu Asp Ala Trp 100 105 110 Gly Gln Gly Thr Thr Val Val Val Ser Ala Ala Ser Thr Lys Gly Pro 115 120 125 Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 130 135 140 Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 145 150 155 160 Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 165 170 175 Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 180 185 190 Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 195 200 205 His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser 210 215 220 Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 225 230 235 240 Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 245 250 255 Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 260 265 270 His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 275 280 285 Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Asn Ala 290 295 300 Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 305 310 315 320 Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 325 330 335 Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 340 345 350 Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val 355 360 365 Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 370 375 380 Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 385 390 395 400 Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 405 410 415 Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 420 425 430 Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 435 440 445 Ser Pro Gly 450 <210> 152 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 152 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Ser Glu Glu Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 153 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 153 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 154 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 154 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 155 <211> 455 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 155 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Ile Ala Tyr Met Asp Ile Arg Gly Leu Lys Pro Asp 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Ser Tyr Gly Asp Ser 100 105 110 Ser Trp Ala Leu Asp Ala Trp Gly Gin Gly Thr Thr Val Val Val Ser 115 120 125 Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser 130 135 140 Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 145 150 155 160 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 165 170 175 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 180 185 190 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys 195 200 205 Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp 210 215 220 Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala 225 230 235 240 Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 245 250 255 Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 260 265 270 Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 275 280 285 Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 290 295 300 Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 305 310 315 320 Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 325 330 335 Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 340 345 350 Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Gln Glu Glu Met Thr 355 360 365 Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 370 375 380 Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 385 390 395 400 Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 405 410 415 Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe 420 425 430 Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 435 440 445 Ser Leu Ser Leu Ser Leu Gly 450 455 <210> 156 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 156 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 157 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 157 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Phe Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 158 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 158 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 159 <211> 455 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 159 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Ile Ala Tyr Met Asp Ile Arg Gly Leu Lys Pro Asp 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Ser Tyr Gly Asp Ser 100 105 110 Ser Trp Ala Leu Asp Ala Trp Gly Gin Gly Thr Thr Val Val Val Ser 115 120 125 Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser 130 135 140 Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 145 150 155 160 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 165 170 175 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 180 185 190 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys 195 200 205 Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp 210 215 220 Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala 225 230 235 240 Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 245 250 255 Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 260 265 270 Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 275 280 285 Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 290 295 300 Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 305 310 315 320 Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 325 330 335 Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 340 345 350 Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Gln Glu Glu Met Thr 355 360 365 Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 370 375 380 Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 385 390 395 400 Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 405 410 415 Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe 420 425 430 Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 435 440 445 Ser Leu Ser Leu Ser Leu Gly 450 455 <210> 160 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 160 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 161 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 161 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 162 <211> 580 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 162 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 325 330 335 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 340 345 350 Ser Cys Asp Lys Thr His Thr Cys Pro Cys Pro Ala Pro Glu Leu 355 360 365 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 370 375 380 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 385 390 395 400 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 405 410 415 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Asn 420 425 430 Ala Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 435 440 445 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 450 455 460 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 465 470 475 480 Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 485 490 495 Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 500 505 510 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 515 520 525 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 530 535 540 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 545 550 555 560 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 565 570 575 Leu Ser Pro Gly 580 <210> 163 <211> 458 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 163 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Ile Ala Tyr Met Asp Ile Arg Gly Leu Lys Pro Asp 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Ser Tyr Gly Asp Ser 100 105 110 Ser Trp Ala Leu Asp Ala Trp Gly Gin Gly Thr Thr Val Val Val Ser 115 120 125 Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 130 135 140 Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 145 150 155 160 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 165 170 175 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 180 185 190 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 195 200 205 Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 210 215 220 Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro 225 230 235 240 Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 245 250 255 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 260 265 270 Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 275 280 285 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 290 295 300 Glu Glu Gln Tyr Asn Asn Ala Ser Arg Val Val Ser Val Leu Thr Val 305 310 315 320 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 325 330 335 Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 340 345 350 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp 355 360 365 Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe 370 375 380 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 385 390 395 400 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 405 410 415 Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 420 425 430 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 435 440 445 Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 450 455 <210> 164 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 164 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 165 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 165 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Phe Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 166 <211> 580 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 166 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 325 330 335 Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys 340 345 350 Ser Cys Asp Lys Thr His Thr Cys Pro Cys Pro Ala Pro Glu Leu 355 360 365 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 370 375 380 Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 385 390 395 400 Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 405 410 415 Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Asn 420 425 430 Ala Ser Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 435 440 445 Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 450 455 460 Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 465 470 475 480 Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 485 490 495 Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 500 505 510 Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 515 520 525 Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 530 535 540 Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 545 550 555 560 Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 565 570 575 Leu Ser Pro Gly 580 <210> 167 <211> 458 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 167 Arg Ala His Leu Val Gln Ser Gly Thr Ala Met Lys Lys Pro Gly Ala 1 5 10 15 Ser Val Arg Val Ser Cys Gln Thr Ser Gly Tyr Thr Phe Thr Ala His 20 25 30 Ile Leu Phe Trp Phe Arg Gln Ala Pro Gly Arg Gly Leu Glu Trp Val 35 40 45 Gly Trp Ile Lys Pro Gln Tyr Gly Ala Val Asn Phe Gly Gly Gly Phe 50 55 60 Arg Asp Arg Val Thr Leu Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Ile Ala Tyr Met Asp Ile Arg Gly Leu Lys Pro Asp 85 90 95 Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Ser Tyr Gly Asp Ser 100 105 110 Ser Trp Ala Leu Asp Ala Trp Gly Gin Gly Thr Thr Val Val Val Ser 115 120 125 Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 130 135 140 Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 145 150 155 160 Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 165 170 175 Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 180 185 190 Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 195 200 205 Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 210 215 220 Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro 225 230 235 240 Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 245 250 255 Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 260 265 270 Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 275 280 285 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 290 295 300 Glu Glu Gln Tyr Asn Asn Ala Ser Arg Val Val Ser Val Leu Thr Val 305 310 315 320 Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 325 330 335 Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 340 345 350 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp 355 360 365 Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe 370 375 380 Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 385 390 395 400 Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 405 410 415 Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 420 425 430 Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 435 440 445 Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 450 455 <210> 168 <211> 210 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 168 Tyr Ile His Val Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Ile Gly 1 5 10 15 Asp Arg Val Thr Ile Asn Cys Gln Thr Ser Gln Gly Val Gly Ser Asp 20 25 30 Leu His Trp Tyr Gln His Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 His His Thr Ser Ser Val Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Phe His Thr Ser Phe Asn Leu Thr Ile Ser Asp Leu Gln Ala 65 70 75 80 Asp Asp Ile Ala Thr Tyr Tyr Cys Gln Val Leu Gln Phe Phe Gly Arg 85 90 95 Gly Ser Arg Leu His Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe 100 105 110 Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val 115 120 125 Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp 130 135 140 Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr 145 150 155 160 Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr 165 170 175 Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val 180 185 190 Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly 195 200 205 Glu Cys 210 <210> 169 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 169 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Gln Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 170 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 170 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 171 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 171 Gln Val Gln Leu Val Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Glu 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asp Cys 20 25 30 Thr Leu Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Leu Lys Pro Arg Trp Gly Ala Val Asn Tyr Ala Arg Pro Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Thr Ala Phe Leu Glu Leu Arg Ser Leu Thr Val Asp 85 90 95 Asp Thr Ala Val Tyr Phe Cys Thr Arg Gly Lys Asn Cys Asp Tyr Asn 100 105 110 Trp Asp Phe Glu His Trp Gly Arg Gly Thr Pro Val Ile Val Ser Ser 115 120 125 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 130 135 140 Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 145 150 155 160 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 165 170 175 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 180 185 190 Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 195 200 205 Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 210 215 220 Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 225 230 235 240 Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 245 250 255 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 260 265 270 Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 275 280 285 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 290 295 300 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 305 310 315 320 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 325 330 335 Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gly Gln Pro Arg 340 345 350 Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Gln Glu Glu Met Thr Lys 355 360 365 Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 370 375 380 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 385 390 395 400 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 405 410 415 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 420 425 430 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 435 440 445 Leu Ser Leu Ser Leu Gly 450 <210> 172 <211> 207 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 172 Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr Ala 1 5 10 15 Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr Gln 20 25 30 Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser Thr 35 40 45 Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly Pro 50 55 60 Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly Val 65 70 75 80 Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val Gln 85 90 95 Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 100 105 110 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 115 120 125 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 130 135 140 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 145 150 155 160 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 165 170 175 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 180 185 190 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 173 <211> 336 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 173 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Val His Glu 20 25 30 Asn Leu Phe Thr Tyr Leu Ser Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Ser Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 50 55 60 Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gly Gln Gly 85 90 95 Thr Gln Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Val Glu Ile Lys 100 105 110 Asp Lys Thr His Thr Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu 115 120 125 Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln 130 135 140 Asn Ile Tyr Val Trp Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala 145 150 155 160 Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu His Thr Gly Val Pro 165 170 175 Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile 180 185 190 Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly 195 200 205 Gln Thr Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 210 215 220 Asp Lys Thr His Thr Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 225 230 235 240 Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 245 250 255 Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 260 265 270 Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 275 280 285 Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 290 295 300 Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 305 310 315 320 Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 325 330 335 <210> 174 <211> 577 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 174 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr 20 25 30 Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 35 40 45 Gly Ser Ile Tyr Pro Gly Asn Val Asn Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Ile Ser Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Thr Arg Ser His Tyr Gly Leu Asp Trp Asn Phe Asp Val Trp Gly Lys 100 105 110 Gly Thr Thr Val Thr Val Ser Ser Asp Lys Thr His Thr Gln Val Gln 115 120 125 Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg 130 135 140 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Thr Lys Ala Trp Met His 145 150 155 160 Trp Val Arg Gln Ala Pro Gly Lys Gln Leu Glu Trp Val Ala Gln Ile 165 170 175 Lys Asp Lys Ser Asn Ser Tyr Ala Thr Tyr Tyr Ala Asp Ser Val Lys 180 185 190 Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Leu Tyr Leu 195 200 205 Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Arg 210 215 220 Gly Val Tyr Tyr Ala Leu Ser Pro Phe Asp Tyr Trp Gly Gln Gly Thr 225 230 235 240 Leu Val Thr Val Ser Ser Asp Lys Thr His Thr Ala Ser Thr Lys Gly 245 250 255 Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser 260 265 270 Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 275 280 285 Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 290 295 300 Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 305 310 315 320 Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val 325 330 335 Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys 340 345 350 Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly 355 360 365 Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 370 375 380 Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu 385 390 395 400 Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 405 410 415 Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg 420 425 430 Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 435 440 445 Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu 450 455 460 Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 465 470 475 480 Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu 485 490 495 Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 500 505 510 Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 515 520 525 Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 530 535 540 Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His 545 550 555 560 Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu 565 570 575 Gly <210> 175 <211> 454 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 175 Gln Val Gln Leu Val Gln Ser Gly Gly Gln Met Lys Lys Pro Gly Glu 1 5 10 15 Ser Met Arg Ile Ser Cys Arg Ala Ser Gly Tyr Glu Phe Ile Asp Cys 20 25 30 Thr Leu Asn Trp Ile Arg Leu Ala Pro Gly Lys Arg Pro Glu Trp Met 35 40 45 Gly Trp Leu Lys Pro Arg Trp Gly Ala Val Asn Tyr Ala Arg Pro Leu 50 55 60 Gln Gly Arg Val Thr Met Thr Arg Gln Leu Ser Gln Asp Pro Asp Asp 65 70 75 80 Pro Asp Trp Gly Thr Ala Phe Leu Glu Leu Arg Ser Leu Thr Val Asp 85 90 95 Asp Thr Ala Val Tyr Phe Cys Thr Arg Gly Lys Asn Cys Asp Tyr Asn 100 105 110 Trp Asp Phe Glu His Trp Gly Arg Gly Thr Pro Val Ile Val Ser Ser 115 120 125 Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 130 135 140 Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 145 150 155 160 Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 165 170 175 Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 180 185 190 Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 195 200 205 Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 210 215 220 Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 225 230 235 240 Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 245 250 255 Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 260 265 270 Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 275 280 285 Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 290 295 300 Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 305 310 315 320 Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 325 330 335 Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gly Gln Pro Arg 340 345 350 Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Gln Glu Glu Met Thr Lys 355 360 365 Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 370 375 380 Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 385 390 395 400 Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 405 410 415 Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 420 425 430 Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 435 440 445 Leu Ser Leu Ser Leu Gly 450 <210> 176 <211> 207 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 176 Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Thr Ala 1 5 10 15 Ile Ile Ser Cys Arg Thr Ser Gln Tyr Gly Ser Leu Ala Trp Tyr Gln 20 25 30 Gln Arg Pro Gly Gln Ala Pro Arg Leu Val Ile Tyr Ser Gly Ser Thr 35 40 45 Arg Ala Ala Gly Ile Pro Asp Arg Phe Ser Gly Ser Arg Trp Gly Pro 50 55 60 Asp Tyr Asn Leu Thr Ile Ser Asn Leu Glu Ser Gly Asp Phe Gly Val 65 70 75 80 Tyr Tyr Cys Gln Gln Tyr Glu Phe Phe Gly Gln Gly Thr Lys Val Gln 85 90 95 Val Asp Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro 100 105 110 Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu 115 120 125 Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp 130 135 140 Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp 145 150 155 160 Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys 165 170 175 Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln 180 185 190 Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 195 200 205 <210> 177 <211> 1014 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 177 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacaacaacg ccaacaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaagggcc agcccaaggc cgccccccgac 360 atccagatga cccagagccc cagcagcctg tctgccagcg tgggcgacag agtgaccatc 420 acctgtcagg ccagccagaa catctacgtg tggctgaact ggtatcagca gaagcccggc 480 aaggccccca agctgctgat ctacaaggcc agcaacctgc acaccggcgt gcccagcaga 540 ttttctggca gcggctccgg caccgacttc accctgacaa tcagctccct gcagcccgag 600 gacattgcca cctactactg ccagcagggc cagacctacc cctacacctt tggccagggc 660 accaagctgg aaatcaagac caagggcccc agccgtacgg tggccgctcc cagcgtgttc 720 atcttcccac ctagcgacga gcagctgaag tccggcacag cctctgtcgt gtgcctgctg 780 aacaacttct acccccgcga ggccaaagtg cagtggaagg tggacaacgc cctgcagagc 840 ggcaacagcc aggaaagcgt gaccgagcag gacagcaagg actccaccta cagcctgagc 900 agcaccctga cactgagcaa ggccgactac gagaagcaca aggtgtacgc ctgcgaagtg 960 acccaccagg gcctgtctag ccccgtgacc aagagcttca accggggcga gtgt 1014 <210> 178 <211> 1725 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 178 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 agccaggtgc agctggtgga atctggcggc ggagtggtgc agcctggcag aagcctgaga 420 ctgagctgtg ccgccagcgg cttcaccttc accaaggcct ggatgcactg ggtgcgccag 480 gcccctggaa agcagctgga atgggtggcc cagatcaagg acaagagcaa cagctacgcc 540 acctactacg ccgacagcgt gaagggccgg ttcaccatca gccgggacga cagcaagaac 600 accctgtacc tgcagatgaa cagcctgcgg gccgaggaca ccgccgtgta ctactgtcgg 660 ggcgtgtact atgccctgag ccccttcgat tactggggcc agggaaccct cgtgaccgtg 720 tctagtcgga ccgccagcac aaagggcccc agcgtgttcc ctctggcccc tagcagcaag 780 agcacatctg gcggaacagc cgccctgggc tgcctcgtga aggactactt tcccgagccc 840 gtgaccgtgt cctggaattc tggcgccctg accagcggcg tgcacacctt tccagctgtg 900 ctgcagtcca gcggcctgta cagcctgagc agcgtcgtga cagtgcccag cagctctctg 960 ggcacccaga cctacatctg caacgtgaac cacaagccca gcaacaccaa ggtggacaag 1020 aaggtggaac ccaagagctg cgacaagacc cacacctgtc ccccttgtcc tgccccccgaa 1080 gccgccggag gcccttccgt gttcctgttc cccccaaagc ccaaggacac cctgatgatc 1140 agccggaccc ccgaagtgac ctgcgtggtg gtggatgtgt cccacgagga ccctgaagtg 1200 aagttcaatt ggtacgtgga cggcgtggaa gtgcacaacg ccaagaccaa gccaagagag 1260 gaacagtaca acagcaccta ccgggtggtg tccgtgctga ccgtgctgca ccaggactgg 1320 ctgaacggca aagagtacaa gtgcaaggtg tccaacaagg ccctggccgc ccccatcgag 1380 aaaaccatca gcaaggccaa gggccagccc cgcgaacccc aggtgtgcac actgccccca 1440 agcagggacg agctgaccaa gaaccaggtg tccctgagct gtgccgtgaa aggcttctac 1500 ccctccgata tcgccgtgga atgggagagc aacggccagc ccgagaacaa ctacaagacc 1560 accccccctg tgctggacag cgacggctca ttcttcctgg tgtccaagct gacagtggac 1620 aagtcccggt ggcagcaggg caacgtgttc agctgctccg tgatgcacga ggccctgcac 1680 aaccactaca cccagaagtc cctgagcctg agccccggct agtga 1725 <210> 179 <211> 1362 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 179 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccgggaca tgtacagcga gacagccttc 240 ctggaactgc ggagcctgac cagcgacgat accgccgtgt acttctgcac ccggggcaag 300 tactgcaccg ccagagacta ctacaactgg gacttcgagc actggggcca gggcacacct 360 gtgacagtgt ctagcgcttc gaccaagggc cccagcgtgt tccctctggc ccctagcagc 420 aagagcacat ctggcggaac agccgccctg ggctgcctcg tgaaggacta ctttcccgag 480 cccgtgaccg tgtcctggaa ttctggcgcc ctgaccagcg gcgtgcacac ctttccagct 540 gtgctgcagt ccagcggcct gtacagcctg agcagcgtcg tgacagtgcc cagcagctct 600 ctgggcaccc agacctacat ctgcaacgtg aaccacaagc ccagcaacac caaggtggac 660 aagaaggtgg aacccaagag ctgcgacaag acccacacct gtcccccttg tcctgccccc 720 gaagccgccg gaggcccttc cgtgttcctg ttccccccaa agcccaagga caccctgatg 780 atcagccgga cccccgaagt gacctgcgtg gtggtggatg tgtccccacga ggaccctgaa 840 gtgaagttca attggtacgt ggacggcgtg gaagtgcaca acgccaagac caagccaaga 900 gaggaacagt acaacagcac ctaccgggtg gtgtccgtgc tgaccgtgct gcaccaggac 960 tggctgaacg gcaaagagta caagtgcaag gtgtccaaca aggccctggc cgcccccatc 1020 gagaaaacca tcagcaaggc caagggccag ccccgcgaac cccaggtgta cacactgccc 1080 ccatgcaggg acgagctgac caagaaccag gtgtccctgt ggtgtctggt gaaaggcttc 1140 tacccctccg atatcgccgt ggaatgggag agcaacggcc agcccgagaa caactacaag 1200 accacccccc ctgtgctgga cagcgacggc tcattcttcc tgtactccaa gctgacagtg 1260 gacaagtccc ggtggcagca gggcaacgtg ttcagctgct ccgtgatgca cgaggccctg 1320 cacaaccact accaccagaa gtccctgagc ctgagccccg gc 1362 <210> 180 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 180 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 181 <211> 1014 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 181 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacaacaacg ccaacaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaagggcc agcccaaggc cgccccccgac 360 atccagatga cccagagccc cagcagcctg tctgccagcg tgggcgacag agtgaccatc 420 acctgtcagg ccagccagaa catctacgtg tggctgaact ggtatcagca gaagcccggc 480 aaggccccca agctgctgat ctacaaggcc agcaacctgc acaccggcgt gcccagcaga 540 ttttctggca gcggctccgg caccgacttc accctgacaa tcagctccct gcagcccgag 600 gacattgcca cctactactg ccagcagggc cagacctacc cctacacctt tggccagggc 660 accaagctgg aaatcaagac caagggcccc agccgtacgg tggccgctcc cagcgtgttc 720 atcttcccac ctagcgacga gcagctgaag tccggcacag cctctgtcgt gtgcctgctg 780 aacaacttct acccccgcga ggccaaagtg cagtggaagg tggacaacgc cctgcagagc 840 ggcaacagcc aggaaagcgt gaccgagcag gacagcaagg actccaccta cagcctgagc 900 agcaccctga cactgagcaa ggccgactac gagaagcaca aggtgtacgc ctgcgaagtg 960 acccaccagg gcctgtctag ccccgtgacc aagagcttca accggggcga gtgt 1014 <210> 182 <211> 1719 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 182 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 agccaggtgc agctggtgga atctggcggc ggagtggtgc agcctggcag aagcctgaga 420 ctgagctgtg ccgccagcgg cttcaccttc accaaggcct ggatgcactg ggtgcgccag 480 gcccctggaa agcagctgga atgggtggcc cagatcaagg acaagagcaa cagctacgcc 540 acctactacg ccgacagcgt gaagggccgg ttcaccatca gccgggacga cagcaagaac 600 accctgtacc tgcagatgaa cagcctgcgg gccgaggaca ccgccgtgta ctactgtcgg 660 ggcgtgtact atgccctgag ccccttcgat tactggggcc agggaaccct cgtgaccgtg 720 tctagtcgga ccgccagcac aaagggcccc agcgtgttcc ctctggcccc tagcagcaag 780 agcacatctg gcggaacagc cgccctgggc tgcctcgtga aggactactt tcccgagccc 840 gtgaccgtgt cctggaattc tggcgccctg accagcggcg tgcacacctt tccagctgtg 900 ctgcagtcca gcggcctgta cagcctgagc agcgtcgtga cagtgcccag cagctctctg 960 ggcacccaga cctacatctg caacgtgaac cacaagccca gcaacaccaa ggtggacaag 1020 aaggtggaac ccaagagctg cgacaagacc cacacctgtc ccccttgtcc tgccccccgaa 1080 ctgctgggag gcccttccgt gttcctgttc cccccaaagc ccaaggacac cctgatgatc 1140 agccggaccc ccgaagtgac ctgcgtggtg gtggatgtgt cccacgagga ccctgaagtg 1200 aagttcaatt ggtacgtgga cggcgtggaa gtgcacaacg ccaagaccaa gccaagagag 1260 gaacagtaca acaatgcctc ccgggtggtg tccgtgctga ccgtgctgca ccaggactgg 1320 ctgaacggca aagagtacaa gtgcaaggtg tccaacaagg ccctgcctgc ccccatcgag 1380 aaaaccatca gcaaggccaa gggccagccc cgcgaacccc aggtgtgcac actgccccca 1440 agcagggacg agctgaccaa gaaccaggtg tccctgagct gtgccgtgaa aggcttctac 1500 ccctccgata tcgccgtgga atgggagagc aacggccagc ccgagaacaa ctacaagacc 1560 accccccctg tgctggacag cgacggctca ttcttcctgg tgtccaagct gacagtggac 1620 aagtcccggt ggcagcaggg caacgtgttc agctgctccg tgatgcacga ggccctgcac 1680 aaccactaca cccagaagtc cctgagcctg agccccggc 1719 <210> 183 <211> 1362 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 183 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccgggaca tgtacagcga gacagccttc 240 ctggaactgc ggagcctgac cagcgacgat accgccgtgt acttctgcac ccggggcaag 300 tactgcaccg ccagagacta ctacaactgg gacttcgagc actggggcca gggcacacct 360 gtgacagtgt ctagcgcttc gaccaagggc ccatcggtct tccccctggc accctcctcc 420 aagagcacct ctgggggcac agcggccctg ggctgcctgg tcaaggacta cttccccgaa 480 ccggtgacgg tgtcgtggaa ctcaggcgcc ctgaccagcg gcgtgcacac cttcccggct 540 gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcagc 600 ttgggcaccc agacctacat ctgcaacgtg aatcacaagc ccagcaacac caaggtggac 660 aagaaagttg agcccaaatc ttgtgacaaa actcacacat gcccaccgtg cccagcacct 720 gaactcctgg ggggaccgtc agtcttcctc ttccccccaa aacccaagga caccctcatg 780 atctcccgga cccctgaggt cacatgcgtg gtggtggacg tgagccacga agaccctgag 840 gtcaagttca actggtatgt tgacggcgtg gaggtgcata atgccaagac aaagccgcgg 900 gaggagcagt acaacaatgc ctcccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac 960 tggctgaatg gcaaggagta caagtgcaag gtctccaaca aagccctccc agcccccatc 1020 gagaaaacca tctccaaagc caaagggcag ccccgagaac cacaggtgta caccctgccc 1080 ccatgccggg atgagctgac caagaatcaa gtcagcctgt ggtgcctggt aaaaggcttc 1140 tatcccagcg acatcgccgt ggagtgggag agcaatgggc agccggagaa caactacaag 1200 accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctattcaaa actcaccgtg 1260 gacaagagca ggtggcagca ggggaacgtc ttctcatgct ccgtgctgca tgaggctctg 1320 cacagccact acaccgcagaa gagcctctcc ctgtctccgg gt 1362 <210> 184 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 184 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 185 <211> 1014 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 185 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacaacaacg ccaacaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaagggcc agcccaaggc cgccccccgac 360 atccagatga cccagagccc cagcagcctg tctgccagcg tgggcgacag agtgaccatc 420 acctgtcagg ccagccagaa catctacgtg tggctgaact ggtatcagca gaagcccggc 480 aaggccccca agctgctgat ctacaaggcc agcaacctgc acaccggcgt gcccagcaga 540 ttttctggca gcggctccgg caccgacttc accctgacaa tcagctccct gcagcccgag 600 gacattgcca cctactactg ccagcagggc cagacctacc cctacacctt tggccagggc 660 accaagctgg aaatcaagac caagggcccc agccgtacgg tggccgctcc cagcgtgttc 720 atcttcccac ctagcgacga gcagctgaag tccggcacag cctctgtcgt gtgcctgctg 780 aacaacttct acccccgcga ggccaaagtg cagtggaagg tggacaacgc cctgcagagc 840 ggcaacagcc aggaaagcgt gaccgagcag gacagcaagg actccaccta cagcctgagc 900 agcaccctga cactgagcaa ggccgactac gagaagcaca aggtgtacgc ctgcgaagtg 960 acccaccagg gcctgtctag ccccgtgacc aagagcttca accggggcga gtgt 1014 <210> 186 <211> 1710 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 186 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 agccaggtgc agctggtgga atctggcggc ggagtggtgc agcctggcag aagcctgaga 420 ctgagctgtg ccgccagcgg cttcaccttc accaaggcct ggatgcactg ggtgcgccag 480 gcccctggaa agcagctgga atgggtggcc cagatcaagg acaagagcaa cagctacgcc 540 acctactacg ccgacagcgt gaagggccgg ttcaccatca gccgggacga cagcaagaac 600 accctgtacc tgcagatgaa cagcctgcgg gccgaggaca ccgccgtgta ctactgtcgg 660 ggcgtgtact atgccctgag ccccttcgat tactggggcc agggaaccct cgtgaccgtg 720 tctagtcgga ccgccagcac aaagggccca tcggtgttcc ctctggcccc ttgcagcaga 780 agcaccagcg aatctacagc cgccctgggc tgcctcgtga aggactactt tcccgagccc 840 gtgaccgtgt cctggaactc tggcgctctg acaagcggcg tgcacacctt tccagccgtg 900 ctccagagca gcggcctgta ctctctgagc agcgtcgtga cagtgcccag cagcagcctg 960 ggcaccaaga cctacacctg taacgtggac cacaagccca gcaacaccaa ggtggacaag 1020 cgggtggaat ctaagtacgg ccctccctgc cctccttgcc cagcccctga agctgccggc 1080 ggaccctccg tgttcctgtt ccccccaaag cccaaggaca ccctgatgat cagccggacc 1140 cccgaagtga cctgcgtggt ggtggatgtg tcccaggaag atcccgaggt gcagttcaat 1200 tggtacgtgg acggcgtgga agtgcacaac gccaagacca agcccagaga ggaacagttc 1260 aacagcacct accgggtggt gtccgtgctg accgtgctgc accaggactg gctgaacggc 1320 aaagagtaca agtgcaaggt gtccaacaag ggcctgccca gctccatcga gaaaaccatc 1380 agcaaggcca agggccagcc ccgcgagcct caagtgtgta ccctgccccc tagccaggaa 1440 gagatgacca agaaccaggt gtccctgagc tgtgccgtga aaggcttcta ccccagcgac 1500 attgccgtgg aatgggagag caacggccag cccgagaaca actacaagac caccccccct 1560 gtgctggaca gcgacggctc attcttcctg gtgtccaagc tgaccgtgga caagagccgg 1620 tggcaggaag gcaacgtgtt cagctgctcc gtgatgcacg aggccctgca caaccactac 1680 acccagaagt ccctgtctct gtccctgggc 1710 <210> 187 <211> 1353 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 187 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccgggaca tgtacagcga gacagccttc 240 ctggaactgc ggagcctgac cagcgacgat accgccgtgt acttctgcac ccggggcaag 300 tactgcaccg ccagagacta ctacaactgg gacttcgagc actggggcca gggcacacct 360 gtgacagtgt ctagcgcttc gaccaagggc ccatcggtgt tccctctggc cccttgcagc 420 agaagcacca gcgaatctac agccgccctg ggctgcctcg tgaaggacta ctttcccgag 480 cccgtgaccg tgtcctggaa ctctggcgct ctgacaagcg gcgtgcacac ctttccagcc 540 gtgctccaga gcagcggcct gtactctctg agcagcgtcg tgacagtgcc cagcagcagc 600 ctgggcacca agacctacac ctgtaacgtg gaccacaagc ccagcaacac caaggtggac 660 aagcgggtgg aatctaagta cggccctccc tgccctcctt gcccagcccc tgaagctgcc 720 ggcggaccct ccgtgttcct gttcccccca aagcccaagg acaccctgat gatcagccgg 780 acccccgaag tgacctgcgt ggtggtggat gtgtcccagg aagatcccga ggtgcagttc 840 aattggtacg tggacggcgt ggaagtgcac aacgccaaga ccaagcccag agaggaacag 900 ttcaacagca cctaccgggt ggtgtccgtg ctgaccgtgc tgcaccagga ctggctgaac 960 ggcaaagagt acaagtgcaa ggtgtccaac aagggcctgc ccagctccat cgagaaaacc 1020 atcagcaagg ccaagggcca gccccgcgag cctcaagtgt ataccctgcc cccttgccag 1080 gaagagatga ccaagaacca ggtgtccctg tggtgtctcg tgaaaggctt ctaccccagc 1140 gacattgccg tggaatggga gagcaacggc cagcccgaga acaactacaa gaccaccccc 1200 cctgtgctgg acagcgacgg ctcattcttc ctgtactcca agctgaccgt ggacaagagc 1260 cggtggcagg aaggcaacgt gttcagctgc tccgtgatgc acgaggccct gcacaaccac 1320 tacacccaga agtccctgtc tctgtccctg ggc 1353 <210> 188 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 188 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 189 <211> 1014 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 189 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg caccagaacg cccagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaagggcc agcccaaggc cgccccccgac 360 atccagatga cccagagccc cagcagcctg tctgccagcg tgggcgacag agtgaccatc 420 acctgtcagg ccagccagaa catctacgtg tggctgaact ggtatcagca gaagcccggc 480 aaggccccca agctgctgat ctacaaggcc agcaacctgc acaccggcgt gcccagcaga 540 ttttctggca gcggctccgg caccgacttc accctgacaa tcagctccct gcagcccgag 600 gacattgcca cctactactg ccagcagggc cagacctacc cctacacctt tggccagggc 660 accaagctgg aaatcaagac caagggcccc agccgtacgg tggccgctcc cagcgtgttc 720 atcttcccac ctagcgacga gcagctgaag tccggcacag cctctgtcgt gtgcctgctg 780 aacaacttct acccccgcga ggccaaagtg cagtggaagg tggacaacgc cctgcagagc 840 ggcaacagcc aggaaagcgt gaccgagcag gacagcaagg actccaccta cagcctgagc 900 agcaccctga cactgagcaa ggccgactac gagaagcaca aggtgtacgc ctgcgaagtg 960 acccaccagg gcctgtctag ccccgtgacc aagagcttca accggggcga gtgt 1014 <210> 190 <211> 1710 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 190 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 agccaggtgc agctggtgga atctggcggc ggagtggtgc agcctggcag aagcctgaga 420 ctgagctgtg ccgccagcgg cttcaccttc accaaggcct ggatgcactg ggtgcgccag 480 gcccctggaa agcagctgga atgggtggcc cagatcaagg acaagagcaa cagctacgcc 540 acctactacg ccgacagcgt gaagggccgg ttcaccatca gccgggacga cagcaagaac 600 accctgtacc tgcagatgaa cagcctgcgg gccgaggaca ccgccgtgta ctactgtcgg 660 ggcgtgtact atgccctgag ccccttcgat tactggggcc agggaaccct cgtgaccgtg 720 tctagtcgga ccgccagcac aaagggccca tcggtgttcc ctctggcccc ttgcagcaga 780 agcaccagcg aatctacagc cgccctgggc tgcctcgtga aggactactt tcccgagccc 840 gtgaccgtgt cctggaactc tggcgctctg acaagcggcg tgcacacctt tccagccgtg 900 ctccagagca gcggcctgta ctctctgagc agcgtcgtga cagtgcccag cagcagcctg 960 ggcaccaaga cctacacctg taacgtggac cacaagccca gcaacaccaa ggtggacaag 1020 cgggtggaat ctaagtacgg ccctccctgc cctccttgcc cagcccctga agctgccggc 1080 ggaccctccg tgttcctgtt ccccccaaag cccaaggaca ccctgatgat cagccggacc 1140 cccgaagtga cctgcgtggt ggtggatgtg tcccaggaag atcccgaggt gcagttcaat 1200 tggtacgtgg acggcgtgga agtgcacaac gccaagacca agcccagaga ggaacagttc 1260 aacagcacct accgggtggt gtccgtgctg accgtgctgc accaggactg gctgaacggc 1320 aaagagtaca agtgcaaggt gtccaacaag ggcctgccca gctccatcga gaaaaccatc 1380 agcaaggcca agggccagcc ccgcgagcct caagtgtgta ccctgccccc tagccaggaa 1440 gagatgacca agaaccaggt gtccctgagc tgtgccgtga aaggcttcta ccccagcgac 1500 attgccgtgg aatgggagag caacggccag cccgagaaca actacaagac caccccccct 1560 gtgctggaca gcgacggctc attcttcctg gtgtccaagc tgaccgtgga caagagccgg 1620 tggcaggaag gcaacgtgtt cagctgctcc gtgatgcacg aggccctgca caaccactac 1680 acccagaagt ccctgtctct gtccctgggc 1710 <210> 191 <211> 1353 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 191 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccgggaca tgtacagcga gacagccttc 240 ctggaactgc ggagcctgac cagcgacgat accgccgtgt acttctgcac ccggggcaag 300 tactgcaccg ccagagacta ctacaactgg gacttcgagc actggggcca gggcacacct 360 gtgacagtgt ctagcgcttc gaccaagggc ccatcggtgt tccctctggc cccttgcagc 420 agaagcacca gcgaatctac agccgccctg ggctgcctcg tgaaggacta ctttcccgag 480 cccgtgaccg tgtcctggaa ctctggcgct ctgacaagcg gcgtgcacac ctttccagcc 540 gtgctccaga gcagcggcct gtactctctg agcagcgtcg tgacagtgcc cagcagcagc 600 ctgggcacca agacctacac ctgtaacgtg gaccacaagc ccagcaacac caaggtggac 660 aagcgggtgg aatctaagta cggccctccc tgccctcctt gcccagcccc tgaagctgcc 720 ggcggaccct ccgtgttcct gttcccccca aagcccaagg acaccctgat gatcagccgg 780 acccccgaag tgacctgcgt ggtggtggat gtgtcccagg aagatcccga ggtgcagttc 840 aattggtacg tggacggcgt ggaagtgcac aacgccaaga ccaagcccag agaggaacag 900 ttcaacagca cctaccgggt ggtgtccgtg ctgaccgtgc tgcaccagga ctggctgaac 960 ggcaaagagt acaagtgcaa ggtgtccaac aagggcctgc ccagctccat cgagaaaacc 1020 atcagcaagg ccaagggcca gccccgcgag cctcaagtgt ataccctgcc cccttgccag 1080 gaagagatga ccaagaacca ggtgtccctg tggtgtctcg tgaaaggctt ctaccccagc 1140 gacattgccg tggaatggga gagcaacggc cagcccgaga acaactacaa gaccaccccc 1200 cctgtgctgg acagcgacgg ctcattcttc ctgtactcca agctgaccgt ggacaagagc 1260 cggtggcagg aaggcaacgt gttcagctgc tccgtgatgc acgaggccct gcacaaccac 1320 tacacccaga agtccctgtc tctgtccctg ggc 1353 <210> 192 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 192 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 193 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 193 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg caccagaacg cccagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 194 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 194 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 195 <211> 1353 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 195 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccgggaca tgtacagcga gacagccttc 240 ctggaactgc ggagcctgac cagcgacgat accgccgtgt acttctgcac ccggggcaag 300 tactgcaccg ccagagacta ctacaactgg gacttcgagc actggggcca gggcacacct 360 gtgacagtgt ctagcgcttc gaccaagggc ccatcggtgt tccctctggc cccttgcagc 420 agaagcacca gcgaatctac agccgccctg ggctgcctcg tgaaggacta ctttcccgag 480 cccgtgaccg tgtcctggaa ctctggcgct ctgacaagcg gcgtgcacac ctttccagcc 540 gtgctccaga gcagcggcct gtactctctg agcagcgtcg tgacagtgcc cagcagcagc 600 ctgggcacca agacctacac ctgtaacgtg gaccacaagc ccagcaacac caaggtggac 660 aagcgggtgg aatctaagta cggccctccc tgccctcctt gcccagcccc tgaagctgcc 720 ggcggaccct ccgtgttcct gttcccccca aagcccaagg acaccctgat gatcagccgg 780 acccccgaag tgacctgcgt ggtggtggat gtgtcccagg aagatcccga ggtgcagttc 840 aattggtacg tggacggcgt ggaagtgcac aacgccaaga ccaagcccag agaggaacag 900 ttcaacagca cctaccgggt ggtgtccgtg ctgaccgtgc tgcaccagga ctggctgaac 960 ggcaaagagt acaagtgcaa ggtgtccaac aagggcctgc ccagctccat cgagaaaacc 1020 atcagcaagg ccaagggcca gccccgcgag cctcaagtgt ataccctgcc cccttgccag 1080 gaagagatga ccaagaacca ggtgtccctg tggtgtctcg tgaaaggctt ctaccccagc 1140 gacattgccg tggaatggga gagcaacggc cagcccgaga acaactacaa gaccaccccc 1200 cctgtgctgg acagcgacgg ctcattcttc ctgtactcca agctgaccgt ggacaagagc 1260 cggtggcagg aaggcaacgt gttcagctgc tccgtgatgc acgaggccct gcacaaccac 1320 tacacccaga agtccctgtc tctgtccctg ggc 1353 <210> 196 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 196 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 197 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 197 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg caccagaacg cccagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 198 <211> 1740 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 198 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc cagcgtgttc 780 cctctggccc ctagcagcaa gagcacatct ggcggaacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaatt ctggcgccct gaccagcggc 900 gtgcacacct ttccagctgt gctgcagtcc agcggcctgt acagcctgag cagcgtcgtg 960 acagtgccca gcagctctct gggcacccag acctacatct gcaacgtgaa ccacaagccc 1020 agcaacacca aggtggacaa gaaggtggaa cccaagagct gcgacaagac ccacacctgt 1080 cccccttgtc ctgcccccga actgctggga ggcccttccg tgttcctgtt ccccccaaag 1140 cccaaggaca ccctgatgat cagccggacc cccgaagtga cctgcgtggt ggtggatgtg 1200 tcccacgagg accctgaagt gaagttcaat tggtacgtgg acggcgtgga agtgcacaac 1260 gccaagacca agccaagaga ggaacagtac aacaatgcct cccgggtggt gtccgtgctg 1320 accgtgctgc accaggactg gctgaacggc aaagagtaca agtgcaaggt gtccaacaag 1380 gccctgcctg cccccatcga gaaaaccatc agcaaggcca agggccagcc ccgcgaaccc 1440 caggtgtgca cactgccccc aagcagggac gagctgacca agaaccaggt gtccctgagc 1500 tgtgccgtga aaggcttcta cccctccgat atcgccgtgg aatgggagag caacggccag 1560 cccgagaaca actacaagac caccccccct gtgctggaca gcgacggctc attcttcctg 1620 gtgtccaagc tgacagtgga caagtcccgg tggcagcagg gcaacgtgtt cagctgctcc 1680 gtgatgcacg aggccctgca caaccactac acccagaagt ccctgagcct gagccccggc 1740 <210> 199 <211> 1362 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 199 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccgggaca tgtacagcga gacagccttc 240 ctggaactgc ggagcctgac cagcgacgat accgccgtgt acttctgcac ccggggcaag 300 tactgcaccg ccagagacta ctacaactgg gacttcgagc actggggcca gggcacacct 360 gtgacagtgt ctagcgcttc gaccaagggc ccatcggtct tccccctggc accctcctcc 420 aagagcacct ctgggggcac agcggccctg ggctgcctgg tcaaggacta cttccccgaa 480 ccggtgacgg tgtcgtggaa ctcaggcgcc ctgaccagcg gcgtgcacac cttcccggct 540 gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcagc 600 ttgggcaccc agacctacat ctgcaacgtg aatcacaagc ccagcaacac caaggtggac 660 aagaaagttg agcccaaatc ttgtgacaaa actcacacat gcccaccgtg cccagcacct 720 gaactcctgg ggggaccgtc agtcttcctc ttccccccaa aacccaagga caccctcatg 780 atctcccgga cccctgaggt cacatgcgtg gtggtggacg tgagccacga agaccctgag 840 gtcaagttca actggtatgt tgacggcgtg gaggtgcata atgccaagac aaagccgcgg 900 gaggagcagt acaacaatgc ctcccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac 960 tggctgaatg gcaaggagta caagtgcaag gtctccaaca aagccctccc agcccccatc 1020 gagaaaacca tctccaaagc caaagggcag ccccgagaac cacaggtgta caccctgccc 1080 ccatgccggg atgagctgac caagaatcaa gtcagcctgt ggtgcctggt aaaaggcttc 1140 tatcccagcg acatcgccgt ggagtgggag agcaatgggc agccggagaa caactacaag 1200 accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctattcaaa actcaccgtg 1260 gacaagagca ggtggcagca ggggaacgtc ttctcatgct ccgtgctgca tgaggctctg 1320 cacagccact acaccgcagaa gagcctctcc ctgtctccgg gt 1362 <210> 200 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 200 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 201 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 201 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgcagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 202 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 202 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 203 <211> 1374 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 203 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcacagcctt cctggaactg cggagcctga ccagcgacga taccgccgtg 300 tacttctgca cccggggcaa gtactgcacc gccagagact actacaactg ggacttcgag 360 cactggggcc agggcacacc tgtgacagtg tctagcgctt cgaccaaggg cccatcggtg 420 ttccctctgg ccccttgcag cagaagcacc agcgaatcta cagccgccct gggctgcctc 480 gtgaaggact actttcccga gcccgtgacc gtgtcctgga actctggcgc tctgacaagc 540 ggcgtgcaca cctttccagc cgtgctccag agcagcggcc tgtactctct gagcagcgtc 600 gtgacagtgc ccagcagcag cctgggcacc aagacctaca cctgtaacgt ggaccacaag 660 cccagcaaca ccaaggtgga caagcgggtg gaatctaagt acggccctcc ctgccctcct 720 tgcccagccc ctgaagctgc cggcggaccc tccgtgttcc tgttcccccc aaagcccaag 780 gacaccctga tgatcagccg gacccccgaa gtgacctgcg tggtggtgga tgtgtcccag 840 gaagatcccg aggtgcagtt caattggtac gtggacggcg tggaagtgca caacgccaag 900 accaagccca gagaggaaca gttcaacagc acctaccggg tggtgtccgt gctgaccgtg 960 ctgcaccagg actggctgaa cggcaaagag tacaagtgca aggtgtccaa caagggcctg 1020 cccagctcca tcgagaaaac catcagcaag gccaagggcc agccccgcga gcctcaagtg 1080 tataccctgc ccccttgcca ggaagagatg accaagaacc aggtgtccct gtggtgtctc 1140 gtgaaaggct tctaccccag cgacattgcc gtggaatggg agagcaacgg ccagcccgag 1200 aacaactaca agaccacccc ccctgtgctg gacagcgacg gctcattctt cctgtactcc 1260 aagctgaccg tggacaagag ccggtggcag gaaggcaacg tgttcagctg ctccgtgatg 1320 cacgaggccc tgcacaacca ctacacccag aagtccctgt ctctgtccct gggc 1374 <210> 204 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 204 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 205 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 205 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgttcaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 206 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 206 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 207 <211> 1374 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 207 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcacagcctt cctggaactg cggagcctga ccagcgacga taccgccgtg 300 tacttctgca cccggggcaa gtactgcacc gccagagact actacaactg ggacttcgag 360 cactggggcc agggcacacc tgtgacagtg tctagcgctt cgaccaaggg cccatcggtg 420 ttccctctgg ccccttgcag cagaagcacc agcgaatcta cagccgccct gggctgcctc 480 gtgaaggact actttcccga gcccgtgacc gtgtcctgga actctggcgc tctgacaagc 540 ggcgtgcaca cctttccagc cgtgctccag agcagcggcc tgtactctct gagcagcgtc 600 gtgacagtgc ccagcagcag cctgggcacc aagacctaca cctgtaacgt ggaccacaag 660 cccagcaaca ccaaggtgga caagcgggtg gaatctaagt acggccctcc ctgccctcct 720 tgcccagccc ctgaagctgc cggcggaccc tccgtgttcc tgttcccccc aaagcccaag 780 gacaccctga tgatcagccg gacccccgaa gtgacctgcg tggtggtgga tgtgtcccag 840 gaagatcccg aggtgcagtt caattggtac gtggacggcg tggaagtgca caacgccaag 900 accaagccca gagaggaaca gttcaacagc acctaccggg tggtgtccgt gctgaccgtg 960 ctgcaccagg actggctgaa cggcaaagag tacaagtgca aggtgtccaa caagggcctg 1020 cccagctcca tcgagaaaac catcagcaag gccaagggcc agccccgcga gcctcaagtg 1080 tataccctgc ccccttgcca ggaagagatg accaagaacc aggtgtccct gtggtgtctc 1140 gtgaaaggct tctaccccag cgacattgcc gtggaatggg agagcaacgg ccagcccgag 1200 aacaactaca agaccacccc ccctgtgctg gacagcgacg gctcattctt cctgtactcc 1260 aagctgaccg tggacaagag ccggtggcag gaaggcaacg tgttcagctg ctccgtgatg 1320 cacgaggccc tgcacaacca ctacacccag aagtccctgt ctctgtccct gggc 1374 <210> 208 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 208 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 209 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 209 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgcagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 210 <211> 1740 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 210 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc cagcgtgttc 780 cctctggccc ctagcagcaa gagcacatct ggcggaacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaatt ctggcgccct gaccagcggc 900 gtgcacacct ttccagctgt gctgcagtcc agcggcctgt acagcctgag cagcgtcgtg 960 acagtgccca gcagctctct gggcacccag acctacatct gcaacgtgaa ccacaagccc 1020 agcaacacca aggtggacaa gaaggtggaa cccaagagct gcgacaagac ccacacctgt 1080 cccccttgtc ctgcccccga actgctggga ggcccttccg tgttcctgtt ccccccaaag 1140 cccaaggaca ccctgatgat cagccggacc cccgaagtga cctgcgtggt ggtggatgtg 1200 tcccacgagg accctgaagt gaagttcaat tggtacgtgg acggcgtgga agtgcacaac 1260 gccaagacca agccaagaga ggaacagtac aacaatgcct cccgggtggt gtccgtgctg 1320 accgtgctgc accaggactg gctgaacggc aaagagtaca agtgcaaggt gtccaacaag 1380 gccctgcctg cccccatcga gaaaaccatc agcaaggcca agggccagcc ccgcgaaccc 1440 caggtgtgca cactgccccc aagcagggac gagctgacca agaaccaggt gtccctgagc 1500 tgtgccgtga aaggcttcta cccctccgat atcgccgtgg aatgggagag caacggccag 1560 cccgagaaca actacaagac caccccccct gtgctggaca gcgacggctc attcttcctg 1620 gtgtccaagc tgacagtgga caagtcccgg tggcagcagg gcaacgtgtt cagctgctcc 1680 gtgatgcacg aggccctgca caaccactac acccagaagt ccctgagcct gagccccggc 1740 <210> 211 <211> 1383 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 211 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcacagcctt cctggaactg cggagcctga ccagcgacga taccgccgtg 300 tacttctgca cccggggcaa gtactgcacc gccagagact actacaactg ggacttcgag 360 cactggggcc agggcacacc tgtgacagtg tctagcgctt cgaccaaggg cccatcggtc 420 ttccccctgg caccctcctc caagagcacc tctgggggca cagcggccct gggctgcctg 480 gtcaaggact acttccccga accggtgacg gtgtcgtgga actcaggcgc cctgaccagc 540 ggcgtgcaca ccttcccggc tgtcctacag tcctcaggac tctactccct cagcagcgtg 600 gtgaccgtgc cctccagcag cttgggcacc cagacctaca tctgcaacgt gaatcacaag 660 cccagcaaca ccaaggtgga caagaaagtt gagcccaaat cttgtgacaa aactcacaca 720 tgcccaccgt gcccagcacc tgaactcctg gggggaccgt cagtcttcct cttcccccca 780 aaacccaagg acaccctcat gatctcccgg acccctgagg tcacatgcgt ggtggtggac 840 gtgagccacg aagaccctga ggtcaagttc aactggtatg ttgacggcgt ggaggtgcat 900 aatgccaaga caaagccgcg ggaggagcag tacaacaatg cctcccgtgt ggtcagcgtc 960 ctcaccgtcc tgcaccagga ctggctgaat ggcaaggagt acaagtgcaa ggtctccaac 1020 aaagccctcc cagcccccat cgagaaaacc atctccaaag ccaaagggca gccccgagaa 1080 ccacaggtgt acaccctgcc cccatgccgg gatgagctga ccaagaatca agtcagcctg 1140 tggtgcctgg taaaaggctt ctatcccagc gacatcgccg tggagtggga gagcaatggg 1200 cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1260 ctctactcaa aactcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1320 tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1380 ggt 1383 <210> 212 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 212 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 213 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 213 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgttcaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 214 <211> 1740 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 214 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc cagcgtgttc 780 cctctggccc ctagcagcaa gagcacatct ggcggaacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaatt ctggcgccct gaccagcggc 900 gtgcacacct ttccagctgt gctgcagtcc agcggcctgt acagcctgag cagcgtcgtg 960 acagtgccca gcagctctct gggcacccag acctacatct gcaacgtgaa ccacaagccc 1020 agcaacacca aggtggacaa gaaggtggaa cccaagagct gcgacaagac ccacacctgt 1080 cccccttgtc ctgcccccga actgctggga ggcccttccg tgttcctgtt ccccccaaag 1140 cccaaggaca ccctgatgat cagccggacc cccgaagtga cctgcgtggt ggtggatgtg 1200 tcccacgagg accctgaagt gaagttcaat tggtacgtgg acggcgtgga agtgcacaac 1260 gccaagacca agccaagaga ggaacagtac aacaatgcct cccgggtggt gtccgtgctg 1320 accgtgctgc accaggactg gctgaacggc aaagagtaca agtgcaaggt gtccaacaag 1380 gccctgcctg cccccatcga gaaaaccatc agcaaggcca agggccagcc ccgcgaaccc 1440 caggtgtgca cactgccccc aagcagggac gagctgacca agaaccaggt gtccctgagc 1500 tgtgccgtga aaggcttcta cccctccgat atcgccgtgg aatgggagag caacggccag 1560 cccgagaaca actacaagac caccccccct gtgctggaca gcgacggctc attcttcctg 1620 gtgtccaagc tgacagtgga caagtcccgg tggcagcagg gcaacgtgtt cagctgctcc 1680 gtgatgcacg aggccctgca caaccactac acccagaagt ccctgagcct gagccccggc 1740 <210> 215 <211> 1383 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 215 caagtgcggc tgtctcagtc tggcggccag atgaagaaac ccggcgacag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc aactgcccca tcaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg atgaagccca gacacggggc cgtgtcctac 180 gccagacagc tgcagggcag agtgaccatg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcacagcctt cctggaactg cggagcctga ccagcgacga taccgccgtg 300 tacttctgca cccggggcaa gtactgcacc gccagagact actacaactg ggacttcgag 360 cactggggcc agggcacacc tgtgacagtg tctagcgctt cgaccaaggg cccatcggtc 420 ttccccctgg caccctcctc caagagcacc tctgggggca cagcggccct gggctgcctg 480 gtcaaggact acttccccga accggtgacg gtgtcgtgga actcaggcgc cctgaccagc 540 ggcgtgcaca ccttcccggc tgtcctacag tcctcaggac tctactccct cagcagcgtg 600 gtgaccgtgc cctccagcag cttgggcacc cagacctaca tctgcaacgt gaatcacaag 660 cccagcaaca ccaaggtgga caagaaagtt gagcccaaat cttgtgacaa aactcacaca 720 tgcccaccgt gcccagcacc tgaactcctg gggggaccgt cagtcttcct cttcccccca 780 aaacccaagg acaccctcat gatctcccgg acccctgagg tcacatgcgt ggtggtggac 840 gtgagccacg aagaccctga ggtcaagttc aactggtatg ttgacggcgt ggaggtgcat 900 aatgccaaga caaagccgcg ggaggagcag tacaacaatg cctcccgtgt ggtcagcgtc 960 ctcaccgtcc tgcaccagga ctggctgaat ggcaaggagt acaagtgcaa ggtctccaac 1020 aaagccctcc cagcccccat cgagaaaacc atctccaaag ccaaagggca gccccgagaa 1080 ccacaggtgt acaccctgcc cccatgccgg gatgagctga ccaagaatca agtcagcctg 1140 tggtgcctgg taaaaggctt ctatcccagc gacatcgccg tggagtggga gagcaatggg 1200 cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1260 ctctactcaa aactcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1320 tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1380 ggt 1383 <210> 216 <211> 624 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 216 agcctgacac agagccctgg caccctgtca ctgagcccag gcgagacagc catcatcagc 60 tgccggacaa gccagtacgg cagcctggcc tggtatcagc agaggcctgg acaggccccc 120 agactcgtga tctacagcgg cagcacaaga gccgccggaa tccccgatag attcagcggc 180 tccagatggg gacccgacta caacctgacc atcagcaacc tggaaagcgg cgacttcggc 240 gtgtactact gccagcagta cgagttcttc ggccagggca ccaaggtgca ggtggacatc 300 aagcgtacgg tggccgctcc cagcgtgttc atcttcccac ctagcgacga gcagctgaag 360 tccggcacag cctctgtcgt gtgcctgctg aacaacttct acccccgcga ggccaaagtg 420 cagtggaagg tggacaacgc cctgcagagc ggcaacagcc aggaaagcgt gaccgagcag 480 gacagcaagg actccaccta cagcctgagc agcaccctga cactgagcaa ggccgactac 540 gagaagcaca aggtgtacgc ctgcgaagtg acccaccagg gcctgtctag ccccgtgacc 600 aagagcttca accggggcga gtgt 624 <210> 217 <211> 1014 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 217 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacaacaacg ccaacaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaagggcc agcccaaggc cgccccccgac 360 atccagatga cccagagccc cagcagcctg tctgccagcg tgggcgacag agtgaccatc 420 acctgtcagg ccagccagaa catctacgtg tggctgaact ggtatcagca gaagcccggc 480 aaggccccca agctgctgat ctacaaggcc agcaacctgc acaccggcgt gcccagcaga 540 ttttctggca gcggctccgg caccgacttc accctgacaa tcagctccct gcagcccgag 600 gacattgcca cctactactg ccagcagggc cagacctacc cctacacctt tggccagggc 660 accaagctgg aaatcaagac caagggcccc agccgtacgg tggccgctcc cagcgtgttc 720 atcttcccac ctagcgacga gcagctgaag tccggcacag cctctgtcgt gtgcctgctg 780 aacaacttct acccccgcga ggccaaagtg cagtggaagg tggacaacgc cctgcagagc 840 ggcaacagcc aggaaagcgt gaccgagcag gacagcaagg actccaccta cagcctgagc 900 agcaccctga cactgagcaa ggccgactac gagaagcaca aggtgtacgc ctgcgaagtg 960 acccaccagg gcctgtctag ccccgtgacc aagagcttca accggggcga gtgt 1014 <210> 218 <211> 1707 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 218 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 agccaggtgc agctggtgga atctggcggc ggagtggtgc agcctggcag aagcctgaga 420 ctgagctgtg ccgccagcgg cttcaccttc accaaggcct ggatgcactg ggtgcgccag 480 gcccctggaa agcagctgga atgggtggcc cagatcaagg acaagagcaa cagctacgcc 540 acctactacg ccgacagcgt gaagggccgg ttcaccatca gccgggacga cagcaagaac 600 accctgtacc tgcagatgaa cagcctgcgg gccgaggaca ccgccgtgta ctactgtcgg 660 ggcgtgtact atgccctgag ccccttcgat tactggggcc agggaaccct cgtgaccgtg 720 tctagtcgga ccgccagcac aaagggccca tcggtgttcc ctctggcccc ttgcagcaga 780 agcaccagcg aatctacagc cgccctgggc tgcctcgtga aggactactt tcccgagccc 840 gtgaccgtgt cctggaactc tggcgctctg acaagcggcg tgcacacctt tccagccgtg 900 ctccagagca gcggcctgta ctctctgagc agcgtcgtga cagtgcccag cagcagcctg 960 ggcaccaaga cctacacctg taacgtggac cacaagccca gcaacaccaa ggtggacaag 1020 cgggtggaat ctaagtacgg ccctccctgc cctccttgcc cagcccctcc tgtggctgga 1080 ccctccgtgt tcctgttccc cccaaagccc aaggacaccc tgatgatcag ccggaccccc 1140 gaagtgacct gcgtggtggt ggatgtgtcc caggaagatc ccgaggtgca gttcaattgg 1200 tacgtggacg gcgtggaagt gcacaacgcc aagaccaagc ccagagagga acagttcaac 1260 agcacctacc gggtggtgtc cgtgctgacc gtgctgcacc aggactggct gaacggcaaa 1320 gagtacaagt gcaaggtgtc caacaagggc ctgcccagct ccatcgagaa aaccatcagc 1380 aaggccaagg gccagccccg cgagcctcaa gtgtgtaccc tgccccctag ccaggaagag 1440 atgaccaaga accaggtgtc cctgagctgt gccgtgaaag gcttctaccc cagcgacatt 1500 gccgtggaat gggagagcaa cggccagccc gagaacaact acaagaccac cccccctgtg 1560 ctggacagcg acggctcatt cttcctggtg tccaagctga ccgtggacaa gagccggtgg 1620 caggaaggca acgtgttcag ctgctccgtg atgcacgagg ccctgcacaa ccactacacc 1680 cagaagtccc tgtctctgtc cctgggc 1707 <210> 219 <211> 1341 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 219 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccct gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctcctgtggc tggaccctcc 720 gtgttcctgt tccccccaaa gcccaaggac accctgatga tcagccggac ccccgaagtg 780 acctgcgtgg tggtggatgt gtcccaggaa gatcccgagg tgcagttcaa ttggtacgtg 840 gacggcgtgg aagtgcacaa cgccaagacc aagcccagag aggaacagtt caacagcacc 900 taccgggtgg tgtccgtgct gaccgtgctg caccaggact ggctgaacgg caaagagtac 960 aagtgcaagg tgtccaacaa gggcctgccc agctccatcg agaaaaccat cagcaaggcc 1020 aagggccagc cccgcgagcc tcaagtgtat accctgcccc cttgccagga agagatgacc 1080 aagaaccagg tgtccctgtg gtgtctcgtg aaaggcttct accccagcga cattgccgtg 1140 gaatgggaga gcaacggcca gcccgagaac aactacaaga ccaccccccc tgtgctggac 1200 agcgacggct cattcttcct gtactccaag ctgaccgtgg acaagagccg gtggcaggaa 1260 ggcaacgtgt tcagctgctc cgtgatgcac gaggccctgc acaaccacta cacccagaag 1320 tccctgtctc tgtccctggg c 1341 <210> 220 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 220 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 221 <211> 1014 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 221 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacaacaacg ccaacaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaagggcc agcccaaggc cgccccccgac 360 atccagatga cccagagccc cagcagcctg tctgccagcg tgggcgacag agtgaccatc 420 acctgtcagg ccagccagaa catctacgtg tggctgaact ggtatcagca gaagcccggc 480 aaggccccca agctgctgat ctacaaggcc agcaacctgc acaccggcgt gcccagcaga 540 ttttctggca gcggctccgg caccgacttc accctgacaa tcagctccct gcagcccgag 600 gacattgcca cctactactg ccagcagggc cagacctacc cctacacctt tggccagggc 660 accaagctgg aaatcaagac caagggcccc agccgtacgg tggccgctcc cagcgtgttc 720 atcttcccac ctagcgacga gcagctgaag tccggcacag cctctgtcgt gtgcctgctg 780 aacaacttct acccccgcga ggccaaagtg cagtggaagg tggacaacgc cctgcagagc 840 ggcaacagcc aggaaagcgt gaccgagcag gacagcaagg actccaccta cagcctgagc 900 agcaccctga cactgagcaa ggccgactac gagaagcaca aggtgtacgc ctgcgaagtg 960 acccaccagg gcctgtctag ccccgtgacc aagagcttca accggggcga gtgt 1014 <210> 222 <211> 1710 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 222 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 agccaggtgc agctggtgga atctggcggc ggagtggtgc agcctggcag aagcctgaga 420 ctgagctgtg ccgccagcgg cttcaccttc accaaggcct ggatgcactg ggtgcgccag 480 gcccctggaa agcagctgga atgggtggcc cagatcaagg acaagagcaa cagctacgcc 540 acctactacg ccgacagcgt gaagggccgg ttcaccatca gccgggacga cagcaagaac 600 accctgtacc tgcagatgaa cagcctgcgg gccgaggaca ccgccgtgta ctactgtcgg 660 ggcgtgtact atgccctgag ccccttcgat tactggggcc agggaaccct cgtgaccgtg 720 tctagtcgga ccgccagcac aaagggccca tcggtgttcc ctctggcccc ttgcagcaga 780 agcaccagcg aatctacagc cgccctgggc tgcctcgtga aggactactt tcccgagccc 840 gtgaccgtgt cctggaactc tggcgctctg acaagcggcg tgcacacctt tccagccgtg 900 ctccagagca gcggcctgta ctctctgagc agcgtcgtga cagtgcccag cagcagcctg 960 ggcaccaaga cctacacctg taacgtggac cacaagccca gcaacaccaa ggtggacaag 1020 cgggtggaat ctaagtacgg ccctccctgc cctccttgcc cagcccctga agctgccggc 1080 ggaccctccg tgttcctgtt ccccccaaag cccaaggaca ccctgatgat cagccggacc 1140 cccgaagtga cctgcgtggt ggtggatgtg tcccaggaag atcccgaggt gcagttcaat 1200 tggtacgtgg acggcgtgga agtgcacaac gccaagacca agcccagaga ggaacagttc 1260 aacagcacct accgggtggt gtccgtgctg accgtgctgc accaggactg gctgaacggc 1320 aaagagtaca agtgcaaggt gtccaacaag ggcctgccca gctccatcga gaaaaccatc 1380 agcaaggcca agggccagcc ccgcgagcct caagtgtgta ccctgccccc tagccaggaa 1440 gagatgacca agaaccaggt gtccctgagc tgtgccgtga aaggcttcta ccccagcgac 1500 attgccgtgg aatgggagag caacggccag cccgagaaca actacaagac caccccccct 1560 gtgctggaca gcgacggctc attcttcctg gtgtccaagc tgaccgtgga caagagccgg 1620 tggcaggaag gcaacgtgtt cagctgctcc gtgatgcacg aggccctgca caaccactac 1680 acccagaagt ccctgtctct gtccctgggc 1710 <210> 223 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 439 <223> n = A,T,C or G <400> 223 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccnt gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 224 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 224 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 225 <211> 1014 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 225 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacaacaacg ccaacaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaagggcc agcccaaggc cgccccccgac 360 atccagatga cccagagccc cagcagcctg tctgccagcg tgggcgacag agtgaccatc 420 acctgtcagg ccagccagaa catctacgtg tggctgaact ggtatcagca gaagcccggc 480 aaggccccca agctgctgat ctacaaggcc agcaacctgc acaccggcgt gcccagcaga 540 ttttctggca gcggctccgg caccgacttc accctgacaa tcagctccct gcagcccgag 600 gacattgcca cctactactg ccagcagggc cagacctacc cctacacctt tggccagggc 660 accaagctgg aaatcaagac caagggcccc agccgtacgg tggccgctcc cagcgtgttc 720 atcttcccac ctagcgacga gcagctgaag tccggcacag cctctgtcgt gtgcctgctg 780 aacaacttct acccccgcga ggccaaagtg cagtggaagg tggacaacgc cctgcagagc 840 ggcaacagcc aggaaagcgt gaccgagcag gacagcaagg actccaccta cagcctgagc 900 agcaccctga cactgagcaa ggccgactac gagaagcaca aggtgtacgc ctgcgaagtg 960 acccaccagg gcctgtctag ccccgtgacc aagagcttca accggggcga gtgt 1014 <210> 226 <211> 1710 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 226 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 agccaggtgc agctggtgga atctggcggc ggagtggtgc agcctggcag aagcctgaga 420 ctgagctgtg ccgccagcgg cttcaccttc accaaggcct ggatgcactg ggtgcgccag 480 gcccctggaa agcagctgga atgggtggcc cagatcaagg acaagagcaa cagctacgcc 540 acctactacg ccgacagcgt gaagggccgg ttcaccatca gccgggacga cagcaagaac 600 accctgtacc tgcagatgaa cagcctgcgg gccgaggaca ccgccgtgta ctactgtcgg 660 ggcgtgtact atgccctgag ccccttcgat tactggggcc agggaaccct cgtgaccgtg 720 tctagtcgga ccgccagcac aaagggccca tcggtgttcc ctctggcccc ttgcagcaga 780 agcaccagcg aatctacagc cgccctgggc tgcctcgtga aggactactt tcccgagccc 840 gtgaccgtgt cctggaactc tggcgctctg acaagcggcg tgcacacctt tccagccgtg 900 ctccagagca gcggcctgta ctctctgagc agcgtcgtga cagtgcccag cagcagcctg 960 ggcaccaaga cctacacctg taacgtggac cacaagccca gcaacaccaa ggtggacaag 1020 cgggtggaat ctaagtacgg ccctccctgc cctccttgcc cagcccctga agctgccggc 1080 ggaccctccg tgttcctgtt ccccccaaag cccaaggaca ccctgatgat cagccggacc 1140 cccgaagtga cctgcgtggt ggtggatgtg tcccaggaag atcccgaggt gcagttcaat 1200 tggtacgtgg acggcgtgga agtgcacaac gccaagacca agcccagaga ggaacagttc 1260 aacagcacct accgggtggt gtccgtgctg accgtgctgc accaggactg gctgaacggc 1320 aaagagtaca agtgcaaggt gtccaacaag ggcctgccca gctccatcga gaaaaccatc 1380 agcaaggcca agggccagcc ccgcgagcct caagtgtgta ccctgccccc tagccaggaa 1440 gagatgacca agaaccaggt gtccctgagc tgtgccgtga aaggcttcta ccccagcgac 1500 attgccgtgg aatgggagag caacggccag cccgagaaca actacaagac caccccccct 1560 gtgctggaca gcgacggctc attcttcctg gtgtccaagc tgaccgtgga caagagccgg 1620 tggcaggaag gcaacgtgtt cagctgctcc gtgatgcacg aggccctgca caaccactac 1680 acccagaagt ccctgtctct gtccctgggc 1710 <210> 227 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 439 <223> n = A,T,C or G <400> 227 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccnt gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 228 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 228 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 229 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 229 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg caccagaacg cccagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 230 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 230 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 231 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 439 <223> n = A,T,C or G <400> 231 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccnt gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 232 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 232 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 233 <211> 1002 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 233 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacaacaacg ccaacaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacaccagt cagcccaagg ctgccccctc ggtcactctg 720 ttcccgccct cgagtgagga gcttcaagcc aacaaggcca cactggtgtg tctcataagt 780 gacttctacc cgggagccgt gacagtggcc tggaaggcag atagcagccc cgtcaaggcg 840 ggagtggaga ccaccacacc ctccaaacaa agcaacaaca agtacgcggc cagcagctac 900 ctgagcctga cgcctgagca gtggaagtcc cacagaagct acagctgcca ggtcacgcat 960 gaagggagca ccgtggagaa gacagtggcc cctacagaat gt 1002 <210> 234 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 234 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 235 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 439 <223> n = A,T,C or G <400> 235 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccnt gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 236 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 236 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 237 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 237 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg caccagaacg cccagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 238 <211> 1740 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 238 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc cagcgtgttc 780 cctctggccc ctagcagcaa gagcacatct ggcggaacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaatt ctggcgccct gaccagcggc 900 gtgcacacct ttccagctgt gctgcagtcc agcggcctgt acagcctgag cagcgtcgtg 960 acagtgccca gcagctctct gggcacccag acctacatct gcaacgtgaa ccacaagccc 1020 agcaacacca aggtggacaa gaaggtggaa cccaagagct gcgacaagac ccacacctgt 1080 cccccttgtc ctgcccccga actgctggga ggcccttccg tgttcctgtt ccccccaaag 1140 cccaaggaca ccctgatgat cagccggacc cccgaagtga cctgcgtggt ggtggatgtg 1200 tcccacgagg accctgaagt gaagttcaat tggtacgtgg acggcgtgga agtgcacaac 1260 gccaagacca agccaagaga ggaacagtac aacaatgcct cccgggtggt gtccgtgctg 1320 accgtgctgc accaggactg gctgaacggc aaagagtaca agtgcaaggt gtccaacaag 1380 gccctgcctg cccccatcga gaaaaccatc agcaaggcca agggccagcc ccgcgaaccc 1440 caggtgtgca cactgccccc aagcagggac gagctgacca agaaccaggt gtccctgagc 1500 tgtgccgtga aaggcttcta cccctccgat atcgccgtgg aatgggagag caacggccag 1560 cccgagaaca actacaagac caccccccct gtgctggaca gcgacggctc attcttcctg 1620 gtgtccaagc tgacagtgga caagtcccgg tggcagcagg gcaacgtgtt cagctgctcc 1680 gtgatgcacg aggccctgca caaccactac acccagaagt ccctgagcct gagccccggc 1740 <210> 239 <211> 1353 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 239 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 420 tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 480 gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 540 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 600 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagaaagtt 660 gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 720 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 780 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 840 aactggtatg ttgacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 900 tacaacaatg cctcccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 960 ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1020 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatgccgg 1080 gatgagctga ccaagaatca agtcagcctg tggtgcctgg taaaaggctt ctatcccagc 1140 gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1200 cccgtgctgg actccgacgg ctccttcttc ctctactcaa aactcaccgt ggacaagagc 1260 aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1320 tacaccgcaga agagcctctc cctgtctccg ggt 1353 <210> 240 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 240 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 241 <211> 1002 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 241 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgacaacg cccagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacaccagt cagcccaagg ctgccccctc ggtcactctg 720 ttcccgccct cgagtgagga gcttcaagcc aacaaggcca cactggtgtg tctcataagt 780 gacttctacc cgggagccgt gacagtggcc tggaaggcag atagcagccc cgtcaaggcg 840 ggagtggaga ccaccacacc ctccaaacaa agcaacaaca agtacgcggc cagcagctac 900 ctgagcctga cgcctgagca gtggaagtcc cacagaagct acagctgcca ggtcacgcat 960 gaagggagca ccgtggagaa gacagtggcc cctacagaat gt 1002 <210> 242 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 242 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 243 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 439 <223> n = A,T,C or G <400> 243 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccnt gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 244 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 244 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 245 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 245 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgcagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 246 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 246 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 247 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 439 <223> n = A,T,C or G <400> 247 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccnt gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 248 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 248 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 249 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 249 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgcgtaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 250 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 250 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 251 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 439 <223> n = A,T,C or G <400> 251 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccnt gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 252 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 252 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 253 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 253 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgttcaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 254 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 254 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 255 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 439 <223> n = A,T,C or G <400> 255 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccnt gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 256 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 256 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 257 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 257 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgcagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 258 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 258 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 259 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 259 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc caccaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccct gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 260 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 260 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagct ccgaagaggg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 261 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 261 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgttcaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 262 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 262 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 263 <211> 1344 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 263 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc caccaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtg ttccctctgg ccccttgcag cagaagcacc 420 agcgaatcta cagccgccct gggctgcctc gtgaaggact actttcccga gcccgtgacc 480 gtgtcctgga actctggcgc tctgacaagc ggcgtgcaca cctttccagc cgtgctccag 540 agcagcggcc tgtactctct gagcagcgtc gtgacagtgc ccagcagcag cctgggcacc 600 aagacctaca cctgtaacgt ggaccacaag cccagcaaca ccaaggtgga caagcgggtg 660 gaatctaagt acggccctcc ctgccctcct tgcccagccc ctgaagctgc cggcggaccc 720 tccgtgttcc tgttcccccc aaagcccaag gacaccctga tgatcagccg gacccccgaa 780 gtgacctgcg tggtggtgga tgtgtcccag gaagatcccg aggtgcagtt caattggtac 840 gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 900 acctaccggg tggtgtccgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagag 960 tacaagtgca aggtgtccaa caagggcctg cccagctcca tcgagaaaac catcagcaag 1020 gccaagggcc agccccgcga gcctcaagtg tataccctgc ccccttgcca ggaagagatg 1080 accaagaacc aggtgtccct gtggtgtctc gtgaaaggct tctaccccag cgacattgcc 1140 gtggaatggg agagcaacgg ccagcccgag aacaactaca agaccacccc ccctgtgctg 1200 gacagcgacg gctcattctt cctgtactcc aagctgaccg tggacaagag ccggtggcag 1260 gaaggcaacg tgttcagctg ctccgtgatg cacgaggccc tgcacaacca ctacacccag 1320 aagtccctgt ctctgtccct gggc 1344 <210> 264 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 264 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagct ccgaagaggg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 265 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 265 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgttcaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 266 <211> 1740 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 266 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc cagcgtgttc 780 cctctggccc ctagcagcaa gagcacatct ggcggaacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaatt ctggcgccct gaccagcggc 900 gtgcacacct ttccagctgt gctgcagtcc agcggcctgt acagcctgag cagcgtcgtg 960 acagtgccca gcagctctct gggcacccag acctacatct gcaacgtgaa ccacaagccc 1020 agcaacacca aggtggacaa gaaggtggaa cccaagagct gcgacaagac ccacacctgt 1080 cccccttgtc ctgcccccga actgctggga ggcccttccg tgttcctgtt ccccccaaag 1140 cccaaggaca ccctgatgat cagccggacc cccgaagtga cctgcgtggt ggtggatgtg 1200 tcccacgagg accctgaagt gaagttcaat tggtacgtgg acggcgtgga agtgcacaac 1260 gccaagacca agccaagaga ggaacagtac aacaatgcct cccgggtggt gtccgtgctg 1320 accgtgctgc accaggactg gctgaacggc aaagagtaca agtgcaaggt gtccaacaag 1380 gccctgcctg cccccatcga gaaaaccatc agcaaggcca agggccagcc ccgcgaaccc 1440 caggtgtgca cactgccccc aagcagggac gagctgacca agaaccaggt gtccctgagc 1500 tgtgccgtga aaggcttcta cccctccgat atcgccgtgg aatgggagag caacggccag 1560 cccgagaaca actacaagac caccccccct gtgctggaca gcgacggctc attcttcctg 1620 gtgtccaagc tgacagtgga caagtcccgg tggcagcagg gcaacgtgtt cagctgctcc 1680 gtgatgcacg aggccctgca caaccactac acccagaagt ccctgagcct gagccccggc 1740 <210> 267 <211> 1353 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 267 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc caccaacttc 180 ggcggaggct tccgggatag agtgaccctg acccgggacg tgtaccgcga gatcgcctac 240 atggacatcc ggggcctgaa gcccgatgac accgccgtgt actactgcgc cagagacaga 300 agctacggcg acagcagctg ggctctggat gcttggggcc agggcacaac cgtggtggtg 360 tctgccgcct ctacaaaggg cccatcggtc ttccccctgg caccctcctc caagagcacc 420 tctgggggca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 480 gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 540 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttgggcacc 600 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagaaagtt 660 gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 720 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 780 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 840 aactggtatg ttgacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 900 tacaacaatg cctcccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 960 ggcaaggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1020 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccatgccgg 1080 gatgagctga ccaagaatca agtcagcctg tggtgcctgg taaaaggctt ctatcccagc 1140 gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1200 cccgtgctgg actccgacgg ctccttcttc ctctactcaa aactcaccgt ggacaagagc 1260 aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1320 tacaccgcaga agagcctctc cctgtctccg ggt 1353 <210> 268 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 268 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagct ccgaagaggg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 269 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 269 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgcagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 270 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 270 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 271 <211> 1365 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 460 <223> n = A,T,C or G <400> 271 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcatcgccta catggacatc cggggcctga agcccgatga caccgccgtg 300 tactactgcg ccagagacag aagctacggc gacagcagct gggctctgga tgcttggggc 360 cagggcacaa ccgtggtggt gtctgccgcc tctacaaagg gcccatcggt gttccctctg 420 gccccttgca gcagaagcac cagcgaatct acagccgccn tgggctgcct cgtgaaggac 480 tactttcccg agcccgtgac cgtgtcctgg aactctggcg ctctgacaag cggcgtgcac 540 acctttccag ccgtgctcca gagcagcggc ctgtactctc tgagcagcgt cgtgacagtg 600 cccagcagca gcctgggcac caagacctac acctgtaacg tggaccacaa gcccagcaac 660 accaaggtgg acaagcgggt ggaatctaag tacggccctc cctgccctcc ttgcccagcc 720 cctgaagctg ccggcggacc ctccgtgttc ctgttccccc caaagcccaa ggacaccctg 780 atgatcagcc ggacccccga agtgacctgc gtggtggtgg atgtgtccca ggaagatccc 840 gaggtgcagt tcaattggta cgtggacggc gtggaagtgc acaacgccaa gaccaagccc 900 agagaggaac agttcaacag cacctaccgg gtggtgtccg tgctgaccgt gctgcaccag 960 gactggctga acggcaaaga gtacaagtgc aaggtgtcca acaagggcct gcccagctcc 1020 atcgagaaaa ccatcagcaa ggccaagggc cagccccgcg agcctcaagt gtataccctg 1080 cccccttgcc aggaagagat gaccaagaac caggtgtccc tgtggtgtct cgtgaaaggc 1140 ttctacccca gcgacattgc cgtggaatgg gagagcaacg gccagcccga gaacaactac 1200 aagaccaccc cccctgtgct ggacagcgac ggctcattct tcctgtactc caagctgacc 1260 gtggacaaga gccggtggca ggaaggcaac gtgttcagct gctccgtgat gcacgaggcc 1320 ctgcacaacc actacaccca gaagtccctg tctctgtccc tgggc 1365 <210> 272 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 272 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 273 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 273 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgttcaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 274 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 274 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 275 <211> 1365 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 460 <223> n = A,T,C or G <400> 275 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcatcgccta catggacatc cggggcctga agcccgatga caccgccgtg 300 tactactgcg ccagagacag aagctacggc gacagcagct gggctctgga tgcttggggc 360 cagggcacaa ccgtggtggt gtctgccgcc tctacaaagg gcccatcggt gttccctctg 420 gccccttgca gcagaagcac cagcgaatct acagccgccn tgggctgcct cgtgaaggac 480 tactttcccg agcccgtgac cgtgtcctgg aactctggcg ctctgacaag cggcgtgcac 540 acctttccag ccgtgctcca gagcagcggc ctgtactctc tgagcagcgt cgtgacagtg 600 cccagcagca gcctgggcac caagacctac acctgtaacg tggaccacaa gcccagcaac 660 accaaggtgg acaagcgggt ggaatctaag tacggccctc cctgccctcc ttgcccagcc 720 cctgaagctg ccggcggacc ctccgtgttc ctgttccccc caaagcccaa ggacaccctg 780 atgatcagcc ggacccccga agtgacctgc gtggtggtgg atgtgtccca ggaagatccc 840 gaggtgcagt tcaattggta cgtggacggc gtggaagtgc acaacgccaa gaccaagccc 900 agagaggaac agttcaacag cacctaccgg gtggtgtccg tgctgaccgt gctgcaccag 960 gactggctga acggcaaaga gtacaagtgc aaggtgtcca acaagggcct gcccagctcc 1020 atcgagaaaa ccatcagcaa ggccaagggc cagccccgcg agcctcaagt gtataccctg 1080 cccccttgcc aggaagagat gaccaagaac caggtgtccc tgtggtgtct cgtgaaaggc 1140 ttctacccca gcgacattgc cgtggaatgg gagagcaacg gccagcccga gaacaactac 1200 aagaccaccc cccctgtgct ggacagcgac ggctcattct tcctgtactc caagctgacc 1260 gtggacaaga gccggtggca ggaaggcaac gtgttcagct gctccgtgat gcacgaggcc 1320 ctgcacaacc actacaccca gaagtccctg tctctgtccc tgggc 1365 <210> 276 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 276 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 277 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 277 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgcagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 278 <211> 1740 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 278 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc cagcgtgttc 780 cctctggccc ctagcagcaa gagcacatct ggcggaacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaatt ctggcgccct gaccagcggc 900 gtgcacacct ttccagctgt gctgcagtcc agcggcctgt acagcctgag cagcgtcgtg 960 acagtgccca gcagctctct gggcacccag acctacatct gcaacgtgaa ccacaagccc 1020 agcaacacca aggtggacaa gaaggtggaa cccaagagct gcgacaagac ccacacctgt 1080 cccccttgtc ctgcccccga actgctggga ggcccttccg tgttcctgtt ccccccaaag 1140 cccaaggaca ccctgatgat cagccggacc cccgaagtga cctgcgtggt ggtggatgtg 1200 tcccacgagg accctgaagt gaagttcaat tggtacgtgg acggcgtgga agtgcacaac 1260 gccaagacca agccaagaga ggaacagtac aacaatgcct cccgggtggt gtccgtgctg 1320 accgtgctgc accaggactg gctgaacggc aaagagtaca agtgcaaggt gtccaacaag 1380 gccctgcctg cccccatcga gaaaaccatc agcaaggcca agggccagcc ccgcgaaccc 1440 caggtgtgca cactgccccc aagcagggac gagctgacca agaaccaggt gtccctgagc 1500 tgtgccgtga aaggcttcta cccctccgat atcgccgtgg aatgggagag caacggccag 1560 cccgagaaca actacaagac caccccccct gtgctggaca gcgacggctc attcttcctg 1620 gtgtccaagc tgacagtgga caagtcccgg tggcagcagg gcaacgtgtt cagctgctcc 1680 gtgatgcacg aggccctgca caaccactac acccagaagt ccctgagcct gagccccggc 1740 <210> 279 <211> 1374 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 279 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcatcgccta catggacatc cggggcctga agcccgatga caccgccgtg 300 tactactgcg ccagagacag aagctacggc gacagcagct gggctctgga tgcttggggc 360 cagggcacaa ccgtggtggt gtctgccgcc tctacaaagg gcccatcggt cttccccctg 420 gcaccctcct ccaagagcac ctctgggggc acagcggccc tgggctgcct ggtcaaggac 480 tacttccccg aaccggtgac ggtgtcgtgg aactcaggcg ccctgaccag cggcgtgcac 540 accttcccgg ctgtcctaca gtcctcagga ctctactccc tcagcagcgt ggtgaccgtg 600 ccctccagca gcttgggcac ccagacctac atctgcaacg tgaatcacaa gcccagcaac 660 accaaggtgg acaagaaagt tgagcccaaa tcttgtgaca aaactcacac atgcccaccg 720 tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccc aaaacccaag 780 gacaccctca tgatctcccg gacccctgag gtcacatgcg tggtggtgga cgtgagccac 840 gaagaccctg aggtcaagtt caactggtat gttgacggcg tggaggtgca taatgccaag 900 acaaagccgc gggaggagca gtacaacaat gcctcccgtg tggtcagcgt cctcaccgtc 960 ctgcaccagg actggctgaa tggcaaggag tacaagtgca aggtctccaa caaagccctc 1020 ccagccccca tcgagaaaac catctccaaa gccaaagggc agccccgaga accacaggtg 1080 tacaccctgc ccccatgccg ggatgagctg accaagaatc aagtcagcct gtggtgcctg 1140 gtaaaaggct tctatcccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1200 aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctactca 1260 aaactcaccg tggacaagag caggtggcag caggggaacg tcttctcatg ctccgtgatg 1320 catgaggctc tgcacaacca ctacaccgcag aagagcctct ccctgtctcc gggt 1374 <210> 280 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 280 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 281 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 281 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgttcaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 282 <211> 1740 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 282 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc cagcgtgttc 780 cctctggccc ctagcagcaa gagcacatct ggcggaacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaatt ctggcgccct gaccagcggc 900 gtgcacacct ttccagctgt gctgcagtcc agcggcctgt acagcctgag cagcgtcgtg 960 acagtgccca gcagctctct gggcacccag acctacatct gcaacgtgaa ccacaagccc 1020 agcaacacca aggtggacaa gaaggtggaa cccaagagct gcgacaagac ccacacctgt 1080 cccccttgtc ctgcccccga actgctggga ggcccttccg tgttcctgtt ccccccaaag 1140 cccaaggaca ccctgatgat cagccggacc cccgaagtga cctgcgtggt ggtggatgtg 1200 tcccacgagg accctgaagt gaagttcaat tggtacgtgg acggcgtgga agtgcacaac 1260 gccaagacca agccaagaga ggaacagtac aacaatgcct cccgggtggt gtccgtgctg 1320 accgtgctgc accaggactg gctgaacggc aaagagtaca agtgcaaggt gtccaacaag 1380 gccctgcctg cccccatcga gaaaaccatc agcaaggcca agggccagcc ccgcgaaccc 1440 caggtgtgca cactgccccc aagcagggac gagctgacca agaaccaggt gtccctgagc 1500 tgtgccgtga aaggcttcta cccctccgat atcgccgtgg aatgggagag caacggccag 1560 cccgagaaca actacaagac caccccccct gtgctggaca gcgacggctc attcttcctg 1620 gtgtccaagc tgacagtgga caagtcccgg tggcagcagg gcaacgtgtt cagctgctcc 1680 gtgatgcacg aggccctgca caaccactac acccagaagt ccctgagcct gagccccggc 1740 <210> 283 <211> 1374 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 283 agagcccacc tggtgcagtc tggcaccgcc atgaagaaac caggcgcctc tgtgcgggtg 60 tcctgtcaga caagcggcta caccttcacc gcccacatcc tgttctggtt ccggcaggcc 120 cctggcagag gactggaatg ggtgggatgg atcaagcccc agtatggcgc cgtgaacttc 180 ggcggaggct tccgggatag agtgaccctg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcatcgccta catggacatc cggggcctga agcccgatga caccgccgtg 300 tactactgcg ccagagacag aagctacggc gacagcagct gggctctgga tgcttggggc 360 cagggcacaa ccgtggtggt gtctgccgcc tctacaaagg gcccatcggt cttccccctg 420 gcaccctcct ccaagagcac ctctgggggc acagcggccc tgggctgcct ggtcaaggac 480 tacttccccg aaccggtgac ggtgtcgtgg aactcaggcg ccctgaccag cggcgtgcac 540 accttcccgg ctgtcctaca gtcctcagga ctctactccc tcagcagcgt ggtgaccgtg 600 ccctccagca gcttgggcac ccagacctac atctgcaacg tgaatcacaa gcccagcaac 660 accaaggtgg acaagaaagt tgagcccaaa tcttgtgaca aaactcacac atgcccaccg 720 tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccc aaaacccaag 780 gacaccctca tgatctcccg gacccctgag gtcacatgcg tggtggtgga cgtgagccac 840 gaagaccctg aggtcaagtt caactggtat gttgacggcg tggaggtgca taatgccaag 900 acaaagccgc gggaggagca gtacaacaat gcctcccgtg tggtcagcgt cctcaccgtc 960 ctgcaccagg actggctgaa tggcaaggag tacaagtgca aggtctccaa caaagccctc 1020 ccagccccca tcgagaaaac catctccaaa gccaaagggc agccccgaga accacaggtg 1080 tacaccctgc ccccatgccg ggatgagctg accaagaatc aagtcagcct gtggtgcctg 1140 gtaaaaggct tctatcccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1200 aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctactca 1260 aaactcaccg tggacaagag caggtggcag caggggaacg tcttctcatg ctccgtgatg 1320 catgaggctc tgcacaacca ctacaccgcag aagagcctct ccctgtctcc gggt 1374 <210> 284 <211> 630 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 284 tacatccacg tgacccagag ccccagcagc ctgtccgtgt ccatcggcga cagagtgacc 60 atcaactgcc agacctctca gggcgtgggc agcgacctgc actggtatca gcacaagcct 120 ggcagagccc ccaagctgct gatccaccac acaagcagcg tggaagatgg cgtgcccagc 180 agattttccg gcagcggctt ccacaccagc ttcaacctga ccatcagcga tctgcaggcc 240 gacgacattg ccacctacta ttgtcaggtg ctgcagttct tcggcagagg cagcagactg 300 cacatcaagc gtacggtggc cgctcccagc gtgttcatct tcccacctag cgacgagcag 360 ctgaagtccg gcacagcctc tgtcgtgtgc ctgctgaaca acttctaccc ccgcgaggcc 420 aaagtgcagt ggaaggtgga caacgccctg cagagcggca acagccagga aagcgtgacc 480 gagcaggaca gcaaggactc cacctacagc ctgagcagca ccctgacact gagcaaggcc 540 gactacgaga agcacaaggt gtacgcctgc gaagtgaccc accagggcct gtctagcccc 600 gtgaccaaga gcttcaaccg gggcgagtgt 630 <210> 285 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 285 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgcagaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 286 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 286 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 287 <211> 1362 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 457, 518, 520 <223> n = A,T,C or G <400> 287 caggtgcagc tggtgcagtc tggcggccag atgaagaaac ccggcgagag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc gactgcaccc tgaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg ctgaagccta gatggggagc cgtgaactac 180 gccagacctc tgcagggcag agtgaccatg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcaccgcctt cctggaactg cggagcctga ccgtggatga taccgccgtg 300 tacttctgca cccggggcaa gaactgcgac tacaactggg acttcgagca ctggggcaga 360 ggcacccctg tgatcgtgtc aagcgcgtcg accaagggcc catcggtgtt ccctctggcc 420 ccttgcagca gaagcaccag cgaatctaca gccgccntgg gctgcctcgt gaaggactac 480 tttcccgagc ccgtgaccgt gtcctggaac tctggcgntn tgacaagcgg cgtgcacacc 540 tttccagccg tgctccagag cagcggcctg tactctctga gcagcgtcgt gacagtgccc 600 agcagcagcc tgggcaccaa gacctacacc tgtaacgtgg accacaagcc cagcaacacc 660 aaggtggaca agcgggtgga atctaagtac ggccctccct gccctccttg cccagcccct 720 gaagctgccg gcggaccctc cgtgttcctg ttccccccaa agcccaagga caccctgatg 780 atcagccgga cccccgaagt gacctgcgtg gtggtggatg tgtcccagga agatcccgag 840 gtgcagttca attggtacgt ggacggcgtg gaagtgcaca acgccaagac caagcccaga 900 gaggaacagt tcaacagcac ctaccgggtg gtgtccgtgc tgaccgtgct gcaccaggac 960 tggctgaacg gcaaagagta caagtgcaag gtgtccaaca agggcctgcc cagctccatc 1020 gagaaaacca tcagcaaggc caagggccag ccccgcgagc ctcaagtgta taccctgccc 1080 ccttgccagg aagagatgac caagaaccag gtgtccctgt ggtgtctcgt gaaaggcttc 1140 taccccagcg acattgccgt ggaatgggag agcaacggcc agcccgagaa caactacaag 1200 accacccccc ctgtgctgga cagcgacggc tcattcttcc tgtactccaa gctgaccgtg 1260 gacaagagcc ggtggcagga aggcaacgtg ttcagctgct ccgtgatgca cgaggccctg 1320 cacaaccact accaccagaa gtccctgtct ctgtccctgg gc 1362 <210> 288 <211> 621 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 288 ctgacacaga gccctggcac cctgtcactg agcccaggcg agacagccat catcagctgc 60 cggacaagcc agtacggcag cctggcctgg tatcagcaga ggcctggaca ggcccccaga 120 ctcgtgatct acagcggcag cacaagagcc gccggaatcc ccgatagatt cagcggctcc 180 agatggggac ccgactacaa cctgaccatc agcaacctgg aaagcggcga cttcggcgtg 240 tactactgcc agcagtacga gttcttcggc cagggcacca aggtgcaggt ggacatcaag 300 cgtacggtgg ccgctcccag cgtgttcatc ttcccaccta gcgacgagca gctgaagtcc 360 ggcacagcct ctgtcgtgtg cctgctgaac aacttctacc cccgcgaggc caaagtgcag 420 tggaaggtgg acaacgccct gcagagcggc aacagccagg aaagcgtgac cgagcaggac 480 agcaaggact ccacctacag cctgagcagc accctgacac tgagcaaggc cgactacgag 540 aagcacaagg tgtacgcctg cgaagtgacc caccagggcc tgtctagccc cgtgaccaag 600 agcttcaacc ggggcgagtg t 621 <210> 289 <211> 1008 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 289 gacatcgtga tgacccagac ccccctgagc ctgagcgtga cacctggaca gcctgccagc 60 atcagctgca agagcagcca gagcctggtg cacgagaacc tgttcaccta cctgagctgg 120 tatctgcaga agcccggcca gagcccccag tccctgatct acaaggtgtc caacagattc 180 agcggcgtgc ccgacagatt ctccggcagc ggctctggca ccgacttcac cctgaagatc 240 agccgggtgg aagccgagga cgtgggcgtg tactattgtg gccagggcac ccagtacccc 300 ttcacctttg gcagcggcac caaggtggaa atcaaggaca aaacccatac cgacatccag 360 atgacccaga gccccagcag cctgtctgcc agcgtgggcg acagagtgac catcacctgt 420 caggccagcc agaacatcta cgtgtggctg aactggtatc agcagaagcc cggcaaggcc 480 cccaagctgc tgatctacaa ggccagcaac ctgcacaccg gcgtgcccag cagattttct 540 ggcagcggct ccggcaccga cttcaccctg acaatcagct ccctgcagcc cgaggacatt 600 gccacctact actgccagca gggccagacc tacccctaca cctttggcca gggcaccaag 660 ctggaaatca aggataagac ccacacccgt acggtggccg ctcccagcgt gttcatcttc 720 ccacctagcg acgagcagct gaagtccggc acagcctctg tcgtgtgcct gctgaacaac 780 ttctaccccc gcgaggccaa agtgcagtgg aaggtggaca acgccctgca gagcggcaac 840 agccaggaaa gcgtgaccga gcaggacagc aaggactcca cctacagcct gagcagcacc 900 ctgacactga gcaaggccga ctacgagaag cacaaggtgt acgcctgcga agtgacccac 960 cagggcctgt ctagccccgt gaccaagagc ttcaaccggg gcgagtgt 1008 <210> 290 <211> 1731 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 290 caggtgcagc tggtgcagtc tggcgccgag gtcgtgaaac ctggcgcctc tgtgaaggtg 60 tcctgcaagg ccagcggcta cacctttacc agctactaca tccactgggt gcgccaggcc 120 cctggacagg gactggaatg gatcggcagc atctaccccg gcaacgtgaa caccaactac 180 gcccagaagt tccagggcag agccaccctg accgtggaca ccagcatcag caccgcctac 240 atggaactga gccggctgag aagcgacgac accgccgtgt actactgcac ccggtcccac 300 tacggcctgg attggaactt cgacgtgtgg ggcaagggca ccaccgtgac agtgtctagc 360 gacaaaaccc atacccaggt gcagctggtg gaatctggcg gcggagtggt gcagcctggc 420 agaagcctga gactgagctg tgccgccagc ggcttcacct tcaccaaggc ctggatgcac 480 tgggtgcgcc aggcccctgg aaagcagctg gaatgggtgg cccagatcaa ggacaagagc 540 aacagctacg ccacctacta cgccgacagc gtgaagggcc ggttcaccat cagccgggac 600 gacagcaaga acaccctgta cctgcagatg aacagcctgc gggccgagga caccgccgtg 660 tactactgtc ggggcgtgta ctatgccctg agccccttcg attactgggg ccagggaacc 720 ctcgtgaccg tgtctagtga taagacccac accgccagca caaagggccc atcggtgttc 780 cctctggccc cttgcagcag aagcaccagc gaatctacag ccgccctggg ctgcctcgtg 840 aaggactact ttcccgagcc cgtgaccgtg tcctggaact ctggcgctct gacaagcggc 900 gtgcacacct ttccagccgt gctccagagc agcggcctgt actctctgag cagcgtcgtg 960 acagtgccca gcagcagcct gggcaccaag acctacacct gtaacgtgga ccacaagccc 1020 agcaacacca aggtggacaa gcgggtggaa tctaagtacg gccctccctg ccctccttgc 1080 ccagcccctg aagctgccgg cggaccctcc gtgttcctgt tccccccaaa gcccaaggac 1140 accctgatga tcagccggac ccccgaagtg acctgcgtgg tggtggatgt gtcccaggaa 1200 gatcccgagg tgcagttcaa ttggtacgtg gacggcgtgg aagtgcacaa cgccaagacc 1260 aagcccagag aggaacagtt caacagcacc taccgggtgg tgtccgtgct gaccgtgctg 1320 caccaggact ggctgaacgg caaagagtac aagtgcaagg tgtccaacaa gggcctgccc 1380 agctccatcg agaaaaccat cagcaaggcc aagggccagc cccgcgagcc tcaagtgtgt 1440 accctgcccc ctagccagga agagatgacc aagaaccagg tgtccctgag ctgtgccgtg 1500 aaaggcttct accccagcga cattgccgtg gaatgggaga gcaacggcca gcccgagaac 1560 aactacaaga ccaccccccc tgtgctggac agcgacggct cattcttcct ggtgtccaag 1620 ctgaccgtgg acaagagccg gtggcaggaa ggcaacgtgt tcagctgctc cgtgatgcac 1680 gaggccctgc acaaccacta cacccagaag tccctgtctc tgtccctggg c 1731 <210> 291 <211> 1362 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> misc_feature <222> 457, 518, 520 <223> n = A,T,C or G <400> 291 caggtgcagc tggtgcagtc tggcggccag atgaagaaac ccggcgagag catgcggatc 60 agctgcagag ccagcggcta cgagttcatc gactgcaccc tgaactggat cagactggcc 120 cctggcaagc ggcctgagtg gatgggatgg ctgaagccta gatggggagc cgtgaactac 180 gccagacctc tgcagggcag agtgaccatg acccggcagc tgagccagga ccctgatgat 240 ccggattggg gcaccgcctt cctggaactg cggagcctga ccgtggatga taccgccgtg 300 tacttctgca cccggggcaa gaactgcgac tacaactggg acttcgagca ctggggcaga 360 ggcacccctg tgatcgtgtc aagcgcgtcg accaagggcc catcggtgtt ccctctggcc 420 ccttgcagca gaagcaccag cgaatctaca gccgccntgg gctgcctcgt gaaggactac 480 tttcccgagc ccgtgaccgt gtcctggaac tctggcgntn tgacaagcgg cgtgcacacc 540 tttccagccg tgctccagag cagcggcctg tactctctga gcagcgtcgt gacagtgccc 600 agcagcagcc tgggcaccaa gacctacacc tgtaacgtgg accacaagcc cagcaacacc 660 aaggtggaca agcgggtgga atctaagtac ggccctccct gccctccttg cccagcccct 720 gaagctgccg gcggaccctc cgtgttcctg ttccccccaa agcccaagga caccctgatg 780 atcagccgga cccccgaagt gacctgcgtg gtggtggatg tgtcccagga agatcccgag 840 gtgcagttca attggtacgt ggacggcgtg gaagtgcaca acgccaagac caagcccaga 900 gaggaacagt tcaacagcac ctaccgggtg gtgtccgtgc tgaccgtgct gcaccaggac 960 tggctgaacg gcaaagagta caagtgcaag gtgtccaaca agggcctgcc cagctccatc 1020 gagaaaacca tcagcaaggc caagggccag ccccgcgagc ctcaagtgta taccctgccc 1080 ccttgccagg aagagatgac caagaaccag gtgtccctgt ggtgtctcgt gaaaggcttc 1140 taccccagcg acattgccgt ggaatgggag agcaacggcc agcccgagaa caactacaag 1200 accacccccc ctgtgctgga cagcgacggc tcattcttcc tgtactccaa gctgaccgtg 1260 gacaagagcc ggtggcagga aggcaacgtg ttcagctgct ccgtgatgca cgaggccctg 1320 cacaaccact accaccagaa gtccctgtct ctgtccctgg gc 1362 <210> 292 <211> 621 <212> DNA <213> Artificial Sequence <220> <223> Synthetic Construct <400> 292 ctgacacaga gccctggcac cctgtcactg agcccaggcg agacagccat catcagctgc 60 cggacaagcc agtacggcag cctggcctgg tatcagcaga ggcctggaca ggcccccaga 120 ctcgtgatct acagcggcag cacaagagcc gccggaatcc ccgatagatt cagcggctcc 180 agatggggac ccgactacaa cctgaccatc agcaacctgg aaagcggcga cttcggcgtg 240 tactactgcc agcagtacga gttcttcggc cagggcacca aggtgcaggt ggacatcaag 300 cgtacggtgg ccgctcccag cgtgttcatc ttcccaccta gcgacgagca gctgaagtcc 360 ggcacagcct ctgtcgtgtg cctgctgaac aacttctacc cccgcgaggc caaagtgcag 420 tggaaggtgg acaacgccct gcagagcggc aacagccagg aaagcgtgac cgagcaggac 480 agcaaggact ccacctacag cctgagcagc accctgacac tgagcaaggc cgactacgag 540 aagcacaagg tgtacgcctg cgaagtgacc caccagggcc tgtctagccc cgtgaccaag 600 agcttcaacc ggggcgagtg t 621 <210> 293 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <220> <221> VARIANT <222> 6 <223> Xaa = Glu or Gln <220> <221> VARIANT <222> 8 <223> Xaa = Ala or Leu <220> <221> VARIANT <222> 9 <223> Xaa = Gln, Arg, or Phe <400> 293 Gln Ser Leu Val His Xaa Asn Xaa Xaa Thr Tyr 1 5 10

Claims (39)

A binding protein comprising four polypeptide chains forming three antigen binding sites that specifically bind to one or more HIV target proteins, wherein the first polypeptide chain comprises a structure represented by the formula
V_L2-L_One-V_L1-L₂-C_L [I]
The second polypeptide chain comprises a structure represented by the formula
V_H1-L₃-V_H2-L₄-C_H1-Hinge-C_H2-C_H3 [II]
The third polypeptide chain comprises a structure represented by the formula
V_H3-C_H1-Hinge-C_H2-C_H3 [III]
The fourth polypeptide chain comprises a structure represented by the formula
V_L3-C_L [IV]
during the meal,
V_L1is a first immunoglobulin light chain variable domain;
V_L2is a second immunoglobulin light chain variable domain;
V_L3is a third immunoglobulin light chain variable domain;
V_H1is a first immunoglobulin heavy chain variable domain;
V_H2is a second immunoglobulin heavy chain variable domain;
V_H3is a third immunoglobulin heavy chain variable domain;
C_Lis an immunoglobulin light chain constant domain;
C_H1Silver Immunoglobulin C_H1 heavy chain constant domain;
C_H2is immunoglobulin C_H2 heavy chain constant domain;
C_H3Silver Immunoglobulin C_H3 heavy chain constant domain;
Hinge is C_H1 domain and c_H2 an immunoglobulin hinge region that connects domains;
L_One, L₂, L₃, and L₄is an amino acid linker;
the polypeptide of formula I and the polypeptide of formula II form a cross light chain-heavy chain pair;
V_H1and V_L1forms a first antigen binding site;
V_H2and V_L2forms a second antigen binding site that binds to the CD3 polypeptide, and V_H2 The domain comprises a CDR-H1 sequence comprising the amino acid sequence of GFTFTKAW (SEQ ID NO: 20), a CDR-H2 sequence comprising the amino acid sequence of IKDKSNSYAT (SEQ ID NO: 21), and a CDR comprising the amino acid sequence of RGVYYALSPFDY (SEQ ID NO: 22) -H3 sequence, and V_L2 The domain is QSLVHX_OneNX₂X₃TY(X_Oneis E or Q, and X₂is A or L, and X₃is Q, R, or F) (SEQ ID NO: 293), a CDR-L2 sequence comprising the amino acid sequence of KVS (SEQ ID NO: 29), and GQGTQYPFT (SEQ ID NO: 30) a CDR-L3 sequence comprising an amino acid sequence;
V_H3and V_L3forms a third antigen binding site that binds to the HIV target protein. The binding protein of claim 1 , wherein the first binding site binds to a CD28 polypeptide. 3. The method of claim 2, wherein the V _H1 domain is a CDR-H1 sequence comprising the amino acid sequence of GYTFTSYY (SEQ ID NO: 31), a CDR-H2 sequence comprising the amino acid sequence of IYPGNVNT (SEQ ID NO: 32), and TRSHYGLDWNFDV (SEQ ID NO: 33) ), wherein the V _L1 domain comprises a CDR-L1 sequence comprising the amino acid sequence of QNIYVW (SEQ ID NO: 34), a CDR-L1 sequence comprising the amino acid sequence of KAS (SEQ ID NO: 35)- A binding protein comprising a L2 sequence and a CDR-L3 sequence comprising the amino acid sequence of QQGQTYPY (SEQ ID NO: 36). 4. The method of claim 3, V _H1 domains, binding protein comprising the amino acid sequence and / or, V _L1 domain of QVQLVQSGAEVVKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWIGSIYPGNVNTNYAQKFQGRATLTVDTSISTAYMELSRLRSDDTAVYYCTRSHYGLDWNFDVWGKGTTVTVSS (SEQ ID NO: 59) comprises the amino acid sequence of DIQMTQSPSSLSASVGDRVTITCQASQNIYVWLNWYQQKPGKAPKLLIYKASNLHTGVPSRFSGSGSGTDFTLTISSLQPEDIATYYCQQGQTYPYTFGQGTKLEIK (SEQ ID NO: 60). 5. The method of any one of claims 1 to 4, wherein _{the CDR-L1 sequence of the V L2} domain is QSLVHQNAQTY (SEQ ID NO: 24), QSLVHENLQTY (SEQ ID NO: 25), QSLVHENLFTY (SEQ ID NO: 26), and QSLVHENLRTY (SEQ ID NO: 27) ), a binding protein comprising an amino acid sequence selected from the group consisting of. 6. The method of claim 5, V _H2 domain QVQLVESGGGVVQPGRSLRLSCAASGFTFTKAWMHWVRQAPGKQLEWVAQIKDKSNSYATYYADSVKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCRGVYYALSPFDYWGQGTLVTVSS comprises the amino acid sequence of (SEQ ID NO: 52) and / or, V _L2 domain DIVMTQTPLSLSVTPGQPASISCKSSQSLVHQNAQTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 54), DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLQTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 55), DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLFTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 56), and DIVMTQTPLSLSVTPGQPASISCKSSQSLVHENLRTYLSWYLQKPGQSPQSLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCGQGTQYPFTFGSGTKVEIK (SEQ ID NO: 57). 7. The binding protein of any one of claims 1-6, wherein the third antigen binding site binds to an HIV target protein selected from the group consisting of glycoprotein 120, glycoprotein 41, and glycoprotein 160. 8. The method of claim 7,
(a) the V _H3 domain comprises a CDR-H1 sequence comprising the amino acid sequence of NCPIN (SEQ ID NO: 1), a CDR-H2 sequence comprising the amino acid sequence of WMKPRHGAVSYARQLQG (SEQ ID NO: 2), and an amino acid of GKYCTARDYYNWDFEH (SEQ ID NO: 3) a CDR-H3 sequence comprising the sequence, wherein the V _L3 domain comprises a CDR-L1 sequence comprising the amino acid sequence of RTSQYGSLA (SEQ ID NO: 4), a CDR-L2 sequence comprising the amino acid sequence of SGSTRAA (SEQ ID NO: 5), and a CDR-L3 sequence comprising the amino acid sequence of QQYEF (SEQ ID NO: 6);
(b) the V _H3 domain comprises a CDR-H1 sequence comprising the amino acid sequence of GYTFTAHI (SEQ ID NO: 7), a CDR-H2 sequence comprising the amino acid sequence of IKPQYGAV (SEQ ID NO: 8) or IKPQYGAT (SEQ ID NO: 9), and DRSYGDSSWALDA (SEQ ID NO: 10) comprising a CDR-H3 sequence comprising the amino acid sequence, V _L3 domain comprising the amino acid sequence of a CDR-L1 sequence comprising the amino acid sequence of QGVGSD (SEQ ID NO: 11), HTS (SEQ ID NO: 12) a CDR-L2 sequence comprising, and a CDR-L3 sequence comprising the amino acid sequence of CQVLQF (SEQ ID NO: 13);
(c) the V _H3 domain comprises a CDR-H1 sequence comprising the amino acid sequence of DCTLN (SEQ ID NO: 14), a CDR-H2 sequence comprising the amino acid sequence of WLKPRWGAVNYARPLQG (SEQ ID NO: 15), and amino acids of GKNCDYNWDFEH (SEQ ID NO: 16) a CDR-H3 sequence comprising the sequence, wherein the V _L3 domain comprises a CDR-L1 sequence comprising the amino acid sequence of RTSQYGSLA (SEQ ID NO: 17), a CDR-L2 sequence comprising the amino acid sequence of SGSTRAA (SEQ ID NO: 18), and a CDR-L3 sequence comprising the amino acid sequence of QQYEF (SEQ ID NO: 19). 9. The method of claim 8,
(a) V _H3 domains QVRLSQSGGQMKKPGDSMRISCRASGYEFINCPINWIRLAPGKRPEWMGWMKPRHGAVSYARQLQGRVTMTRDMYSETAFLELRSLTSDDTAVYFCTRGKYCTARDYYNWDFEHWGQGTPVTVSS (SEQ ID NO: 43) comprising the amino acid sequence and / or the, V _L3 domain comprises the amino acid sequence of SLTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQRPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNLTISNLESGDFGVYYCQQYEFFGQGTKVQVDIK (SEQ ID NO: 45) or;
(b) V is QVRLSQSGGQMKKPGDSMRISCRASGYEFINCPINWIRLAPGKRPEWMGWMKPRHGAVSYARQLQGRVTMTRQLSQDPDDPDWGTAFLELRSLTSDDTAVYFCTRGKYCTARDYYNWDFEHWGQGTPVTVSS _H3 domain (SEQ ID NO: 44) comprising the amino acid sequence and / or the, V _L3 domain comprises the amino acid sequence of SLTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQRPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNLTISNLESGDFGVYYCQQYEFFGQGTKVQVDIK (SEQ ID NO: 45) or;
(c) V domain RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA _H3 comprises the amino acid sequence of (SEQ ID NO: 46) and / or, V _L3 domain comprises the amino acid sequence of YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK (SEQ ID NO: 49) or;
(d) V is RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGATNFGGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA _H3 domain comprises the amino acid sequence of (SEQ ID NO: 47) and / or, V _L3 domain comprises the amino acid sequence of YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK (SEQ ID NO: 49) or;
(e) V is RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRQLSQDPDDPDWGIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA _H3 domain comprises the amino acid sequence of (SEQ ID NO: 48) and / or, V _L3 domain comprises the amino acid sequence of YIHVTQSPSSLSVSIGDRVTINCQTSQGVGSDLHWYQHKPGRAPKLLIHHTSSVEDGVPSRFSGSGFHTSFNLTISDLQADDIATYYCQVLQFFGRGSRLHIK (SEQ ID NO: 49) or;
(f) V _H3 domains, binding protein comprising the amino acid sequence of the amino acid sequence and / or, V _L3 of QVQLVQSGGQMKKPGESMRISCRASGYEFIDCTLNWIRLAPGKRPEWMGWLKPRWGAVNYARPLQGRVTMTRQLSQDPDDPDWGTAFLELRSLTVDDTAVYFCTRGKNCDYNWDFEHWGRGTPVIVSS domain (SEQ ID NO: 50) LTQSPGTLSLSPGETAIISCRTSQYGSLAWYQQRPGQAPRLVIYSGSTRAAGIPDRFSGSRWGPDYNLTISNLESGDFGVYYCQQYEFFGQGTKVQVDIK (SEQ ID NO: 51). 10. The binding protein of any one of claims 1-9, wherein _{at least one of L 1} , L ₂ , L ₃ , or L ₄ is independently 0 amino acids in length. 10. The method of any one of claims 1 to 9, wherein (a) L ₁ , L ₂ , L ₃ , and L ₄ are each independently 0 amino acids in length or GGGGSGGGGS (SEQ ID NO: 40), GGGGSGGGGSGGGGS (SEQ ID NO: 41) ), S, RT, TKGPS (SEQ ID NO: 39), GQPKAAP (SEQ ID NO: 38), and GGSGSSGSGG (SEQ ID NO: 42); (b) L ₁ , L ₂ , L ₃ , and L ₄ are each independently GGGGSGGGGS (SEQ ID NO: 40), GGGGSGGGGSGGGGS (SEQ ID NO: 41), S, RT, TKGPS (SEQ ID NO: 39), GQPKAAP (SEQ ID NO: 38) , and a sequence selected from the group consisting of GGSGSSGSGG (SEQ ID NO: 42). 10. The method of any one of claims 1 to 9, wherein L ₁ comprises the sequence GQPKAAP (SEQ ID NO: 38), L ₂ comprises the sequence TKGPS (SEQ ID NO: 39), L ₃ comprises the sequence S and , L ₄ comprises the sequence RT. 10. The binding protein of any one of claims 1-9, wherein _{at least one of L 1} , L ₂ , L ₃ , or L ₄ comprises the sequence DKTHT (SEQ ID NO: 37). The binding protein of claim 13 , wherein L ₁ , L ₂ , L ₃ , and L ₄ comprise the sequence DKTHT (SEQ ID NO: 37). 15. The method according to any one of claims 1 to 14, wherein the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG4 hinge-C _H2 -C _H3 domains, and the hinge-C _H2 -C _{H3 domains.} wherein the domain comprises amino acid substitutions at positions corresponding to positions 234 and 235 of human IgG4 according to the EU index, respectively, wherein the amino acid substitutions are F234A and L235A. 15. The method according to any one of claims 1 to 14, wherein the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG4 hinge-C _H2 -C _H3 domains, and the hinge-C _H2 -C _{H3 domains.} wherein the domain comprises an amino acid substitution at a position corresponding to positions 233 to 236 of human IgG4 according to the EU index, respectively, wherein the amino acid substitution is a deletion at E233P, F234V, L235A, and 236. 17. The method of any one of claims 1 to 16, wherein the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG4 hinge-C _H2 -C _H3 domains, and the hinge-C _H2 -C _{H3 domains.} and the domain comprises amino acid substitutions at positions corresponding to positions 228 and 409 of human IgG4 according to the EU index, respectively, wherein the amino acid substitutions are S228P and R409K. 15. The method according to any one of claims 1 to 14, wherein the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG1 hinge-C _H2 -C _H3 domains, and the hinge-C _H2 -C _{H3 domains.} wherein the domain comprises amino acid substitutions at positions corresponding to positions 234, 235, and 329 of human IgG1 according to the EU index, respectively, wherein the amino acid substitutions are L234A, L235A, and P329A. 15. The method according to any one of claims 1 to 14, wherein the hinge-C _H2 -C _H3 domains of the second and third polypeptide chains are human IgG1 hinge-C _H2 -C _H3 domains, and the hinge-C _H2 -C _{H3 domains.} wherein the domain comprises amino acid substitutions at positions corresponding to positions 298, 299, and 300 of human IgG1 according to the EU index, respectively, wherein the amino acid substitutions are S298N, T299A, and Y300S. 20. The method according to any one of claims 1 to 19, wherein the hinge-C _H2- C _H3 domain of the second polypeptide chain corresponds to positions 349, 366, 368, and 407 of human IgG1 or IgG4 according to the EU index. an amino acid substitution at the position, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; The hinge-C _H2- C _H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 or IgG4 according to the EU index, the amino acid substitutions being S354C and T366W. 20. The method according to any one of claims 1 to 19, wherein the hinge-C _H2- C _H3 domain of the second polypeptide chain has amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 or IgG4 according to the EU index. wherein the amino acid substitutions are S354C and T366W; the hinge-C _H2- C _H3 domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 or IgG4 according to the EU index, wherein the amino acid substitutions are Y349C, T366S , L368A, and Y407V. According to claim 1,
(a) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 61 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 61; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 62 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 62; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 63; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 64 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 64;
(b) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68;
(c) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 69 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 69; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 70 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 70; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 71 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 71; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 72 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 72;
(d) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 73 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 73; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 74 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 74; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 75 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 75; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 76 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 76;
(e) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 77 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 77; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 78 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 78; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 79 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 79; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 80 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 80;
(f) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 81 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 81; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 82 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 82; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 83 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 83; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 84 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 84;
(g) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 85 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 85; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:86 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:86; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 87 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 87; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 88 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 88;
(h) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 89 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 89; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 90 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 90; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 91 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 91; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 92 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 92;
(i) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 93 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 93; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 94 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 94; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 95 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 95; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 96 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 96;
(j) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 97 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 97; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 98 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 98; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 99 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 99; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 100 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 100;
(k) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 101 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 101; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 102 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 102; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 103 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 103; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 104 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 104;
(l) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 105 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 106 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 106; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 107 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 107; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 108 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 108;
(m) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 109 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 109; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 110 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 110; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 111 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 111; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 112 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 112;
(n) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 113 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 114 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 114; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 115 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 115; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 116 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 116;
(o) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 117 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 117; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 118 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 118; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 119 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 119; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 120 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 120;
(p) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 121 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 121; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 122 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 122; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 123 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 124 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 124;
(q) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 129 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 129; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 130 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 130; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 131 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 131; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 132 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 132;
(r) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 133 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 134 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 134; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 135 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 135; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 136 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 136;
(s) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 137 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 137; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 138 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 138; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 139 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 139; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 140 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 140;
(t) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 141 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 141; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 142 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 142; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 143 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 143; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 144 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 144;
(u) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 145 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 145; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 146 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 146; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 147 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 147; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 148 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 148;
(v) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 149 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 149; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 150 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 150; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 151 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 151; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 152 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 152;
(x) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 153 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 153; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 154 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 154; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 155 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 155; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 156 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 156;
(y) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 157 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 157; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 158 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 158; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 159 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 159; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 160 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 160;
(z) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 161 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 161; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 162 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 162; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO:163 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:163; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 164 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 164;
(aa) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 165 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 165; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 166 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 166; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 167 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 167; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 168 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168;
(bb) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 169 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 169; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 170 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 170; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 171 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 171; the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 172 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 172;
(cc) the first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 173 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 173; the second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 174 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 174; the third polypeptide chain comprises the amino acid sequence of SEQ ID NO: 175 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 175; wherein the fourth polypeptide chain comprises the amino acid sequence of SEQ ID NO: 176 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 176. 23. An isolated nucleic acid molecule comprising a nucleotide sequence encoding the binding protein of any one of claims 1-22. An expression vector comprising the nucleic acid molecule of claim 23 . An isolated host cell comprising the nucleic acid molecule of claim 23 or the expression vector of claim 24 . The isolated host cell of claim 25 , wherein the host cell is a mammalian or insect cell. 23. A pharmaceutical composition comprising the binding protein of any one of claims 1-22 and a pharmaceutically acceptable carrier. 29. A method of preventing and/or treating HIV infection in a patient comprising administering to the patient a therapeutically effective amount of at least one binding protein of any one of claims 1-22 or a pharmaceutical composition of claim 27. . 29. The method of claim 28, wherein the binding protein is co-administered with standard antiretroviral therapy. 30. The method of claim 28 or 29, wherein administration of the at least one binding protein results in clearance of one or more latent and/or chronic HIV-infected cells in the patient. 31. The method of any one of claims 28-30, wherein the patient is a human. The binding protein or pharmaceutical composition according to any one of claims 1 to 22 or the pharmaceutical composition according to claim 27 , for preventing and/or treating HIV infection in a patient. 33. The binding protein of claim 32, wherein the binding protein is co-administered with standard antiretroviral therapy. 34. The binding protein of claim 32 or 33, which results in clearance of one or more latent and/or chronic HIV-infected cells in the patient. 35. The binding protein of any one of claims 32-34, wherein the patient is a human. 23. A vector system comprising one or more vectors encoding the first, second, third, and fourth polypeptide chains of the binding protein of any one of claims 1-22. 37. The method of claim 36, wherein a first vector encoding a first polypeptide chain of a binding protein, a second vector encoding a second polypeptide chain of a binding protein, a third vector encoding a third polypeptide chain of a binding protein, and binding A vector system comprising a fourth vector encoding a fourth polypeptide chain of a protein. (a) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 177, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 178, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 179, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 180;
(b) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 181, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 182, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 183, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 184;
(c) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 185, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 186, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 187, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 188;
(d) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 189, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 190, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 191, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 192;
(e) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 193, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 194, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 195, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 196;
(f) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 197, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 198, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 199, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 200;
(g) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 201, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 202, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 203, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 204;
(h) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 205, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 206, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 207, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 208;
(i) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 209, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 210, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 211, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 212;
(j) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 213, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 214, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 215, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 216;
(k) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 217, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 218, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 219, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 220;
(l) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 221, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 222, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 223, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 224;
(m) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 225, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 226, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 227, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 228;
(n) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 229, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 230, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 231, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 232;
(o) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 233, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 234, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 235, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 236;
(p) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 237, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 238, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 239, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 240;
(q) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 241, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 242, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 243, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 244;
(r) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 245, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 246, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 247, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 248;
(s) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 249, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 250, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 251, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of No. 252;
(t) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 253, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 254, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 255, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 256;
(u) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 257, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 258, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 259, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 260;
(v) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 261, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 262, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 263, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 264;
(w) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 265, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 266, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 267, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 268;
(x) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 269, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 270, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 271, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 272;
(y) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 273, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 274, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 275, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 276;
(z) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 277, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 278, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 279, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 280;
(aa) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 281, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 282, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 283, and the sequence a fourth polynucleotide comprising the polynucleotide sequence of number 284;
(bb) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 285, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 286, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 287, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 288; or
(cc) a first polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 289, a second polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 290, a third polynucleotide comprising the polynucleotide sequence of SEQ ID NO: 291, and a sequence a fourth polynucleotide comprising the polynucleotide sequence of number 292
A kit of polynucleotides comprising a. The kit of claim 38 , wherein the first, second, third, and fourth polynucleotides are present in one or more expression vectors.

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