RU2795625C2 - Antigen-binding proteins against gitr and methods of their use - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: invention relates to the recombinant production of an antibody or its antigen-binding fragment that binds GITR, and can be used in medicine for tumor therapy.

EFFECT: invention makes it possible to obtain an antibody or its antigen-binding fragment capable of specifically binding GITR and acting as a human GITR agonist with improved activity.

110 cl, 15 dwg, 14 tbl, 9 ex

Description

FIELD OF THE INVENTION

[1] The present invention relates to antigen-binding proteins (ABPs) with binding specificity for glucocorticoid-inducible tumor necrosis factor receptor (GITR)-related protein, and compositions containing such ABPs, including pharmaceutical compositions, diagnostic compositions, and kits. The invention relates to methods of obtaining ABP GITR, and to methods of using ABP GITR, for example, for therapeutic purposes, diagnostic purposes and research purposes.

BACKGROUND OF THE INVENTION

[2] GITR is a member of the tumor necrosis factor receptor (TNFR) superfamily. GITR is expressed in many cells of the innate and adaptive immune system, and membrane surface expression is increased in activated T cells. See Hanabuchib et al., Blood , 2006, 107:3617-3623; and Nocentini et al., Eur. J. Immunol. , 2005, 35:1016-1022; the full content of all of which is given in the present description by reference. GITR is activated by the GITR ligand (GITRL).

[3] GITR agonism has a costimulatory effect on effector T cells. See Schaer et al., Curr. Opin. Immunol. , 2012, 24:217-224, the full content of which is given as a reference. GITR agonists have been proposed as drugs for the treatment of malignant tumors. See Schaer et al., supra; Melero et al., Clin Cancer Res. , 2013, 19:1044-1053; Cohen et al., J. Clin. oncol. , 2007, 25:3058; Cohen et al., PLoS One , 2010, 5:e10436; Nocentini et al., Br. J Pharmacol. , 2012, 165:2089-2099; and US Patent Publication No. 2007/0098719; the full content of all of which is given in the present description by reference.

[4] Although GITR agonist antibodies have been shown to be promising in mouse models, it has been difficult to generate anti-human GITR agonist antibodies. In Nocentini et al. ( Br. J. Pharmacol. , 2012, 165:2089-2099) noted that "anti-GITR mAbs have a much weaker triggering potential in humans than in mice." The authors of the paper hypothesized that this may be a result of the fact that human GITR must be multimerized into stable trimers or superclusters (eg, trimer tetramers) in order to be highly activated.

[5] Thus, there is a need for an ABP that can act as a human GITR agonist more potently than known antibodies. The present invention relates to ABPs that meet this need.

SUMMARY OF THE INVENTION

[6] The present invention relates to ABPs that specifically bind GITR and methods of using such ABPs.

[7] In one aspect, the present invention provides an isolated multivalent antigen-binding protein (ABP) specifically binding to human GITR (hGITR; SEQ ID NO: 1) comprising the following six CDR sequences: (a) a CDR-H3 having the sequence X₁X₂X₃X₄X₅RGYGDYGGHHAFDI, where X₁ represents A or V, X₂ is H, D, L or R, X₃ represents E or D, X₄ is R, N, S, or A, and X₅ is V, D or G (SEQ ID NO:141); (b) CDR-H2 having the sequence X₁IX₂X₃SGX₄TYYNPSLKS where X₁ is G, L, or S, X₂represents Y, A, or V, X₃represents E, Y or H, and X₄represents S or K (SEQ ID NO:142); (c) CDR-H1 having the sequence X₁SISSX₂X₃X₄X₅WX₆, where X₁ represents Y or G, X₂represents G, S, or E X₃represents L, G, S, Y, or A, X₄represents G, A, Y, M, or G, X₅ is V, A, or absent, and X6 is S or G (SEQ ID NO:143); (d) a CDR-L3 having the sequence QQEYX₁TPPX₂, where X₁ is A or N, and X₂ is T or S (SEQ ID NO:144); (e) a CDR-L2 having the sequence X₁AX₂SLX₃X₄, where X₁ is A or S, X₂ is D or S, X₃represents Q, D, K or E, and X₄ is S or Y (SEQ ID NO:145); and (f) a CDR-L1 having the sequence X₁ASX₂SIX₃X4YLN, where X₁ is G or R, X₂ is Q or K, X3 is S, D or N, and X₄ is S or T (SEQ ID NO:146).

[8] In one embodiment, the ABP of (a) contains the V _H sequence of SEQ ID NO:9 and the V _L sequence of SEQ ID NO:10; in another embodiment, the ABP of (b) contains the V _H sequence of SEQ ID NO:19 and the V _L sequence of SEQ ID NO:20; in another embodiment, the ABP of (c) contains the V _H sequence of SEQ ID NO:26 and the V _L sequence of SEQ ID NO:27; in another embodiment, the ABP of (d) contains the V _H sequence from SEQ ID NO:26 or SEQ ID NO:34 and the V _L sequence from SEQ ID NO:35; in another embodiment, the ABP of (e) contains the V _H sequence of SEQ ID NO:26 and the V _L sequence of SEQ ID NO:40; in another embodiment, the ABP of (f) contains the V _H sequence of SEQ ID NO:44 and the V _L sequence of SEQ ID NO:45; in another embodiment, the ABP of (g) contains the V _H sequence of SEQ ID NO:44 and the V _L sequence of SEQ ID NO:53; in another embodiment, the ABP of (h) contains the V _H sequence of SEQ ID NO:58 and the V _L sequence of SEQ ID NO:10; in another embodiment, the ABP of (i) contains the V _H sequence of SEQ ID NO:104 and the V _L sequence of SEQ ID NO:10; and in another embodiment, the ABP of (j) contains the V _H sequence of SEQ ID NO:105 and the V _L sequence of SEQ ID NO:10.

[9] In one embodiment, the ABP of (b) contains the heavy chain of SEQ ID NO:7 and the light chain of SEQ ID NO:8; In another embodiment, the ABP of (b) contains the heavy chain of SEQ ID NO:17 and the light chain of SEQ ID NO:18. In another embodiment, the ABP of (c) contains the heavy chain of SEQ ID NO:24 and the light chain of SEQ ID NO:25. In another embodiment, the ABP of (d) comprises (i) the heavy chain from SEQ ID NO:32 and the light chain from SEQ ID NO:33, or (ii) the heavy chain from SEQ ID NO:37 and the light chain from SEQ ID NO:37 NO:33. In another embodiment, the ABP of (e) comprises (i) the heavy chain of SEQ ID NO:38 and the light chain of SEQ ID NO:39. In another embodiment, the ABP of (f) contains the heavy chain of SEQ ID NO:42 and the light chain of SEQ ID NO:43; in another embodiment, the ABP of (g) comprises (i) the heavy chain of SEQ ID NO:51 and the light chain of SEQ ID NO:52; In another embodiment, the ABP of (h) contains (i) the heavy chain of SEQ ID NO:57 and the light chain of SEQ ID NO:8; In another embodiment, the ABP of (i) comprises (i) the heavy chain from SEQ ID NO:114 and the light chain from SEQ ID NO:8, or (ii) the heavy chain from SEQ ID NO:120 and the light chain from SEQ ID NO:120 NO:8; or (iii) a heavy chain from SEQ ID NO:122 and a light chain from SEQ ID NO:8; or in another embodiment, the ABP of (j) comprises (i) the heavy chain from SEQ ID NO:115 and the light chain from SEQ ID NO:8, or (ii) the heavy chain from SEQ ID NO:121 and the light chain from SEQ ID NO:8; or (iii) a heavy chain from SEQ ID NO:123 and a light chain from SEQ ID NO:8.

[10] In another embodiment, the ABP comprises the heavy chain of SEQ ID NO:7 and the light chain of SEQ ID NO:8; or a heavy chain from SEQ ID NO:17 and a light chain from SEQ ID NO:18; or a heavy chain from SEQ ID NO:24 and a light chain from SEQ ID NO:25; the heavy chain from SEQ ID NO:32 and the light chain from SEQ ID NO:33, or (ii) the heavy chain from SEQ ID NO:37 and the light chain from SEQ ID NO:33; the heavy chain from SEQ ID NO:38 and the light chain from SEQ ID NO:39; the heavy chain from SEQ ID NO:42 and the light chain from SEQ ID NO:43; the heavy chain from SEQ ID NO:51 and the light chain from SEQ ID NO:52; the heavy chain from SEQ ID NO:57 and the light chain from SEQ ID NO:8; the heavy chain from SEQ ID NO:114 and the light chain from SEQ ID NO:8, or (ii) the heavy chain from SEQ ID NO:120 and the light chain from SEQ ID NO:8; or (iii) a heavy chain from SEQ ID NO:122 and a light chain from SEQ ID NO:8; or a heavy chain from SEQ ID NO:115 and a light chain from SEQ ID NO:8, or (ii) a heavy chain from SEQ ID NO:121 and a light chain from SEQ ID NO:8; or (iii) a heavy chain from SEQ ID NO:123 and a light chain from SEQ ID NO:8.

[11] In another aspect, the present invention provides an isolated multivalent antigen-binding protein (ABP) specifically binding human GITR (hGITR; SEQ ID NO: 1) comprising the following six CDR sequences: (a) a CDR-H3 having the sequence shown in SEQ ID NO:66; (b) a CDR-H2 having the sequence shown in SEQ ID NO:65; (c) a CDR-H1 having the sequence shown in SEQ ID NO:64; (d) a CDR-L3 having the sequence shown in SEQ ID NO:69; (e) a CDR-L2 having the sequence shown in SEQ ID NO:68; and (f) a CDR-L1 having the sequence shown in SEQ ID NO:67.

[12] In one embodiment, the ABP contains the V _H sequence of SEQ ID NO:62 and the V _L sequence of SEQ ID NO:63; the V _H sequence of SEQ ID NO:70 and the V _L sequence of SEQ ID NO:63; or the V _H sequence of SEQ ID NO:97 and the V _L sequence of SEQ ID NO:63.

[13] In another embodiment, the ABP comprises (i) the heavy chain of SEQ ID NO:171 and the light chain of SEQ ID NO:172; the heavy chain from SEQ ID NO:173 and the light chain from SEQ ID NO:174; the heavy chain sequence from SEQ ID NO:106 and the light chain sequence from SEQ ID NO:107; or (ii) the heavy chain sequence from SEQ ID NO:116 and the light chain sequence from SEQ ID NO:107.

[14] In another aspect, the present invention provides an isolated multivalent antigen-binding protein (ABP) specifically binding human GITR (hGITR; SEQ ID NO: 1) comprising the following six CDR sequences: (a) a CDR-H3 having the sequence shown in SEQ ID NO:75; (b) a CDR-H2 having the sequence shown in SEQ ID NO:74; (c) a CDR-H1 having the sequence shown in SEQ ID NO:73; (d) a CDR-L3 having the sequence shown in SEQ ID NO:78; (e) a CDR-L2 having the sequence shown in SEQ ID NO:77; and (f) a CDR-L1 having the sequence shown in SEQ ID NO:75.

[15] In one embodiment, the ABP contains the V _H sequence of SEQ ID NO:71 and the V _L sequence of SEQ ID NO:72; or the V _H sequence of SEQ ID NO:98 and the V _L sequence of SEQ ID NO:72.

[16] In another embodiment, the ABP comprises the heavy chain of SEQ ID NO:173 and the light chain of SEQ ID NO:109; or ABP contains (i) a heavy chain from SEQ ID NO:108 and a light chain from SEQ ID NO:109; or (ii) a heavy chain from SEQ ID NO:117 and a light chain from SEQ ID NO:109.

[17] In another aspect, the present invention provides an isolated multivalent antigen-binding protein (ABP) specifically binding human GITR (hGITR; SEQ ID NO: 1) comprising the following six CDR sequences: (a) a CDR-H3 having the sequence shown in SEQ ID NO:83; (b) a CDR-H2 having the sequence shown in (i) SEQ ID NO:82, or (ii) SEQ ID NO:100; (c) a CDR-H1 having the sequence shown in SEQ ID NO:81; (d) a CDR-L3 having the sequence shown in SEQ ID NO:86; (e) a CDR-L2 having the sequence shown in SEQ ID NO:85; and (f) a CDR-L1 having the sequence shown in SEQ ID NO:84.

[18] In one embodiment, the ABP contains the CDR-H2 sequence of (b)(i) of the above paragraph and the V _H sequence of SEQ ID NO:79 and the V _L sequence of SEQ ID NO:80. In another embodiment, the ABP contains the CDR-H2 sequence of (b)(i) of the above paragraph and the V _H sequence of SEQ ID NO:87 and the V _L sequence of SEQ ID NO:80. In another embodiment, the ABP contains the CDR-H2 sequence of (b)(i) of the above paragraph and the V _H sequence of SEQ ID NO:88 and the V _L sequence of SEQ ID NO:80. In another embodiment, the ABP contains the CDR-H2 sequence of (b)(ii) of the above paragraph and the V _H sequence of SEQ ID NO:99 and the V _L sequence of SEQ ID NO:80.

[19] In one embodiment, the ABP contains the heavy chain of SEQ ID NO:174 and the light chain of SEQ ID NO:111; In another embodiment, the ABP contains the heavy chain of SEQ ID NO:175 and the light chain of SEQ ID NO:111; in another embodiment, the ABP contains the heavy chain of SEQ ID NO:176 and the light chain of SEQ ID NO:111; In another embodiment, the ABP contains the heavy chain of SEQ ID NO:110 and the light chain of SEQ ID NO:111; or (ii) a heavy chain from SEQ ID NO:118 and a light chain from SEQ ID NO:111.

[20] In another aspect, the present invention relates to an isolated multivalent antigen-binding protein (ABP) specifically binding human GITR (hGITR; SEQ ID NO:1) containing the following six CDR sequences: (a) a CDR-H3 having the sequence specified in SEQ ID NO:93; (b) a CDR-H2 having the sequence GIIPIFGEAQYAQX ₁ FX ₂ G, where X ₁ is K or R and X ₂ is Q or R (SEQ ID NO:215); (c) a CDR-H1 having the sequence shown in SEQ ID NO:91; (d) a CDR-L3 having the sequence shown in SEQ ID NO:94; (d) a CDR-L2 having the sequence shown in SEQ ID NO:85; and (e) a CDR-L1 having the sequence shown in SEQ ID NO:84.

[21] In one embodiment, the ABP contains: CDR-H2 of SEQ ID NO:92; CDR-H2 of SEQ ID NO:96; or CDR-H2 of SEQ ID NO:102.

[22] In another embodiment, the ABP contains the V _H sequence of SEQ ID NO:89 and the V _L sequence of SEQ ID NO:90. In another embodiment, the ABP contains the V _H sequence from SEQ ID NO:95 and the V _L sequence from SEQ ID NO:90. In another embodiment, the ABP contains the V _H sequence from SEQ ID NO:101 and the V _L sequence from SEQ ID NO:90.

[23] In another embodiment, the ABP contains the heavy chain of SEQ ID NO:177 and the light chain of SEQ ID NO:113. In another embodiment, the ABP contains the heavy chain of SEQ ID NO:178 and the light chain of SEQ ID NO:113. In another embodiment, the ABP contains the heavy chain of SEQ ID NO:112 and the light chain of SEQ ID NO:113; or (ii) a heavy chain from SEQ ID NO:119 and a light chain from SEQ ID NO:113.

[24] In another aspect, the present invention relates to an isolated multivalent antigen-binding protein (ABP) specifically binding human GITR (hGITR; SEQ ID NO: 1) containing the following six CDR sequences: (a) a CDR-H3 having the sequence specified in SEQ ID NO:134; (b) CDR-H2 having the sequence shown in SEQ ID NO:133; CDR-H1 having the sequence shown in SEQ ID NO:132; (c) a CDR-L3 having the sequence shown in SEQ ID NO:135; (d) a CDR-L2 having the sequence shown in SEQ ID NO:68; and (e) a CDR-L1 having the sequence shown in SEQ ID NO:67.

[25] In one embodiment, the ABP comprises (i) a V _H sequence from SEQ ID NO:126 and a V _L sequence from SEQ ID NO:128; or (ii) the V _H sequence of SEQ ID NO:127 and the V _L sequence of SEQ ID NO:128.

[26] In one embodiment, the ABP comprises (i) the heavy chain of SEQ ID NO:124 and the light chain of SEQ ID NO:125; or (ii) a heavy chain from SEQ ID NO:136 and a light chain from SEQ ID NO:125.

[27] In another aspect, the present invention provides an isolated multivalent antigen-binding protein (ABP) specifically binding human GITR (hGITR; SEQ ID NO: 1) comprising: (a) a CDR-H3 having at least about 60% of at least about 70%, at least about 80%, at least about 90%, or at least about 95% identity with a CDR-H3 from a V _H region selected from SEQ ID NOs: 9, 19, 26, 34 , 44, 58, 62, 70, 71, 79, 87, 88, 89, 95, 97, 98, 99, 101, 104, 105, 126 and 127; (b) a CDR-H2 having at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% identity with a CDR-H2 from the region VH selected from SEQ ID NOs: 9, 19, 26, 34, 44, 58, 62, 70, 71, 79, 87, 88, 89, 95, 97, 98, 99, 101, 104, 105, 126 and 127; (c) a CDR-H1 having at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% identity with a CDR-H1 from the region VH selected from SEQ ID NOs: 9, 19, 26, 34, 44, 58, 62, 70, 71, 79, 87, 88, 89, 95, 97, 98, 99, 101, 104, 105, 126 and 127; (d) a CDR-L3 having at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% identity with a CDR-L3 from the region V _L selected from SEQ ID NOs: 10, 20, 27, 35, 40, 45, 53, 63, 72, 80, 90 and 128; (e) a CDR-L2 having at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% identity with a CDR-L2 from the region VL selected from SEQ ID NOs: 10, 20, 27, 35, 40, 45, 53, 63, 72, 80, 90, and 128; and (f) a CDR-L1 having at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% identity with a CDR-L1 of VL region selected from SEQ ID NOs: 10, 20, 27, 35, 40, 45, 53, 63, 72, 80, 90, and 128.

[28] In one embodiment, each of CDR-H3, CDR-H2, CDR-H1, CDR-L3, CDR-L2, and CDR-L1 is identified according to a numbering scheme selected from a Kabat numbering scheme, a Chothia numbering scheme, or IMGT numbering schemes. In another embodiment, CDR-H1 is identified as defined by both the Chothia and Kabat numbering schemes, including the boundaries of both numbering schemes.

[29] In one embodiment, the CDR-H3 comprises a CDR-H3 selected from SEQ ID NOs: 13, 23, 30, 48, 61, 66, 75, 83, 93, 103, 131, or a variant thereof having 1 , 2 or 3 amino acid substitutions. In another embodiment, the CDR-H2 comprises a CDR-H2 selected from SEQ ID NOs: 12, 22, 29, 47, 60, 65, 74, 82, 92, 96, 100, 102, 130, and 133, or a variant thereof having 1, 2 or 3 amino acid substitutions. In another embodiment, the CDR-H1 comprises a CDR-H1 selected from SEQ ID NOs: 11, 21, 28, 46, 59, 64, 73, 81, 91, 129, 132, or a variant thereof having 1 or 2 amino acids replacements. In another embodiment, the CDR-L3 comprises a CDR-L3 selected from SEQ ID NOs: 16, 17, 56, 69, 78, 86, 94, 135, or a variant thereof having 1, 2, or 3 amino acid substitutions. In another embodiment, the CDR-L2 comprises a CDR-L2 selected from SEQ ID NOs: 15, 31, 41, 50, 55, 68, 77 and 85, or a 1 amino acid substitution variant thereof. In another embodiment, the CDR-L1 comprises a CDR-L1 selected from SEQ ID NOs: 14, 36, 49, 54, 67, 76, and 84, or a variant thereof having 1, 2, or 3 amino acid substitutions. In one embodiment, the amino acid substitutions are conservative amino acid substitutions.

[30] In one embodiment of any of the above aspects, ABP: (a) competes for binding to GITR with an antibody selected from ABP1, ABP2, ABP3, ABP4, ABP5, ABP6, ABP7, ABP8, ABP9, ABP10, ABP11, ABP12 . A of this description; or (b) has at least three antigen-binding domains specifically binding an epitope on the GITR; or (c) has at least three antigen-binding domains specifically binding one epitope per GITR; or (d) has at least four antigen-binding domains specifically binding an epitope on the GITR; or (e) has at least four antigen-binding domains specifically binding one epitope per GITR; or (f) acts as a GITR agonist expressed on the surface of the target cell; or (g) enhances the binding of GITRL to GITR; or (h) co-stimulating an effector T cell in combination with antigen presentation from an antigen presenting cell; or (i) inhibits suppression of an effector T cell by a regulatory T cell; or (j) reduces the number of regulatory T cells in tissue or in the systemic circulation; (k) is capable of binding to one or more of the GITR residues (SEQ ID NO:1) from the group consisting of R56, C58, R59, D60, Y61, P62, E64, E65, C66 and C67; or (l) is capable of any combination of (a) - (k).

[31] In one embodiment of any of the above aspects, GITR is selected from hGITR (SEQ ID NO: 1), hGITR-T43R (SEQ ID NO: 2), cGITR (SEQ ID NO: 3), mGITR (SEQ ID NO: 4) and their combinations. In another embodiment, ABP (a) specifically binds cynomolgus monkey GITR (cGITR; SEQ ID NO: 3); (b) binds mouse GITR (mGITR; SEQ ID NO: 4) with an affinity lower (as indicated by higher KD) than ABP's affinity for hGITR, or does not bind mGITR; or (c) is capable of any combination of (a) - (b). In another embodiment, ABP: (a) specifically binds cGITR (SEQ ID NO: 3); (b) binds mGITR (SEQ ID NO: 4) with an affinity lower (as indicated by higher KD) than ABP's affinity for hGITR and cGITR; and (c) enhances the binding of GITRL to GITR.

[32] In another aspect, the present invention provides an ABP that competes for GITR binding with an ABP according to any one of paragraphs. 1-26, where ABP: (a) specifically binds cGITR (SEQ ID NO: 3); (b) binds mGITR (SEQ ID NO: 4) with an affinity lower (as indicated by higher KD) than ABP's affinity for hGITR and cGITR; and (c) enhances the binding of GITRL to GITR. In one embodiment, the ABP contains an antibody. In another embodiment, the antibody is a monoclonal antibody. In another embodiment, the antibody is selected from a human antibody, a humanized antibody, or a chimeric antibody. In another embodiment, ABP is multivalent. In another embodiment, the ABP contains an antibody fragment.

[33] In another embodiment, the ABP contains an alternative scaffold. In another embodiment, the ABP contains an immunoglobulin constant region. In another embodiment, the ABP contains a heavy chain constant region from a class selected from IgA, IgD, IgE, IgG, or IgM. In another embodiment, the ABP contains a heavy chain constant region from the IgG class and subclass selected from IgG4, IgG1, IgG2, or IgG3.

[34] In one embodiment of any of the above aspects, at least one Fab is fused to the C-terminus of an IgG Fc domain. In another embodiment, the ABP further comprises at least one linker. In another embodiment, the IgG is IgG4. In another embodiment, the IgG is IgG1. In another embodiment, at least one Fab is fused to the N-terminus of an IgG Fc domain. In one embodiment, at least one Fab is at least two Fabs. In another embodiment, at least one Fab is at least three Fabs. In another embodiment, at least one Fab is at least four Fabs. In another embodiment, the two Fabs are independently fused to the N-terminus of an IgG. In another embodiment, the two Fabs are independently fused to the C-terminus of an IgG. In another embodiment, a Fab is attached to each N-terminus of the IgG, a linker is attached to each specified Fab, and a Fab is attached to each linker. In another embodiment, a Fab is attached to each C-terminus of the IgG, a linker is attached to each specified Fab, and a Fab is attached to each linker. In another embodiment, each linker contains SEQ ID NO:5. In another embodiment, each linker contains SEQ ID NO:6.

[35] In one embodiment of any of the above aspects, the ABP comprises an antibody with a common light chain, an antibody with a ridge-in-the-depression modification, an scFv attached to an IgG, a Fab attached to an IgG, a diabody, a tetravalent bispecific antibody, a DVD-Ig ™, DART™, DuoBody®, CovX-Body, Fcab antibody, TandAb®, Fab tandem, Zybody™, or combinations thereof. In one embodiment, ABP binds more than one GITR molecule. In another embodiment, the ABP is independent of the GITRL binding. In another embodiment, ABP enhances the binding of GITRL to GITR by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%. , at least about 60%, at least about 70%, at least about 80%, or at least about 90%. In another embodiment, ABP enhances the binding of GITRL to GITR by at least about 50%. In another embodiment, the target cell is selected from an effector T cell, a regulatory T cell, a natural killer (NK) cell, a natural killer T (NKT) cell, a dendritic cell, and a B cell. In another embodiment, the target cell is an effector T cell selected from a helper T cell (CD4+), a cytotoxic T cell (CD8+), and combinations thereof. In another embodiment, the target cell is a regulatory T cell selected from CD4+CD25+Foxp3+ regulatory T cell, CD8+CD25+ regulatory T cell, and combinations thereof. In another embodiment, the tissue is a tumor.

[36] In one embodiment of any of the above aspects, the KD of the first antigen-binding domain for hGITR (SEQ ID NO: 1) or hGITR-T43R (SEQ ID NO: 2) is less than about 20 nM. In one embodiment, the KD of the first antigen-binding domain for cGITR (SEQ ID NO: 3) is less than about 200 nM. In another embodiment, the KD of the second antigen binding domain for hGITR (SEQ ID NO: 1) or hGITR-T43R (SEQ ID NO: 2) is less than about 100 nM. In another embodiment, the KD of the second antigen-binding domain for cGITR (SEQ ID NO: 3) is less than about 1 μM. In another embodiment, the ABP contains an Fc domain with reduced effector function compared to an IgG1 Fc domain. In another embodiment, the ABP contains an aglycosylated Fc domain. In another embodiment, the ABP contains an IgG1 Fc domain with an alanine at one or more of positions 234, 235, 265, and 297.

[37] In one embodiment of any of the above aspects, GITR is expressed on the surface of the target cell. In one embodiment, ABP causes multimerization of GITR expressed on the surface of the target cell. In one embodiment, ABP causes multimerization of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 GITR molecules.

[38] In one embodiment of any of the above aspects, the ABP specifically binds a human GITR epitope (hGITR; SEQ ID NO:1) and is capable of binding one or more residues from the group consisting of R56, C58, R59, D60, Y61, P62, E64, E65, C66 and C67.

[39] In one embodiment of any of the above aspects, the ABP comprises an immunoglobulin consisting of at least two distinct (i.e., having different sequences and/or binding to different residues) heavy chain variable regions, each paired with a heavy chain variable common light chain region. In another embodiment, the common light chain variable region forms a separate antigen binding domain with each of two different heavy chain variable regions. In another embodiment, the ABP comprises a first VH variable domain having SEQ ID NO:189, a second VH variable domain having SEQ ID NO:215, and a common light chain variable having SEQ ID NO:190. In another embodiment, the ABP comprises a first VH variable domain having SEQ ID NO:199, a second VH variable domain having SEQ ID NO:216, and a common light chain variable having SEQ ID NO:200.

[40] In another aspect, the present invention relates to a kit containing an ABP from any of the above aspects or listed in Appendix A, and instructions for using the ABP. In one embodiment, the ABP is lyophilized. In another embodiment, the kit further comprises a liquid for reconstituting the lyophilized ABP.

[41] It is known that when an antibody is expressed in cells, the antibody undergoes modification after translation. Examples of post-translational modification include cleavage of the lysine at the C-terminus of the heavy chain by carboxypeptidase; modification of glutamine or glutamic acid at the N-terminus of the heavy chain and light chain to pyrolutamic acid by pyroglutamylation; glycosylation; oxidation; deamidation; and glycation, and such post-translational modifications are known to occur in various antibodies (See journal of Pharmaceutical Sciences, 2008, Vol. 97, p. 2426-2447, the entire content of which is incorporated by reference). In some embodiments, the ABP of the invention is a post-translationally modified antibody or antigen-binding fragment thereof. Examples of an antibody or antigen-binding fragment thereof that have undergone post-translational modification include an antibody or antigen-binding fragment thereof that has undergone pyroglutamylation at the N-terminus of the heavy chain variable region and/or a lysine deletion at the C-terminus of the heavy chain. It is known in the art that such post-translational modification, due to pyroglutamilation at the N-terminus and deletion of lysine at the C-terminus, does not have any effect on the activity of the antibody or its fragment (Analytical Biochemistry, 2006, Vol. 348, p. 24- 39, the full content of which is given by reference).

[42] In one embodiment of any of the above aspects, the ABP contains a polypeptide sequence having a pyroglutamate (pE) residue at the N-terminus. In one embodiment, the ABP contains a V _H sequence in which the N-terminal Q is replaced by pE. In another embodiment, the ABP contains a V _L sequence in which the N-terminal E is replaced by pE. In another embodiment, the ABP contains a heavy chain sequence in which the N-terminal Q has been replaced with pE.

[43] In one embodiment of any of the above aspects, the ABP contains a light chain sequence in which the N-terminal E is replaced with pE. In another embodiment, the ABP is for use as a drug. In another embodiment, the ABP is for use in the treatment of cancer or a viral infection.

[44] In one embodiment, the ABP is for use in the treatment of cancer, where the cancer is selected from a solid tumor and a hematologic tumor.

[45] In another aspect, the present invention provides an isolated polynucleotide encoding an ABP of any of the above aspects or specified in Appendix A, its VH, its VL, its light chain, its heavy chain, or its antigen-binding portion.

[46] In another aspect, the present invention relates to a vector containing a polynucleotide of interest from the above aspect. In another aspect, the present invention relates to a host cell containing a polynucleotide or vector from any of the above aspects. In one embodiment, the host cell is selected from a bacterial cell, a fungal cell, and a mammalian cell. In another embodiment, the host cell is selected from an E. coli cell, a Saccharomyces cerevisiae cell, and a CHO cell.

[47] In another aspect, the present invention relates to a cell-free expression reaction mixture containing a polynucleotide or vector from the above aspects.

[48] In another aspect, the present invention relates to a method for obtaining ABP from any of the above aspects or specified in Appendix A, including the expression of ABP in a host cell and isolation of the expressed ABP.

[49] In another aspect, the present invention relates to a pharmaceutical composition containing an ABP from any of the above aspects or specified in Appendix A, and a pharmaceutically acceptable excipient. In one embodiment, the amount of ABP in the pharmaceutical composition is sufficient to (a) decrease the suppression of effector T cells by regulatory T cells; (b) activation of effector T cells; (c) reducing the number of regulatory T cells in tissue or systemically; (d) inducing or enhancing the proliferation of effector T cells; (e) slowing down the rate of tumor growth; (f) inducing tumor regression; or (g) combinations thereof, in a subject. In one embodiment, the pharmaceutical composition is for use as a drug, for example, for use in the treatment of cancer or a viral infection. In one embodiment, the pharmaceutical composition is for use in the treatment of cancer, where the cancer is selected from a solid tumor and a hematologic tumor.

[50] In another embodiment, the amount of ABP in the pharmaceutical composition is sufficient to (a) reduce the suppression of effector T cells by regulatory T cells; (b) activation of effector T cells; (c) reducing the number of regulatory T cells in tissue or systemically; (d) inducing or enhancing the proliferation of effector T cells; (e) slowing down the rate of tumor growth; (f) inducing tumor regression; or (g) combinations thereof, in a subject.

[51] In another aspect, the present invention relates to a method of treating or preventing a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of ABP from any of the above aspects or specified in Appendix A, or a pharmaceutical composition thereof.

[52] In another aspect, the present invention relates to a method of methods for increasing immunocyte activation in a subject, comprising administering to the subject an effective amount of ABP from any of the above aspects or specified in Appendix A, or a pharmaceutical composition thereof. In one embodiment, the disease or condition is cancer.

[53] In another embodiment, the method induces or enhances an immune response to a cancer-associated antigen. In another embodiment, ABP is administered in an amount sufficient to (a) decrease the suppression of effector T cells by regulatory T cells; (b) activation of effector T cells; (c) reducing the number of regulatory T cells in tissue or systemically; (d) inducing or enhancing the proliferation of effector T cells; (e) slowing down the rate of tumor growth; (f) inducing tumor regression; or (g) combinations thereof. In another embodiment, the cancer is a solid tumor. In another embodiment, the cancer is a hematological tumor. In another embodiment, the method further comprises administering one or more additional drugs. In one embodiment, the additional drug is selected from radiation exposure, a cytotoxic agent, a chemotherapeutic agent, a cytostatic agent, an antihormonal agent, an EGFR inhibitor, an immunostimulatory agent, an antiangiogenic agent, and combinations thereof. In one embodiment, the additional drug is an immunostimulatory agent. In one embodiment, the immunostimulatory agent comprises an agent that blocks the signaling of an inhibitory receptor expressed by the immunocyte, or a ligand thereof. In one embodiment, the immunocyte-expressed inhibitory receptor or ligand thereof is selected from CTLA-4, PD-1, PD-L1, NRP1, LAG-3, Tim3, TIGIT, neuritin, BTLA, KIR, and combinations thereof. In one embodiment, the immunostimulatory agent comprises a stimulatory receptor agonist expressed by an immunocyte. In another embodiment, the stimulatory receptor expressed by the immunocyte is selected from OX40, ICOS, CD27, CD28, 4-1BB, CD40, and combinations thereof. In another embodiment, the immunostimulatory agent contains a cytokine. In another embodiment, the cytokine is selected from IL-2, IL-5, IL-7, IL-12, IL-15, IL-21, and combinations thereof. In another embodiment, the immunostimulatory agent comprises an oncolytic virus. In another embodiment, the oncolytic virus is selected from herpes simplex virus, vesicular stomatitis virus, adenovirus, Newcastle disease virus, vaccinia virus, Marab virus, and combinations thereof. In another embodiment, the immunostimulatory agent comprises a T cell expressing a chimeric antigen receptor. In another embodiment, the immunostimulatory agent comprises a bi- or multispecific T cell-targeted antibody. In another embodiment, the immunostimulatory agent comprises an anti-TGF-β antibody, a TGF-β decoy, or a combination thereof. In another embodiment, the immunostimulatory agent comprises a cancer-associated antigen vaccine.

[54] In another aspect, the present invention relates to a method for modulating an immune response in a subject in need thereof, comprising administering to the subject an effective amount of ABP from any of the above aspects or specified in Appendix A, or a pharmaceutical composition thereof. In one embodiment, the method further comprises administering one or more additional drugs to the subject. In one embodiment, the additional drug is an immunocyte stimulatory receptor agonist and the immunocyte stimulatory receptor is selected from OX40, CD2, CD27, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), 4-1BB (CD137), CD28, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, CD83 ligand, and combinations thereof. In one embodiment, the additional drug is a cytokine selected from IL-2, IL-5, IL-7, IL-12, IL-15, IL-21, and combinations thereof. In one embodiment, the additional drug is an oncolytic virus selected from herpes simplex virus, vesicular stomatitis virus, adenovirus, Newcastle disease virus, vaccinia virus, Marab virus, and combinations thereof. In one embodiment, the additional drug is formulated in the same pharmaceutical composition as the ABP. In one embodiment, the additional drug is formulated in a pharmaceutical composition other than ABP. In one embodiment, the additional drug is administered prior to the administration of the ABP. In one embodiment, the additional drug is administered after administration of the ABP. In one embodiment, the additional drug is administered concurrently with the ABP.

[55] In another aspect, the present invention relates to an isolated multivalent antigen-binding protein (ABP) specifically binding to human GITR (hGITR; SEQ ID NO: 1), where ABP competes for binding with one or more of ABP1, ABP2, ABP3, ABP4, ABP5, ABP6, ABP7, ABP8, ABP9, ABP10, ABP11, ABP12, ABP13, ABP14, ABP15, ABP16, ABP17, ABP18, ABP19, ABP20, ABP21, ABP22, ABP23, ABP24, ABP25, ABP26, ABP27, ABP28, ABP29, ABP30, ABP31, ABP32, ABP33, and ABP34, ABP50, ABP51, ABP52, ABP53, ABP54, ABP55, ABP56, ABP57, ABP62, ABP63, ABP64, ABP65, ABP66, ABP67, ABP68, ABP67, ABP68, ABP69, ABP70, A BP71 . .ABP96 , ABP97, ABP98, ABP99, ABP100, ABP102, ABP103, ABP104, ABP105, ABP106, ABP107, ABP108 and ABP109, each as shown in Appendix A of this specification.

[56] In another aspect, the present invention relates to a human anti-GITR antibody, or antigen-binding fragment thereof, comprising four heavy chain variable regions and four light chain variable regions, wherein the heavy chain variable region comprises a CDR-H3 consisting of SEQ ID NO:13, CDR-H2 consisting of SEQ ID NO:12 and CDR-H1 consisting of SEQ ID NO:11; and the light chain variable region comprises a CDR-L3 consisting of SEQ ID NO:16, a CDR-L2 consisting of SEQ ID NO:15, and a CDR-L1 consisting of SEQ ID NO:14; and one heavy chain variable region and one light chain variable region constitute one antigen-binding site, and the antibody or antigen-binding fragment contains four antigen-binding sites.

[57] In one embodiment, the human anti-GITR antibody, or antigen-binding fragment thereof, comprises four heavy chain variable regions and four light chain variable regions, wherein the heavy chain variable region consists of SEQ ID NO: 9, the light chain variable region consists of SEQ ID NO: 10, and one heavy chain variable region and one light chain variable region constitute one antigen-binding site, and the antibody or antigen-binding fragment contains four antigen-binding sites.

[58] In one embodiment, the human anti-GITR antibody, or antigen-binding fragment thereof, comprises four heavy chain variable regions and four light chain variable regions, wherein the heavy chain variable region consists of SEQ ID NO: 9, wherein the Q at position 1 of the sequence is modified to pyroglutamate, the light chain variable region consists of SEQ ID NO: 10, and one heavy chain variable region and one light chain variable region constitute one antigen-binding site, and the antibody or antigen-binding fragment contains four antigen-binding sites.

[59] In one embodiment, the human GITR antibody comprises two heavy chains and four light chains, each heavy chain comprising two structures consisting of a heavy chain variable region and a CH1 region, a CH2 region and a CH3 region, and the C-terminus of one of structures is linked to the N-terminus of another structure via a linker, and each light chain contains a light chain variable region and a light chain constant region (left panel in FIG. 1B).

[60] In one embodiment, the human GITR antibody comprises two heavy chains and four light chains, wherein each heavy chain comprises a first heavy chain variable region and a first CH1 region, a linker, a second heavy chain variable region, a second CH1 region, a CH2 region and a CH3 region, and each light chain contains a light chain variable region and a light chain constant region (left panel in FIG. 1B).

[61] In one embodiment, the human anti-GITR antibody comprises two heavy chains and four light chains; each heavy chain contains two structures consisting of a heavy chain variable region containing a CDR-H3 consisting of SEQ ID NO:13, a CDR-H2 consisting of SEQ ID NO:12, and a CDR-H1 consisting of SEQ ID NO: 11 and the CH1 region, the CH2 region and the CH3 region, and the carboxy-terminus (C-terminus) of one of the structures is linked to the amino-terminus (N-terminus) of the other structure via a linker; and each light chain contains a light chain variable region comprising a CDR-L3 consisting of SEQ ID NO:16, a CDR-L2 consisting of SEQ ID NO:15, and a CDR-L1 consisting of SEQ ID NO:14.

[62] In one embodiment, the human anti-GITR antibody comprises two heavy chains and four light chains; each heavy chain comprises a first heavy chain variable region and a second heavy chain variable region, each comprising a CDR-H3 consisting of SEQ ID NO:13, a CDR-H2 consisting of SEQ ID NO:12, and a CDR-H1 consisting of SEQ ID NO:11; a first CH1 region, a linker, a second CH1 region, a CH2 region, and a CH3 region; and each light chain contains a light chain variable region comprising a CDR-L3 consisting of SEQ ID NO:16, a CDR-L2 consisting of SEQ ID NO:15, and a CDR-L1 consisting of SEQ ID NO:14.

[63] In one embodiment, the human anti-GITR antibody comprises two heavy chains and four light chains, wherein each heavy chain contains two structures consisting of a heavy chain variable region of SEQ ID NO: 9 and a CH1 region, a CH2 region, and a CH3, and the C-terminus of one of the structures is linked to the N-terminus of the other structure by a linker, and each light chain contains the light chain variable region of SEQ ID NO: 10 and the light chain constant region.

[64] In one embodiment, the human anti-GITR antibody comprises two heavy chains and four light chains, wherein each heavy chain comprises a first heavy chain variable region and a second heavy chain variable region, each as set forth in SEQ ID NO: 9; a first CH1 region, a linker, a second CH1 region, a CH2 region, and a CH3 region; and wherein each light chain comprises a light chain variable region of SEQ ID NO: 10 and a light chain constant region.

[65] In one embodiment, the human anti-GITR antibody comprises two heavy chains and four light chains, wherein each heavy chain comprises two structures consisting of a heavy chain variable region of SEQ ID NO: 9 and a CH1 region, a CH2 region, and a CH3, and the C-terminus of one of the structures is linked to the N-terminus of the other structure via a linker, where the Q at position 1 of the sequence is modified to pyroglutamate, and each light chain contains the light chain variable region of SEQ ID NO: 10 and the light chain constant region.

[66] In one embodiment, the human GITR antibody comprises two heavy chains and four light chains, wherein each heavy chain comprises a first heavy chain variable region and a second heavy chain variable region, each as set forth in SEQ ID NO: 9; a first CH1 region, a linker, a second CH1 region, a CH2 region, and a CH3 region; where Q at position 1 of the sequence is modified to pyroglutamate and each light chain contains the light chain variable region of SEQ ID NO: 10 and a light chain constant region.

[67] In one embodiment, the human anti-GITR antibody comprises two heavy chains, each having two variable regions, from SEQ ID NO: 7, and four light chains from SEQ ID NO: 8.

[68] In one embodiment, the human anti-GITR antibody comprises two heavy chains, each having two variable regions, from SEQ ID NO: 7, where Q at position 1 of the sequence is modified to pyroglutamate, and four light chains from SEQ ID NO: 8.

[69] In one embodiment, the human anti-GITR antibody comprises two heavy chains, each having two variable regions consisting of an amino acid sequence ranging from Q at position 1 to G at position 686 of SEQ ID NO: 7, and four light chains. chains from SEQ ID NO: 8.

[70] In one embodiment, the human anti-GITR antibody comprises two heavy chains consisting of an amino acid sequence ranging from Q at position 1 to G at position 686 of SEQ ID NO: 7, where Q is modified to pyroglutamate, and four light chains from SEQ ID NO: 8.

BRIEF DESCRIPTION OF THE DRAWINGS

[71] In FIG. 1 is a schematic illustration of the mechanism of action of specific exemplary GITR ABPs provided herein. FIG. 1A shows three GITR molecules (one labeled 101) embedded in a cell membrane (102). Shown is a drawing of a traditional format antibody that binds only two molecules of GITR (103). FIG. 1B shows a drawing of an antibody of the tetravalent monospecific (TM) format described herein: left panel (105) shows TM containing two N-terminal IgG1 Fabs, with a C-terminal IgG4 S228P antibody; the right panel (106) shows a TM containing two C-terminal IgG1 Fabs and an N-terminal IgG4 S228P antibody. Antigen binding domains are illustrated with open circles (107). FIG. 1C shows a drawing of an antibody of the tetravalent bispecific format described herein: left panel (105) shows a bispecific antibody containing two N-terminal IgG1 Fabs with a C-terminal IgG4 S228P antibody; right panel (106) shows a bispecific antibody containing two C-terminal IgG1 Fabs and an N-terminal IgG4 S228P antibody. Antigen binding domains having specificity for two non-overlapping epitope specificities are illustrated by open circles (107 and 108). FIG. 1D shows GITR multimerization after binding of three exemplary tetravalent monospecific (TM) format ABPs. Multimerization is expected to act as a GITR signaling agonist as described elsewhere herein.

[72] FIG. 2 is a graph showing exemplary results of K _D determination by OCTET for ABP format with N-terminal Fab 1-8.

[73] FIG. 3 is a series of graphs showing the results of a FACS analysis showing the binding of an exemplary TM format ABP panel to an N-terminal Fab with CD4+ (FIG. 3A) and CD8+ (FIG. 3B) T cells. The distribution of CD4+ and CD8+ is shown in the upper left panel of each figure. Top row, from left to right, shows a positive control against GITR and an isotype control against human IgG4, ABP9, ABP2, ABP1, and ABP7. The bottom row shows ABP8, ABP3, ABP4, ABP5, ABP6, ABP23 and ABP24. The percentage of positively stained IgG4+ CD4/8+ cells is indicated; MRI is in brackets.

[74] FIG. 4 is a series of graphs showing the activity of eight optimized agonist antibodies in TM format with an N-terminal Fab. HT1080 cells stably expressing human GITR (left panels) or cynomolgus monkey (right panels) were then incubated with ABP1 (FIG. 4A), ABP2 (FIG. 4B), ABP3 (FIG. 4C), ABP4 (FIG. 4D), ABP5 (FIG. 4E), ABP6 (FIG. 4F), ABP7 (FIG. 4G) and ABP8 (FIG 4H) (shown as circles in FIG.), and IL-8 induction was measured. GITRL was used as a control (squares). A table of EC ₅₀ values is shown at the bottom of each panel in each FIG.

[75] FIG. 5 is a series of graphs comparing agonist activity in GITR expressing HT1080 cells of the original TM N-terminal Fab format antibody, ABP43, with a range of further optimized antibodies having either N-terminal or C-terminal format. FIG. 5A shows ABP43 (squares), ABP23 (circles), ABP24 (triangles) and ABP29 (open circles), ABP30 (open triangles), ABP31 (open circles), and ABP32 (open triangles), all compared to GITRL (+ sign) . FIG. 5B shows ABP19 (N-terminal Fab, triangles) and ABP25 (C-terminal Fab, inverted triangles). GITRL is shown as plus signs. FIG. 5C shows ABP21 (N-terminal Fab, triangles) and ABP27 (C-terminal Fab, inverted triangles). GITRL is shown as plus signs. FIG. 5D shows ABP20 (N-terminal Fab, triangles) and ABP26 (C-terminal Fab, inverted triangles). GITRL is shown as plus signs. FIG. 5E shows ABP22 (N-terminal Fab, triangles) and ABP28 (C-terminal Fab, inverted triangles). GITRL is shown as plus signs. The IgG4 control is shown as an X in each figure.

[76] FIG. 6 shows the EC ₅₀ results for ABP33 and ABP34 in the HT1080 assay as described in the examples. ABP33 (a tetravalent variant combining IgG4 ABP61 with an IgG1 Fab from ABP58 at the N-terminus) and ABP34 (a tetravalent variant combining IgG4 from ABP61 with an IgG1 Fab from ABP58 at the C-terminus) were compared with bivalent ABP 59 and 61 (IgG4 S228P), which were the basis for ABP33 and ABP34. As shown in FIG., both bispecific tetravalent antibodies have a superior EC ₅₀ as measured by IL-8 induction compared to the individual bispecific antibodies used to construct the bispecific tetravalent antibodies.

[77] FIG. 7 shows the results of EC ₅₀ determination in the Jurkat T cell assay as described for HT1080 cells above. Optimized TM format ABPs with N-terminal Fab were compared to GITRL for their ability to act as a GITR agonist as measured by IL-8 production. FIG. 7A-7H show ABPs 1-8, respectively.

[78] In FIG. 8A shows FACS analysis for triplicate quantification of T cells isolated from two human donors and shows the percentage of GITR+ CD4+ cells (left) and CD8+ cells (right) at different time points +/- stimulation with PHA.

[79] FIG. 8B-8M show the results of treatment of T-blasts from 4 different donors after control or ABP treatments, and the resulting IL-2 production (data normalized to levels of IL-2 production achieved in control media). On each FIG. top row, left to right, is a FACS measurement of ABP binding to CD4+ cells, IL-2 production in cells from donor 1, IL-2 production in cells from donor 2. Bottom row, left to right, is a FACS measurement of ABP binding to CD8+ cells cells, IL-2 production in cells from donor 3, IL-2 production in cells from donor 4. Data are shown as follows: 8B: IgG4 isotype control; 8C: SEC4 antibody; 8D: TM format IgG4 negative control; 8E: ABP9 (TM format IgG4, non-optimized precursor of ABP 1-8). 8F: ABP1; 8G: ABP2; 8H: ABP3; 8I: ABP4; 8J: ABP5; 8K:ABP6; 8L: ABP7; 8M: ABP8.

[80] FIG. 9A-9H are a series of graphs showing a comparison of the activity of optimized ABP TM with N-terminal Fab ("IgG4 TM") against the corresponding optimized non-TM ABP IgG1 N297A ("IgG1"). HT1080 cells stably expressing human (left panel) or cynomolgus monkey (right panel) GITR were then treated with each TM with N-terminal ABP Fab and the corresponding IgG1 ABP as follows: ABP1 IgG4 TM /ABP35 IgG1 (FIG. 9A), ABP2 IgG4 TM /ABP36 IgG1 (FIG. 9B), ABP3 IgG4 TM /ABP37 IgG1 (FIG. 9C), ABP4 IgG4 TM /ABP38 IgG1 (FIG. 9D), ABP5 IgG4 TM /ABP38 P45L IgG1 (FIG. 9E), ABP6 IgG4 TM /ABP39 IgG1 (FIG. 9F), ABP7 IgG4 TM /ABP40 IgG1 (FIG. 9G) and ABP8 IgG4 TM /ABP41 IgG1 (FIG. 9H) and IgG4 as a positive control. IL-8 induction by GITRL is shown as circles, by TM format IgG4 ABP as triangles, by corresponding IgG1 ABP as diamonds, and by control IgG4 antibodies as squares. A table of EC ₅₀ values is shown at the bottom of each panel in each FIG.

[81] FIG. 10 is a graph showing EC ₅₀ data in the HT1080 assay, as described, comparing the non-TM parent antibody to the corresponding TM format variants. ABP43 (diamonds) is a non-TM IgG4 S228P precursor of ABP9 (IgG4 N-terminal Fab, squares) and ABP10 (IgG4 C-terminal Fab, circles). IL-8 induction by GITRL (positive control) is shown as a single data point (star). IL-8 production is shown in pg/ml.

[82] FIG. 11A is a graph showing the induction of IL-8 by representative reference antibodies SEC4 and SEC9 in HT1080 cells modified to stably express human GITR. Cultured cells were treated for six hours using a range of concentrations of two reference agonist antibodies, SEC4 (35E6 formatted to have mouse variable regions with human IgG4 S228P/kappa regions, diamonds) and SEC9 (humanized 6C8 N62Q IgG1 N297A, circles), also as an IgG4 negative control (solid triangles), an IgG1 negative control (open triangles), and a human GITR trimeric ligand ("hGITRL", squares) as a positive control. IL-8 induction was measured by ELISA. As shown in the figure, GITRL had better EC ₅₀ (inset) and maximum induction compared to both SEC4 and SEC9. FIG. 11B-11I show a comparison of ABP 1-8, respectively, with SEC4 and SEC9. TM ABPs are indicated by circles, SEC4 squares and SEC9 triangles. IL-8 production is shown in pg/ml.

[83] FIG. 12 are two graphs showing cytokine production in stimulated isolated human adenocarcinoma NSCLC cells after treatment with ABP1 TM format, alone or in combination with pembrolizumab. Cells were either unstimulated controls or stimulated with 1 μg/ml αCD3 (soluble) + 2 μg/ml αCD28 (soluble) + IL-2 (50 ng/ml); cells were either unimmunotreated (to assess checkpoint protein levels) or treated with pembrolizumab (10 μg/mL), TM format control ABP (2 μg/mL), ABP1 (2 μg/mL), or ABP1+pembrolizumab. Cells were incubated for 48 hours before supernatant collection and cells were stained for checkpoint protein expression. In some samples, brefeldin A (an inhibitor of cytokine secretion) was added during the last five hours of stimulation to detect cytokines by intracellular cytokine staining. TNF production (FIG. 12A) and IFNγ production (FIG. 12B) are shown.

[84] FIG. 13 is a series of graphs showing GITR clustering and internalization after antibody binding. GITR internalization was measured in CD4+ cells (FIGS. 13A-E) and CD8+ cells (Figures 13F-J) from either donor 1 (Figures 13A-B, 13F-G) or donor 2 (Figures 13C-D, 13H-I ). Cells were treated with either ABP1 TM antibody format or standard ABP35 divalent antibody. As can be observed, incubation with either ABP1 or ABP35 inhibits subsequent staining with ABP1Dylight650 (Figures 13A, 13C, 13F, 13H), but only incubation with ABP1 induces GITR internalization as measured by staining using non-competing clone 108-17 (figures 13B, 13D, 13G, 13I). Determination of EC50 ABP1 on cells from both donors is shown in Figure 13E (CD4+ cells) and Figure 13J (CD8+ cells).

[85] FIG. 14 shows cytokine (IL-2) production by activated T-blasts from two healthy human donors (donor 1 and donor 2, FIGS. 14A and 14B, respectively) after treatment with ABP1 against GITR TM format with IgG4 antibody, its equivalent with ABP35 IgG1 format, and isotype controls IgG4 format TM and IgG1. Activated CD4+/CD8+ T cells were treated with medium alone, recombinant GITR ligand, ABP1, TM format hIgG4 isotype control, ABP35, or standard format hIgG1 isotype control, at nine doses each: 10 μg/mL, 2 μg/mL, 0.4 mcg/mL, 80 ng/mL, 16 ng/mL, 3.2 ng/mL, 0.64 ng/mL, 0.13 ng/mL, and 0.026 ng/mL. Cells were stimulated by adding 1 μg/ml anti-CD3 antibody and 2 μg/ml anti-CD28 antibody. FIG. 14C shows the same data for ABP1 as in FIG. 14A and 14B, calculating the determination of EC ₅₀ for each donor.

[86] FIG. 15 shows cytokine (IL-2) production by activated T-blasts from two healthy human donors (donor 1 and donor 2, FIGS. 15A and 15B, respectively) after treatment with ABP1 against GITR TM format with IgG4 antibody, control IgG4 TM format ("Iso-TM"), SEC4, SEC9, recombinant hGITRL and IgG1 and IgG4 isotype controls. Activated CD4+/CD8+ T cells were treated with medium, recombinant GITR Ligand, ABP1, hIgG4 isotype control TM format, SEC4, SEC9, standard format IgG1 isotype control, or standard format hIgG1 isotype control, at nine doses each: 10 µg/mL, 2 µg/mL, 0.4 µg/mL, 80 ng/mL, 16 ng/mL, 3.2 ng/mL, 0.64 ng/mL, 0.13 ng/mL, and 0.026 ng/mL. Cells were stimulated by adding 1 μg/ml anti-CD3 antibody and 2 μg/ml anti-CD28 antibody. FIG. 15C (donor 1) and 15D (donor 2) show the same data for ABP1 as in 15A and 15B, calculating the determination of EC ₅₀ for each donor.

DETAILED DESCRIPTION

Definitions

[87] Unless otherwise specified, all terms of the art, designations and other scientific terminology used in the present description have the meaning well known to a person skilled in the field to which this invention pertains. In some instances, terms with commonly known meanings are defined herein for clarity and/or ease of reference, and the inclusion of such definitions in the present specification should not necessarily be construed as representing a departure from what is commonly known in the art. The techniques and methods described or cited herein are generally well understood and widely practiced using conventional methods by those skilled in the art, such as, for example, the commonly used molecular cloning methods described in Sambrook et al., Molecular Cloning: A Laboratory Manual 4th ed. (2012) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. Suitably, methods involving the use of commercially available kits and reagents are generally performed according to the protocols and conditions specified by the manufacturer, unless otherwise indicated.

[88] Within the scope of the invention, the singular forms include references to the plural, unless the context clearly indicates otherwise. The terms "include", "such as", and the like. are intended to express inclusion without restriction, unless specifically stated otherwise.

[89] As used herein, the term "comprising" also specifically includes "consisting of" and "essentially consisting of" the listed elements, unless specifically stated otherwise. For example, a multispecific "diabody" ABP includes a "diabody" multispecific ABP and a "primarily diabody" multispecific ABP.

[90] The term "about" means and includes the specified value and the range above and below this value. In particular embodiments, the term "about" means the specified value of ±10%, ±5%, or ±1%. In particular embodiments, the term "approximately" means a specified value ± one standard deviation from that value.

[91] The terms "GITR", "GITR protein", and "GITR antigen" are used interchangeably herein to refer to human GITR or any variants (e.g., splicing variants and allelic variants), isoforms, and species homologues of human GITR that are naturally expressed. in cells, or which are expressed in cells transfected with the gitr gene. In some aspects, the GITR protein is a GITR protein naturally expressed in a primate (eg, monkey or human), rodent (eg, mouse or rat), dog, camel, cat, cow, goat, horse, or sheep. In some aspects, the GITR protein is human GITR (hGITR; SEQ ID NO: 1). In some aspects, the GITR protein is a T43R human GITR variant (hGITR-T43R; SEQ ID NO: 2). In some aspects, the GITR protein contains an extracellular hGITR domain located at positions 26-162 of SEQ ID NOs: 1-2. In some aspects, the GITR protein is cynomolgus monkey GITR (cGITR; SEQ ID NO: 3). In some aspects, the GITR protein comprises an extracellular cGITR domain located at positions 20-156 of SEQ ID NO: 3. In some aspects, the GITR protein is mouse GITR (mGITR; SEQ ID NO: 4). In some aspects, the GITR protein contains an extracellular mGITR domain located at positions 20-153 of SEQ ID NO: 4. In some aspects, the GITR protein is a full length or full length GITR protein. In some aspects, the GITR protein is a truncated or truncated GITR protein obtained through post-translational modification. GITR is also known by a variety of synonyms, including member 18 of the tumor necrosis factor receptor superfamily, (TNFRSF18); AITR, glucocorticoid-induced TNFR-related protein; activation inducible receptor of the TNFR family; an activation inducible TNF receptor superfamily protein; CD357; and GITR-D.

[92] The term "immunoglobulin" refers to a class of structurally related proteins, typically containing two pairs of polypeptide chains: one pair of light (L) chains and one pair of heavy (H) chains. In "intact immunoglobulin", all four of these chains are connected to each other by disulfide bonds. The structure of immunoglobulins is well characterized. See , for example, Paul, Fundamental Immunology 7th ed., Ch. 5 (2013) Lippincott Williams & Wilkins, Philadelphia, PA. Briefly, each heavy chain typically contains a heavy chain variable region (V _H ) and a heavy chain constant region ( _CH ). The heavy chain constant region typically contains three domains, designated C _H1 , C _H2 , and C _H3 . Each light chain typically contains a light chain variable region (V _L ) and a light chain constant region. The light chain constant region typically contains a single domain, designated C _L .

[93] The term "antigen-binding protein" (ABP) refers to a protein containing one or more antigen-binding domains that specifically bind an antigen or epitope. In some embodiments, the antigen-binding domain binds an antigen or epitope with a specificity and affinity similar to that of natural antibodies. In some embodiments, the ABP comprises, consists of, or primarily consists of an antibody. In some embodiments, the ABP comprises, consists of, or primarily consists of an antibody fragment. In some embodiments, the ABP comprises, consists of, or primarily consists of an alternative scaffold. "ABP GITR", "ABP against GITR", or "GITR-specific ABP" is an ABP, within the meaning of the invention, that specifically binds the GITR antigen. In some embodiments, ABP binds the extracellular domain of GITR. In specific embodiments, the GITR ABP, within the scope of the invention, binds a GITR epitope that is conserved between GITR proteins or among GITR proteins from different species.

[94] The term "antibody" is used in the present description in the broadest sense and includes specific types of immunoglobulin molecules containing one or more antigen-binding domains that specifically bind an antigen or epitope. An antibody specifically includes intact antibodies (eg, intact immunoglobulins), antibody fragments, and multispecific antibodies. One example of an antigen-binding domain is an antigen-binding domain formed by a V _H -V _L dimer. The antibody is one type of ABP.

[95] The term "alternative framework" refers to a molecule in which one or more regions can be diversified to obtain one or more antigen-binding domains that specifically bind an antigen or epitope. In some embodiments, the antigen-binding domain binds an antigen or epitope with a specificity and affinity similar to that of natural antibodies. Exemplary alternative scaffolds include scaffolds derived from fibronectin (eg, adnectin™), β-sandwich (eg, iMab), lipocalin (eg, ^anticalin® ), EETI-II/AGRP, BPTI/LACI-D1/ITI-D2 (eg , Kunitz domains), thioredoxin-based peptide aptamers, protein A (e.g. affitelo ^® ), ankyrin repeats (e.g. darpins), gamma-B-crystallin/ubiquitin (e.g. affilins), CTLD ₃ (e.g. tetranectins), finomers and an LDLR-A module (e.g. avimers). For more information on alternative scaffolds, see Binz et al., Nat. Biotechnol. , 2005 23:1257-1268; Skerra, Current Opin. in Biotech. , 2007 18:295-304; and Silacci et al., J. Biol. Chem. , 2014, 289:14392-14398; the full content of all of which is given in the present description by reference. The alternative frame is one type of ABP.

[96] The term "antigen-binding domain" refers to the part of the ABP that can specifically bind an antigen or epitope.

[97] The terms "full antibody", "intact antibody", and "complete antibody" are used interchangeably herein to refer to an antibody having a structure substantially similar to that of a native antibody and having heavy chains containing an Fc region.

[98] The term "Fc region" refers to the C-terminal region of the heavy chain of an immunoglobulin, which, in natural antibodies, interacts with Fc receptors and certain proteins of the complement system. The structures of the Fc regions of various immunoglobulins and the glycosylation sites they contain are known in the art. See Schroeder and Cavacini, J. Allergy Clin. Immunol. , 2010, 125:S41-52, the entire content of which is provided by reference. The Fc region may be a natural Fc region, or a modified Fc region as described elsewhere in this specification.

[99] The V _H and V _L regions can be further subdivided into regions of hypervariability ("hypervariable regions (HVR);" also referred to as "complementarity determining regions" (CDR)), interspersed with regions that are more conserved. More conservative regions are called framework regions (FR). Each V _H and V _L typically contains three CDRs and four FRs in the following order (from N-terminus to C-terminus): FR1 - CDR1 - FR2 - CDR2 - FR3 - CDR3 - FR4. CDRs are involved in antigen binding and affect the antigen specificity and binding affinity of an antibody. See Kabat et al., Sequences of Proteins of Immunological Interest 5th ed. (1991) Public Health Service, National Institutes of Health, Bethesda, MD, the entire contents of which are incorporated by reference.

[100] A light chain from any vertebrate species can be assigned to one of two types, called kappa (κ) and lambda (λ), based on the sequence of its constant domain.

[101] A heavy chain from any vertebrate species can be assigned to one of five different classes (or isotypes): IgA, IgD, IgE, IgG, and IgM. These classes are also denoted α, δ, ε, γ and μ, respectively. The IgG and IgA classes are further subclassified based on differences in sequence and function. The following subclasses are expressed in humans: IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2.

[102] CDR amino acid sequence boundaries can be defined by one of ordinary skill in the art using any of a number of known numbering schemes, including those described in Kabat et al., supra ("Kabat" numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol. , 273:927-948 (Chothia numbering scheme); MacCallum et al., 1996, J. Mol. Biol. 262:732-745 ("contact" numbering scheme); Lefranc et al., Dev. Comp. Immunol. , 2003, 27:55-77 (numbering scheme "IMGT"); and Honegge and Plückthun, J. Mol. Biol. , 2001, 309:657-70 (numbering scheme "AHo"); the full content of all of which is given in the present description by reference.

[103] Table 1 shows the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 as identified by the Kabat and Chothia schemes. For CDR-H1, residue numbering is shown using both Kabat and Chothia numbering schemes.

[104] Unless otherwise indicated, the numbering scheme used to identify a particular CDR in the present specification is the Kabat/Chothia numbering scheme. When the residues covered by these two numbering schemes are different (eg, CDR-H1 and/or CDR-H2), the numbering scheme is defined as either Kabat or Chothia. For convenience, CDR-H3 is sometimes referred to herein as either Kabat or Chothia. However, it is not intended to introduce sequence differences when they do not exist, and one skilled in the art can easily confirm whether the sequences are the same or different by checking the sequences.

[105] CDRs can be assigned, for example, using antibody numbering software such as Abnum available at www.bioinf.org.uk/abs/abnum/ and described in Abhinandan and Martin, Immunology , 2008, 45:3832 -3839, the full content of which is provided by reference.

Table 1. CDR balances according to the Kabat and Chothia numbering schemes.

CDR Kabat Chothia L1 L24-L34 L24-L34 L2 L50-L56 L50-L56 L3 L89-L97 L89-L97 H1 (Kabat numbering) H31-H35B H26-H32 or H34* H1 (Chothia numbering) H31-H35 H26-H32 H2 H50-H65 H52-H56 H3 H95-H102 H95-H102

* The C-terminus of CDR-H1, when numbered using the Kabat numbering system, differs between H32 and H34, depending on the length of the CDR.

[106] "EU Numbering Scheme" is typically used when referring to a residue in an antibody heavy chain constant region (eg, as published in Kabat et al., supra). Unless otherwise indicated, the EU numbering scheme is used to refer to residues in the antibody heavy chain constant regions described herein.

[107] An "antibody fragment" or "antigen-binding fragment" contains a portion of an intact antibody, such as an antigen-binding or variable region of an intact antibody. antibody fragments include, for example, Fv fragments, Fab fragments, F(ab') ₂ fragments, Fab' fragments, scFv (sFv) fragments, and scFv-Fc fragments.

[108] Fv fragments contain a non-covalently linked dimer of one heavy chain variable domain and one light chain variable domain.

[109] Fab fragments contain, in addition to the heavy and light chain variable domains, a light chain constant domain and a heavy chain first constant domain (C _H1 ). Fab fragments can be generated, for example, by recombinant methods or by papain digestion of a full-length antibody.

[110] F(ab') ₂ fragments contain two Fab' fragments linked near the hinge region by disulfide bonds. F(ab') ₂ fragments can be generated, for example, by recombinant methods or by pepsin digestion of an intact antibody. fragments F(ab') can be dissociated, for example, by treatment with β-mercaptoethanol.

[111] "Single chain Fv" or "sFv" or "scFv" antibody fragments contain a V _H domain and a V _L domain on the same polypeptide chain. V _H and V _L are typically linked via a peptide linker. See Pluckthun A. (1994). In some embodiments, the linker is (GGGGS) _n (SEQ ID NO: 5). In other embodiments, the linker is GGGGSGGGGSGGGGS (SEQ ID NO:6). In some embodiments, n=1, 2, 3, 4, 5, or 6. See Antibodies from Escherichia coli . In Rosenberg M. & Moore G.P. (Eds.), The Pharmacology of Monoclonal Antibodies vol. 113 (pp. 269-315). Springer-Verlag, New York, the contents of which are incorporated by reference.

[112] Fragments "scFv-Fc" contain scFv attached to the Fc domain. For example, an Fc domain may be attached to the C-terminus of a scFv. The Fc domain may be followed by V _H or V _L , depending on the orientation of the variable domains in the scFv (ie, V _H -V _L or V _L -V _H ). Any suitable Fc domain known in the art or described herein can be used. In some cases, the Fc domain contains an IgG4 Fc domain.

[113] The term "single domain antibody" refers to a molecule in which one antibody variable domain specifically binds an antigen without the presence of another variable domain. Single domain antibodies and fragments thereof are described in Arabi Ghahroudi et al., FEBS Letters , 1998, 414:521-526 and Muyldermans et al., Trends in Biochem. sci. , 2001, 26:230-245, all of which are incorporated herein by reference in their entirety.

[114] "Multispecific ABP" is an ABP containing two or more different antigen-binding domains that together specifically bind two or more different epitopes. The two or more different epitopes may be epitopes on the same antigen (eg, a single GITR molecule expressed in a cell) or on different antigens (eg, different GITR molecules expressed in the same cell). In some aspects, multispecific ABP binds two different epitopes (ie, "bispecific ABP"). In some aspects, a multispecific ABP binds three different epitopes (ie, "trispecific ABP"). In some aspects, multispecific ABP binds four different epitopes (ie, "quad-specific ABP"). In some aspects, multispecific ABP binds six different epitopes (ie, "quintospecific ABP"). In some aspects, multispecific ABP binds 6, 7, 8 or more different epitopes. Each binding specificity may be present in any suitable valency. Examples of multispecific ABP are presented elsewhere in this specification.

[115] A "monospecific ABP" is an ABP that contains a binding site that specifically binds a single epitope. An example of a monospecific ABP is the naturally occurring IgG molecule, which, while divalent, recognizes the same epitope on each antigen-binding domain. Binding specificity may be present in any suitable valency.

[116] The term "monoclonal antibody" refers to an antibody from a population of essentially homogeneous antibodies. A population of essentially homogeneous antibodies contains antibodies that are essentially similar and that bind the same epitope(s), with the exception of variants that may normally occur during the production of a monoclonal antibody. Such variants are usually present only in small quantities. A monoclonal antibody is typically prepared by a method involving selecting one antibody from a plurality of antibodies. For example, the selection method may be to select a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further modified, for example, to improve affinity for the target ("affinity maturation"), to humanize the antibody, to improve its production in cell culture, and/or to reduce its immunogenicity in a subject.

[117] The term "chimeric antibody" refers to an antibody in which part of the heavy and/or light chain is from a particular source or species, while the remainder of the heavy and/or light chain is from a different source or species.

[118] "Humanized" forms of a non-human antibody are chimeric antibodies containing a minimal sequence derived from a non-human antibody. A humanized antibody is generally a human antibody (recipient antibody) in which residues from one or more CDRs are replaced with residues from one or more CDRs from a non-human antibody (donor antibody). The donor antibody can be any suitable non-human antibody, such as a mouse, rat, rabbit, chicken, or non-human primate antibody, having the desired specificity, affinity, or biological effect. In some cases, selected framework region residues of the recipient antibody are replaced with the corresponding framework region residues from the donor antibody. Humanized antibodies may also contain residues not found in the recipient antibody or donor antibody. Such modifications can be made to further refine the function of the antibody. For additional details See Jones et al., Nature , 1986, 321:522-525; Riechmann et al., Nature , 1988, 332:323-329; and Presta, Curr. Op. Struct. Biol. , 1992, 2:593-596, all of which are incorporated herein by reference in their entirety.

[119] A "human antibody" is an antibody having an amino acid sequence corresponding to the amino acid sequence of an antibody produced by a human or a human cell, or derived from a non-human source that uses the human antibody repertoire or sequences encoding a human antibody (e.g., derived from human sources or constructed de novo ). Human antibodies specifically exclude humanized antibodies.

[120] "Isolated ABP" or "isolated nucleic acid" is an ABP or nucleic acid separated from and/or isolated from a component of their natural environment. Components of the natural environment may include enzymes, hormones, and other proteinaceous or non-proteinaceous materials. In some embodiments, the isolated ABP is purified to a degree sufficient to obtain at least 15 residues of the N-terminal or internal amino acid sequence, for example, using a rotary beaker sequencer. In some embodiments, the isolated ABP is purified to homogeneity by gel electrophoresis (eg, SDS-PAGE) under reducing or non-reducing conditions, detected by Coomassie® blue or silver staining. The isolated ABP includes ABP in situ within the recombinant cell, since at least one component of the natural environment of ABP is not present. In some aspects, the isolated ABP or isolated nucleic acid is obtained through at least one purification step. In some embodiments, the isolated ABP or isolated nucleic acid is purified to at least 80%, 85%, 90%, 95%, or 99% by weight. In some embodiments, the isolated ABP or isolated nucleic acid is purified to at least 80%, 85%, 90%, 95%, or 99% by volume. In some embodiments, the isolated ABP or isolated nucleic acid is in the form of a solution containing at least 85%, 90%, 95%, 98%, 99%-100% ABP or nucleic acid by weight. In some embodiments, the isolated ABP or isolated nucleic acid is in the form of a solution containing at least 85%, 90%, 95%, 98%, 99%-100% ABP or nucleic acid by volume.

[121] "Affinity" refers to the strength of the overall net non-covalent interactions of one binding site of a molecule (eg, an ABP) and its binding partner (eg, antigen or epitope). Unless otherwise indicated, as used herein, "affinity" refers to intrinsic binding affinity, reflecting a 1:1 interaction between members of a binding pair (eg, ABP and antigen or epitope). The affinity of a molecule X for its partner Y can be represented by the equilibrium dissociation constant (K _D ). The kinetic components that contribute to the equilibrium dissociation constant are described in more detail below. Affinity can be measured by conventional methods known in the art, including those described herein. Affinity can be determined, for example, using a surface plasmon resonance (SPR) method (eg BIACORE ^® ) or biolayer interferometry (eg FORTEBIO ^® ).

[122] In relation to the binding of ABP to a target molecule, the terms "bind", "specific binding", "specifically binds", "specific for", "selectively binds" and "selective for" a particular antigen (e.g., target polypeptide) or epitope of a particular antigen denotes a binding that is measurably different from a non-specific or non-selective interaction (eg, with a non-target molecule). Specific binding can be measured, for example, by measuring binding to a target molecule and comparing it to binding to a non-target molecule. Specific binding can also be determined by competition with a control molecule that mimics an epitope recognized on the target molecule. In this case, specific binding is shown if ABP binding to the target molecule is competitively inhibited by the control molecule. In some aspects, the GITR ABP affinity for the non-target molecule is less than about 50% of the GITR affinity. In some aspects, the GITR ABP affinity for the non-target molecule is less than about 40% of the GITR affinity. In some aspects, the GITR ABP affinity for the non-target molecule is less than about 30% of the GITR affinity. In some aspects, the GITR ABP affinity for the non-target molecule is less than about 20% of the GITR affinity. In some aspects, the GITR ABP affinity for the non-target molecule is less than about 10% of the GITR affinity. In some aspects, the GITR ABP affinity for a non-target molecule is less than about 1% of the GITR affinity. In some aspects, the GITR ABP affinity for the non-target molecule is less than about 0.1% of the GITR affinity.

[123] The term “k _d ” (c ^-1 ), as used herein, refers to the dissociation rate constant for a particular ABP-antigen interaction. This value is also referred to as the k _off value.

[124] The term " _ka " (M ^-1 ×c ^-1 ), as used herein, refers to the binding rate constant for a particular ABP-antigen interaction. This value is also referred to as the k _on value.

[125] The term "K _D "(M), within the scope of the invention, refers to the equilibrium dissociation constant of a particular ABP-antigen interaction. K _D \u003d k _d / k _a .

[126] The term “K _A ” (M ^-1 ), within the scope of the invention, refers to the equilibrium binding constant of a particular ABP-antigen interaction. K _A \u003d k _a / k _d .

[127] An "affinity-matured" ABP is an ABP with one or more changes (e.g., in one or more CDRs or FRs) resulting in an improvement in the ABP's affinity for its antigen compared to the original ABP having no change(s) . In one embodiment, the affinity-matured ABP has nanomolar or picomolar affinity for the target antigen. Affinity-matured ABP can be obtained using a variety of methods known in the art. For example, Marks et al. ( Bio/Technology , 1992, 10:779-783, the entire content of which is incorporated by reference), describes affinity maturation by shuffling the V _H and V _L domains. Random mutagenesis of CDRs and/or framework residues is described, for example, in Barbas et al. ( Proc. Nat. Acad. Sci. USA , 1994, 91:3809-3813); Schier et al., Gene , 1995, 169:147-155; Yelton et al., J. Immunol. , 1995, 155:1994-2004; Jackson et al., J. Immunol. , 1995, 154:3310-33199; and Hawkins et al, J. Mol. Biol. , 1992, 226:889-896; the full content of all of which is given in the present description by reference.

[128] An "immunoconjugate" is an ABP conjugated to one or more heterologous molecule(s).

[129] "Effector functions" refers to those types of biological activity mediated by the Fc region of an antibody, the activity of which may vary depending on the isotype of the antibody. Examples of antibody effector functions include C1q binding to activate complement-dependent cytotoxicity (CDC), Fc receptor binding to activate antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP).

[130] When used herein in the context of two or more ABPs, the term "competes with" or "cross-competes with" indicates that two or more ABPs compete for binding to an antigen (eg, GITR). In one exemplary assay, the surface is coated with GITR and contacted with a first GITR ABP followed by a second GITR ABP. In another exemplary assay, the surface is coated with a first ABP GITR and contacted with GITR, and then a second ABP GITR is added. If the presence of the first GITR ABP reduces the binding of the second GITR ABP, in any assay, then the ABPs compete. The term "competes with" also includes combinations of ABPs where the ABP reduces the binding of another ABP, but where no competition is observed when the ABPs are added in reverse order. However, in some embodiments, the first and second ABPs inhibit each other's binding, regardless of the order in which they are added. In some embodiments, one ABP reduces the binding of another ABP to its antigen by at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%.

[131] The term "epitope" refers to the portion of an antigen that specifically binds to ABP. Epitopes often consist of surface accessible amino acid residues and/or sugars and may have specific three-dimensional structure characteristics as well as specific charge characteristics. Conformational and non-conformational epitopes differ in that binding to the former, but not to the latter, can be lost in the presence of denaturing solvents. An epitope may contain amino acid residues directly involved in binding and other amino acid residues not directly involved in binding. The epitope to which ABP binds can be determined using known epitope determination methods, such as, for example, testing ABP binding to GITR variants with different point mutations or to chimeric GITR variants.

[132] The percentage of "identity" between a polypeptide sequence and a control sequence is defined as the percentage of amino acid residues in the polypeptide sequence that are identical to the amino acid residues in the control sequence, aligning the sequences and introducing gaps, if necessary, to achieve the maximum percentage of sequence identity. Alignment to determine percent amino acid sequence identity can be performed in a variety of ways within the skill of the art, for example, using publicly available computer software such as BLAST software, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA or MUSCLE. One skilled in the art can determine suitable parameters for sequence alignment, including any algorithms necessary to achieve maximum alignment over the full length of the compared sequences.

[133] "Conservative substitution" or "conservative amino acid substitution" refers to the replacement of an amino acid with a chemically or functionally similar amino acid. Conservative substitution tables providing similar amino acids are well known in the art. By way of example, the amino acid groups shown in Tables 2-4 are considered, in some embodiments, as conservative substitutions for each other.

Table 2. Selected groups of amino acids that are considered conservative substitutions for each other, in specific embodiments.

acid residue D and E Basic remains K, R and H Hydrophilic uncharged residues S, T, N and Q Aliphatic uncharged residues G, A, V, L and I Non-polar uncharged residues C, M and P aromatic residues F, Y and W

Table 3. Additional selected groups of amino acids that are considered conservative substitutions for each other, in specific embodiments.

Group 1 A, S, and T Group 2 D and E Group 3 N and Q Group 4 R and K Group 5 I, L and M Group 6 F, Y and W

Table 4. Additional selected groups of amino acids that are considered conservative substitutions for each other, in specific embodiments.

Group A A and G Group B D and E Group C N and Q Group D R, K and H Group E I, L, M, V Group F F, Y and W Group G S and T Group H C and M

[134] Additional conservative substitutions can be found, for example, in Creighton, Proteins: Structures and Molecular Properties 2nd ed. (1993) W.H. Freeman & Co., New York, NY. An ABP obtained by introducing one or more conservative amino acid residue substitutions into the original ABP is referred to as a "conservatively modified variant".

[135] The term "amino acid" refers to the twenty common natural amino acids. Natural amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), glutamine (Gln; Q), glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V).

[136] The term "vector", as used herein, refers to a nucleic acid molecule capable of propagating another nucleic acid to which it is linked. The term includes a vector as a self-replicating nucleic acid structure, as well as a vector inserted into the genome of the host cell into which it has been introduced. Certain vectors are capable of directing the expression of the nucleic acids to which they are operably linked. Such vectors are referred to herein as "expression vectors".

[137] The terms "host cell", "host cell line" and "host cell culture" are used interchangeably and refer to cells into which exogenous nucleic acid has been introduced, including the progeny of such cells. Host cells include "transformants" (or "transformed cells") and "transfectants" (or "transfected cells"), where each includes the primary transformed or transfected cell and its progeny. Such progeny may not be completely identical to the parent cell in terms of nucleic acid content and may contain mutations.

[138] The term "treatment" (and variants thereof such as "treat" or "treatment") refers to clinical intervention to alter the natural course of a disease or condition in a subject in need thereof. Treatment can be carried out both for prevention and during the course of clinical pathology. Desirable effects of treatment include preventing the onset or recurrence of the disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, alleviating or alleviating the condition of the disease, and remission or improved prognosis.

[139] In the context of the invention, the term "therapeutically effective amount" or "effective amount" refers to the amount of ABP or pharmaceutical composition, within the scope of the invention, which, when administered to a subject, is effective for the treatment of a disease or disorder.

[140] In the context of the invention, the term "subject" refers to a mammalian subject. Illustrative subjects include humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, goats, rabbits, and sheep. In specific embodiments, the subject is a human. In some embodiments, the subject has a disease or condition that can be treated using ABP, within the scope of the invention. In some aspects, the disease or condition is a cancer.

[141] The term "package insert" is used to refer to instructions commonly included in commercial packages of therapeutic or diagnostic products (e.g., kits) that contain information regarding indications, use, dosing, administration, combination therapy, contraindications, and/or warnings, concerning the use of such therapeutic or diagnostic products.

[142] The term "cytotoxic agent", within the scope of the invention, refers to a substance that inhibits or prevents cellular function and/or causes cell death or destruction.

[143] "Chemotherapeutic agent" refers to a chemical compound that can be used in the treatment of cancer. Chemotherapeutic agents include "anti-hormonal agents" or "endocrine drugs" that act to regulate, reduce, block or suppress the effects of hormones that can stimulate the growth of malignant tumors.

[144] The term "cytostatic agent" refers to a compound or composition that causes cell growth arrest in vitro or in vivo . In some embodiments, the cytostatic agent is an agent that reduces the percentage of cells in S phase. In some embodiments, the cytostatic agent reduces the percentage of cells in S phase by at least about 20%, at least about 40%, at least about 60%, or at least about 80%.

[145] The term "tumor" refers to any growth and proliferation of neoplastic cells, either malignant or benign, and all premalignant and malignant cells and tissues. The terms "cancer", "malignant", "cell proliferative disorder", "proliferation disorder" and "tumor" are not mutually exclusive as used herein. The terms "cell proliferation disorder" and "proliferation disorder" refer to disorders associated with some degree of abnormal cell proliferation. In some embodiments, the cell proliferation disorder is a cancer.

[146] The term "pharmaceutical composition" refers to a preparation that is in such a form as to ensure the effectiveness of the biological activity of the active ingredient contained therein in the treatment of a subject, and which does not contain additional components that are unacceptably toxic to the subject.

[147] The terms "modulate" and "modulation" refer to the reduction or inhibition, or alternatively, the activation or increase, of the specified variable.

[148] The terms "increase" and "activate" refer to an increase of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95% , 100%, 2x, 3x, 4x, 5x, 10x, 20x, 50x, 100x or more of a specified variable such as GITR signaling activity.

[149] The terms "reduce" and "inhibit" refer to a reduction of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95% , 2 times, 3 times, 4 times, 5 times, 10 times, 20 times, 50 times, 100 times or more, a specified variable such as (a) the number of regulatory T cells and/or (b) disease symptoms or conditions such as the presence or size of metastases or the size of the primary tumor.

[150] The term "act as an agonist" refers to the activation of receptor signaling to induce a biological response associated with receptor activation. An "agonist" is a molecule, such as ABP, within the meaning of the invention, that binds to a receptor and acts as its agonist.

[151] The term "acting as an antagonist" refers to inhibition of receptor signaling to inhibit the biological response associated with receptor activation. An "antagonist" is a molecule, such as ABP, that binds to a receptor and acts as its antagonist.

[152] The term "multimerization" refers to the act of forming "multimers" of a molecule by assembling the molecule to form a supramolecular structure held together by non-covalent or covalent interactions. Multimers include "homomultimers", which are assemblies formed from multiple units of the same molecule, or "heteromultimers", which are assemblies containing at least one first molecule unit and at least one second molecule unit. As used herein in relation to GITR, the term multimerize refers to an ensemble of GITR molecules expressed on the cell surface, induced, for example, by ABP binding, within the scope of the invention, or by GITRL. Such multimerization is associated with activation of GITR signaling. See Nocentini et al., Br. J Pharmacol. , 2012, 165:2089-2099, the entire content of which is incorporated by reference.

[153] The term "effector T cell" includes helper T cells (ie, CD4+) and cytotoxic (ie, CD8+) T cells. CD4+ effector T cells contribute to several immunological processes, including the maturation of B cells into plasma cells and memory B cells, and the activation of cytotoxic T cells and macrophages. CD8+ effector T cells destroy virus-infected cells and tumor cells. See Seder and Ahmed, Nature Immunol. , 2003, 4:835-842, the contents of which are incorporated by reference, for further information on effector T cells.

[154] The term "regulatory T cells" includes cells that regulate immunological resistance, for example, by suppressing effector T cells. In some aspects, the regulatory T cell has a CD4+CD25+Foxp3+ phenotype. In some aspects, the regulatory T cell has a CD8+CD25+ phenotype. See Nocentini et al., Br. J Pharmacol. , 2012, 165:2089-2099, the contents of which are incorporated by reference, for further information on regulatory T cells expressing GITR.

[155] The term "dendritic cell" refers to a professional antigen-presenting cell capable of activating a naive T cell and stimulating B cell growth and differentiation.

Antigen-binding proteins against GITR

1.1. Binding of GITR and target cell

[156] The present invention relates to ABPs that specifically bind GITR. In some aspects, GITR is hGITR (SEQ ID NO: 1). In some aspects, GITR is hGITR-T43R (SEQ ID NO: 2). In some aspects, GITR is cGITR (SEQ ID NO: 3). In some embodiments, the GITR is mGITR (SEQ ID NO: 4).

[157] In some embodiments, ABPs within the scope of the invention specifically bind hGITR (SEQ ID NO: 1), hGITR-T43R (SEQ ID NO: 2), cGITR (SEQ ID NO: 3), and mGITR (SEQ ID NO: 3). : 4). In some embodiments, ABPs within the scope of the invention specifically bind hGITR (SEQ ID NO: 1), hGITR-T43R (SEQ ID NO: 2), and cGITR (SEQ ID NO: 3). In some embodiments, ABPs within the scope of the invention specifically bind hGITR (SEQ ID NO: 1) and hGITR-T43R (SEQ ID NO: 2). In some embodiments, ABPs, within the scope of the invention, do not bind mGITR (SEQ ID NO: 4).

[158] In some embodiments, ABPs, within the scope of the invention, specifically bind the extracellular domain of GITR.

[159] GITR can be expressed on the surface of any suitable target cell. In some embodiments, the target cell is an effector T cell. In some embodiments, the target cell is a regulatory T cell. In some embodiments, the target cell is a natural killer (NK) cell. In some embodiments, the target cell is a natural killer T cell (NKT). In some embodiments, the target cell is a dendritic cell. In some aspects, the dendritic cell is a plasmacytoid dendritic cell. In some embodiments, the target cell is a B cell. In some aspects, the B cell is a plasma cell. See Nocentini et al., Br. J Pharmacol. , 2012, 165:2089-2099, the entire content of which is incorporated by reference.

[160] In some embodiments, the ABPs, within the scope of the invention, specifically bind the GITR monomer.

[161] In some embodiments, the ABPs, within the scope of the invention, specifically bind the GITR multimer. In some aspects, the multimer contains two GITR molecules. In some aspects, the multimer contains three GITR molecules. In some aspects, the multimer contains four GITR molecules. In some aspects, the multimer contains five GITR molecules. In some aspects, the multimer contains six GITR molecules. In some aspects, the multimer contains more than six GITR molecules.

[162] In some embodiments, the implementation, ABP, in the framework of the invention, contains, consists of or mainly consists of an immunoglobulin molecule. In some aspects, the immunoglobulin molecule comprises, consists of, or primarily consists of an antibody.

[163] In some embodiments, the implementation, ABP, in the framework of the invention, contains a light chain. In some aspects, the light chain is a kappa light chain. In some aspects, the light chain is a lambda light chain.

[164] In some embodiments, the implementation, ABP, in the framework of the invention, contains a heavy chain. In some aspects, the heavy chain is IgA. In some aspects, the heavy chain is IgD. In some aspects, the heavy chain is IgE. In some aspects, the heavy chain is an IgG. In some aspects, the heavy chain is an IgM. In some aspects, the heavy chain is IgG1. In some aspects, the heavy chain is IgG2. In some aspects, the heavy chain is IgG3. In some aspects, the heavy chain is IgG4. In some aspects, the heavy chain is IgA1. In some aspects, the heavy chain is IgA2.

[165] In some embodiments, the implementation, ABP, in the framework of the invention, contains, consists of or mainly consists of an antibody fragment. In some aspects, the antibody fragment is an Fv fragment. In some aspects, the antibody fragment is a Fab fragment. In some aspects, the antibody fragment is an F(ab') ₂ fragment. In some aspects, the antibody fragment is a Fab' fragment. In some aspects, the antibody fragment is an scFv (sFv) fragment. In some aspects, the antibody fragment is a scFv-Fc. In some aspects, the antibody fragment is a single domain antibody fragment.

[166] In some embodiments, the implementation, ABP, in the framework of the invention, are monoclonal antibodies. In some embodiments, the ABPs within the scope of the invention are polyclonal antibodies.

[167] In some embodiments, the implementation, ABP, in the framework of the invention, contain, consist of or mainly consist of chimeric antibodies. In some embodiments, the ABPs within the scope of the invention comprise, consist of, or primarily consist of humanized antibodies. In some embodiments, the ABPs within the scope of the invention comprise, consist of, or primarily consist of human antibodies.

[168] In some embodiments, the implementation, ABP, in the framework of the invention, contain, consist of, or mainly consist of subjected to affinity maturation of ABP. In some aspects, ABPs are affinity-matured ABPs derived from ABPs within the scope of the invention.

[169] In some embodiments, the implementation, ABP, in the framework of the invention, contain, consist of, or mainly consist of an alternative framework. Any suitable alternative framework may be used. In some aspects, ABPs within the scope of the invention comprise, consist of, or primarily consist of an alternative scaffold selected from Adnectin™, iMab, ^Antikalin® , EETI-II/AGRP, Kunitz domain, thioredoxin-based peptide aptamer, ^Affitel® , darpin, affilin, tetranectin, finomer and avimer.

[170] In some embodiments, ABP, within the scope of the invention, inhibits the binding of GITR to GITRL. In some aspects, ABP inhibits the binding of GITR to GITRL by at least about 50%. In some aspects, ABP inhibits the binding of GITR to GITRL by at least about 75%. In some aspects, ABP inhibits the binding of GITR to GITRL by at least about 90%. In some aspects, ABP inhibits the binding of GITR to GITRL by at least about 95%.

1.2. Monospecific and multispecific antigen-binding proteins against GITR

[171] In some embodiments, the ABPs within the scope of the invention are monospecific ABPs. In some aspects, monospecific ABPs bind the same epitope on two or more different GITR molecules. In some aspects, monospecific ABPs bind the same epitope on two GITR molecules. In some aspects, monospecific ABPs bind the same epitope on three GITR molecules. In some aspects, monospecific ABPs bind the same epitope on four GITR molecules. In some aspects, monospecific ABPs bind the same epitope on five GITR molecules. In some aspects, monospecific ABPs bind the same epitope on six GITR molecules. In some aspects, monospecific ABPs bind the same epitope on more than six GITR molecules.

[172] In some embodiments, monospecific ABPs, within the scope of the invention, are multivalent. Within the scope of the invention, the term "multivalent" refers to an antibody with, for example, more than two binding regions (ie, containing V _H and V _L regions). In some aspects, monospecific ABPs are divalent. In some aspects, monospecific ABPs are trivalent. In some aspects, monospecific ABPs are tetravalent. In some aspects, monospecific ABPs are pentavalent. In some aspects, monospecific ABPs are hexavalent. In some aspects, monospecific ABPs are septivalent. In some aspects, monospecific ABPs are octavalent.

[173] In some embodiments, the monospecific multivalent ABPs described herein are tetravalent.

[174] In some embodiments, the ABPs within the scope of the invention are multispecific ABPs. In some aspects, multispecific ABPs bind two or more epitopes on two or more different GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on two GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on three GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on four GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on five GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on six GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on seven GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on eight GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on nine GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on ten GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on eleven GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on twelve GITR molecules. In some aspects, multispecific ABPs bind two or more epitopes on more than twelve GITR molecules.

[175] Multispecific ABPs, within the scope of the invention, can bind any suitable number of epitopes on the GITR. In some aspects, multispecific ABPs bind two epitopes on the GITR. In some aspects, multispecific ABPs bind three epitopes on the GITR. In some aspects, multispecific ABPs bind four epitopes on the GITR. In some aspects, multispecific ABPs bind five epitopes on the GITR. In some aspects, multispecific ABPs bind six epitopes on the GITR. In some aspects, multispecific ABPs bind seven epitopes on the GITR. In some aspects, multispecific ABPs bind eight epitopes per GITR. In some aspects, multispecific ABPs bind nine epitopes per GITR. In some aspects, multispecific ABPs bind ten epitopes per GITR. In some aspects, the multispecific ABPs bind eleven epitopes on the GITR. In some aspects, multispecific ABPs bind twelve epitopes on the GITR. In some aspects, multispecific ABPs bind more than twelve epitopes on the GITR.

[176] In some aspects, the multispecific ABP, within the scope of the invention, binds at least two different epitopes on at least two different GITR molecules. In some aspects, the multispecific ABP, within the scope of the invention, binds at least three different epitopes on at least three different GITR molecules. In some aspects, the multispecific ABP, within the scope of the invention, binds at least four different epitopes on at least four different GITR molecules. In some aspects, the multispecific ABP, within the scope of the invention, binds at least five different epitopes on at least five different GITR molecules.

[177] In some embodiments, a multispecific ABP, within the scope of the invention, comprises a first antigen-binding domain that specifically binds a first epitope on the GITR and a second antigen-binding domain that specifically binds a second epitope on the GITR, wherein the first epitope and the second epitope are different. In some aspects, the multispecific ABP further comprises one or more additional antigen-binding domains that specifically bind one or more additional epitopes on the GITR, where each of the additional epitopes is different from the epitopes bound by the first antigen-binding domain, the second antigen-binding domain, or any other of the following antigen-binding domains. ABP.

[178] In some embodiments, a multispecific ABP, within the scope of the invention, binds an epitope on a GITR molecule and an epitope on another non-GITR molecule. Any suitable non-GITR molecule can be linked by ABP, within the scope of the invention. In some aspects, the non-GITR molecule is another member of the tumor necrosis factor receptor (TNFRSF) superfamily. In some aspects, the other TNFRSF member is selected from CD27, CD40, EDA2R, EDAR, FAS, LTBR, NGFR, RELT, TNFRSF1A, TNFRSF1B, TNFRSF4, TNFRSF6B, TNFRSF8, TNFRSF9, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TFNRSF11A , TNFRSF11B, TNFRSF12A , TNFRSF13B, TNFRSF13C, TNFRSF14, TNFRSF17, TNFRSF18, TNFRSF19, TNFRSF21 and TNFRSF25.

[179] A variety of multispecific ABP constructs are known in the art, and the ABP, within the scope of the invention, can be provided in the form of any suitable multispecific construct.

[180] In some embodiments, the multispecific ABP comprises an immunoglobulin comprising at least two different heavy chain variable regions, each paired with a common light chain variable region (i.e., "common light chain antibody"). The common light chain variable region forms a separate antigen binding domain with each of two different heavy chain variable regions. See Merchant et al., Nature Biotechnol. , 1998, 16:677-681, the entire content of which is incorporated by reference.

[181] In some embodiments, the multivalent ABPs described herein comprise an immunoglobulin comprising an antibody or fragment thereof fused to one or more of the N- or C-termini of such immunoglobulin heavy or light chains. See, for example, US Patent No. 8722859 and Coloma and Morrison, Nature Biotechnol. , 1997, 15:159-163, the full contents of each of which are provided by reference. In some aspects, such ABP contains a tetravalent bispecific antibody. In some aspects, such an ABP contains a tetravalent monospecific (TM) antibody.

[182] In some embodiments, the multivalent ABP comprises a hybrid immunoglobulin comprising at least two different heavy chain variable regions and at least two different light chain variable regions. See Milstein and Cuello, Nature , 1983, 305:537-540; and Staerz and Bevan, Proc. Natl. Acad. sci. USA , 1986, 83:1453-1457; the full content of all of which is given in the present description by reference.

[183] In some embodiments, the implementation, multivalent ABP contains immunoglobulin chains with changes to reduce the formation of side products that do not have multispecificity. In some aspects, ABPs comprise one or more ridge-to-bottom modifications as described in US Patent No. 5731168, the full content of which is given as a reference.

[184] In some embodiments, the multivalent ABP comprises immunoglobulin chains with one or more electrostatic modifications to stimulate the assembly of Fc heteromultimers. See WO 2009/089004, the contents of which are incorporated by reference.

[185] In some embodiments, the multivalent ABP comprises a bispecific single chain molecule. See Traunecker et al., EMBO J. 1991, 10:3655-3659; and Gruber et al., J. Immunol. , 1994, 152:5368-5374; the full content of all of which is given in the present description by reference.

[186] In some embodiments, the multivalent ABP comprises a heavy chain variable domain and a light chain variable domain, or V _H H domain of a single domain antibody, joined by a polypeptide linker, wherein the length of the linker is chosen to promote assembly of the multivalent ABP with the desired multispecificity. For example, monospecific scFvs are typically formed when heavy chain V residues prevent pairing of heavy and light chain variable domains on the same polypeptide chain, thus allowing heavy and light chain variable domains from one chain to pair with complementary domains on the other chain. . The resulting ABPs are thus multispecific, with the specificity of each binding site being contributed by more than one polypeptide chain. Polypeptide chains containing heavy and light chain variable domains connected by linkers of between 3 and 12 amino acid residues preferentially form dimers (called diabodies). With linkers of between 0 and 2 amino acid residues, trimers (called tribodies) and tetramers (called tetrabodies) are predominantly formed. However, the exact type of oligomerization appears to depend on the composition of the amino acid residues and the order of the variable domains in each polypeptide chain (e.g., V _H -linker-V _L vs. V _L -linker-V _H ), in addition to the length of the linker . One of skill in the art can select an appropriate linker length based on the desired multispecificity.

[187] In some embodiments, the monospecific or multispecific ABP comprises a diabody. See Hollinger et al., Proc. Natl. Acad. sci. USA , 1993, 90:6444-6448, the entire content of which is incorporated by reference. In some embodiments, the monospecific or multispecific ABP comprises a tribody. See Todorovska et al., J. Immunol. Methods , 2001, 248:47-66, the entire content of which is incorporated by reference. In some embodiments, the monospecific or multispecific ABP contains a tetrabody. See the same document, the full content of which is given as a reference.

[188] In some embodiments, the multispecific ABP contains a trispecific F(ab')3 derivative. See Tutt et al. J. Immunol. , 1991, 147:60-69, the entire content of which is incorporated by reference.

[189] In some embodiments, the monospecific or multispecific ABP contains a cross-linked antibody. See US Patent No. 4676980; Brennan et al., Science , 1985, 229:81-83; Staerz, et al. Nature , 1985, 314:628-631; and EP 0453082; the full content of all of which is given in the present description by reference.

[190] In some embodiments, the monospecific or multispecific ABP contains antigen-binding domains assembled by leucine zippers. See Kostelny et al., J. Immunol. , 1992, 148:1547-1553, the entire content of which is incorporated by reference.

[191] In some embodiments, a monospecific or multispecific ABP contains complementary protein domains. In some aspects, the complementary protein domains comprise an anchoring domain (AD) and dimerizing and docking domains (DDD). In some embodiments, AD and DDD communicate with each other and thus allow assembly of multispecific ABP structures in a lock-on-dock (DNL) manner. It is possible to assemble ABPs with a variety of specificities, including bispecific ABPs, trispecific ABPs, tetraspecific ABPs, pentaspecific ABPs, and hexaspecific ABPs. Multispecific ABPs containing complementary protein domains are described, for example, in US Patent No. 7521056; 7550143; 7534866; and 7527787; the full content of all of which is given in the present description by reference.

[192] In some embodiments, the monospecific or multispecific ABP comprises a hybrid of an antibody molecule and a non-antibody molecule with specificity for GITR or another target. See WO 93/08829, the contents of which are incorporated by reference, for examples of such ABPs. In some aspects, the non-antibody molecule is GITRL.

[193] In some embodiments, the monospecific or multispecific ABP comprises a dual-functioning Fab (DAF) antibody as described in US Patent Publication No. 2008/0069820, the contents of which are hereby incorporated by reference.

[194] In some embodiments, the implementation, multispecific ABP contains an antibody formed by reducing the two original molecules, followed by mixing these two original molecules and re-oxidation to assemble a hybrid structure. See Carlring et al., PLoS One , 2011, 6:e22533, the entire content of which is incorporated by reference.

[195] In some embodiments, the monospecific or multispecific ABP contains a DVD-Ig™. DVD-Ig™ is a dual variable domain immunoglobulin that can bind two or more antigens. DVD-Ig™ are described in US Patent No. 7612181, the full content of which is given as a reference.

[196] In some embodiments, the monospecific or multispecific ABP contains DART™. DART™ described in Moore et al.,Blood, 2011, 117:454-451, the entire content of which is provided by reference.

[197] In some embodiments, the implementation, multispecific ABP contains DuoBody ^® . ^DuoBodies® are described in Labrijn et al., Proc. Natl. Acad. sci. USA , 2013, 110:5145-5150; Gramer et al., mAbs , 2013, 5:962-972; and Labrijn et al., Nature Protocols , 2014, 9:2450-2463; the full content of all of which is given in the present description by reference.

[198] In some embodiments, the implementation, monospecific or multispecific ABP described in the present description, contains an antibody fragment attached to another antibody or fragment. The attachment may be covalent or non-covalent. When the attachment is covalent, it may be present in the form of a fusion protein or be via a chemical linker. Illustrative examples of multispecific ABPs containing antibody fragments fused to other antibodies include tetravalent bispecific antibodies, where the scFv is fused to the C-terminus of C _H3 from IgG. See Coloma and Morrison, Nature Biotechnol. , 1997, 15:159-163. Other examples include antibodies in which a Fab molecule is attached to an immunoglobulin constant region. See Miler et al., J. Immunol. , 2003, 170:4854-4861, the entire content of which is incorporated by reference. You can use any suitable fragment, including any of the fragments described in the present description or known in this field.

[199] In some embodiments, the implementation, monospecific or multispecific ABP contains CovX-Body. CovX-Bodies are described, for example, in Doppalapudi et al., Proc. Natl. Acad. sci. USA , 2010, 107:22611-22616, the entire content of which is incorporated by reference.

[200] In some embodiments, the monospecific or multispecific ABP comprises an Fcab antibody wherein one or more antigen-binding domains are introduced into the Fc region. Fcab antibodies are described in Wozniak-Knopp et al., Protein Eng. Des. Sel. , 2010, 23:289-297, the full content of which is given as a reference.

[201] In some embodiments, the implementation, monospecific or multispecific ABP contains the antibody TandAb ^® . Antibodies TandAb ^® described in Kipriyanov et al., J. Mol. Biol. , 1999, 293:41-56 and Zhukovsky et al., Blood , 2013, 122:5116, all of which are incorporated herein by reference in their entirety.

[202] In some embodiments, the multispecific ABP contains a tandem Fab. Tandem Fabs are described in WO 2015/103072, the entire content of which is incorporated by reference.

[203] In some embodiments, the implementation, multispecific ABP contains Zybody™. Zybodies™ are described in LaFleur et al., mAbs , 2013, 5:208-218, the entire content of which is incorporated by reference.

1.3. Antigen-binding proteins causing GITR multimerization

[204] In some embodiments, the implementation, ABP, in the framework of the invention, cause the multimerization of GITR, expressed on the surface of the target cell. ABPs, within the scope of the invention, can be designed, based on their valency and specificity, to cause multimerization of any suitable number of GITR molecules.

[205] In some embodiments, the implementation, ABP, in the framework of the invention, cause the multimerization of two molecules of GITR. In some embodiments, the ABPs, within the scope of the invention, cause multimerization of three GITR molecules. In some embodiments, the ABPs, within the scope of the invention, cause multimerization of four GITR molecules. In some embodiments, the ABPs, within the scope of the invention, cause multimerization of five GITR molecules. In some embodiments, the ABPs, within the scope of the invention, cause the multimerization of six GITR molecules. In some embodiments, the ABPs, within the scope of the invention, cause the multimerization of seven GITR molecules. In some embodiments, the ABPs, within the scope of the invention, cause multimerization of eight GITR molecules. In some embodiments, the ABPs, within the scope of the invention, cause the multimerization of nine GITR molecules. In some embodiments, the ABPs within the scope of the invention cause ten GITR molecules to multimerize. In some embodiments, the ABPs within the scope of the invention cause the multimerization of eleven GITR molecules. In some embodiments, the ABPs within the scope of the invention cause twelve GITR molecules to multimerize.

[206] In some embodiments, the implementation, ABP, in the framework of the invention, cause multimerization of at least two molecules of GITR. In some embodiments, the ABPs within the scope of the invention cause multimerization of at least three GITR molecules. In some embodiments, the ABPs, within the scope of the invention, cause multimerization of at least four GITR molecules. In some embodiments, the ABPs within the scope of the invention cause multimerization of at least five GITR molecules. In some embodiments, the ABPs within the scope of the invention cause multimerization of at least six GITR molecules. In some embodiments, the ABPs within the scope of the invention cause multimerization of at least seven GITR molecules. In some embodiments, the ABPs within the scope of the invention cause multimerization of at least eight GITR molecules. In some embodiments, the ABPs within the scope of the invention cause multimerization of at least nine GITR molecules. In some embodiments, the ABPs within the scope of the invention cause multimerization of at least ten GITR molecules. In some embodiments, the ABPs, within the scope of the invention, cause multimerization of at least eleven GITR molecules. In some embodiments, the ABPs within the scope of the invention cause multimerization of at least twelve GITR molecules.

[207] In some embodiments, the implementation, ABP, in the framework of the invention, cause multimerization of two to twelve molecules of GITR. In some embodiments, the ABPs within the scope of the invention cause the multimerization of three to ten GITR molecules. In some embodiments, the ABPs within the scope of the invention cause the multimerization of three to six GITR molecules. In some embodiments, ABPs, within the scope of the invention, cause the multimerization of three to five GITR molecules. In some embodiments, ABPs, within the scope of the invention, cause the multimerization of three to four GITR molecules.

1.4. GITR agonism

[208] In some embodiments, the implementation, ABP, in the framework of the invention, acts as a GITR agonist when binding. Such agonism may result from multimerization of GITR by ABP, as described elsewhere herein. See FIG. 1.

[209] In some embodiments, GITR agonism by ABP, within the scope of the invention, results in modulation of NF-κB activity in the target cell. See US Patent No. 7812135, the full content of which is given in the present description by reference. In some aspects, GITR agonism results in modulation of IκB activity or stability in the target cell.

[210] In some embodiments, GITR agonism by ABP, within the scope of the invention, results in activation of the MAPK pathway in the target cell. In some aspects, components of the MAPK pathway activated by ABP, within the scope of the invention, include one or more of p38, JNK, and ERK. See Nocentini et al., Proc. Natl. Acad. sci. USA , 1997, 94:6216-6221; Ronchetti et al., Eur. J. Immunol. , 2004, 34:613-622; and Esparza et al., J. Immunol. , 2005, 174:7869-7874; the full content of all of which is given in the present description by reference.

[211] In some embodiments, GITR agonism by ABP, within the scope of the invention, results in increased production of IL-2Rα, IL-2, IL-8, and/or IFNγ in the target cell. See Ronchetti et al., Eur. J. Immunol. , 2004, 34:613-622, the entire content of which is incorporated by reference.

[212] In some embodiments, GITR agonism by ABP, within the scope of the invention, enhances proliferation, survival, and/or function of an effector T cell. In some aspects, the effector T cell is a CD4+ effector T cell. In some aspects, the effector T cell is a CD8+ effector T cell.

[213] In some embodiments, GITR agonism by ABP, within the scope of the invention, abolishes suppression of an effector T cell by a regulatory T cell. In some aspects, the regulatory T cell is a CD4+CD25+Foxp3+ regulatory T cell. In some aspects, the regulatory T cell is a CD8+CD25+ regulatory T cell.

[214] In some embodiments, GITR agonism by ABP, within the scope of the invention, alters the occurrence or distribution of regulatory T cells. In some aspects, the frequency of regulatory T cells is reduced. In some aspects, the frequency of regulatory T cells is reduced in a particular tissue. In some aspects, the accumulation of regulatory T cells within the tumor is reduced, resulting in a more favorable ratio of effector T cells to regulatory T cells, and increased activity of CD8+ T cells. See Cohen et al., PLoS One , 2010, 5:e10436.

[215] In some embodiments, GITR agonism by ABP, within the scope of the invention, increases natural killer (NK) cell activity. In some embodiments, GITR agonism by ABP, within the scope of the invention, increases the activity of an antigen presenting cell. In some embodiments, GITR agonism by ABP, within the scope of the invention, increases dendritic cell activity. In some embodiments, GITR agonism by ABP, within the scope of the invention, increases B cell activity.

[216] In some embodiments, GITR agonism by ABP, within the scope of the invention, results in an enhanced immune response. In some embodiments, GITR agonism by ABP, within the scope of the invention, results in a delay in the onset of tumor development. In some embodiments, GITR agonism by ABP, within the scope of the invention, results in a reduction in tumor size. In some embodiments, GITR agonism by ABP, within the scope of the invention, results in a reduction in the number of metastases.

[217] In some embodiments, GITR agonism by a multivalent monospecific ABP, within the scope of the invention, results in a greater maximum level of agonism than for a divalent monospecific antibody. In some embodiments, the extra valency results in an effect on EC ₅₀ greater than the additive effects of each of the binding domains. In some embodiments, the tetravalent monospecific ABP, within the meaning of the invention, has a greater maximum level of agonism than the divalent monospecific antibody.

[218] In some embodiments, the multispecific ABPs, within the scope of the invention, are more potent GITR agonists than mixtures of the corresponding monospecific ABPs. For example, if a multispecific ABP, within the scope of the invention, contains two different epitope specificities (e.g., A and B), then, in some embodiments, the GITR agonism by such a multispecific ABP is greater than the GITR agonism by a mixture of two monospecific ABPs each containing one of two specificities (for example, A or B). In some embodiments, the additional specificities of the multispecific ABP, within the scope of the invention, result in a synergistic (i.e., greater than additive) increase in activity compared to mixtures of monospecific ABPs each having only one of the specificities of the multispecific ABP.

1.5. Affinity of antigen-binding proteins for GITR

[219] In some embodiments, the affinity of ABP, within the scope of the invention, for GITR, as shown by K _D , is less than about 10 ^-5 M, less than about 10 ^-6 M, less than about 10 ^-7 M, less than about 10 ^-8 M, less than about 10 ^-9 M, less than about 10 ^-10 M, less than about 10 ^-11 M, or less than about 10 ^-12 M. In some embodiments, the affinity of ABP is between about 10 ^-7 M and 10 ^-12 M. In some embodiments, the affinity of ABP is between about 10 ^-7 M and 10 ^-11 M. In some embodiments, the affinity of ABP is between about 10 ^{- 7} M and 10 ^-10 M. In some embodiments, the affinity of ABP is between about 10 ^-7 M and 10 ^-9 M. In some embodiments, the affinity of ABP is between about 10 ^-7 M and 10 ^-8 M. In some embodiments, the affinity of ABP is between about 10 ^-8 M and 10 ^-12 M. In some embodiments, the affinity of ABP is between about 10 ^-8 M and 10 ^-11 M. In some embodiments, the affinity of ABP is between about 10 ^{- 9} M and 10 ^-11 M. In some embodiments, the affinity of ABP is between about 10 ^-10 M and 10 ^-11 M.

[220] In some embodiments, ABPs within the scope of the invention specifically bind hGITR (SEQ ID NO: 1) to K _D X and cGITR to K _D ≤10 X . In some embodiments, ABPs within the scope of the invention specifically bind hGITR (SEQ ID NO: 1) to K _D X and cGITR to K _D ≤5 X . In some embodiments, ABPs within the scope of the invention specifically bind hGITR (SEQ ID NO: 1) to K _D X and cGITR to K _D ≤2 X . In some aspects, X is any K _D described in this description. In some aspects, X is 0.01 nM, 0.1 nM, 1 nM, 10 nM, 20 nM, 50 nM, or 100 nM.

[221] In some embodiments, K _{D ,} k _a and k _d are determined using surface plasmon resonance (SPR). In some aspects, a ^BIACORE® device is used in the SPR assay. In some aspects, the antigen is immobilized on a carboxymethylated dextran (CM4 or CM5) biosensor chip and contacted with ABP, within the scope of the invention. Binding and dissociation rate constants can be calculated using ^{BIAevaluation®} software and Langmuir's one-to-one binding model. In some aspects, the analysis is carried out at 25°C. In some aspects, the analysis is carried out at 37°C.

[222] In some embodiments, K _{D , ka} and k _d are determined using biolayer interferometry (BLI). Any suitable BLI method may be used. In some aspects, the BLI assay uses the ^FORTEBIO® device. In some aspects, a human IgG Fc (AHC) binding biosensor is used to fix the ABP to the surface of the sensor. Then, the association of ABP and antigen is monitored by bringing the immobilized ABP into contact with various concentrations of GITR. The dissociation of antigen and ABP is then measured in buffer without GITR. Binding and dissociation rate constants are calculated using the kinetic modules of the ^FORTEBIO® analysis software. In some aspects, the analysis is carried out at 30°C.

[223] In other embodiments, K _D can be determined by a radiolabeled antigen binding assay, as described in Chen et al. J. Mol. Biol ., 1999, 293:865-881, the entire content of which is incorporated by reference.

1.5.1. Glycosylation Variants

[224] In specific embodiments, the implementation, ABP, within the scope of the invention, you can change to increase, decrease or eliminate the degree to which it is glycosylated. Glycosylation of polypeptides is typically either "N-linked" or "O-linked".

[225] "N-linked" glycosylation refers to the attachment of a carbohydrate group to the side chain of an asparagine residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are recognition sequences for the enzymatic attachment of a carbohydrate group to the asparagine side chain. Thus, the presence of any of these tripeptide sequences in a polypeptide creates a potential glycosylation site.

[226] "O-linked" glycosylation refers to the attachment of one of the sugars N-acetylgalactosamine, galactose or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.

[227] The addition or deletion of N-linked glycosylation sites to or from ABP, within the scope of the invention, can be accomplished by changing the amino acid sequence so as to create or remove one or more of the above tripeptide sequences. The addition or deletion of O-linked glycosylation sites can be accomplished by adding, deleting or substituting one or more serine or threonine residues to or to the sequence (as the case may be) of the ABP.

[228] In some embodiments, the ABP, within the scope of the invention, contains a glycosylation motif that is different from natural ABP. Any suitable natural glycosylation motif can be modified in ABP, within the scope of the invention. The structural and glycosylation properties of immunoglobulins, for example, are known in the art and are summarized in, for example, Schroeder and Cavacini, J. Allergy Clin. Immunol. , 2010, 125:S41-52, the entire content of which is provided by reference.

[229] In some embodiments, the implementation, ABP, within the framework of the invention, contains the Fc region of IgG1 with the modification of the oligosaccharide attached to asparagine 297 (Asn 297). Natural IgG1 antibodies produced by mammalian cells typically contain a branched, dual-antennary oligosaccharide that is typically N-linked to Asn 297 of the C _H2 domain of the Fc region. See Wright et al., TIBTECH , 1997, 15:26-32, the entire content of which is incorporated by reference. The oligosaccharide attached to Asn 297 may include various carbohydrates such as mannose, N-acetylglucosamine (GlcNAc), galactose, and sialic acid, as well as fucose attached to GlcNAc in the stem of the oligosaccharide's dual antenna structure.

[230] In some embodiments, the oligosaccharide attached to Asn 297 is modified to produce an ABP having an altered ADCC. In some embodiments, the oligosaccharide is modified to improve ADCC. In some embodiments, the oligosaccharide is modified to reduce ADCC.

[231] In some aspects, ABP, within the scope of the invention, contains a reduced fucose IgG1 domain at position Asn 297 compared to the native IgG1 domain. Such Fc domains are known to have improved ADCC. See Shields et al., J. Biol. Chem. , 2002, 277:26733-26740, the entire content of which is incorporated by reference. In some aspects, such ABP does not contain fucose at position Asn 297. The amount of fucose can be determined using any suitable method, for example, as described in WO 2008/077546, the entire content of which is given by reference.

[232] In some embodiments, the ABP, within the scope of the invention, comprises a bisected oligosaccharide, such as a two-antennary oligosaccharide, attached to the Fc region of the ABP, separated by GlcNAc. Such ABP variants may have reduced fucosylation and/or improved ADCC function. Examples of such ABP variants are described, for example, in WO 2003/011878; US Patent No. 6602684; and US Patent Publication No. 2005/0123546; the full content of all of which is given in the present description by reference.

[233] Other exemplary glycosylation variants are described, for example, in US Patent Publications Nos. 2003/0157108 2004/0093621 2003/0157108 2003/0115614 2002/0164328 2004/0093621 2004/0132140 2004/0110704 2004/0110 282, 2004/0109865; in International Patent Publications No. 2000/61739, 2001/29246, 2003/085119, 2003/084570, 2005/035586, 2005/035778; 2005/053742, 2002/031140; Okazaki et al., J. Mol. Biol. , 2004, 336:1239-1249; and Yamane-Ohnuki et al., Biotech. Bioeng. , 2004, 87: 614-622; the full content of all of which is given in the present description by reference.

[234] In some embodiments, the implementation, ABP, in the framework of the invention, contains the Fc region with at least one residue of galactose in the oligosaccharide attached to the Fc region. Such ABP variants may have improved CDC function. Examples of such ABP variants are described, for example, in WO 1997/30087; WO 1998/58964; and WO 1999/22764; the full contents of each are provided by reference.

[235] Examples of cell lines capable of producing defucosylated ABPs include Lec13 CHO cells deficient in protein fucosylation (See Ripka et al., Arch. Biochem. Biophys. , 1986, 249:533-545; US Patent Publication No.. 2003/0157108; WO 2004/056312; the entire contents of all of which are incorporated herein by reference), and knockout cell lines such as alpha-1,6-fucosyltransferase or FUT8 gene knockout cells (See Yamane-Ohnuki et al., Biotech Bioeng. , 2004, 87:614-622; Kanda et al., Biotechnol. Bioeng. , 2006, 94:680-688; and WO 2003/085107, all of which are described in full herein. as a reference).

[236] In some embodiments, the ABP, within the scope of the invention, is an aglycosylated ABP. Aglycosylated ABP can be obtained using any method known in the art or described in the present description. In some aspects, aglycosylated ABP is obtained by modifying the ABP to remove all glycosylation sites. In some aspects, glycosylation sites are removed only from the Fc region of the ABP. In some aspects, aglycosylated ABP is obtained by expressing ABP in an organism incapable of glycosylation, such as E. coli , or by expressing ABP in a cell-free reaction mixture.

[237] In some embodiments, the implementation, ABP, within the framework of the invention, has a constant region with reduced effector function compared to natural IgG1 antibody. In some embodiments, the affinity of a constant region from the Fc region of an ABP, within the scope of the invention, for an Fc receptor is less than the affinity of a native IgG1 constant region for that Fc receptor.

1.6. Fc region amino acid sequence variants

[238] In specific embodiments, the ABP, within the scope of the invention, contains an Fc region with one or more amino acid substitutions, insertions, or deletions compared to the natural Fc region. In some aspects, such substitutions, insertions, or deletions result in an ABP with altered stability, glycosylation, or other characteristics. In some aspects, such substitutions, insertions or deletions result in aglycosylated ABP.

[239] In some aspects, the Fc region of the ABP, within the scope of the invention, is modified to produce an ABP with an altered affinity for the Fc receptor, or an ABP that is more immunologically inert. In some embodiments, ABP variants within the scope of the invention have some, but not all, effector functions. Such an ABP can be used, for example, when the half-life of the ABP is important in vivo , but when specific effector functions (eg, complement activation and ADCC) are unnecessary or detrimental.

[240] In some embodiments, the ABP Fc region, within the scope of the invention, is a human IgG4 Fc region containing the hinge-stabilizing mutation S228P or L235E. In some embodiments, the IgG4 Fc region contains the S228P and L235E hinge stabilizing mutations. See Aalberse et al., Immunology , 2002, 105:9-19, the entire content of which is incorporated by reference. In some embodiments, the IgG4 Fc region contains one or more of the following mutations: E233P, F234V, and L235A. See Armor et al., Mol. Immunol. , 2003, 40:585-593, the entire content of which is incorporated by reference. In some embodiments, the IgG4 Fc region contains a deletion at position G236.

[241] In some embodiments, the Fc region of an ABP, within the scope of the invention, is a human IgG1 Fc region containing one or more mutations to reduce Fc receptor binding. In some aspects, one or more mutations are present at residues selected from S228 (eg S228A), L234 (eg L234A), L235 (eg L235A), D265 (eg D265A), and N297 (eg N297A). In some aspects, the ABP contains the PVA236 mutation. PVA236 means that the amino acid sequence of ELLG, from amino acid positions 233-236 of IgG1 or EFLG of IgG4, is changed to PVA. See US Patent Publication No. 2013/0065277, the full content of which is provided by reference.

[242] In some embodiments, the Fc region of ABP is modified as described in Armor et al., Eur. J. Immunol. , 1999, 29:2613-2624; WO 1999/058572; and/or UK Pat. app. no. 98099518; the full content of all of which is given in the present description by reference.

[243] In some embodiments, the ABP Fc region, within the scope of the invention, is a human IgG2 Fc region containing one or more of the A330S and P331S mutations.

[244] In some embodiments, the Fc region of ABP, within the scope of the invention, has an amino acid substitution at one or more positions selected from 238, 265, 269, 270, 297, 327, and 329. See US Pat. 6737056, the full content of which is given as a reference. Such Fc mutants include Fc mutants with substitutions at two or more of amino acid positions 265, 269, 270, 297 and 327, including the so-called "DANA" Fc mutant with residues 265 and 297 replaced by alanine. See US Patent No. 7332581, the full content of which is provided by reference. In some embodiments, ABP contains alanine at amino acid position 265. In some embodiments, ABP contains alanine at amino acid position 297.

[245] In specific embodiments, the ABP, within the scope of the invention, comprises an Fc region with one or more amino acid substitutions that improve ADCC, such as a substitution at one or more of positions 298, 333, and 334 of the Fc region. In some embodiments, the ABP, within the scope of the invention, contains an Fc region with one or more amino acid substitutions at positions 239, 332, and 330 as described in Lazar et al., Proc. Natl. Acad. sci. USA , 2006,103:4005-4010, the entire content of which is incorporated by reference.

[246] In some embodiments, the implementation, ABP, in the framework of the invention, contains one or more changes that improve or reduce the binding of C1q and/or CDC. See US Patent No. 6194551; W099/51642; and Idusogie et al., J. Immunol. , 2000, 164:4178-4184; the full content of all of which is given in the present description by reference.

[247] In some embodiments, the implementation, ABP, within the scope of the invention, contains one or more changes to increase the half-life. ABPs with extended half-life and improved binding to the neonatal Fc receptor (FcRn) are described, for example, in Hinton et al., J. Immunol. , 2006, 176:346-356; and US Patent Publication No. 2005/0014934; the full content of all of which is given in the present description by reference. Such Fc variants include those with substitutions at one or more of the residues from the Fc region: 238, 250, 256, 265, 272, 286, 303, 305, 307, 311, 312, 314, 317, 340, 356, 360, 362 , 376, 378, 380, 382, 413, 424, 428 and 434 from IgG.

[248] In some embodiments, the ABP, within the scope of the invention, contains one or more variants of the Fc region, as described in US Patent No. 7371826 5648260 and 5624821; Duncan and Winter, Nature , 1988, 322:738-740; and WO 94/29351; the full content of all of which is given in the present description by reference.

1.7. Cysteine-engineered antigen-binding protein variants

[249] In specific embodiments, the present invention relates to cysteine-engineered ABPs, also known as "thioMAbs", in which one or more ABP residues are replaced with cysteine residues. In specific embodiments, the substituted residues occur in solvent-accessible ABP residues. By replacing such residues with cysteine, reactive thiol groups are introduced into solvent-accessible regions of the ABP and can be used to conjugate ABP to other groups, such as drug or linker-drug groups, for example, to prepare an immunoconjugate.

[250] In specific embodiments, any one or more of the following residues can be replaced with a cysteine: V205 light chain; A118 heavy chain Fc region; and the S400 region of the heavy chain Fc. Cysteine-engineered ABPs can be prepared as described, for example, in US Patent No. 7521541, the full content of which is given as a reference.

1.7.1. Immunoconjugates

1.7.1.1. Antigen-binding protein-polymer conjugates

[251] In some embodiments, the implementation, ABP, in the framework of the invention, derivatized by conjugation with a polymer. Any suitable polymer can be conjugated to ABP.

[252] In some embodiments, the polymer is a water-soluble polymer. Illustrative examples of water-soluble polymers include polyethylene glycol (PEG), ethylene glycol/propylene glycol copolymers, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone, poly-1,3-dioxolane, poly-1,3,6-trioxane, ethylene/maleic anhydride copolymer, polyamino acids ( either homopolymers or random copolymers), (n-vinylpyrrolidone)-polyethylene glycol copolymer, propylene glycol homopolymers, polypropylene oxide/ethylene oxide copolymers, polyoxyethylated polyols (eg glycerol), polyvinyl alcohol and mixtures thereof. In some aspects, polyethylene glycol propionaldehyde may provide manufacturing advantages due to its stability in water.

[253] The polymer may be of any molecular weight, and may be branched or unbranched. The number of polymers attached to each ABP may vary, and if more than one polymer is attached, they may be the same polymer or different polymers. Generally, the amount and/or type of polymers used for derivatization can be determined based on considerations including the specific properties or functions of the ABP to be improved and the intended use of the ABP.

1.7.1.2. Antigen-binding protein-drug conjugates

[254] In some embodiments, the implementation, ABP, in the framework of the invention, are conjugated to one or more drugs. Any suitable drug can be conjugated to ABP. Exemplary drugs include cytokines, chemokines, and other agents that induce desired T cell activity such as GITRL, OX40L, 4-1BBL, TNF-alpha, IL-2, IL-15 fusion protein, CXCL9, CXCL10, IL-trap 10, IL-27 trap and IL-35 trap. Cytokine decoys and their use are known in the art and are described, for example, in Economides et al., Nature Medicine , 2003, 9:47-52, the entire content of which is incorporated by reference.

Methods for producing antigen-binding proteins against GITR

1.8. Obtaining the GITR antigen

[255] The GITR antigen used to isolate ABP, within the scope of the invention, may be an intact GITR or a fragment of a GITR. The GITR antigen may be in the form of an isolated protein or a protein expressed on the cell surface.

[256] In some embodiments, the GITR antigen is a non-natural GITR variant, such as a GITR protein, having an amino acid sequence or post-translational modification not naturally occurring.

[257] In some embodiments, the GITR antigen is shortened by removing, for example, intracellular or membrane-crossing sequences, or signal sequences. In some embodiments, the GITR antigen is C-terminally fused to a human IgG1 Fc domain or polyhistidine tag.

1.9. Methods for obtaining monoclonal antibodies

[258] Monoclonal antibodies can be generated, for example, using the hybridoma method first described in Kohler et al., Nature , 1975, 256:495-497 (the entire content of which is given by reference), and/or through recombinant DNA methods ( See , for example, US Patent No. 4816567, the entire content of which is given by reference). Monoclonal antibodies can also be generated, for example, using phage or yeast based libraries. See , for example, US Patent No. 8258082 and 8691730, the full content of all of which is given in the present description by reference.

[259] In the hybridoma method, a mouse or other suitable host animal is immunized to activate lymphocytes that produce or are capable of producing antibodies that can specifically bind the protein used for immunization. Alternatively, lymphocytes can be immunized in vitro . The lymphocytes are then fused with myeloma cells using a suitable fusion-inducing agent, such as polyethylene glycol, to obtain hybridoma cells. See Goding JW, Monoclonal Antibodies: Principles and Practice ^3rd ed. (1986) Academic Press, San Diego, CA, the entire contents of which are incorporated by reference.

[260] Hybridoma cells are seeded and grown in a suitable culture medium containing one or more substances that inhibit the growth or survival of non-fused, parental myeloma cells. For example, if parental myeloma cells lack the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT), hybridoma culture media typically contains hypoxanthine, aminopterine, and thymidine (HAT medium), which prevent the growth of HGPRT-deficient cells.

[261] Myeloma cells that can be used are cells that fuse efficiently, maintain a consistently high level of antibody expression by selected antibody-producing cells, and are sensitive to environmental conditions such as the presence or absence of HAT media. Of these, preferred myeloma cell lines are mouse myeloma lines such as those derived from MOP-21 and MC-11 mouse tumors (available from Salk Institute Cell Distribution Center, San Diego, CA) and SP-2 or X63- Ag8-653 (available from the American Type Culture Collection, Rockville, MD). Human myeloma and mouse-human heteromyeloma cell lines have also been described for the production of human monoclonal antibodies. See , for example, Kozbor, J. Immunol. , 1984, 133:3001, the entire content of which is incorporated by reference.

[262] Once hybridoma cells have been identified that produce antibodies with the desired specificity, affinity, and/or biological activity, selected clones can be subcloned by limiting dilution methods and grown by standard methods. See Goding, supra . Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, hybridoma cells can be grown in vivo as ascitic tumors in an animal.

[263] DNA encoding monoclonal antibodies can be easily isolated and sequenced using conventional methods (eg, using oligonucleotide probes capable of specifically binding to genes encoding heavy and light chains of monoclonal antibodies). Thus, hybridoma cells can serve as a useful source of DNA encoding antibodies with desirable properties. Once isolated, the DNA can be placed into expression vectors that are then transfected into host cells such as bacteria (eg E. coli ), yeast (eg Saccharomyces or Pichia spp.), COS cells, Chinese hamster ovary (CHO) cells, or myelomas that do not otherwise produce antibody to produce monoclonal antibodies.

1.10. Methods for obtaining chimeric antibodies

[264] Illustrative methods for producing chimeric antibodies are described, for example, in US Patent No. 4816567; and Morrison et al., Proc. Natl. Acad. sci. USA , 1984, 81:6851-6855; the full content of all of which is given in the present description by reference. In some embodiments, a chimeric antibody is generated using recombinant techniques to combine a non-human variable region (e.g., a variable region derived from a mouse, rat, hamster, rabbit, or non-human primate such as a monkey) with a human constant region.

1.11. Methods for obtaining humanized antibodies

[265] Humanized antibodies can be generated by replacing most, or all, of the structural portions of a non-human monoclonal antibody with the corresponding human antibody sequences. Therefore, a hybrid molecule is obtained in which only the antigen-specific variable region, or CDR, consists of a non-human sequence. Methods for making humanized antibodies include those described in, for example, Winter and Milstein, Nature , 1991, 349:293-299; Rader et al., Proc. Nat. Acad. sci. USA , 1998, 95:8910-8915; Steinberger et al., J. Biol. Chem. , 2000, 275:36073-36078; Queen et al., Proc. Natl. Acad. sci. USA , 1989, 86:10029-10033; and US Patent No. 5585089, 5693761, 5693762 and 6180370; the full content of all of which is given in the present description by reference.

1.12. Methods for obtaining human antibodies

[266] Human antibodies can be produced by a variety of methods known in the art, for example, using transgenic animals (eg, humanized mice). See , for example, Jakobovits et al., Proc. Natl. Acad. sci. USA ., 1993, 90:2551; Jakobovits et al., Nature , 1993, 362:255-258; Bruggermann et al., Year in Immuno. , 1993, 7:33; and US Patent No. 5591669, 5589369 and 5545807; the full content of all of which is given in the present description by reference. Human antibodies can also be obtained from phage display libraries (See , for example, Hoogenboom et al., J. Mol. Biol. , 1991, 227:381-388; Marks et al., J. Mol. Biol. , 1991, 222 :581-597; and U.S. Patent Nos. 5,565,332 and 5,573,905, all of which are incorporated herein by reference in their entirety). Human antibodies can also be generated by in vitro activated B cells (See , for example, US Pat. Nos. 5,567,610 and 5,229,275, all of which are incorporated herein by reference in their entireties). Human antibodies can also be obtained from yeast-based libraries (See , for example, US Patent No. 8691730, the entire content of which is given as a reference).

1.13. Methods for obtaining antibody fragments

[267] Antibody fragments, within the scope of the invention, can be obtained by any suitable method, including the illustrative methods described in the present description, or methods known in this field. Suitable methods include recombinant methods and proteolytic cleavage of full length antibodies. Illustrative methods for producing antibody fragments are described, for example, in Hudson et al., Nat. Med. , 2003, 9:129-134, the entire content of which is incorporated by reference. Methods for making scFv antibodies are described, for example, in Plückthun, in The Pharmacology of Monoclonal Antibodies , vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994); WO 93/16185; and US Patent No. 5571894 and 5587458; the full content of all of which is given in the present description by reference.

1.14. Methods for obtaining alternative scaffolds

[268] Alternative frameworks, within the scope of the invention, can be obtained by any suitable method, including the illustrative methods described in the present description, or methods known in this field. For example, methods for producing Adnectin™ are described in Emanuel et al., mAbs , 2011, 3:38-48, the entire content of which is incorporated by reference. Methods for making iMabs are described in US Patent Publication No. 2003/0215914, the contents of which are incorporated by reference. Methods for preparing ^anticalins® are described in Vogt and Skerra, Chem. Biochem. , 2004, 5:191-199, the entire content of which is incorporated by reference. Methods for obtaining marten domains are described in Wagner et al., Biochem. & Biophys. Res. Comm. , 1992, 186:118-1145, the entire content of which is incorporated by reference. Methods for preparing thioredoxin-based peptide aptamers are presented in Geyer and Brent, Meth. Enzymol. , 2000, 328:171-208, the entire content of which is incorporated by reference. Methods for obtaining affitels are presented in Fernandez, Curr. Opinion in Biotech. , 2004, 15:364-373, the entire content of which is incorporated by reference. Methods for producing darpins are presented in Zahnd et al., J. Mol. Biol. , 2007, 369:1015-1028, the entire content of which is incorporated by reference. Methods for preparing affilins are presented in Ebersbach et al., J. Mol. Biol. , 2007, 372:172-185, the entire content of which is incorporated by reference. Methods for preparing tetranectins are presented in Graversen et al., J. Biol. Chem. , 2000, 275:37390-37396, the entire content of which is incorporated by reference. Methods for making avimers are presented in Silverman et al., Nature Biotech. , 2005, 23:1556-1561, the entire content of which is incorporated by reference. Methods for preparing finomers are presented in Silacci et al., J. Biol. Chem. , 2014, 289:14392-14398, the entire content of which is incorporated by reference.

[269] For more information on alternative scaffolds, see Binz et al., Nat. Biotechnol. , 2005 23:1257-1268; and Skerra, Current Opin. in Biotech. , 2007 18:295-304, all of which are incorporated herein by reference in their entirety.

1.15. Methods for obtaining multispecific ABPs

[270] Multispecific or multivalent monospecific ABP, within the scope of the invention, can be obtained by any suitable method, including the illustrative methods described in the present description, or methods known in this field. Methods for making a common light chain antibody are described in Merchant et al.,Nature Biotechnol., 1998, 16:677-681, the entire content of which is incorporated by reference. Methods for making tetravalent bispecific antibodies are described in Coloma and Morrison,Nature Biotechnol., 1997, 15:159-163, the entire content of which is incorporated by reference. Methods for making hybrid immunoglobulins are described in Milstein and Cuello,Nature, 1983, 305:537-540; and Staerz and Bevan,Proc. Natl. Acad. sci. USA, 1986, 83:1453-1457; the full content of all of which is given in the present description by reference. Methods for producing immunoglobulins with ridge-to-cavity modification are described in U.S. Patent No. 5731168, the full content of which is given as a reference. Methods for producing immunoglobulins with electrostatic modifications are presented in WO 2009/089004, the contents of which are incorporated by reference. Methods for making multivalent (eg, tetravalent) monospecific antibodies are described in Miller et al., 2003, US Patent No. 8722859, the full content of which is provided by reference. Methods for making bispecific single chain antibodies are described in Traunecker et al.,EMBO J., 1991, 10:3655-3659; and Gruber et al.J. Immunol., 1994, 152:5368-5374; the full content of all of which is given in the present description by reference. Methods for preparing single chain antibodies whose linker length can be changed are described in US Patent Nos. 4946778 and 5132405, the full content of all of which is given in the present description by reference. Methods for preparing diabodies are described in Hollinger et al.,Proc. Natl. Acad. sci. USA, 1993, 90:6444-6448, the entire content of which is incorporated by reference. Methods for preparing triobodies and tetrabodies are described in Todorovska et al.,J. Immunol. methods, 2001, 248:47-66, the entire content of which is incorporated by reference. Methods for preparing trispecific derivatives of F(ab')3 are described in Tutt et al.J. Immunol., 1991, 147:60-69, the entire content of which is incorporated by reference. Methods for making cross-linked antibodies are described in U.S. Patent No. 4676980; Brennan et al.Science, 1985, 229:81-83; Staerz, et al.Nature, 1985, 314:628-631; and EP 0453082; the full content of all of which is given in the present description by reference. Methods for obtaining antigen-binding domains assembled by leucine zippers are described in Kostelny et al.,J. Immunol., 1992, 148:1547-1553, the entire content of which is incorporated by reference. Methods for producing ABP by the DNL process are described in U.S. Patent Nos. 7521056; 7550143; 7534866; and 7527787; the full content of all of which is given in the present description by reference. Methods for making hybrids of antibodies and non-antibody molecules are described in WO 93/08829, the contents of which are incorporated by reference, for examples of such ABPs. Methods for making DAF antibodies are described in US Patent Publication No. 2008/0069820, the contents of which are hereby incorporated by reference. Methods for producing ABP through reduction and oxidation are described in Carlring et al.,PLOS One, 2011, 6:e22533, the full content of which is provided by reference. Methods for obtaining DVD-Ig™ described in US Patent No. 7612181, the full content of which is given as a reference. Ways to get DART™ described in Moore et al.,Blood, 2011, 117:454-451, the entire content of which is provided by reference. Ways to get DuoBodies^® described in Labrijn et al.,Proc. Natl. Acad. sci. USA, 2013, 110:5145-5150; Gramer et al.mAbs, 2013, 5:962-972; and Labrijn et al.,Nature Protocols, 2014, 9:2450-2463; the full content of all of which is given in the present description by reference. Methods for producing antibodies containing scFv fused to the C-terminus of C_H3 of IgG are described in Coloma and Morrison,Nature Biotechnol., 1997, 15:159-163, the entire content of which is incorporated by reference. Methods for producing antibodies in which a Fab molecule is fused to an immunoglobulin constant region are described in Miler et al.,J. Immunol., 2003, 170:4854-4861, the entire content of which is incorporated by reference. Methods for making CovX-Bodies are described in Doppalapudi et al.,Proc. Natl. Acad. sci. USA, 2010, 107:22611-22616, the entire content of which is incorporated by reference. Methods for making Fcab antibodies are described in Wozniak-Knopp et al.,protein Eng. Des. Sel., 2010, 23:289-297, the full content of which is given as a reference. Methods for obtaining TandAb antibodies^® described in Kipriyanov et al.,J. Mol. Biol., 1999, 293:41-56 and Zhukovsky et al.,Blood, 2013, 122:5116, all of which are incorporated herein by reference in their entirety. Methods for producing tandem Fabs are described in WO 2015/103072, the contents of which are incorporated by reference. Methods for making Zybodies™ are described in LaFleur et al.,mAbs, 2013, 5:208-218, the entire content of which is provided by reference.

[271] In another aspect, the present invention relates to a method for producing an anti-human GITR antibody, or antigen-binding fragment thereof, comprising culturing a host cell(s) selected from the group consisting of (a) to (c) below, to express a tetravalent an anti-human GITR antibody or antigen-binding fragment thereof: (a) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the heavy chain variable region of an anti-human GITR antibody or antigen-binding fragment thereof, within the scope of the invention, and a polynucleotide containing the sequence bases encoding the variable region of the light chain of the antibody or antigennegative fragment; (b) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the heavy chain variable region of a human anti-GITR antibody or antigen-binding fragment thereof, within the scope of the invention, and an expression vector containing a polynucleotide containing a base sequence encoding the variable region the light chain of an antibody or antigen-binding fragment thereof; and (c) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the heavy chain variable region of a human anti-GITR antibody or an antigen-binding fragment thereof, within the scope of the invention, and a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the light chain variable region of an antibody or antigen-binding fragment thereof.

[272] In another aspect, the present invention relates to a method for producing an anti-human GITR antibody, comprising culturing a host cell(s) selected from the group consisting of (a) to (c) below, to express an anti-human GITR antibody: (a) a host cell transformed with an expression vector comprising a polynucleotide containing a base sequence encoding the heavy chain of an anti-human GITR antibody of the invention and a polynucleotide containing a base sequence encoding the light chain of an antibody; (b) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the heavy chain of an anti-human GITR antibody of the invention and an expression vector containing a polynucleotide containing a base sequence encoding an antibody light chain; and (c) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the heavy chain of an anti-human GITR antibody of the invention and a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding a light chain antibodies.

1.16. Ways to get options

[273] In some embodiments, the ABP, within the scope of the invention, is an affinity-matured variant of the original ABP, which can be obtained, for example, using phage display-based affinity maturation methods. Briefly, one or more CDR residues can be mutated and the ABP variant or portion thereof is displayed on phage and screened for affinity. Such changes can be made at CDR hotspots, or residues encoded by codons that are susceptible to mutation at high rates during the somatic maturation process (See Chowdhury, Methods Mol. Biol. , 2008, 207:179-196, full contents which is given as a reference), and/or in residues in contact with the antigen. In some embodiments, affinity maturation can be used to change or introduce binding species, i.e., an anti-mouse antibody can be modified to bind to human and cynomolgus monkey variants of the same target antigen, etc.

[274] Any suitable method can be used to introduce variability into the ABP-encoding polynucleotide sequence(s), including reduced precision PCR, strand shuffling, and oligonucleotide-directed mutagenesis, such as trinucleotide-directed mutagenesis (TRIM). In some aspects, multiple CDR residues are randomized (eg, 4-6 residues at a time). CDR residues involved in antigen binding can be specifically identified, for example, using alanine scanning mutagenesis or modeling. CDR-H3 and CDR-L3 are especially frequently targeted for mutation.

[275] Introduction of diversity into variable regions and/or CDRs can be used to generate a secondary library. The secondary library is then screened to identify ABP variants with improved affinity. Affinity maturation through construction and reselection from secondary libraries is described, for example, in Hoogenboom et al., Methods in Molecular Biology , 2001, 178:1-37, the entire content of which is incorporated by reference.

1.17. Vectors, host cells and recombinant methods

[276] The present invention also relates to isolated nucleic acids encoding ABP GITR, vectors containing nucleic acids, and host cells containing vectors and nucleic acids, as well as recombinant methods for producing ABP.

[277] In another aspect, the present invention provides a polynucleotide comprising a base sequence encoding the heavy chain variable region of a human anti-GITR antibody or antigen-binding fragment thereof, within the scope of the invention. In another aspect, the present invention provides a polynucleotide comprising a base sequence encoding a light chain variable region of an anti-GITR human antibody or antigen-binding fragment thereof, within the scope of the invention.

[278] In another aspect, the present invention provides a polynucleotide comprising a base sequence encoding a heavy chain of an anti-human GITR antibody, within the scope of the invention. In another aspect, the present invention provides a polynucleotide comprising a base sequence encoding a light chain of an anti-human GITR antibody, within the scope of the invention.

[279] For recombinant production of ABP, the nucleic acid(s) encoding it can be isolated and inserted into a replicable vector for further cloning (ie, DNA amplification) or expression. In some aspects, the nucleic acid can be obtained through homologous recombination, for example, as described in US Patent No. 5204244, the full content of which is provided by reference.

[280] In another aspect, the present invention provides an expression vector comprising (a) a polynucleotide comprising a base sequence encoding the heavy chain variable region of an anti-GITR human antibody or antigen-binding fragment thereof, within the scope of the invention, and/or (b) a polynucleotide comprising a base sequence encoding the light chain variable region of a human anti-GITR antibody, or an antigen-binding fragment thereof.

[281] In another aspect, the present invention provides an expression vector comprising (a) a polynucleotide comprising a base sequence encoding the heavy chain of an anti-GITR antibody of the invention, and/or (b) a polynucleotide comprising a base sequence encoding a light chain antibodies against human GITR.

[282] Many different vectors are known in the art. Vector components typically include one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence, for example, as described in U.S. Patent No. 5534615, the full content of which is given as a reference.

[283] Illustrative examples of suitable host cells are provided below. These host cells are not limiting, and any suitable host cell can be used to produce ABP, within the scope of the invention.

[284] In another aspect, the present invention relates to a host cell transformed with an expression vector selected from the group consisting of (a) to (d): (a) a host cell transformed with an expression vector containing a polynucleotide containing the base sequence, coding for the heavy chain variable region of an anti-GITR human antibody or antigen-binding fragment thereof, within the scope of the invention, and a polynucleotide containing a base sequence encoding the light chain variable region of the antibody or antigen-binding fragment thereof; (b) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the heavy chain variable region of a human anti-GITR antibody or antigen-binding fragment thereof, within the scope of the invention, and an expression vector containing a polynucleotide containing a base sequence encoding the variable region the light chain of an antibody or antigen-binding fragment thereof; (c) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the heavy chain variable region of a human anti-GITR antibody or antigen-binding fragment thereof, within the scope of the invention; and (d) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding a light chain variable region of an anti-GITR antibody or antigen-binding fragment thereof, within the scope of the invention.

[285] In another aspect, the present invention relates to a host cell transformed with an expression vector selected from the group consisting of (a) to (d): (a) a host cell transformed with an expression vector containing a polynucleotide containing the base sequence, coding for the heavy chain of an antibody against human GITR, within the scope of the invention, and a polynucleotide containing a base sequence encoding a light chain of an antibody; (b) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the heavy chain of an anti-human GITR antibody of the invention and an expression vector containing a polynucleotide containing a base sequence encoding an antibody light chain; (c) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding the heavy chain of an anti-human GITR antibody, within the scope of the invention; and (d) a host cell transformed with an expression vector containing a polynucleotide containing a base sequence encoding an anti-human GITR antibody light chain, within the scope of the invention.

[286] Suitable host cells include any cells of prokaryotes (eg bacteria), lower eukaryotes (eg yeast), or higher eukaryotes (eg mammals). Suitable prokaryotes include eubacteria such as Gram-negative or Gram-positive organisms, e.g. Enterobacteriaceae such as Escherichia ( E. coli ), Enterobacter , Erwinia , Klebsiella , Proteus , Salmonella ( S. typhimurium ), Serratia ( S. marcescans ), Shigella , Bacilli ( B. subtilis and B. licheniformis ), Pseudomonas ( P. aeruginosa ), and Streptomyces . One useful E. coli cloning host is E. coli 294, although other strains such as E. coli B, E. coli X1776 and E. coli W3110 are also suitable.

[287] In addition to prokaryotes, eukaryotic microorganisms such as filamentous fungi or yeast are also suitable cloning or expression hosts for vectors encoding ABP GITR. Saccharomyces cerevisiae , or common baker's yeast, is a commonly used lower eukaryotic host microorganism. However, a number of other genera, species, and strains are available and can be used, such as Schizosaccharomyces pombe , Kluyveromyces ( K. lactis , K. fragilis, K. bulgaricus , K. wickeramii , K. waltii , K. drosophilarum , K. thermotolerans , and K. marxianus ), Yarrowia , Pichia pastoris , Candida ( C. albicans ), Trichoderma reesia , Neurospora crassa , Schwanniomyces ( S. occidentalis ), and filamentous fungi such as Penicillium , Tolypocladium and Aspergillus ( A. nidulans and A. niger ).

[288] Mammalian host cells that can be used include COS-7 cells, HEK293 cells; baby hamster kidney (BHK) cells; Chinese hamster ovary (CHO) cells; mice Sertoli cells; African green monkey kidney cells (VERO-76); and the like.

[289] The host cells used to obtain ABP GITR according to this invention can be cultured in a variety of media. Commercially available media such as Ham's F10, Minimal Maintenance Medium (MEM), RPMI-1640, and Dulbecco's Modified Eagle's Medium (DMEM) are suitable for culturing host cells. In addition, any of the media described in Ham et al., Meth. Enz. , 1979, 58:44; Barnes et al., Anal. Biochem. , 1980, 102:255; and US Patent No. 4767704, 4657866, 4927762, 4560655 and 5122469; or WO 90/03430 and WO 87/00195. The full contents of each of the above links are provided by reference.

[290] Any of these media can be supplemented as needed with hormones and/or other growth factors (such as insulin, transferrin, or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium, and phosphate), buffers (such as HEPES ), nucleotides (such as adenosine and thymidine), antibiotics, micronutrients (defined as inorganic compounds typically present in final concentrations in the micromolar range), and glucose or an equivalent energy source. Any other necessary additives can also be included at suitable concentrations known to the person skilled in the art.

[291] Culture conditions such as temperature, pH, and the like are those previously used for the host cell selected for expression, and are obvious to a person skilled in the art.

[292] When using recombinant methods, ABP can be produced inside cells, in the periplasmic space, or directly secreted into the environment. If ABP is produced intracellularly, as a first step, particulate debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration. For example, in Carter et al. ( Bio/Technology , 1992, 10:163-167, the contents of which are incorporated by reference) describe a method for isolating ABP that is secreted into the periplasmic space of E. coli . Briefly, the cell mass is thawed in the presence of sodium acetate (pH 3.5), EDTA, and phenylmethylsulfonyl fluoride (PMSF) for approximately 30 minutes. Cellular debris can be removed by centrifugation.

[293] In some embodiments, the ABP is produced in a cell-free system. In some aspects, the cell-free system is an in vitro transcription and translation system as described in Yin et al., mAbs , 2012, 4:217-225, the entire content of which is incorporated by reference. In some aspects, the cell-free system uses a cell-free extract from a eukaryotic cell or from a prokaryotic cell. In some aspects, the prokaryotic cell is E. coli . Cell-free expression of ABP may be useful, for example, when ABP accumulates in the cell in the form of an insoluble aggregate, or when yields after periplasmic expression are low.

[294] When ABP is secreted into the medium, supernatants from such expression systems are typically first concentrated using a commercially available protein concentration filter, such as an ^Amicon® or ^Millipore® , ^Pellcon® ultrafiltration unit. A protease inhibitor such as PMSF may be included in any of the above steps to inhibit proteolysis, and antibiotics may be included to prevent the growth of unintended contaminating organisms.

[295] ABP composition derived from cells can be purified using, for example, hydroxyapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, where affinity chromatography is a particularly useful purification method. The suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc domain that is present in the ABP. Protein A can be used to purify ABPs containing human γ1, γ2 or γ4 heavy chains (Lindmark et al., J. Immunol. Meth. , 1983, 62:1-13, the entire content of which is incorporated by reference). Protein G represents can be used for all mouse isotypes and for human γ3 (Guss et al., EMBO J. , 1986, 5:1567-1575, the entire content of which is incorporated by reference).

[296] The matrix to which the affinity ligand is attached is most often agarose, however, other matrices are available. Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzene provide higher flow rates and shorter processing times than can be achieved using agarose. When the ABP contains a C _H3 domain, BakerBond ^ABX® resin can be used for cleaning.

[297] Other protein purification methods, such as ion exchange column fractionation, ethanol precipitation, reverse phase HPLC, silica gel chromatography, heparin- ^sepharose® chromatography, chromatography, SDS-PAGE, and ammonium sulfate precipitation, are also available and may use a specialist in the field.

[298] After any pre-purification step(s), the mixture containing the ABP of interest and contaminants can be subjected to low pH hydrophobic interaction chromatography using an elution buffer with a pH between about 2.5 and about 4.5, as usually carried out at a low salt concentration (eg, from about 0 to about 0.25 M salt).

Analyzes

[299] A variety of assays known in the art can be used to identify and characterize ABP GITR, within the scope of the invention.

1.18. Binding, competition and epitope mapping assays

[300] Specific antigen binding activity for ABP, within the scope of the invention, can be assessed by any suitable method, including the use of SPR, BLI and RIA, as described elsewhere in this description. In addition, antigen binding activity can be assessed by ELISA assays and Western blot assays.

[301] Assays for measuring competition between two ABPs, or between an ABP and another molecule (eg, GITRL) are described elsewhere in this specification and, for example, in Harlow and Lane, Antibodies: A Laboratory Manual ch.14, 1988, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, the entire contents of which are incorporated by reference.

[302] Assays for mapping epitopes that bind ABP within the scope of the invention are described, for example, in Morris "Epitope Mapping Protocols", in Methods in Molecular Biology vol. 66, 1996, Humana Press, Totowa, NJ, the entire content of which is incorporated by reference. In some embodiments, the epitope is determined by peptide competition. In some embodiments, the epitope is determined by mass spectrometry. In some embodiments, the epitope is determined by crystallography.

1.19. GITR agonism assays

[303] In some embodiments, the ABP is screened to identify or characterize an ABP with anti-GITR agonistic activity as part of the invention. Any suitable assay can be used to identify or characterize such ABPs. In some aspects, the assay measures the amount of a cytokine secreted by an effector T cell after the effector T cell is brought into contact with an ABP, within the scope of the invention. In some aspects, the cytokine is selected from IL-2Rα, IL-2, IL-8, IFNγ, and combinations thereof. In some aspects, the cytokine is selected from sCD40L, VEGF, TNF-β, TNF-α, TGF-α, RANTES, PDGF-AB/BB, PDGF-AA, MIP-1β, MIP-1α, MDC (CCL22), MCP- 3, MCP-1, IP-10, IL-17A, IL-15, IL-13, IL-12 (p70), IL-12 (p40), IL-10, IL-9, IL-8, IL- 7, IL-6, IL-5, IL-4, IL-3, IL-2, IL-2Rα, IL-1RA, IL-1β, IL-1α, IFNγ, IFNα2, GRO, GM-CSF, G- CSF, fractalkine, Flt-3 ligand, FGF-2, eotaxin, EGF and combinations thereof.

[304] In some embodiments, the effector cells are co-stimulated using a CD3 agonist to stimulate the secretion of cytokines by the effector cell. In some aspects, the CD3 agonist is provided at a submaximal level.

[305] In some embodiments, functional assays are used, such as HT1080 or Jurkat cell-based assays, described in more detail in Example 2. Additional assays are described in Wyzgol et al., J Immunol 2009; 183:1851-1861, the contents of which are incorporated herein by reference.

[306] In some aspects, such assays can measure the proliferation of an effector T cell after the effector T cell is brought into contact with ABP, within the scope of the invention. In some aspects, effector T cell proliferation is measured by dye dilution (e.g., carboxyfluorescein diacetate succinimidyl ester; CFSE), by tritiated thymidine uptake, by fluorescent cell viability assays, or by other assays known in the art.

[307] In some aspects, such assays can measure differentiation, cytokine production, viability (eg, survival), proliferation, or suppressive activity of a regulatory T cell after the regulatory T cell is contacted with ABP, within the scope of the invention.

[308] In some aspects, such assays can measure the cytotoxic activity of the NK cell after bringing the NK cell into contact with ABP, within the scope of the invention. In some aspects, the cytotoxic activity of an NK cell is measured using a cytotoxicity assay that quantifies NK-mediated killing of target cells (eg, K562 cell line). See Jang et al., Ann. Clin. Lab. sci. , 2012, 42:42-49, the full content of which is given as a reference.

[309] Additional assays for measuring GITR agonism are described elsewhere in this specification, including the Examples, and are known in the art. One of skill in the art can easily select an appropriate assay to assess GITR agonism.

1.20. Effector Function Analyzes

[310] The effector function of ABP, within the scope of the invention, can be assessed using a variety of in vitro and in vivo assays known in the art, including those described in Ravetch and Kinet, Annu. Rev. Immunol. , 1991, 9:457-492; US Patent No. 5500362, 5821337; Hellstrom et al., Proc. Nat'l Acad. sci. USA , 1986, 83:7059-7063; Hellstrom et al., Proc. Nat'l Acad. sci. USA , 1985, 82:1499-1502; Bruggemann et al., J. Exp. Med. , 1987, 166:1351-1361; Clynes et al., Proc. Nat'l Acad. sci. USA , 1998, 95:652-656; W02006/029879; WO2005/100402; Gazzano-Santoro et al., J. Immunol. Methods , 1996, 202:163-171; Cragg et al., Blood , 2003, 101:1045-1052; Cragg et al. Blood , 2004, 103:2738-2743; and Petkova et al., Int'l. Immunol. , 2006, 18:1759-1769; the full content of all of which is given in the present description by reference.

Pharmaceutical compositions

[311] ABP, within the scope of the invention, can be formulated into any suitable pharmaceutical composition and administered by any suitable route of administration. Suitable routes of administration include, but are not limited to, intra-arterial, intradermal, intramuscular, intraperitoneal, intravenous, nasal, parenteral, pulmonary, and subcutaneous routes.

[312] In another aspect, the present invention provides a pharmaceutical composition comprising a plurality of anti-human GITR antibodies, or antigen-binding fragments thereof, within the scope of the invention. For example, the pharmaceutical composition contains an antibody or antigen-binding fragment thereof that has not undergone post-translational modification, and an antibody or antigen-binding fragment thereof resulting from post-translational modification of the antibody or antigen-binding fragment thereof.

[313] In one embodiment, the pharmaceutical composition comprises at least two kinds of anti-human GITR antibodies selected from (1) to (4): (1) an anti-human GITR antibody comprising two heavy chains consisting of SEQ ID NO: 7 and four light chains, consisting of SEQ ID NO: 8; (2) an anti-human GITR antibody comprising two heavy chains consisting of SEQ ID NO: 7, where Q at position 1 is modified to pyroglutamate, and four light chains consisting of SEQ ID NO: 8; (3) an anti-human GITR antibody comprising two heavy chains consisting of an amino acid sequence ranging from Q at position 1 to G at position 686 of SEQ ID NO: 7 and four light chains consisting of SEQ ID NO: 8; and (4) an anti-human GITR antibody comprising two heavy chains consisting of an amino acid sequence ranging from Q at position 1 to G at position 686 of SEQ ID NO: 7, where Q at position 1 is modified to pyroglutamate, and four light chains from SEQ ID NO: 8.

[314] In one embodiment, the pharmaceutical composition comprises an anti-human GITR antibody comprising two heavy chains consisting of SEQ ID NO: 7 and four light chains consisting of SEQ ID NO: 8; and an anti-human GITR antibody comprising two heavy chains consisting of an amino acid sequence ranging from Q at position 1 to G at position 686 of SEQ ID NO: 7, where Q at position 1 is modified to pyroglutamate, and four light chains from SEQ ID NO: 8, and a pharmaceutically acceptable excipient.

[315] The pharmaceutical composition may contain one or more pharmaceutical excipients. Any suitable pharmaceutical excipient may be used, and one skilled in the art will be able to select suitable pharmaceutical excipients. Accordingly, the pharmaceutical excipients set forth below are illustrative and not restrictive. Additional pharmaceutical excipients include, for example, the pharmaceutical excipients described in Handbook of Pharmaceutical Excipients , Rowe et al. (Eds.) 6th Ed. (2009), the full content of which is given by reference.

[316] In some embodiments, the pharmaceutical composition contains an antifoaming agent. Any suitable antifoaming agent may be used. In some aspects, the antifoam agent is selected from alcohol, ether, oil, wax, silicone, surfactant, and combinations thereof. In some aspects, the antifoam agent is selected from mineral oil, vegetable oil, ethylene bis stearamide, paraffin wax, ester wax, fatty alcohol wax, long chain fatty alcohol, fatty acid soap, fatty acid ester, silicone glycol, fluorosilicone , polyethylene glycol-polypropylene glycol copolymer, polydimethylsiloxane-silica, ether, octyl alcohol, caprylic alcohol, sorbitan trioleate, ethyl alcohol, 2-ethyl-hexanol, dimethicone, oleyl alcohol, simethicone, and combinations thereof.

[317] In some embodiments, the pharmaceutical composition contains a co-solvent. Illustrative examples of co-solvents include ethanol, poly(ethylene) glycol, butylene glycol, dimethylacetamide, glycerol, propylene glycol, and combinations thereof.

[318] In some embodiments, the pharmaceutical composition contains a buffer. Illustrative examples of buffers include acetate, borate, carbonate, lactate, malate, phosphate, citrate, hydroxide, diethanolamine, monoethanolamine, glycine, methionine, guar gum, sodium monoglutamate, and combinations thereof.

[319] In some embodiments, the pharmaceutical composition contains a carrier or excipient. Illustrative examples of carriers or excipients include lactose, maltodextrin, mannitol, sorbitol, chitosan, stearic acid, xanthan gum, guar gum, and combinations thereof.

[320] In some embodiments, the pharmaceutical composition contains a surfactant. Illustrative examples of surfactants include d -alpha-tocopherol, benzalkonium chloride, benzethonium chloride, cetrimide, cetylpyridinium chloride, sodium docusate, glyceryl behenate, glyceryl monooleate, lauric acid, macrogol-15-hydroxystearate, myristyl alcohol, phospholipids, polyoxyethylene alkyl ethers, polyoxyethyl ensorbitan complex fatty acid esters, polyoxyethylene stearates, polyoxylglycerides, sodium lauryl sulfate, sorbitan esters, vitamin E polyethylene (glycol) succinate, and combinations thereof.

[321] In some embodiments, the pharmaceutical composition contains an anti-caking agent. Illustrative examples of anti-caking agents include calcium phosphate (tribasic), hydroxymethylcellulose, hydroxypropylcellulose, magnesium oxide, and combinations thereof.

[322] Other excipients that can be used in pharmaceutical compositions include, for example, albumin, antioxidants, antibacterial agents, antifungal agents, bioabsorbable polymers, chelating agents, release control agents, diluents, dispersing agents, dissolution enhancers, emulsifiers, gelling agents, ointment bases, penetration enhancers, preservatives, solubilizing agents, solvents, stabilizers, sugars, and combinations thereof. Specific examples of each of these agents are described, for example, in Handbook of Pharmaceutical Excipients , Rowe et al. (Eds.) 6th Ed. (2009), The Pharmaceutical Press, the entire contents of which are incorporated by reference.

[323] In some embodiments, the pharmaceutical composition contains a solvent. In some aspects, the solvent is a saline solution, such as sterile saline or dextrose solution. In some aspects, the solvent is water for injection.

[324] In some embodiments, the pharmaceutical compositions are in the form of solid particles, such as microparticles or nanoparticles. Microparticles and nanoparticles can be formed from any suitable material such as a polymer or lipid. In some aspects, microparticles or nanoparticles are micelles, liposomes or polymerosomes.

[325] In addition, the present invention relates to anhydrous pharmaceutical compositions and dosage forms containing ABP, since water can facilitate the degradation of some ABP.

[326] Anhydrous pharmaceutical compositions and dosage forms, within the scope of the invention, can be obtained using anhydrous ingredients or ingredients with a low moisture content or under conditions of low humidity. Pharmaceutical compositions and dosage forms that contain lactose and at least one active ingredient containing a primary or secondary amine may be anhydrous if significant contact with moisture and/or moisture is expected during manufacture, packaging and/or storage.

[327] Anhydrous pharmaceutical composition should be obtained and stored in such a way as to maintain its anhydrous state. Accordingly, anhydrous compositions can be packaged using materials known to prevent exposure to water so that they can be included in suitable formulation kits. Examples of suitable packaging include, but are not limited to, sealed foils, plastics, unit dose containers (eg, ampoules), blister packs, and strip packs.

1.21. Parenteral dosage forms

[328] In specific embodiments, the implementation, ABP, in the framework of the invention, are in parenteral dosage forms. Parenteral dosage forms can be administered to subjects by a variety of routes, including, but not limited to, subcutaneous, intravenous (including infusions and bolus injections), intramuscular, and intra-arterial. Since their administration generally bypasses the subject's natural defenses against contaminants, parenteral dosage forms are generally sterile or sterilizable prior to administration to the subject. Examples of parenteral dosage forms include, but are not limited to, injectable solutions, dry (eg, lyophilized) products ready to be dissolved or suspended in a pharmaceutically acceptable carrier, injectable suspensions, and emulsions.

[329] Suitable carriers that can be used to obtain parenteral dosage forms are well known to specialists in this field. Examples include, but are not limited to: water for injection USP; aqueous vehicles such as, but not limited to, sodium chloride injection, Ringer's solution for injection, dextrose for injection, dextrose and sodium chloride for injection, and lactated Ringer's solution for injection; water-miscible carriers such as, but not limited to, ethyl alcohol, polyethylene glycol, and polypropylene glycol; and non-aqueous carriers such as, but not limited to, corn oil, cottonseed oil, peanut oil, sesame oil, ethyl oleate, isopropyl myristate, and benzyl benzoate.

[330] Fillers that increase the solubility of one or more of the ABP described in the present description, can also be included in parenteral dosage forms.

[331] In some embodiments, the parenteral dosage form is lyophilized. Exemplary lyophilized formulations are described, for example, in US Patent No. 6267958 and 6171586; and WO 2006/044908; the full content of all of which is given in the present description by reference.

Doses and unit dosage forms

[332] In the case of medicinal products for humans, the medical professional may determine the posology that should be considered the most appropriate according to prophylactic or curative treatment and according to age, weight, condition and other factors specific to the subject to be treated.

[333] In specific embodiments, the implementation, the composition, in the framework of the invention, is a pharmaceutical composition or a single unit dosage form. Pharmaceutical compositions and unit dosage forms, within the scope of the invention, contain a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic ABPs.

[334] The amount of ABP or composition that may be effective in preventing or treating a disorder or one or more of its symptoms may vary depending on the nature and severity of the disease or condition, and the manner in which the ABP is administered. The frequency and dose may also be varied according to factors specific to each subject, depending on the specific drugs administered (eg, therapeutic or prophylactic agents), the severity of the disorder, disease or condition, route of administration, as well as age, body weight, response. and the subject's prior history. Effective doses can be extrapolated from dose-response curves derived from in vitro test systems or test systems in animal models.

[335] In specific embodiments, exemplary dosages of the composition include milligram or microgram amounts of ABP per kilogram of subject or sample weight (e.g., from about 100 micrograms per kilogram to about 25 milligrams per kilogram, or from about 100 micrograms per kilogram to about 10 milligrams per kilogram). In a specific embodiment, the dose of ABP, within the scope of the invention, based on the mass of ABP administered to prevent, treat, manage or alleviate a disorder or one or more of its symptoms in a subject, is 0.1 mg/kg, 1 mg/kg , 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg or 40 mg/kg or more, per subject's body weight.

[336] the Dose can be entered in accordance with a suitable schedule, for example, weekly, once every two weeks, once every three weeks, or once every four weeks. In some embodiments, the antibody to be administered once every three or four weeks may be administered at a higher dose than the antibody administered every one or two weeks. In some embodiments, the loading dose administered is higher than the maintenance dose administered later. It may be necessary to use doses of ABP outside the ranges described herein in some instances, as will be apparent to those skilled in the art. In addition, it should be noted that the healthcare professional or treating therapist knows how and when to interrupt, adjust, or discontinue therapy in accordance with the subject's response.

[337] Various therapeutically effective amounts may be applicable for various diseases and conditions, as is well known to the person skilled in the art. Similarly, amounts sufficient to prevent, manage, treat, or alleviate such disorders, but not sufficient to cause, or sufficient to reduce, the adverse effects associated with ABP, within the scope of the invention, are also included in dosing levels and dosing frequency schedules, in within the scope of the invention. In addition, when multiple doses of a composition are administered to a subject, within the scope of the invention, not all of the doses need be the same. For example, the dose administered to a subject may be increased to improve the prophylactic or therapeutic effect of the composition, or may be reduced to reduce one or more side effects experienced by a particular subject.

[338] In specific embodiments, treatment or prevention may begin with one or more loading doses of an ABP or composition, within the scope of the invention, followed by one or more maintenance doses.

[339] In specific embodiments, a dose of ABP or compositions within the scope of the invention may be administered to achieve an equilibrium state of ABP concentration in the subject's blood or serum. The concentration at equilibrium can be determined by measurement in accordance with the methods available to a person skilled in the art, or it can be based on the physical characteristics of the subject, such as height, weight and age.

[340] In specific embodiments, administration of the same composition may be repeated and administrations may be separated by at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days, 3 months or 6 months.

[341] As discussed in more detail elsewhere in this specification, ABP, within the scope of the invention, may optionally be administered along with one or more additional agents that may be used to prevent or treat a disease or disorder. The effective amount of such additional agents may depend on the amount of ABP present in the formulation, the type of disorder or treatment, and other factors known in the art or described herein.

Therapeutic Applications

[342] For therapeutic applications, the ABP of the invention is administered to a mammal, typically a human, in a pharmaceutically acceptable dosage form such as those known in the art and described above. For example, the ABP of the invention may be administered to a human intravenously as a bolus or by continuous infusion over a period of time, via intramuscular, intraperitoneal, intracerebrospinal, subcutaneous, intraarticular, intraarticular, intrathecal, or intratumoral routes. ABP mono is also suitably administered by peritumoral, intralesional, or perilesional routes to achieve local, as well as systemic, therapeutic effects. The intraperitoneal method may be particularly useful, for example, in the treatment of ovarian tumors.

[343] ABP, within the scope of the invention, can be used to treat any disease or condition involving GITR. In some embodiments, the disease or condition is a disease or condition that would benefit from treatment with an anti-GITR ABP. In some embodiments, the disease or condition is a tumor. In some embodiments, the disease or condition is a cell proliferation disorder. In some embodiments, the disease or condition is cancer.

[344] In some embodiments, the implementation, ABP, within the scope of the invention, are intended for use as a drug. In some embodiments, the ABPs within the scope of the invention are for use in the manufacture or preparation of a drug. In some embodiments, the drug is for the treatment of a disease or condition that would benefit from ABP versus GITR. In some embodiments, the disease or condition is a tumor. In some embodiments, the disease or condition is a cell proliferation disorder. In some embodiments, the disease or condition is cancer.

[345] Any suitable cancer can be treated using ABP, within the scope of the invention. Illustrative suitable cancers include, for example, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), adrenocortical carcinoma, anal cancer, appendix cancer, astrocytoma, basal cell carcinoma, brain tumor, bile duct cancer, urinary tract cancer. bladder cancer, bone cancer, breast cancer, bronchial tumor, carcinoma of unknown primary origin, heart tumor, cervical cancer, chordoma, colon cancer, colorectal cancer, craniopharyngioma, ductal carcinoma, fetal tumor, endometrial cancer, ependymoma, esophageal cancer, esthesioneuroblastoma , fibrous histiocytoma, Ewing's sarcoma, ophthalmic malignancy, germ cell tumor, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, gestational trophoblastic tumor, glioma, head and neck cancer, hepatocellular malignancy tumor, histiocytosis, Hodgkin's lymphoma, hypopharyngeal malignancy, intraocular melanoma, pancreatic islet tumor, Kaposi's sarcoma, kidney cancer, Langerhans cell histiocytosis, laryngeal malignancy, lip and mouth cancer, liver cancer, lobular carcinoma in situ , lung cancer, macroglobulinemia, malignant fibrous histiocytoma, melanoma, Merkel cell carcinoma, mesothelioma, clinically unidentified metastatic primary squamous cell carcinoma of the neck, midline carcinoma involving the NUT gene, malignant tumor of the oral cavity, multiple endocrine neoplasia syndrome, multiple myeloma, mycosis fungoides, myelodysplastic syndrome, myelodysplastic/myeloproliferative neoplasia, nasal and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-small cell lung cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, papillomatosis, paraganglioma, parathyroid cancer, penile cancer, malignancy pharynx, pheochromocytomas, pituitary tumor, pleuropulmonary blastoma, primary central nervous system lymphoma, prostate cancer, rectal cancer, renal cell carcinoma, renal pelvis and ureter cancer, retinoblastoma, rhabdoid tumor, salivary gland cancer, Cesari syndrome, skin cancer, small cell lung cancer, small intestine cancer, soft tissue sarcoma, spinal cord tumor, gastric cancer, T-cell lymphoma, teratoid tumor, testicular cancer, throat cancer, thymoma and thymus carcinoma, thyroid cancer, urethral cancer, body cancer uterus, vaginal cancer, vulvar cancer, and Wilms tumor.

[346] In some embodiments, the present invention relates to a method of treating a disease or condition in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject. In some aspects, the disease or condition is a cancer.

[347] In some embodiments, the present invention relates to a method for multimerizing GITR in a target cell of a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[348] In some embodiments, the present invention relates to a method of agonizing GITR in a target cell of a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject. In some aspects, GITR agonism by ABP, within the scope of the invention, results in increased secretion of IL-2Rα, IL-2, IL-8 and/or IFNγ by the target cell.

[349] In some embodiments, the present invention relates to a method for modulating NF-κB activity in a target cell of a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[350] In some embodiments, the present invention relates to a method for modulating IκB degradation in a target cell of a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[351] In some embodiments, the present invention provides a method for activating the MAPK pathway in a target cell of a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject. In some aspects, components of the MAPK pathway activated by ABP, within the scope of the invention, include one or more of p38, JNK, and ERK.

[352] In some embodiments, the present invention relates to a method of increasing the proliferation, survival and/or function of an effector T cell in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject. In some aspects, the effector T cell is a CD4+ effector T cell. In some aspects, the effector T cell is a CD8+ effector T cell.

[353] In some embodiments, the present invention relates to a method of terminating suppression of an effector T cell by a regulatory T cell in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject. In some aspects, the regulatory T cell is a CD4+CD25+Foxp3+ regulatory T cell. In some aspects, the regulatory T cell is a CD8+CD25+ regulatory T cell.

[354] In some embodiments, the present invention relates to a method for altering the frequency or distribution or regulatory T cells in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject. In some aspects, the frequency of regulatory T cells is reduced. In some aspects, the frequency of regulatory T cells is reduced in a particular tissue. In some aspects, the accumulation of regulatory T cells within the tumor is reduced, resulting in a more favorable ratio of effector T cells to regulatory T cells, and increased activity of CD8+ T cells.

[355] In some embodiments, the present invention relates to a method for increasing natural killer (NK) cell activity in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[356] In some embodiments, the present invention provides a method for increasing dendritic cell activity in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[357] In some embodiments, the present invention relates to a method for increasing B cell activity in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[358] In some embodiments, the present invention relates to a method for enhancing an immune response in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[359] In some embodiments, the present invention relates to a method of delaying the onset of tumor development in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[360] In some embodiments, the present invention relates to a method of delaying the onset of cancer in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[361] In some embodiments, the present invention relates to a method for reducing the size of a tumor in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

[362] In some embodiments, the present invention relates to a method for reducing the number of metastases in a subject in need thereof by administering an effective amount of ABP, within the scope of the invention, to the subject.

Methods of combination therapy

[363] In some embodiments, the implementation, ABP, in the framework of the invention, administered with at least one additional drug. Any suitable additional drug can be administered with ABP, within the scope of the invention. In some aspects, the additional drug is selected from radiation exposure, a cytotoxic agent, a chemotherapeutic agent, a cytostatic agent, an antihormonal agent, an EGFR inhibitor, an immunostimulatory agent, an antiangiogenic agent, and combinations thereof.

[364] In some embodiments, the additional drug contains an immunostimulatory agent.

[365] In some embodiments, the immunostimulatory agent is an agent that blocks the signaling of an inhibitory receptor on an immunocyte or a ligand thereof. In some aspects, the inhibitory receptor or ligand is selected from CTLA-4, PD-1, PD-L1, NRP-1, LAG-3, Tim3, TIGIT, neuritin, BTLA, KIR, and combinations thereof. In some aspects, the agent is selected from pembrolizumab (anti-PD-1 antibodies), nivolumab (anti-PD-1 antibodies), atezolizumab (anti-PD-L1 antibodies), ipilimumab (anti-CTLA-4 antibodies, and combinations thereof.

[366] In some embodiments, the immunostimulatory agent is an agonist of an immunocyte co-stimulatory receptor. In some aspects, the costimulatory receptor is selected from OX40, ICOS, CD27, CD28, 4-1BB, or CD40. In some embodiments, the agonist is an antibody.

[367] In some embodiments, the immunostimulatory agent is a cytokine. In some aspects, the cytokine is selected from IL-2, IL-5, IL-7, IL-12, IL-15, IL-21, and combinations thereof.

[368] In some embodiments, the immunostimulatory agent is an oncolytic virus. In some aspects, the oncolytic virus is selected from herpes simplex virus, vesicular stomatitis virus, adenovirus, Newcastle disease virus, vaccinia virus, and Marab virus.

[369] In some embodiments, the immunostimulatory agent is a chimeric antigen receptor T cell (CAR-T cell). In some embodiments, the immunostimulatory agent is a bi- or multispecific T cell-targeted antibody. In some embodiments, the immunostimulatory agent is an anti-TGF-β antibody. In some embodiments, the immunostimulatory agent is a TGF-β decoy.

[370] In some embodiments, the additional drug is a tumor antigen vaccine. The vaccine may be targeted to any suitable antigen, as long as it is present in the tumor being treated by the methods of the invention. In some aspects, the tumor antigen is a tumor antigen overexpressed compared to its expression levels in normal tissue. In some aspects, the tumor antigen is selected from cancer-testicular antigen, differentiation antigen, NY-ESO-1, MAGE-A1, MART, and combinations thereof.

[371] Additional examples of additional drugs include a taxane (eg, paclitaxel or docetaxel); a platinum-based agent (eg, carboplatin, oxaliplatin, and/or cisplatin); a topoisomerase inhibitor (eg, irinotecan, topotecan, etoposide and/or mitoxantrone); folinic acid (eg leucovorin); or a nucleoside metabolic inhibitor (eg, fluorouracil, capecitabine and/or gemcitabine). In some embodiments, the additional drug is folinic acid, 5-fluorouracil, and/or oxaliplatin. In some embodiments, the additional drug is 5-fluorouracil and irinotecan. In some embodiments, the additional drug is a taxane and a platinum based agent. In some embodiments, the additional drug is paclitaxel and carboplatin. In some embodiments, the additional drug is pemetrexate. In some embodiments, the additional drug is a targeted drug, such as an agent that targets EGFR, RAF, or MEK.

[372] The additional drug can be administered by any suitable means. In some embodiments, the ABP, within the scope of the invention, and the additional drug are included in the same pharmaceutical composition. In some embodiments, the ABP, within the scope of the invention, and the additional drug are included in various pharmaceutical compositions.

[373] In embodiments where an ABP, within the scope of the invention, and an additional drug are included in different pharmaceutical compositions, the administration of the ABP may be before, during, and/or after the administration of the additional drug. In some aspects, the administration of the ABP, within the scope of the invention, and the additional drug is within about one month of each other. In some aspects, the administration of the ABP, within the scope of the invention, and the additional drug is within about one week of each other. In some aspects, the introduction of ABP, within the scope of the invention, and additional drug is carried out within approximately one day from each other. In some aspects, the administration of the ABP, within the scope of the invention, and the additional drug is within about twelve hours of each other. In some aspects, the administration of the ABP, within the scope of the invention, and the additional drug is within approximately one hour of each other.

Diagnostic methods

[374] The present invention also relates to methods for detecting the presence of GITR on cells from a subject. Such methods can be used, for example, to predict and evaluate the ability to respond to ABP treatment, within the scope of the invention.

[375] In some embodiments, a blood sample is obtained from a subject and the fraction of cells expressing GITR is determined. In some aspects, the relative amount of GITR expressed by such cells is determined. the fraction of cells expressing GITR and the relative amount of GITR expressed by such cells can be determined by any suitable method. In some embodiments, flow cytometry is used to make such measurements. In some embodiments, fluorescence-activated cell sorting (FACS) is used to make such a measurement. See Li et al., J. Autoimmunity , 2003, 21:83-92 for methods of assessing peripheral blood GITR expression.

Sets

[376] The present invention also relates to kits containing ABP. The kits can be used to treat, prevent and/or diagnose a disease or disorder as described herein.

[377] In some embodiments, the kit comprises a container and a label or package insert on or attached to the container. Suitable containers include, for example, vials, ampoules, syringes and IV solution bags. Containers can be made from a variety of materials such as glass or plastic. The container contains a composition that, alone or in combination with another composition, is effective in treating, preventing and/or diagnosing a disease or disorder. The container may have a sterile access port. For example, if the container may be an intravenous solution bag or vial, it may have an exit that can be pierced with a needle. At least one active ingredient in the composition is an ABP, within the scope of the invention. The label or package insert indicates that the composition is used to treat the selected condition.

[378] In some embodiments, the kit comprises (a) a first container containing a first composition, wherein the first composition contains ABP, within the scope of the invention; and (b) a second container containing a second composition, wherein the second composition contains an additional drug. The kit in this embodiment of the invention may further comprise a package leaflet stating that the composition can be used to treat a particular condition.

[379] Alternatively or additionally, the kit may further comprise a second (or third) container containing a pharmaceutically acceptable excipient. In some aspects, the filler is a buffer. The kit may additionally include other materials desirable from a commercial and user point of view, including filters, needles and syringes.

Other Illustrative Embodiments

[380] The embodiments presented below are non-limiting and are presented for the purpose of illustrating specific embodiments and aspects of the invention, in addition to those described throughout this specification.

[381] Embodiment 1: An ABP that specifically binds human GITR and/or a human GITR complex and is capable of at least one of the following: a) cross-competes with GITRL for binding to GITR; b) can be internalized into a human cell; c) inhibits effector T cell suppression; d) suppresses the inhibition of effector T cells by regulatory T cells; e) reduces the number of regulatory T cells in tissues or in the bloodstream; f) activates an effector T cell; g) associates the GITR into the GITR complex; h) modulates the activity of human GITR and/or the GITR complex.

[382] Embodiment 2: The ABP of Embodiment 1, wherein the ABP has one or more of the following: a) is a monoclonal antibody; b) is a human antibody, a humanized antibody, or a chimeric antibody; c) is a multispecific or multivalent antibody, eg a tetravalent antibody; d) contains at least one Fab at the N-terminus or C-terminus; e) belongs to the IgG1, IgG2, IgG3 or IgG4 type; f) is an antigen-binding fragment of an antibody; g) is a Fab fragment, a Fab' fragment, an F(ab')2 fragment or an Fv fragment; h) is a bispecific antibody, diabody, single chain antibody, single domain antibody, VH domain antibody, or nanobody.

[383] Embodiment 3: An ABP of Embodiment 1, wherein the ABP has one or more of the following characteristics: a) binds a human GITR polypeptide of SEQ ID NOs: 1-2 or a variant thereof, or as otherwise described herein, with K _D less than about 20 nm; or b) binds the cynomolgus monkey GITR polypeptide of SEQ ID NO: 3 or a variant thereof, or as otherwise described herein, with a K _D of less than about 200 nM.

[384] Embodiment 4: The ABP of Embodiment 1 comprising a first antigen-binding domain that specifically binds a first antibody recognition domain on human GITR and a second antigen-binding domain that specifically binds a second antibody recognition domain on human GITR, wherein the first antibody recognition domain and the second recognition domain of the antibody are not identical.

[385] Embodiment 5: An ABP of Embodiment 4 comprising a bispecific binding protein in a format selected from the group consisting of DVD-Ig™ molecule, ^BiTe® molecule, DART™ molecule, DuoBody® molecule, scFv/diabody-IgG molecule , cross-multispecificity molecule, 2-in-1 bispecific molecule, ridge-to-trough multispecific molecule, Fab+IgG molecule, CovX-Body molecule, affitel molecule, scFv/diatelo-CH2/CH3 bispecific molecule, based multispecific molecule an IgG-non-Ig protein scaffold, a ^finomer® molecule, an Fcab™ molecule, TandAb®, a Zybody™, and a bispecific scFV/diabody molecule linked to a normal human protein like human serum albumin.

[386] Embodiment 6: An ABP of Embodiment 4, wherein the first antigen-binding domain has a K _D of less than about 20 nM and is capable of exhibiting human GITR agonism, and wherein the second antigen-binding domain has a K _D of less than about 100 nM.

[387] Embodiment 7: An ABP that competes or is capable of competing for binding to human GITR with a reference ABP, where the reference ABP is the ABP from Embodiment 1.

[388] Embodiment 8: The ABP of Embodiment 7, wherein the ABP and the reference antibody cross-compete or are capable of cross-competing for binding to human GITR.

[389] Embodiment 9: An ABP of Embodiment 1 comprising a heavy chain constant region comprising a human heavy chain constant region or a fragment or variant thereof, wherein the constant region variant contains up to 20 modified amino acid substitutions, where from 0 to up to 20 modified amino acid substitutions are conservative amino acid substitutions.

[390] Embodiment 10: An ABP from Embodiment 1 that competes or is capable of competing for binding to human GITRL with the GITR protein.

[391] Embodiment 11: The ABP of Embodiment 1 capable of activating GITR signaling in a ligand-independent manner.

[392] Embodiment 12: An ABP from Embodiment 1 capable of enhancing ligand-dependent binding of GITR and GITRL.

[393] Embodiment 13: A pharmaceutical composition comprising an ABP from any of Embodiments 1-12 in a pharmaceutically acceptable carrier.

[394] Embodiment 14: A bispecific antibody comprising a first antigen-binding domain that specifically binds a first antibody recognition domain on human GITR and a second antigen-binding domain that specifically binds a second antibody recognition domain on human GITR, wherein the first antibody recognition domain and the second recognition domain antibodies are not identical.

[395] Embodiment 15: The bispecific antibody of Embodiment 14, wherein the first antibody recognition domain and the second antibody recognition domain are present in the extracellular domain of human GITR.

[396] Embodiment 16: The bispecific antibody of Embodiment 14, wherein the first antibody recognition domain and the second antibody recognition domain are capable of associating at least two human GITR proteins into a functional complex.

[397] Embodiment 17: A complexing ABP comprising a first antigen binding domain that specifically binds the first antibody recognition domain on a human GITR protein or on a human GITR complex comprising at least two GITR proteins and is capable of at least one of the following : a) cross-competes with GITRL for binding to GITR; b) can be internalized into a human cell; c) inhibits effector T cell suppression; d) suppresses the inhibition of effector T cells by regulatory T cells; e) reduces the number of regulatory T cells in tissues or in the bloodstream; f) activates an effector T cell; g) associates the GITR into the GITR complex; h) modulates the activity of human GITR and/or the GITR complex.

[398] Embodiment 18: An isolated nucleic acid encoding an ABP of any of Embodiments 1-12, or a bispecific antibody of any of Embodiments 14-16, or a complexing ABP of Embodiment 17.

[399] Embodiment 19: An expression vector containing the nucleic acid according to Embodiment 18.

[400] Embodiment 20: Prokaryotic or eukaryotic host cell containing the vector of Embodiment 19.

[401] Embodiment 21: A method for producing a recombinant protein comprising the steps of expressing the nucleic acid of Embodiment 18 in a prokaryotic or eukaryotic host cell and isolating said protein from said cell or cell culture supernatant.

[402] Embodiment 22: A method of treating a subject suffering from a cancer or inflammatory disease, comprising the step of administering to the subject a pharmaceutical composition comprising an ABP of any of Embodiments 1-12, or a bispecific antibody of any of Embodiments 14-16, or a complexing ABP from Embodiment 17.

[403] Embodiment 23: A method of inducing or enhancing an immune response in a subject, comprising the step of administering to the subject a pharmaceutical composition comprising an ABP of any one of Embodiments 1-12 or a bispecific antibody of any of Embodiments 14-16, or a complexing ABP of Embodiment implementation 17, where the immune response is caused against the antigen of the tumor.

[404] Embodiment 24: The method of Embodiment 23, wherein the ABP, the bispecific antibody, or the complexing ABP is administered in an amount sufficient to achieve one or more of the following in the subject: a) reducing suppression of effector T cell activity by regulatory T cells; b) decreasing levels of regulatory T cells; c) activation of effector T cells; d) inducing or enhancing the proliferation of effector T cells; e) slowing down the rate of tumor growth; and f) inducing tumor regression.

[405] Embodiment 25: The method of Embodiment 22, wherein the cancer is a solid tumor.

[406] Embodiment 26: The method of Embodiment 22, wherein the cancer is a hematological tumor.

[407] Embodiment 27: The method of any one of embodiments 22-26, wherein the method further comprises one or more of the following a) administering chemotherapy; b) administering radiotherapy; or c) administering one or more additional drugs.

[408] Embodiment 28: The method of Embodiment 27, wherein the additional drug comprises an immunostimulatory agent.

[409] Embodiment 29: The method of Embodiment 27, wherein the immunostimulatory agent comprises an immunocyte inhibitory receptor antagonist.

[410] Embodiment 30: The method of Embodiment 29, wherein the inhibitory receptor comprises CTLA-4, PD-1, PD-L1, LAG-3, Tim3, TIGIT, neuritin, BTLA, or KIR, or a functional fragment thereof.

[411] Embodiment 31: The method of Embodiment 27, wherein the immunostimulatory agent comprises an immunocyte costimulatory receptor agonist, or a functional fragment thereof.

[412] Embodiment 32: The method of Embodiment 31, wherein the costimulatory receptor comprises OX40, ICOS, CD27, CD28, 4-1BB, or CD40.

[413] Embodiment 33: The method of Embodiment 27, wherein the immunostimulatory agent comprises a cytokine.

[414] Embodiment 34: The method of Embodiment 27, wherein the cytokine comprises IL-2, IL-5, IL-7, IL-12, IL-15, or IL-21.

[415] Embodiment 35: The method of Embodiment 27, wherein the immunostimulatory agent comprises an oncolytic virus.

[416] Embodiment 36: The method of Embodiment 35, wherein the oncolytic virus comprises herpes simplex virus, vesicular stomatitis virus, adenovirus, Newcastle disease virus, vaccinia virus, or Marab virus.

[417] Embodiment 37: The method of Embodiment 27, wherein the immunostimulatory agent comprises a chimeric engineered T cell.

[418] Embodiment 38: The method of Embodiment 27, wherein the immunostimulatory agent comprises a bi- or multi-specific T cell-targeted antibody.

[419] Embodiment 39: The method of Embodiment 27, wherein the additional drug comprises an anti-TGF-β antibody or a TGF-β receptor decoy.

[420] Embodiment 40: The method of any one of embodiments 22-39, wherein administration of the pharmaceutical composition results in induction or enhancement of proliferation of an effector T cell, or I-kappaB and/or NF-κB in the T cell, or modulation GITR activity in a T cell, or T cell receptor induced signaling in an effector T cell, or a combination thereof.

[421] Embodiment 41: A method for screening test compounds containing the ABP of any one of Embodiments 1-12 capable of inhibiting the interaction of GITRL with the GITR complex, comprising the steps of: contacting a sample containing GITRL and the GITR complex with a compound; and determining whether the interaction of GITRL with the GITR complex in the sample is reduced compared to the interaction of GITRL with the GITR complex in the sample not contacted with the compound, based on which, to reduce the interaction of GITRL with GITR in the sample brought into contact with the compound, the compound is identified as a compound that inhibits the interaction of GITRL with the GITR complex.

EXAMPLES

[422] The following are examples of the methods and compositions of the invention. It is understood that various other embodiments may be practiced given the general description provided herein.

Example 1 Selection of antigen-binding proteins against GITR

Materials and methods

Antigens were biotinylated using Pierce's EZ-Link® Sulfo-NHS Biotinylation Kit. Goat anti-human kappa F(ab') ₂ with FITC (LC-FITC), extravidin®-PE (EA-PE) and streptavidin-AF633 (SA-633) were obtained from Southern Biotech, Sigma, and Molecular Probes, respectively. Streptavidin MicroBeads® and MACS LC separation columns were purchased from Miltenyi Biotec. Goat anti-human IgG with PE (Human-PE) obtained from Southern Biotech.

Study naive libraries

Eight naive human synthetic libraries in yeast, each with ~10 ⁹ diversity, were propagated as previously described (See, for example, Y. Xu et al, Addressing polyspecificity of antibodies selected from an in vitro yeast presentation system: a FACS-based, high-throughput selection and analytical tool PEDS 26.10, 663-70 (2013); WO2009036379; WO2010105256; and WO2012009568.) For the first two rounds of selection, a magnetic bead sorting method was carried out using the Miltenyi MACS system as described previously (See eg Siegel et al, High efficiency recovery and epitope-specific sorting of an scFv yeast display library J Immunol Methods 286(1-2), 141-153 (2004). Briefly, yeast cells (~10 ¹⁰ cells/ library) were incubated with 5 ml of 10 nM biotinylated Fc fusion antigen for 30 min at 30° C. in wash buffer (phosphate buffered saline (PBS)/0.1% bovine serum albumin (BSA)). After washing once with 40 ml ice-cold wash buffer, the cell pellet was resuspended in 20 ml wash buffer and Streptavidin MicroBeads® (500 μl) were added to the yeast and incubated for 15 min at 4°C. The yeast was then pelleted, resuspended in 20 ml wash buffer, and applied to a Miltenyi LS column. After loading with 20 ml, the column was washed 3 times with 3 ml of wash buffer. The column was then removed from the magnetic field and the yeast was eluted using 5 ml growth media and then grown overnight. The following selection cycles were performed using flow cytometry. Approximately 2×10 ⁷ yeasts were precipitated, washed three times with wash buffer and incubated at 30° C. or with decreasing concentrations of biotinylated Fc fusion antigen (10-1 nM) under equilibrium conditions, 10 nM biotinylated Fc fusion antigens of various species to obtain species cross-reactivity, or with a polyspecific depletion reagent (PSR) to remove non-specific antibodies from selection. To deplete PSR, libraries were incubated with a 1:10 dilution of biotinylated PSR reagent as described previously (See, for example, Y. Xu et al, Addressing polyspecificity of antibodies selected from an in vitro yeast presentation system: a FACS-based, high- throughput selection and analytical tool PEDS 26.10, 663-70 (2013).) Yeast was then washed twice with wash buffer and stained using LC-FITC (1:100 diluted) and either SA-633 (1:500 diluted) or EAPE (1:50 diluted) secondary reagents for 15 min at 4°C. After washing twice with wash buffer, the cell pellets were resuspended in 0.3 ml of wash buffer and transferred to filtered tubes for sorting. Sorting was performed using a FACS ARIA sorter (BD Biosciences) and sorting windows were determined to select antibodies with the desired characteristics. Selection cycles were repeated until a population with all the desired characteristics was obtained. After the final sorting cycle, the yeasts were seeded and individual colonies were selected for characterization.

Optimization antibodies

Antibody optimization was performed by the light chain diversification method, and then by introducing diversity into the heavy chain and light chain variable regions, as described below. A combination of some of these methods was used for each antibody.

Light chain periodic diversification method: Heavy chain plasmids derived from selection from a naive library were isolated from yeast by disruption and harvest, propagated in E. coli and subsequently purified from E. coli , and transformed into a light chain library with 5× diversity 10 ⁶ . Selections were made using one MACS cycle and four FACS cycles, using the same conditions as in the naive library study.

Light chain diversification: The heavy chain variable region of a single antibody was amplified by PCR and transformed, along with a heavy chain expression vector, into a 5×10 ⁶ diversity light chain library. Selections were made using one MACS cycle and three FACS cycles, using the same conditions as in the naive library study. For each FACS cycle, libraries were checked for PSR binding, species cross-reactivity, and affinity pressure, and sorted to obtain a population with the desired characteristics.

Selection of CDRH1 and CDRH2: CDRH3 of a single antibody was introduced by recombination into a pre-prepared library with 1x10 ⁸ diversity of CDRH1 and CDRH2 variants, and selections were made using one MACS cycle and four FACS cycles as described for naive library testing. For each FACS cycle, libraries were checked for PSR binding, species cross-reactivity, and affinity pressure, and sorted to obtain a population with the desired characteristics. For these selections, affinity pressure was applied by pre-incubating the biotinylated antigen with the original IgG for 30 minutes and then adding this precomplexed mixture to the yeast library for a period of time to allow equilibrium in the selection mixture to be reached. Then it was possible to sort antibodies with higher affinity.

Selection of mutant CDRH3/VH: Oligonucleotides ("oligs") containing CDRH3 were ordered from IDT, as well as a flanking region on either side of CDRH3. Amino acid positions in the CDRH3-encoding portion of the oligonucleotide were changed by NNK diversity. CDRH3 oligonucleotides were made double stranded using primers hybridizing to the flanking region of CDRH3. The remainder of the heavy chain variable region was subjected to mutagenesis by PCR with error insertion to introduce additional diversity in the non-CDR3 regions of the heavy chain. The library was then prepared by transforming the double stranded CDRH3 oligonucleotide mutated with the rest of the heavy chain variable region and the heavy chain expression vector into yeast already containing the parental light chain plasmid. The selections were carried out similarly to the previous cycles, using four cycles of FACS sorting. For each FACS cycle, libraries were checked for PSR binding, species cross-reactivity, and affinity pressure, and sorted to obtain a population with the desired characteristics. The affinity pressure for these selections was applied as described above for the selection of CDRH1 and CDRH2.

Selection of CDRL1, CDRL2 and CDRL3: Oligonucleotides containing CDRL3 were ordered from IDT, as well as a flanking region on either side of CDRL3. The positions of amino acids in the CDRL3-encoding portion of the oligonucleotide were changed by NNK diversity. CDRL3 oligonucleotides were made double stranded using primers hybridizing to the CDRL3 flanking region. These double-stranded CDRL3 oligonucleotides were then recombinantly introduced into a pre-prepared CDRL1 and CDRL2 variant library with 3×10 ⁵ diversity, and selections were made using one MACS cycle and four FACS cycles as described for naïve library testing. For each FACS cycle, libraries were checked for PSR binding, species cross-reactivity, and affinity pressure, and sorted to obtain a population with the desired characteristics. The affinity pressure for these selections was applied as described above for the selection of CDRH1 and CDRH2.

Products And cleaning antibodies

Yeast clones were grown to saturation and then subjected to induction for 48 hours at 30°C with shaking. After induction, the yeast cells were pelleted and the supernatants were collected for purification. IgG was purified using a protein A column and eluted using acetic acid, pH 2.0. Fab fragments were generated by papain digestion and purified using KappaSelect® (GE Healthcare LifeSciences).

measurements K _D With using ForteBio

Affinity measurements using ForteBio® were performed in Octet® RED384, essentially as previously described (See, e.g., Estep et al, High throughput solution-based measurement of antibody-antigen affinity and epitope binning. Mabs 5(2), 270 -278 (2013)). Briefly, affinity measurements using ForteBio were performed by applying computer controlled IgG to AHQ sensors. The sensors were equilibrated offline in assay buffer for 30 min and then monitored under computer control for 60 seconds to determine background. IgG-loaded sensors were exposed to 100 nM antigen for 3 minutes and then transferred to assay buffer for 3 minutes to measure the dissociation rate. Fab was used instead of IgG to assess monovalent affinity. For this evaluation, a non-biotinylated Fc fusion antigen was applied in computer control mode to AHQ sensors. The sensors were equilibrated offline in assay buffer for 30 min and then monitored under computer control for 60 seconds to determine background. Antigen-loaded sensors were exposed to 200 nM Fab for 3 minutes and then transferred to assay buffer for 3 minutes to measure dissociation rate. All kinetics were analyzed using a 1:1 binding model.

grouping epitopes/blocking ligand With using ForteBio

Epitope grouping/ligand blocking was performed using a standard sandwich cross-blocking assay. Control anti-target IgG was applied to AHQ sensors and unoccupied Fc binding sites on the sensor were blocked using an irrelevant human IgG1 antibody. The sensors were then exposed to 100 nM of the target antigen, followed by exposure to a second anti-target antibody or ligand. Additional binding by a second antibody or ligand after antigen association indicates an unoccupied epitope (non-competitor), while no binding indicates blocking of the epitope (competitor or ligand blocking).

Analysis binding cells

Approximately 100,000 antigen overexpressing cells were washed with wash buffer and incubated with 100 μl of 100 nM IgG for 5 minutes at room temperature. Cells were then washed twice with wash buffer and incubated with 100 μl 1:100 Human-PE for 15 minutes on ice. Cells were then washed twice with wash buffer and analyzed in a FACS Canto II analyzer (BD Biosciences.)

Exclusive chromatography

The TSKgel® SuperSW mAb HTP column (22855) was used for rapid SEC analysis of mammalian-produced mAbs at 0.4 ml/min with a cycle time of 6 min/cycle. 200 mM sodium phosphate and 250 mM sodium chloride were used as the mobile phase.

Dynamic scanning fluorometry

10 µl of 20x Sypro Orange is added to 20 µl of a 0.2-1 mg/ml mAb or Fab solution. An RT-PCR device (BioRad CFX96 RT PCR) was used to ramp the temperature of the sample plate from 40 to 95°C in 0.5°C increments, equilibrating 2 minutes at each temperature. The negative first derivative of the raw data is used to derive Tm.

Example 2 Characteristics of TM Format Antibodies

affinity ABP format IgG1 And TM For GITR from several species

[423] GITR ABPs were evaluated for their ability to bind recombinant hGITR (SEQ ID NO: 1), hGITR-T43R (SEQ ID NO: 2), cGITR (SEQ ID NO: 3), and mGITR (SEQ ID NO: 4) using FORTEBIO ^® OCTET devices. The assay was performed at 30°C using 1x kinetic buffer (ForteBio, Inc.) as assay buffer. Anti-human IgG Fc (AHC) binding biosensors (ForteBio, Inc.) were used to bind ABP to GITR on the sensors. The sensors were equilibrated in assay buffer for 600 seconds prior to assay. Background was established by immersing the sensors in 1x assay buffer for 60 seconds. ABP was loaded onto the sensors by immersing the sensors in the ABP solution for 300 seconds. Background was established by immersing the sensors in 1× assay buffer for 120 seconds. The reaction on the sensors was stopped by immersion in 200 μg/ml human IgG for 300 seconds to prevent non-specific binding of GITR-Fc antigens to the sensor. Background was established by immersing the sensors in 1x assay buffer for 60 seconds. Binding was then monitored for 300 seconds in 25 nM recombinant antigens and dissociation was monitored for 1200 seconds in buffer alone. K _D was determined using the kinetics function of the ^FORTEBIO® analysis software using a 1:1 binding model. The results are shown in Table 5.

Table 5: K _D ABP by OCTET using Single Concentration Kinetics

ABP Format K _D by OCTET, one concentration of human Fc GITR-, (nM) K _D by OCTET, one concentration of human T43R-Fc GITR (nM) K _D by OCTET, one concentration of Fc GITR cynomolgus monkey- (nM) K _D by OCTET, one mouse Fc GITR concentration (nM) 1 TM with N-terminal Fab 0.77 0.94 0.88 No binding 2 TM with N-terminal Fab 0.55 0.73 0.79 No binding 3 TM with N-terminal Fab 0.58 0.71 1.1 No binding 4 TM with N-terminal Fab 0.5 0.72 1.19 No binding 5 TM with N-terminal Fab 0.57 0.7 1.21 No binding 6 TM with N-terminal Fab 0.63 0.71 1.09 No binding 7 TM with N-terminal Fab 0.76 1.1 1.9 No binding 8 TM with N-terminal Fab 0.73 1.02 0.94 No binding

[424] Other GITR ABPs were evaluated for their ability to bind recombinant hGITR and cGITR (SEQ ID NO: 3) using the ^FORTEBIO® Octet RED384 device, generally as described previously (See, e.g., Estep et al, High throughput solution- based measurement of antibody-antigen affinity and epitope binning Mabs 5(2), 270-278 (2013)). AHQ biosensors (ForteBio, Inc.) were used to bind ABP to GITR on the sensors. The reaction on the sensors was stopped by immersion in an unrelated human IgG1 antibody to prevent non-specific binding of GITR-Fc antigens to the sensor. The sensors were equilibrated in assay buffer for 30 minutes. The background was established by immersing the sensors in the assay buffer for 60 seconds. Binding was monitored for 180 seconds in 100 nM recombinant antigens and dissociation was monitored for 180 seconds in buffer alone. K _D was determined using the kinetics function of the ^FORTEBIO® analysis software using a 1:1 binding model. The results are shown in Table 6.

Table 6: ABP K _D by OCTET using Single Concentration Kinetics

ABP Format K _D by OCTET, one concentration of human GITR-Fc, (nM) K _D by OCTET, one concentration of cynomolgus monkey-Fc GITR (nM) 35 (non-TM ABP, corresponding to ABP1) IgG1 N297A 1.5 5.7 36 (non-TM ABP, corresponding to ABP2) IgG1 N297A 1.4 7.5 37 (non-TM ABP, ABP3 compliant) IgG1 N297A 0.7 8.1 38 (non-TM ABP, compliant with ABP4/5) IgG1 N297A 0.6 11.1 39 (non-TM ABP, ABP6 compliant) IgG1 N297A 0.7 8.2 40 (non-TM ABP, ABP7 compliant) IgG1 N297A 2.2 4.9 41 (non-TM ABP, corresponding to ABP8) IgG1 N297A 2.3 6.9 19 TM with N-terminal Fab 5.2 12.6 20 TM with N-terminal Fab 4.4 5.2 21 TM with N-terminal Fab 4.2 5.5 22 TM with N-terminal Fab 4.0 4.6 23 TM with N-terminal Fab 3.7 No binding 24 TM with N-terminal Fab 6.6 No binding 25 TM with C-terminal Fab, linker=15-member 4.5 11.0 26 TM with C-terminal Fab, linker=15-member 5.1 5.1 27 TM with C-terminal Fab, linker=15-member 4.2 7.3 28 TM with C-terminal Fab, linker=15-member 3.2 4.3 29 TM with C-terminal Fab, linker=15-member 5.7 No binding thirty TM with C-terminal Fab, linker=15-member 5.6 No binding 31 TM with C-terminal Fab, linker=5-member 7.6 No binding 32 TM with C-terminal Fab, linker=5-member 6.4 No binding 42 (ABP 1-10, 23, 24, 29-32, 35-41, 43, 48, 49) IgG1 N297A* 11.5 No binding 44 (ABP 11, 12, 19, 25) IgG1 N297A# 46.5 Poor match 45 (ABP 13, 20, 26, 45, 52) IgG1 N297A# 112.2 Poor match 46 (ABP 14-16, 21, 27, 53-55) IgG1 N297A# 59.8 110.9 47 (ABP 17, 18, 22, 28, 56, 57) IgG1 N297A# 44.3 88.1 48 (ABP 10, 29, 31) IgG1 N297A# 14.8 No binding 49 (ABP 24, 30, 32) IgG1 N297A# 63.5 No binding eleven IgG1 format 3.1 8.5 12 IgG1 format 2.8 7.9 13 IgG1 format 5.5 6.4 14 IgG1 format 2.8 5.9 15 IgG1 format 3.3 5.2 16 IgG1 format 2.9 5.4 17 IgG1 format 4.2 4.6 18 IgG1 format 4.0 8.4

* non-optimized, non-TM ABP IgG1 corresponding to ABP in brackets

# H1H2-optimized, non-TM ABP IgG1 corresponding to ABP in brackets

[425] Additional K _D measurements were performed on 8 N-terminal Fab TM format antibodies using multiple concentration kinetics. GITR ABPs were evaluated for their ability to bind recombinant hGITR (SEQ ID NO: 1), hGITR-T43R (SEQ ID NO: 2) and cGITR (SEQ ID NO: 3) using the ^FORTEBIO® OCTET device. The assay was performed at 30°C using 1x kinetic buffer (ForteBio, Inc.) as assay buffer. Anti-human IgG Fc (AHC) binding biosensors (ForteBio, Inc.) were used to bind ABP to GITR on the sensors. The sensors were saturated in assay buffer for 600 seconds prior to assay. Background was established by immersing the sensors in 1x assay buffer for 60 seconds. ABP was loaded onto the sensors by immersing the sensors in the ABP solution for 300 seconds. Background was established by immersing the sensors in 1× assay buffer for 120 seconds. Binding was then monitored for 300 seconds at various concentrations of recombinant antigens (50 nM - 0.78 nM, 2-fold dilutions in assay buffer) and dissociation was monitored for 600 or 1200 seconds in buffer alone. K _D was determined using the kinetics function of the ^FORTEBIO® analysis software using a 1:1 binding model. The results of K _D determination by OCTET are shown in FIG. 2 and Table 7. As can be seen in the figure, each of the K _D for human GITR was less than 1nM and the K _D for cynomolgus monkey GITR are within 15 times the K _D for human . In addition, TM format antibodies bind the human GITR variant to the T43R SNP.

Table 7. Binding characteristics of TM format ABP to N-terminal Fab

ABP GITR Human-Fc
K _D (M), n=3 GITR Human-Fc T43R
K _D (M), n=1 GITR cynomolgus-Fc
K _D (M), n=3 1 3.2E-10 5.3E-10 6.2E-10 2 2.3E-10 1.0E-10 7.1E-10 3 1.2E-10 2.7E-12 1.1E-09 4 1.1E-10 4.5E-12 1.5E-09 5 1.2E-10 7.3E-11 1.1E-09 6 1.5E-10 3.5E-11 1.6E-09 7 4.5E-10 7.0E-10 1.7E-09 8 5.2E-10 6.6E-10 6.6E-10

Analyzes binding GITR

[426] Peripheral blood mononuclear cells (PBMC) were cultured in growth medium in the presence of phytohemagglutinin (PHA) for 5 days at 37°C to upregulate GITR expression. T cells were harvested and washed, and then incubated at 4° C. with one of eight TM format GITR ABPs or a human isotype control antibody. After washing, cells were incubated at 4° C. with fluorochrome-conjugated anti-human CD4 antibody and anti-human CD8 antibody, as well as fluorochrome-conjugated anti-human IgG antibody to detect bound human anti-GITR ABP. The percentage of GITR+ CD4 and CD8 cells, as well as the mean fluorescence intensity (MFI) is determined by flow cytometry.

[427] Illustrative results are shown in FIG. 3. Figure 3A shows CD4+ cells and Figure 3B shows CD8+ cells. Top row, left to right, shows anti-GITR positive control and anti-human IgG4 isotype control, and TM format ABP with N-terminal Fab ABP9, ABP2, ABP1, and ABP7. The bottom row shows ABP8, ABP3, ABP4, ABP5, ABP6, ABP23 and ABP24. The percentage of IgG4+ CD4/8+ cells is indicated.

[428] Cell surface binding to human, cynomolgus, and mouse GITRs is assessed by transfection of HT1080, CHO, or 293T-cells with the appropriate GITR (human, cynomolgus, or mouse). Binding to cynomolgus monkey GITR was further assessed using primary cynomolgus monkey T cells and the HSC-F T cell line, each after stimulation with an anti-CD3 antibody, to increase GITR expression.

Analyzes activity antigen-binding proteins For GITR

[429] GITR ABPs were tested for their ability to act as a GITR agonist. In one assay, HT1080 cells stably expressing human or cynomolgus monkey GITR were contacted with ABP TM format GITR or trimeric human GITRL. After 24 hours, the amount of IL-8 secreted by the cells was assessed by ELISA analysis. Increased secretion of IL-8 corresponds to an increase in GITR agonism. The results for antibodies 1-8 format TM with N-terminal Fab are shown in FIG. 4. Shows IL-8 yield based on antibody or ligand concentration for ABP1 (FIG. 4A), ABP2 (FIG. 4B), ABP3 (FIG. 4C), ABP4 (FIG. 4D), ABP5 (FIG. 4E), ABP6 (FIG. 4F), ABP7 (FIG. 4G) and ABP8 (FIG. 4H). Antibodies are shown as circles in FIG. and the GITRL control is shown as squares. The EC ₅₀ values are compared with those for the GITR ligand (GITRL).

[430] Table 8. Agonist activity of TM antibodies against human and cynomolgus monkey GITR on HT1080 cells

ABP Average EC ₅₀ for human HT1080, GITRL on the same plate (pM) % maximal IL-8 induction relative to GITRL in human HT1080, GITRL on the same plate n Average EC ₅₀ in HT1080 cynomolgus monkey, GITRL on the same plate (pM) % maximum induction of IL-8 relative to GITRL in cynomolgus monkey HT1080, GITRL on the same plate n 1 118 97 2 104 91 2 2 126 97 2 61 80 2 3 97 96 2 72 92 2 4 92 85 2 44 102 2 5 107 95 2 62 103 2 6 83 96 2 77 92 2 7 217 124 2 128 95 2 8 255 100 2 201 89 2 GITRL 120 - 16 76 - 16

[431] The same analysis was performed using non-TM variants of ABP 1-8 from IgG1 N297A (See FIG. 4) and the data are summarized in Table 9.

Table 9. Activity of IgG1 N297A antibodies against human and cynomolgus monkey GITR on HT1080 cells

ABP (corresponding to TM ABP) Average EC ₅₀ for human HT1080, GITRL on 1 single plate (nM) n Average EC ₅₀ for HT1080 cynomolgus monkey, GITRL on 1 single plate (nM) n 35(1) 0.88 1 2 1 36(2) 0.58 1 8.8 1 37(3) 0.19 1 1.7 1 38(4) 0.33 1 14.3 1 39(6) 0.44 1 2.3 1 40 (7) 0.34 1 1.1 1 41 (8) 0.44 1 2 1 GITRL 0.43 2 0.17 2

[432] The assay was again used to test the activity of additional TM format antibodies with N-terminal Fab and C-terminal Fab, as well as IgG1 N297A variants of these antibodies. The data are summarized in Table 10 and Table 11 and shown in FIG. 5. In FIG. 5A shows ABP43 (squares), ABP23 (circles), ABP24 (triangles) and ABP29 (open circles), ABP30 (open triangles), ABP31 (open circles), and ABP32 (open triangles), all compared to GITRL (+ sign) . FIG. 5B shows ABP19 (N-terminal Fab, triangles) and ABP25 (C-terminal Fab, inverted triangles). GITRL is shown as plus signs. FIG. 5C shows ABP21 (N-terminal Fab, triangles) and ABP27 (C-terminal Fab, inverted triangles). GITRL is shown as plus signs. FIG. 5D shows ABP20 (N-terminal Fab, triangles) and ABP26 (C-terminal Fab, inverted triangles). GITRL is shown as plus signs. FIG. 5E shows ABP22 (N-terminal Fab, triangles) and ABP28 (C-terminal Fab, inverted triangles). GITRL is shown as plus signs. As shown in FIG., N-terminal Fab format ABPs tended to induce more IL-8 than their C-terminal Fab equivalents.

[433] In FIG. 10 shows a further comparison of ABP43 (non-optimized IgG4 format) with two corresponding TM format ABPs where the IgG1 Fab equivalent of ABP43 is added to the N- or C-terminus of ABP43. As can be seen in the figure, TM format ABP9 with N-terminal Fab (squares) induced the highest level of IL-8 (and had the best EC ₅₀ ) compared to TM format ABP10 with C-terminal Fab (circles) and non-terminal ABP43. TM format (diamonds). Both TM format ABPs had better activity than the original non-TM format ABP, as well as GITRL. IL-8 induction by GITRL (positive control) is shown as a single data point (star). IL-8 production is shown in pg/ml.

Table 10 Agonist activity of TM antibodies with N-terminal Fab and C-terminal Fab against human GITR on HT1080 cells

ABP Format Average EC ₅₀ for human HT1080, GITRL on 1 single plate (nM) n GITRL -- 0.37 1 9 TM with N-terminal Fab 0.18 1 19 TM with N-terminal Fab 0.25 1 20 TM with N-terminal Fab 0.63 1 21 TM with N-terminal Fab 0.18 1 22 TM with N-terminal Fab 0.30 1 23 TM with N-terminal Fab 0.30 1 24 TM with N-terminal Fab 0.17 1 25 TM with C-terminal Fab, linker=15-member 0.46 26 TM with C-terminal Fab, linker=15-member 0.63 1 27 TM with C-terminal Fab, linker=15-member 0.35 1 28 TM with C-terminal Fab, linker=15-member 0.63 1 29 TM with C-terminal Fab, linker=15-member 0.27 1 thirty TM with C-terminal Fab, linker=15-member 0.31 1 31 TM with C-terminal Fab, linker=5-member 0.18 1 32 TM with C-terminal Fab, linker=5-member 0.30 1

Table 11. Agonistic activity of IgG1 N297A antibodies against human GITR on HT1080 cells

ABP Format EC ₅₀ for human HT1080, GITRL on a separate plate (nM), n=2 EC ₅₀ for HT1080 cynomolgus monkey, GITRL on a separate plate (nM), n=1 42 IgG1 N297A 17.8 no activity 44 IgG1 N297A 4.2 28.0 45 IgG1 N297A 10.5 15.1 46 IgG1 N297A 1.2 6.9 47 IgG1 N297A 4.1 11.8 48 IgG1 N297A 0.8 minimal activity 49 IgG1 N297A 2.7 65.8

[434] Additional variants of the IgG1 N297A optimized H1H2/VH antibodies were generated and shown in Table 12 below, and their agonist activity as determined by the HT1080 assay as described above is indicated. These antibodies are suitable for production in TM format.

Table 12 Agonist activity of IgG1 N297A antibodies against human GITR on HT1080 cells

ABP Format EC ₅₀ for human HT1080, GITRL on separate plate (nM) EC ₅₀ for HT1080 cynomolgus monkey, GITRL on separate plate (nM) eleven IgG1 N297A 3.9 21.6 12 IgG1 N297A 3.5 28.4 13 IgG1 N297A 7.8 15.0 14 IgG1 N297A 0.6 4.1 15 IgG1 N297A 0.6 4.5 16 IgG1 N297A 0.6 3.8 17 IgG1 N297A 5.3 8.4 18 IgG1 N297A 2.1 13.2 GITRL -- 0.4 0.2

[435] A similar assay was performed on Jurkat cells, a T cell-based cell line modified to express human GITR and the NF-κB luciferase reporter (Promega®). Eight optimized TM format antibodies with N-terminal Fab, ABP 1-8, were compared to GITRL for their ability to induce IL-8 in T cells. As shown in FIG. 7A-H (for ABPs 1-8) and in Table 13, all eight ABPs were superior to GITRL in inducing cytokine production.

Table 13. 8 Optimized TM formats with N-terminal Fab outperform GITRL

ABP EC ₅₀ (nM) % activity compared to GITRL 1 0.30 104 GITRL 0.90 2 0.21 114 GITRL 0.91 3 0.19 120 GITRL 0.85 4 0.22 117 GITRL 1.13 5 0.25 104 GITRL 1.01 6 0.29 121 GITRL 0.90 7 0.20 108 GITRL 0.81 8 0.30 114 GITRL 0.89

Agonistic activity antibodies TM format With N-terminal fab V primary cells

[436] In one embodiment, GITR ABPs are further tested for their ability to produce a co-stimulatory signal to CD4+CD25 effector T cells in combination with TCR signaling via an anti-CD3 antibody. An increase in T cell activation is measured by quantifying proliferation, and/or measuring an increase in the production and secretion of cytokines, including IFN-gamma, using an ELISA assay.

[437] In another embodiment, GITR ABPs are further analyzed to evaluate their ability to prevent suppression of effector T cells by regulatory T cells. Human CD4+ T cells are isolated using a human CD4+ T cell isolation kit (Miltenyi #130-096). Regulatory T cells are further enriched using MicroBeads® II anti-human CD25 beads (Miltenyi #130-092-983) following the manufacturer's instructions. CD25-depleted CD4+ T cells are used as effector T cells in the suppression assay. Beads conjugated to anti-human CD2, CD3 and CD28 antibodies are used to activate effector T cells in the assay (Treg Suppression Inspector; also called T cell activation beads, Miltenyi #130-092-909). In a 96-well plate, 50,000 each of regulatory T cells and effector T cells are seeded into each well and incubated with an equivalent number of beads to activate the T cells. Mixtures of cells and beads are brought into contact with various concentrations of ABP GITR for five days. Effector T cell proliferation is measured by stimulating cell cultures with tritiated thymidine during the last 16 hours of culture, washing and measuring the level of radioactivity incorporated into the cells.

Agonistic activity antibodies TM format With N-terminal fab V analysis primary cells T-blasts

Pre-stimulated T cells (T blasts) were used to evaluate the activity of eight N-terminal Fab TM format antibodies (ABP 1-8).

To obtain T-blasts, PBMCs are stimulated with PHA for 5-7 days to expand the cells and induce GITR expression. Cells are washed and frozen in preparation for functional analysis.

To evaluate the functional activity of ABP 1-8, cells are stimulated by adding 1 mg/ml anti-CD3 antibody + 2 mg/ml anti-CD28 antibody, 0.003-10 mg/ml ABP 1-8, and 10 mg/ml GITRL as a positive control . Cells are incubated at 37° C. and supernatants are harvested 48 hours later. IL-2 production is measured by AlphaLISA® (Perkin Elmer®). FIG. 8A shows the percentage of GITR+ CD4+ cells (left) and CD8+ cells (right) in cells from two human donors at different time points, +/- stimulation with PHA.

FIG. 8B-8M show the results of treating T-blasts from 4 different donors after control or ABP treatments, and the resulting IL-2 production. On each FIG. top row, left to right, is a FACS measurement of ABP binding to CD4+ cells, IL-2 production in cells from donor 1, IL-2 production in cells from donor 2. Bottom row, left to right, is a FACS measurement of ABP binding to CD8+ cells cells, IL-2 production in cells from donor 3, IL-2 production in cells from donor 4. Data are shown as follows: 8B: IgG4 isotype control; 8C: SEC4 antibody; 8D: TM format IgG4 negative control; 8E: non-TM IgG4 non-optimized progenitor of the ABP 1-8 (ABP9) lineage. 8F: ABP1; 8G: ABP2; 8H: ABP3; 8I: ABP4; 8J: ABP5; 8K: ABP6; 8L: ABP7; 8M:ABP8.

As shown in FIG., T-blasts from different donors showed variability in response to treatment with ABP 1-8; however, treatment with all eight TM format ABPs had agonist activity at most concentrations tested, as measured by IL-2 production and compared to control antibodies.

Comparison activity agonism GITR optimized ABP format TM With N-terminal fab And Not related To format TM ABP IgG1

[438] The same eight optimized TM format ABPs with N-terminal Fab (1-8) as in the above examples were compared with non-optimized control progenitors in the same IL-8 induction assay described above and this is shown in FIG. . 4. In each FIG. shows a comparison of TM format ABP 1-8 with N-terminal Fab (IgG4 S228P with IgG1 N-terminal Fab, "IgG4 TM") and the corresponding non-TM format IgG1 ABP (IgG1 N297, "IgG1"), as well as GITRL as positive control and negative IgG4 control (GITRL and IgG4 were analyzed in a plate separate from ABP). Left panels show results for cells expressing hGITR and right panels show results for cells expressing cGITR. IL-8 induction as a function of ABP concentration is shown for ABP 1 (FIG. 9A), ABP 2 (FIG. 9B), ABP3 (FIG. 9C), ABP4 (FIG. 9D), ABP5 (FIG. 9E), ABP6 ( FIG. 9F), ABP7 (FIG. 9G) and ABP8 (FIG. 9H). IL-8 induction by GITRL is shown as circles, by TM format antibodies as triangles, by parent IgG1 antibodies as diamonds, and by control IgG4 antibodies as squares. A table of EC ₅₀ values is shown at the bottom of each panel in each FIG.

[439] The results shown in Figure 9 demonstrate that the eight optimized ABPs are able to induce IL-8 production in cells expressing human or cynomolgus GITR to a much greater extent in the form of TM format antibodies with an N-terminal Fab compared to with divalent IgG1 N297A. TM format antibodies with N-terminal Fab had lower EC ₅₀ values and higher maximum IL-8 production compared to N297A divalent IgG1 format. In addition, all TM antibodies had a higher affinity for GITR than the non-TM form of the parent antibody (compare Tables 5 and 7 with Table 6).

Grade blocking GITRL

[440] In another embodiment, GITR blocking was assessed using the ^FORTEBIO® OCTET device. The assay was performed at 30° C. using 1x kinetic buffer (ForteBio, Inc.) as assay buffer. Anti-human IgG Fc (AHC) binding biosensors (ForteBio, Inc.) were used to bind human GITR ABP on the sensors. The sensors were saturated in assay buffer for 300 seconds prior to assay. ABP was loaded onto the sensors by immersing the sensors in the ABP supernatant solution for 300 seconds. Background was established by immersing the sensors in 1x assay buffer for 200 seconds. Recombinant GITR binding was then monitored for 180 seconds. The ability of recombinant GITRL to subsequently bind to ABP/GITR complex was determined by immersing the sensors in GITRL for 180 seconds.

[441] GITR blocking was evaluated according to the above methods using ABP 1-8. All eight ABPs were capable of blocking GITRL binding.

[442] In one embodiment, to evaluate whether human anti-GITR ABPs block GITR ligand (GITRL, R&D Systems #6987-GL-CF) binding to GITR, various concentrations of unlabeled GITR ABP are incubated with human pan-T cells at 4°C in staining buffer (e.g. phosphate buffered saline with 0.5% bovine serum albumin) for 10 min. Without washing, 4 nM HA labeled human GITRL is added and incubated at 4° C. for a further 30 min. The cells are then washed twice with staining buffer, and incubated with anti-HA antibody with PE (Miltenyi #130-092-257) in staining buffer at 4°C for 30 min. The cells are then washed twice with staining buffer and fixed using 2% paraformaldehyde in PBS for flow cytometry analysis. The decrease in PE staining indicates that ABP blocks the GITR-GITRL interaction.

Example 3: Multispecific Antigen Binding Proteins

[443] One embodiment of multispecific GITR agonist ABPs comprises an antibody with a common light chain. ABPs have been identified linking two distinct epitopes on the GITR. These two ABPs share the same light chain. ABP61 is an agonist antibody and ABP59 has less agonist activity but does not compete with ABP61 for GITR binding. Multivalent, multispecific antibodies with common light chains were generated by transfection of HEK-293 host cells with vectors encoding two heavy chains and one common light chain. The first illustrative ABP described herein with a common light chain (SEQ ID NO:125) is ABP33 having an IgG4 heavy chain (ABP61) with an N-terminal Fab (from ABP58 (IgG1 equivalent to ABP59)), and the full length sequence SEQ ID NO:124 (HC) and SEQ ID NO:125 (LC). A second illustrative ABP described herein with a common light chain is ABP34 having an IgG4 heavy chain (ABP61) with a C-terminal Fab (from ABP58 (IgG1 equivalent to ABP59) and the full length sequence of SEQ ID NO:136 (HC) and SEQ ID NO:125 (LC).

[444] Each multispecific ABP binds two separate epitopes on the GITR. ABP is characterized as described in the examples above. Other multispecific ABP described in the present description, received and characterized in a similar way. FIG. 6 shows the results of the EC ₅₀ determination for ABP33 and ABP34 in the HT1080 assay as described in Example 2 above. ABP33 (a tetravalent variant combining ABP61 IgG4 with an IgG1 Fab from ABP58 [IgG1 equivalent of ABP59] at the N-terminus) and ABP34 (tetravalent variant , combining ABP61 IgG4 with an IgG1 Fab from ABP58 [IgG1 equivalent of ABP59] at the C-terminus) was compared to bivalent ABP 59 and 61 (IgG4 S228P). As shown in FIG., both tetravalent antibodies had a superior EC ₅₀ as measured by IL-8 induction compared to their divalent equivalents.

Example 4 Comparison of TM Format Antibody with Anti-GITR Reference Antibodies

[445] The activity of TM-format antibodies with an N-terminal Fab was tested against two known anti-GITR antibodies, SEC4 and SEC9, in HT1080 cells modified to stably express human GITR. Cultured cells were treated for six hours using a range of concentrations of two reference agonist antibodies, SEC4 ("35E6" formatted to have mouse variable regions with human IgG4 S228P/kappa regions, orange diamonds) and SEC9 (humanized 6C8 N62Q IgG1 N297A). SEC4 is described, for example, in US Patent No. 8709424; variable regions are found in SEQ ID NOs 1 and 12. SEC9 is described, for example, in US Patent No. 7812135; full length sequences are shown in SEQ ID NOs 58 and 63. A dose of 1 μg/ml of divalent antibody is equivalent to 6.67 nM; a dose of 1 μg/ml of a tetravalent antibody is equivalent to 4 nM.

[446] IL-8 induction was measured by ELISA and EC ₅₀ was calculated. FIG. 11A shows comparison of hGITRL with SEC4 (diamonds) and SEC9 (circles), as well as IgG4 negative control (solid triangles), IgG1 negative control (open triangles), and human GITR trimeric ligand ("hGITRL", squares) as positive control. GITRL had better EC ₅₀ (inset) and maximum induction compared to both SEC4 and SEC9.

[447] Comparisons of GITRL with ABP1 (FIG. 11B), ABP2 (FIG. 11C), ABP3 (FIG. 11D), ABP4 (FIG. 11E), ABP5 (FIG. 11F), ABP6 (FIG. 11G), ABP7 (FIG. 11H) and ABP8 (FIG. 11I). As shown in the figure, all eight N-terminal Fab TM format antibodies had a more preferential EC ₅₀ than either SEC4 or SEC9. All eight N-terminal Fab TM format antibodies also had a higher induction of IL-8 production than either SEC4 or SEC9.

[448] SEC4 was tested as described above in the analysis of primary T-blast cells. As shown in FIG. 8, induction of IL-2 in primary cells by SEC4 was less for all four donors than TM antibodies.

Example 5 Anti-GITR ABPs Increase Cytokine Production in Patient's Tumor-Infiltrating Lymphocytes and in GITR+ T Cells

materials And ways

[449] Dissociated tumor samples were purchased from Conversant Bio. Samples were NSCLC adenocarcinoma isolated from a 75 year old male ex-smoker with stage Ia disease prior to any treatment. The sample was rapidly thawed, then re-stimulated under several conditions, in the presence and absence of immunotherapeutic agents, as follows: cells were either a no-stimulation control or were stimulated with 1 μg/ml αCD3 (soluble) + 2 μg/ml αCD28 ( soluble) + IL-2 (50 ng/ml); cells were either unimmunotreated (to evaluate checkpoint protein levels) or treated with pembrolizumab (10 μg/mL), TM format control ABP (2 μg/mL), ABP1 (2 μg/mL), or ABP1+pembrolizumab. Cells were incubated for 48 hours before supernatant collection and staining for checkpoint protein expression. In some samples, brefeldin A (an inhibitor of cytokine secretion) was added during the last five hours of stimulation to detect cytokines by intracellular cytokine staining.

results

[450] Cells were selected as GITR positive T cells and the results are shown in Figure 12A (TNF production) and Figure 12B (IFNγ production). As shown in the figures, treatment with a single anti-GITR agent (ABP1) resulted in an increase in cytokine production. In this assay, there was no significant increase in cytokine production in cells treated with the combined ABP1+pembrolizumab treatment.

Example 6 Epitope Mutagenesis Assay: Alanine Scan

[451] To identify an epitope for ABP1 binding to human GITR, single point mutations were introduced into the extracellular domain of human GITR to determine if APB1 binding is reduced. Either alanine substitutions or specific mouse residues were used (ABP1 does not bind mouse GITR). Proteins were expressed in Fc-tagged HEK-293 cells, secreted as soluble protein, purified on MabSelect® Sure® Lx resin, and characterized by SDS-PAGE. Binding was assessed by biolayer interferometry (BLI) using the Octet platform. Wild-type human GITR-Fc or GITR-mutant-Fc were coupled to anti-human Fc sensors, washed and exposed to ABP1 Fab. For residues considered part of the binding epitope, reduced or no binding is shown (eg, K _D , more than 3-fold weaker than binding to wild-type human GITR). Alanine substitutions at C58, R59, Y61, E64, C67 and aspartic acid at C66 resulted in no binding, while alanine substitutions at R56, D60, P62 or E65 resulted in reduced binding.

Example 7 Evaluation of antigen-binding proteins against GITR in vivo

[452] In vivo studies are conducted to demonstrate the ability of ABP to reduce the number of circulating regulatory T cells in a humanized NSG mouse model. Neonatal NSG mice are transplanted with CD34 ⁺ human fetal liver cells by retroorbital injection. After 16 weeks, animals develop a diverse repertoire of human immunocytes, including CD4 ⁺ and CD8 ⁺ effector T cells, and regulatory T cells. A single 25 mg/kg intraperitoneal dose of human anti-GITR ABP or human isotype control is administered to mice, and the percentage of circulating human CD4+ T cells expressing the regulatory T cell marker FoxP3 is determined by flow cytometry on day 4 post dosing.

Example 8 Incubation of Activated T Cells with TM Format ABP1 or Its Predecessor of the Common ABP35 Format

Receipt activated T-blasts

[453] Activated T-blasts were generated by stimulation of freshly isolated PBMCs from two healthy donors for 7 days with PHA (final conc. 10 μg/ml) and IL-2 (final conc. 4 ng/ml, added only for the last 24 hour) at 37°C and 5% CO _2.

Internalization GITR after binding antibodies

[454] Activated CD4+/CD8+ T-blasts were plated at 2×10 ⁵ per well in 96-well U-bottom plates. Wells were treated with media only, recombinant GITR Ligand (10 µg/ml, R&D Systems, cat# 6987-GL-025/CF), ABP1 (~250 kDa), hIgG4 isotype control TM format, ABP35 (~150 kDa), or standard format hIgG1 isotype control, nine doses each: 10 µg/mL, 2 µg/mL, 0.4 µg/mL, 80 ng/mL, 16 ng/mL, 3.2 ng/mL, 0.64 ng/mL ml, 0.13 ng/ml and 0.026 ng/ml.

Internalization GITR after binding antibodies

[455] Antibody-mediated clustering stimulates endocytosis and signaling by members of the TNF receptor superfamily, such as GITR. The ability of ABP1 and ABP35 (as well as isotype controls) to mediate clustering and internalization was measured.

[456] Activated T-blasts were first stained for FACS sorting. Fc receptors were blocked using human TruStain® FcX for 10 minutes at room temperature. Cells were incubated with fluorescently labeled antibodies for 30 minutes at 4°C as in Table 14. Cells were then washed 2X with FACS buffer, fixed in paraformaldehyde for 30 minutes in the dark, washed again and resuspended in 200 μl of FACS buffer , and collected data in a BD Fortessa device.

[457] GITR internalization was measured in CD4+ cells (Figures 13A-E) and CD8+ cells (Figures 13F-J) from either donor 1 (Figures 13A-B, 13F-G) or donor 2 (Figures 13C-D, 13H -I). Cells were treated with either ABP1 TM antibody format or standard ABP35 divalent antibody. As can be observed, incubation with either ABP1 or ABP35 inhibits subsequent staining with ABP1Dylight650 (Figures 13A, 13C, 13F, 13H), but only incubation with ABP1 induces GITR internalization as measured by staining using non-competing clone 108-17 (figures 13B, 13D, 13G, 13I). Determination of EC50 ABP1 on cells from both donors is shown in Figure 13E (CD4+ cells) and Figure 13J (CD8+ cells).

Table 14. Fluorochrome Labeling

Antigen Clone Isotype control Fluorochrome CD3 UCHT-1 --- PE/Cy 7 CD4 OKT4 --- BV421 CD8 RPA-T8 --- FITC GITR "ABP1" hIgG4TM format Dylight-650 GITR 108-17 mIgG2a BV605

Products cytokines V activated T cells processed ABP1 or ABP35

[458] Activated CD4+/CD8+ T-blasts were plated at 5×10 ⁴ per well in 96-well U-bottom plates. Wells were treated with media only, recombinant GITR Ligand (10 µg/mL, R&D Systems, cat# 6987-GL-025/CF), ABP1, hIgG4 isotype control TM format, ABP35, or standard format hIgG1 isotype control at nine doses each : 10 µg/mL, 2 µg/mL, 0.4 µg/mL, 80 ng/mL, 16 ng/mL, 3.2 ng/mL, 0.64 ng/mL, 0.13 ng/mL and 0.026 ng/ml.

[459] Cells were stimulated by the addition of 1 μg/ml anti-CD3 antibody (mouse anti-human protein, clone UCHT-1), R&D Systems cat#MAB100) and 2 μg/ml anti-CD28 antibody (mouse anti-human protein, clone 37407), R&D Systems cat# MAB342) antibodies. Assay reaction mixtures were incubated at 37°C and 5% CO2 for 48 hours. IL-2 production was measured by AlphaLISA® (Perkin Elmer).

[460] Incubation of T-blasts with the TM format ABP1 antibody, but not the same antibody in the standard bivalent format (ABP35) or any of the isotype controls, results in GITR internalization by activated CD4+ and CD8+ T cells (FIG. 13) .

[461] In addition, superclustering of the GITR receptor by ABP1, but not binding by conventional divalent ABP, stimulates IL-2 secretion by activated T-blasts in a dose-dependent manner (FIG. 14). Together, these data indicate that T-blasts that do not respond to conventional anti-GITR therapy can respond to the corresponding antibody in TM format.

Example 9 Cytokine Production in ABP1-Treated Activated T Cells Compared to Two Reference Antibodies, SEC4 and SEC9

[462] Activated T-blasts were obtained as described in example 8, and used to compare the activity of ABP1 with reference antibodies against GITR SEC4 and SEC9. Activated T-blasts were generated by stimulation of freshly isolated PBMCs from two healthy donors for 7 days with PHA (final conc. 10 μg/ml) and IL-2 (final conc. 4 ng/ml, added only for the last 24 hours) at 37°C and 5% CO2 _.

[463] Activated CD4+/CD8+ T-blasts were plated at 5×10 ⁴ per well in 96-well U-bottom plates. Wells were treated with media only, recombinant GITR Ligand, ABP1, SEC4, SEC9, hIgG4 isotype control TM format ("Iso-TM"), standard format hIgG1 isotype control, and standard format hIgG4 isotype control, at nine doses each: 10 µg/mL , 2 µg/ml, 0.4 µg/ml, 80 ng/ml, 16 ng/ml, 3.2 ng/ml, 0.64 ng/ml, 0.13 ng/ml and 0.026 ng/ml.

Products cytokines V activated T cells processed ABP1, SEC4 And SEC9

[464] Cells were stimulated by adding 1 μg/ml of anti-CD3 antibody and 2 μg/ml of anti-CD28 antibody. Cells were incubated at 37°C and 5% CO ₂ for 48 hours. IL-2 production was measured by AlphaLISA® (Perkin Elmer). As seen in Example 8, TM1 format ABP stimulates IL-2 secretion by activated T-blasts in a dose dependent manner. IL-2 production by activated T cells is shown in Figures 15A (donor 1) and 15B (donor 2). The corresponding EC50 is shown in Figures 15C (donor 1) and 15D (donor 2).

[465] As can be seen in the figures, SEC4 and SEC9 do not effectively induce IL-2 in a dose-dependent manner, ABP1 induced IL-2 production to a greater extent than SEC4 and SEC9 in a clearly dose-dependent manner. Together, these data support the conclusion that T-blasts that do not respond to conventional anti-GITR therapy may respond to the appropriate antibody in TM format.

EQUIVALENTS

[466] The description above may include many individual inventions with independent utility. While each of these inventions has been described in its preferred form(s), the specific embodiments thereof as described and illustrated herein are not to be construed in a limiting sense as numerous variations are possible. The object of the invention includes all new and non-obvious combinations and subcombinations of various elements, features, functions and/or properties described in the present description. In the following claims, specific combinations and sub-combinations are especially highlighted as being novel and non-obvious. Inventions embodied in other combinations and subcombinations of features, functions, elements and/or properties may be claimed in this application, in applications claiming priority for this application, or in related applications. Such claims, whether they relate to another invention or to the same invention, and whether they have a broader, narrower, equal or different scope than the original claims, are also considered to be included in the subject matter. inventions according to the present description. APPENDIX A: SEQUENCES

SEQID NO Molecule Description Subsequence 1 Human GITR NP_004186.1 (ref seq) or Q9Y5U5 (UniProt) MAQHGAMGAFRALCGLALLCALSLGQRPTGGPGCGPGRLLLGTGTDARCCRVHTTRCCRDYPGEECCSEWDCMCVQPEFHCGDPCCTTCRHHPCPPGQGVQSQGKFSFGFQCIDCASGTFSGGHEGHCKPWTDCTQFGFLTVFPGNKTHNAVCVPGSPPAEPLGWLTVVLLAVAACVLLLTSAQLGLHIWQLRSQ CMWPRETQLLLEVPPSTEDARSCQFPEEERGERSAEEKGRLGDLWV 2 Human GITR, SNP T43R variant MAQHGAMGAFRALCGLALLCALSLGQRPTGGPGCGPGRLLLGRGTDARCCRVHTTRCCRDYPGEECCSEWDCMCVQPEFHCGDPCCTTCRHHPCPPGQGVQSQGKFSFGFQCIDCASGTFSGGHEGHCKPWTDCTQFGFLTVFPPGNKTHNAVCVPGSPPAEPLGWLTVVLLAVAACVLLLTSAQLGLHIWQLRSQ CMWPRETQLLLEVPPSTEDARSCQFPEEERGERSAEEKGRLGDLWV 3 GITR of the cynomolgus macaque XP_005545180.1 MCACGTLCCLALLCAASLGQRPTGGPGCGPGRLLLGTGKDARCCRVHPTRCCRDYQSEECCSEWDCVCVQPEFHCGNPCCTTCQHHPCPSGQGVQPQGKFSFGFRCVDCALGTFSRGHDGHCKPWTDCTQFGFLTVFPPGNKTHNAVCVPGSPPAEPPGWLTIVLLAVAACVLLLTSAQLGLHIWQLGSQPTG PRETQLLLEVPPSTEDASSCQFPEEERGERLAEEKGRLGDLWV 4 Mouse GITR MGAWAMLYGVSMLCVLDLGQPSVVEEPGCGPGKVQNGSGNNTRCCSLYAPGKEDCPKERCICVTPEYHCGDPQCKICKHYPCQPGQRVESQGDIVFGFRCVACAMGTFSAAGRDGHCRLWTNCSQFGFLTMFPGNKTHNAVCIPEPLPTEQYGHLTVIFLVMAACIFFLTTVQLGLHIWQLRRQHMCPRETQPFAEVQLSAED ACSFQFPEEERGEQTEEKCHLGGRWP 5 Linker 1 GGGGS 6 Linker 2 GGGGSGGGGSGGGGS 7 ABP1 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGLGWGWIRQPPGKGLEWIGGIYESGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAHERVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGLGWGWIRQPPGKGLEWIGGIYESGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAHERVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 17 ABP2 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCADENVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCADENVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 24 ABP3 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 32 ABP4 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGPEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGPEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 37 ABP5 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 38 ABP6 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 42 ABP7 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 51 ABP8 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 57 ABP9 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) qlqlqesgpglvkpsetlsltctvsggsissssyawgwirqppgkglewigsiyysgstyynpslksrvtisvdtsknqfslklssvtaadtavyycardsgrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqss glyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscggggsqlqlqesgpglvkpsetlsltctvsggsissssyawgwirqppgkglewigsiyysgstyynpslksrvtisvdtsknqfslklssvtaadtavyycardsgrgygdygghhafdiwgqgtmvtvssastkgpsvfplapcs rstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvs vltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 57 ABP10 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) qlqlqesgpglvkpsetlsltctvsggsissssyawgwirqppgkglewigsiyysgstyynpslksrvtisvdtsknqfslklssvtaadtavyycardsgrgygdygghhafdiwgqgtmvtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssg lyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlpp sqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkggggsqlqlqesgpglvkpsetlsltctvsggsissssyawgwirqppgkglewigsiyysgstyynpslksrvtisvdtsknqfslklssvta adtavyycardsgrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 171 ABP11 Full length heavy chain (IgG1) qvqlvqsgaevkrpgssvkvsckasggtfssyyiswvrqvpgqglewmggiipvpgtanyaqkfqgrvtitadeststaymelsslrsedtavyycaragggyargdhyygmdvwgqgttvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvy tlppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 172 ABP12 Full length heavy chain (IgG1) qvqlvqsgaevkkpgssvkvsckasggtfssyyiswvrqapgqrlewmggiipvpgtanyaqkfqgrvtitadeststaymelsslrsedtavyycaragggyargdhyygmdvwgqgttvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavl qssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvy tlppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 173 ABP13 Full length heavy chain (IgG1) qvqlvqsgaevkkpgssvkvsckasggtfsrgaiswvrqapgqglewmggiipiegtayyaqkfqgrvtitadestgtaymelsslrsedtavyycarqsdyglprgmdvwgqgttvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 174 ABP14 Full length heavy chain (IgG1) qvqlvqsgaevkkpgssvkvsckasggtfssyaiswvrqapgqglewmggiipisgftnyaqkfqgrvtitadeststaymelsslrsedtavyycaregghyysgwpywgqgtlvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsrdel tknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 175 ABP15 Full length heavy chain (IgG1) qvqlvqsgaevkkpgssvkvsckasggtfssyaiswvrqapgqrlewmggiipisgftnyaqkfqgrvtitadeststaymelsslrsedtavyycaregghyysgwpywgqgtlvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsr deltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgk 176 ABP16 Full length heavy chain (IgG1) qvqlvqsgaevkkpgssvkvsckasggtfssyaiswvrqapgqglewmggiipisgftnyaqkfqgkvtitadeststaymelsslrsedtavyycaregghyysgwpywgqgtlvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsr deltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgk 177 ABP17 Full length heavy chain (IgG1) qvqlvqsgaevkkpgssvkvsckasggtfvryaiswvrqapgqglewmggiipifgeaqyaqrfqgrvtitadeststaymelsslrsedtavyycaregyyygalpywgqgtlvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglysls svvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsrdelt knqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 178 ABP18 Full length heavy chain (IgG1) qvqlvqsgaevkkpgssvkvsckasggtfvryaiswvrqapgqglewmggiipifgeaqyaqkfrgratitadeststaymelsslrsedtavyycaregyyygalpywgqgtlvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsrdeltknq vsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 106 ABP19 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG 108 ABP20 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG TQTYICNVNHKPSNTKVDKRVEPKSCGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG 110 ABP21 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT QTYICNVNHKPSNTKVDKRVEPKSCGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG 112 ABP22 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG TQTYICNVNHKPSNTKVDKRVEPKSCGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA LTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG 114 ABP23 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSV VTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQ PREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG 115 ABP24 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 1+IgG4 S228P (with or without C-terminal Lys) QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSVRGYGDYGGHHAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSVRGYGDYGGHHAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG 116 ABP25 Full length heavy chain, heavy chain variable region 1+IgG4 S228P (with or without C-terminal Lys)+GGGGSGGGGSGGGGS+ heavy chain variable region 1+CH1 IgG1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP SSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHY YGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC 117 ABP26 Full length heavy chain, heavy chain variable region 1+IgG4 S228P (with or without C-terminal Lys)+GGGGSGGGGSGGGGS+ heavy chain variable region 1+CH1 IgG1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGT TVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC 118 ABP27 Full length heavy chain, heavy chain variable region 1+IgG4 S228P (with or without C-terminal Lys)+GGGGSGGGGSGGGGS+ heavy chain variable region 1+CH1 IgG1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTY TCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC 119 ABP28 Full length heavy chain, heavy chain variable region 1+IgG4 S228P (with or without C-terminal Lys)+GGGGSGGGGSGGGGS+ heavy chain variable region 1+CH1 IgG1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTL VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC 120 ABP29 Full length heavy chain, heavy chain variable region 1+IgG4 S228P (with or without C-terminal Lys)+GGGGSGGGGSGGGGS+ heavy chain variable region 1+CH1 IgG1 QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGGGGSGGGGSGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGD YGGHHAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC 121 ABP30 Full length heavy chain, heavy chain variable region 1+IgG4 S228P (with or without C-terminal Lys)+GGGGSGGGGSGGGGS+ heavy chain variable region 1+CH1 IgG1 QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSVRGYGDYGGHHAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP SSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGGGGSGGGGSGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSVRGYGDYG GHHAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC 122 ABP31 Full-length heavy chain, heavy chain variable region 1+IgG4 S228P (with or without C-terminal Lys)+GGGGS+heavy chain variable region 1+CH1 IgG1 QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT VPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQ GTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC 123 ABP32 Full-length heavy chain, heavy chain variable region 1+IgG4 S228P (with or without C-terminal Lys)+GGGGS+heavy chain variable region 1+CH1 IgG1 QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSVRGYGDYGGHHAFDIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP SSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSVRGYGDYGGHHAFDIWGQGTM VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC 124 ABP33 Full-length heavy chain, heavy chain variable region 1+CH1 IgG1+GGGGS+variable heavy chain 2+IgG4 S228P (with or without C-terminal Lys) qvqlvqsgaevkkpgasvkvsckasgytftsyymhwvrqapgqglewmgiinpsggsttyaqkfqgrvtmtrdtststvymelsslrsedtavyycargqygyyggrldvwgqgttvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqss glyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscggggsqvqlvesgggvvqpgrslrlscaasgftfssygmhwvrqapgkglewvavisydgsnkyyadsvkgrftisrdnskntlylqmnslraedtavyycardglgymawgqgttvtvssastkgpsvfplapcsrstsestaal gclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlh qdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 136 ABP34 Full-length heavy chain, C-terminal Fab, common bispecific light chain: heavy chain variable region 2+IgG4 S228P (with or without C-terminal Lys)+GGGGS+heavy chain variable region 1+CH1 IgG1 qvqlvesgggvvqpgrslrlscaasgftfssygmhwvrqapgkglewvavisydgsnkyyadsvkgrftisrdnskntlylqmnslraedtavyycardglgymawgqgttvtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtv pssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtkn qvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkggggsqvqlvqsgaevkkpgasvkvsckasgytftsyymhwvrqapgqglewmgiinpsggsttyaqkfqgrvtmtrdtststvymelsslrsedtavyy cargqygyyggrldvwgqgttvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc N-TERMINAL Fab TM=heavy chain variable region 1+CH1 IgG1+GGGGS+heavy chain variable region 1+IgG4 S228P (with or without C-terminal Lys) 8 ABP1 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 18 ABP2 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 25 ABP3 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLKYGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 33 ABP4 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 33 ABP5 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 39 ABP6 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAADSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 43 ABP7 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSINSYLNWYQQKPGKAPKLLIYAASSLDSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 52 ABP8 Full length light chain DIQMTQSPSSLSASVGDRVTITCGASQSISTYLNWYQQKPGKAPKLLIYSASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPSFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 8 ABP9 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 8 ABP10 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 172 ABP11 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 174 ABP12 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 176 ABP13 Full length light chain diqltqspssvsasvgdrvtitcrasqgisswlawyqqkpgkapklliygasslqsgvpsrfsgsgsgtdftltisslqpedfatyycqqaslfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsst ltlskadyekhkvyacevthqglsspvtksfnrgec 178 ABP14 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 180 ABP15 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 182 ABP16 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 184 ABP17 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec 186 ABP18 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec 107 ABP19 Full length light chain DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQKIGTPLTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlska dyekhkvyacevthqglsspvtksfnrgec 109 ABP20 Full length light chain DIQLTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQASLFPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 111 ABP21 Full length light chain EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGTDFTLTISSLEPEDFAVYYCQQRLVFPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekhkvyacev thqglsspvtksfnrgec 113 ABP22 Full length light chain EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGTDFTLTISSLEPEDFAVYYCQQHSVFPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekhkvyacev thqglsspvtksfnrgec 8 ABP23 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 8 ABP24 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 107 ABP25 Full length light chain DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQKIGTPLTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlska dyekhkvyacevthqglsspvtksfnrgec 109 ABP26 Full length light chain DIQLTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQASLFPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 111 ABP27 Full length light chain EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGTDFTLTISSLEPEDFAVYYCQQRLVFPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekhkvyacev thqglsspvtksfnrgec 113 ABP28 Full length light chain EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGTDFTLTISSLEPEDFAVYYCQQHSVFPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekhkvyacev thqglsspvtksfnrgec 8 ABP29 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 8 ABP30 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 8 ABP31 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 8 ABP32 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 125 ABP33 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqalqtpitfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdsty slsstltlskadyekhkvyacevthqglsspvtksfnrgec 125 ABP34 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqalqtpitfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdsty slsstltlskadyekhkvyacevthqglsspvtksfnrgec 9 ABP1 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSGLGWGWIRQPPGKGLEWIGGIYESGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAHERVRGYGDYGGHHAFDIWGQGTMVTVSS 19 ABP2 V _H QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCADENVRGYGDYGGHHAFDIWGQGTMVTVSS 26 ABP3 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSS 34 ABP4 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGPEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSS 26 ABP5 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSS 26 ABP6 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSS 44 ABP7 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSS 44 ABP8 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSS 58 ABP9 V _H QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYAWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQGTMVTVSS 58 ABP10 V _H QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYAWGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQGTMVTVSS 62 ABP11 V _H QVQLVQSGAEVKRPGSSVKVSCKASGGTFSSYYISWVRQVPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSS 70 ABP12 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQRLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSS 71 ABP13 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTGTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSS 79 ABP14 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSS 87 ABP15 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQRLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSS 88 ABP16 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGKVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSS 89 ABP17 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSS 95 ABP18 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFRGRATITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSS 97 ABP19 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSS 98 ABP20 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSS 99 ABP21 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSS 101 ABP22 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSS 104 ABP23 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQGTMVTVSS 105 ABP24 V _H QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSVRGYGDYGGHHAFDIWGQGTMVTVSS 97 ABP25 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSS 98 ABP26 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSS 99 ABP27 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSS 101 ABP28 V _H QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSS 104 ABP29 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQGTMVTVSS 105 ABP30 V _H QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSVRGYGDYGGHHAFDIWGQGTMVTVSS 104 ABP31 V _H QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSGRGYGDYGGHHAFDIWGQGTMVTVSS 105 ABP32 V _H QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDSVRGYGDYGGHHAFDIWGQGTMVTVSS 126 ABP33 V _H , variable region 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGQYGYYGGRLDVWGQGTTVTVSS 126 ABP34 V _H , variable region 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGQYGYYGGRLDVWGQGTTVTVSS 127 ABP33 V _H , variable region 2 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGLGYMAWGQGTTVTVSS 127 ABP34 V _H , variable region 2 QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGLGYMAWGQGTTVTVSS 10 ABP1 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIK 20 ABP2 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIK 27 ABP3 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLKYGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIK 35 ABP4 V _L DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIK 35 ABP5 V _L DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIK 40 ABP6 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAADSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIK 45 ABP7 V _L DIQMTQSPSSLSASVGDRVTITCRASQSINSYLNWYQQKPGKAPKLLIYAASSLDSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIK 53 ABP8 V _L DIQMTQSPSSLSASVGDRVTITCGASQSISTYLNWYQQKPGKAPKLLIYSASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPSFGGGTKVEIK 10 ABP9 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIK 10 ABP10 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIK 63 ABP11 V _L DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQKIGTPLTFGGGTKVEIK 63 ABP12 V _L DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQKIGTPLTFGGGTKVEIK 72 ABP13 V _L DIQLTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQASLFPPTFGGGTKVEIK 80 ABP14 V _L EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRLVFPPTFGGGTKVEIK 80 ABP15 V _L EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRLVFPPTFGGGTKVEIK 80 ABP16 V _L EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRLVFPPTFGGGTKVEIK 90 ABP17 V _L EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQHSVFPPTFGGGTKVEIK 90 ABP18 V _L EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQHSVFPPTFGGGTKVEIK 63 ABP19 V _L DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQKIGTPLTFGGGTKVEIK 72 ABP20 V _L DIQLTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQASLFPPTFGGGTKVEIK 80 ABP21 V _L EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRLVFPPTFGGGTKVEIK 90 ABP22 V _L EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQHSVFPPTFGGGTKVEIK 10 ABP23 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIK 10 ABP24 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIK 63 ABP25 V _L DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQKIGTPLTFGGGTKVEIK 72 ABP26 V _L DIQLTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQASLFPPTFGGGTKVEIK 80 ABP27 V _L EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRLVFPPTFGGGTKVEIK 90 ABP28 V _L EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQHSVFPPTFGGGTKVEIK 10 ABP29 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIK 10 ABP30 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIK 10 ABP31 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIK 10 ABP32 V _L DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIK 128 ABP33 V _L DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPITFGGGTKVEIK 128 ABP34 V _L DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPITFGGGTKVEIK eleven ABP1 CDR3 V _H AHERVRGYGDYGGHHAFDI 21 ABP2 CDR3 V _H ADENVRGYGDYGGHHAFDI 28 ABP3 CDR3 V _H VLESVRGYGDYGGHHAFDI 28 ABP4 CDR3 V _H VLESVRGYGDYGGHHAFDI 28 ABP5 CDR3 V _H VLESVRGYGDYGGHHAFDI 28 ABP6 CDR3 V _H VLESVRGYGDYGGHHAFDI 46 ABP7 CDR3 V _H AREADRGYGDYGGHHAFDI 46 ABP8 CDR3 V _H AREADRGYGDYGGHHAFDI 59 ABP9 CDR3 V _H ARDSGRGYGDYGGHHAFDI 59 ABP10 CDR3 V _H ARDSGRGYGDYGGHHAFDI 64 ABP11 CDR3 V _H ARAGGGYARGDHYYGMDV 64 ABP12 CDR3 V _H ARAGGGYARGDHYYGMDV 73 ABP13 CDR3 V _H ARQSDYGLPRGMDV 81 ABP14 CDR3 V _H AREGGHYYSGWPY 81 ABP15 CDR3 V _H AREGGHYYSGWPY 81 ABP16 CDR3 V _H AREGGHYYSGWPY 91 ABP17 CDR3 V _H AREGYYYGALPY 91 ABP18 CDR3 V _H AREGYYYGALPY 64 ABP19 CDR3 V _H ARAGGGYARGDHYYGMDV 73 ABP20 CDR3 V _H ARQSDYGLPRGMDV 81 ABP21 CDR3 V _H AREGGHYYSGWPY 91 ABP22 CDR3 V _H AREGYYYGALPY 46 ABP23 CDR3 V _H ARDSGRGYGDYGGHHAFDI 21 ABP24 CDR3 V _H ARDSVRGYGDYGGHHAFDI 64 ABP25 CDR3 V _H ARAGGGYARGDHYYGMDV 73 ABP26 CDR3 V _H ARQSDYGLPRGMDV 81 ABP27 CDR3 V _H AREGGHYYSGWPY 91 ABP28 CDR3 V _H AREGYYYGALPY 46 ABP29 CDR3 V _H ARDSGRGYGDYGGHHAFDI 21 ABP30 CDR3 V _H ARDSVRGYGDYGGHHAFDI 46 ABP31 CDR3 V _H ARDSGRGYGDYGGHHAFDI 21 ABP32 CDR3 V _H ARDSVRGYGDYGGHHAFDI 131 ABP33 CDR3 V _H v1 ARGQYGYYGGRLDV 131 ABP34 CDR3 V _H v1 ARGQYGYYGGRLDV 134 ABP33 CDR3 V _H v2 ARDGLGYMA 134 ABP34 CDR3 V _H v2 ARDGLGYMA 12 ABP1 CDR2 _VH GIYESGSTYYNPSLKS 22 ABP2 CDR2 _VH GIAYSGSTYYNPSLKS 29 ABP3 CDR2 _VH LIVHSGSTYYNPSLKS 29 ABP4 CDR2 _VH LIVHSGSTYYNPSLKS 29 ABP5 CDR2 _VH LIVHSGSTYYNPSLKS 29 ABP6 CDR2 _VH LIVHSGSTYYNPSLKS 47 ABP7 CDR2 _VH LIYHSGKTYYNPSLKS 47 ABP8 CDR2 V _H LIYHSGKTYYNPSLKS 60 ABP9 CDR2 _VH SIYYSGSTYYNPSLKS 60 ABP10 CDR2 _VH SIYYSGSTYYNPSLKS 65 ABP11 CDR2 _VH GIIPVPGTANYAQKFQG 65 ABP12 CDR2 _VH GIIPVPGTANYAQKFQG 74 ABP13 CDR2 _VH GIIPIEGTAYYAQKFQG 82 ABP14 CDR2 _VH GIIPISGFTNYAQKFQG 82 ABP15 CDR2 V _H GIIPISGFTNYAQKFQG 82 ABP16 CDR2 V _H GIIPISGFTNYAQKFQG 92 ABP17 CDR2 _VH GIIPIFGEAQYAQRFQG 96 ABP18 CDR2 _VH GIIPIFGEAQYAQKFRG 65 ABP19 CDR2 _VH GIIPVPGTANYAQKFQG 74 ABP20 CDR2 _VH GIIPIEGTAYYAQKFQG 100 ABP21 CDR2 _VH GIIPISGFANYAQKFQG 102 ABP22 CDR2 _VH GIIPIFGEAQYAQKFQG 47 ABP23 CDR2 _VH LIYHSGKTYYNPSLKS 22 ABP24 CDR2 V _H GIAYSGSTYYNPSLKS 65 ABP25 CDR2 _VH GIIPVPGTANYAQKFQG 74 ABP26 CDR2 V _H GIIPIEGTAYYAQKFQG 100 ABP27 CDR2 _VH GIIPISGFANYAQKFQG 102 ABP28 CDR2 V _H GIIPIFGEAQYAQKFQG 47 ABP29 CDR2 _VH LIYHSGKTYYNPSLKS 22 ABP30 CDR2 _VH GIAYSGSTYYNPSLKS 47 ABP31 CDR2 _VH LIYHSGKTYYNPSLKS 22 ABP32 CDR2 _VH GIAYSGSTYYNPSLKS 130 ABP33 CDR2 V _H v1 IINPSGGSTTYAQKFQG 130 ABP34 CDR2 V _H v1 IINPSGGSTTYAQKFQG 133 ABP33 CDR2 V _H v2 VISYDGSNKKYYADSVKG 133 ABP34 CDR2 V _H v2 VISYDGSNKKYYADSVKG eleven ABP1 V _H CDR1 YSISSGLGWG 21 ABP2 V _H CDR1 GSISSGGAVWS 28 ABP3 V _H CDR1 YSISSGAGWG 28 ABP4 V _H CDR1 YSISSGAGWG 28 ABP5 V _H CDR1 YSISSGAGWG 28 ABP6 V _H CDR1 YSISSGAGWG 46 ABP7 V _H CDR1 YSISSEYMWG 46 ABP8 V _H CDR1 YSISSEYMWG 59 ABP9 V _H CDR1 GSISSSSYAWG 59 ABP10 V _H CDR1 GSISSSSYAWG 64 ABP11 V _H CDR1 GTFSSYYIS 64 ABP12 V _H CDR1 GTFSSYYIS 73 ABP13 V _H CDR1 GTFSRGAIS 81 ABP14 V _H CDR1 GTFSSYAIS 81 ABP15 V _H CDR1 GTFSSYAIS 81 ABP16 V _H CDR1 GTFSSYAIS 91 ABP17 V _H CDR1 GTFVRYAIS 91 ABP18 V _H CDR1 GTFVRYAIS 64 ABP19 V _H CDR1 GTFSSYYIS 73 ABP20 V _H CDR1 GTFSRGAIS 81 ABP21 V _H CDR1 GTFSSYAIS 91 ABP22 V _H CDR1 GTFVRYAIS 46 ABP23 V _H CDR1 YSISSEYMWG 21 ABP24 V _H CDR1 GSISSGGAVWS 64 ABP25 V _H CDR1 GTFSSYYIS 73 ABP26 V _H CDR1 GTFSRGAIS 81 ABP27 V _H CDR1 GTFSSYAIS 91 ABP28 V _H CDR1 GTFVRYAIS 46 ABP29 V _H CDR1 YSISSEYMWG 21 ABP30 V _H CDR1 GSISSGGAVWS 46 ABP31 V _H CDR1 YSISSEYMWG 21 ABP32 V _H CDR1 GSISSGGAVWS 129 ABP33 V _H CDR1 v1 YTFTSYYMH 129 ABP34 V _H CDR1 v1 YTFTSYYMH 132 ABP33 V _H CDR1 v2 FTFSSYGMH 132 ABP34 V _H CDR1 v2 FTFSSYGMH 16 ABP1 V _L CDR3 QQEYATPPT 17 ABP2 V _L CDR3 QQEYNTPPT 17 ABP3 V _L CDR3 QQEYNTPPT 17 ABP4 V _L CDR3 QQEYNTPPT 17 ABP5 V _L CDR3 QQEYNTPPT 17 ABP6 V _L CDR3 QQEYNTPPT 17 ABP7 V _L CDR3 QQEYNTPPT 56 ABP8 V _L CDR3 QQEYNTPPS 16 ABP9 V _L CDR3 QQEYATPPT 16 ABP10 V _L CDR3 QQEYATPPT 69 ABP11 V _L CDR3 MQKIGTPLT 69 ABP12 V _L CDR3 MQKIGTPLT 78 ABP13 V _L CDR3 QQASLFPT 86 ABP14 V _L CDR3 QQRLVFPPT 86 ABP15 V _L CDR3 QQRLVFPPT 86 ABP16 V _L CDR3 QQRLVFPPT 94 ABP17 V _L CDR3 QQHSVFPPT 94 ABP18 V _L CDR3 QQHSVFPPT 69 ABP19 V _L CDR3 MQKIGTPLT 78 ABP20 V _L CDR3 QQASLFPT 86 ABP21 V _L CDR3 QQRLVFPPT 94 ABP22 V _L CDR3 QQHSVFPPT 16 ABP23 V _L CDR3 QQEYATPPT 16 ABP24 V _L CDR3 QQEYATPPT 69 ABP25 V _L CDR3 MQKIGTPLT 78 ABP26 V _L CDR3 QQASLFPT 86 ABP27 V _L CDR3 QQRLVFPPT 94 ABP28 V _L CDR3 QQHSVFPPT 16 ABP29 V _L CDR3 QQEYATPPT 16 ABP30 V _L CDR3 QQEYATPPT 16 ABP31 V _L CDR3 QQEYATPPT 16 ABP32 V _L CDR3 QQEYATPPT 135 ABP33 V _L CDR3 MQALQTPIT 135 ABP34 V _L CDR3 MQALQTPIT 15 ABP1 V _L CDR2 AASSLQS 15 ABP2 V _L CDR2 AASSLQS 31 ABP3 V _L CDR2 AASSLKY 15 ABP4 V _L CDR2 AASSLQS 15 ABP5 V _L CDR2 AASSLQS 41 ABP6 V _L CDR2 AADSLQS 50 ABP7 V _L CDR2 AASSLDS 55 ABP8 V _L CDR2 SASSLES 15 ABP9 V _L CDR2 AASSLQS 15 ABP10 V _L CDR2 AASSLQS 68 ABP11 V _L CDR2 LGSNRAS 68 ABP12 V _L CDR2 LGSNRAS 77 ABP13 V _L CDR2 GASSLQS 85 ABP14 V _L CDR2 DASNRAT 85 ABP15 V _L CDR2 DASNRAT 85 ABP16 V _L CDR2 DASNRAT 85 ABP17 V _L CDR2 DASNRAT 85 ABP18 V _L CDR2 DASNRAT 68 ABP19 V _L CDR2 LGSNRAS 77 ABP20 V _L CDR2 GASSLQS 85 ABP21 V _L CDR2 DASNRAT 85 ABP22 V _L CDR2 DASNRAT 15 ABP23 V _L CDR2 AASSLQS 15 ABP24 V _L CDR2 AASSLQS 68 ABP25 V _L CDR2 LGSNRAS 77 ABP26 V _L CDR2 GASSLQS 85 ABP27 V _L CDR2 DASNRAT 85 ABP28 V _L CDR2 DASNRAT 15 ABP29 V _L CDR2 AASSLQS 15 ABP30 V _L CDR2 AASSLQS 15 ABP31 V _L CDR2 AASSLQS 15 ABP32 V _L CDR2 AASSLQS 68 ABP33 V _L CDR2 LGSNRAS 68 ABP34 V _L CDR2 LGSNRAS 14 ABP1 V _L CDR1 RASQSISSYLN 14 ABP2 V _L CDR1 RASQSISSYLN 14 ABP3 V _L CDR1 RASQSISSYLN 36 ABP4 V _L CDR1 RASKSIDSYLN 36 ABP5 V _L CDR1 RASKSIDSYLN 14 ABP6 V _L CDR1 RASQSISSYLN 49 ABP7 V _L CDR1 RASQSINSYLN 54 ABP8 V _L CDR1 GASQSISTYLN 14 ABP9 V _L CDR1 RASQSISSYLN 14 ABP10 V _L CDR1 RASQSISSYLN 67 ABP11 V _L CDR1 RSSQSLLHSNGYNYLD 67 ABP12 V _L CDR1 RSSQSLLHSNGYNYLD 76 ABP13 V _L CDR1 RASQGISSWLA 84 ABP14 V _L CDR1 RASQSVSSYLA 84 ABP15 V _L CDR1 RASQSVSSYLA 84 ABP16 V _L CDR1 RASQSVSSYLA 84 ABP17 V _L CDR1 RASQSVSSYLA 84 ABP18 V _L CDR1 RASQSVSSYLA 67 ABP19 V _L CDR1 RSSQSLLHSNGYNYLD 76 ABP20 V _L CDR1 RASQGISSWLA 84 ABP21 V _L CDR1 RASQSVSSYLA 84 ABP22 V _L CDR1 RASQSVSSYLA 14 ABP23 V _L CDR1 RASQSISSYLN 14 ABP24 V _L CDR1 RASQSISSYLN 67 ABP25 V _L CDR1 RSSQSLLHSNGYNYLD 76 ABP26 V _L CDR1 RASQGISSWLA 84 ABP27 V _L CDR1 RASQSVSSYLA 84 ABP28 V _L CDR1 RASQSVSSYLA 14 ABP29 V _L CDR1 RASQSISSYLN 14 ABP30 V _L CDR1 RASQSISSYLN 14 ABP31 V _L CDR1 RASQSISSYLN 14 ABP32 V _L CDR1 RASQSISSYLN 67 ABP33 V _L CDR1 RSSQSLLHSNGYNYLD 67 ABP34 V _L CDR1 RSSQSLLHSNGYNYLD 137 CH1 IgG1 constant region astkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 138 IgG4 S228P constant region astkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 139 IgG4 S228P without C-terminal Lys constant region astkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpre eqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslg 140 Kappa constant region rtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekhkvyacevthqglsspvtksfnrgec 141 CDRH3 Generalized Sequence 1 X ₁ X ₂ X ₃ X ₄ X ₅ RGYGDYGGHHAFDI where X ₁ is A or V, X ₂ IS H, D, L, or R, X ₃ IS E or D, X ₄ IS R, N, S or A AND X ₅ IS V, D or G 142 CDRH2 Generalized Sequence 1 X₁IX₂X₃SGX₄TYYNPSLKS, where X₁ IS G, L, or S, X₂REPRESENTS Y, A or V, X₃REPRESENTS E, Y or H, and X₄REPRESENTS S or K 143 CDRH1 Generalized Sequence 1 X₁sissx₂X₃X₄X₅wx₆, where X₁ REPRESENTS Y or G, X₂REPRESENTS G, S, or E X₃REPRESENTS L, G, S, Y or A, X₄REPRESENTS G, A, Y, M or G, X₅ IS V, A, or NONE AND X6 IS S or G 144 CDRL3 Generalized Sequence 1 QQEYX ₁ TPPX ₂ where X ₁ IS A or N AND X ₂ IS T or S 145 CDRL2 Generalized Sequence 1 X₁AX₂SLX₃X₄, where X₁ IS A or S, X₂ IS D or S, X₃REPRESENTS Q, D, K or E, and X₄ REPRESENTS S or Y 146 CDRL1 Generalized Sequence 1 X ₁ ASX ₂ SIX ₃ X4YLN where X ₁ IS G or R, X ₂ IS Q or K, X3 IS S, D or N, AND X ₄ IS S or T 147 CDRH2 Generalized Sequence 2 GIIPIFGEAQYAQX ₁ FX ₂ G where X ₁ IS K or R AND X ₂ IS Q or R 148 ABP35 Full length heavy chain, IgG1 N297A qvqlqesgpglvkpsetlsltcavsgysissglgwgwirqppgkglewiggiyesgstyynpslksrvtisvdtsknqfslklssvtaadtavyycahervrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 149 ABP36 Full length heavy chain, IgG1 N297A qvqlqesgpglvkpsqtlsltctvsggsissggavwswirqhpgkglewiggiaysgstyynpslksrvtisvdtsknqfslklssvtaadtavyycadenvrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 150 ABP37 Full length heavy chain, IgG1 N297A qvqlqesgpglvkpsetlsltcavsgysissgagwgwirqppgkglewiglivhsgstyynpslksrvtisvdtsknqfslklssvtaadtavyycvlesvrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 151 ABP38 Full length heavy chain, IgG1 N297A qvqlqesgpglvkpsetlsltcavsgysissgagwgwirqppgkgpewiglivhsgstyynpslksrvtisvdtsknqfslklssvtaadtavyycvlesvrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 152 ABP39 Full length heavy chain, IgG1 N297A qvqlqesgpglvkpsetlsltcavsgysissgagwgwirqppgkglewiglivhsgstyynpslksrvtisvdtsknqfslklssvtaadtavyycvlesvrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 153 ABP40 Full length heavy chain, IgG1 N297A qvqlqesgpglvkpsetlsltcavsgysisseymwgwirqppgkglewigliyhsgktyynpslksrvtisvdtsknqfslklssvtaadtavyycareadrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 154 ABP41 Full length heavy chain, IgG1 N297A qvqlqesgpglvkpsetlsltcavsgysisseymwgwirqppgkglewigliyhsgktyynpslksrvtisvdtsknqfslklssvtaadtavyycareadrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 155 ABP42 Full length heavy chain, IgG1 N297A qlqlqesgpglvkpsetlsltctvsggsissssyawgwirqppgkglewigsiyysgstyynpslksrvtisvdtsknqfslklssvtaadtavyycardsgrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqss glyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlpp srdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 156 ABP43 Full length heavy chain,
IgG4 S228P qlqlqesgpglvkpsetlsltctvsggsissssyawgwirqppgkglewigsiyysgstyynpslksrvtisvdtsknqfslklssvtaadtavyycardsgrgygdygghhafdiwgqgtmvtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssg lyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlpp sqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 157 ABP44 Full length heavy chain, IgG1 N297A qvqlvqsgaevkkpgssvkvsckasggtfssyyiswvrqapgqglewmggiipvpgtanyaqkfqgrvtitadeststaymelsslrsedtavyycaragggyargdhyygmdvwgqgttvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlq ssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvyt lppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 158 ABP45 Full length heavy chain, IgG1 N297A qvqlvqsgaevkkpgssvkvsckasggtfsrgaiswvrqapgqglewmggiipiegtayyaqkfqgrvtitadeststaymelsslrsedtavyycarqsdyglprgmdvwgqgttvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqss glyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlpp srdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 159 ABP46 Full length heavy chain, IgG1 N297A qvqlvqsgaevkkpgssvkvsckasggtfssyaiswvrqapgqglewmggiipisgfanyaqkfqgrvtitadeststaymelsslrsedtavyycaregghyysgwpywgqgtlvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsrdel tknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 160 ABP47 Full length heavy chain, IgG1 N297A qvqlvqsgaevkkpgssvkvsckasggtfvryaiswvrqapgqglewmggiipifgeaqyaqkfqgrvtitadeststaymelsslrsedtavyycaregyyygalpywgqgtlvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglysls svvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsrdelt knqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 161 ABP48 Full length heavy chain, IgG1 N297A qvqlqesgpglvkpsetlsltcavsgysisseymwgwirqppgkglewigliyhsgktyynpslksrvtisvdtsknqfslklssvtaadtavyycardsgrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 162 ABP49 Full length heavy chain, IgG1 N297A qvqlqesgpglvkpsqtlsltctvsggsissggavwswirqhpgkglewiggiaysgstyynpslksrvtisvdtsknqfslklssvtaadtavyycardsvrgygdygghhafdiwgqgtmvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqs sglyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytl ppsrdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 163 ABP50 Full length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG4 S228P) QVQLVQSGAEVKRPGSSVKVSCKASGGTFSSYYISWVRQVPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKRPGSSVKVSCKASGGTFSSYYISWVRQVPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 164 ABP51 Full length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG4 S228P) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQRLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQRLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapcsrs tsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsv ltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 165 ABP52 Full length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG4 S228P) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTGTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslss vvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTGTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSSastkgpsvfplapcsrstsestaalgcl vkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvvsvltvlhqd wlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 166 ABP53 Full length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG4 S228P) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapcsrstsestaalgclvkdyf pepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkey kckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 167 ABP54 Full length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG4 S228P) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQRLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQRLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapcsrstsestaalgclvkdyf pepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkey kckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 168 ABP55 Full length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG4 S228P) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGKVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssv vtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGKVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapcsrstsestaalgclvk dyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwl ngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 169 ABP56 Full length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG4 S228P) QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYGALPYWGQGTLVTVSSastkgpsvfplapcsrstsestaalgclvkdyf pepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkey kckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 170 ABP57 Full length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG4 S228P) QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFRGRATITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFRGRATITADESTSTAYMELSSLRSEDTAVYYCAREGYYGALPYWGQGTLVTVSSastkgpsvfplapcsrstsestaalgclvkdyf pepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkey kckvsnkglpssiektiskakgqprepqvytlppsqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 179 ABP58 Full length heavy chain, IgG1 N297A qvqlvqsgaevkkpgasvkvsckasgytftsyymhwvrqapgqglewmgiinpsggsttyaqkfqgrvtmtrdtststvymelsslrsedtavyycargqygyyggrldvwgqgttvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqss glyslssvvtvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlpp srdeltknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 180 ABP59 Full length heavy chain,
IgG4 S228P qvqlvqsgaevkkpgasvkvsckasgytftsyymhwvrqapgqglewmgiinpsggsttyaqkfqgrvtmtrdtststvymelsslrsedtavyycargqygyyggrldvwgqgttvtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssg lyslssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlpp sqeemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 181 ABP60 Full length heavy chain,
IgG1 N297A qvqlvesgggvvqpgrslrlscaasgftfssygmhwvrqapgkglewvavisydgsnkyyadsvkgrftisrdnskntlylqmnslraedtavyycardglgymawgqgttvtvssastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkkvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqyastyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsrdeltknq vsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 182 ABP61 Full length heavy chain, IgG4 S228P qvqlvesgggvvqpgrslrlscaasgftfssygmhwvrqapgkglewvavisydgsnkyyadsvkgrftisrdnskntlylqmnslraedtavyycardglgymawgqgttvtvssastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtv pssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtkn qvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgk 183 ABP62 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGLGWGWIRQPPGKGLEWIGGIYESGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAHERVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGLGWGWIRQPPGKGLEWIGGIYESGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAHERVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapssk stsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvs vltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 184 ABP63 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCADENVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapss kstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssg lyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCADENVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplaps skstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvv svltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 185 ABP64 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapssk stsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvs vltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 186 ABP65 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGPEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGPEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapssk stsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvs vltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 187 ABP66 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapssk stsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvs vltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 188 ABP67 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapssk stsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvs vltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 189 ABP68 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapssk stsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvs vltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 190 ABP69 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapssk stsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvs vltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 191 ABP70 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGLGWGWIRQPPGKGLEWIGGIYESGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAHERVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGLGWGWIRQPPGKGLEWIGGIYESGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAV YYCAHERVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 192 ABP71 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCADENVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAV YYCADENVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 193 ABP72 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVY YCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 194 ABP73 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGPEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGPEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVY YCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 195 ABP74 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVY YCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 196 ABP75 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVY YCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 197 ABP76 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADT AVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 198 ABP77 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADT AVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 199 ABP78 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLVQSGAEVKRPGSSVKVSCKASGGTFSSYYISWVRQVPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKRPGSSVKVSCKASGGTFSSYYISWVRQVPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapssk stsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvs vltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 200 ABP79 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQRLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQRLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapssk stsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpsssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvs vltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 201 ABP80 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTGTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslss vvtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTGTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalg clvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhq dwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgk 202 ABP81 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdy fpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlng keykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 203 ABP82 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQRLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQRLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdy fpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlng keykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 204 ABP83 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGKVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssv vtvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGKVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclv kdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdw lngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 205 ABP84 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdy fpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlng keykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 206 ABP85 Full-length heavy chain, TM with N-terminal Fab (Fab IgG1, IgG1 (G1m(3))) QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFRGRATITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFRGRATITADESTSTAYMELSSLRSEDTAVYYCAREGYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdy fpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlng keykckvsnkalpapiektiskakgqprepqvytlppsreemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgk 207 ABP86 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLVQSGAEVKRPGSSVKVSCKASGGTFSSYYISWVRQVPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLVQSGAEVKRPGSSVKVSCKASGGTFSSYYISWVRQVPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAV YYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 208 ABP87 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQRLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssgly slssvvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsre emtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQRLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAV YYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 209 ABP88 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTGTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslss vvtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtk nqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslslspgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTGTAYMELSSLRSEDTAVYY CARQSDYGLPRGMMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 210 ABP89 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknq vsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGG HYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 211 ABP90 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQRLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknq vsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQRLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGG HYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 212 ABP91 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGKVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssv vtvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtkn qvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGKVTITADESTSTAYMELSSLRSEDTAVYYCAR EGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 213 ABP92 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknq vsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGY YYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 214 ABP93 Full-length heavy chain, TM with C-terminal Fab, linker=5-member (IgG1 (G1m(3)), Fab IgG1) QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFRGRATITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtqtyicnvnhkpsntkvdkrvepkscdkthtcppcpapellggpsvflfppkpkdtlmisrtpevtcvvvdvshedpevkfnwyvdgvevhnaktkpreeqynstyrvvsvltvlhqdwlngkeykckvsnkalpapiektiskakgqprepqvytlppsreemtknq vsltclvkgfypsdiavewesngqpennykttppvldsdgsfflyskltvdksrwqqgnvfscsvmhealhnhytqkslslspgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFRGRATITADESTSTAYMELSSLRSEDTAVYYCAREGY YYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 8 ABP35 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 18 ABP36 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 25 ABP37 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLKYGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 33 ABP38 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 39 ABP39 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAADSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 43 ABP40 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSINSYLNWYQQKPGKAPKLLIYAASSLDSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 52 ABP41 Full length light chain DIQMTQSPSSLSASVGDRVTITCGASQSISTYLNWYQQKPGKAPKLLIYSASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPSFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 8 ABP42 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 8 ABP43 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 107 ABP44 Full length light chain DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQKIGTPLTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlska dyekhkvyacevthqglsspvtksfnrgec 109 ABP45 Full length light chain DIQLTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQASLFPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 111 ABP46 Full length light chain EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGTDFTLTISSLEPEDFAVYYCQQRLVFPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekhkvyacev thqglsspvtksfnrgec 113 ABP47 Full length light chain EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGTDFTLTISSLEPEDFAVYYCQQHSVFPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekhkvyacev thqglsspvtksfnrgec 8 ABP48 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 8 ABP49 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 107 ABP50 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 107 ABP51 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 109 ABP52 Full length light chain diqltqspssvsasvgdrvtitcrasqgisswlawyqqkpgkapklliygasslqsgvpsrfsgsgsgtdftltisslqpedfatyycqqaslfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsst ltlskadyekhkvyacevthqglsspvtksfnrgec 111 ABP53 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 111 ABP54 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 111 ABP55 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 113 ABP56 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec 113 ABP57 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec 107 ABP58 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqalqtpitfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdsty slsstltlskadyekhkvyacevthqglsspvtksfnrgec 107 ABP59 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqalqtpitfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdsty slsstltlskadyekhkvyacevthqglsspvtksfnrgec 109 ABP60 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqalqtpitfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdsty slsstltlskadyekhkvyacevthqglsspvtksfnrgec 111 ABP61 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqalqtpitfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdsty slsstltlskadyekhkvyacevthqglsspvtksfnrgec 8 ABP62 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 18 ABP63 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 25 ABP64 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLKYGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 33 ABP65 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 33 ABP66 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 39 ABP67 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAADSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 43 ABP68 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSINSYLNWYQQKPGKAPKLLIYAASSLDSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 52 ABP69 Full length light chain DIQMTQSPSSLSASVGDRVTITCGASQSISTYLNWYQQKPGKAPKLLIYSASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPSFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 8 ABP70 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 18 ABP71 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 25 ABP72 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLKYGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 33 ABP73 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 33 ABP74 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 39 ABP75 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAADSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 43 ABP76 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSINSYLNWYQQKPGKAPKLLIYAASSLDSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 52 ABP77 Full length light chain DIQMTQSPSSLSASVGDRVTITCGASQSISTYLNWYQQKPGKAPKLLIYSASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPSFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 107 ABP78 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 107 ABP79 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 109 ABP80 Full length light chain diqltqspssvsasvgdrvtitcrasqgisswlawyqqkpgkapklliygasslqsgvpsrfsgsgsgtdftltisslqpedfatyycqqaslfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsst ltlskadyekhkvyacevthqglsspvtksfnrgec 111 ABP81 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 111 ABP82 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 111 ABP83 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 113 ABP84 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec 113 ABP85 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec 107 ABP86 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 107 ABP87 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 109 ABP88 Full length light chain diqltqspssvsasvgdrvtitcrasqgisswlawyqqkpgkapklliygasslqsgvpsrfsgsgsgtdftltisslqpedfatyycqqaslfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsst ltlskadyekhkvyacevthqglsspvtksfnrgec 111 ABP89 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 111 ABP90 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 111 ABP91 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 113 ABP92 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec 113 ABP93 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec 114 ABP94 Full length heavy chain QVQLQESGPGLVKPSETLSLTCAVSGYSISSGLGWGWIRQPPGKGLEWIGGIYESGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAHERVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGLGWGWIRQPPGKGLEWIGGIYESGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCAHERVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 115 ABP95 Full length heavy chain QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCADENVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGAVWSWIRQHPGKGLEWIGGIAYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAA DTAVYYCADENVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 116 ABP96 Full length heavy chain QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADT AVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 117 ABP97 Full length heavy chain QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGPEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGPEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADT AVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 118 ABP98 Full length heavy chain QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADT AVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 119 ABP99 Full length heavy chain QVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSGAGWGWIRQPPGKGLEWIGLIVHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADT AVYYCVLESVRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 120 ABP100 Full length heavy chain QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVT AADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 121 ABP101 Full length heavy chain QVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLQESGPGLVKPSETLSLTCAVSGYSISSEYMWGWIRQPPGKGLEWIGLIYHSGKTYYNPSLKSRVTISVDTSKNQFSLKLSSVT AADTAVYYCAREADRGYGDYGGHHAFDIWGQGTMVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 122 ABP102 Full length heavy chain QVQLVQSGAEVKRPGSSVKVSCKASGGTFSSYYISWVRQVPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLVQSGAEVKRPGSSVKVSCKASGGTFSSYYISWVRQVPGQGLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSED TAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 123 ABP103 Full length heavy chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQRLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglys lssvvtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsq eemtknqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYISWVRQAPGQRLEWMGGIIPVPGTANYAQKFQGRVTITADESTSTAYMELSSLRSED TAVYYCARAGGGYARGDHYYGMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 124 ABP104 Full length heavy chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTGTAYMELSSLRSEDTAVYYCARQSDYGLPRGMDVWGQGTTVTVSSastkgpsvfplapcsrsstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssv vtvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemt knqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSRGAISWVRQAPGQGLEWMGGIIPIEGTAYYAQKFQGRVTITADESTGTAYMELSSLRSEDTAV YYCARQSDYGLPRGMMDVWGQGTTVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 125 ABP105 Full length heavy chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtv pssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtkn qvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR EGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 126 ABP106 Full length heavy chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQRLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtv pssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtkn qvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQRLEWMGGIIPISGFTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR EGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 127 ABP107 Full length heavy chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGKVTITADESTSTAYMELSSLRSEDTAVYYCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapcsrsstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvv tvpssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtk nqvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPISGFTNYAQKFQGKVTITADESTSTAYMELSSLRSEDTAVY YCAREGGHYYSGWPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 128 ABP108 Full length heavy chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtv pssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtkn qvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQRFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAR EGYYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 129 ABP109 Full length heavy chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFRGRATITADESTSTAYMELSSLRSEDTAVYYCAREGYYYGALPYWGQGTLVTVSSastkgpsvfplapcsrstsestaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtv pssslgtktytcnvdhkpsntkvdkrveskygppcppcpapeflggpsvflfppkpkpkdtlmisrtpevtcvvvdvsqedpevqfnwyvdgvevhnaktkpreeqfnstyrvvsvltvlhqdwlngkeykckvsnkglpssiektiskakgqprepqvytlppsqeemtkn qvsltclvkgfypsdiavewesngqpennykttppvldsdgsfflysrltvdksrwqegnvfscsvmhealhnhytqkslslslgkGGGGSQVQLVQSGAEVKKPGSSVKVSCKASGGTFVRYAISWVRQAPGQGLEWMGGIIPIFGEAQYAQKFRGRATITADESTSTAYMELSSLRSEDTAVYYCAR EGYYYGALPYWGQGTLVTVSSastkgpsvfplapsskstsggtaalgclvkdyfpepvtvswnsgaltsgvhtfpavlqssglyslssvvtvpssslgtqtyicnvnhkpsntkvdkrvepksc 8 ABP94 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYATPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 18 ABP95 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 25 ABP96 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLKYGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 33 ABP97 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 33 ABP98 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASKSIDSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 39 ABP99 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAADSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 43 ABP100 Full length light chain DIQMTQSPSSLSASVGDRVTITCRASQSINSYLNWYQQKPGKAPKLLIYAASSLDSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPTFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 52 ABP101 Full length light chain DIQMTQSPSSLSASVGDRVTITCGASQSISTYLNWYQQKPGKAPKLLIYSASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQEYNTPPSFGGGTKVEIKrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadyekh kvyacevthqglsspvtksfnrgec 107 ABP102 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 107 ABP103 Full length light chain divmtqsplslpvtpgepasiscrssqsllhsngynyldwylqkpgqspqlliylgsnrasgvpdrfsgsgsgtdftlkisrveaedvgvyycmqkigtpltfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskd styslsstltlskadyekhkvyacevthqglsspvtksfnrgec 109 ABP104 Full length light chain diqltqspssvsasvgdrvtitcrasqgisswlawyqqkpgkapklliygasslqsgvpsrfsgsgsgtdftltisslqpedfatyycqqaslfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsst ltlskadyekhkvyacevthqglsspvtksfnrgec 111 ABP105 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 111 ABP106 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 111 ABP107 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqrlvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskadye khkvyacevthqglsspvtksfnrgec 113 ABP108 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec 113 ABP109 Full length light chain eivltqspatlslspgeratlscrasqsvssylawyqqkpgqaprlliydasnratgiparfsgsgsgtdftltisslepedfavyycqqhsvfpptfgggtkveikrtvaapsvfifppsdeqlksgtasvvcllnnfypreakvqwkvdnalqsgnsqesvteqdskdstyslsstltlskady ekhkvyacevthqglsspvtksfnrgec

--->

SEQUENCE LIST

<110> POTENZA THERAPEUTICS, INC.

<120> ANTIGEN-BINDING PROTEINS AGAINST GITR AND METHODS OF THEIR USE

<130> 32248-38337/PCT

<140> PCT/US2017/062443

<141> 2017-11-19

<150> GC 2017/34287

<151> 2017-11-19

<150> 62/448.644

<151> 2017-01-20

<150> 62/497.428

<151> 2016-11-19

<160> 233

<170> PatentIn version 3.5

<210> 1

<211> 241

<212> PROTEIN

<213> Homo sapiens

<400> 1

Met Ala Gln His Gly Ala Met Gly Ala Phe Arg Ala Leu Cys Gly Leu

1 5 10 15

Ala Leu Leu Cys Ala Leu Ser Leu Gly Gln Arg Pro Thr Gly Gly Pro

20 25 30

Gly Cys Gly Pro Gly Arg Leu Leu Leu Gly Thr Gly Thr Asp Ala Arg

35 40 45

Cys Cys Arg Val His Thr Thr Arg Cys Cys Arg Asp Tyr Pro Gly Glu

50 55 60

Glu Cys Cys Ser Glu Trp Asp Cys Met Cys Val Gln Pro Glu Phe His

65 70 75 80

Cys Gly Asp Pro Cys Cys Thr Thr Cys Arg His His Pro Cys Pro Pro

85 90 95

Gly Gln Gly Val Gln Ser Gln Gly Lys Phe Ser Phe Gly Phe Gln Cys

100 105 110

Ile Asp Cys Ala Ser Gly Thr Phe Ser Gly Gly His Glu Gly His Cys

115 120 125

Lys Pro Trp Thr Asp Cys Thr Gln Phe Gly Phe Leu Thr Val Phe Pro

130 135 140

Gly Asn Lys Thr His Asn Ala Val Cys Val Pro Gly Ser Pro Pro Ala

145 150 155 160

Glu Pro Leu Gly Trp Leu Thr Val Val Leu Leu Ala Val Ala Ala Cys

165 170 175

Val Leu Leu Leu Thr Ser Ala Gln Leu Gly Leu His Ile Trp Gln Leu

180 185 190

Arg Ser Gln Cys Met Trp Pro Arg Glu Thr Gln Leu Leu Leu Glu Val

195 200 205

Pro Pro Ser Thr Glu Asp Ala Arg Ser Cys Gln Phe Pro Glu Glu Glu

210 215 220

Arg Gly Glu Arg Ser Ala Glu Glu Lys Gly Arg Leu Gly Asp Leu Trp

225 230 235 240

Val

<210> 2

<211> 241

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 2

Met Ala Gln His Gly Ala Met Gly Ala Phe Arg Ala Leu Cys Gly Leu

1 5 10 15

Ala Leu Leu Cys Ala Leu Ser Leu Gly Gln Arg Pro Thr Gly Gly Pro

20 25 30

Gly Cys Gly Pro Gly Arg Leu Leu Leu Gly Arg Gly Thr Asp Ala Arg

35 40 45

Cys Cys Arg Val His Thr Thr Arg Cys Cys Arg Asp Tyr Pro Gly Glu

50 55 60

Glu Cys Cys Ser Glu Trp Asp Cys Met Cys Val Gln Pro Glu Phe His

65 70 75 80

Cys Gly Asp Pro Cys Cys Thr Thr Cys Arg His His Pro Cys Pro Pro

85 90 95

Gly Gln Gly Val Gln Ser Gln Gly Lys Phe Ser Phe Gly Phe Gln Cys

100 105 110

Ile Asp Cys Ala Ser Gly Thr Phe Ser Gly Gly His Glu Gly His Cys

115 120 125

Lys Pro Trp Thr Asp Cys Thr Gln Phe Gly Phe Leu Thr Val Phe Pro

130 135 140

Gly Asn Lys Thr His Asn Ala Val Cys Val Pro Gly Ser Pro Pro Ala

145 150 155 160

Glu Pro Leu Gly Trp Leu Thr Val Val Leu Leu Ala Val Ala Ala Cys

165 170 175

Val Leu Leu Leu Thr Ser Ala Gln Leu Gly Leu His Ile Trp Gln Leu

180 185 190

Arg Ser Gln Cys Met Trp Pro Arg Glu Thr Gln Leu Leu Leu Glu Val

195 200 205

Pro Pro Ser Thr Glu Asp Ala Arg Ser Cys Gln Phe Pro Glu Glu Glu

210 215 220

Arg Gly Glu Arg Ser Ala Glu Glu Lys Gly Arg Leu Gly Asp Leu Trp

225 230 235 240

Val

<210> 3

<211> 235

<212> PROTEIN

<213> Macaca fascicularis

<400> 3

Met Cys Ala Cys Gly Thr Leu Cys Cys Leu Ala Leu Leu Cys Ala Ala

1 5 10 15

Ser Leu Gly Gln Arg Pro Thr Gly Gly Pro Gly Cys Gly Pro Gly Arg

20 25 30

Leu Leu Leu Gly Thr Gly Lys Asp Ala Arg Cys Cys Arg Val His Pro

35 40 45

Thr Arg Cys Cys Arg Asp Tyr Gln Ser Glu Glu Cys Cys Ser Glu Trp

50 55 60

Asp Cys Val Cys Val Gln Pro Glu Phe His Cys Gly Asn Pro Cys Cys

65 70 75 80

Thr Thr Cys Gln His His Pro Cys Pro Ser Gly Gln Gly Val Gln Pro

85 90 95

Gln Gly Lys Phe Ser Phe Gly Phe Arg Cys Val Asp Cys Ala Leu Gly

100 105 110

Thr Phe Ser Arg Gly His Asp Gly His Cys Lys Pro Trp Thr Asp Cys

115 120 125

Thr Gln Phe Gly Phe Leu Thr Val Phe Pro Gly Asn Lys Thr His Asn

130 135 140

Ala Val Cys Val Pro Gly Ser Pro Pro Ala Glu Pro Pro Gly Trp Leu

145 150 155 160

Thr Ile Val Leu Leu Ala Val Ala Ala Cys Val Leu Leu Leu Thr Ser

165 170 175

Ala Gln Leu Gly Leu His Ile Trp Gln Leu Gly Ser Gln Pro Thr Gly

180 185 190

Pro Arg Glu Thr Gln Leu Leu Leu Glu Val Pro Ser Thr Glu Asp

195 200 205

Ala Ser Ser Cys Gln Phe Pro Glu Glu Glu Arg Gly Glu Arg Leu Ala

210 215 220

Glu Glu Lys Gly Arg Leu Gly Asp Leu Trp Val

225 230 235

<210> 4

<211> 228

<212> PROTEIN

<213> Mus musculus

<400> 4

Met Gly Ala Trp Ala Met Leu Tyr Gly Val Ser Met Leu Cys Val Leu

1 5 10 15

Asp Leu Gly Gln Pro Ser Val Val Glu Glu Pro Gly Cys Gly Pro Gly

20 25 30

Lys Val Gln Asn Gly Ser Gly Asn Thr Arg Cys Cys Ser Leu Tyr

35 40 45

Ala Pro Gly Lys Glu Asp Cys Pro Lys Glu Arg Cys Ile Cys Val Thr

50 55 60

Pro Glu Tyr His Cys Gly Asp Pro Gln Cys Lys Ile Cys Lys His Tyr

65 70 75 80

Pro Cys Gln Pro Gly Gln Arg Val Glu Ser Gln Gly Asp Ile Val Phe

85 90 95

Gly Phe Arg Cys Val Ala Cys Ala Met Gly Thr Phe Ser Ala Gly Arg

100 105 110

Asp Gly His Cys Arg Leu Trp Thr Asn Cys Ser Gln Phe Gly Phe Leu

115 120 125

Thr Met Phe Pro Gly Asn Lys Thr His Asn Ala Val Cys Ile Pro Glu

130 135 140

Pro Leu Pro Thr Glu Gln Tyr Gly His Leu Thr Val Ile Phe Leu Val

145 150 155 160

Met Ala Ala Cys Ile Phe Phe Leu Thr Thr Val Gln Leu Gly Leu His

165 170 175

Ile Trp Gln Leu Arg Arg Gln His Met Cys Pro Arg Glu Thr Gln Pro

180 185 190

Phe Ala Glu Val Gln Leu Ser Ala Glu Asp Ala Cys Ser Phe Gln Phe

195 200 205

Pro Glu Glu Glu Arg Gly Glu Gln Thr Glu Glu Lys Cys His Leu Gly

210 215 220

Gly Arg Trp Pro

225

<210> 5

<211> 5

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide"

<400> 5

Gly Gly Gly Gly Ser

15

<210> 6

<211> 15

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 6

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1 5 10 15

<210> 7

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 7

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Leu Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Gly Ile Tyr Glu Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala His Glu Arg Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Leu Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile Tyr Glu

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala His Glu Arg Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

450 455 460

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

465 470 475 480

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

485 490 495

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

500 505 510

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

515 520 525

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

530 535 540

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

545 550 555 560

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

565 570 575

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

580 585 590

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

595 600 605

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

610 615 620

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

625 630 635 640

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

645 650 655

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

660 665 670

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

675 680 685

<210> 8

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 8

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Ala Thr Pro Pro

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 9

<211> 126

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 9

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Leu Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Gly Ile Tyr Glu Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala His Glu Arg Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 10

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 10

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Ala Thr Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 11

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 11

Tyr Ser Ile Ser Ser Gly Leu Gly Trp Gly

1 5 10

<210> 12

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 12

Gly Ile Tyr Glu Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser

1 5 10 15

<210> 13

<211> 19

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 13

Ala His Glu Arg Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

1 5 10 15

Phe Asp Ile

<210> 14

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 14

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

1 5 10

<210> 15

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 15

Ala Ala Ser Ser Leu Gln Ser

15

<210> 16

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 16

Gln Gln Glu Tyr Ala Thr Pro Pro Thr

15

<210> 17

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 17

Gln Gln Glu Tyr Asn Thr Pro Pro Thr

15

<210> 18

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 18

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 19

<211> 127

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 19

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Asp Glu Asn Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 20

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 20

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 21

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 21

Gly Ser Ile Ser Ser Gly Gly Ala Val Trp Ser

1 5 10

<210> 22

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 22

Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser

1 5 10 15

<210> 23

<211> 19

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide"

<400> 23

Ala Asp Glu Asn Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

1 5 10 15

Phe Asp Ile

<210> 24

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 24

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Val His

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

450 455 460

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

465 470 475 480

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

485 490 495

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

500 505 510

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

515 520 525

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

530 535 540

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

545 550 555 560

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

565 570 575

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

580 585 590

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

595 600 605

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

610 615 620

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

625 630 635 640

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

645 650 655

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

660 665 670

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

675 680 685

<210> 25

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 25

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Lys Tyr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 26

<211> 126

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 26

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 27

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 27

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Lys Tyr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 28

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 28

Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly

1 5 10

<210> 29

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 29

Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser

1 5 10 15

<210> 30

<211> 19

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 30

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

1 5 10 15

Phe Asp Ile

<210> 31

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 31

Ala Ala Ser Ser Leu Lys Tyr

15

<210> 32

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 32

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp Ile Gly Leu Ile Val His

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

450 455 460

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

465 470 475 480

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

485 490 495

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

500 505 510

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

515 520 525

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

530 535 540

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

545 550 555 560

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

565 570 575

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

580 585 590

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

595 600 605

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

610 615 620

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

625 630 635 640

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

645 650 655

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

660 665 670

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

675 680 685

<210> 33

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 33

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Lys Ser Ile Asp Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 34

<211> 126

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 34

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 35

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 35

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Lys Ser Ile Asp Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 36

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 36

Arg Ala Ser Lys Ser Ile Asp Ser Tyr Leu Asn

1 5 10

<210> 37

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 37

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Val His

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

450 455 460

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

465 470 475 480

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

485 490 495

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

500 505 510

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

515 520 525

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

530 535 540

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

545 550 555 560

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

565 570 575

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

580 585 590

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

595 600 605

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

610 615 620

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

625 630 635 640

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

645 650 655

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

660 665 670

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

675 680 685

<210> 38

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 38

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Val His

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

450 455 460

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

465 470 475 480

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

485 490 495

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

500 505 510

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

515 520 525

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

530 535 540

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

545 550 555 560

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

565 570 575

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

580 585 590

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

595 600 605

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

610 615 620

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

625 630 635 640

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

645 650 655

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

660 665 670

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

675 680 685

<210> 39

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 39

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Asp Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 40

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 40

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Asp Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 41

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 41

Ala Ala Asp Ser Leu Gln Ser

15

<210> 42

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 42

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Tyr His

275 280 285

Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Ala Asp Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

450 455 460

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

465 470 475 480

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

485 490 495

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

500 505 510

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

515 520 525

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

530 535 540

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

545 550 555 560

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

565 570 575

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

580 585 590

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

595 600 605

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

610 615 620

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

625 630 635 640

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

645 650 655

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

660 665 670

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

675 680 685

<210> 43

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 43

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Asn Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Asp Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 44

<211> 126

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 44

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 45

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 45

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Asn Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Asp Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 46

<211> 10

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide"

<400> 46

Tyr Ser Ile Ser Glu Tyr Met Trp Gly

1 5 10

<210> 47

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide"

<400> 47

Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser

1 5 10 15

<210> 48

<211> 19

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide"

<400> 48

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

1 5 10 15

Phe Asp Ile

<210> 49

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 49

Arg Ala Ser Gln Ser Ile Asn Ser Tyr Leu Asn

1 5 10

<210> 50

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 50

Ala Ala Ser Ser Leu Asp Ser

15

<210> 51

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 51

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Tyr His

275 280 285

Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Ala Asp Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

450 455 460

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

465 470 475 480

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

485 490 495

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

500 505 510

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

515 520 525

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

530 535 540

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

545 550 555 560

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

565 570 575

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

580 585 590

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

595 600 605

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

610 615 620

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

625 630 635 640

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

645 650 655

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

660 665 670

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

675 680 685

<210> 52

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 52

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 Gly Ala Ser Gln Ser Ile Ser Thr Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ser Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 53

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 53

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 Gly Ala Ser Gln Ser Ile Ser Thr Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ser Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Glu Tyr Asn Thr Pro Pro

85 90 95

Ser Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 54

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 54

Gly Ala Ser Gln Ser Ile Ser Thr Tyr Leu Asn

1 5 10

<210> 55

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 55

Ser Ala Ser Ser Leu Glu Ser

15

<210> 56

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 56

Gln Gln Glu Tyr Asn Thr Pro Pro Ser

15

<210> 57

<211> 689

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 57

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser

20 25 30

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

35 40 45

Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

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

130 135 140

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

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

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

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

195 200 205

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Leu Gln Leu Gln

225 230 235 240

Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr

245 250 255

Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser Ser Tyr Ala Trp Gly

260 265 270

Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Ser Ile

275 280 285

Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val

290 295 300

Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser

305 310 315 320

Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ser

325 330 335

Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp

340 345 350

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

355 360 365

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

370 375 380

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

385 390 395 400

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

405 410 415

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

420 425 430

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp

435 440 445

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr

450 455 460

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro

465 470 475 480

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

485 490 495

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp

500 505 510

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

515 520 525

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

530 535 540

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys

645 650 655

Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu

660 665 670

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

675 680 685

Lys

<210> 58

<211> 127

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 58

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser

20 25 30

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

35 40 45

Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 59

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 59

Gly Ser Ile Ser Ser Ser Ser Tyr Ala Trp Gly

1 5 10

<210> 60

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 60

Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser

1 5 10 15

<210> 61

<211> 19

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 61

Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

1 5 10 15

Phe Asp Ile

<210> 62

<211> 125

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 62

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Val Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

<210> 63

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 63

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Lys

85 90 95

Ile Gly Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 64

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 64

Gly Thr Phe Ser Ser Tyr Tyr Ile Ser

15

<210> 65

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 65

Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 66

<211> 18

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 66

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

1 5 10 15

Asp Val

<210> 67

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 67

Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu Asp

1 5 10 15

<210> 68

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 68

Leu Gly Ser Asn Arg Ala Ser

15

<210> 69

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 69

Met Gln Lys Ile Gly Thr Pro Leu Thr

15

<210> 70

<211> 125

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 70

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

<210> 71

<211> 121

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 71

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 72

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 72

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

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

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 73

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 73

Gly Thr Phe Ser Arg Gly Ala Ile Ser

15

<210> 74

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 74

Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 75

<211> 14

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 75

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val

1 5 10

<210> 76

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 76

Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala

1 5 10

<210> 77

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 77

Gly Ala Ser Ser Leu Gln Ser

15

<210> 78

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 78

Gln Gln Ala Ser Leu Phe Pro Pro Thr

15

<210> 79

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 79

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 80

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 80

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

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

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

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Leu Val Phe Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 81

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 81

Gly Thr Phe Ser Ser Tyr Ala Ile Ser

15

<210> 82

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 82

Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 83

<211> 13

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 83

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr

1 5 10

<210> 84

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 84

Arg Ala Ser Gln Ser Val Ser Ser Tyr Leu Ala

1 5 10

<210> 85

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 85

Asp Ala Ser Asn Arg Ala Thr

15

<210> 86

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 86

Gln Gln Arg Leu Val Phe Pro Pro Thr

15

<210> 87

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 87

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 88

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 88

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Lys Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 89

<211> 119

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 89

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Arg Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 90

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 90

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

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

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

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln His Ser Val Phe Pro Pro

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 91

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 91

Gly Thr Phe Val Arg Tyr Ala Ile Ser

15

<210> 92

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 92

Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Arg Phe Gln

1 5 10 15

gly

<210> 93

<211> 12

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 93

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr

1 5 10

<210> 94

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 94

Gln Gln His Ser Val Phe Pro Pro Thr

15

<210> 95

<211> 119

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 95

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 96

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 96

Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe Arg

1 5 10 15

gly

<210> 97

<211> 125

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 97

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 125

<210> 98

<211> 121

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 98

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 99

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 99

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 100

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 100

Gly Ile Ile Pro Ile Ser Gly Phe Ala Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 101

<211> 119

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 101

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 102

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 102

Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 103

<211> 19

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 103

Ala Arg Asp Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

1 5 10 15

Phe Asp Ile

<210> 104

<211> 126

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 104

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 105

<211> 127

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 105

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Arg Asp Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 106

<211> 684

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 106

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Arg Val Glu

210 215 220

Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser

225 230 235 240

Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys

245 250 255

Ala Ser Gly Gly Thr Phe Ser Ser Tyr Tyr Ile Ser Trp Val Arg Gln

260 265 270

Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Val Pro

275 280 285

Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr

290 295 300

Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg

305 310 315 320

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly Gly Gly Tyr

325 330 335

Ala Arg Gly Asp His Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr

340 345 350

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

355 360 365

Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly

370 375 380

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

385 390 395 400

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

405 410 415

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

420 425 430

Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser

435 440 445

Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys

450 455 460

Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu

465 470 475 480

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

485 490 495

Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln

500 505 510

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

515 520 525

Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu

530 535 540

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

545 550 555 560

Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys

565 570 575

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

580 585 590

Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

595 600 605

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

610 615 620

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

625 630 635 640

Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln

645 650 655

Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

660 665 670

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

675 680

<210> 107

<211> 219

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 107

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Lys

85 90 95

Ile Gly Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

115 120 125

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

130 135 140

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150 155 160

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

165 170 175

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

180 185 190

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

195 200 205

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 108

<211> 676

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 108

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

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

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

210 215 220

Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

225 230 235 240

Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly

245 250 255

Thr Phe Ser Arg Gly Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln

260 265 270

Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr

275 280 285

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser

290 295 300

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

305 310 315 320

Ala Val Tyr Tyr Cys Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly

325 330 335

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser

340 345 350

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

355 360 365

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

370 375 380

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

385 390 395 400

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

405 410 415

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

420 425 430

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

435 440 445

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

450 455 460

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

465 470 475 480

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

485 490 495

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

500 505 510

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

515 520 525

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

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

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

660 665 670

Leu Ser Leu Gly

675

<210> 109

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 109

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 110

<211> 674

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 110

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

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

115 120 125

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

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly

210 215 220

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

225 230 235 240

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

245 250 255

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly

260 265 270

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Ala Asn Tyr

275 280 285

Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr

290 295 300

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

305 310 315 320

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

325 330 335

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

340 345 350

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu

355 360 365

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

370 375 380

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

385 390 395 400

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

405 410 415

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn

420 425 430

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser

435 440 445

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly

450 455 460

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

465 470 475 480

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln

485 490 495

Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val

500 505 510

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

515 520 525

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val

625 630 635 640

Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met

645 650 655

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

660 665 670

Leu Gly

<210> 111

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 111

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

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

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

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Leu Val Phe Pro Pro

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 112

<211> 672

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 112

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

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

115 120 125

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

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

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

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly Gly

210 215 220

Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

225 230 235 240

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

245 250 255

Val Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

260 265 270

Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala

275 280 285

Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser

290 295 300

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

305 310 315 320

Tyr Tyr Cys Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp

325 330 335

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

340 345 350

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

355 360 365

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

370 375 380

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

385 390 395 400

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

405 410 415

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp

420 425 430

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr

435 440 445

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro

450 455 460

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

465 470 475 480

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp

485 490 495

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

500 505 510

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

515 520 525

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys

625 630 635 640

Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu

645 650 655

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

660 665 670

<210> 113

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 113

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

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

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

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln His Ser Val Phe Pro Pro

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Phe Asn Arg Gly Glu Cys

210

<210> 114

<211> 686

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 114

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Tyr His

275 280 285

Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ser Gly Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

450 455 460

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

465 470 475 480

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

485 490 495

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

500 505 510

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

515 520 525

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

530 535 540

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

545 550 555 560

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

565 570 575

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

580 585 590

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

595 600 605

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

610 615 620

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

625 630 635 640

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

645 650 655

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

660 665 670

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

675 680 685

<210> 115

<211> 688

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 115

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Arg Asp Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

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

130 135 140

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

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

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

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

195 200 205

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln

225 230 235 240

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

245 250 255

Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly Gly Ala Val Trp Ser

260 265 270

Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile

275 280 285

Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val

290 295 300

Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser

305 310 315 320

Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ser

325 330 335

Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp

340 345 350

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

355 360 365

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

370 375 380

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

385 390 395 400

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

405 410 415

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

420 425 430

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp

435 440 445

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr

450 455 460

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro

465 470 475 480

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

485 490 495

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp

500 505 510

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

515 520 525

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

530 535 540

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys

645 650 655

Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu

660 665 670

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

675 680 685

<210> 116

<211> 694

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 116

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Phe 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

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 Ser Gln Glu Glu Met Thr Lys Asn Gln Val

355 360 365

Ser Leu Thr 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 Arg 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 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

450 455 460

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

465 470 475 480

Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser

485 490 495

Ser Tyr Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu

500 505 510

Trp Met Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln

515 520 525

Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr

530 535 540

Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr

545 550 555 560

Tyr Cys Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr

565 570 575

Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala

580 585 590

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

595 600 605

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

610 615 620

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

625 630 635 640

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

645 650 655

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

660 665 670

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

675 680 685

Val Glu Pro Lys Ser Cys

690

<210> 117

<211> 686

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 117

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

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

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly 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 Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 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 Arg 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 Gly

435 440 445

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

450 455 460

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

465 470 475 480

Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly Ala Ile

485 490 495

Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly

500 505 510

Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe Gln Gly

515 520 525

Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu

530 535 540

Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

545 550 555 560

Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly Gln Gly

565 570 575

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

580 585 590

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

595 600 605

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

610 615 620

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

625 630 635 640

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

645 650 655

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

660 665 670

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 118

<211> 684

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 118

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

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

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

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

435 440 445

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln

450 455 460

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

465 470 475 480

Val Ser Cys Lys Ala Ser Gly Thr Phe Ser Ser Tyr Ala Ile Ser

485 490 495

Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile

500 505 510

Ile Pro Ile Ser Gly Phe Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg

515 520 525

Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu

530 535 540

Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser

645 650 655

Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn

660 665 670

Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680

<210> 119

<211> 682

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 119

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

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

115 120 125

Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

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

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val

260 265 270

Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

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

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

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

435 440 445

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu

450 455 460

Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val

465 470 475 480

Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr Ala Ile Ser Trp

485 490 495

Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile

500 505 510

Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe Gln Gly Arg Val

515 520 525

Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser

530 535 540

Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Gly

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly

645 650 655

Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys

660 665 670

Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680

<210> 120

<211> 696

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 120

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

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

245 250 255

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

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

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

290 295 300

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

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

450 455 460

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

465 470 475 480

Pro Ser Glu Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile

485 490 495

Ser Ser Glu Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly

500 505 510

Leu Glu Trp Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn

515 520 525

Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn

530 535 540

Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val

545 550 555 560

Tyr Tyr Cys Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly

565 570 575

His His Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser

580 585 590

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

595 600 605

Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp

610 615 620

Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr

625 630 635 640

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

645 650 655

Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln

660 665 670

Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp

675 680 685

Lys Arg Val Glu Pro Lys Ser Cys

690 695

<210> 121

<211> 698

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 121

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Arg Asp Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

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

130 135 140

Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

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

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr

195 200 205

Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

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

225 230 235 240

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

245 250 255

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

260 265 270

Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly

275 280 285

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn

290 295 300

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

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

Ser Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

450 455 460

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

465 470 475 480

Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser

485 490 495

Ile Ser Ser Gly Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly

500 505 510

Lys Gly Leu Glu Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr

515 520 525

Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser

530 535 540

Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr

545 550 555 560

Ala Val Tyr Tyr Cys Ala Arg Asp Ser Val Arg Gly Tyr Gly Asp Tyr

565 570 575

Gly Gly His His Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly

660 665 670

Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys

675 680 685

Val Asp Lys Arg Val Glu Pro Lys Ser Cys

690 695

<210> 122

<211> 686

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 122

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

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

245 250 255

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

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

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

290 295 300

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

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

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

450 455 460

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

465 470 475 480

Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp Gly Trp Ile Arg

485 490 495

Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Tyr His Ser

500 505 510

Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Ser

515 520 525

Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr

530 535 540

Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ser Gly Arg Gly

545 550 555 560

Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln Gly

565 570 575

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

580 585 590

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

595 600 605

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

610 615 620

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

625 630 635 640

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

645 650 655

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

660 665 670

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 123

<211> 688

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 123

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Arg Asp Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

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

130 135 140

Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

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

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr

195 200 205

Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

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

225 230 235 240

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

245 250 255

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

260 265 270

Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly

275 280 285

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn

290 295 300

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

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

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

450 455 460

Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys

465 470 475 480

Thr Val Ser Gly Gly Ser Ile Ser Ser Gly Gly Ala Val Trp Ser Trp

485 490 495

Ile Arg Gln His Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile Ala

500 505 510

Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr

515 520 525

Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser

530 535 540

Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ser Val

545 550 555 560

Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly

565 570 575

Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

580 585 590

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

595 600 605

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

610 615 620

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

625 630 635 640

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

645 650 655

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

660 665 670

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 124

<211> 672

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 124

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Ser Thr Thr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gln Tyr Gly Tyr Tyr Gly Gly Arg Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

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

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

210 215 220

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

225 230 235 240

Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

245 250 255

Thr Phe Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys

260 265 270

Gly Leu Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr

275 280 285

Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser

290 295 300

Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr

305 310 315 320

Ala Val Tyr Tyr Cys Ala Arg Asp Gly Leu Gly Tyr Met Ala Trp Gly

325 330 335

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

340 345 350

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

355 360 365

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

370 375 380

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

385 390 395 400

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

405 410 415

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

420 425 430

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

435 440 445

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser

450 455 460

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

465 470 475 480

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro

485 490 495

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

500 505 510

Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val

515 520 525

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

530 535 540

Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr

545 550 555 560

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

565 570 575

Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

580 585 590

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

595 600 605

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

610 615 620

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser

625 630 635 640

Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

645 650 655

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

660 665 670

<210> 125

<211> 219

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 125

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Ile Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

115 120 125

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

130 135 140

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150 155 160

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

165 170 175

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

180 185 190

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

195 200 205

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

210 215

<210> 126

<211> 121

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 126

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Ser Thr Thr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gln Tyr Gly Tyr Tyr Gly Gly Arg Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 127

<211> 116

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 127

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 Ser Ser Tyr

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

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

85 90 95

Ala Arg Asp Gly Leu Gly Tyr Met Ala Trp Gly Gln Gly Thr Thr Val

100 105 110

Thr Val Ser Ser

115

<210> 128

<211> 112

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 128

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Ile Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 129

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 129

Tyr Thr Phe Thr Ser Tyr Tyr Met His

15

<210> 130

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide"

<400> 130

Ile Ile Asn Pro Ser Gly Gly Ser Thr Thr Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 131

<211> 14

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide"

<400> 131

Ala Arg Gly Gln Tyr Gly Tyr Tyr Gly Gly Arg Leu Asp Val

1 5 10

<210> 132

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 132

Phe Thr Phe Ser Ser Tyr Gly Met His

15

<210> 133

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 133

Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys

1 5 10 15

gly

<210> 134

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 134

Ala Arg Asp Gly Leu Gly Tyr Met Ala

15

<210> 135

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<400> 135

Met Gln Ala Leu Gln Thr Pro Ile Thr

15

<210> 136

<211> 672

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 136

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 Ser Ser Tyr

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

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

85 90 95

Ala Arg Asp Gly Leu Gly Tyr Met Ala Trp Gly Gln Gly Thr Thr Val

100 105 110

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

115 120 125

Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu

130 135 140

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

145 150 155 160

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

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr

195 200 205

Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro

210 215 220

Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro

225 230 235 240

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

245 250 255

Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn

260 265 270

Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg

275 280 285

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val

290 295 300

Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser

305 310 315 320

Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys

325 330 335

Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu

340 345 350

Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe

355 360 365

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu

370 375 380

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

385 390 395 400

Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly

405 410 415

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr

420 425 430

Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser

435 440 445

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

450 455 460

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

465 470 475 480

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

485 490 495

Gly Ile Ile Asn Pro Ser Gly Ser Thr Thr Tyr Ala Gln Lys Phe

500 505 510

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

515 520 525

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

530 535 540

Ala Arg Gly Gln Tyr Gly Tyr Tyr Gly Gly Arg Leu Asp Val Trp Gly

545 550 555 560

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

565 570 575

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

580 585 590

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

595 600 605

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

610 615 620

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

625 630 635 640

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

645 650 655

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

660 665 670

<210> 137

<211> 103

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 137

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

1 5 10 15

Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

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

50 55 60

Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr

65 70 75 80

Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Arg Val Glu Pro Lys Ser Cys

100

<210> 138

<211> 327

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 138

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

1 5 10 15

Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

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

50 55 60

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

65 70 75 80

Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro

100 105 110

Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

115 120 125

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

130 135 140

Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp

145 150 155 160

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe

165 170 175

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

180 185 190

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu

195 200 205

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

210 215 220

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

225 230 235 240

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

245 250 255

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

260 265 270

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

275 280 285

Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser

290 295 300

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

305 310 315 320

Leu Ser Leu Ser Leu Gly Lys

325

<210> 139

<211> 326

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 139

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

1 5 10 15

Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr

20 25 30

Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser

35 40 45

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

50 55 60

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

65 70 75 80

Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys

85 90 95

Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro

100 105 110

Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

115 120 125

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

130 135 140

Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp

145 150 155 160

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe

165 170 175

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

180 185 190

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu

195 200 205

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

210 215 220

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

225 230 235 240

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

245 250 255

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

260 265 270

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

275 280 285

Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser

290 295 300

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

305 310 315 320

Leu Ser Leu Ser Leu Gly

325

<210> 140

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 140

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

1 5 10 15

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

20 25 30

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

35 40 45

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

50 55 60

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

65 70 75 80

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

85 90 95

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

100 105

<210> 141

<211> 19

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<220>

<221> OPTION

<222> (1)..(1)

<223> /replace="Val"

<220>

<221> OPTION

<222> (2)..(2)

<223> /replace="Asp" or "Leu" or "Arg"

<220>

<221> OPTION

<222> (3)..(3)

<223> /replace="Asp"

<220>

<221> OPTION

<222> (4)..(4)

<223> /replace="Asn" or "Ser" or "Ala"

<220>

<221> OPTION

<222> (5)..(5)

<223> /replace="Asp" or "Gly"

<220>

<221> UNDETERMINATED SIGN

<222> (1)..(19)

<223> /note="Residual options given in

sequences have no advantage over residues in

annotations of the positions of options"

<400> 141

Ala His Glu Arg Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

1 5 10 15

Phe Asp Ile

<210> 142

<211> 16

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<220>

<221> OPTION

<222> (1)..(1)

<223> /replace="Leu" or "Ser"

<220>

<221> OPTION

<222> (3)..(3)

<223> /replace="Ala" or "Val"

<220>

<221> OPTION

<222> (4)..(4)

<223> /replace="Tyr" or "His"

<220>

<221> OPTION

<222>(7)..(7)

<223> /replace="Lys"

<220>

<221> UNDETERMINATED SIGN

<222> (1)..(16)

<223> /note="Residual options given in

sequences have no advantage over residues in

annotations of the positions of options"

<400> 142

Gly Ile Tyr Glu Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser

1 5 10 15

<210> 143

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide"

<220>

<221> OPTION

<222> (1)..(1)

<223> /replace="Gly"

<220>

<221> OPTION

<222>(6)..(6)

<223> /replace="Ser" or "Glu"

<220>

<221> OPTION

<222>(7)..(7)

<223> /replace="Gly" or "Ser" or "Tyr" or "Ala"

<220>

<221> OPTION

<222>(8)..(8)

<223> /replace="Ala" or "Tyr" or "Met"

<220>

<221> OPTION

<222>(9)..(9)

<223> /replace="Ala" or " "

<220>

<221> OPTION

<222> (11)..(11)

<223> /replace="Gly"

<220>

<221> UNDETERMINATED SIGN

<222> (1)..(11)

<223> /note="Residual options given in

sequences have no advantage over residues in

annotations of the positions of options"

<400> 143

Tyr Ser Ile Ser Ser Gly Leu Gly Val Trp Ser

1 5 10

<210> 144

<211> 9

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<220>

<221> OPTION

<222> (5)..(5)

<223> /replace="Asn"

<220>

<221> OPTION

<222>(9)..(9)

<223> /replace="Ser"

<220>

<221> UNDETERMINATED SIGN

<222> (1)..(9)

<223> /note="Residual options given in

sequences have no advantage over residues in

annotations of the positions of options"

<400> 144

Gln Gln Glu Tyr Ala Thr Pro Pro Thr

15

<210> 145

<211> 7

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<220>

<221> OPTION

<222> (1)..(1)

<223> /replace="Ser"

<220>

<221> OPTION

<222> (3)..(3)

<223> /replace="Ser"

<220>

<221> OPTION

<222>(6)..(6)

<223> /replace="Asp" or "Lys" or "Glu"

<220>

<221> OPTION

<222>(7)..(7)

<223> /replace="Tyr"

<220>

<221> UNDETERMINATED SIGN

<222> (1)..(7)

<223> /note="Residual options given in

sequences have no advantage over residues in

annotations of the positions of options"

<400> 145

Ala Ala Asp Ser Leu Gln Ser

15

<210> 146

<211> 11

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<220>

<221> OPTION

<222> (1)..(1)

<223> /replace="Arg"

<220>

<221> OPTION

<222> (4)..(4)

<223> /replace="Lys"

<220>

<221> OPTION

<222>(7)..(7)

<223> /replace="Asp" or "Asn"

<220>

<221> OPTION

<222>(8)..(8)

<223> /replace="Thr"

<220>

<221> UNDETERMINATED SIGN

<222> (1)..(11)

<223> /note="Residual options given in

sequences have no advantage over residues in

annotations of options positions"

<400> 146

Gly Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn

1 5 10

<210> 147

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic

peptide"

<220>

<221> OPTION

<222> (14)..(14)

<223> /replace="Arg"

<220>

<221> OPTION

<222> (16)..(16)

<223> /replace="Arg"

<220>

<221> UNDETERMINATED SIGN

<222> (1)..(17)

<223> /note="Residual options given in

sequences do not take precedence over residues in

annotations of options positions"

<400> 147

Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 148

<211> 456

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 148

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Leu Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Gly Ile Tyr Glu Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala His Glu Arg Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val

210 215 220

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

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr Ala 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 Ala

325 330 335

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

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys

450 455

<210> 149

<211> 457

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 149

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Asp Glu Asn Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

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

130 135 140

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

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

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

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

195 200 205

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys

210 215 220

Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro

225 230 235 240

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

245 250 255

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

260 265 270

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

275 280 285

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

290 295 300

Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

305 310 315 320

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

325 330 335

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

340 345 350

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu

355 360 365

Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro

370 375 380

Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn

385 390 395 400

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

405 410 415

Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

420 425 430

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

435 440 445

Lys Ser Leu Ser Leu Ser Pro Gly Lys

450 455

<210> 150

<211> 456

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 150

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val

210 215 220

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

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr Ala 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 Ala

325 330 335

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

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys

450 455

<210> 151

<211> 456

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 151

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val

210 215 220

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

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr Ala 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 Ala

325 330 335

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

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys

450 455

<210> 152

<211> 456

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 152

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val

210 215 220

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

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr Ala 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 Ala

325 330 335

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

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys

450 455

<210> 153

<211> 456

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 153

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val

210 215 220

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

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr Ala 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 Ala

325 330 335

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

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys

450 455

<210> 154

<211> 456

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 154

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val

210 215 220

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

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr Ala 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 Ala

325 330 335

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

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys

450 455

<210> 155

<211> 457

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 155

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser

20 25 30

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

35 40 45

Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

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

130 135 140

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

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

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

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

195 200 205

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys

210 215 220

Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro

225 230 235 240

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

245 250 255

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

260 265 270

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

275 280 285

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

290 295 300

Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

305 310 315 320

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

325 330 335

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

340 345 350

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu

355 360 365

Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro

370 375 380

Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn

385 390 395 400

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

405 410 415

Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

420 425 430

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

435 440 445

Lys Ser Leu Ser Leu Ser Pro Gly Lys

450 455

<210> 156

<211> 454

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 156

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser

20 25 30

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

35 40 45

Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

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

130 135 140

Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

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

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr

195 200 205

Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

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

225 230 235 240

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

245 250 255

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

260 265 270

Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly

275 280 285

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn

290 295 300

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

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

Ser Leu Ser Leu Gly Lys

450

<210> 157

<211> 455

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 157

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 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

Ala 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

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 Ser Arg Asp Glu Leu Thr Lys

355 360 365

Asn Gln Val Ser Leu Thr 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 Lys

450 455

<210> 158

<211> 451

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 158

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

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

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys

210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

225 230 235 240

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

245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

260 265 270

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

275 280 285

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

290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

Pro Gly Lys

450

<210> 159

<211> 450

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 159

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

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

115 120 125

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

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp

210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

260 265 270

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

275 280 285

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

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

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

325 330 335

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

340 345 350

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450

<210> 160

<211> 449

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 160

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

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

115 120 125

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

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

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

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 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 His Glu Asp

260 265 270

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

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala 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 Ala Leu Pro Ala Pro 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 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

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 Gln 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 Pro Gly

435 440 445

Lys

<210> 161

<211> 456

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 161

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val

210 215 220

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

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr Ala 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 Ala

325 330 335

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

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys

450 455

<210> 162

<211> 457

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 162

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Arg Asp Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

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

130 135 140

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

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

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

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

195 200 205

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys

210 215 220

Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro

225 230 235 240

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

245 250 255

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

260 265 270

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

275 280 285

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

290 295 300

Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

305 310 315 320

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

325 330 335

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

340 345 350

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Asp Glu Leu

355 360 365

Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro

370 375 380

Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn

385 390 395 400

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

405 410 415

Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

420 425 430

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

435 440 445

Lys Ser Leu Ser Leu Ser Pro Gly Lys

450 455

<210> 163

<211> 685

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 163

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Val Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Arg Val Glu

210 215 220

Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser

225 230 235 240

Gly Ala Glu Val Lys Arg Pro Gly Ser Ser Val Lys Val Ser Cys Lys

245 250 255

Ala Ser Gly Gly Thr Phe Ser Ser Tyr Tyr Ile Ser Trp Val Arg Gln

260 265 270

Val Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Val Pro

275 280 285

Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr

290 295 300

Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg

305 310 315 320

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly Gly Gly Tyr

325 330 335

Ala Arg Gly Asp His Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr

340 345 350

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

355 360 365

Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly

370 375 380

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

385 390 395 400

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

405 410 415

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

420 425 430

Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser

435 440 445

Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys

450 455 460

Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu

465 470 475 480

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

485 490 495

Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln

500 505 510

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

515 520 525

Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu

530 535 540

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

545 550 555 560

Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys

565 570 575

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

580 585 590

Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

595 600 605

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

610 615 620

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

625 630 635 640

Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln

645 650 655

Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

660 665 670

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

675 680 685

<210> 164

<211> 685

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 164

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Arg Val Glu

210 215 220

Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser

225 230 235 240

Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys

245 250 255

Ala Ser Gly Gly Thr Phe Ser Ser Tyr Tyr Ile Ser Trp Val Arg Gln

260 265 270

Ala Pro Gly Gln Arg Leu Glu Trp Met Gly Gly Ile Ile Pro Val Pro

275 280 285

Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr

290 295 300

Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg

305 310 315 320

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly Gly Gly Tyr

325 330 335

Ala Arg Gly Asp His Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr

340 345 350

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

355 360 365

Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly

370 375 380

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

385 390 395 400

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

405 410 415

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

420 425 430

Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser

435 440 445

Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys

450 455 460

Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu

465 470 475 480

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

485 490 495

Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln

500 505 510

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

515 520 525

Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu

530 535 540

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

545 550 555 560

Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys

565 570 575

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

580 585 590

Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

595 600 605

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

610 615 620

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

625 630 635 640

Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln

645 650 655

Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

660 665 670

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

675 680 685

<210> 165

<211> 677

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 165

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

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

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

210 215 220

Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

225 230 235 240

Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly

245 250 255

Thr Phe Ser Arg Gly Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln

260 265 270

Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr

275 280 285

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser

290 295 300

Thr Gly Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

305 310 315 320

Ala Val Tyr Tyr Cys Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly

325 330 335

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser

340 345 350

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

355 360 365

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

370 375 380

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

385 390 395 400

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

405 410 415

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

420 425 430

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

435 440 445

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

450 455 460

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

465 470 475 480

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

485 490 495

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

500 505 510

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

515 520 525

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

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

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

660 665 670

Leu Ser Leu Gly Lys

675

<210> 166

<211> 675

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 166

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

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

115 120 125

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

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly

210 215 220

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

225 230 235 240

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

245 250 255

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly

260 265 270

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr

275 280 285

Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr

290 295 300

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

305 310 315 320

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

325 330 335

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

340 345 350

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu

355 360 365

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

370 375 380

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

385 390 395 400

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

405 410 415

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn

420 425 430

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser

435 440 445

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly

450 455 460

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

465 470 475 480

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln

485 490 495

Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val

500 505 510

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

515 520 525

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val

625 630 635 640

Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met

645 650 655

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

660 665 670

Leu Gly Lys

675

<210> 167

<211> 675

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 167

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

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

115 120 125

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

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly

210 215 220

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

225 230 235 240

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

245 250 255

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg

260 265 270

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr

275 280 285

Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr

290 295 300

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

305 310 315 320

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

325 330 335

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

340 345 350

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu

355 360 365

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

370 375 380

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

385 390 395 400

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

405 410 415

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn

420 425 430

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser

435 440 445

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly

450 455 460

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

465 470 475 480

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln

485 490 495

Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val

500 505 510

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

515 520 525

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val

625 630 635 640

Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met

645 650 655

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

660 665 670

Leu Gly Lys

675

<210> 168

<211> 675

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 168

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Lys Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

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

115 120 125

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

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly

210 215 220

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

225 230 235 240

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

245 250 255

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly

260 265 270

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr

275 280 285

Ala Gln Lys Phe Gln Gly Lys Val Thr Ile Thr Ala Asp Glu Ser Thr

290 295 300

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

305 310 315 320

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

325 330 335

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

340 345 350

Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu

355 360 365

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

370 375 380

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

385 390 395 400

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

405 410 415

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn

420 425 430

Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser

435 440 445

Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly

450 455 460

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

465 470 475 480

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln

485 490 495

Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val

500 505 510

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

515 520 525

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val

625 630 635 640

Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met

645 650 655

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

660 665 670

Leu Gly Lys

675

<210> 169

<211> 673

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 169

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Arg Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

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

115 120 125

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

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

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

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly Gly

210 215 220

Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

225 230 235 240

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

245 250 255

Val Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

260 265 270

Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala

275 280 285

Gln Arg Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser

290 295 300

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

305 310 315 320

Tyr Tyr Cys Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp

325 330 335

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

340 345 350

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

355 360 365

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

370 375 380

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

385 390 395 400

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

405 410 415

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp

420 425 430

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr

435 440 445

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro

450 455 460

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

465 470 475 480

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp

485 490 495

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

500 505 510

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

515 520 525

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys

625 630 635 640

Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu

645 650 655

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

660 665 670

Lys

<210> 170

<211> 673

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 170

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

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

115 120 125

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

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

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

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly Gly

210 215 220

Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

225 230 235 240

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

245 250 255

Val Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

260 265 270

Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala

275 280 285

Gln Lys Phe Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu Ser Thr Ser

290 295 300

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

305 310 315 320

Tyr Tyr Cys Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp

325 330 335

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

340 345 350

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

355 360 365

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

370 375 380

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

385 390 395 400

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

405 410 415

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp

420 425 430

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr

435 440 445

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro

450 455 460

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

465 470 475 480

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp

485 490 495

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

500 505 510

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

515 520 525

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys

625 630 635 640

Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu

645 650 655

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

660 665 670

Lys

<210> 171

<211> 455

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 171

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Val Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 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

Ala 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

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 Ser Arg Asp Glu Leu Thr Lys

355 360 365

Asn Gln Val Ser Leu Thr 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 Lys

450 455

<210> 172

<211> 455

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 172

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 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

Ala 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

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 Ser Arg Asp Glu Leu Thr Lys

355 360 365

Asn Gln Val Ser Leu Thr 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 Lys

450 455

<210> 173

<211> 451

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 173

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

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

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys

210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

225 230 235 240

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

245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

260 265 270

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

275 280 285

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

290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

Pro Gly Lys

450

<210> 174

<211> 450

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 174

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

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

115 120 125

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

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp

210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

260 265 270

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

275 280 285

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

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

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

325 330 335

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

340 345 350

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450

<210> 175

<211> 450

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 175

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

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

115 120 125

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

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp

210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

260 265 270

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

275 280 285

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

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

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

325 330 335

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

340 345 350

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450

<210> 176

<211> 450

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 176

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Lys Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

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

115 120 125

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

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp

210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

260 265 270

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

275 280 285

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

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

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

325 330 335

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

340 345 350

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys

450

<210> 177

<211> 449

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 177

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Arg Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

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

115 120 125

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

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

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

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 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 His Glu Asp

260 265 270

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

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala 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 Ala Leu Pro Ala Pro 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 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

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 Gln 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 Pro Gly

435 440 445

Lys

<210> 178

<211> 449

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 178

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

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

115 120 125

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

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

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

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 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 His Glu Asp

260 265 270

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

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala 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 Ala Leu Pro Ala Pro 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 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

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 Gln 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 Pro Gly

435 440 445

Lys

<210> 179

<211> 451

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 179

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Ser Thr Thr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gln Tyr Gly Tyr Tyr Gly Gly Arg Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

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

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys

210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

225 230 235 240

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

245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

260 265 270

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

275 280 285

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

290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

Pro Gly Lys

450

<210> 180

<211> 448

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 180

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Ser Thr Thr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gly Gln Tyr Gly Tyr Tyr Gly Gly Arg Leu Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

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

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly 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 Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 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 Arg 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 Lys

435 440 445

<210> 181

<211> 446

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 181

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 Ser Ser Tyr

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

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

85 90 95

Ala Arg Asp Gly Leu Gly Tyr Met Ala Trp Gly Gln Gly Thr Thr Val

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr

195 200 205

Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val

260 265 270

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

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

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

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

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

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

435 440 445

<210> 182

<211> 443

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 182

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 Ser Ser Tyr

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

65 70 75 80

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

85 90 95

Ala Arg Asp Gly Leu Gly Tyr Met Ala Trp Gly Gln Gly Thr Thr Val

100 105 110

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

115 120 125

Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu

130 135 140

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

145 150 155 160

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

165 170 175

Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu

180 185 190

Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr

195 200 205

Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro

210 215 220

Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro

225 230 235 240

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

245 250 255

Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn

260 265 270

Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg

275 280 285

Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val

290 295 300

Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser

305 310 315 320

Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys

325 330 335

Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu

340 345 350

Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe

355 360 365

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu

370 375 380

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

385 390 395 400

Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly

405 410 415

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr

420 425 430

Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440

<210> 183

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 183

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Leu Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Gly Ile Tyr Glu Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala His Glu Arg Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Leu Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile Tyr Glu

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala His Glu Arg Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

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

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

450 455 460

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

465 470 475 480

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

485 490 495

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

500 505 510

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

515 520 525

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

530 535 540

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

660 665 670

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

675 680 685

Gly Lys

690

<210> 184

<211> 692

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 184

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

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

85 90 95

Cys Ala Asp Glu Asn Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

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

130 135 140

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

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

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

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

195 200 205

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln

225 230 235 240

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

245 250 255

Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly Gly Ala Val Trp Ser

260 265 270

Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile

275 280 285

Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val

290 295 300

Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser

305 310 315 320

Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Asp Glu Asn

325 330 335

Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp

340 345 350

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

355 360 365

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

370 375 380

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

385 390 395 400

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

405 410 415

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

420 425 430

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

435 440 445

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser

450 455 460

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

465 470 475 480

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

485 490 495

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

500 505 510

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

515 520 525

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

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

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

660 665 670

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

675 680 685

Ser Pro Gly Lys

690

<210> 185

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 185

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Val His

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

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

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

450 455 460

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

465 470 475 480

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

485 490 495

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

500 505 510

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

515 520 525

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

530 535 540

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

660 665 670

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

675 680 685

Gly Lys

690

<210> 186

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 186

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp Ile Gly Leu Ile Val His

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

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

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

450 455 460

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

465 470 475 480

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

485 490 495

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

500 505 510

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

515 520 525

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

530 535 540

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

660 665 670

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

675 680 685

Gly Lys

690

<210> 187

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 187

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Val His

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

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

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

450 455 460

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

465 470 475 480

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

485 490 495

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

500 505 510

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

515 520 525

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

530 535 540

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

660 665 670

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

675 680 685

Gly Lys

690

<210> 188

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 188

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Val His

275 280 285

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

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

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

450 455 460

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

465 470 475 480

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

485 490 495

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

500 505 510

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

515 520 525

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

530 535 540

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

660 665 670

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

675 680 685

Gly Lys

690

<210> 189

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 189

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Tyr His

275 280 285

Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Ala Asp Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

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

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

450 455 460

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

465 470 475 480

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

485 490 495

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

500 505 510

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

515 520 525

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

530 535 540

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

660 665 670

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

675 680 685

Gly Lys

690

<210> 190

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 190

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

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

130 135 140

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

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

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

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

225 230 235 240

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

245 250 255

Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp Gly Trp Ile

260 265 270

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Tyr His

275 280 285

Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

290 295 300

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

305 310 315 320

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Ala Asp Arg

325 330 335

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

340 345 350

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

355 360 365

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

370 375 380

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

385 390 395 400

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

405 410 415

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

420 425 430

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

435 440 445

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

450 455 460

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

465 470 475 480

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

485 490 495

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

500 505 510

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

515 520 525

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

530 535 540

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

625 630 635 640

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

645 650 655

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

660 665 670

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

675 680 685

Gly Lys

690

<210> 191

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 191

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Leu Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Gly Ile Tyr Glu Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala His Glu Arg Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

130 135 140

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr 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 Ala

325 330 335

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys Gly Gly Gly Gly Ser Gln Val Gln

450 455 460

Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser

465 470 475 480

Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Leu Gly Trp

485 490 495

Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly

500 505 510

Ile Tyr Glu Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg

515 520 525

Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu

530 535 540

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala His Glu

545 550 555 560

Arg Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile

565 570 575

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly

580 585 590

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly

595 600 605

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

610 615 620

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

625 630 635 640

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

645 650 655

Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val

660 665 670

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys

675 680 685

Ser Cys

690

<210> 192

<211> 692

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 192

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Asp Glu Asn Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser

130 135 140

Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

195 200 205

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro

225 230 235 240

Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys

245 250 255

Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val

260 265 270

Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr

275 280 285

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

290 295 300

Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

305 310 315 320

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

325 330 335

Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

340 345 350

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met

355 360 365

Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro

370 375 380

Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn

385 390 395 400

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu

405 410 415

Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

420 425 430

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

435 440 445

Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Gly Gly Ser Gln Val

450 455 460

Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu

465 470 475 480

Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly Gly Ala

485 490 495

Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu Trp Ile

500 505 510

Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys

515 520 525

Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu

530 535 540

Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

545 550 555 560

Asp Glu Asn Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe

565 570 575

Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr

580 585 590

Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser

595 600 605

Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu

610 615 620

Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His

625 630 635 640

Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser

645 650 655

Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys

660 665 670

Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu

675 680 685

Pro Lys Ser Cys

690

<210> 193

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 193

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

130 135 140

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr 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 Ala

325 330 335

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys Gly Gly Gly Gly Ser Gln Val Gln

450 455 460

Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser

465 470 475 480

Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp

485 490 495

Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu

500 505 510

Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg

515 520 525

Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu

530 535 540

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu

545 550 555 560

Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile

565 570 575

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly

580 585 590

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly

595 600 605

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

610 615 620

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

625 630 635 640

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

645 650 655

Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val

660 665 670

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys

675 680 685

Ser Cys

690

<210> 194

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 194

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

130 135 140

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr 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 Ala

325 330 335

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys Gly Gly Gly Gly Ser Gln Val Gln

450 455 460

Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser

465 470 475 480

Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp

485 490 495

Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp Ile Gly Leu

500 505 510

Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg

515 520 525

Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu

530 535 540

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu

545 550 555 560

Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile

565 570 575

Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly

580 585 590

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly

595 600 605

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

610 615 620

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

625 630 635 640

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

645 650 655

Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val

660 665 670

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys

675 680 685

Ser Cys

690

<210> 195

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 195

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

130 135 140

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr 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 Ala

325 330 335

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys Gly Gly Gly Gly Ser Gln Val Gln

450 455 460

Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser

465 470 475 480

Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp

485 490 495

Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu

500 505 510

Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg

515 520 525

Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu

530 535 540

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu

545 550 555 560

Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile

565 570 575

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly

580 585 590

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly

595 600 605

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

610 615 620

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

625 630 635 640

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

645 650 655

Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val

660 665 670

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys

675 680 685

Ser Cys

690

<210> 196

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 196

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

130 135 140

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr 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 Ala

325 330 335

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys Gly Gly Gly Gly Ser Gln Val Gln

450 455 460

Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser

465 470 475 480

Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp

485 490 495

Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu

500 505 510

Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg

515 520 525

Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu

530 535 540

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu

545 550 555 560

Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile

565 570 575

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly

580 585 590

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly

595 600 605

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

610 615 620

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

625 630 635 640

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

645 650 655

Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val

660 665 670

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys

675 680 685

Ser Cys

690

<210> 197

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 197

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

130 135 140

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr 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 Ala

325 330 335

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys Gly Gly Gly Gly Ser Gln Val Gln

450 455 460

Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser

465 470 475 480

Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp

485 490 495

Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu

500 505 510

Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg

515 520 525

Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu

530 535 540

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu

545 550 555 560

Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile

565 570 575

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly

580 585 590

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly

595 600 605

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

610 615 620

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

625 630 635 640

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

645 650 655

Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val

660 665 670

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys

675 680 685

Ser Cys

690

<210> 198

<211> 690

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 198

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

130 135 140

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

195 200 205

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

225 230 235 240

Pro Glu Leu Leu 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 His Glu Asp Pro Glu Val Lys 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

Tyr 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 Ala

325 330 335

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

340 345 350

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr

355 360 365

Lys Asn Gln Val Ser Leu Thr 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 Gln 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 Pro Gly Lys Gly Gly Gly Gly Ser Gln Val Gln

450 455 460

Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser

465 470 475 480

Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp

485 490 495

Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu

500 505 510

Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg

515 520 525

Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu

530 535 540

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu

545 550 555 560

Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile

565 570 575

Trp Gly Glyn Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly

580 585 590

Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly

595 600 605

Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val

610 615 620

Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe

625 630 635 640

Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

645 650 655

Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val

660 665 670

Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys

675 680 685

Ser Cys

690

<210> 199

<211> 688

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 199

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Val Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Arg Val Glu

210 215 220

Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser

225 230 235 240

Gly Ala Glu Val Lys Arg Pro Gly Ser Ser Val Lys Val Ser Cys Lys

245 250 255

Ala Ser Gly Gly Thr Phe Ser Ser Tyr Tyr Ile Ser Trp Val Arg Gln

260 265 270

Val Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Val Pro

275 280 285

Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr

290 295 300

Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg

305 310 315 320

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly Gly Gly Tyr

325 330 335

Ala Arg Gly Asp His Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr

340 345 350

Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro

355 360 365

Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly

370 375 380

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

385 390 395 400

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

405 410 415

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

420 425 430

Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser

435 440 445

Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr

450 455 460

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

465 470 475 480

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

485 490 495

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

500 505 510

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

515 520 525

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

530 535 540

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

545 550 555 560

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

565 570 575

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

580 585 590

Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

595 600 605

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

610 615 620

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

625 630 635 640

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

645 650 655

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

660 665 670

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

675 680 685

<210> 200

<211> 688

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 200

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Arg Val Glu

210 215 220

Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser

225 230 235 240

Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys

245 250 255

Ala Ser Gly Gly Thr Phe Ser Ser Tyr Tyr Ile Ser Trp Val Arg Gln

260 265 270

Ala Pro Gly Gln Arg Leu Glu Trp Met Gly Gly Ile Ile Pro Val Pro

275 280 285

Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr

290 295 300

Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg

305 310 315 320

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly Gly Gly Tyr

325 330 335

Ala Arg Gly Asp His Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr

340 345 350

Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro

355 360 365

Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly

370 375 380

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

385 390 395 400

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

405 410 415

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

420 425 430

Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser

435 440 445

Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr

450 455 460

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

465 470 475 480

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

485 490 495

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

500 505 510

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

515 520 525

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

530 535 540

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

545 550 555 560

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

565 570 575

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

580 585 590

Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys

595 600 605

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

610 615 620

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

625 630 635 640

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

645 650 655

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

660 665 670

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

675 680 685

<210> 201

<211> 680

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 201

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

210 215 220

Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

225 230 235 240

Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly

245 250 255

Thr Phe Ser Arg Gly Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln

260 265 270

Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr

275 280 285

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser

290 295 300

Thr Gly Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

305 310 315 320

Ala Val Tyr Tyr Cys Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly

325 330 335

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser

340 345 350

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

355 360 365

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

370 375 380

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

385 390 395 400

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

405 410 415

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

420 425 430

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

435 440 445

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala

450 455 460

Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro

465 470 475 480

Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val

485 490 495

Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val

500 505 510

Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln

515 520 525

Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln

530 535 540

Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala

545 550 555 560

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

565 570 575

Arg Glu Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr

580 585 590

Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser

595 600 605

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr

610 615 620

Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

625 630 635 640

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe

645 650 655

Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys

660 665 670

Ser Leu Ser Leu Ser Pro Gly Lys

675 680

<210> 202

<211> 678

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 202

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly

210 215 220

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

225 230 235 240

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

245 250 255

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly

260 265 270

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr

275 280 285

Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr

290 295 300

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

305 310 315 320

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

325 330 335

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys

340 345 350

Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly

355 360 365

Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro

370 375 380

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

385 390 395 400

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

405 410 415

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn

420 425 430

Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro

435 440 445

Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

450 455 460

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

465 470 475 480

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

485 490 495

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

500 505 510

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

515 520 525

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

530 535 540

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

545 550 555 560

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

565 570 575

Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr Lys Asn

580 585 590

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

595 600 605

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

610 615 620

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

625 630 635 640

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

645 650 655

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

660 665 670

Ser Leu Ser Pro Gly Lys

675

<210> 203

<211> 678

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 203

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly

210 215 220

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

225 230 235 240

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

245 250 255

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg

260 265 270

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr

275 280 285

Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr

290 295 300

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

305 310 315 320

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

325 330 335

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys

340 345 350

Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly

355 360 365

Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro

370 375 380

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

385 390 395 400

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

405 410 415

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn

420 425 430

Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro

435 440 445

Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

450 455 460

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

465 470 475 480

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

485 490 495

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

500 505 510

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

515 520 525

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

530 535 540

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

545 550 555 560

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

565 570 575

Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr Lys Asn

580 585 590

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

595 600 605

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

610 615 620

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

625 630 635 640

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

645 650 655

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

660 665 670

Ser Leu Ser Pro Gly Lys

675

<210> 204

<211> 678

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 204

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Lys Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly

210 215 220

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

225 230 235 240

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

245 250 255

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly

260 265 270

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr

275 280 285

Ala Gln Lys Phe Gln Gly Lys Val Thr Ile Thr Ala Asp Glu Ser Thr

290 295 300

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

305 310 315 320

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

325 330 335

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys

340 345 350

Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly

355 360 365

Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro

370 375 380

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

385 390 395 400

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

405 410 415

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn

420 425 430

Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro

435 440 445

Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

450 455 460

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

465 470 475 480

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

485 490 495

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

500 505 510

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

515 520 525

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

530 535 540

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

545 550 555 560

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

565 570 575

Pro Gln Val Tyr Thr Leu Pro Ser Arg Glu Glu Met Thr Lys Asn

580 585 590

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

595 600 605

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

610 615 620

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

625 630 635 640

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

645 650 655

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

660 665 670

Ser Leu Ser Pro Gly Lys

675

<210> 205

<211> 676

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 205

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Arg Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly Gly

210 215 220

Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

225 230 235 240

Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe

245 250 255

Val Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

260 265 270

Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala

275 280 285

Gln Arg Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser

290 295 300

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

305 310 315 320

Tyr Tyr Cys Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp

325 330 335

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

340 345 350

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

355 360 365

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

370 375 380

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

385 390 395 400

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

405 410 415

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

420 425 430

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser

435 440 445

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

450 455 460

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

465 470 475 480

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

485 490 495

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

500 505 510

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

515 520 525

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

530 535 540

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

545 550 555 560

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

565 570 575

Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val

580 585 590

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

595 600 605

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

610 615 620

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

625 630 635 640

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

645 650 655

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

660 665 670

Ser Pro Gly Lys

675

<210> 206

<211> 676

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 206

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Gly Gly

210 215 220

Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

225 230 235 240

Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe

245 250 255

Val Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

260 265 270

Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala

275 280 285

Gln Lys Phe Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu Ser Thr Ser

290 295 300

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

305 310 315 320

Tyr Tyr Cys Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp

325 330 335

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

340 345 350

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

355 360 365

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

370 375 380

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

385 390 395 400

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

405 410 415

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

420 425 430

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser

435 440 445

Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

450 455 460

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

465 470 475 480

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

485 490 495

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

500 505 510

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

515 520 525

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

530 535 540

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

545 550 555 560

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

565 570 575

Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val

580 585 590

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

595 600 605

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

610 615 620

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

625 630 635 640

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

645 650 655

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

660 665 670

Ser Pro Gly Lys

675

<210> 207

<211> 688

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 207

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Val Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Arg 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 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

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 Ser Arg Glu Glu Met Thr Lys

355 360 365

Asn Gln Val Ser Leu Thr 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 Lys Gly Gly Gly Gly Ser Gln Val Gln Leu

450 455 460

Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser Ser Val Lys Val

465 470 475 480

Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr Tyr Ile Ser Trp

485 490 495

Val Arg Gln Val Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile

500 505 510

Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val

515 520 525

Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser

530 535 540

Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly

545 550 555 560

Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met Asp Val Trp Gly

565 570 575

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

580 585 590

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

595 600 605

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

610 615 620

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

625 630 635 640

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

645 650 655

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

660 665 670

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 208

<211> 688

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 208

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Arg 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 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

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 Ser Arg Glu Glu Met Thr Lys

355 360 365

Asn Gln Val Ser Leu Thr 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 Lys Gly Gly Gly Gly Ser Gln Val Gln Leu

450 455 460

Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val

465 470 475 480

Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr Tyr Ile Ser Trp

485 490 495

Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met Gly Gly Ile Ile

500 505 510

Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val

515 520 525

Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser

530 535 540

Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly

545 550 555 560

Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met Asp Val Trp Gly

565 570 575

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

580 585 590

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

595 600 605

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

610 615 620

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

625 630 635 640

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

645 650 655

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

660 665 670

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 209

<211> 680

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 209

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

275 280 285

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr

290 295 300

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

305 310 315 320

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

325 330 335

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val

340 345 350

Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser

355 360 365

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu

370 375 380

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

385 390 395 400

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

405 410 415

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

420 425 430

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

435 440 445

Pro Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly

450 455 460

Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala

465 470 475 480

Ser Gly Gly Thr Phe Ser Arg Gly Ala Ile Ser Trp Val Arg Gln Ala

485 490 495

Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Glu Gly

500 505 510

Thr Ala Tyr Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala

515 520 525

Asp Glu Ser Thr Gly Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser

530 535 540

Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gln Ser Asp Tyr Gly Leu

545 550 555 560

Pro Arg Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser

565 570 575

Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser

580 585 590

Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp

595 600 605

Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr

610 615 620

Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Ser Gly Leu Tyr

625 630 635 640

Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln

645 650 655

Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp

660 665 670

Lys Arg Val Glu Pro Lys Ser Cys

675 680

<210> 210

<211> 678

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 210

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala

450 455 460

Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser

465 470 475 480

Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro

485 490 495

Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe

500 505 510

Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp

515 520 525

Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu

530 535 540

Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser

545 550 555 560

Gly Trp Pro Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala

565 570 575

Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser

580 585 590

Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

595 600 605

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

610 615 620

Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu

625 630 635 640

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

645 650 655

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

660 665 670

Val Glu Pro Lys Ser Cys

675

<210> 211

<211> 678

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 211

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala

450 455 460

Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser

465 470 475 480

Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro

485 490 495

Gly Gln Arg Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe

500 505 510

Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp

515 520 525

Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu

530 535 540

Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser

545 550 555 560

Gly Trp Pro Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala

565 570 575

Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser

580 585 590

Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

595 600 605

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

610 615 620

Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu

625 630 635 640

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

645 650 655

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

660 665 670

Val Glu Pro Lys Ser Cys

675

<210> 212

<211> 678

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 212

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Lys Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp

210 215 220

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

225 230 235 240

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

245 250 255

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

260 265 270

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

275 280 285

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

290 295 300

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

305 310 315 320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330 335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345 350

Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu

355 360 365

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

370 375 380

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395 400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410 415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425 430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440 445

Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala

450 455 460

Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser

465 470 475 480

Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro

485 490 495

Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe

500 505 510

Thr Asn Tyr Ala Gln Lys Phe Gln Gly Lys Val Thr Ile Thr Ala Asp

515 520 525

Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu

530 535 540

Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser

545 550 555 560

Gly Trp Pro Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala

565 570 575

Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser

580 585 590

Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

595 600 605

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

610 615 620

Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu

625 630 635 640

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

645 650 655

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

660 665 670

Val Glu Pro Lys Ser Cys

675

<210> 213

<211> 676

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 213

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Arg Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 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 His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 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 Ala Leu Pro Ala Pro 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 Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

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 Gln 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 Pro Gly

435 440 445

Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu

450 455 460

Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly

465 470 475 480

Gly Thr Phe Val Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly

485 490 495

Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala

500 505 510

Gln Tyr Ala Gln Arg Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu

515 520 525

Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp

530 535 540

Thr Ala Val Tyr Tyr Cys Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu

545 550 555 560

Pro Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr

565 570 575

Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser

580 585 590

Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu

595 600 605

Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His

610 615 620

Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser

625 630 635 640

Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys

645 650 655

Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu

660 665 670

Pro Lys Ser Cys

675

<210> 214

<211> 676

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 214

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 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 His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 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 Ala Leu Pro Ala Pro 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 Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

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 Gln 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 Pro Gly

435 440 445

Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu

450 455 460

Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly

465 470 475 480

Gly Thr Phe Val Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly

485 490 495

Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala

500 505 510

Gln Tyr Ala Gln Lys Phe Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu

515 520 525

Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp

530 535 540

Thr Ala Val Tyr Tyr Cys Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu

545 550 555 560

Pro Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr

565 570 575

Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser

580 585 590

Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu

595 600 605

Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His

610 615 620

Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser

625 630 635 640

Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys

645 650 655

Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu

660 665 670

Pro Lys Ser Cys

675

<210> 215

<211> 17

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic peptide

<220>

<221> OPTION

<222> (14)..(14)

<223> /replace="Arg"

<220>

<221> OPTION

<222> (16)..(16)

<223> /replace="Arg"

<220>

<221> UNDETERMINATED SIGN

<222> (1)..(17)

<223> /note="Residual options given in

sequences have no advantage over residues in

annotations of the positions of options"

<400> 215

Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe Gln

1 5 10 15

gly

<210> 216

<211> 675

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 216

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Gly

435 440 445

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

450 455 460

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

465 470 475 480

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg

485 490 495

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr

500 505 510

Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr

515 520 525

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

530 535 540

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

545 550 555 560

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys

565 570 575

Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly

580 585 590

Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro

595 600 605

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

610 615 620

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

625 630 635 640

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn

645 650 655

Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro

660 665 670

Lys Ser Cys

675

<210> 217

<211> 675

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 217

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Lys Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Gly

435 440 445

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

450 455 460

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

465 470 475 480

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly

485 490 495

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr

500 505 510

Ala Gln Lys Phe Gln Gly Lys Val Thr Ile Thr Ala Asp Glu Ser Thr

515 520 525

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

530 535 540

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

545 550 555 560

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys

565 570 575

Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly

580 585 590

Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro

595 600 605

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

610 615 620

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

625 630 635 640

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn

645 650 655

Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro

660 665 670

Lys Ser Cys

675

<210> 218

<211> 673

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 218

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Arg Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val

260 265 270

Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Gly Gly

435 440 445

Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

450 455 460

Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe

465 470 475 480

Val Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

485 490 495

Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala

500 505 510

Gln Arg Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser

515 520 525

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

530 535 540

Tyr Tyr Cys Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp

545 550 555 560

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

565 570 575

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

580 585 590

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

595 600 605

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

610 615 620

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

625 630 635 640

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

645 650 655

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser

660 665 670

Cys

<210> 219

<211> 673

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 219

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Val Arg Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala Gln Lys Phe

50 55 60

Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro

210 215 220

Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe

225 230 235 240

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

245 250 255

Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val

260 265 270

Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

275 280 285

Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val

290 295 300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315 320

Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser

325 330 335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345 350

Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360 365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375 380

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

385 390 395 400

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp

405 410 415

Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425 430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Gly Gly

435 440 445

Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys

450 455 460

Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe

465 470 475 480

Val Arg Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu

485 490 495

Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Glu Ala Gln Tyr Ala

500 505 510

Gln Lys Phe Arg Gly Arg Ala Thr Ile Thr Ala Asp Glu Ser Thr Ser

515 520 525

Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val

530 535 540

Tyr Tyr Cys Ala Arg Glu Gly Tyr Tyr Tyr Gly Ala Leu Pro Tyr Trp

545 550 555 560

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

565 570 575

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

580 585 590

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

595 600 605

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

610 615 620

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

625 630 635 640

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

645 650 655

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser

660 665 670

Cys

<210> 220

<211> 689

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 220

Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser

20 25 30

Ser Tyr Ala Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Ser Ile Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg Asp Ser Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser

130 135 140

Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr

195 200 205

Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu

225 230 235 240

Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

245 250 255

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

260 265 270

Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly

275 280 285

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn

290 295 300

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

305 310 315 320

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro

325 330 335

Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

340 345 350

Pro Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn

355 360 365

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

370 375 380

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

385 390 395 400

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg

405 410 415

Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys

420 425 430

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

435 440 445

Ser Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gln Leu Gln Leu Gln

450 455 460

Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr

465 470 475 480

Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser Ser Tyr Ala Trp Gly

485 490 495

Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Ser Ile

500 505 510

Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val

515 520 525

Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser

530 535 540

Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Ser

545 550 555 560

Gly Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp

565 570 575

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

580 585 590

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

595 600 605

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

610 615 620

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

625 630 635 640

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

645 650 655

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

660 665 670

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser

675 680 685

Cys

<210> 221

<211> 689

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 221

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Asp Glu Asn Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser

130 135 140

Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

195 200 205

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

Val Glu Pro Lys Ser Cys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln

225 230 235 240

Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr

245 250 255

Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly Gly Ala Val Trp Ser

260 265 270

Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile

275 280 285

Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val

290 295 300

Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser

305 310 315 320

Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Asp Glu Asn

325 330 335

Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp

340 345 350

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

355 360 365

Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr

370 375 380

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

385 390 395 400

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

405 410 415

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

420 425 430

Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp

435 440 445

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr

450 455 460

Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro

465 470 475 480

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

485 490 495

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp

500 505 510

Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

515 520 525

Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val

530 535 540

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

545 550 555 560

Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys

565 570 575

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

580 585 590

Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

595 600 605

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

610 615 620

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

625 630 635 640

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys

645 650 655

Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu

660 665 670

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly

675 680 685

Lys

<210> 222

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 222

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Leu Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Gly Ile Tyr Glu Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala His Glu Arg Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr

130 135 140

Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

245 250 255

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

290 295 300

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

305 310 315 320

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

325 330 335

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

340 345 350

Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

355 360 365

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

370 375 380

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

385 390 395 400

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

405 410 415

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

420 425 430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

435 440 445

Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

450 455 460

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

465 470 475 480

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Leu Gly Trp Gly Trp Ile

485 490 495

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile Tyr Glu

500 505 510

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

515 520 525

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

530 535 540

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala His Glu Arg Val Arg

545 550 555 560

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

565 570 575

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

580 585 590

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

595 600 605

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

610 615 620

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

625 630 635 640

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

645 650 655

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

660 665 670

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 223

<211> 689

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 223

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly

20 25 30

Gly Ala Val Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Gly Ile Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Asp Glu Asn Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His

100 105 110

Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala

115 120 125

Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser

130 135 140

Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe

145 150 155 160

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

165 170 175

Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu

180 185 190

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr

195 200 205

Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

210 215 220

Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu

225 230 235 240

Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

245 250 255

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

260 265 270

Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly

275 280 285

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn

290 295 300

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

305 310 315 320

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro

325 330 335

Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

340 345 350

Pro Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn

355 360 365

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

370 375 380

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

385 390 395 400

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg

405 410 415

Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys

420 425 430

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

435 440 445

Ser Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln

450 455 460

Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr

465 470 475 480

Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly Gly Ala Val Trp Ser

485 490 495

Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu Trp Ile Gly Gly Ile

500 505 510

Ala Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val

515 520 525

Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser

530 535 540

Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Asp Glu Asn

545 550 555 560

Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp

565 570 575

Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

580 585 590

Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr

595 600 605

Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr

610 615 620

Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro

625 630 635 640

Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr

645 650 655

Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn

660 665 670

His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser

675 680 685

Cys

<210> 224

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 224

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr

130 135 140

Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

245 250 255

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

290 295 300

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

305 310 315 320

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

325 330 335

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

340 345 350

Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

355 360 365

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

370 375 380

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

385 390 395 400

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

405 410 415

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

420 425 430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

435 440 445

Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

450 455 460

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

465 470 475 480

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

485 490 495

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Val His

500 505 510

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

515 520 525

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

530 535 540

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

545 550 555 560

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

565 570 575

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

580 585 590

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

595 600 605

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

610 615 620

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

625 630 635 640

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

645 650 655

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

660 665 670

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 225

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 225

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr

130 135 140

Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

245 250 255

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

290 295 300

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

305 310 315 320

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

325 330 335

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

340 345 350

Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

355 360 365

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

370 375 380

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

385 390 395 400

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

405 410 415

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

420 425 430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

435 440 445

Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

450 455 460

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

465 470 475 480

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

485 490 495

Arg Gln Pro Pro Gly Lys Gly Pro Glu Trp Ile Gly Leu Ile Val His

500 505 510

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

515 520 525

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

530 535 540

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

545 550 555 560

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

565 570 575

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

580 585 590

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

595 600 605

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

610 615 620

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

625 630 635 640

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

645 650 655

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

660 665 670

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 226

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 226

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr

130 135 140

Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

245 250 255

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

290 295 300

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

305 310 315 320

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

325 330 335

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

340 345 350

Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

355 360 365

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

370 375 380

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

385 390 395 400

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

405 410 415

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

420 425 430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

435 440 445

Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

450 455 460

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

465 470 475 480

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

485 490 495

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Val His

500 505 510

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

515 520 525

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

530 535 540

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

545 550 555 560

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

565 570 575

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

580 585 590

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

595 600 605

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

610 615 620

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

625 630 635 640

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

645 650 655

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

660 665 670

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 227

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 227

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly

20 25 30

Ala Gly Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Val His Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Leu Glu Ser Val Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr

130 135 140

Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

245 250 255

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

290 295 300

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

305 310 315 320

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

325 330 335

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

340 345 350

Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

355 360 365

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

370 375 380

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

385 390 395 400

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

405 410 415

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

420 425 430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

435 440 445

Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

450 455 460

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

465 470 475 480

Ala Val Ser Gly Tyr Ser Ile Ser Ser Gly Ala Gly Trp Gly Trp Ile

485 490 495

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Val His

500 505 510

Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

515 520 525

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

530 535 540

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Val Leu Glu Ser Val Arg

545 550 555 560

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

565 570 575

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

580 585 590

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

595 600 605

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

610 615 620

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

625 630 635 640

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

645 650 655

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

660 665 670

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 228

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 228

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr

130 135 140

Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

245 250 255

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

290 295 300

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

305 310 315 320

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

325 330 335

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

340 345 350

Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

355 360 365

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

370 375 380

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

385 390 395 400

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

405 410 415

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

420 425 430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

435 440 445

Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

450 455 460

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

465 470 475 480

Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp Gly Trp Ile

485 490 495

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Tyr His

500 505 510

Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

515 520 525

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

530 535 540

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Ala Asp Arg

545 550 555 560

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

565 570 575

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

580 585 590

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

595 600 605

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

610 615 620

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

625 630 635 640

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

645 650 655

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

660 665 670

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 229

<211> 687

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 229

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu

20 25 30

Tyr Met Trp Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp

35 40 45

Ile Gly Leu Ile Tyr His Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu

50 55 60

Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser

65 70 75 80

Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Ala Asp Arg Gly Tyr Gly Asp Tyr Gly Gly His His Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser

115 120 125

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr

130 135 140

Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

145 150 155 160

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

165 170 175

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

180 185 190

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr

195 200 205

Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

210 215 220

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe

225 230 235 240

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

245 250 255

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

260 265 270

Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val

275 280 285

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser

290 295 300

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

305 310 315 320

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser

325 330 335

Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

340 345 350

Gln Val Tyr Thr Leu Pro Ser Gln Glu Glu Met Thr Lys Asn Gln

355 360 365

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

370 375 380

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

385 390 395 400

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu

405 410 415

Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser

420 425 430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

435 440 445

Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Glu

450 455 460

Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser Leu Thr Cys

465 470 475 480

Ala Val Ser Gly Tyr Ser Ile Ser Ser Glu Tyr Met Trp Gly Trp Ile

485 490 495

Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly Leu Ile Tyr His

500 505 510

Ser Gly Lys Thr Tyr Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile

515 520 525

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val

530 535 540

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Ala Asp Arg

545 550 555 560

Gly Tyr Gly Asp Tyr Gly Gly His His Ala Phe Asp Ile Trp Gly Gln

565 570 575

Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

580 585 590

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

595 600 605

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

610 615 620

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

625 630 635 640

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

645 650 655

Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys

660 665 670

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 230

<211> 685

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 230

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Val Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Phe 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

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 Ser Gln Glu Glu Met Thr Lys Asn Gln Val

355 360 365

Ser Leu Thr 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 Arg 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 Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser

450 455 460

Gly Ala Glu Val Lys Arg Pro Gly Ser Ser Val Lys Val Ser Cys Lys

465 470 475 480

Ala Ser Gly Gly Thr Phe Ser Ser Tyr Tyr Ile Ser Trp Val Arg Gln

485 490 495

Val Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Val Pro

500 505 510

Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr

515 520 525

Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg

530 535 540

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly Gly Gly Tyr

545 550 555 560

Ala Arg Gly Asp His Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr

565 570 575

Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro

580 585 590

Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly

595 600 605

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

610 615 620

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

625 630 635 640

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

645 650 655

Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser

660 665 670

Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 231

<211> 685

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 231

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Tyr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Val Pro Gly Thr Ala Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Gly Gly Gly Tyr Ala Arg Gly Asp His Tyr Tyr Gly Met

100 105 110

Asp Val Trp Gly Gln Gly Thr Thr 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 Phe 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

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 Ser Gln Glu Glu Met Thr Lys Asn Gln Val

355 360 365

Ser Leu Thr 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 Arg 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 Lys Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser

450 455 460

Gly Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys

465 470 475 480

Ala Ser Gly Gly Thr Phe Ser Ser Tyr Tyr Ile Ser Trp Val Arg Gln

485 490 495

Ala Pro Gly Gln Arg Leu Glu Trp Met Gly Gly Ile Ile Pro Val Pro

500 505 510

Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr

515 520 525

Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg

530 535 540

Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Ala Gly Gly Gly Tyr

545 550 555 560

Ala Arg Gly Asp His Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr

565 570 575

Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro

580 585 590

Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly

595 600 605

Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

610 615 620

Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

625 630 635 640

Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

645 650 655

Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser

660 665 670

Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys

675 680 685

<210> 232

<211> 677

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 232

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Arg Gly

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Gly Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly Met Asp Val Trp Gly

100 105 110

Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser

115 120 125

Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala

130 135 140

Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His

195 200 205

Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly

210 215 220

Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly 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 Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 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 Arg 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 Lys

435 440 445

Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val

450 455 460

Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly

465 470 475 480

Thr Phe Ser Arg Gly Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln

485 490 495

Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Glu Gly Thr Ala Tyr

500 505 510

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser

515 520 525

Thr Gly Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

530 535 540

Ala Val Tyr Tyr Cys Ala Arg Gln Ser Asp Tyr Gly Leu Pro Arg Gly

545 550 555 560

Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser

565 570 575

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr

580 585 590

Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro

595 600 605

Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val

610 615 620

His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser

625 630 635 640

Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile

645 650 655

Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val

660 665 670

Glu Pro Lys Ser Cys

675

<210> 233

<211> 675

<212> PROTEIN

<213> Artificial sequence

<220>

<221> source

<223> /note="Description of the artificial sequence:

synthetic polypeptide

<400> 233

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr

20 25 30

Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro Tyr Trp Gly Gln

100 105 110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120 125

Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala

130 135 140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro

210 215 220

Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val

225 230 235 240

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

245 250 255

Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu

260 265 270

Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

275 280 285

Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser

290 295 300

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

305 310 315 320

Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile

325 330 335

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

340 345 350

Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

355 360 365

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

370 375 380

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

385 390 395 400

Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg

405 410 415

Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys Gly

435 440 445

Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys

450 455 460

Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr

465 470 475 480

Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly

485 490 495

Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Ser Gly Phe Thr Asn Tyr

500 505 510

Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr

515 520 525

Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala

530 535 540

Val Tyr Tyr Cys Ala Arg Glu Gly Gly His Tyr Tyr Ser Gly Trp Pro

545 550 555 560

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys

565 570 575

Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly

580 585 590

Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro

595 600 605

Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr

610 615 620

Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val

625 630 635 640

Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn

645 650 655

Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro

660 665 670

Lys Ser Cys

675

<---

Claims (179)

1. An isolated antibody or antigen-binding fragment thereof specifically binding human GITR of SEQ ID NO: 1, wherein the antibody or antigen-binding fragment thereof contains: a. CDR-H3 of SEQ ID NO:13, CDR-H2 of SEQ ID NO:12, CDR-H1 of SEQ ID NO:11, CDR-L3 of SEQ ID NO:16, CDR-L2 of SEQ ID NO:15 and CDR-L1 of SEQ ID NO:14; b. CDR-H3 of SEQ ID NO:23, CDR-H2 of SEQ ID NO:22, CDR-H1 of SEQ ID NO:21, CDR-L3 of SEQ ID NO:17, CDR-L2 of SEQ ID NO:15 and CDR-L1 of SEQ ID NO:14; c. CDR-H3 of SEQ ID NO:30, CDR-H2 of SEQ ID NO:29, CDR-H1 of SEQ ID NO:28, CDR-L3 of SEQ ID NO:17, CDR-L2 of SEQ ID NO:31 and CDR-L1 of SEQ ID NO:14; d. CDR-H3 of SEQ ID NO:30, CDR-H2 of SEQ ID NO:29, CDR-H1 of SEQ ID NO:28, CDR-L3 of SEQ ID NO:17, CDR-L2 of SEQ ID NO:15 and CDR-L1 of SEQ ID NO:36; e. CDR-H3 of SEQ ID NO:30, CDR-H2 of SEQ ID NO:29, CDR-H1 of SEQ ID NO:28, CDR-L3 of SEQ ID NO:17, CDR-L2 of SEQ ID NO:41 and CDR-L1 of SEQ ID NO:14; f. CDR-H3 of SEQ ID NO:48, CDR-H2 of SEQ ID NO:47, CDR-H1 of SEQ ID NO:46, CDR-L3 of SEQ ID NO:17, CDR-L2 of SEQ ID NO:50 and CDR-L1 of SEQ ID NO:49; g. CDR-H3 of SEQ ID NO:48, CDR-H2 of SEQ ID NO:47, CDR-H1 of SEQ ID NO:46, CDR-L3 of SEQ ID NO:56, CDR-L2 of SEQ ID NO:55 and CDR-L1 of SEQ ID NO:54; h. CDR-H3 of SEQ ID NO:61, CDR-H2 of SEQ ID NO:60, CDR-H1 of SEQ ID NO:59, CDR-L3 of SEQ ID NO:16, CDR-L2 of SEQ ID NO:15 and CDR-L1 of SEQ ID NO:14; i. CDR-H3 of SEQ ID NO:61, CDR-H2 of SEQ ID NO:47, CDR-H1 of SEQ ID NO:46, CDR-L3 of SEQ ID NO:16, CDR-L2 of SEQ ID NO:15 and CDR-L1 of SEQ ID NO:14; or j. CDR-H3 of SEQ ID NO:103, CDR-H2 of SEQ ID NO:22, CDR-H1 of SEQ ID NO:21, CDR-L3 of SEQ ID NO:16, CDR-L2 of SEQ ID NO:15 and CDR-L1 of SEQ ID NO:14. 2. An antibody or its antigen-binding fragment according to claim 1, where: a. the antibody or antigen-binding fragment thereof contains the V _H sequence from SEQ ID NO:9 and the V _L sequence from SEQ ID NO:10; b. the antibody or antigen-binding fragment thereof contains the V _H sequence from SEQ ID NO:19 and the V _L sequence from SEQ ID NO:20; c. the antibody or antigen-binding fragment thereof contains the V _H sequence from SEQ ID NO:26 and the V _L sequence from SEQ ID NO:27; d. the antibody or antigen-binding fragment thereof contains the V _H sequence from SEQ ID NO:26 or SEQ ID NO:34 and the V _L sequence from SEQ ID NO:35; e. the antibody or antigen-binding fragment thereof contains the V _H sequence from SEQ ID NO:26 and the V _L sequence from SEQ ID NO:40; f. the antibody or antigen-binding fragment contains the V _H sequence from SEQ ID NO:44 and the V _L sequence from SEQ ID NO:45; g. the antibody or antigen-binding fragment thereof contains the V _H sequence from SEQ ID NO:44 and the V _L sequence from SEQ ID NO:53; h. the antibody or its antigen-binding fragment contains the V _H sequence from SEQ ID NO:58 and the V _L sequence from SEQ ID NO:10; i. the antibody or antigen-binding fragment thereof contains the V _H sequence from SEQ ID NO:104 and the V _L sequence from SEQ ID NO:10; or j. the antibody or antigen-binding fragment thereof contains the V _H sequence from SEQ ID NO:105 and the V _L sequence from SEQ ID NO:10. 3. An antibody or its antigen-binding fragment according to claim 2, where: a. the antibody or antigen-binding fragment thereof contains the heavy chain of SEQ ID NO:7 and the light chain of SEQ ID NO:8; b. the antibody or antigen-binding fragment thereof contains the heavy chain of SEQ ID NO:17 and the light chain of SEQ ID NO:18; c. the antibody or antigen-binding fragment thereof contains the heavy chain of SEQ ID NO:24 and the light chain of SEQ ID NO:25; d. the antibody or antigen-binding fragment thereof comprises (i) a heavy chain from SEQ ID NO:32 and a light chain from SEQ ID NO:33 or (ii) a heavy chain from SEQ ID NO:37 and a light chain from SEQ ID NO:33; e. the antibody or antigen-binding fragment thereof comprises (i) a heavy chain from SEQ ID NO:38 and a light chain from SEQ ID NO:39; f. the antibody or antigen-binding fragment thereof comprises (i) a heavy chain from SEQ ID NO:42 and a light chain from SEQ ID NO:43; g. the antibody or antigen-binding fragment thereof comprises (i) a heavy chain from SEQ ID NO:51 and a light chain from SEQ ID NO:52; h. the antibody or antigen-binding fragment thereof comprises (i) a heavy chain from SEQ ID NO:57 and a light chain from SEQ ID NO:8; i. the antibody or antigen-binding fragment thereof comprises (i) a heavy chain from SEQ ID NO:114 and a light chain from SEQ ID NO:8, or (ii) a heavy chain from SEQ ID NO:120 and a light chain from SEQ ID NO:8; or (iii) a heavy chain from SEQ ID NO:122 and a light chain from SEQ ID NO:8; or j. the antibody or antigen-binding fragment thereof comprises (i) a heavy chain from SEQ ID NO:115 and a light chain from SEQ ID NO:8, or (ii) a heavy chain from SEQ ID NO:121 and a light chain from SEQ ID NO:8; or (iii) a heavy chain from SEQ ID NO:123 and a light chain from SEQ ID NO:8. 4. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the amino acid substitutions are conservative amino acid substitutions. 5. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the antibody or its antigen-binding fragment: a. has at least three antigen-binding domains specifically binding an epitope on the GITR; b. has at least three antigen-binding domains specifically binding one epitope per GITR; c. has at least four antigen-binding domains specifically binding an epitope on the GITR; d. has at least four antigen-binding domains specifically binding one epitope per GITR; e. acts as a GITR agonist expressed on the surface of the target cell; f. blocks linking GITRL to GITR; g. co-stimulating an effector T cell in combination with antigen presentation from an antigen presenting cell; h. inhibits suppression of an effector T cell by a regulatory T cell; i. reduces the number of regulatory T cells in tissue or in the systemic circulation; j. is capable of binding to one or more of the GITR residues of SEQ ID NO:1 selected from the group consisting of R56, C58, R59, D60, Y61, P62, E64, E65, C66 and C67; or k. is capable of any combination of (a) - (j). 6. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where GITR is selected from hGITR of SEQ ID NO: 1, hGITR-T43R of SEQ ID NO: 2, cGITR of SEQ ID NO: 3, mGITR of SEQ ID NO: 4, and combinations thereof. 7. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the antibody is a monoclonal antibody. 8. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody is selected from a human antibody, a humanized antibody, or a chimeric antibody. 9. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody or antigen-binding fragment thereof is trivalent, tetravalent, pentavalent, hexavalent, septivalent, or octavalent. 10. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the antibody or antigen-binding fragment contains an antibody fragment. 11. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody or antigen-binding fragment thereof contains an alternative scaffold. 12. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody or antigen-binding fragment thereof contains an immunoglobulin constant region. 13. An antibody or antigen-binding fragment thereof according to claim 12, wherein the antibody or antigen-binding fragment thereof contains a heavy chain constant region from a class selected from IgA, IgD, IgE, IgG, or IgM. 14. An antibody or antigen-binding fragment thereof according to claim 13, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain constant region from the IgG class and subclass selected from IgG4, IgG1, IgG2, or IgG3. 15. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein at least one Fab is fused to the C-terminus of an IgG Fc domain. 16. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, additionally containing at least one linker. 17. The antibody or antigen-binding fragment thereof according to claim 14, where the IgG is IgG4. 18. An antibody or antigen-binding fragment thereof according to claim 14, where the IgG is IgG1. 19. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein at least one Fab is fused to the N-terminus of an IgG Fc domain. 20. An antibody or antigen-binding fragment thereof according to claim 19, wherein at least one Fab is at least two Fabs. 21. An antibody or antigen-binding fragment thereof according to claim 19, wherein at least one Fab is at least three Fabs. 22. An antibody or antigen-binding fragment thereof according to claim 19, wherein at least one Fab is at least four Fabs. 23. An antibody or antigen-binding fragment according to any one of paragraphs. 20-22, where two Fabs are independently fused to the N-terminus of IgG. 24. The antibody or antigennegative fragment according to any one of paragraphs. 20-22, where two Fabs are independently fused to the C-terminus of IgG. 25. An antibody or antigen-binding fragment thereof according to claim 23, wherein a Fab is attached to each N-terminus of the IgG, a linker is attached to each of said Fab, and a Fab is attached to each linker. 26. An antibody or antigen-binding fragment thereof according to claim 24, wherein a Fab is attached to each C-terminus of the IgG, a linker is attached to each of said Fab, and a Fab is attached to each linker. 27. An antibody or antigen-binding fragment thereof according to claim 25 or 26, wherein each linker contains SEQ ID NO:5. 28. An antibody or antigen-binding fragment thereof according to claim 25 or 26, wherein each linker contains SEQ ID NO:6. 29. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody, or antigen-binding fragment thereof, comprises a common light chain antibody, ridge-to-cavity antibody, scFv attached to IgG, Fab attached to IgG, diabody, tetravalent bispecific antibody, CovX-Body, antibody Fcab , tandem Fab or a combination. 30. The antibody or antigen-binding fragment thereof according to claim 9, wherein the antibody or antigen-binding fragment binds more than one GITR molecule. 31. An antibody or antigen-binding fragment thereof according to claim 5, wherein the antibody or antigen-binding fragment thereof acts as a GITR agonist expressed on the surface of the target cell, and GITR agonism by the antibody or antigen-binding fragment thereof is independent of GITRL binding. 32. The antibody or antigen-binding fragment thereof according to claim 5, wherein the antibody or antigen-binding fragment thereof acts as a GITR agonist expressed on the surface of the target cell, and the antibody or antigen-binding fragment enhances GITRL binding to GITR by at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least at least about 80%, or at least about 90%. 33. The antibody or antigen-binding fragment thereof according to claim 32, wherein the antibody or antigen-binding fragment thereof enhances the binding of GITRL to GITR by at least about 50%. 34. The antibody or antigen-binding fragment thereof according to claim 5, wherein the target cell is selected from an effector T cell, a regulatory T cell, a natural killer (NK) cell, a natural killer T (NKT) cell, a dendritic cell, and a B cell . 35. An antibody or antigen-binding fragment thereof according to claim 5, wherein the target cell is an effector T cell selected from a helper T cell (CD4+), a cytotoxic T cell (CD8+), and combinations thereof. 36. The antibody or antigen-binding fragment thereof according to claim 5, wherein the target cell is a regulatory T cell selected from CD4+CD25+Foxp3+ regulatory T cell, CD8+CD25+ regulatory T cell, and combinations thereof. 37. An antibody or antigen-binding fragment thereof according to claim 5, wherein the tissue is a tumor. 38. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the K _D of the first antigen-binding domain for hGITR of SEQ ID NO: 1 or hGITR-T43R of SEQ ID NO: 2 is less than about 20 nM. 39. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the K _D of the first antigen-binding domain for cGITR of SEQ ID NO: 3 is less than about 200 nM. 40. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the K _D of the second antigen-binding domain for hGITR of SEQ ID NO: 1 or hGITR-T43R of SEQ ID NO: 2 is less than about 100 nM. 41. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the K _D of the second antigen-binding domain for cGITR of SEQ ID NO: 3 is less than about 1 μM. 42. The antibody or antigennegative fragment according to any one of paragraphs. 1-3, wherein the antibody or antigen-binding fragment thereof contains an Fc domain with reduced effector function compared to an IgG1 Fc domain. 43. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the antibody or antigen-binding fragment contains an aglycosylated Fc domain. 44. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody or antigen-binding fragment thereof contains an IgG1 Fc domain with alanine at one or more of positions 234, 235, 265, and 297. 45. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3 where GITR is expressed on the cell surface i-targets. 46. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the antibody or antigen-binding fragment causes multimerization of GITR expressed on the surface of the target cell. 47. An antibody or antigen-binding fragment thereof according to claim 46, wherein the antibody or antigen-binding fragment thereof causes multimerization of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 GITR molecules. 48. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody or antigen-binding fragment thereof comprises an immunoglobulin containing at least two different heavy chain variable regions, each paired with a common light chain variable region. 49. An antibody or antigen-binding fragment thereof according to claim 48, wherein the common light chain variable region forms a separate antigen-binding domain with each of two different heavy chain variable regions. 50. An antibody or antigen-binding fragment thereof according to claim 48, wherein the antibody or antigen-binding fragment thereof comprises a first VH variable domain having SEQ ID NO:189, a second VH variable domain having SEQ ID NO:215, and a common variable light chain having SEQ ID NO:190. 51. An antibody or antigen-binding fragment thereof according to claim 48, wherein the antibody or antigen-binding fragment thereof comprises a first VH variable domain having SEQ ID NO:199, a second VH variable domain having SEQ ID NO:216, and a common variable light chain having SEQ ID NO:200. 52. Set for specific binding to human GITR (hGITR) with SEQ ID NO:1, containing the antibody or antigennegative fragment according to any one of paragraphs. 1-51 and instructions for using the antibody or antigen-binding fragment thereof. 53. The kit of claim 52, wherein the antibody or antigen-binding fragment thereof is lyophilized. 54. The kit according to claim 53, additionally containing a liquid for diluting the lyophilized antibody or its antigen-binding fragment. 55. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody or antigen-binding fragment thereof contains a polypeptide sequence having a pyroglutamate (pE) residue at the N-terminus. 56. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the antibody or antigen-binding fragment contains a VH sequence in which the N-terminal Q is replaced by pE. 57. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody or antigen-binding fragment thereof contains a VL sequence in which the N-terminal E has been replaced by pE. 58. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, wherein the antibody or antigen-binding fragment thereof contains a heavy chain sequence in which the N-terminal Q has been replaced with pE. 59. An antibody or antigen-binding fragment according to any one of paragraphs. 1-3, where the antibody or antigen-binding fragment contains a light chain sequence in which the N-terminal E is replaced by pE. 60. The use of an antibody or antigen-binding fragment according to any one of paragraphs. 1-51 in the treatment of malignant tumors. 61. Use according to claim 60, wherein the malignant tumor is selected from a solid tumor and a hematological tumor. 62. An isolated polynucleotide encoding an antibody or antigen-binding fragment specifically binding human GITR (hGITR) with SEQ ID NO: 1, where the polynucleotide encodes an antibody or antigen-binding fragment according to any one of claims. 1-51. 63. A vector for propagating a polynucleotide encoding an antibody or an antigen-binding fragment thereof specifically binding human GITR (hGITR) of SEQ ID NO: 1, where the vector contains the polynucleotide according to claim 62. 64. A host cell for propagating a polynucleotide encoding an antibody or an antigen-binding fragment thereof specifically binding human GITR (hGITR) of SEQ ID NO: 1, wherein the host cell contains the polynucleotide of claim 62 or the vector of claim 63, and wherein the cell is the host is selected from the group consisting of a bacterial cell, a fungal cell, a COS-7 cell, a baby hamster kidney (BHK) cell; Chinese hamster ovary (CHO) cells; mice Sertoli cells and African green monkey kidney cells. 65. A host cell according to claim 64, selected from a bacterial cell, a fungal cell, and a mammalian cell. 66. A host cell according to claim 64 selected from an E. coli cell, a Saccharomyces cerevisiae cell, and a CHO cell. 67. The method of obtaining an antibody or antigennegative fragment according to any one of paragraphs. 1-51, including the expression of the antibody or its antigennegative fragment in the host cell according to claim 65 and the isolation of the expressed antibody or its antigennegative fragment. 68. Pharmaceutical composition for use in the treatment of cancer, containing a therapeutically effective amount of an antibody or antigen-binding fragment according to any one of paragraphs. 1-51 and a pharmaceutically acceptable excipient. 69. The pharmaceutical composition of claim 68, wherein the amount of the antibody or antigen-binding fragment thereof in the pharmaceutical composition is sufficient to (a) reduce the suppression of effector T cells by regulatory T cells; (b) activation of effector T cells; (c) reducing the number of regulatory T cells in tissue or systemically; (d) inducing or enhancing the proliferation of effector T cells; (e) slowing down the rate of tumor growth; (f) induction of tumor regression or (g) a combination of both in a subject. 70. The pharmaceutical composition according to claim 68 or 69, wherein the malignant tumor is selected from a solid tumor and a hematological tumor. 71. A method of treating or preventing a malignant tumor in a subject in need thereof, comprising administering to the subject an effective amount of an antibody or antigen-binding fragment according to any one of paragraphs. 1-51 or a pharmaceutical composition according to claim 68 or 69. 72. A method of activating immunocytes expressing GITR in a subject, comprising administering to the subject an effective amount of an antibody or antigen-binding fragment according to any one of paragraphs. 1-51 or a pharmaceutical composition according to claim 68 or 69. 73. The method of claim 71 or 72 for inducing or enhancing an immune response to a cancer-associated antigen. 74. The method according to any one of paragraphs. 71-73, wherein the antibody or antigen-binding fragment thereof is administered in an amount sufficient to (a) decrease the suppression of effector T cells by regulatory T cells; (b) activation of effector T cells; (c) inducing or enhancing the proliferation of effector T cells; (d) slowing down the rate of tumor growth; (e) inducing tumor regression, or (f) a combination thereof. 75. The method of claim 73 or 74, wherein the cancer is a solid tumor. 76. The method of claim 73 or 74, wherein the cancer is a hematological tumor. 77. The method according to any one of paragraphs. 71-76, further comprising administering one or more additional drugs. 78. The method of claim 77, wherein the additional drug is selected from a cytotoxic agent, a chemotherapeutic agent, a cytostatic agent, an antihormonal agent, an EGFR inhibitor, an immunostimulatory agent, an antiangiogenic agent, and combinations thereof. 79. The method according to p. 77, where the additional drug is an immunostimulatory agent. 80. The method of claim 79, wherein the immunostimulatory agent comprises an agent that blocks the signaling of an inhibitory receptor expressed by the immunocyte or a ligand thereof. 81. The method according to p. 80, where the inhibitory receptor expressed by the immunocyte, or its ligand is selected from CTLA-4, PD-1, PD-L1, NRP-1, LAG-3, Tim3, TIGIT, neuritin, BTLA, KIR and their combinations. 82. The method of claim 79 wherein the immunostimulatory agent comprises a stimulatory receptor agonist expressed by the immunocyte. 83. The method of claim 81 wherein the stimulatory receptor expressed by the immunocyte is selected from OX40, CD2, CD27, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), 4-1BB (CD137), CD28, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, CD83 ligand, and combinations thereof. 84. The method of claim 79, wherein the immunostimulatory agent contains a cytokine. 85. The method of claim 84 wherein the cytokine is selected from IL-2, IL-5, IL-7, IL-12, IL-15, IL-21, and combinations thereof. 86. The method of claim 79 wherein the immunostimulatory agent comprises an oncolytic virus. 87. The method of claim 86 wherein the oncolytic virus is selected from herpes simplex virus, vesicular stomatitis virus, adenovirus, Newcastle disease virus, vaccinia virus, Marab virus, and combinations thereof. 88. The method of claim 79 wherein the immunostimulatory agent comprises a T cell expressing a chimeric antigen receptor. 89. The method of claim 79, wherein the immunostimulatory agent comprises a bi- or multi-specific T cell-targeted antibody. 90. The method of claim 79, wherein the immunostimulatory agent comprises an anti-TGF-β antibody, a TGF-β decoy, or a combination thereof. 91. The method of claim 79, wherein the immunostimulatory agent comprises a cancer-associated antigen vaccine. 92. A method of enhancing the immune response in a subject in need thereof, comprising administering to the subject an effective amount of an antibody or antigen-binding fragment according to any one of paragraphs. 1-51 or a pharmaceutical composition according to any one of paragraphs. 86-70, where the immune response is elicited against a tumor antigen. 93. The method according to any one of paragraphs. 77-91, where the additional drug is formulated in the same pharmaceutical composition as the antibody or antigen-binding fragment. 94. The method according to any one of paragraphs. 77-91, wherein the additional drug is formulated in a pharmaceutical composition other than the antibody or antigen-binding fragment thereof. 95. The method according to any one of paragraphs. 77-91 or 94, wherein the additional drug is administered prior to the administration of the antibody or antigen-binding fragment thereof. 96. The method according to any one of paragraphs. 77-91 or 94, where the additional drug is administered after administration of the antibody or antigen-binding fragment. 97. The method according to any one of paragraphs. 77-91 and 93-96, where the additional drug is administered simultaneously with the antibody or antigen-binding fragment. 98. An antibody or antigen-binding fragment according to any one of paragraphs. 1-51 that specifically binds the human GITR (hGITR) epitope of SEQ ID NO:1 and is capable of binding one or more residues from the group consisting of R56, C58, R59, D60, Y61, P62, E64, E65, C66, and C67 . 99. Anti-GITR human antibody or antigen-binding fragment containing four heavy chain variable regions and four light chain variable regions, where the variable regions of the heavy chain contain CDR-H3, consisting of SEQ ID NO:13, CDR-H2, consisting of SEQ ID NO:12, and CDR-H1, consisting of SEQ ID NO:11; and light chain variable regions comprise CDR-L3 consisting of SEQ ID NO:16, CDR-L2 consisting of SEQ ID NO:15 and CDR-L1 consisting of SEQ ID NO:14; And wherein one heavy chain variable region and one light chain variable region constitute one antigen-binding site; and wherein the anti-human GITR antibody or antigen-binding fragment contains a total of four antigen-binding sites. 100. An anti-GITR human antibody or antigen-binding fragment thereof according to claim 99, selected from (1) or (2): (1) an anti-GITR human antibody or antigen-binding fragment thereof comprising four heavy chain variable regions and four light chain variable regions, wherein the heavy chain variable region consists of SEQ ID NO: 9, the light chain variable region consists of SEQ ID NO: 10, and one heavy chain variable region and one light chain variable region constitute one antigen-binding site, and the antibody or antigen-binding fragment contains four antigen-binding sites; And (2) a human anti-GITR antibody or antigen-binding fragment thereof comprising four heavy chain variable regions and four light chain variable regions, wherein each heavy chain variable region consists of SEQ ID NO: 9, wherein Q at position 1 of the sequence is modified to pyroglutamate, the light chain variable region consists of SEQ ID NO: 10, and one heavy chain variable region and one light chain variable region constitute one antigen-binding site, and the antibody or antigen-binding fragment contains four antigen-binding sites. 101. An anti-GITR human antibody according to claim 99, containing two heavy chains and four light chains; where each heavy chain contains a first heavy chain variable region and a second heavy chain variable region, where each contains a CDR-H3 consisting of SEQ ID NO:13, a CDR-H2 consisting of SEQ ID NO:12, and a CDR-H1 consisting of from SEQ ID NO:11; first CH1 region, linker, second CH1 region, CH2 region, CH3 region; and each light chain contains a light chain variable region comprising a CDR-L3 consisting of SEQ ID NO:16, a CDR-L2 consisting of SEQ ID NO:15, and a CDR-L1 consisting of SEQ ID NO:14. 102. Antibody against human GITR according to item 99, selected from (1) or (2): (1) an anti-human GITR antibody containing two heavy chains and four light chains, in which each heavy chain contains two structures consisting of a heavy chain variable region of SEQ ID NO: 9 and a CH1 region, a CH2 region and a CH3 region, and the C-terminus of one of the structures is linked to the N-terminus of the other structure via a linker; And each light chain contains a light chain variable region of SEQ ID NO: 10 and a light chain constant region; And (2) an anti-human GITR antibody containing two heavy chains and four light chains, in which each heavy chain contains two structures consisting of the heavy chain variable region of SEQ ID NO: 9 and a CH1 region, a CH2 region and a CH3 region, and the C-terminus of one of the structures is linked to the N-terminus of the other structure via a linker, where Q is at position 1 sequence modified to pyroglutamate; And each light chain contains a light chain variable region of SEQ ID NO: 10 and a light chain constant region. 103. Antibody against human GITR according to item 99, selected from (1) - (4): (1) an anti-human GITR antibody comprising two heavy chains consisting of SEQ ID NO: 7 and four light chains consisting of SEQ ID NO: 8, (2) an anti-human GITR antibody comprising two heavy chains consisting of SEQ ID NO: 7, where Q at position 1 is modified to pyroglutamate, and four light chains consisting of SEQ ID NO: 8, (3) an anti-human GITR antibody comprising two heavy chains consisting of an amino acid sequence ranging from Q at position 1 to G at position 686 of SEQ ID NO: 7 and four light chains consisting of SEQ ID NO: 8, (4) an anti-human GITR antibody comprising two heavy chains consisting of an amino acid sequence ranging from Q at position 1 to G at position 686 of SEQ ID NO: 7, where Q at position 1 is modified to pyroglutamate, and four light chains, consisting of SEQ ID NO: 8. 104. A polynucleotide encoding the variable region of an anti-GITR human antibody or antigen-binding fragment thereof, wherein the polynucleotide is selected from the group consisting of (a) and (b): (a) a polynucleotide encoding the heavy chain variable region of an anti-GITR human antibody or antigen-binding fragment of claim 103, wherein the heavy chain variable region consists of SEQ ID NO:9; And (b) a polynucleotide encoding a light chain variable region of an anti-human GITR antibody or antigen-binding fragment thereof according to claim 103, wherein the light chain variable region consists of SEQ ID NO:10. 105. A polynucleotide encoding the heavy chain or light chain of an anti-human GITR antibody, wherein the polynucleotide is selected from the group consisting of (a) and (b): (a) a polynucleotide encoding the heavy chain of the anti-human GITR antibody of claim 103, wherein the heavy chain consists of SEQ ID NO:7; And (b) a polynucleotide encoding the light chain of the anti-human GITR antibody of claim 103, wherein the light chain consists of SEQ ID NO:8. 106. An expression vector for expressing the variable region of the heavy chain and/or the variable region of the light chain of an antibody against human GITR or its antigen-binding fragment, containing: (a) a polynucleotide encoding the heavy chain variable region of an anti-GITR human antibody or antigen-binding fragment thereof according to claim 100, wherein the heavy chain variable region consists of SEQ ID NO:9, and/or (b) a polynucleotide encoding the light chain variable region of the human anti-GITR antibody or antigen-binding fragment thereof according to claim 100, wherein the light chain variable region consists of SEQ ID NO:10. 107. An expression vector for expressing the variable region of the heavy chain and/or the variable region of the light chain of an antibody against human GITR or its antigen-binding fragment, containing: (a) a polynucleotide encoding the heavy chain of the human anti-GITR antibody of claim 103, wherein the heavy chain consists of SEQ ID NO:7, and/or (b) a polynucleotide encoding the light chain of the anti-human GITR antibody of claim 103, wherein the light chain consists of SEQ ID NO:8. 108. A pharmaceutical composition for specific binding of human GITR, comprising a therapeutically effective amount of an anti-human GITR antibody according to claim 103 and a pharmaceutically acceptable excipient. 109. The use of the anti-human GITR antibody of claim 103 for the manufacture of a pharmaceutical composition for the prevention or treatment of cancer. 110. A method for preventing or treating cancer, comprising administering a therapeutically effective amount of an anti-human GITR antibody according to claim 103.

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