Anti-lag3 antibodies and antigen-binding fragments

Abstract

The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAG3 as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.

1 . An antibody or antigen-binding fragment thereof that specifically binds human LAGS comprising:
 (a) the CDR1, CDR2, and CDR3 of a V L  domain of an immunoglobulin chain that comprises the amino acid sequence set forth in SEQ ID NO: 7, 17, 27, 37, 57, 59, 61, 63, 65, 101, 126, 130, 132, 136, 138, 208, 210, 224, 226, 228, 230, 232, 241, 257, 259, 261, 263, 351, 369, 371, 373, 375, 401, 403, 405, 426, 427, 450-453 or 459-461; and/or   (b) the CDR1, CDR2, and CDR3 of a V H  domain of an immunoglobulin chain that comprises the amino acid sequence set forth in SEQ ID NO: 2, 12, 22, 32, 45, 47, 49, 51, 53, 55, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 103, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 128, 134, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 212, 214, 216, 218, 220, 222, 234, 235, 237, 239, 243, 245, 247, 249, 251, 253, 255, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 353, 355, 357, 359, 361, 363, 365, 367, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 406-419, 434-442, 448, 449, 462, 463 or 464.   
     
     
         2 . The antibody or fragment of  claim 1  which is an antibody comprising:
 (1) 
 a light chain variable domain comprising: 
 CDR-L1 that comprises the amino acid sequence:  KASQSLDYEGDSDMN  (SEQ ID NO: 38); 
 CDR-L2 that comprises the amino acid sequence:  GASNLES  (SEQ ID NO: 39); and 
 CDR-L3 that comprises the amino acid sequence:  QQSTEDPRT  (SEQ ID NO: 40); and/or 
 a heavy chain variable domain comprising: 
 CDR-H1 that comprises the amino acid sequence:  DYNVD  (SEQ ID NO: 33); 
 CDR-H2 that comprises the amino acid sequence:  DINPNNGGTIYAQKFQE  (SEQ ID NO: 458); and 
 CDR-H3 that comprises the amino acid sequence:  NYRWFGAMDH  (SEQ ID NO: 35); or 
 (2) 
 a light chain variable domain comprising: 
 CDR-L1 that comprises the amino acid sequence:  KASQSLDYEGDSDMN  (SEQ ID NO: 38); 
 CDR-L2 that comprises the amino acid sequence:  GASNLES  (SEQ ID NO: 39); and 
 CDR-L3 that comprises the amino acid sequence:  QQSTEDPRT  (SEQ ID NO: 40); and/or 
 a heavy chain variable domain comprising: 
 CDR-H1 that comprises the amino acid sequence:  DYNVD  (SEQ ID NO: 33); 
 CDR-H2 that comprises the amino acid sequence:  DINPNSGGTIYAQKFQE  (SEQ ID NO: 456); and 
 CDR-H3 that comprises the amino acid sequence:  NYRWFGAMDH  (SEQ ID NO: 35); or 
 (3) 
 a light chain variable domain comprising: 
 CDR-L1 that comprises the amino acid sequence:  KASQSLDYEGDSDMN  (SEQ ID NO: 38); 
 CDR-L2 that comprises the amino acid sequence:  GASNLES  (SEQ ID NO: 39); and 
 CDR-L3 that comprises the amino acid sequence:  QQSTEDPRT  (SEQ ID NO: 40); and/or 
 a heavy chain variable domain comprising: 
 CDR-H1 that comprises the amino acid sequence:  DYNVD  (SEQ ID NO: 33); 
 CDR-H2 that comprises the amino acid sequence:  DINPNDGGTIYAQKFQE  (SEQ ID NO: 457); and 
 CDR-H3 that comprises the amino acid sequence:  NYRWFGAMDH  (SEQ ID NO: 35); or 
 (4) 
 a light chain variable domain comprising: 
 CDR-L1 that comprises the amino acid sequence:  KASQSLDYEGDSDMN  (SEQ ID NO: 38); 
 CDR-L2 that comprises the amino acid sequence:  GASNLES  (SEQ ID NO: 39); and 
 CDR-L3 that comprises the amino acid sequence:  QQSTEDPRT  (SEQ ID NO: 40); and/or 
 a heavy chain variable domain comprising: 
 CDR-H1 that comprises the amino acid sequence:  DYNVD  (SEQ ID NO: 33); 
 CDR-H2 that comprises the amino acid sequence:  DINPNQGGTIYAQKFQE  (SEQ ID NO: 455); and 
 CDR-H3 that comprises the amino acid sequence:  NYRWFGAMDH  (SEQ ID NO: 35); or 
 (5) 
 a light chain variable domain comprising: 
 CDR-L1 that comprises the amino acid sequence:  KASQSLDYEGDSDMN  (SEQ ID NO: 38); 
 CDR-L2 that comprises the amino acid sequence:  GASNLES  (SEQ ID NO: 39); and 
 CDR-L3 that comprises the amino acid sequence:  QQSTEDPRT  (SEQ ID NO: 40); and/or 
 a heavy chain variable domain comprising: 
 CDR-H1 that comprises the amino acid sequence:  DYNVD  (SEQ ID NO: 33); 
 CDR-H2 that comprises the amino acid sequence:  DINPNGGGTIYAQKFQE  (SEQ ID NO: 454); and 
 CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35). 
 
     
     
         3 . An antibody or antigen-binding fragment thereof that specifically binds human LAG3 comprising a light chain immunogoblin, a heavy chain immunogoblin, or both a light and heavy chain immunoglobulin, selected from the group consisting of:
 (1)   a light chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or   a heavy chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 106 or amino acids 1-119 thereof;   (2)   a light chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or   a heavy chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 108 or amino acids 1-119 thereof;   (3)   a light chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or   a heavy chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 110 or amino acids 1-119 thereof;   (4)   a light chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or   a heavy chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 112 or amino acids 1-119 thereof;   (5)   a light chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or   a heavy chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 114 or amino acids 1-119 thereof;   (6)   a light chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or   a heavy chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 116 or amino acids 1-119 thereof;   (7)   a light chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or   a heavy chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 118 or amino acids 1-119 thereof;   (8)   a light chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or   a heavy chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 120 or amino acids 1-119 thereof; and   (9)   a light chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or   a heavy chain immunoglobulin comprising an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 122 or amino acids 1-119 thereof.   
     
     
         4 . The antibody or antigen-binding fragment of  claim 3  comprising:
 (1) 
 a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 126 or amino acids 21-131 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 106 or amino acids 1-119 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 106 or amino acids 1-119 thereof; or 
 (2) 
 a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 126 or amino acids 21-131 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 108 or amino acids 1-119 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 108 or amino acids 1-119 thereof; or 
 (3) 
 a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 126 or amino acids 21-131 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 110 or amino acids 1-119 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 110 or amino acids 1-119 thereof; or 
 (4) 
 a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 126 or amino acids 21-131 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 112 or amino acids 1-119 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 112 or amino acids 1-119 thereof; or 
 (5) 
 a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 126 or amino acids 21-131 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 114 or amino acids 1-119 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 114 or amino acids 1-119 thereof; or 
 (6) 
 a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 126 or amino acids 21-131 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 116 or amino acids 1-119 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 116 or amino acids 1-119 thereof; or 
 (7) 
 a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 126 or amino acids 21-131 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 118 or amino acids 1-119 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 118 or amino acids 1-119 thereof; or 
 (8) 
 a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 126 or amino acids 21-131 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 120 or amino acids 1-119 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 120 or amino acids 1-119 thereof; or 
 (9) 
 a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 126 or amino acids 21-131 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 122 or amino acids 1-119 thereof, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 122 or amino acids 1-119 thereof. 
 
     
     
         5 . The antibody or antigen-binding fragment of  claim 3  wherein said sequence identity is at least 95%, 96%, 97%, 98%, 99% or 100%. 
     
     
         6 . The antibody or antigen-binding fragment of  claim 5  comprising:
 (1) 
 a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 106 or amino acids 1-119 thereof; or 
 (2) 
 a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 108 or amino acids 1-119 thereof; or 
 (3) 
 a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 110 or amino acids 1-119 thereof; or 
 (4) 
 a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 112 or amino acids 1-119 thereof; or 
 (5) 
 a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 114 or amino acids 1-119 thereof; or 
 (6) 
 a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 116 or amino acids 1-119 thereof; or 
 (7) 
 a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 118 or amino acids 1-119 thereof; or 
 (8) 
 a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 120 or amino acids 1-119 thereof; or 
 (9) 
 a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 126 or amino acids 21-131 thereof, and/or 
 a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 122 or amino acids 1-119 thereof. 
 
     
     
         7 . The antibody or antigen-binding fragment thereof of  claim 1  comprising:
 a mature or unprocessed V L  domain or light chain immunoglobulin of SEQ ID NO: 7, 17, 27, 37, 57, 59, 61, 63, 65, 101, 126, 130, 132, 136, 138, 208, 210, 224, 226, 228, 230, 232, 241, 257, 259, 261, 263, 351, 369, 371, 373, 375, 401, 403, 405 or 422-430; and/or 
 a mature or unprocessed V H  domain or heavy chain immunoglobulin of SEQ ID NO: 2, 12, 22, 32, 45, 47, 49, 51, 53, 55, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 103, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 128, 134, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 212, 214, 216, 218, 220, 222, 234, 235, 237, 239, 243, 245, 247, 249, 251, 253, 255, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 353, 355, 357, 359, 361, 363, 365, 367, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 406-421 or 431-442. 
 
     
     
         8 . An antibody or antigen-binding fragment thereof that specifically binds human LAG3 that:
 (i) binds to human LAG3 by contacting residues  QEGAPAQL  (amino acids 35-42 of SEQ ID NO: 443) and  RPARRADAGEYRAAVH  (amino acids 137-152 of SEQ ID NO: 443) and, optionally, residues  DERGRQRGDFSLW  (amino acids 123-135 of SEQ ID NO: 443) of LAG3; or residues  SPTIPLQDL  (amino acids 45-53 of SEQ ID NO: 443) and, optionally  DERGRQRGDFSL  (amino acids 123-134 of SEQ ID NO: 443); or residues  HPLAPGPHPAAPSSWGPRPRRYTVL  (amino acids 78-102 of SEQ ID NO: 443); and/or   (ii) specifically binds to human LAG3 and comprises a heavy chain immunoglobulin variable region having at least 78.99% amino acid sequence identity to amino acids 1-119 of SEQ ID NO: 106; and/or a light chain immunoglobulin variable region having at least 78.38% amino acid sequence identity to amino acids 1-111 of SEQ ID NO: 224;   wherein the antibody or fragment optionally cross-blocks or is cross-blocked by an antibody or fragment of any one of  claims 1 - 7 .   
     
     
         9 . The antibody or fragment of  claim 1  which is glycosylated with engineered yeast N-linked glycans or CHO N-linked glycans. 
     
     
         10 . The antibody or fragment of  claim 1  which is an antibody. 
     
     
         11 . A composition or kit comprising the antibody or fragment of  claim 1  in association with a further therapeutic agent. 
     
     
         12 . A polypeptide comprising an amino acid sequence selected from the group consisting of 2, 3, 4, 5, 7, 8, 9, 10, 12, 13, 14, 15, 17, 18, 19, 20, 22, 23, 24, 25, 27, 28, 29, 30, 32, 33, 34, 35, 37, 38, 39, 40, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 426, 427, 434, 435, 436, 437, 438, 439, 440, 441, 442, 446, 448, 449, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463 and 464; or a mature fragment and/or variable immunoglobulin domain thereof. 
     
     
         13 . A polynucleotide encoding the polypeptide of  claim 12 . 
     
     
         14 . A vector comprising the polynucleotide of  claim 13 . 
     
     
         15 . A host cell comprising the antibody of  claim 1 . 
     
     
         16 . A composition comprising the antibody, antigen-binding fragment, polypeptide, polynucleotide or vector of  claim 1  and a pharmaceutically acceptable carrier or diluent; optionally in association with a further therapeutic agent. 
     
     
         17 . A vaccine comprising an antigen and a pharmaceutically acceptable carrier in association with an antibody or fragment or composition of  claim 1 . 
     
     
         18 . A vessel or injection device comprising the antibody, antigen-binding fragment, composition, polypeptide, polynucleotide or vector of  claim 1 ; optionally, wherein the vessel or device includes a pharmaceutically acceptable carrier or diluent. 
     
     
         19 . The composition or kit of  claim 11  wherein the further therapeutic agent is a member selected from the group consisting of:
 an anti-cancer therapeutic agent, an inhibitor of an immunomodulatory receptor, an anti-emetic, an MTOR (mammalian target of rapamycin) inhibitor, a cytotoxic agent, a platinum agent, an EGFR inhibitor, a VEGF inhibitor, a microtubule stabilizer, a taxane, a CD20 inhibitor, a CD52 inhibitor, a CD30 inhibitor, a RANK (Receptor activator of nuclear factor kappa-B) inhibitor, a RANKL (Receptor activator of nuclear factor kappa-B ligand) inhibitor, an ERK inhibitor, a MAP Kinase inhibitor, an AKT inhibitor, a MEK inhibitor, a PI3K inhibitor, a HER1 inhibitor, a HER2 inhibitor, a HER3 inhibitor, a HER4 inhibitor, a Bcl2 inhibitor, a CD22 inhibitor, a CD79b inhibitor, an ErbB2 inhibitor, a farnesyl protein transferase inhibitor, an anti-PD1 antibody or an antigen-binding fragment thereof, pembrolizumab, nivolumab, CT-011, anti-CTLA4 antibody or an antigen-binding fragment thereof, anti-TIM3 antibody or an antigen-binding fragment thereof, anti-CS1 antibody or an antigen-binding fragment thereof, elotuzumab, anti-KIR2DL1/2/3 antibody or an antigen-binding fragment thereof, lirilumab, anti-CD137 antibody or an antigen-binding fragment thereof, urelumab, anti-GITR antibody or an antigen-binding fragment thereof, TRX518, anti-PD-L1 antibody or an antigen-binding fragment thereof, BMS-936559, MSB0010718C, MPDL3280A, anti-PD-L2 antibody or an antigen-binding fragment thereof, anti-ILT1 antibody or an antigen-binding fragment thereof, anti-ILT2 antibody or an antigen-binding fragment thereof, anti-ILT3 antibody or an antigen-binding fragment thereof, anti-ILT4 antibody or an antigen-binding fragment thereof, anti-ILT5 antibody or an antigen-binding fragment thereof, anti-ILT6 antibody or an antigen-binding fragment thereof, anti-ILT7 antibody or an antigen-binding fragment thereof, anti-ILT8 antibody or an antigen-binding fragment thereof, anti-CD40 antibody or an antigen-binding fragment thereof, anti-OX40 antibody or an antigen-binding fragment thereof, anti-CD137 antibody or an antigen-binding fragment thereof, anti-KIR2DL1 antibody or an antigen-binding fragment thereof, anti-KIR2DL2/3 antibody or an antigen-binding fragment thereof, anti-KIR2DL4 antibody or an antigen-binding fragment thereof, anti-KIR2DL5A antibody or an antigen-binding fragment thereof, anti-KIR2DL5B antibody or an antigen-binding fragment thereof, anti-KIR3DL1 antibody or an antigen-binding fragment thereof, anti-KIR3DL2 antibody or an antigen-binding fragment thereof, anti-KIR3DL3 antibody or an antigen-binding fragment thereof, anti-NKG2A antibody or an antigen-binding fragment thereof, anti-NKG2C antibody or an antigen-binding fragment thereof, anti-NKG2E antibody or an antigen-binding fragment thereof, IL-10, anti-IL10, anti-TSLP, PEGylated IL-10, 13-cis-retinoic acid, 3-[5-(methylsulfonylpiperadinemethyl)-indolyl]-quinolone, 4-hydroxytamoxifen, 5-deooxyuridine, 5′-deoxy-5-fluorouridine, 5-fluorouracil, 6-mecaptopurine, 7-hydroxystaurosporine, A-443654, abirateroneacetate, abraxane, ABT-578, acolbifene, ADS-100380, aflibercept, ALT-110, altretamine, amifostine, aminoglutethimide, amrubicin, Amsacrine, anagrelide, anastrozole, angiostatin, AP-23573, ARQ-197, arzoxifene, AS-252424, AS-605240, asparaginase, AT-9263, ATI3387, atrasentan, axitinib, AZD1152 , Bacillus Calmette - Guerin  (BCG) vaccine, batabulin, BC-210, BGJ398, besodutox, bevacizumab, bicalutamide, Bio111, BIO140, BKM120, bleomycin, BMS-214662, BMS-247550, BMS-275291, BMS-310705, bortezimib, buserelin, busulfan, calcitriol, camptothecin, canertinib, capecitabine, carboplatin, carmustine, CC8490, CEA vaccine, cediranib, CG-1521, CG-781, chlamydocin, chlorambucil, chlorotoxin, cilengitide, cimetidine, cisplatin, cladribine, clodronate, cobimetnib, COL-3, CP-724714, cyclophosphamide, cyproterone, cyproteroneacetate, cytarabine, cytosinearabinoside, dabrafenib, dacarbazine, dacinostat, dactinomycin, dalotuzumab, danusertib, dasatanib, daunorubicin, decatanib, deguelin, denileukin, deoxycoformycin, depsipeptide, diarylpropionitrile, diethylstilbestrol, diftitox, DNE03, docetaxel, dovitinib, doxorubicin, droloxifene, edotecarin, yttrium-90 labeled-edotreotide, edotreotide, EKB-569, EMD121974, encorafenib, endostatin, enzalutamide, enzastaurin, epirubicin, epithilone B, ERA-923, erbitux, erlotinib, estradiol, estramustine, etoposide, everolimus, exemestane, ficlatuzumab, finasteride, flavopiridol, floxuridine, fludarabine, fludrocortisone, fluoxymesterone, flutamide, FOLFOX regimen, fulvestrant, galeterone, ganetespib, gefitinib, gemcitabine, gimatecan, glucopyranosyl lipid A, goserelin, goserelin acetate, gossypol, GSK461364, GSK690693, HMR-3339, hydroxyprogesteronecaproate, hydroxyurea, IC87114, idarubicin, idoxyfene, ifosfamide, IM862, imatinib, imiquimod, IMC-1C11, INCB24360, INC280, INO1001, interferon, interleukin-2, interleukin-12, ipilimumab, irinotecan, JNJ-16241199, ketoconazole, KRX-0402, lapatinib, lasofoxifene, LEE011, letrozole, leucovorin, leuprolide, leuprolide acetate, levamisole, liposome entrapped paclitaxel, lomustine, lonafarnib, lucanthone, LY292223, LY292696, LY293646, LY293684, LY294002, LY3009120, LY317615, marimastat, mechlorethamine, medroxyprogesteroneacetate, megestrolacetate, MEK162, melphalan, mercaptopurine, mesna, methotrexate, mithramycin, mitomycin, mitotane, mitoxantrone, tozasertib, MLN8054, a suspension of heat killed  Mycobacterium obuense , natitoclax, neovastat, neratinib, neuradiab, nilotinib, nilutimide, nolatrexed, NVP-BEZ235, oblimersen, octreotide, ofatumumab, oregovomab, ornatuzumab, orteronel, oxaliplatin, paclitaxel, palbociclib, pamidronate, panitumumab, pazopanib, PD0325901, PD184352, PEG-interferon, pemetrexed, pentostatin, perifosine, phenylalanine mustard, PI-103, pictilisib, PIK-75, pipendoxifene, PKI-166, plicamycin, PLX8394, poly-ICLC, porfimer, prednisone, procarbazine, progestins, PSK, PX-866, R-763, raloxifene, raltitrexed, razoxin, ridaforolimus, rituximab, romidepsin, RTA744, rubitecan, scriptaid, Sdx102, seliciclib, selumetinib, semaxanib, SF1126, sirolimus, SN36093, sorafenib, spironolactone, squalamine, SR13668, streptozocin, SU6668, suberoylanalide hydroxamic acid, sunitinib, synthetic estrogen, talampanel, talimogene laherparepvec, tamoxifen, temozolomide, temsirolimus, teniposide, tesmilifene, testosterone, tetrandrine, TGX-221, thalidomide, 6-thioguanine, thiotepa, ticilimumab, tipifarnib, tivozanib, TKI-258, TLK286, TNFα, topotecan, toremifene citrate, trabectedin, trametinib, trastuzumab, tretinoin, trichostatin A, triciribinephosphate monohydrate, triptorelin pamoate, TSE-424, uracil mustard, valproic acid, valrubicin, vandetanib, vatalanib, VEGF trap, vemurafenib, vinblastine, vincristine, vindesine, vinorelbine, vitaxin, vitespan, vorinostat, VX-745, wortmannin, Xr311, zanolimumab, ZK186619, ZK-304709, ZM336372, ZSTK474, Z-100, casopitant, netupitant, palonosetron, aprepitant, diphenhydramine, hydroxyzine, metoclopramide, lorazepam, alprazolam, haloperidol, droperidol, dronabinol, dexamethasone, methylprednisolone, prochlorperazine, granisetron, ondansetron, dolasetron, tropisetron, GCSF, PEG-GCSF, erythropoietin, epoetin alfa, darbepoetin alfa, a Bruton's tyrosine kinase (BTK) inhibitor, a prostate specific antigen vaccine, azacitidine, eribulin mesylate, lenvatinib mesylate, epacadostat, an anti-4-1BB agonist antibody or antigen-binding fragment, crizotinib, a CSF1 receptor kinase inhibitor, entinostat, birinapant, and niraparib. 
 
     
     
         20 . A method for antagonizing LAGS in a human patient in need thereof comprising administering, to the subject, an effective amount of the antibody or fragment of  claim 1 . 
     
     
         21 . A method of treating a cancer in a subject, comprising administering to the subject an effective amount of the antibody or antigen-binding fragment  claim 1  optionally, in association with a therapeutic procedure. 
     
     
         22 . The method of  claim 21  wherein the cancer is a member selected from the group consisting of cancer, metastatic cancer, a solid tumor, a hematologic cancer, leukemia, lymphoma, osteosarcoma, rhabdomyosarcoma, neuroblastoma, kidney cancer, leukemia, renal transitional cell cancer, bladder cancer, Wilm's cancer, ovarian cancer, pancreatic cancer, breast cancer, prostate cancer, bone cancer, lung cancer, non-small cell lung cancer, gastric cancer, colorectal cancer, cervical cancer, synovial sarcoma, head and neck cancer, squamous cell carcinoma, multiple myeloma, renal cell cancer, retinoblastoma, hepatoblastoma, hepatocellular carcinoma, melanoma, rhabdoid tumor of the kidney, Ewing's sarcoma, chondrosarcoma, brain cancer, glioblastoma, meningioma, pituitary adenoma, vestibular schwannoma, a primitive neuroectodermal tumor, medulloblastoma, astrocytoma, anaplastic astrocytoma, oligodendroglioma, ependymoma, choroid plexus papilloma, polycythemia vera, thrombocythemia, idiopathic myelfibrosis, soft tissue sarcoma, thyroid cancer, endometrial cancer, carcinoid cancer or liver cancer, breast cancer and gastric cancer. 
     
     
         23 . A method of administering the antibody or antigen-binding fragment of  claim 1 , to a subject, comprising injecting the antibody, fragment, polypeptide, vaccine or polynucleotide into the body of the subject using an injection device; and, optionally, also administering a further therapeutic agent or therapeutic procedure to the subject. 
     
     
         24 . A method of producing an antibody or antigen-binding fragment thereof of  claim 1  comprising:
 a. culturing a host cell comprising a polynucleotide encoding the polypeptide or an immunoglobulin chain of the antibody or antigen-binding fragment in a culture medium under conditions favorable to expression of the polynucleotide; and 
 b. optionally, recovering the antibody, antigen-binding fragment or polypeptide from the host cell and/or culture medium. 
 
     
     
         25 . The method of  claim 24  wherein the host cell is a Chinese hamster ovary cell. 
     
     
         26 . An antibody or antigen-binding fragment thereof that specifically binds human LAG3 or polypeptide which is the product of the method of  claim 24 . 
     
     
         27 . A method for detecting the presence of a LAG3 peptide or a fragment thereof in a sample comprising contacting the sample with an antibody or antigen-binding fragment of  claim 1  and detecting the presence of a complex between the antibody or fragment and the peptide; wherein detection of the complex indicates the presence of the LAG3 peptide.