CD112R targeting antibody or antigen binding fragment thereof and application thereof

Abstract

The invention relates to an anti-CD112R antibody or an antigen binding fragment thereof, and a preparation method and application thereof. The invention also relates to therapeutic and diagnostic uses of these antibodies, antibody fragments.

Description

An antibody targeting CD112R or its antigen-binding fragment and its application Technical Field

[0001] The present application relates to antibodies or antigen-binding fragments thereof that specifically recognize CD112R, as well as preparation methods and uses thereof. Background Art

[0002] CD112R, also known as poliovirus receptor-associated immunoglobulin domain-containing protein, Q6DKI7, or C7orf15, is a 326-amino acid transmembrane domain protein with a signal peptide (spanning amino acids 1 to 40), an extracellular domain (spanning amino acids 41 to 171), a transmembrane domain (spanning amino acids 172 to 190), and a cytoplasmic domain (spanning amino acids 191 to 326). CD112R binds to poliovirus receptor-associated protein 2 (PVLR2, also known as nectin2, CD112, or herpesvirus entry mediator B (HVEB), a human plasma membrane glycoprotein), a binding partner of CD112R.

[0003] Administration of anti-CD112R immunotherapy offers the opportunity to increase, enhance, and sustain immune responses. CD112R is an inhibitory receptor expressed primarily by T cells and NK cells, competing with the activating receptor CD226 for binding to CD112. CD112 interacts with CD112R with higher affinity than with CD226, effectively modulating CD226-mediated cell activation. Anti-CD112R antibodies that block the interaction with CD112 directly limit inhibitory signaling downstream of CD112R while promoting greater immune cell activation by increasing the interaction of CD226 with CD112. Treatment with anti-CD112R antibodies offers the opportunity to downregulate inhibitory signals that may occur when CD112R-expressing immune cells bind to CD112 on tumor cells and / or myeloid cells within the tumor microenvironment, potentially enhancing, increasing, and sustaining anti-tumor immune responses.

[0004] Although there are public anti-CD112R antibodies under development in the prior art, there is still an urgent need to develop high-quality anti-CD112R antibodies.

[0005] Summary of the Invention

[0006] In a first aspect, the present invention provides an antibody targeting human CD112R, which has the following advantages:

[0007] (1) Binds to human / cynomolgus monkey CD112R protein with high affinity;

[0008] (2) inhibiting or blocking the binding of human CD112R protein to human CD112 or cells expressing human CD112;

[0009] (3) After blocking the binding of CD112R protein to CD112, CD8 T cells are stimulated to kill tumor cells.

[0010] In one embodiment, the present invention provides an anti-CD112R antibody and an antigen-binding fragment thereof that specifically binds to CD112R, comprising:

[0011] 1) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 430, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 431;

[0012] 2) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 432, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 433;

[0013] 3) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 434, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 435;

[0014] 4) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 436, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 437;

[0015] 5) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 438, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 439;

[0016] 6) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 438, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 440;

[0017] 7) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 441, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 442;

[0018] 8) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 443, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 444;

[0019] 9) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 445, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 446;

[0020] 10) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 447, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 448;

[0021] 11) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 449 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 450;

[0022] 12) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 451, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 452;

[0023] 13) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 453, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 454;

[0024] 14) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 455, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 456;

[0025] 15) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 457 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 458;

[0026] 16) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 459 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 460;

[0027] 17) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 461, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 462;

[0028] 18) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 463, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 464;

[0029] 19) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 465, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 466;

[0030] 20) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 467, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 468;

[0031] 21) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 469 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 470;

[0032] 22) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 471, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 472;

[0033] 23) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 473, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 474;

[0034] 24) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 475 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 476;

[0035] 25) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 477 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 478;

[0036] 26) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 479 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 480;

[0037] 27) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 481 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 482;

[0038] 28) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 483 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 484;

[0039] 29) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 485 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 486;

[0040] 30) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 487 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 456;

[0041] 31) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 488 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 489;

[0042] 32) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 490 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 491;

[0043] 33) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 492 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 489;

[0044] 34) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 493, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 494;

[0045] 35) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 493, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 495;

[0046] 36) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 496, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 497;

[0047] 37) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 498 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 497;

[0048] 38) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 499 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 500;

[0049] 39) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 501 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 503;

[0050] 40) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 502, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 503;

[0051] 41) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 504, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 505;

[0052] 42) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 499 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 506;

[0053] 43) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 507, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 503;

[0054] 44) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 508 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 509;

[0055] 45) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 510 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 511;

[0056] 46) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 512, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 513;

[0057] 47) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 514 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 515;

[0058] 48) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 501 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 516;

[0059] 49) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 517 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 518;

[0060] 50) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 519 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 520;

[0061] 51) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 521, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 522;

[0062] 52) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 523, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 524;

[0063] 53) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 525 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 486;

[0064] 54) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 526, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 527;

[0065] 55) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 528 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 529;

[0066] 56) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 530 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 531;

[0067] 57) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 530 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 533;

[0068] 58) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 532 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 531;

[0069] 59) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 532 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 533;

[0070] 60) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 534 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 535;

[0071] 61) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 536, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 537;

[0072] 62) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 538 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 539;

[0073] 63) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 540 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 541;

[0074] 64) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 540 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 542;

[0075] 65) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 543 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 544;

[0076] 66) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 545 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 546;

[0077] 67) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 547 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 548;

[0078] 68) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 549 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 550;

[0079] 69) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 551 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 552;

[0080] 70) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 553 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 554;

[0081] 71) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 555 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 556;

[0082] 72) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 557 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 558;

[0083] 73) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 559 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 560;

[0084] 74) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 561 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 554;

[0085] 75) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 562, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 563;

[0086] 76) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 564 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 565;

[0087] 77) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 566, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 567;

[0088] 78) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 568 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 569;

[0089] 79) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 570 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 571;

[0090] 80) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 572, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 573;

[0091] 81) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 574, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 575;

[0092] 82) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 576 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 578;

[0093] 83) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 577 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 578;

[0094] 84) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 579 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 580;

[0095] 85) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 581 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 582;

[0096] 86) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 583 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 584;

[0097] 87) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 585 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 586;

[0098] 88) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 587 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 588;

[0099] 89) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 587 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 589;

[0100] 90) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 590 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 591;

[0101] 91) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 592, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 593;

[0102] 92) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 592, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 594;

[0103] 93) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 595 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 596;

[0104] 94) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 595, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 594;

[0105] 95) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 597 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 598;

[0106] 96) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 597 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 594;

[0107] 97) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 599 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 600;

[0108] 98) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 601 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 602;

[0109] 99) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 603 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 604;

[0110] 100) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 605, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 606;

[0111] 101) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 607, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 608;

[0112] 102) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 609, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 610;

[0113] 103) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 611, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 612;

[0114] 104) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 613, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 614;

[0115] 105) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 615, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 616;

[0116] 106) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 617, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 618;

[0117] 107) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 619, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 620;

[0118] 108) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 621, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 622;

[0119] 109) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 623, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 624;

[0120] 110) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 625, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 626;

[0121] 111) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 627, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 628;

[0122] 112) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 629, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 630;

[0123] 113) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 631, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 632;

[0124] 114) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 617, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 633;

[0125] 115) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 634, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 635;

[0126] 116) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 636, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 637;

[0127] 117) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 638, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 639;

[0128] 118) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 640, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 641;

[0129] 119) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 642, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 643;

[0130] 120) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 644, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 645;

[0131] 121) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 646, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 647;

[0132] 122) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 648, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 649;

[0133] 123) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 650, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 651;

[0134] 124) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 652, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 653;

[0135] 125) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 654, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 655;

[0136] 126) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 656 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 653.

[0137] In one embodiment, the present invention provides an anti-CD112R antibody and an antigen-binding fragment thereof that specifically binds to CD112R, comprising:

[0138] 1) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NOs: 1, 64, and 162, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NOs: 239, 307, and 357, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0139] 2) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NOs: 2, 65, and 162, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NOs: 239, 308, and 358, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0140] 3) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 3, 66, 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 240, 309, 359, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0141] 4) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 4, 67, 164, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 239, 310, 360, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0142] 5) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 5, 68, 165, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 241, 311, 361, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0143] 6) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 5, 68, 165, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 242, 312, 362, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0144] 7) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 6, 69, 166, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 243, 313, 363, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0145] 8) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 7, 70, 167, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 244, 314, 364, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0146] 9) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 8, 71, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 245, 313, 365, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0147] 10) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NOs: 3, 72, 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NOs: 241, 311, 359, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0148] 11) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 9, 73, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 245, 313, 363, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0149] 12) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NOs: 3, 74, 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NOs: 246, 311, 359, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0150] 13) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 10, 75, 169, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 247, 315, 366, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0151] 14) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 10, 75, 170, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 247, 315, 366, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0152] 15) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 9, 76, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 243, 313, 363, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0153] 16) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 9, 77, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 248, 313, 363, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0154] 17) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 8, 77, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 243, 313, 365, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0155] 18) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 7, 78, 167, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 244, 314, 364, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0156] 19) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 11, 79, 171, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 249, 316, 367, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0157] 20) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 2, 80, 162, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 239, 317, 368, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0158] 21) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 12, 81, 172, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 250, 315, 369, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0159] 22) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 10, 82, 169, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 247, 315, 370, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0160] 23) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 2, 83, 173, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 242, 312, 371, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0161] 24) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 13, 84, 173, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 242, 312, 372, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0162] 25) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 2, 85, 174, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 251, 318, 373, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0163] 26) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 14, 86, 175, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 252, 319, 374, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0164] 27) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 15, 87, 176, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 253, 320, 375, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0165] 28) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 16, 88, 177, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 254, 321, 376, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0166] 29) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 2, 89, or 178, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 241, 311, or 377, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0167] 30) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 17, 75, 169, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 247, 315, 366, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0168] 31) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 18, 85, 162, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 239, 322, 378, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0169] 32) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 2, 90, 162, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 255, 308, 368, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0170] 33) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 19, 91, 179, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 239, 322, 378, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0171] 34) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 2, 85, 180, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 256, 323, 379, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0172] 35) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 2, 85, 180, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 239, 308, 380, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0173] 36) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 20, 92, 181, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 257, 324, 381, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0174] 37) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 21, 93, 182, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 258, 325, 382, ​​or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0175] 38) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 22, 94, 183, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 259, 323, 383, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0176] 39) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 23, 94, 183, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 259, 323, 383, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0177] 40) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 24, 95, 184, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 247, 326, 384, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0178] 41) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 21, 93, 182, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 247, 326, 385, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0179] 42) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 22, 94, 183, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 259, 323, 383, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0180] 43) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 25, 96, 185, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 260, 327, 386, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0181] 44) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NOs: 26, 97, 186, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NOs: 261, 328, 387, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0182] 45) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 27, 98, 187, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 262, 328, 388, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0183] 46) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 28, 99, 188, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 263, 328, 388, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0184] 47) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 22, 94, 183, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 239, 308, 389, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0185] 48) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 5, 100, or 189, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 264, 329, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0186] 49) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 24, 101, 190, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 247, 326, 385, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0187] 50) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 28, 102, 191, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 265, 328, 391, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0188] 51) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 28, 103, 192, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 266, 328, 388, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0189] 52) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 29, 104, 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 241, 311, 377, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0190] 53) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 30, 105, 193, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 267, 330, 392, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0191] 54) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 5, 106, 194, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 268, 331, 393, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0192] 55) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 31, 107, 195, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 256, 318, 392, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0193] 56) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 31, 107, 195, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 269, 332, 394, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0194] 57) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 32, 108, 196, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 256, 318, 392, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0195] 58) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 32, 108, 196, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 269, 332, 394, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0196] 59) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 29, 109, 197, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 241, 311, 395, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0197] 60) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 33, 110, or 198, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 270, 333, or 396, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0198] 61) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 5, 111, 199, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 256, 318, 397, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0199] 62) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 34, 112, 200, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 269, 334, 398, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0200] 63) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 34, 112, 200, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 271, 335, 399, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0201] 64) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 35, 113, or 201, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 241, 311, or 400, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0202] 65) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 36, 114, or 202, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 272, 336, or 401, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0203] 66) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 29, 115, 203, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 241, 311, 402, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0204] 67) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 37, 116, 204, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 273, 337, 403, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0205] 68) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 5, 117, 205, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 274, 338, 404, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0206] 69) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 38, 110, 198, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 270, 333, 405, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0207] 70) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 39, 118, 204, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 275, 337, 406, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0208] 71) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 5, 119, 206, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 276, 338, 407, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0209] 72) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 29, 109, 197, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 241, 311, 395, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0210] 73) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 38, 110, 198, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 270, 333, 405, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0211] 74) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 5, 120, 205, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 277, 338, 407, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0212] 75) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 5, 121, 207, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 278, 338, 404, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0213] 76) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 35, 122, or 201, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 279, 311, or 408, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0214] 77) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 35, 123, 208, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 280, 311, 400, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0215] 78) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 5, 124, or 209, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 281, 338, or 407, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0216] 79) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 40, 125, 210, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 282, 339, 409, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0217] 80) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 41, 126, 211, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 245, 333, 410, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0218] 81) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 10, 127, or 212, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 239, 308, or 411, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0219] 82) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 40, 125, 213, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 239, 308, 411, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0220] 83) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 42, 128, or 214, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 283, 324, or 412, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0221] 84) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 43, 129, or 215, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 284, 339, or 409, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0222] 85) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 42, 130, or 216, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 285, 340, or 409, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0223] 86) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 44, 131, 217, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 286, 341, 413, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0224] 87) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 44, 132, 218, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 282, 341, 414, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0225] 88) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 44, 132, 218, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 287, 342, 415, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0226] 89) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 45, 133, or 219, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 288, 343, or 416, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0227] 90) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 46, 134, or 220, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 289, 324, or 417, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0228] 91) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 46, 134, or 220, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 290, 344, or 418, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0229] 92) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 47, 135, or 221, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 291, 345, or 407, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0230] 93) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 47, 135, or 221, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 290, 344, or 418, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0231] 94) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 48, 136, or 222, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 292, 346, or 409, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0232] 95) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 48, 136, or 222, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 290, 344, or 418, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0233] 96) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 49, 137, 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 240, 347, 419, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0234] 97) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 45, 138, 223, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 288, 343, 416, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0235] 98) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 50, 139, 224, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 249, 348, 420, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0236] 99) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 51, 140, 225, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 256, 349, 421, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0237] 100) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 47, 141, 221, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 293, 345, 407, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0238] 101) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 52, 142, 226, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 294, 350, 422, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0239] 102) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 53, 143, 178, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 295, 311, 423, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0240] 103) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 53, 144, or 178, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 241, 311, or 361, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0241] 104) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 53, 145, or 227, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 241, 311, or 361, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0242] 105) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 54, 146, 228, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 296, 328, 391, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0243] 106) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 55, 147, 228, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 266, 328, 391, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0244] 107) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 50, 148, 229, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 297, 351, 424, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0245] 108) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 56, 149, 230, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 298, 323, 425, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0246] 109) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 57, 150, 231, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 299, 338, 407, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0247] 110) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 58, 151, or 232, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 300, 352, or 426, or a sequence containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0248] 111) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 59, 152, 233, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 301, 328, 388, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0249] 112) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 60, 153, 234, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 239, 308, 360, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0250] 113) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 54, 146, 228, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 302, 328, 391, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0251] 114) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 61, 154, 235, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 241, 311, 361, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0252] 115) comprising a HCDR1, HCDR2, or HCDR3 of a sequence as shown in SEQ ID NO: 40, 125, or 210, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, or LCDR3 of a sequence as shown in SEQ ID NO: 282, 353, or 409, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0253] 116) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 44, 155, 236, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 303, 324, 409, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0254] 117) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 44, 156, 217, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 282, 341, 414, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0255] 118) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 62, 157, 237, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 304, 332, 427, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0256] 119) comprising HCDR1, HCDR2, HCDR3 of the sequences shown in SEQ ID NO: 24, 158, 184, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 of the sequences shown in SEQ ID NO: 247, 326, 428, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences;

[0257] 120) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 3, 159, 189, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 249, 354, 382, ​​or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence;

[0258] 121) comprising a HCDR1, HCDR2, HCDR3 of a sequence as shown in SEQ ID NO: 63, 160, 238, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; and a LCDR1, LCDR2, LCDR3 of a sequence as shown in SEQ ID NO: 305, 355, 429, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequence; or

[0259] 122) comprises HCDR1, HCDR2, HCDR3 of the sequence shown in SEQ ID NO: 42, 161, 214, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to the sequence; and LCDR1, LCDR2, LCDR3 of the sequence shown in SEQ ID NO: 306, 356, 409, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to the sequence.

[0260] In one embodiment, the present invention provides an anti-CD112R antibody and an antigen-binding fragment thereof that specifically binds to CD112R, comprising a heavy chain variable region, wherein:

[0261] 1) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 430, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 430, or consists of SEQ ID NO: 430;

[0262] 2) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 432, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 432, or consists of SEQ ID NO: 432;

[0263] 3) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 434, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 434;

[0264] 4) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 436, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 436, or consists of SEQ ID NO: 436;

[0265] 5) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 438, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 438;

[0266] 6) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 441, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 441, or consists of SEQ ID NO: 441;

[0267] 7) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 443, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 443, or consists of SEQ ID NO: 443;

[0268] 8) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 445, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 445, or consists of SEQ ID NO: 445;

[0269] 9) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 447, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 447, or consists of SEQ ID NO: 447;

[0270] 10) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 449, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 449, or consists of SEQ ID NO: 449;

[0271] 11) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 451, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 451, or consists of SEQ ID NO: 451;

[0272] 12) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 453, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 453, or consists of SEQ ID NO: 453;

[0273] 13) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 455, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 455, or consists of SEQ ID NO: 455;

[0274] 14) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 457, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 457, or consists of SEQ ID NO: 457;

[0275] 15) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 459, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 459, or consists of SEQ ID NO: 459;

[0276] 16) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 461, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 461, or consists of SEQ ID NO: 461;

[0277] 17) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 463, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 463, or consists of SEQ ID NO: 463;

[0278] 18) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 465, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 465, or consists of SEQ ID NO: 465;

[0279] 19) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 467, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 467, or consists of SEQ ID NO: 467;

[0280] 20) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 469, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 469, or consists of SEQ ID NO: 469;

[0281] 21) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 471, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 471, or consists of SEQ ID NO: 471;

[0282] 22) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 473, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 473, or consists of SEQ ID NO: 473;

[0283] 23) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 475, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 475, or consists of SEQ ID NO: 475;

[0284] 24) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 477, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 477, or consists of SEQ ID NO: 477;

[0285] 25) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 479, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 479, or consists of SEQ ID NO: 479;

[0286] 26) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 481, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 481, or consists of SEQ ID NO: 481;

[0287] 27) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 483, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 483, or consists of SEQ ID NO: 483;

[0288] 28) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 485, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 485, or consists of SEQ ID NO: 485;

[0289] 29) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 487, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 487, or consists of SEQ ID NO: 487;

[0290] 30) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 488, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 488, or consists of SEQ ID NO: 488;

[0291] 31) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 490, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 490, or consists of SEQ ID NO: 490;

[0292] 32) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 492, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 492, or consists of SEQ ID NO: 492;

[0293] 33) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 493, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 493, or consists of SEQ ID NO: 493;

[0294] 34) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 496, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 496, or consists of SEQ ID NO: 496;

[0295] 35) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 498, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 498, or consists of SEQ ID NO: 498;

[0296] 36) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 499, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 499, or consists of SEQ ID NO: 499;

[0297] 37) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 501, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 501, or consists of SEQ ID NO: 501;

[0298] 38) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 502, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 502, or consists of SEQ ID NO: 502;

[0299] 39) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 504, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 504, or consists of SEQ ID NO: 504;

[0300] 40) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 507, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 507, or consists of SEQ ID NO: 507;

[0301] 41) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 508, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 508, or consists of SEQ ID NO: 508;

[0302] 42) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 510, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 510, or consists of SEQ ID NO: 510;

[0303] 43) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 512, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 512, or consists of SEQ ID NO: 512;

[0304] 44) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 514, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 514, or consists of SEQ ID NO: 514;

[0305] 45) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 517, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 517, or consists of SEQ ID NO: 517;

[0306] 46) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 519, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 519, or consists of SEQ ID NO: 519;

[0307] 47) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 521, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 521, or consists of SEQ ID NO: 521;

[0308] 48) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 523, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 523, or consists of SEQ ID NO: 523;

[0309] 49) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 525, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 525, or consists of SEQ ID NO: 525;

[0310] 50) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 526, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 526, or consists of SEQ ID NO: 526;

[0311] 51) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 528, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 528, or consists of SEQ ID NO: 528;

[0312] 52) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 530, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 530, or consists of SEQ ID NO: 530;

[0313] 53) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 532, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 532, or consists of SEQ ID NO: 532;

[0314] 54) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 534, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 534, or consists of SEQ ID NO: 534;

[0315] 55) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 536, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 536, or consists of SEQ ID NO: 536;

[0316] 56) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 538, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 538, or consists of SEQ ID NO: 538;

[0317] 57) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 540, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 540, or consists of SEQ ID NO: 540;

[0318] 58) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 543, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 543, or consists of SEQ ID NO: 543;

[0319] 59) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 545, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 545, or consists of SEQ ID NO: 545;

[0320] 60) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 547, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 547, or consists of SEQ ID NO: 547;

[0321] 61) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 549, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 549, or consists of SEQ ID NO: 549;

[0322] 62) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 551, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 551, or consists of SEQ ID NO: 551;

[0323] 63) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 553, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 553, or consists of SEQ ID NO: 553;

[0324] 64) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 555, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 555, or consists of SEQ ID NO: 555;

[0325] 65) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 557, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 557, or consists of SEQ ID NO: 557;

[0326] 66) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 559, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 559, or consists of SEQ ID NO: 559;

[0327] 67) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 561, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 561, or consists of SEQ ID NO: 561;

[0328] 68) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 562, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 562, or consists of SEQ ID NO: 562;

[0329] 69) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 564, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 564, or consists of SEQ ID NO: 564;

[0330] 70) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 566, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 566, or consists of SEQ ID NO: 566;

[0331] 71) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 568, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 568, or consists of SEQ ID NO: 568;

[0332] 72) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 570, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 570, or consists of SEQ ID NO: 570;

[0333] 73) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 572, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 572, or consists of SEQ ID NO: 572;

[0334] 74) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 574, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 574, or consists of SEQ ID NO: 574;

[0335] 75) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 576, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 576, or consists of SEQ ID NO: 576;

[0336] 76) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 577, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 577, or consists of SEQ ID NO: 577;

[0337] 77) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 579, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 579, or consists of SEQ ID NO: 579;

[0338] 78) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 581, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 581, or consists of SEQ ID NO: 581;

[0339] 79) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 583, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 583, or consists of SEQ ID NO: 583;

[0340] 80) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 585, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 585, or consists of SEQ ID NO: 585;

[0341] 81) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 587, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 587, or consists of SEQ ID NO: 587;

[0342] 82) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 590, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 590, or consists of SEQ ID NO: 590;

[0343] 83) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 592, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 592, or consists of SEQ ID NO: 592;

[0344] 84) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 595, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 595, or consists of SEQ ID NO: 595;

[0345] 85) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 597, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 597, or consists of SEQ ID NO: 597;

[0346] 86) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 599, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 599, or consists of SEQ ID NO: 599;

[0347] 87) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 601, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 601, or consists of SEQ ID NO: 601;

[0348] 88) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 603, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 603, or consists of SEQ ID NO: 603;

[0349] 89) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 605, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 605, or consists of SEQ ID NO: 605;

[0350] 90) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 607, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 607, or consists of SEQ ID NO: 607;

[0351] 91) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 609, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 609, or consists of SEQ ID NO: 609;

[0352] 92) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 611, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 611, or consists of SEQ ID NO: 611;

[0353] 93) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 613, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 613, or consists of SEQ ID NO: 613;

[0354] 94) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 615, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 615, or consists of SEQ ID NO: 615;

[0355] 95) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 617, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 617, or consists of SEQ ID NO: 617;

[0356] 96) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 619, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 619, or consists of SEQ ID NO: 619;

[0357] 97) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 621, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 621, or consists of SEQ ID NO: 621;

[0358] 98) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 623, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 623, or consists of SEQ ID NO: 623;

[0359] 99) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 625, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 625, or consists of SEQ ID NO: 625;

[0360] 100) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 627, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 627, or consists of SEQ ID NO: 627;

[0361] 101) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 629, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 629, or consists of SEQ ID NO: 629;

[0362] 102) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 631, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 631, or consists of SEQ ID NO: 631;

[0363] 103) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 634, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 634, or consists of SEQ ID NO: 634;

[0364] 104) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 636, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 636, or consists of SEQ ID NO: 636;

[0365] 105) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 638, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 638, or consists of SEQ ID NO: 638;

[0366] 106) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 640, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 640, or consists of SEQ ID NO: 640;

[0367] 107) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 642, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 642, or consists of SEQ ID NO: 642;

[0368] 108) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 644, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 644, or consists of SEQ ID NO: 644;

[0369] 109) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 646, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 646, or consists of SEQ ID NO: 646;

[0370] 110) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 648, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 648, or consists of SEQ ID NO: 648;

[0371] 111) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 650, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 650, or consists of SEQ ID NO: 650;

[0372] 112) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 652, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 652, or consists of SEQ ID NO: 652;

[0373] 113) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 654, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 654, or consists of SEQ ID NO: 654; or

[0374] 114) The heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 656, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 656, or consists of SEQ ID NO: 656.

[0375] In one embodiment, the present invention provides an anti-CD112R antibody and an antigen-binding fragment thereof that specifically binds to CD112R, comprising a light chain variable region, wherein:

[0376] 1) the light chain variable region comprises the amino acid sequence of SEQ ID NO:431, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:431, or consists of SEQ ID NO:431;

[0377] 2) the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 433, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 433;

[0378] 3) the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 435, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 435;

[0379] 4) the light chain variable region comprises the amino acid sequence of SEQ ID NO:437, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:437, or consists of SEQ ID NO:437;

[0380] 5) the light chain variable region comprises the amino acid sequence of SEQ ID NO:439, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:439, or consists of SEQ ID NO:439;

[0381] 6) the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 440, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 440;

[0382] 7) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 442, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 442, or consists of SEQ ID NO: 442;

[0383] 8) the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 444, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 444;

[0384] 9) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 446, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 446, or consists of SEQ ID NO: 446;

[0385] 10) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 448, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 448, or consists of SEQ ID NO: 448;

[0386] 11) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 450, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 450, or consists of SEQ ID NO: 450;

[0387] 12) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 452, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 452, or consists of SEQ ID NO: 452;

[0388] 13) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 454, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 454, or consists of SEQ ID NO: 454;

[0389] 14) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 456, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 456, or consists of SEQ ID NO: 456;

[0390] 15) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 458, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 458, or consists of SEQ ID NO: 458;

[0391] 16) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 460, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 460, or consists of SEQ ID NO: 460;

[0392] 17) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 462, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 462, or consists of SEQ ID NO: 462;

[0393] 18) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 464, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 464, or consists of SEQ ID NO: 464;

[0394] 19) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 466, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 466, or consists of SEQ ID NO: 466;

[0395] 20) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 468, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 468, or consists of SEQ ID NO: 468;

[0396] 21) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 470, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 470, or consists of SEQ ID NO: 470;

[0397] 22) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 472, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 472, or consists of SEQ ID NO: 472;

[0398] 23) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 474, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 474, or consists of SEQ ID NO: 474;

[0399] 24) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 476, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 476, or consists of SEQ ID NO: 476;

[0400] 25) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 478, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 478, or consists of SEQ ID NO: 478;

[0401] 26) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 480, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 480, or consists of SEQ ID NO: 480;

[0402] 27) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 482, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 482, or consists of SEQ ID NO: 482;

[0403] 28) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 484, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 484, or consists of SEQ ID NO: 484;

[0404] 29) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 486, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 486, or consists of SEQ ID NO: 486;

[0405] 30) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 489, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 489, or consists of SEQ ID NO: 489;

[0406] 31) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 491, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 491, or consists of SEQ ID NO: 491;

[0407] 32) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 494, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 494, or consists of SEQ ID NO: 494;

[0408] 33) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 495, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 495, or consists of SEQ ID NO: 495;

[0409] 34) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 497, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 497, or consists of SEQ ID NO: 497;

[0410] 35) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 500, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 500, or consists of SEQ ID NO: 500;

[0411] 36) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 503, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 503, or consists of SEQ ID NO: 503;

[0412] 37) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 505, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 505, or consists of SEQ ID NO: 505;

[0413] 38) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 506, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 506, or consists of SEQ ID NO: 506;

[0414] 39) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 509, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 509, or consists of SEQ ID NO: 509;

[0415] 40) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 511, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 511, or consists of SEQ ID NO: 511;

[0416] 41) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 513, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 513, or consists of SEQ ID NO: 513;

[0417] 42) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 515, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 515, or consists of SEQ ID NO: 515;

[0418] 43) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 516, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 516, or consists of SEQ ID NO: 516;

[0419] 44) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 518, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 518, or consists of SEQ ID NO: 518;

[0420] 45) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 520, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 520, or consists of SEQ ID NO: 520;

[0421] 46) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 522, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 522, or consists of SEQ ID NO: 522;

[0422] 47) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 524, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 524, or consists of SEQ ID NO: 524;

[0423] 48) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 527, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 527, or consists of SEQ ID NO: 527;

[0424] 49) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 529, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 529, or consists of SEQ ID NO: 529;

[0425] 50) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 531, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 531, or consists of SEQ ID NO: 531;

[0426] 51) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 533, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 533, or consists of SEQ ID NO: 533;

[0427] 52) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 535, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 535, or consists of SEQ ID NO: 535;

[0428] 53) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 537, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 537, or consists of SEQ ID NO: 537;

[0429] 54) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 539, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 539, or consists of SEQ ID NO: 539;

[0430] 55) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 541, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 541, or consists of SEQ ID NO: 541;

[0431] 56) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 542, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 542, or consists of SEQ ID NO: 542;

[0432] 57) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 544, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 544, or consists of SEQ ID NO: 544;

[0433] 58) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 546, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 546, or consists of SEQ ID NO: 546;

[0434] 59) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 548, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 548, or consists of SEQ ID NO: 548;

[0435] 60) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 550, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 550, or consists of SEQ ID NO: 550;

[0436] 61) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 552, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 552, or consists of SEQ ID NO: 552;

[0437] 62) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 554, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 554, or consists of SEQ ID NO: 554;

[0438] 63) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 556, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 556, or consists of SEQ ID NO: 556;

[0439] 64) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 558, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 558, or consists of SEQ ID NO: 558;

[0440] 65) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 560, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 560, or consists of SEQ ID NO: 560;

[0441] 66) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 563, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 563, or consists of SEQ ID NO: 563;

[0442] 67) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 565, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 565, or consists of SEQ ID NO: 565;

[0443] 68) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 567, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 567, or consists of SEQ ID NO: 567;

[0444] 69) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 569, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 569, or consists of SEQ ID NO: 569;

[0445] 70) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 571, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 571, or consists of SEQ ID NO: 571;

[0446] 71) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 573, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 573, or consists of SEQ ID NO: 573;

[0447] 72) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 575, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 575, or consists of SEQ ID NO: 575;

[0448] 73) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 578, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 578, or consists of SEQ ID NO: 578;

[0449] 74) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 580, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 580, or consists of SEQ ID NO: 580;

[0450] 75) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 582, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 582, or consists of SEQ ID NO: 582;

[0451] 76) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 584, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 584, or consists of SEQ ID NO: 584;

[0452] 77) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 586, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 586, or consists of SEQ ID NO: 586;

[0453] 78) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 588, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 588, or consists of SEQ ID NO: 588;

[0454] 79) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 589, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 589, or consists of SEQ ID NO: 589;

[0455] 80) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 591, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 591, or consists of SEQ ID NO: 591;

[0456] 81) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 593, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 593, or consists of SEQ ID NO: 593;

[0457] 82) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 594, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 594, or consists of SEQ ID NO: 594;

[0458] 83) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 596, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 596, or consists of SEQ ID NO: 596;

[0459] 84) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 598, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 598, or consists of SEQ ID NO: 598;

[0460] 85) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 600, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 600, or consists of SEQ ID NO: 600;

[0461] 86) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 602, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 602, or consists of SEQ ID NO: 602;

[0462] 87) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 604, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 604, or consists of SEQ ID NO: 604;

[0463] 88) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 606, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 606, or consists of SEQ ID NO: 606;

[0464] 89) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 608, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 608, or consists of SEQ ID NO: 608;

[0465] 90) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 610, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 610, or consists of SEQ ID NO: 610;

[0466] 91) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 612, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 612, or consists of SEQ ID NO: 612;

[0467] 92) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 614, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 614, or consists of SEQ ID NO: 614;

[0468] 93) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 616, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 616, or consists of SEQ ID NO: 616;

[0469] 94) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 618, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 618, or consists of SEQ ID NO: 618;

[0470] 95) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 620, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 620, or consists of SEQ ID NO: 620;

[0471] 96) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 622, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 622, or consists of SEQ ID NO: 622;

[0472] 97) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 624, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 624, or consists of SEQ ID NO: 624;

[0473] 98) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 626, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 626, or consists of SEQ ID NO: 626;

[0474] 99) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 628, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 628, or consists of SEQ ID NO: 628;

[0475] 100) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 630, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 630, or consists of SEQ ID NO: 630;

[0476] 101) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 632, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 632, or consists of SEQ ID NO: 632;

[0477] 102) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 633, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 633, or consists of SEQ ID NO: 633;

[0478] 103) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 635, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 635, or consists of SEQ ID NO: 635;

[0479] 104) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 637, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 637, or consists of SEQ ID NO: 637;

[0480] 105) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 639, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 639, or consists of SEQ ID NO: 639;

[0481] 106) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 641, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 641, or consists of SEQ ID NO: 641;

[0482] 107) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 643, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 643, or consists of SEQ ID NO: 643;

[0483] 108) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 645, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 645, or consists of SEQ ID NO: 645;

[0484] 109) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 647, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 647, or consists of SEQ ID NO: 647;

[0485] 110) The light chain variable region comprises the amino acid sequence of SEQ ID NO: 649, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 649, or consists of SEQ ID NO: 649;

[0486] 111) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 651, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 651, or consists of SEQ ID NO: 651;

[0487] 112) the light chain variable region comprises the amino acid sequence of SEQ ID NO: 653, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 653, or consists of SEQ ID NO: 653; or

[0488] 113) The light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 655, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 655, or consists of SEQ ID NO: 655.

[0489] In another embodiment, the present invention provides an anti-CD112R antibody and an antigen-binding fragment thereof that specifically binds to CD112R, comprising a heavy chain variable region and a light chain variable region, wherein:

[0490] 1) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:430, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:430, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:431, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:431;

[0491] 2) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:432, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:432, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:433, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:433;

[0492] 3) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:434, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:434, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:435, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:435;

[0493] 4) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:436, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:436, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:437, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:437;

[0494] 5) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:438, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:438, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:439, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:439;

[0495] 6) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:438, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:438, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:440, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:440;

[0496] 7) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:441, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:441, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:442, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:442;

[0497] 8) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:443, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:443, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:444, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:444;

[0498] 9) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:445, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:445, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:446, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:446;

[0499] 10) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:447, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:447, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:448, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:448;

[0500] 11) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:449, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:449, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:450, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:450;

[0501] 12) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:451, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:451, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:452, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:452;

[0502] 13) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:453, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:453, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:454, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:454;

[0503] 14) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:455, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:455, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:456, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:456;

[0504] 15) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:457, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:457, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:458, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:458;

[0505] 16) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:459, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:459, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:460, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:460;

[0506] 17) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:461, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:461, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:462, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:462;

[0507] 18) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:463, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:463, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:464, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:464;

[0508] 19) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 465, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 465, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 466, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 466;

[0509] 20) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:467, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:467, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:468, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:468;

[0510] 21) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 469, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 469, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 470, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 470;

[0511] 22) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:471, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:471, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:472, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:472;

[0512] 23) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 473, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 473, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 474, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 474;

[0513] 24) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 475, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 475, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 476, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 476;

[0514] 25) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 477, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 477, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 478, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 478;

[0515] 26) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 479, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 479, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 480, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 480; or

[0516] 27) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 481, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 481, or consists of SEQ ID NO: 481, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 482, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 482, or consists of SEQ ID NO: 482.

[0517] 28) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 483, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 483, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 484, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 484;

[0518] 29) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 485, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 485, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 486, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 486;

[0519] 30) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 487, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 487, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 456, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 456;

[0520] 31) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 488, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 488, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 489, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 489;

[0521] 32) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 490, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 490, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 491, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 491;

[0522] 33) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 492, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 492, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 489, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 489;

[0523] 34) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 493, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 493, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 494, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 494;

[0524] 35) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 493, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 493, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 495, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 495;

[0525] 36) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 496, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 496, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 497, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 497;

[0526] 37) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 498, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 498, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 497, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 497;

[0527] 38) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 499, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 499, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 500, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 500;

[0528] 39) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:501, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:501, or consists of SEQ ID NO:501, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:503, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:503, or consists of SEQ ID NO:503;

[0529] 40) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:502, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:502, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:503, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:503;

[0530] 41) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:504, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:504, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:505, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:505;

[0531] 42) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 499, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 499, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 506;

[0532] 43) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:507, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:507, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:503, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:503;

[0533] 44) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:508, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:508, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:509, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:509;

[0534] 45) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:510, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:510, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:511, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:511;

[0535] 46) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 512, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 512, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 513, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 513; or

[0536] 47) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 514, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 514, or consists of SEQ ID NO: 514, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 515, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 515, or consists of SEQ ID NO: 515.

[0537] 48) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:501, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:501, or consists of SEQ ID NO:501, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:516, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:516, or consists of SEQ ID NO:516;

[0538] 49) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:517, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:517, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:518, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:518;

[0539] 50) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:519, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:519, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:520, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:520;

[0540] 51) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:521, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:521, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:522, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:522;

[0541] 52) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:523, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:523, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:524, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:524;

[0542] 53) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:525, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:525, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:486, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:486;

[0543] 54) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:526, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:526, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:527, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:527;

[0544] 55) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:528, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:528, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:529, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:529;

[0545] 56) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:530, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:530, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:531, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:531;

[0546] 57) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:530, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:530, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:533, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:533;

[0547] 58) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:532, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:532, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:531, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:531;

[0548] 59) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:532, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:532, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:533, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:533;

[0549] 60) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:534, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:534, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:535, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:535;

[0550] 61) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:536, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:536, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:537, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:537;

[0551] 62) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:538, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:538, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:539, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:539;

[0552] 63) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:540, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:540, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:541, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:541;

[0553] 64) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:540, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:540, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:542, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:542;

[0554] 65) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:543, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:543, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:544, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:544;

[0555] 66) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:545, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:545, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:546, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:546; or

[0556] 67) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 547, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 547, or consists of SEQ ID NO: 547, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 548, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 548, or consists of SEQ ID NO: 548.

[0557] 68) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:549, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:549, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:550, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:550;

[0558] 69) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:551, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:551, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:552, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:552;

[0559] 70) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 553, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 553, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 554, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 554;

[0560] 71) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:555, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:555, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:556, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:556;

[0561] 72) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:557, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:557, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:558, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:558;

[0562] 73) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 559, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 559, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 560, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 560;

[0563] 74) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:561, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:561, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:554, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:554;

[0564] 75) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:562, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:562, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:563, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:563;

[0565] 76) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:564, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:564, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:565, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:565;

[0566] 77) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:566, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:566, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:567, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:567;

[0567] 78) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:568, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:568, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:569, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:569;

[0568] 79) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 570, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 570, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 571, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 571;

[0569] 80) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:572, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:572, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:573, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:573;

[0570] 81) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:574, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:574, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:575, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:575;

[0571] 82) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:576, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:576, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:578, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:578;

[0572] 83) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 577, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 577, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 578, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 578;

[0573] 84) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 579, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 579, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 580, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 580;

[0574] 85) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:581, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:581, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:582, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:582;

[0575] 86) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 583, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 583, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 584, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 584; or

[0576] 87) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 585, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 585, or consists of SEQ ID NO: 585, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 586, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 586, or consists of SEQ ID NO: 586.

[0577] 88) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:587, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:587, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:588, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:588;

[0578] 89) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:587, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:587, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:589, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:589;

[0579] 90) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:590, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:590, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:591, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:591;

[0580] 91) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:592, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:592, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:593, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:593;

[0581] 92) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:592, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:592, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:594, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:594;

[0582] 93) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:595, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:595, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:596, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:596;

[0583] 94) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:595, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:595, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:594, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:594;

[0584] 95) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:597, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:597, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:598, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:598;

[0585] 96) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:597, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:597, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:594, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:594;

[0586] 97) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:599, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:599, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:600, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:600;

[0587] 98) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:601, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:601, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:602, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:602;

[0588] 99) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:603, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:603, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:604, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:604;

[0589] 100) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:605, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:605, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:606, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:606;

[0590] 101) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:607, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:607, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:608, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:608;

[0591] 102) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:609, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:609, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:610, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:610;

[0592] 103) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:611, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:611, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:612, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:612;

[0593] 104) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:613, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:613, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:614, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:614;

[0594] 105) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:615, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:615, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:616, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:616;

[0595] 106) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:617, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:617, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:618, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO:618; or

[0596] 107) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 619, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 619, or consists of SEQ ID NO: 619, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 620, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 620, or consists of SEQ ID NO: 620.

[0597] 108) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:621, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:621, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:622, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:622;

[0598] 109) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 623, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 623, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 624, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 624;

[0599] 110) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:625, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:625, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:626, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:626;

[0600] 111) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:627, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:627, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:628, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:628;

[0601] 112) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 629, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 629, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 630, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 630;

[0602] 113) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 631, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 631, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 632, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 632;

[0603] 114) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:617, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:617, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:633, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:633;

[0604] 115) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 634, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 634, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 635, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 635;

[0605] 116) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 636, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 636, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 637, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 637;

[0606] 117) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 638, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 638, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 639, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 639;

[0607] 118) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 640, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 640, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 641, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 641;

[0608] 119) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 642, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 642, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 643, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 643;

[0609] 120) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:644, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:644, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:645, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:645;

[0610] 121) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 646, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 646, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 647, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 647;

[0611] 122) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 648, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 648, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 649, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 649;

[0612] 123) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 650, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 650, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 651, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 651;

[0613] 124) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 652, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 652, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO: 653, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO: 653;

[0614] 125) the heavy chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:654, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:654, and the light chain variable region comprises, or consists of, the amino acid sequence of SEQ ID NO:655, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence of SEQ ID NO:655;

[0615] 126) The heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 656, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 656, or consists of SEQ ID NO: 656, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 653, or an amino acid sequence that is at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of SEQ ID NO: 653, or consists of SEQ ID NO: 653.

[0616] In some embodiments, the above-mentioned antibodies or antigen-binding fragments thereof further comprise heavy chain and / or light chain constant region sequences derived from the human antibody germline consensus sequence. The light chain constant region is preferably a human kappa or lambda chain constant region. The heavy chain constant region can be a gamma, mu, alpha, delta, or epsilon chain. In some embodiments, the heavy chain constant region is preferably derived from the constant region sequence of human IgG1, IgG2, IgG3, or IgG4. In one embodiment, the light chain constant region comprises the sequence shown in SEQ ID NO: 660, or consists of the sequence. In another embodiment, the heavy chain constant region comprises the Fc sequence shown in SEQ ID NO: 661. In yet another embodiment, the heavy chain constant region comprises the sequence shown in SEQ ID NO: 659, or consists of the sequence.

[0617] It will be appreciated that sequence variants of these constant region domains may also be used, for example comprising one or more amino acid modifications, wherein amino acid positions are identified according to the EU index system of Kabat et al. (1991).

[0618] In certain embodiments of any of the foregoing antibodies, the antibody is a monoclonal antibody.

[0619] In certain embodiments of the antibody of any of the foregoing, the antibody is a full-length antibody.

[0620] In one embodiment, the anti-CD112R antibodies of the present invention are complete antibodies, such as IgG1, IgG2, IgG3, IgG4 antibodies. In another embodiment, the anti-CD112R antibodies of the present invention only encompass their antigen-binding portions, such as Fab, Fab'-SH, Fv, scFv or (Fab')2 fragments.

[0621] In a second aspect, the present invention provides an isolated polynucleotide molecule encoding any one of the antibodies or antigen-binding fragments thereof described in the first aspect.

[0622] In a third aspect, the present invention provides an expression vector comprising the nucleotide molecule of the second aspect. In one embodiment, the vector is a eukaryotic expression vector.

[0623] In a fourth aspect, the present invention provides a host cell comprising the vector of the third aspect or the nucleotide molecule of the second aspect. In some embodiments, the host cell is prokaryotic, such as Escherichia coli. In other embodiments, the host cell is eukaryotic, such as 293 cells, CHO cells, yeast cells, or plant cells.

[0624] In a fifth aspect, the present invention provides a pharmaceutical composition comprising (1) the antibody or antigen-binding fragment thereof of the first aspect, or the polynucleotide molecule of the second aspect, or the expression vector of the third aspect, or the host cell of the fourth aspect, and (2) a pharmaceutically acceptable carrier or excipient.

[0625] In a sixth aspect, the present invention provides a method for preparing the anti-CD112R antibody or its antigen-binding fragment described herein, the method comprising expressing the antibody or its antigen-binding fragment in a host cell described herein under conditions suitable for expression of the antibody or its antigen-binding fragment, and recovering the expressed antibody or its antigen-binding fragment from the host cell.

[0626] In a seventh aspect, the antibodies or antigen-binding fragments thereof or pharmaceutical compositions of the present invention can also be administered in combination with one or more other therapies, such as treatment modalities and / or other therapeutic agents, for the purposes described herein, such as for preventing and / or treating the related diseases or conditions mentioned herein.

[0627] In an eighth aspect, the present invention provides a pharmaceutical combination comprising an antibody or antigen-binding fragment thereof or a pharmaceutical composition as described herein, and one or more additional therapeutic agents.

[0628] In a ninth aspect, the present invention provides a method for preventing or treating a CD112R-mediated disease in a subject in need thereof, comprising administering to the subject a preventively effective amount or a therapeutically effective amount of the antibody or antigen-binding fragment thereof of the present invention, the polynucleotide molecule described herein, the expression vector described herein, the host cell described herein, the pharmaceutical composition described herein, or the drug combination described herein, preferably the disease or condition is a CD112R-related cancer, more preferably the cancer is selected from melanoma, renal cancer, prostate cancer, breast cancer, colon cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, uterine cancer, ovarian cancer, and rectal cancer.

[0629] In a tenth aspect, the present invention provides the use of the antibody or antigen-binding fragment thereof described herein, the polynucleotide molecule described herein, the expression vector described herein, the host cell described herein, the pharmaceutical composition described herein, or the drug combination described herein in the preparation of a medicament for treating and / or preventing a CD112R-mediated disease or condition, preferably the disease or condition is a CD112R-related cancer, more preferably the cancer is selected from melanoma, renal cancer, prostate cancer, breast cancer, colon cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, uterine cancer, ovarian cancer, and rectal cancer.

[0630] In the eleventh aspect, the present invention provides an antibody or antigen-binding fragment thereof as described herein, a polynucleotide molecule as described herein, an expression vector as described herein, a host cell as described herein, a pharmaceutical composition as described herein, or a drug combination as described herein, for treating and / or preventing a CD112R-mediated disease or condition, preferably the disease or condition is cancer, more preferably the cancer is selected from melanoma, renal cancer, prostate cancer, breast cancer, colon cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, uterine cancer, ovarian cancer, and rectal cancer.

[0631] In a twelfth aspect, the present invention further provides a kit comprising an anti-CD112R antibody or antigen-binding fragment thereof of the present invention, a polynucleotide molecule of the present invention, an expression vector of the present invention, a host cell of the present invention, a pharmaceutical composition of the present invention, or a pharmaceutical combination of the present invention, or a pharmaceutical composition, and instructions for use. The kit may also include a suitable container. In certain embodiments, the kit further includes a device for administration. The kit generally includes a label indicating the intended use and / or method of use of the contents of the kit. The term "label" includes any written or recorded material provided on or with the kit or otherwise provided with the kit.

[0632] In another aspect, the present invention provides a method for detecting the presence of CD112R in a sample using the antibody or antigen-binding fragment thereof of the present invention or a detection composition containing the antibody or antigen-binding fragment thereof.

[0633] Detailed Description of the Invention

[0634] Before describing the present invention in detail, it should be understood that the present invention is not limited to the specific methods and experimental conditions in this specification, because the methods and conditions can be varied. In addition, the terminology used herein is only for describing specific embodiments and is not intended to be limiting.

[0635] I. Definition

[0636] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. For the purposes of the present invention, the following terms are defined below.

[0637] The term "about" when used in conjunction with a numerical value is meant to encompass the numerical value within a range having a lower limit that is 10% less than the specified numerical value and an upper limit that is 10% greater than the specified numerical value.

[0638] The term "and / or" when used to link two or more alternatives should be understood to mean any one of the alternatives or any two or more of the alternatives.

[0639] As used herein, the terms "comprising" or "including" are intended to include the recited elements, integers, or steps, but do not exclude any other elements, integers, or steps. In this document, when the terms "comprising" or "including" are used, unless otherwise indicated, the context of consisting of the recited elements, integers, or steps is also encompassed. For example, when reference is made to an antibody variable region "comprising" a specific sequence, it is intended to encompass an antibody variable region consisting of that specific sequence.

[0640] The terms "CD112R", "immunoglobulin domain associated with PVR", "CD112 receptor", "immunoglobulin domain associated with poliovirus receptor", "Nectin2 receptor", "C7orfl5", "transmembrane protein PVRIG" are all used interchangeably and include variants, isoforms, species homologs of human CD112R or CD112R of other species and analogs having at least one common epitope of CD112R, unless otherwise indicated. The term includes unprocessed full-length CD112R as well as any form of CD112R produced as a result of processing in the cell. The term encompasses "full-length" unprocessed CD112R as well as any form of CD112R or any fragment thereof, such as a splice variant or allelic variant, produced by intracellular processing. The variant or homolog maintains, for example, at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% of the activity of CD112R. The variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity with the naturally occurring CD112R protein over the entire sequence or a partial sequence (e.g., a 50, 100, 150 or 200 consecutive amino acid portion).

[0641] The term "antibody" is used in the broadest sense herein and encompasses a variety of antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired antigen-binding activity. A complete antibody will generally comprise at least two full-length heavy chains and two full-length light chains, but may comprise fewer chains in certain circumstances, e.g., antibodies naturally occurring in camels may comprise only heavy chains.

[0642] The term "antibody fragment" refers to a molecule other than an intact antibody that comprises a portion of an intact antibody and is capable of binding to the antigen to which the intact antibody binds. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2; diabodies; linear antibodies; single-chain antibodies (e.g., scFv); single-domain antibodies; bivalent or bispecific antibodies or fragments thereof; camelid antibodies (heavy chain antibodies); and multispecific antibodies formed from antibody fragments.

[0643] The term "variable region" or "variable domain" refers to the domain of an antibody heavy chain or light chain that is involved in binding an antibody to an antigen. The variable domains of the heavy and light chains of natural antibodies generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three complementarity determining regions (CDRs) (see, e.g., Kindt et al., Kuby Immunology, 6th ed., WH Freeman and Co., p. 91 (2007)). A single VH or VL domain is sufficient to confer antigen binding specificity.

[0644] "Complementarity determining region" or "CDR region" or "CDR" is a region of an antibody variable domain that is highly variable in sequence and forms structurally defined loops ("hypervariable loops") and / or contains antigen contact residues ("antigen contact points"). CDRs are primarily responsible for binding to antigenic epitopes. The CDRs in the variable domain are typically referred to as CDR1, CDR2, and CDR3 and are numbered sequentially starting from the N-terminus. In a given variable region amino acid sequence, the precise amino acid sequence boundaries of each CDR can be determined using any one or a combination of a number of well-known antibody CDR assignment systems, including, for example, Chothia based on the three-dimensional structure of antibodies and the topology of the CDR loops (Chothia et al. (1989) Nature 342:877-883, Al-Lazikani et al., "Standard conformations for the canonical structures of immunoglobulins", Journal of Molecular Biology, 273, 927-948 (1997)), Kabat based on antibody sequence variability (Kabat et al., Sequences of Proteins of Immunological Interest, 4th Edition, US Department of Health and Human Services, National Institutes of Health (1987)), AbM (University of Bath), Contact (University College London), International ImMunoGeneTics The IMGT database (http: / / imgt.cines.fr / ) and the North CDR definition were based on affinity propagation clustering using a large number of crystal structures.

[0645] Unless otherwise indicated, in the present invention, the term "CDR" or "CDR sequence" encompasses CDR sequences determined in any of the above-mentioned ways.

[0646] CDRs can also be identified based on having the same AbM numbering position as a reference CDR sequence (eg, any of the exemplified CDRs of the present invention). In one embodiment, the CDRs of the antibodies of the present invention are positioned according to the AbM numbering scheme.

[0647] Unless otherwise indicated, throughout this invention, references to residue positions in antibody variable regions and CDRs (including heavy chain variable region residues) refer to positions numbered according to the AbM numbering system.

[0648] "Humanized antibody" refers to a chimeric antibody comprising amino acid residues from non-human CDRs and amino acid residues from human FRs. In some embodiments, all or substantially all of the CDRs (e.g., CDRs) in the humanized antibody correspond to those of non-human antibodies, and all or substantially all of the FRs correspond to those of human antibodies. The humanized antibody optionally may comprise at least a portion of an antibody constant region derived from a human antibody. A "humanized form" of an antibody (e.g., a non-human antibody) refers to an antibody that has been humanized.

[0649] As used herein, the term "binding" or "specific binding" means that the binding is selective for the antigen and can be distinguished from unwanted or non-specific interactions. The ability of an antigen binding site to bind to a specific antigen can be determined by methods such as enzyme-linked immunosorbent assay (ELISA).

[0650] The term "median effective concentration (EC50) 50 )" refers to the concentration of drug, antibody or toxic agent that induces a response that is 50% between baseline and maximum after a specified exposure time.

[0651] The term "therapeutic agent" as used herein encompasses any substance effective in preventing or treating tumors, such as cancer, including chemotherapeutic agents, cytokines, angiogenesis inhibitors, cytotoxic agents, other antibodies, small molecule drugs, or immunomodulators (e.g., immunosuppressants).

[0652] The term "treat" refers to slowing, interrupting, arresting, alleviating, stopping, reducing, or reversing the progression or severity of an existing symptom, disorder, condition, or disease. Desired therapeutic effects include, but are not limited to, preventing the onset or recurrence of a disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, reducing the rate of disease progression, ameliorating or alleviating the disease state, and alleviating or improving prognosis. In some embodiments, the antibodies of the present invention are used to delay disease development or to slow the progression of a disease.

[0653] The term "prevent" includes the inhibition of the development or progression of a disease or condition or symptoms of a particular disease or condition. In some embodiments, subjects with a family history of cancer are candidates for a preventative regimen. Generally, in the context of cancer, the term "prevent" refers to the administration of a drug before the development of signs or symptoms of cancer, particularly in a subject at risk for cancer.

[0654] The term "effective amount" refers to the amount or dosage of an antibody, conjugate, or composition of the invention that produces the desired effect in a patient in need of treatment or prevention after administration to the patient in single or multiple doses. The effective amount can be readily determined by the attending physician, who is skilled in the art, by considering a variety of factors such as the species of mammal; weight, age, and general health; the specific disease involved; the extent or severity of the disease; the response of the individual patient; the specific antibody administered; the mode of administration; the bioavailability characteristics of the administered formulation; the selected dosing regimen; and the use of any concomitant therapy.

[0655] The term "therapeutically effective amount" refers to an amount effective to achieve the desired therapeutic outcome at the desired dosage and for the desired period of time. The therapeutically effective amount of an antibody or antibody fragment or conjugate or composition thereof can vary depending on a variety of factors such as the disease state, age, sex, and weight of the individual, and the ability of the antibody or antibody portion to elicit the desired response in the individual. A therapeutically effective amount is also an amount in which any toxic or deleterious effects of the antibody or antibody fragment or conjugate or composition are outweighed by the therapeutically beneficial effects. A "therapeutically effective amount" preferably inhibits a measurable parameter (e.g., tumor growth rate, tumor volume, etc.) by at least about 20%, more preferably at least about 40%, even more preferably at least about 50%, 60%, or 70%, and still more preferably at least about 80% or 90% relative to an untreated subject. The ability of a compound to inhibit a measurable parameter (e.g., cancer) can be evaluated in an animal model system that is predictive of efficacy in human tumors.

[0656] The term "prophylactically effective amount" refers to an amount effective to achieve the desired preventive result at the required dosage and for the required period of time. Typically, a prophylactic effective amount will be less than a therapeutically effective amount because a prophylactic dose is used in a subject prior to or at an earlier stage of disease.

[0657] The term "pharmaceutical composition" refers to a composition that is in form permitting the biological activity of the active ingredient contained therein to be effective, and that contains no additional ingredients that are unacceptably toxic to a subject to which the composition would be administered.

[0658] II. Compositions of the Invention

[0659] In some embodiments, the present invention provides a composition comprising any anti-CD112R antibody and antigen binding fragment thereof described herein, preferably a composition is a pharmaceutical composition. In one embodiment, the composition further comprises a pharmaceutical excipient, such as a pharmaceutical carrier, a pharmaceutical excipient as known in the art, including a buffer. In one embodiment, a composition (e.g., a pharmaceutical composition) comprises an anti-CD112R antibody of the present invention and an antigen binding fragment thereof, and a combination of one or more other therapeutic agents.

[0660] As used herein, "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, isotonic and absorption delaying agents, and the like that are physiologically compatible.

[0661] For the use of pharmaceutical excipients and their applications, see also "Handbook of Pharmaceutical Excipients", 8th edition, RC Rowe, PJ Eskey and S C Owen, Pharmaceutical Press, London, Chicago.

[0662] The compositions of the present invention can be in a variety of forms. These forms include, for example, liquid, semisolid and solid dosage forms, such as liquid solutions (e.g., injectable solutions and infusible solutions), powders or suspensions, liposomes and suppositories. The preferred form depends on the intended mode of administration and therapeutic use.

[0663] The administration route of the composition of the present invention is according to known methods, for example, orally, by intravenous injection, intraperitoneally, intracerebral (intraparenchymal), intracerebroventricular, intramuscularly, intraocularly, intraarterially, intraportally or intralesionally; by sustained release system or by implant device. In certain embodiments, the composition can be administered by bolus injection or by continuous infusion or by implant device.

[0664] The subject can be a mammal, e.g., a primate, preferably a higher primate, e.g., a human (e.g., an individual suffering from a disease described herein or at risk of suffering from a disease described herein). In one embodiment, the subject suffers from a disease described herein (e.g., cancer) or is at risk of suffering from a disease described herein. In certain embodiments, the subject receives or has received other treatments, e.g., chemotherapy and / or radiotherapy. In some embodiments, the subject has previously received or is currently receiving immunotherapy.

[0665] Medicaments comprising the antibodies described herein can be prepared by mixing the anti-CD112R antibodies and antigen-binding fragments thereof of the present invention having a desired degree of purity with one or more optional pharmaceutical excipients, preferably in the form of a lyophilized formulation or an aqueous solution.

[0666] The pharmaceutical composition or preparation of the present invention may also include more than one active ingredient, which is required for the specific indication being treated, preferably having those active ingredients of complementary activities that do not adversely affect each other. For example, it is desirable to also provide other therapeutic agents, including chemotherapeutics, angiogenesis inhibitors, cytokines, cytotoxic agents, other antibodies, small molecule drugs or immunomodulators (such as immune checkpoint inhibitors or agonists). The active ingredient is suitably present in combination in an amount effective for the purpose.

[0667] III. Preparation of Antibodies of the Invention

[0668] In one embodiment, the invention provides a method for preparing an anti-CD112R antibody, wherein the method includes culturing a host cell comprising a nucleic acid encoding an anti-CD112R antibody or an expression vector comprising the nucleic acid under conditions suitable for expressing the nucleic acid encoding the anti-CD112R antibody, and optionally isolating the anti-CD112R antibody. In a certain embodiment, the method further comprises recovering the anti-CD112R antibody from the host cell (or host cell culture medium).

[0669] In order to recombinantly produce an anti-CD112R antibody of the present invention, the nucleic acid encoding the anti-CD112R antibody of the present invention is first isolated, and the nucleic acid is inserted into a vector for further cloning and / or expression in a host cell. Such nucleic acids are easy to separate and sequenced using conventional procedures, for example, by using oligonucleotide probes that can specifically bind to nucleic acids encoding the anti-CD112R antibodies of the present invention.

[0670] The anti-CD112R antibodies of the present invention prepared as described herein can be purified by known techniques such as high performance liquid chromatography, ion exchange chromatography, gel electrophoresis, affinity chromatography, size exclusion chromatography, etc. The actual conditions used to purify a particular protein will also depend on factors such as net charge, hydrophobicity, hydrophilicity, etc., and these will be apparent to those skilled in the art. Example

[0671] The following examples further illustrate the present invention, however, it should be understood that the examples are described in an illustrative rather than a limiting manner, and that various modifications may be made by those skilled in the art. The present disclosure is further described in detail below in conjunction with specific examples, but these examples are not intended to limit the scope of the present invention. The experimental methods in the examples disclosed herein that do not specify specific conditions are generally conventional conditions, or according to the conditions recommended by the raw material or commodity manufacturer; reagents for which the source is not specified are generally conventional reagents available through commercial channels.

[0672] The practice of the present invention will employ, unless explicitly indicated to the contrary, conventional methods of chemistry, biochemistry, organic chemistry, molecular biology, microbiology, recombinant DNA techniques, genetics, immunology and cell biology, which are within the skill of the art.

[0673] Example 1: Preparation and identification of raw materials

[0674] 1.1 Preparation and identification of CD112R control antibodies

[0675] Preparation of CD112R control antibody: This application uses the anti-CD112R antibody CHA.7.518 (hereinafter referred to as Tab-1) as a positive control antibody. According to the sequence disclosed in WO / 2016 / 134333, gene synthesis was performed by KingScript Biotechnology to construct an expression plasmid. The specific VH and VL sequences of Tab-1 are shown in SEQ ID NOs: 657 and 658. Expi293F cells were transiently transfected and cultured for 6 days. The supernatant was collected and the antibody was affinity purified using Protein A Magnetic Beads (KingScript Biotechnology). Protein A Magnetic Beads were added to the supernatant and incubated at room temperature for 2 hours. After incubation, Protein A Magnetic Beads were equilibrated with Binding buffer (PBS, pH 7.4) for 10 column volumes. Elute the Protein A Magnetic Beads with Elution Buffer (0.1M Citrate Buffer, pH 3.0). Collect the eluate and adjust the pH to neutral by adding Neutralizing Buffer (0.1M Tris pH 9.0) at 1 / 10 the volume of the eluate. After elution, equilibrate the Protein A Magnetic Beads with Binding Buffer for 10 column volumes. Place the eluted and neutralized antibody into a dialysis bag and dialyze it against Dialysis Buffer (PBS, pH 7.4) at room temperature for 2 hours. Then, replace the Dialysis Buffer and dialyze it at 2-8°C for 16 hours. Transfer the antibody from the dialysis bag to a centrifuge tube and record the volume.

[0676] Identification of CD112R control antibody: The activity of the prepared positive control antibody Tab-1 was detected using the purchased CD112R-His antigen protein (Acro Biosysterm, PVG-H52H4). The specific method is as follows: CD112R-His (0.5 μg / mL, 100 μL / well) was coated on a 96-well ELISA plate and coated at 37°C for 1 hour; after washing the plate once, it was blocked with 1% BSA prepared in PBS for 1 hour; after washing the plate three times, the control antibody Tab-1 diluted in a gradient with PBS was added and incubated at room temperature for 1 hour; after washing the plate, the secondary antibody (Peroxidase-AffiniPure Goat Anti-Mouse IgG, FcγFragment Specific) diluted in PBS (1:6000) was added and incubated at 37°C for 0.5 hour, the plate was washed three times, TMB was added for color development for 5-20 minutes, and the data was read by OD450 on a microplate reader after color development was stopped. The results showed that the expressed control antibody Tab-1 could bind to CD112R protein, and as the antibody concentration decreased, the OD450 reading decreased, indicating that the control antibody had normal anti-CD112R activity.

[0677] Example 2: Construction and identification of cell lines overexpressing human and monkey CD112R

[0678] Construction of CHOK1 cell lines overexpressing human and monkey CD112R (hereinafter referred to as huCD112R-CHO K1; cynoCD112R-CHO K1): The coding nucleic acid sequences of full-length human (Uniprot ID: Q6DKI7) and monkey CD112R (Uniprot ID: A0A2K5WVV8) were constructed into lentiviral vectors. Then, the lentiviral plasmid was transfected into HEK293T cells for viral packaging, and after 4 days of culture, the cell culture supernatant was collected. The harvested lentiviral supernatant was used to transfect CHO-K1 cells, and Puromycin was used as the screening pressure. After 3 days of screening, the cell pool was screened for antigen expression by flow cytometry. After obtaining the positive cell pool, the positive cell pool was selected for single cell clones by limiting dilution or flow sorting. After monoclonal selection, the culture was continued for 1 week for the right to identify the cell line antigen expression.

[0679] Flow cytometric identification of cell line antigen expression: The above cell lines in the logarithmic growth phase were digested and plated into 96-well plates. After washing with FACS buffer (1× PBS buffer containing 2% FBS by volume), the primary antibody Mouse anti-human PVRIG antibody (GenScript Probio, Cat. No.: C523UGG270-2D) diluted in PBS was added and incubated at 4°C for 30 minutes. After washing, the prepared fluorescent secondary antibody PE Goat anti-mouse IgG antibody (BioLegend, Cat. No. 405307) was added and incubated at 4°C for 30 minutes. Finally, the cells were detected by flow cytometry (Beckman, CytoFLEXAOO-1-1102). The test results showed that huCD112R-CHO K1 and cynoCD112R-CHO K1 cell lines with high surface expression of human and monkey CD112R were obtained.

[0680] Example 3: Animal immunization and immune library construction

[0681] 3.1 Immunization regimen

[0682] Use CD112R-His or CD112R-mFc protein antigen (Acro Biosysterm, PVG-H5259); CD112R expression plasmid-DNA antigen; CD112R overexpression CHO cells and multiple immunogens, alone or in turn, to immunize mice of different species (Balb / c, SJL, A / J). Depending on the type of antigen selected, mice were immunized subcutaneously / intraperitoneally or by gene gun injection, once every two weeks, for a total of 3-5 immunizations. One week after the last immunization, mice were blooded for immune titer testing, and finally, the above antigens were used for booster immunization once more.

[0683] Table 1. Summary of immunization methods used in this example

[0684] 3.2 Detection of serum antibody titers in mice after immunization

[0685] Dilute the antigen to 0.5 μg / mL in coating buffer (PBS, pH 7.4), mix well, and add 100 μL / well to the ELISA plate. Refrigerate at 4°C overnight for 16 hours. Discard the coating buffer, wash the plate once, and pat dry. Add 150 μL of blocking buffer (3% BSA solution) to each well and incubate at 37°C for 1 hour. Remove the plate and discard the blocking buffer. Serially dilute mouse serum and add 100 μL / well to the plate. Incubate at 37°C for 1 hour. Remove the plate, discard the liquid, and wash three times. Add 100 μL of the diluted enzyme-linked secondary antibody, Peroxidase-AffiniPure Goat Anti-Mouse IgG, FcγFragment Specific (min X Hu, Bov, Hrs Sr Prot), to each well and incubate at 37°C for 0.5 hour. Remove the ELISA plate, discard the liquid, wash the plate three times, pat dry, add 100 μL of colorimetric solution, and incubate at 25°C for 15 minutes. Terminate the reaction by adding 50 μL of 1M HCl and read the OD450 value on a microplate reader. Select mice with an immune titer greater than 512,000 (dilution factor) for hybridoma fusion.

[0686] 3.3 Hybridoma Cell Fusion

[0687] Prepare a myeloma cell (SP2 / 0) suspension and use a hemocytometer to count the total number of SP2 / 0 cells. Prepare a spleen cell suspension and use a hemocytometer to count and calculate the total number of cells. Take myeloma cells and spleen cells and mix them in a ratio of 1:2 for cell electrofusion. After cell fusion, mix the fused cells with HAT selective medium to make a cell suspension, and then use a multichannel pipette to spread the cells into a 96-well cell plate. Place the fused 96-well cell culture plate in a 5.5% carbon dioxide incubator and culture at a constant temperature of 37°C. After hybridoma cell culture, take the supernatant for mother clone screening, and screen the cell culture supernatant for antigen binding ability at the protein and cell levels to obtain a mother clone cell line that can bind to the antigen.

[0688] 3.4 Hybridoma subclone screening

[0689] Pick out the mother clone cell line obtained by screening in step 3.3, and gently blow the cells in the wells to be subcloned with a pipette to mix them. Take out 20μl of cell suspension and add it to 20μl of trypan blue solution and mix it. Take out 20μl and count it with a hemocytometer. Using the limiting dilution method, replace the feeder cell culture medium with 1×HT and plate the cells in a 96-well cell culture plate. Mark the 96-well plate and culture it in a CO2 incubator. After subcloning, place the 96-well plate in a 37°C, 5.5% carbon dioxide incubator for culture. After 7 days of culture, take the supernatant for single clone screening.

[0690] After subclone screening, the obtained antibodies were selected for sequencing, and the CDR sequences of the antibodies are shown in Tables 2 and 3. The CDR sequences were determined using the AbM definition method.

[0691] Table 2. Heavy chain CDR sequences of anti-CD112R antibodies

[0692] Table 3. Light chain CDR sequences of anti-CD112R antibodies

[0693] Example 4: Antibody construction, expression and purification

[0694] 4.1 Plasmid construction

[0695] The VH coding sequence from the screened monoclonal Fab sequence was ligated to the coding sequence of the heavy chain constant region of human IgG1 (SEQ ID NO: 659) to obtain the heavy chain coding sequence of the human-mouse chimeric antibody. The VL coding sequence from the Fab sequence was ligated to the coding sequence of the kappa type human light chain constant region (CL) (SEQ ID NO: 660) to obtain the light chain coding sequence of the human-mouse chimeric antibody. The coding sequences for the antibody heavy and light chains were separately inserted into eukaryotic expression vector plasmids, transformed into Escherichia coli DH5α (Shanghai Biotechnology), and cultured overnight at 37°C. Plasmids were extracted using an endotoxin-free plasmid extraction kit (Qiagen) to obtain endotoxin-free antibody plasmids for eukaryotic expression.

[0696] 4.2 Antibody Expression and Purification

[0697] The full-length antibody sequence obtained above was expressed using the Expi293F transient expression system (Thermo Fisher, A14635) or the ExpiCHO transient expression system (Thermo Fisher, A29133). For specific methods, please refer to the supplier's corresponding kit operating instructions. The antibody isolation and purification refer to the antibody purification steps in Example 1.

[0698] Example 5: Detection of physicochemical properties of antibodies

[0699] 5.1 Antibody SDS-PAGE Identification

[0700] Preparation of non-reducing solution: 3 μg of each obtained antibody was added to 2× SDS loading buffer and 40 mM iodoacetamide, heated in a 75°C dry bath for 10 min, cooled to room temperature, and centrifuged at 12,000 rpm for 5 min to obtain the supernatant.

[0701] Reducing solution preparation: 3 μg of each antibody was added to 2× SDS loading buffer and 5 mM DTT, heated in a 99°C dry bath for 5 min, cooled to room temperature, and centrifuged briefly. The supernatant was loaded onto a Bis-tris 4-15% gradient gel (GenScript Biotech) for gel electrophoresis and visualized using Coomassie Brilliant Blue staining.

[0702] The protein gel with chromogenic protein bands was photographed using the Odyssey 9140 dual-color infrared laser imaging system (decolorization with destaining buffer was performed until the gel background was transparent), and the purity of the reduced and non-reduced bands was calculated using the built-in software.

[0703] The test results showed that the bands of each antibody in non-reduced gel were around 150kD, and the bands in reduced gel were around 55kD and 25kD, which were in line with the expected size.

[0704] Example 6: Antigen Binding Activity Detection of Antibodies

[0705] In this example, the binding of the expressed antibody to the human CD112R antigen protein huCD112R-His was detected based on the ELISA method, and the binding of the expressed antibody to the human CD112R overexpressing cell huCD112R-CHO K1 was also detected based on the FACS method.

[0706] 6.1 ELISA-based detection of antibody binding ability to antigen protein huCD112R-His

[0707] A 96-well ELISA plate (30 μL / well) was coated with 0.5 μg / mL of the human CD112R antigen protein huCD112R-His (Acro Biosysterm, PVG-H52H4) at 4°C overnight. The next day, the plate was washed three times with PBST and blocked with 5% skim milk for 2 hours. After washing the plate three times with PBST, a gradient dilution (1 μg / ml, 3-fold gradient dilution, 9 concentration points) of each antibody and the positive control antibody Tab-1 were added and incubated for 1 hour. After washing three times with PBST, the secondary antibody Goat-anti-human Fc-HRP (Abcam, ab97225) was added and incubated for 30 minutes. After incubation, the plate was washed 6 times with PBST, the plate was patted dry, TMB was added for color development, and the color development was carried out at 25°C for 15 minutes. 1M HCl was added to terminate the reaction, and the absorbance was read at OD450 using a microplate reader.

[0708] The results showed (Table 4) that the antibodies obtained in the present application had good binding ability to the antigen protein huCD112R, and the binding ability of some antibodies to the antigen protein was better than that of the positive control antibody Tab-1.

[0709] Table 4: EC50 values ​​of antibodies and human antigen proteins

[0710] 6.2 FACS-based detection of antibody binding ability to huCD112R-CHO K1 cells

[0711] In this example, human CD112R-overexpressing cells huCD112R-CHO K1 were used to evaluate the binding activity of the antibody.

[0712] The specific method is as follows: huCD112R-CHO K1 cells in the logarithmic growth phase were prepared into a single cell suspension and the density was adjusted to 2×10 6 10 cells / mL, 50 μL per well was added to a 96-well round-bottom plate. The cells were centrifuged at 300 g at 4°C, and the supernatant was removed. The detection antibody and positive control antibody Tab-1 were added to the corresponding wells, mixed, and incubated at 4°C for 40 minutes. After washing the cell mixture three times, 100 μL of diluted secondary antibody Goat F(ab')2 Anti-Human IgG-Fc (Abcam, ab98596) was added and incubated at 4°C in the dark for 30 minutes. After washing three times, the cells were analyzed by flow cytometry and the fluorescence intensity (MFI) was measured.

[0713] Conclusion: On huCD112R-CHO K1 cells, the antibody of the present invention has the ability to bind to cells over-expressing CD112R antigen.

[0714] Example 7: Antibody species and homologous cross-reactivity detection (ELISA method)

[0715] In this example, the cross-reactivity of each antibody obtained in this application was tested against human and monkey species. The antibodies prepared in Example 4 were used to determine their binding ability to monkey antigen protein (Uniprot ID: A0A2K5WVV8) and the monkey CD112R-expressing cell line cynoCD112R-CHO K1. For specific procedures, see Example 6.1.

[0716] The results show (Table 5) that all antibodies obtained in this application can bind to monkey antigen proteins and cell lines overexpressing monkey proteins, showing good human-monkey cross-reactivity. Therefore, the antibodies obtained in this application have a wide range of uses in experiments and tests based on monkey models.

[0717] The antibodies of the present invention all have good human-monkey species cross-activity.

[0718] Table 5: EC50 values ​​of antibodies and monkey antigen proteins

[0719] Example 8: Antibody affinity kinetics (Biacore) analysis

[0720] In the present embodiment, the affinity of antibody and positive control antibody Tab-1 and antigen protein huCD112R-His is obtained based on Biacore equipment detection. Anti-CD112R antibody samples are diluted to 10 μg / mL respectively using running buffer HBS-EP+ (10mM HEPES, 150mM NaCl, 3mM EDTA and 0.05% P20, pH 7.4) (BR100826, GE), and human CD112R antigen protein huCD112R-His (Acro Biosysterm, PVG-H52H4) is diluted to between 0.03125nM and 2nM with 2 times of gradient with HBS-EP+ buffer. Anti-CD112R antibodies are captured with Protein A biosensor chip (BR100354, GE) affinity, and capture time is set to 60s, and flow rate is 30 μL / min. The human CD112R samples diluted to different concentrations were then injected sequentially from zero to the highest concentration, with the binding time set to 120s, the dissociation time set to 360s, and the flow rate set to 30μL / min. The Biacore X100 instrument was used to detect the reaction signal in real time to obtain the binding and dissociation curves. After each experimental cycle of dissociation was completed, the Protein A biosensor chip was cleaned and regenerated with 10mM Glycine-HCl (pH1.5) (29127558, GE), and the regeneration time was set to 30s and the flow rate was 30μL / min. Parameter fitting: The experiment was run in single cycle mode, with the analysis time as the horizontal axis and the response value as the vertical axis. After the obtained data were double-referenced and subtracted, they were fitted by BIAcore X100 (GE) analysis software, and the fitting model used was a 1:1 Langmuir binding model to determine its affinity indicators such as the binding dissociation constant. The results showed that the affinity of the antibodies of the present invention was better than or equivalent to that of Yangshen (Tab-1).

[0721] Table 6: KD values ​​of antibodies binding to antigen protein huCD112R-His

[0722] Example 9: Detection of Antibody Blocking CD112R and CD112 Binding Signaling Pathway (Reporter Gene Method)

[0723] The reporter gene method consists of two genetically engineered cell lines: one is the GS-J2C / CD112R effector cell line that expresses human CD112R and a luciferase reporter gene driven by NFAT-RE, and the other is the GS-C2 / CD112 target cell line that expresses human CD112 on an engineered cell surface protein designed to activate the cognate TCR in an antigen-independent manner. When the GS-J2C / CD112R effector cell line is co-cultured with the GS-C2 / CD112 target cell line, the CD112R / CD112 interaction inhibits the activation of the TCR signaling pathway, thereby inhibiting the expression of NFAT-driven luciferase, and the corresponding fluorescence signal is relatively low; the addition of CD112R therapeutic antibodies blocks the CD112R / CD112 interaction, thereby restoring the TCR signaling pathway and increasing the fluorescence signal value.

[0724] First, GS-2 / CD112 target cells were constructed. The full-length human CD112 DNA fragment (NP_001036189.1) was inserted into a lentiviral expression vector (Blasticidin resistance), mixed with a helper plasmid, and transfected into 293T cells for packaging into CD112-Blasticidin recombinant lentivirus. The above recombinant lentivirus was infected with CHO-K1 / APC cells (named GS-C2), and a cell pool successfully infected with CD112 was obtained by screening with 10 μg / ml Blasticidin. GS-C2 / CD112 monoclonal cells were selected by limiting dilution.

[0725] GS-J2C / CD112R effector cells were constructed. The full-length human CD112R DNA fragment (XP_011514877.1) was inserted into a lentiviral expression vector containing puromycin resistance, mixed with a helper plasmid, and transfected into 293T cells. The resulting recombinant CD112-Puromycin lentivirus was then packaged into Jurkat-Luc reporter cells (designated GS-J2C). Cell pools successfully infected with CD112R were screened with 1 μg / ml puromycin. GS-J2C / PVRIG monoclonal cells were selected by limiting dilution.

[0726] Collect the target cells by centrifugation and resuspend the cells in their corresponding complete culture medium (10% FBS F-12K). Adjust the target cell density, inoculate them in the experimental plate, and transfer the experimental plate to a cell culture incubator (37°C / 5% CO2) for incubation for about 16 hours. Collect the effector cells by centrifugation, resuspend the cells in experimental buffer (1.25% FBS RPMI 1640) and adjust the cell density. Remove the experimental plate incubated with target cells from the cell culture incubator and remove the culture medium. Transfer the control and test working solutions and effector cell suspension to the experimental plate in sequence. Transfer the experimental plate to a cell culture incubator (37°C / 5% CO2) and incubate for 6 hours. Remove the incubated experimental plate from the cell culture incubator, transfer the luciferase detection reagent working solution to the corresponding wells of the experimental plate, and incubate at room temperature for 3-5 minutes. Use PHERA star to read the chemiluminescence value and record the data.

[0727] The results showed that the antibodies of the present invention can effectively block the binding between CD112R and CD112.

[0728] Table 7: Blocking effect of antibodies

[0729] Example 10: Antibody blocking CD112R binding to CD112 enhances antigen-specific CD8 T cell activation (primary immune cell method)

[0730] Detection of antigen-specific CD8 + T cell activation. PBMC cells of a specific genotype (HLA-A*0201) were collected by centrifugation and resuspended in RPMI-1640 medium (Gibco) containing 10% FBS (Gibco). A certain volume of pp65 (495–503) peptide (CEF20, Cytomegalovirus, CMV pp65 (495-503), GenScript) and cytokines (IL-2 Human and IL-7 Human, GenScript) were added to the PBMC cell suspension to induce the production of antigen-specific CD8 + After 11 days of culture, PBMC cells were collected by centrifugation and human CD8 + CD8 T cell isolation kit (17953, STEMCELL) + T cells. 5×10 4 Target cells (Ksaumi-1 and Colo-205) were added to a 96-well flat-bottom plate, and pp65 (495–503) peptide working solution was added to each well and incubated in a cell culture incubator for 1 hour. 4 CD8 +T cells were added to the corresponding 96-well plates. The test antibodies were then added to the corresponding wells at the assay concentration. The 96-well plates were placed in a cell culture incubator (37°C / 5% CO2) and incubated for 18 to 22 hours. After incubation, the 96-well flat-bottom plates were removed, centrifuged at 2000 rpm for 5 minutes, and the supernatant was transferred to a new 96-well plate. The cytokine interferon gamma (IFN-γ) was detected according to the instructions of the cytokine kit (62HIFNGPEH, Cisbio).

[0731] Table 8

[0732] The results showed that the antibodies of the present invention can effectively block the binding of CD112R to CD112, thereby enhancing the activation of antigen-specific CD8 T cells and secreting the cytokine interferon gamma (IFN-γ).

[0733] In addition to those described herein, various modifications of the present invention are also intended to fall within the scope of the appended claims in light of the foregoing description. Each reference cited in this application (including all patents, patent applications, journal articles, books and any other disclosures) is incorporated herein by reference in its entirety.

[0734] Sequence Listing

Claims

1. An anti-CD112R antibody or an antigen-binding fragment thereof that specifically binds to CD112R, comprising: 1) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 430, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 431; 2) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 432, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 433; 3) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 434, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 435; 4) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 436, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 437; 5) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 438, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 439; 6) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 438, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 440; 7) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 441, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 442; 8) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 443, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 444; 9) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 445, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 446; 10) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 447, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 448; 11) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 449 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 450; 12) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 451, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 452; 13) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 453, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 454; 14) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 455 and the three light chain CDRs (LCDR1, LCDR2, LCDR3); 15) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 457 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 458; 16) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 459 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 460; 17) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 461, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 462; 18) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 463, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 464; 19) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 465, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 466; 20) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 467, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 468; 21) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 469 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 470; 22) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 471, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 472; 23) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 473, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 474; 24) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 475 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 476; 25) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 477 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 478; 26) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 479 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 480; 27) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 481 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 482; 28) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 483 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 484; 29) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) and three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as shown in SEQ ID NO: 486; 30) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 487 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 456; 31) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 488 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 489; 32) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 490 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 491; 33) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 492 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 489; 34) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 493, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 494; 35) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 493, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 495; 36) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 496 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 497; 37) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 498 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 497; 38) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 499 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 500; 39) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 501 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 503; 40) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 502, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 503; 41) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 504, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 505; 42) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 499 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 506; 43) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 507, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 503; 44) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 508 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 509; 45) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 510 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 511; 46) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 512, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 513; 47) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 514 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 515; 48) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 501 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 516; 49) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 517 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 518; 50) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 519 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 520; 51) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 521, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 522; 52) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 523, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 524; 53) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 525 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 486; 54) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 526, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 527; 55) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 528 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 529; 56) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 530 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 531; 57) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 530 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 533; 58) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 532 and the three light chain CDRs (LCDR1, LCDR2, LCDR3); 59) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 532 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 533; 60) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 534 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 535; 61) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 536, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 537; 62) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 538 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 539; 63) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 540 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 541; 64) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 540 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 542; 65) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 543 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 544; 66) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 545 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 546; 67) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 547 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 548; 68) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 549 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 550; 69) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 551 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 552; 70) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 553 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 554; 71) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 555 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 556; 72) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 557 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 558; 73) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) and three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as shown in SEQ ID NO: 560; 74) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 561 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 554; 75) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 562, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 563; 76) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 564 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 565; 77) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 566, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 567; 78) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 568 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 569; 79) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 570 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 571; 80) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 572, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 573; 81) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 574, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 575; 82) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 576 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 578; 83) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 577 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 578; 84) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 579 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 580; 85) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 581 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 582; 86) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 583 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 584; 87) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 585 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 586; 88) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 587 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 588; 89) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 587 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 589; 90) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 590 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 591; 91) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 592, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 593; 92) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 592, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 594; 93) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 595 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 596; 94) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 595, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 594; 95) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 597 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 598; 96) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 597 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 594; 97) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 599 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 600; 98) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 601 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 602; 99) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 603 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 604; 100) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 605, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 606; 101) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 607, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 608; 102) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 609 and the three light chain CDRs (LCDR1, LCDR2, LCDR3); 103) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 611, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 612; 104) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 613, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 614; 105) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 615, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 616; 106) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 617, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 618; 107) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 619, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 620; 108) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 621, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 622; 109) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 623, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 624; 110) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 625, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 626; 111) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 627, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 628; 112) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 629, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 630; 113) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 631, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 632; 114) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 617, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 633; 115) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 634, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 635; 116) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 636, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 637; 117) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) and three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as shown in SEQ ID NO: 639; 118) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 640, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 641; 119) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 642, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 643; 120) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 644, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 645; 121) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 646, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 647; 122) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 648, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 649; 123) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as set forth in SEQ ID NO: 650, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as set forth in SEQ ID NO: 651; 124) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) comprised by the heavy chain variable region as set forth in SEQ ID NO: 652, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) comprised by the light chain variable region as set forth in SEQ ID NO: 653; 125) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 654 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 655; or 126) the three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 656 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:

653.

2. An anti-CD112R antibody or an antigen-binding fragment thereof that specifically binds to CD112R, comprising: 1) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 1, 64 and 162, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 239, 307 and 357, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 2) HCDR1, HCDR2 and HCDR3 comprising the sequences shown in SEQ ID NOs: 2, 65 and 162, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences shown in SEQ ID NOs: 239, 308 and 358, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 3) HCDR1, HCDR2 and HCDR3 comprising the sequences shown in SEQ ID NOs: 3, 66, and 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and sequences shown in SEQ ID NOs: 240, 309, and 359, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences. LCDR1, LCDR2, and LCDR3; 4) HCDR1, HCDR2 and HCDR3 comprising the sequences shown in SEQ ID NOs: 4, 67, and 164, respectively, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences shown in SEQ ID NOs: 239, 310, and 360, respectively, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 5) HCDR1, HCDR2 and HCDR3 comprising the sequences shown in SEQ ID NOs: 5, 68, and 165, respectively, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences shown in SEQ ID NOs: 241, 311, and 361, respectively, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 6) HCDR1, HCDR2 and HCDR3 comprising the sequences shown in SEQ ID NOs: 5, 68, 165, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences shown in SEQ ID NOs: 242, 312, 362, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 7) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 6, 69, 166, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 243, 313, 363, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 8) HCDR1, HCDR2 and HCDR3 comprising the sequences shown in SEQ ID NOs: 7, 70, 167, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences shown in SEQ ID NOs: 244, 314, 364, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 9) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 8, 71, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 245, 313, 365, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 10) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 3, 72, 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 359, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 11) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 9, 73, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 245, 313, 363, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 12) HCDR1, HCDR2 and HCDR3 comprising the sequences shown in SEQ ID NOs: 3, 74, 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and sequences shown in SEQ ID NOs: 246, 311, 359, or sequences containing LCDR1, LCDR2 and LCDR3 having sequences with one or more, but not more than three, amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids; 13) HCDR1, HCDR2 and HCDR3 comprising the sequences shown in SEQ ID NOs: 10, 75, 169, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences shown in SEQ ID NOs: 247, 315, 366, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 14) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 10, 75, 170, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 247, 315, 366, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 15) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 9, 76, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 243, 313, 363, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 16) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 9, 77, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 248, 313, 363, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 17) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 8, 77, 168, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 243, 313, 365, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 18) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 7, 78, 167, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 244, 314, 364, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 19) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 11, 79 and 171, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 249, 316 and 367, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 20) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 2, 80, 162, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 239, 317, 368, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 21) HCDR1, HCDR2, HCDR3, HCDR4, HCDR5, HCDR6, HCDR7, HCDR8, HCDR9, HCDR10, HCDR11, HCDR12, HCDR13, HCDR14, HCDR15, HCDR16, HCDR17, HCDR18, HCDR19, HCDR20, HCDR21, HCDR22, HCDR23, HCDR24, HCDR25, HCDR26, HCDR27, HCDR28, HCDR2 ...1, HCDR21, HCDR22, HCDR23, HC HCDR2 and HCDR3; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NO: 250, 315, 369, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 22) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 10, 82, 169, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 247, 315, 370, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 23) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 2, 83, 173, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 242, 312, 371, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 24) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 13, 84, 173, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 242, 312, 372, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 25) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 2, 85, 174, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 251, 318, 373, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 26) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 14, 86, 175, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 252, 319, 374, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 27) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 15, 87, 176, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 253, 320, 375, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 28) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 16, 88, 177, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 254, 321, 376, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 29) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 2, 89, 178, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 377, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 30) comprising the sequences shown in SEQ ID NO: 17, 75, 169, or containing one or more HCDR1, HCDR2 and HCDR3 of a sequence having no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids; and LCDR1, LCDR2 and LCDR3 of a sequence as shown in SEQ ID NO: 247, 315, 366, respectively, or a sequence having one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 31) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 18, 85, 162, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 239, 322, 378, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 32) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 2, 90, 162, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 255, 308, 368, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 33) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 19, 91, 179, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 239, 322, 378, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 34) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 2, 85, 180, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 256, 323, 379, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 35) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 2, 85, 180, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 239, 308, 380, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 36) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 20, 92, 181, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 257, 324, 381, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 37) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 21, 93, 182, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 258, 325, 382, ​​or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 38) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 22, 94, 183, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 259, 323, 383, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 39) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 23, 94, 183, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 259, 323, 383, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 40) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 24, 95, 184, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 247, 326, 384, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 41) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 21, 93, 182, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 247, 326, 385, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 42) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 22, 94, 183, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 259, 323, 383, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 43) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 25, 96, 185, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 260, 327, 386, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 44) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 26, 97, 186, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 261, 328, 387, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 45) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 27, 98, 187, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 262, 328, 388, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 46) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 28, 99, 188, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 263, 328, 388, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 47) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 22, 94 and 183, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and sequences shown in SEQ ID NOs: 239, 308 and 389, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences. LCDR1, LCDR2, and LCDR3; 48) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 5, 100, 189, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 264, 329, 390, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 49) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 24, 101, 190, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 247, 326, 385, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 50) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 28, 102, 191, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 265, 328, 391, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 51) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 28, 103, 192, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 266, 328, 388, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 52) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 29, 104, 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 377, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 53) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 30, 105, 193, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 267, 330, 392, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 54) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 5, 106, 194, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 268, 331, 393, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 55) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 31, 107, 195, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 256, 318, 392, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 56) HCDR1, HCDR2 and HCDR3 comprising the sequences shown in SEQ ID NOs: 31, 107, 195, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and sequences shown in SEQ ID NOs: 269, 332, 394, or sequences containing LCDR1, LCDR2 and LCDR3 having sequences with one or more, but not more than three, amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids; 57) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 32, 108, 196, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 256, 318, 392, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 58) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 32, 108, 196, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 269, 332, 394, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 59) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 29, 109, 197, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 395, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 60) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 33, 110, 198, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 270, 333, 396, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 61) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 5, 111 and 199, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 256, 318 and 397, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 62) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 34, 112, 200, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 269, 334, 398, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 63) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 34, 112, 200, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 271, 335, 399, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 64) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 35, 113, 201, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 400, or sequences containing one or more and no more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 65) comprising the sequences shown in SEQ ID NO: 36, 114, 202, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids in the sequences; HCDR2 and HCDR3; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NO: 272, 336, 401, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 66) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 29, 115, 203, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 402, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 67) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 37, 116, 204, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 273, 337, 403, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 68) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 5, 117, 205, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 274, 338, 404, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 69) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 38, 110, 198, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 270, 333, 405, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 70) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 39, 118, 204, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 275, 337, 406, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 71) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 5, 119, 206, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 276, 338, 407, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 72) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 29, 109, 197, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 395, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 73) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 38, 110, 198, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 270, 333, 405, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 74) comprising the sequences shown in SEQ ID NO: 5, 120, 205, or containing one or more HCDR1, HCDR2 and HCDR3 of a sequence having no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions; and LCDR1, LCDR2 and LCDR3 of a sequence as shown in SEQ ID NO: 277, 338, 407, respectively, or a sequence having one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequence; 75) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 5, 121, 207, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 278, 338, 404, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 76) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 35, 122, 201, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 279, 311, 408, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 77) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 35, 123, 208, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 280, 311, 400, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 78) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 5, 124, 209, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 281, 338, 407, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 79) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 40, 125, 210, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 282, 339, 409, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 80) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 41, 126, 211, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 245, 333, 410, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 81) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 10, 127, 212, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 239, 308, 411, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 82) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 40, 125, 213, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 239, 308, 411, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 83) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 42, 128, 214, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 283, 324, 412, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 84) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 43, 129, 215, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 284, 339, 409, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 85) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 42, 130, 216, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 285, 340, 409, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 86) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 44, 131, 217, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 286, 341, 413, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 87) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 44, 132, 218, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 282, 341, 414, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 88) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 44, 132, 218, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 287, 342, 415, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 89) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 45, 133, 219, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 288, 343, 416, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 90) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 46, 134, 220, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 289, 324, 417, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 91) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 46, 134, 220, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and sequences shown in SEQ ID NOs: 290, 344, 418, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences. LCDR1, LCDR2, and LCDR3; 92) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 47, 135, 221, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 291, 345, 407, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 93) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 47, 135, 221, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 290, 344, 418, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 94) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 48, 136, 222, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 292, 346, 409, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 95) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 48, 136, 222, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 290, 344, 418, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 96) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 49, 137, 163, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 240, 347, 419, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 97) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 45, 138, 223, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 288, 343, 416, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 98) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 50, 139, 224, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 249, 348, 420, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 99) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 51, 140, 225, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 256, 349, 421, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 100) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 47, 141, 221, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and sequences shown in SEQ ID NOs: 293, 345, 407, or sequences containing LCDR1, LCDR2 and LCDR3 having sequences with one or more, but not more than three, amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids; 101) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 52, 142, 226, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 294, 350, 422, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 102) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 53, 143, 178, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 295, 311, 423, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 103) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 53, 144, 178, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 361, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 104) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 53, 145, 227, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 361, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 105) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 54, 146, 228, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 296, 328, 391, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 106) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 55, 147, 228, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 266, 328, 391, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 107) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 50, 148, 229, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 297, 351, 424, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 108) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 56, 149, 230, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 298, 323, 425, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 109) comprising the sequences shown in SEQ ID NO: 57, 150, 231, or HCDR1, 150, 231, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions, or insertions of amino acids relative to said sequences; HCDR2 and HCDR3; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NO: 299, 338, 407, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 110) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 58, 151, 232, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 300, 352, 426, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 111) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 59, 152, 233, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 301, 328, 388, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 112) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 60, 153, 234, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 239, 308, 360, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 113) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 54, 146, 228, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 302, 328, 391, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 114) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 61, 154, 235, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 241, 311, 361, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 115) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 40, 125, 210, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 282, 353, 409, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 116) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 44, 155, 236, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 303, 324, 409, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 117) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 44, 156, 217, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 282, 341, 414, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 118) comprising the sequences shown in SEQ ID NO: 62, 157, 237, or containing one or more relative to the sequences HCDR1, HCDR2 and HCDR3 of a sequence having multiple and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions; and LCDR1, LCDR2 and LCDR3 of a sequence as shown in SEQ ID NO: 304, 332, 427, respectively, or a sequence containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to said sequences; 119) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 24, 158, 184, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 247, 326, 428, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 120) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 3, 159, 189, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 249, 354, 382, ​​or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to the sequences; 121) comprising HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NOs: 63, 160, 238, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NOs: 305, 355, 429, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; or 122) comprises HCDR1, HCDR2 and HCDR3 of the sequences shown in SEQ ID NO: 42, 161, 214, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to the sequences; and LCDR1, LCDR2 and LCDR3 of the sequences shown in SEQ ID NO: 306, 356, 409, respectively, or sequences containing one or more and no more than 3 amino acid substitutions (e.g., conservative substitutions), deletions or insertions of amino acids relative to the sequences.

3. The anti-CD112R antibody or antigen-binding fragment thereof according to any one of claims 1 to 2, wherein the antigen-binding fragment is selected from Fab, Fab'-SH, Fv (eg, scFv), or (Fab')2 fragment. 4 . The anti-CD112R antibody or antigen-binding fragment thereof according to claim 1 , comprising a constant region sequence, wherein at least a portion of the constant region sequence is a human consensus constant region sequence.

5. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the heavy chain constant region of the antibody comprises the amino acid sequence shown in SEQ ID NO: 659, and the light chain constant region comprises the amino acid sequence shown in SEQ ID NO:

660.

6. An isolated polynucleotide molecule encoding the anti-CD112R antibody or antigen-binding fragment thereof according to any one of claims 1 to 5.

7. An expression vector comprising the nucleotide molecule according to claim 6, preferably, the expression vector is a eukaryotic expression vector. A host cell comprising the expression vector according to claim 7 or the polynucleotide molecule according to claim 6.

9. A pharmaceutical composition comprising (1) the anti-CD112R antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, or the polynucleotide molecule according to claim 6, or the expression vector according to claim 7, or the host cell according to claim 8, and (2) a pharmaceutically acceptable carrier or excipient.

10. A method for preventing or treating a CD112R-mediated disease in a subject in need thereof, comprising administering to the subject a prophylactic or therapeutically effective amount of the antibody or antigen-binding fragment thereof as described in any one of claims 1 to 5, or the polynucleotide molecule according to claim 6, or the expression vector according to claim 7, or the host cell according to claim 8, or the pharmaceutical composition according to claim 9.

11. Use of the anti-CD112R antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, or the polynucleotide molecule according to claim 6, or the expression vector according to claim 7, or the host cell according to claim 8, or the pharmaceutical composition according to claim 9 in the preparation of a medicament for treating and / or preventing a disease or condition mediated by CD112R.

12. The method of claim 10 or the use of claim 11, wherein the disease or condition mediated by CD112R is a CD112R-associated cancer, preferably selected from melanoma, renal cancer, prostate cancer, breast cancer, colon cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, uterine cancer, ovarian cancer and rectal cancer.