Antibodies or antigen-binding fragments thereof targeting CD112R and uses thereof

Abstract

The present application relates to anti-CD112R antibodies or antigen-binding fragments thereof, and methods for their preparation and use. The present invention further relates to therapeutic and diagnostic uses of the antibodies and antibody fragments.

Description

[Technical Field]

[0001] The present invention relates to an antibody or antigen-binding fragment thereof that specifically recognizes CD112R, as well as methods for producing and using the same. [Background technology]

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

[0003] Anti-CD112R immunotherapy offers an opportunity to enhance, strengthen, and sustain immune responses. CD112R is an inhibitory receptor primarily expressed by T cells and NK cells, and binds to CD112 in competition with the activating receptor CD226. The interaction between CD112 and CD112R has higher affinity than the interaction with CD226, effectively suppressing CD226-mediated cell activation. Anti-CD112R antibodies that block the interaction with CD112 directly limit downstream CD112R inhibitory signaling while simultaneously promoting immune cell activation by increasing the interaction between CD226 and CD112. Treatment with anti-CD112R antibodies provides an opportunity to suppress the inhibitory signals that can be generated when CD112R-expressing immune cells bind to CD112 on tumor cells and / or myeloid cells within the tumor microenvironment, thereby enhancing, enhancing, and sustaining anti-tumor immune responses.

[0004] Although anti-CD112R antibodies have been disclosed in the prior art, there is still an urgent need to develop high-quality anti-CD112R antibodies.

[0005] In a first aspect, the present disclosure provides antibodies targeting human CD112R, which have the following advantages: (1) High affinity binding to human / cynomolgus monkey CD112R protein; (2) inhibiting or blocking the binding of human CD112R protein to human CD112 or cells expressing human CD112; (3) After blocking the binding of CD112R protein to CD112, CD8 T cells are stimulated to kill tumor cells.

[0006] In one embodiment, the present invention provides anti-CD112R antibodies and antigen-binding fragments thereof that specifically bind to CD112R, including: 1) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 430 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 431; 2) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 432 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 433; 3) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 434 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 435; 4) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 436 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 437; 5) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 438 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 439; 6) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 438 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 440; 7) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 441 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 442; 8) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 443 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 444; 9) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 445 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 446; 10) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 447 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 448; 11) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 449 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 450; 12) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 451 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 452; 13) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 453 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 454; 14) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 455 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 456; 15) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 457 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 458; 16) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 459 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 460; 17) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 461 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 462; 18) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 463 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 464; 19) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 465 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 466; 20) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 467 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 468; 21) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 469 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 470; 22) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 471 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 472; 23) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 473 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 474; 24) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 475 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 476; 25) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 477 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 478; 26) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 479 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 480; 27) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 481 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 482; 28) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 483 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 484; 29) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 485 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 486; 30) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 487 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 456; 31) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 488 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 489; 32) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 490 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 491; 33) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 492 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 489; 34) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 493 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 494; 35) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 493 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 495; 36) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 496 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 497; 37) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 498 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 497; 38) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 499 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 500; 39) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 501 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 503; 40) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 502 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 503; 41) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 504 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 505; 42) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 499 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 506; 43) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 507 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 503; 44) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 508 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 509; 45) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 510 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 511; 46) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 512 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 513; 47) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 514 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 515; 48) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 501 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 516; 49) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 517 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 518; 50) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 519 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 520; 51) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 521 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 522; 52) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 523 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 524; 53) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 525 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 486; 54) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 526 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 527; 55) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 528 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 529; 56) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 530 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 531; 57) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 530 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 533; 58) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 532 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 531; 59) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 532 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 533; 60) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 534 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 535; 61) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 536 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 537; 62) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 538 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 539; 63) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 540 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 541; 64) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 540 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 542; 65) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 543 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 544; 66) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 545 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 546; 67) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 547 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 548; 68) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 549 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 550; 69) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 551 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 552; 70) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 553 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 554; 71) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 555 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 556; 72) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 557 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 558; 73) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 559 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 560; 74) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 561 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 554; 75) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 562 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 563; 76) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 564 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 565; 77) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 566 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 567; 78) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 568 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 569; 79) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 570 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 571; 80) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 572 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 573; 81) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 574 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 575; 82) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 576 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 578; 83) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 577 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 578; 84) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 579 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 580; 85) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 581 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 582; 86) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 583 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 584; 87) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 585 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 586; 88) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 587 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 588; 89) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 587 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 589; 90) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 590 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 591; 91) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 592 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 593; 92) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 592 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 594; 93) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 595 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 596; 94) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 595 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 594; 95) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 597 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 598; 96) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 597 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 594; 97) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 599 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 600; 98) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 601 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 602; 99) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 603 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 604; 100) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 605 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 606; 101) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 607 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 608; 102) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 609 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 610; 103) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 611 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 612; 104) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 613 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 614; 105) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 615 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 616; 106) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 617 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 618; 107) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 619 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 620; 108) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 621 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 622; 109) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 623 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 624; 110) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 625 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 626; 111) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 627 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 628; 112) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 629 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 630; 113) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 631 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 632; 114) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 617 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 633; 115) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 634 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 635; 116) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 636 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 637; 117) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 638 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 639; 118) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 640 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 641; 119) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 642 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 643; 120) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 644 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 645; 121) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 646 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 647; 122) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 648 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 649; 123) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 650 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 651; 124) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 652 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 653; 125) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 654 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 655; 126) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 654 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 653.

[0007] In one embodiment, the present invention provides anti-CD112R antibodies and antigen-binding fragments thereof that specifically bind to CD112R, including: 1) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 1, 64, and 162, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 307, and 357, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 2) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 65, and 162, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, and 358, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 3) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 3, 66, 163, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 240, 309, 359, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 4) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 4, 67, 164, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 310, 360, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 5) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 68, 165, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 361, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 6) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 68, 165, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 242, 312, 362, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 7) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 6, 69, 166, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 243, 313, 363, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 8) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 7, 70, 167, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 244, 314, 364, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 9) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 8, 71, 168, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 245, 313, 365, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 10) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 3, 72, 163, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 359, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 11) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 9, 73, 168, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 245, 313, 363, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 12) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 3, 74, 163, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 246, 311, 359, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 13) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 10, 75, 169, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 315, 366, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 14) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 10, 75, 170, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 315, 366, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 15) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 9, 76, 168, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 243, 313, 363, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 16) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 9, 77, 168, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 248, 313, 363, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 17) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 8, 77, 168, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 243, 313, 365, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 18) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 7, 78, 167, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 244, 314, 364, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 19) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 11, 79, 171, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 249, 316, 367, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 20) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 80, 162, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 317, 368, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 21) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 12, 81, 172, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 250, 315, 369, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 22) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 10, 82, 169, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 315, 370, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 23) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 83, 173, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 242, 312, 371, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 24) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 13, 84, 173, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 242, 312, 372, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 25) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 85, 174, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 251, 318, 373, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 26) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 14, 86, 175, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 252, 319, 374, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 27) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 15, 87, 176, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 253, 320, 375, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 28) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 16, 88, 177, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 254, 321, 376, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 29) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 89, 178, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 377, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 30) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 17, 75, 169, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 315, 366, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 31) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 18, 85, 162, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 322, 378, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 32) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 90, 162, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 255, 308, 368, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 33) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 19, 91, 179, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 322, 378, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 34) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 85, 180, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 323, 379, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 35) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 85, 180, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 380, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 36) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 20, 92, 181, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 257, 324, 381, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 37) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 21, 93, 182, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 258, 325, 382, ​​or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 38) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 22, 94, 183, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 259, 323, 383, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 39) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 23, 94, 183, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 259, 323, 383, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 40) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 24, 95, 184, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 326, 384, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 41) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 21, 93, 182, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 326, 385, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 42) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 22, 94, 183, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 259, 323, 383, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 43) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 25, 96, 185, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 260, 327, 386, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 44) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 26, 97, 186, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 261, 328, 387, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 45) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 27, 98, 187, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 262, 328, 388, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 46) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 28, 99, 188, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 263, 328, 388, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 47) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 22, 94, 183, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 389, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 48) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 100, 189, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 264, 329, 390, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 49) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 24, 101, 190, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 326, 385, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 50) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 28, 102, 191, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 265, 328, 391, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 51) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 28, 103, 192, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 266, 328, 388, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 52) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 29, 104, 163, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 377, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 53) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 30, 105, 193, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 267, 330, 392, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 54) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 106, 194, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 268, 331, 393, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 55) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 31, 107, 195, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 318, 392, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 56) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 31, 107, 195, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 269, 332, 394, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 57) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 32, 108, 196, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 318, 392, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 58) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 32, 108, 196, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 269, 332, 394, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 59) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 29, 109, 197, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 395, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 60) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 33, 110, 198, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 270, 333, 396, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 61) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 111, 199, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 318, 397, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 62) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 34, 112, 200, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 269, 334, 398, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 63) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 34, 112, 200, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 271, 335, 399, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 64) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 35, 113, 201, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 400, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 65) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 36, 114, 202, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 272, 336, 401, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 66) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 29, 115, 203, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 402, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 67) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 37, 116, 204, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 273, 337, 403, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 68) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 117, 205, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 274, 338, 404, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 69) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 38, 110, 198, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 270, 333, 405, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 70) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 39, 118, 204, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 275, 337, 406, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 71) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 119, 206, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 276, 338, 407, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 72) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 29, 109, 197, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 395, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 73) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 38, 110, 198, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 270, 333, 405, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 74) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 120, 205, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 277, 338, 407, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 75) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 121, 207, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 278, 338, 404, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 76) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 35, 122, 201, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 279, 311, 408, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 77) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 35, 123, 208, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 280, 311, 400, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 78) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 124, 209, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 281, 338, 407, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 79) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 40, 125, 210, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 282, 339, 409, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 80) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 41, 126, 211, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 245, 333, 410, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 81) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 10, 127, 212, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 411, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 82) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 40, 125, 213, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 411, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 83) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 42, 128, 214, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 283, 324, 412, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 84) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 43, 129, 215, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 284, 339, 409, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 85) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 42, 130, 216, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 285, 340, 409, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 86) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 131, 217, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 286, 341, 413, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 87) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 132, 218, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 282, 341, 414, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 88) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 132, 218, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 287, 342, 415, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 89) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 45, 133, 219, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 288, 343, 416, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 90) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 46, 134, 220, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 289, 324, 417, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 91) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 46, 134, 220, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 290, 344, 418, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 92) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 47, 135, 221, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 291, 345, 407, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 93) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 47, 135, 221, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 290, 344, 418, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 94) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 48, 136, 222, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 292, 346, 409, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 95) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 48, 136, 222, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 290, 344, 418, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 96) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 49, 137, 163, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 240, 347, 419, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 97) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 45, 138, 223, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 288, 343, 416, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 98) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 50, 139, 224, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 249, 348, 420, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 99) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 51, 140, 225, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 349, 421, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 100) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 47, 141, 221, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 293, 345, 407, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 101) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 52, 142, 226, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 294, 350, 422, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 102) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 53, 143, 178, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 295, 311, 423, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 103) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 53, 144, 178, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 361, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 104) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 53, 145, 227, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 361, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 105) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 54, 146, 228, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 296, 328, 391, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 106) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 55, 147, 228, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 266, 328, 391, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 107) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 50, 148, 229, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 297, 351, 424, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 108) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 56, 149, 230, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 298, 323, 425, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 109) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 57, 150, 231, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 299, 338, 407, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 110) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 58, 151, 232, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 300, 352, 426, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 111) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 59, 152, 233, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 301, 328, 388, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 112) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 60, 153, 234, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 360, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 113) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 54, 146, 228, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 302, 328, 391, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 114) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 61, 154, 235, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 361, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 115) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 40, 125, 210, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 282, 353, 409, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 116) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 155, 236, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 303, 324, 409, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 117) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 156, 217, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 282, 341, 414, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 118) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 62, 157, 237, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 304, 332, 427, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 119) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 24, 158, 184, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 326, 428, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 120) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 3, 159, 189, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 249, 354, 382, ​​or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 121) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 63, 160, 238, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 305, 355, 429, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; or 122) HCDR1, HCDR2, HCDR3 comprising the sequences set forth in SEQ ID NOs: 42, 161, 214, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences set forth in SEQ ID NOs: 306, 356, 409, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences.

[0008] In one embodiment, the present invention provides anti-CD112R antibodies and antigen-binding fragments thereof that specifically bind to CD112R, comprising the following heavy chain variable region: 1) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:430, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO:430, or alternatively consists of SEQ ID NO:430; 2) the heavy chain variable region comprises, or consists of, the amino acid sequence set forth in SEQ ID NO:432, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:432; 3) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO:434, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:434, or alternatively consists of SEQ ID NO:434; 4) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 436, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 436; 5) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 438, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 438; 6) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 441, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 441; 7) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 443, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 443; 8) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 445, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 445; 9) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 447, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 447; 10) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 449, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 449; 11) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 451, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 451; 12) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 453, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 453; 13) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 455, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 455; 14) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 457, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 457; 15) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 459, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 459; 16) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 461, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 461, or alternatively consists of SEQ ID NO: 461; 17) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 463, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 463; 18) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 465, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 465; 19) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 467, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 467; 20) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 469, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 469; 21) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 471, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 471, or alternatively consists of SEQ ID NO: 471; 22) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 473, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 473; 23) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 475, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 475; 24) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 477, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 477; 25) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 479, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 479; 26) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 481, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 481, or alternatively consists of SEQ ID NO: 481; 27) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 483, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 483; 28) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 485, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 485; 29) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 487, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 487; 30) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 488, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 488; 31) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 490, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 490; 32) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 492, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 492; 33) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 493, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 493; 34) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 496, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 496; 35) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 498, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 498; 36) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 499, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 499; 37) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 501, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 501; 38) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 502, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 502; 39) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 504, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 504; 40) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 507, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 507; 41) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 508, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 508; 42) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 510, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 510; 43) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 512, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 512; 44) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 514, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 514; 45) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 517, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 517; 46) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 519, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 519; 47) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 521, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 521, or alternatively consists of SEQ ID NO: 521; 48) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 523, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 523; 49) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 525, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 525, or alternatively consists of SEQ ID NO: 525; 50) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 526, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 526, or alternatively consists of SEQ ID NO: 526; 51) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 528, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 528; 52) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 530, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 530, or alternatively consists of SEQ ID NO: 530; 53) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 532, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 532, or alternatively consists of SEQ ID NO: 532; 54) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 534, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 534, or alternatively consists of SEQ ID NO: 534; 55) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 536, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 536, or alternatively consists of SEQ ID NO: 536; 56) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 538, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 538; 57) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 540, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 540, or alternatively consists of SEQ ID NO: 540; 58) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 543, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 543; 59) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 545, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 545; 60) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 547, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 547; 61) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 549, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 549; 62) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 551, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 551; 63) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 553, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 553; 64) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 555, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 555; 65) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 557, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 557; 66) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 559, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 559; 67) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 561, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 561, or alternatively consists of SEQ ID NO: 561; 68) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 562, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 562; 69) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 564, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 564, or alternatively consists of SEQ ID NO: 564; 70) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 566, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 566, or alternatively consists of SEQ ID NO: 566; 71) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 568, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 568; 72) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 570, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 570; 73) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 572, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 572; 74) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 574, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 574; 75) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 576, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 576; 76) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 577, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 577; 77) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 579, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 579; 78) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 581, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 581, or alternatively consists of SEQ ID NO: 581; 79) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 583, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 583; 80) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 585, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 585, or alternatively consists of SEQ ID NO: 585; 81) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 587, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 587; 82) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 590, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 590; 83) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 592, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 592; 84) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 595, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 595; 85) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 597, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 597; 86) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 599, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 599; 87) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 601, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 601; 88) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 603, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 603; 89) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 605, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 605; 90) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 607, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 607; 91) The heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 609, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 609; 92) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 611, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 611, or alternatively consists of SEQ ID NO: 611; 93) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 613, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 613; 94) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 615, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 615, or alternatively consists of SEQ ID NO: 615; 95) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 617, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 617; 96) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 619, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 619; 97) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 621, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 621, or alternatively consists of SEQ ID NO: 621; 98) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 623, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 623; 99) The heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 625, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 625, or alternatively consists of SEQ ID NO: 625; 100) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 627, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 627; 101) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 629, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 629; 102) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 631, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 631, or alternatively consists of SEQ ID NO: 631; 103) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 634, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 634, or alternatively consists of SEQ ID NO: 634; 104) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 636, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 636, or alternatively consists of SEQ ID NO: 636; 105) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 638, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 638; 106) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 640, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 640, or alternatively consists of SEQ ID NO: 640; 107) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 642, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 642; 108) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 644, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 644, or alternatively consists of SEQ ID NO: 644; 109) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 646, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 646, or alternatively consists of SEQ ID NO: 646; 110) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 648, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 648; 111) The heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 650, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 650, or alternatively consists of SEQ ID NO: 650; 112) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 652, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 652; 113) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 654, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 654; or 14) The heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 656, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 656, or alternatively consists of SEQ ID NO: 656.

[0009] In one embodiment, the present invention provides anti-CD112R antibodies and antigen-binding fragments thereof that specifically bind to CD112R, comprising the following light chain variable region: 1) the light chain variable region comprises, or consists of, the amino acid sequence set forth in SEQ ID NO:431, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:431; 2) the light chain variable region comprises, or consists of, the amino acid sequence set forth in SEQ ID NO:433, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:433; 3) the light chain variable region comprises, or consists of, the amino acid sequence set forth in SEQ ID NO:435, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:435; 4) the light chain variable region comprises, or consists of, the amino acid sequence set forth in SEQ ID NO:437, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:437; 5) the light chain variable region comprises, or consists of, the amino acid sequence set forth in SEQ ID NO: 439, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 439; 6) the light chain variable region comprises, or consists of, the amino acid sequence set forth in SEQ ID NO: 440, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 440; 7) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 442, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 442; 8) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 444, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 444; 9) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 446, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 446; 10) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 448, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 448; 11) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 450, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 450, or alternatively consists of SEQ ID NO: 450; 12) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 452, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 452; 13) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 454, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 454; 14) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 456, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 456; 15) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 458, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 458; 16) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 460, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 460, or alternatively consists of SEQ ID NO: 460; 17) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 462, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 462; 18) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 464, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 464, or alternatively consists of SEQ ID NO: 464; 19) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 466, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 466, or alternatively consists of SEQ ID NO: 466; 20) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 468, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 468; 21) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 470, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 470; 22) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 472, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 472; 23) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 474, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 474; 24) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 476, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 476; 25) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 478, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 478; 26) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 480, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 480, or alternatively consists of SEQ ID NO: 480; 27) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 482, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 482; 28) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 484, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 484, or alternatively consists of SEQ ID NO: 484; 29) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 486, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 486, or alternatively consists of SEQ ID NO: 486; 30) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 489, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 489; 31) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 491, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 491, or alternatively consists of SEQ ID NO: 491; 32) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 494, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 494; 33) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 495, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 495; 34) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 497, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 497; 35) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 500, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 500, or alternatively consists of SEQ ID NO: 500; 36) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 503, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 503; 37) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 505, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 505; 38) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 506, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 506; 39) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 509, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 509; 40) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 511, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 511, or alternatively consists of SEQ ID NO: 511; 41) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 513, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 513; 42) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 515, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 515; 43) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 516, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 516, or alternatively consists of SEQ ID NO: 516; 44) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 518, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 518; 45) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 520, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 520; 46) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 522, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 522; 47) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 524, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 524, or alternatively consists of SEQ ID NO: 524; 48) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 527, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 527; 49) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 529, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 529; 50) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 531, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 531, or alternatively consists of SEQ ID NO: 531; 51) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 533, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 533; 52) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 535, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 535, or alternatively consists of SEQ ID NO: 535; 53) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 537, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 537; 54) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 539, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 539; 55) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 541, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 541, or alternatively consists of SEQ ID NO: 541; 56) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 542, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 542; 57) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 544, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 544, or alternatively consists of SEQ ID NO: 544; 58) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 546, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 546, or alternatively consists of SEQ ID NO: 546; 59) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 548, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 548; 60) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 550, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 550, or alternatively consists of SEQ ID NO: 550; 61) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 552, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 552; 62) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 554, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 554; 63) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 556, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 556; 64) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 558, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 558; 65) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 560, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 560, or alternatively consists of SEQ ID NO: 560; 66) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 563, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 563; 67) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 565, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 565, or alternatively consists of SEQ ID NO: 565; 68) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 567, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 567; 69) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 569, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 569; 70) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 571, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 571, or alternatively consists of SEQ ID NO: 571; 71) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 573, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 573; 72) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 575, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 575; 73) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 578, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 578; 74) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 580, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 580, or alternatively consists of SEQ ID NO: 580; 75) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 582, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 582; 76) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 584, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 584, or alternatively consists of SEQ ID NO: 584; 77) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 586, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 586; 78) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 588, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 588; 79) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 589, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 589; 80) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 591, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 591, or alternatively consists of SEQ ID NO: 591; 81) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 593, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 593; 82) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 594, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 594, or alternatively consists of SEQ ID NO: 594; 83) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 596, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 596; 84) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 598, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 598; 85) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 600, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 600, or alternatively consists of SEQ ID NO: 600; 86) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 602, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 602; 87) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 604, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 604; 88) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 606, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 606; 89) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 608, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 608; 90) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 610, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 610, or alternatively consists of SEQ ID NO: 610; 91) The light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 612, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 612; 92) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 614, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 614, or alternatively consists of SEQ ID NO: 614; 93) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 616, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 616, or alternatively consists of SEQ ID NO: 616; 94) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 618, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 618; 95) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 620, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 620, or alternatively consists of SEQ ID NO: 620; 96) The light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 622, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 622, or alternatively consists of SEQ ID NO: 622; 97) The light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 624, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 624, or alternatively consists of SEQ ID NO: 624; 98) The light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 626, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 626, or alternatively consists of SEQ ID NO: 626; 99) The light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 628, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 628, or alternatively consists of SEQ ID NO: 628; 100) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 630, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 630, or alternatively consists of SEQ ID NO: 630; 101) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 632, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 632; 102) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 633, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 633; 103) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 635, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 635, or alternatively consists of SEQ ID NO: 635; 104) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 637, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 637; 105) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 639, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 639; 106) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 641, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 641, or alternatively consists of SEQ ID NO: 641; 107) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 643, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 643; 108) the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 645, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 645, or alternatively consists of SEQ ID NO: 645; 109) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 647, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 647; 110) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 649, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 649; 111) The light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 651, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 651, or alternatively consists of SEQ ID NO: 651; 112) the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 653, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 653; or 113) The light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:655, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:655, or alternatively consists of SEQ ID NO:655.

[0010] In another embodiment, the present invention provides a method for the treatment of rhesus macular degeneration (HMD) comprising administering to a mammalian subject the following heavy chain variable region and light chain variable region: Anti-CD112R antibodies and antigen-binding fragments thereof that specifically bind to CD112R are provided: 1) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO:430, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:430, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO:431, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:431; 2) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO:432, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO:432, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO:433, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO:433; 3) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO:434, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO:434, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO:435, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO:435; 4) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO:436, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:436, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO:437, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO:437; 5) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 438, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 438, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 439, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 439; 6) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 438, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 438, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 440, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 440; 7) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 441, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 441, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 442, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 442; 8) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 443, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 443, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 444, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 444; 9) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 445, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 445, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 446, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 446; 10) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 447, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 447, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 448, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 448; 11) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 449, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 449, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 450, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 450; 12) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 451, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 451, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 452, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 452; 13) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 453, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 453, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 454, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 454; 14) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 455, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 455, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 456, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 456; 15) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 457, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 457, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 458, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 458; 16) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 459, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 459, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 460, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 460; 17) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 461, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 461, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 462, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 462; 18) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 463, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 463, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 464, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 464; 19) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 465, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 465, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 466, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 466; 20) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 467, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 467, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 468, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 468; 21) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 469, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 469, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 470, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 470; 22) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 471, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 471, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 472, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 472; 23) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 473, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 473, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 474, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 474; 24) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 475, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 475, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 476, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 476; 25) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 477, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 477, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 478, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 478; 26) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 479, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 479, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 480, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 480; or 27) The heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 481, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 481, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 482, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 482, or

[0011] 28) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 483, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 483, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 484, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 484; 29) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 485, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 485, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 486, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 486; 30) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 487, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 487, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 456, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 456; 31) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 488, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 488, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 489, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 489; 32) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 490, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 490, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 491, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 491; 33) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 492, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 492, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 489, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 489; 34) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 493, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 493, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 494, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 494; 35) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 493, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 493, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 495, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 495; 36) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 496, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 496, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 497, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 497; 37) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 498, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 498, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 497, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 497; 38) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 499, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 499, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 500, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 500; 39) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 501, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 501, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 503, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 503; 40) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 502, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 502, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 503, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 503; 41) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 504, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 504, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 505, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 505; 42) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 499, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 499, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 506, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 506; 43) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 507, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 507, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 503, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 503; 44) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 508, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 508, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 509, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 509; 45) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 510, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 510, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 511, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 511; 46) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 512, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 512, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 513, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 513; or 47) The heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 514, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 514, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 515, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 515.

[0012] 48) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 501, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 501, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 516, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 516; 49) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 517, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 517, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 518, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 518; 50) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 519, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 519, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 520, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 520; 51) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 521, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 521, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 522, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 522; 52) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 523, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 523, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 524, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 524; 53) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 525, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 525, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 486, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 486; 54) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 526, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 526, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 527, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 527; 55) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 528, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 528, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 529, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 529; 56) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 530, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 530, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 531, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 531; 57) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 530, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 530, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 533, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 533; 58) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 532, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 532, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 531, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 531; 59) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 532, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 532, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 533, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 533; 60) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 534, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 534, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 535, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 535; 61) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 536, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 536, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 537, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 537; 62) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 538, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 538, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 539, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 539; 63) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 540, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 540, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 541, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 541; 64) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 540, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 540, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 542, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 542; 65) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 543, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 543, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 544, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 544; 66) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 545, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 545, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 546, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 546; or 67) The heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 547, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 547, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 548, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 548.

[0013] 68) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 549, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 549, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 550, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 550; 69) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 551, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 551, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 552, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 552; 70) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 553, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 553, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 554, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 554; 71) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 555, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 555, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 556, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 556; 72) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 557, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 557, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 558, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 558; 73) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 559, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 559; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 560, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 560; 74) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 561, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 561, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 554, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 554; 75) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 562, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 562, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 563, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 563; 76) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 564, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 564, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 565, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 565; 77) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 566, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 566, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 567, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 567; 78) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 568, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 568, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 569, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 569; 79) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 570, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 570, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 571, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 571; 80) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 572, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 572; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 573, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 573; 81) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 574, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 574, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 575, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 575; 82) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 576, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 576, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 578, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 578; 83) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 577, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 577, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 578, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 578; 84) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 579, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 579; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 580, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 580; 85) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 581, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 581, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 582, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 582; 86) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 583, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 583, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 584, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 584; or 87) The heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 585, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 585; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 586, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 586.

[0014] 88) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 587, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 587, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 588, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 588; 89) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 587, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 587, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 589, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 589; 90) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 590, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 590, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 591, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 591; 91) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 592, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 592, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 593, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 593; 92) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 592, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 592, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 594, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 594; 93) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 595, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 595, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 596, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 596; 94) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 595, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 595, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 594, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 594; 95) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 597, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 597, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 598, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 598; 96) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 597, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 597, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 594, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 594; 97) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 599, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 599; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 600, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 600; 98) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 601, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 601, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 602, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 602; 99) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 603, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 603, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 604, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 604; 100) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 605, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 605, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 606, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 606; 101) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 607, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 607, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 608, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 608; 102) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 609, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 609, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 610, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 610; 103) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 611, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 611, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 612, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 612; 104) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 613, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 613, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 614, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 614; 105) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 615, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 615, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 616, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 616; 106) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 617, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 617, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 618, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 618; or 107) The heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 619, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 619, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 620, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 620, or

[0015] 108) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 621, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 621, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 622, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 622; 109) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 623, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 623, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 624, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 624; 110) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 625, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 625, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 626, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 626; 111) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 627, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 627, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 628, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 628; 112) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 629, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 629, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 630, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 630; 113) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 631, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 631, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 632, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 632; 114) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 617, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 617, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 633, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 633; 115) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 634, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 634, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 635, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 635; 116) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 636, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 636, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 637, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 637; 117) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 638, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 638, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 639, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 639; 118) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 640, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 640, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 641, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 641; 119) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 642, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 642; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 643, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 643; 120) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 644, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 644; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 645, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 645; 121) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 646, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 646; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 647, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 647; 122) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 648, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 648, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 649, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 649; 123) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 650, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 650, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 651, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 651; 124) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 652, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 652; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 653, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 653; 125) the heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 654, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the amino acid sequence of SEQ ID NO: 654, and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 655, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 655; 126) The heavy chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 656, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 656; and the light chain variable region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 653, or an amino acid sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to the amino acid sequence of SEQ ID NO: 653.

[0016] In some embodiments, the antibody or antigen-binding fragment thereof further comprises heavy and / or light chain constant region sequences derived from a human antibody germline consensus sequence. The light chain constant region is preferably a human-derived kappa or lambda chain constant region. The heavy chain constant region can be a gamma, mu, alpha, delta, or epsilon chain, and in some embodiments, the heavy chain constant region is preferably a human IgG1, IgG2, IgG3, or IgG4 constant region sequence. In one embodiment, the light chain constant region comprises or consists of the sequence set forth in SEQ ID NO: 660. In another embodiment, the heavy chain constant region comprises the Fc sequence set forth in SEQ ID NO: 661. In yet another embodiment, the heavy chain constant region comprises or consists of the sequence set forth in SEQ ID NO: 659.

[0017] It should be understood that sequence variants of these constant region domains may also be used, such as those containing one or more amino acid modifications, where these amino acid positions are designated according to the EU index system of Kabat et al. (1991).

[0018] In certain embodiments of any of the foregoing antibodies, the antibody is a monoclonal antibody.

[0019] In certain embodiments of any of the foregoing antibodies, the antibody is a full-length antibody.

[0020] In one embodiment, an anti-CD112R antibody of the invention is a complete antibody, e.g., an IgG1, IgG2, IgG3, or IgG4 antibody. In another embodiment, an anti-CD112R antibody of the invention includes only an antigen-binding portion thereof, e.g., a Fab, Fab'-SH, Fv, scFv, or (Fab')2 fragment.

[0021] In a second aspect, the present invention provides an isolated polynucleotide encoding any antibody or antigen-binding fragment thereof according to the first aspect.

[0022] In a third aspect, the present invention provides an expression vector comprising a nucleotide molecule according to the second aspect. In one embodiment, the vector is a eukaryotic expression vector.

[0023] In a fourth aspect, the present invention provides a host cell comprising a vector according to the third aspect or a nucleotide molecule according to the second aspect. In some embodiments, the host cell is, for example, Escherichia coli. In other embodiments, the host cell is a eukaryote, for example, a 293 cell, a CHO cell, a yeast cell, or a plant cell.

[0024] In a fifth aspect, the present invention provides a pharmaceutical composition comprising (1) an antibody or antigen-binding fragment thereof according to the first aspect, or a polynucleotide molecule according to the second aspect, or an expression vector according to the third aspect, or a host cell according to the fourth aspect, and (2) a pharmaceutically acceptable carrier or excipient.

[0025] In a sixth aspect, the present invention provides a method for preparing an anti-CD112R antibody or antigen-binding fragment thereof described herein, the method comprising expressing the antibody or antigen-binding fragment thereof in a host cell described herein under conditions suitable for expression of the antibody or antigen-binding fragment thereof, and recovering the expressed antibody or antigen-binding fragment thereof from the host cell.

[0026] In a seventh aspect, the antibody or antigen-binding fragment thereof, or pharmaceutical composition according to the present invention may also be administered in combination with one or more other therapies, e.g., therapeutic modalities and / or other therapeutic agents, for the uses described herein, e.g., for the prevention and / or treatment of the associated diseases or conditions described herein.

[0027] In an eighth aspect, the present invention provides a pharmaceutical combination comprising an antibody or antigen-binding fragment thereof, or pharmaceutical composition described herein, and one or more additional therapeutic agents.

[0028] 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 prophylactically or therapeutically effective amount of an antibody or antigen-binding fragment thereof according to the present invention, a polynucleotide molecule described herein, an expression vector described herein, a host cell described herein, a pharmaceutical composition described herein, or a pharmaceutical combination described herein, wherein preferably the disease or condition is a CD112R-associated cancer, and more preferably the cancer is selected from melanoma, kidney 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.

[0029] In a tenth aspect, the present invention provides the use of an antibody or antigen-binding fragment thereof described herein, a polynucleotide molecule described herein, an expression vector described herein, a host cell described herein, a pharmaceutical composition described herein, or a pharmaceutical combination described herein in the preparation of a medicament for the treatment and / or prevention of a CD112R-mediated disease or condition, wherein preferably the disease or condition is a CD112R-associated cancer, more preferably the cancer is selected from melanoma, kidney 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.

[0030] In an 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 pharmaceutical combination as described herein for the treatment and / or prevention of a CD112R-mediated disease or condition, wherein preferably the disease or condition is cancer, more preferably the cancer is selected from melanoma, kidney 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.

[0031] In a twelfth aspect, the present invention further provides a kit comprising an anti-CD112R antibody or antigen-binding fragment thereof according to the present invention, a polynucleotide molecule according to the present invention, an expression vector according to the present invention, a host cell according to the present invention, a pharmaceutical composition according to the present invention, or a pharmaceutical combination according to the present invention, or a pharmaceutical composition, and instructions for use. The kit may also comprise a suitable container. In certain embodiments, the kit further comprises an administration device. The kit generally comprises a label indicating the intended use and / or manner 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.

[0032] In another aspect, the present invention provides a method for detecting the presence of CD112R in a sample using an antibody or antigen-binding fragment thereof described herein, or a detection composition comprising the antibody or antigen-binding fragment thereof.

[0033] Detailed Description of the Invention Before describing the present invention in detail, it is to be understood that this invention is not limited to the particular methods and experimental conditions described herein, as these methods and conditions may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0034] I. Definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. For purposes of the present invention, the following terms are defined below.

[0035] When the term "about" is used in conjunction with a numerical value, it is intended to encompass values ​​within a range of 10% below the specified numerical value and 10% above the specified numerical value.

[0036] The term "and / or," when used to connect two or more alternatives, should be understood to mean any two or more of the alternatives.

[0037] As used herein, the term "comprise" or "comprising" is intended to include the listed elements, integers, or steps, but does not exclude other elements, integers, or steps. Unless otherwise specified, the use of the term "comprise" or "comprising" also encompasses cases where the listed elements, integers, or steps are present. For example, when referring to an antibody variable region that "comprises" a particular sequence, it is intended to encompass antibody variable regions consisting of that particular sequence.

[0038] The terms "CD112R," "PVR-related immunoglobulin domain," "CD112 receptor," "poliovirus receptor-related immunoglobulin domain," "nectin 2 receptor," "C7orfl5," and "transmembrane protein PVRIG" are all used interchangeably and, unless otherwise specified, include variants, subtypes, species homologs, or CD112R from other species of human CD112R, as well as analogs that share at least one common epitope with CD112R. This term encompasses full-length, unprocessed CD112R and any form of CD112R produced by intracellular processing. This term encompasses "full-length," unprocessed CD112R, and any form of CD112R or any fragment thereof, such as a splice variant or allelic variant, produced by intracellular processing. Variants or homologs retain, for example, at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% of CD112R activity. A variant or homologue has at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity over the complete or partial sequence (e.g., a 50, 100, 150 or 200 contiguous amino acid portion) compared to a naturally occurring CD112R protein.

[0039] The term "antibody" is used herein in the broadest sense and encompasses a wide 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 typically contains at least two full-length heavy chains and two full-length light chains, but may contain fewer chains in some cases. For example, antibodies naturally occurring in camels may contain only heavy chains.

[0040] The term "antibody fragment" refers to a molecule that contains a portion of an intact antibody that differs from the intact antibody and that is capable of binding to the antigen that 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.

[0041] The term "variable region" or "variable domain" refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to an antigen. The variable domains of the heavy and light chains of natural antibodies generally have similar structures, with each domain containing four conserved framework regions (FR) and three complementarity-determining regions (CDR) (see, for example, Kindt et al. Kuby Immunology, 6th ed., WH Freeman and Co., page 91 (2007)). A single VH or VL domain is sufficient to confer antigen-binding specificity.

[0042] "Complementarity determining regions" or "CDR regions" or "CDRs" are regions of antibody variable domains that are highly variable in sequence, form structurally determined loops ("hypervariable loops"), and / or contain antigen contact residues ("antigen contact sites"). CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs within a variable domain are commonly referred to as CDR1, CDR2, and CDR3, and are numbered sequentially from the N-terminus. For a given variable region amino acid sequence, the precise amino acid sequence boundaries of each CDR can be determined using, for example, Chothia's method based on the three-dimensional structure of an antibody and the topology of the CDR loops (Chothia et al. (1989) Nature 342:877-883, Al-L azikani et al., "Standard formulations for the canonical structures of immunoglobulins", Journal of Molecular Biology, 273, 927-948 (1997)), Kabat's method based on antibody sequence variability (Kabat et al., Sequences of Proteins of Immunological Interest, 4th ed., US Department of Health and Human Services, National Institutes of Health (1987)), AbM (University of Bath), Contact (University College London), the International ImMunoGeneTics database (IMGT), and North American CDR clustering based on affinity propagation clustering with a large number of crystal structures. The CDR definitions can be determined using any one or combination of many well-known antibody CDR designation systems.

[0043] Unless otherwise specified, in the present invention, the term "CDR" or "CDR sequence" encompasses CDR sequences determined by any of the above methods.

[0044] CDRs may also be determined based on having the same AbM numbering position as a reference CDR sequence (e.g., any of the CDRs in this example). In one embodiment, the positions of the CDRs of the antibodies of the present invention are determined according to the AbM numbering scheme.

[0045] Unless otherwise specified, in the present invention, when referring to the positions of residues in antibody variable regions, including heavy chain variable region residues, and CDRs, it means the numbered positions according to the AbM numbering system.

[0046] "Humanized antibody" refers to a chimeric antibody comprising amino acid residues derived from non-human CDRs and human FRs. In some embodiments, all or substantially all CDRs (e.g., CDRs) in a humanized antibody correspond to those of a non-human antibody, and all or substantially all FRs correspond to those of a human antibody. A humanized antibody may optionally 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.

[0047] As used herein, the terms "bind" or "specifically bind" mean that the binding effect 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 measured by methods such as enzyme-linked immunosorbent assay (ELISA).

[0048] The term "median effective concentration (EC 50 )" means the concentration of a drug, antibody, or toxin that induces a 50% response between baseline and maximum after a specified exposure time.

[0049] As used herein, the term "therapeutic agent" includes any substance effective in the prevention or treatment of tumors, such as cancer, including chemotherapeutic agents, cytokines, angiogenesis inhibitors, cytotoxic agents, other antibodies, small molecule drugs, or immunomodulatory agents (e.g., immunosuppressants).

[0050] The term "treatment" means to slow, interrupt, prevent, alleviate, stop, reduce, or reverse the progression or severity of an existing symptom, disorder, condition, or disease. Desirable therapeutic effects include, but are not limited to, preventing the onset or recurrence of disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, slowing the rate of disease progression, improving or alleviating the disease state, and alleviating or improving prognosis. In some embodiments, the antibodies of the present invention are used to slow the progression of disease or to slow the progression of disease.

[0051] The term "prevention" includes inhibiting the onset or progression of a disease or disorder, or the symptoms of a particular disease or disorder. In some embodiments, subjects with a family history of cancer are candidates for a preventive regimen. Generally, in the context of cancer, the term "prevention" refers to the administration of a drug before the onset of signs or symptoms of cancer, particularly in subjects at risk of having cancer.

[0052] The term "effective amount" refers to an amount or dosage that produces the desired effect when administered once or multiple times to a patient in need of treatment or prevention, of an antibody, conjugate, or composition of the present invention. The effective amount can be easily determined by an attending physician skilled in the art, taking into consideration various factors, such as the species of mammal; body weight, age, and general condition; 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 administration regimen; and the presence or absence of concomitant therapy.

[0053] The term "therapeutically effective amount" refers to an amount effective to achieve a desired therapeutic effect at a desired dose and for a desired duration. A therapeutically effective amount of an antibody or antibody fragment, or a conjugate thereof, or a composition may vary depending on various factors, such as the disease state, the age, sex, and weight of the subject, and the ability of the antibody or antibody portion to elicit a desired response in the subject. A therapeutically effective amount is also an amount in which the toxic or harmful effects of an antibody or antibody fragment, or a conjugate thereof, or a composition are less than 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 even more preferably at least about 80% or 90% compared to untreated subjects. The ability of a compound to inhibit a measurable parameter (e.g., cancer) can be evaluated in an animal model system predictive of efficacy in human tumors.

[0054] The term "prophylactically effective amount" refers to an amount effective to achieve a desired prophylactic result at a desired dosage and for a desired period of time. Generally, a prophylactically effective amount will be less than a therapeutically effective amount, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease.

[0055] The term "pharmaceutical composition" means a composition that allows the active ingredient contained therein to exist in a biologically active form and that does not contain additional ingredients that are unacceptably toxic to the subject to which the composition is administered.

[0056] II. Compositions of the Invention In some embodiments, the present invention provides compositions comprising any of the anti-CD112R antibodies and antigen-binding fragments thereof described herein, preferably pharmaceutical compositions. In one embodiment, the composition further comprises a pharmaceutical adjuvant, such as a pharmaceutically acceptable carrier, and a pharmaceutically acceptable excipient, including a buffer, as known in the art. In one embodiment, the composition (e.g., pharmaceutical composition) comprises a combination of the anti-CD112R antibodies and antigen-binding fragments thereof of the present invention and one or more other therapeutic agents.

[0057] 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.

[0058] For a review of the uses and applications of pharmaceutical adjuvants, see also "Handbook of Pharmaceutical Excipients," Eighth Edition, R.C. Rowe, P.J. Seskey and S.C. Owen, Pharmaceutical Press, London, Chicago.

[0059] The compositions of the present invention can be in various forms. These forms include, for example, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., solutions for injection, solutions for infusion), powders or suspensions, liposome preparations and suppositories. The preferred form depends on the intended mode of administration and therapeutic use.

[0060] The administration route of the compositions of the present invention is known method, for example, by oral, intravenous injection, intraperitoneal, intracerebral (intraparenchymal), intraventricular, intramuscular, intraocular, intraarterial, intraportal or intralesional route, by sustained release system or implantable device.In certain embodiments, the compositions can be administered by bolus injection or continuous infusion, or by implantable device.

[0061] The subject can be a mammal, for example, a primate, preferably a higher primate, for example, a human (e.g., a subject with a disease described herein or a subject at risk of having a disease described herein).In one embodiment, the subject has or is at risk of having a disease described herein (e.g., cancer).In certain embodiments, the subject is undergoing or has undergone other treatments, such as chemotherapy and / or radiation therapy.In some embodiments, the subject has previously undergone or is currently undergoing immunotherapy.

[0062] Drugs containing the antibodies described herein can be prepared by mixing the anti-CD112R antibodies and antigen-binding fragments thereof of the present invention having the desired purity, preferably in the form of a lyophilized formulation or an aqueous solution, with one or more optional pharmaceutical adjuvants.

[0063] The pharmaceutical compositions or formulations of the present invention can further contain more than one active ingredient as needed for the specific indication to be treated, preferably active ingredients with complementary activities that do not adversely affect each other. For example, it may be desirable to provide other therapeutic agents, including chemotherapeutic agents, angiogenesis inhibitors, cytokines, cytotoxic agents, other antibodies, small molecule drugs, or immunomodulators (e.g., immune checkpoint inhibitors or agonists). The active ingredients are appropriately formulated in an amount effective for the intended use.

[0064] III. Preparation of Antibodies of the Invention In one embodiment, the invention provides a method for preparing an anti-CD112R antibody, comprising culturing a host cell containing a nucleic acid encoding the anti-CD112R antibody, or an expression vector containing the nucleic acid, under conditions suitable for expression of the nucleic acid encoding the anti-CD112R antibody, and optionally isolating the anti-CD112R antibody. In one embodiment, the method further comprises recovering the anti-CD112R antibody from the host cell (or host cell culture medium).

[0065] To recombinantly produce an anti-CD112R antibody of the invention, nucleic acid encoding the anti-CD112R antibody of the invention is first isolated and then incorporated into a vector for cloning and / or expression in a host cell. Such nucleic acid can be readily isolated and sequenced using conventional protocols, such as using oligonucleotide probes capable of specifically binding to nucleic acid encoding an anti-CD112R antibody of the invention.

[0066] The anti-CD112R antibodies of the invention prepared as described herein can be purified by known prior art 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 will be apparent to one of skill in the art. [Example]

[0067] The present invention will be further described by the following examples, which are intended for illustrative purposes rather than limiting, and it should be understood that various modifications may be made by those skilled in the art. The present disclosure will be described in more detail below with reference to specific examples, which are not intended to limit the scope of the present invention. Experimental methods for which no specific conditions are given in the examples of the present disclosure are generally carried out under conventional conditions or according to the conditions recommended by the raw materials or commercial manufacturers. Unspecified reagents are commonly available commercially.

[0068] Unless otherwise indicated, embodiments of the present invention employ conventional methods of chemistry, biochemistry, organic chemistry, molecular biology, microbiology, recombinant DNA technology, genetics, immunology and cell biology, within the skill of the art.

[0069] Example 1: Preparation and identification of raw materials 1.1 Preparation and identification of CD112R control antibodies Preparation of CD112R control antibody: In this application, the anti-CD112R antibody CHA.7.518 (hereinafter referred to as Tab-1) was used as a positive control antibody. Gene synthesis was performed by GenScript Biotech Corporation according to the sequence disclosed in WO / 2016 / 134333, and an expression plasmid was constructed. 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 subjected to antibody affinity purification using Protein A Magnetic Beads (GenScript Biotech Corporation). Protein A Magnetic Beads were added to the supernatant and incubated at room temperature for 2 hours. After incubation, the Protein A Magnetic Beads were equilibrated with binding buffer (PBS, pH 7.4) for 10 column volumes. Protein A magnetic beads were eluted with elution buffer (0.1 M citrate buffer, pH 3.0). The eluate was collected and neutralized by adding 1 / 10 the volume of neutralization buffer (0.1 M Tris pH 9.0) to adjust the pH to neutral. After elution, the Protein A magnetic beads were equilibrated with binding buffer for 10 column volumes. The antibody was eluted, neutralized, placed in a dialysis bag, and dialyzed against dialysis buffer (PBS, pH 7.4) at room temperature for 2 hours. The dialysis buffer was then replaced at 2-8°C for 16 hours. The antibody was transferred from the dialysis bag to a centrifuge tube, and the volume was recorded.

[0070] Identification of CD112R control antibody: The activity of the prepared positive control antibody Tab-1 was detected using purchased CD112R-His antigen protein (Acro Biosystems, PVG-H52H4). The specific method was as follows: CD112R-His (0.5 μg / mL, 100 μL / well) was coated onto a 96-well ELISA plate for 1 hour at 37°C; after washing once, the plate was blocked with 1% BSA prepared in PBS for 1 hour; after washing three times, the control antibody Tab-1 serially diluted in PBS was added and incubated at room temperature for 1 hour; after washing the plate, the secondary antibody (Peroxidase-AffiniPure Goat Anti-Mouse IgG, Fcγ Fragment 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 were read at OD450 using a reader after color development had stopped. The results showed that the expressed control antibody Tab-1 was able to bind to the CD112R protein and the OD450 readings decreased with decreasing antibody concentration, indicating that the control antibody had normal anti-CD112R activity.

[0071] Example 2: Construction and identification of cell lines expressing human and monkey CD112R Construction of CHOK1 cell lines overexpressing human and monkey CD112R (hereafter referred to as huCD112R-CHO K1; cynoCD112R-CHO K1): Nucleic acid sequences encoding full-length human (Uniprot ID: Q6DKI7) and monkey CD112R (Uniprot ID: A0A2K5WVV8) were constructed on lentiviral vectors. The lentiviral plasmids were then transfected into HEK293T cells for viral packaging, cultured for 4 days, and the cell culture supernatant was collected. CHO-K1 cells were transfected with the collected lentiviral supernatant and puromycin was used as a screening pressure. After 3 days of screening, the cell pools were screened for antigen expression by flow cytometry. After obtaining positive cell pools, positive cell pools were selected using limiting dilution or flow sorting. After monoclonal selection, culture was continued for approximately 1 week to identify antigen expression in the cell lines.

[0072] Flow identification of antigen expression in cell lines: Logarithmically growing cell lines were digested, seeded into 96-well plates, washed with FACS buffer (1x PBS buffer containing 2% FBS v / v), and incubated with a primary mouse anti-human PVRIG antibody (GenScript Probio, catalog number: C523UGG270-2D) serially diluted in PBS for 30 minutes. After washing, a prepared fluorescent secondary PE goat anti-mouse IgG antibody (BioLegend, catalog number: 405307) was added and incubated at 4°C for 30 minutes. Finally, detection was performed by flow cytometry (Beckman, CytoFLEXA00-1-1102). Results showed that huCD112R-CHO K1 and cynoCD112R-CHO K1 cell lines with high surface expression of human and monkey CD112R were obtained.

[0073] Example 3: Animal immunization and construction of immune library 3.1 Immunization Protocol Various strains of mice (Balb / c, SJL, and A / J) were immunized with various immunogens, either alone or in combination: CD112R-His or CD112R-mFc protein antigens (Acro Biosystems, PVG-H5259), CD112R-expressing plasmid DNA antigens, and CD112R-overexpressing CHO cells. Mice were immunized every two weeks using subcutaneous or intraperitoneal injection or a gene gun, depending on the antigen selected, for a total of three to five immunizations. One week after the final immunization, blood was collected from the mice to detect immune titers, after which a booster immunization was performed using the above antigens.

[0074] [Table 1]

[0075] 3.2 Detection of antibody titers in mouse serum after immunization The antigen was diluted to 0.5 μg / mL in coating solution (PBS, pH 7.4), mixed well, and then added to the ELISA plate at 100 μL / well. The plate was then left to stand in a 4°C refrigerator for 16 hours (overnight). The coating solution was discarded, and the plate was washed once and dried. 150 μL of blocking solution (3% BSA solution) was added to each well and incubated in a 37°C incubator for 1 hour. The plate was then removed, and the blocking solution was discarded. Serially diluted mouse serum was then added to the plate at 100 μL / well. The plate was then incubated in a 37°C incubator for 1 hour. The plate was then removed, the liquid discarded, and the plate was washed three times. 100 μL of diluted enzyme-labeled secondary antibody (Peroxidase-AffiniPure Goat Anti-Mouse IgG, Fcγ Fragment Specific) was added to each well and incubated at 37°C for 0.5 hours. The ELISA plate was removed, the liquid discarded, washed three times, and allowed to dry. 100 μL of color-developing solution was added and incubated at 25°C for 15 minutes. The reaction was stopped by adding 50 μL of 1M HCl, and the OD450 was read using a microplate reader. Mice with a titer exceeding 512,000 (dilution factor) were selected for hybridoma fusion.

[0076] 3.3 Hybridoma cell fusion A myeloma cell (SP2 / 0) suspension was prepared, and the total number of SP2 / 0 cells was counted using a hemocytometer. A spleen cell suspension was prepared, and the total cell number was counted using a hemocytometer plate. Myeloma cells and spleen cells were mixed at a 1:2 ratio and subjected to cell electrofusion. After cell fusion, the fused cells were mixed with the cell suspension using HAT selection medium and then seeded into a 96-well cell culture plate using a multichannel pipette. The fused 96-well cell culture plate was placed in a 5.5% CO2 incubator and cultured at a constant temperature of 37°C. After hybridoma cell culture, the supernatant was collected and subjected to mother clone screening. Antigen-binding ability was evaluated at the protein and cellular levels to identify mother clone cell lines capable of binding to the antigen.

[0077] 3.4 Hybridoma subclone screening Cells were harvested from the parent clonal cell line obtained in the screening in step 3.3. The cells to be subcloned were gently pipetted and mixed thoroughly. 20 μL of the cell suspension was collected and added to 20 μL of trypan blue solution and mixed evenly. 20 μL of the solution was removed and the cell number was counted using a hemocytometer. Using the limiting dilution method, the cells were seeded into a 96-well cell culture plate in 1x HT replacement feeder cell culture medium, marked, and cultured in a CO2 incubator. The subcloned 96-well plate was cultured at 37°C in a 5.5% CO2 incubator. After 7 days of culture, the supernatant was collected and subjected to monoclonal screening.

[0078] The resulting antibodies were selected for sequencing by subclone screening, and the CDR sequences of the antibodies are shown below in Tables 2 and 3. The CDR sequences are determined by defining the CDRs using AbM.

[0079] [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4]

[0080] [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5] [Table 3-6]

[0081] Example 4: Antibody construction, expression and purification 4.1 Plasmid construction The VH coding sequence from the Fab sequence of the screened monoclonal was linked 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 a human-mouse chimeric antibody. The VL coding sequence from the Fab sequence was linked 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. The antibody heavy and light chain coding sequences were each inserted into a eukaryotic expression vector plasmid, transformed into Escherichia coli DH5α (Shanghai Sangon), and cultured overnight at 37°C. Plasmid extraction was performed using an endotoxin-free plasmid extraction kit (Qiagen), yielding an endotoxin-free antibody plasmid for eukaryotic expression.

[0082] 4.2 Antibody expression and purification The full-length antibody sequences obtained were expressed using the Expi293F transient expression system (Thermo Fisher Scientific, A14635) or the ExpiCHO transient expression system (Thermo Fisher Scientific, A29133). The manufacturer's operating guidelines for each kit are provided for specific methods. The antibody was isolated and purified as described in Example 1.

[0083] Example 5: Testing the physical and chemical properties of antibodies 5.1 Antibody characterization by SDS-PAGE Preparation of non-reducing solution: 3 μg of each obtained antibody was added to 2×SDS loading buffer and 40 mM iodoacetamide, heated at 75° C. for 10 minutes, cooled to room temperature, and centrifuged at 12,000 rpm for 5 minutes to obtain the supernatant.

[0084] Preparation of reducing solution: 3 μg of each antibody was added to 2x SDS loading buffer and 5 mM DTT, heated at 99°C for 5 minutes, cooled to room temperature, and immediately centrifuged. The resulting supernatant was loaded onto a Bis-Tris 4-15% gradient gel (GenScript Biotech Corporation) for gel electrophoresis, and protein bands were stained with Coomassie Brilliant Blue.

[0085] The gels with the stained protein bands (the background of the gel was destained with a destaining solution) were photographed using an Odyssey 9140 dual-color infrared laser imaging system, and the purity of the reduced and non-reduced bands was calculated using the software provided with the instrument.

[0086] The test results showed that the bands for each antibody in the non-reducing gel were approximately 150 kD, and the bands in the reducing gel were approximately 55 kD and 25 kD, which were the expected sizes.

[0087] Example 6: Detection of antigen-binding activity of antibodies In this example, the binding of the expressed antibodies to the human CD112R antigen protein huCD112R-His was detected by ELISA, and the binding of the expressed antibodies to the human CD112R-overexpressing cells huCD112R-CHO K1 was detected by FACS.

[0088] 6.1 ELISA-based detection of antibody binding to the antigen protein huCD112R-His 0.5 μg / mL of human CD112R antigen protein, huCD112R-His (Acro Biosystems, PVG-H52H4), was coated onto a 96-well ELISA plate (30 μL / well) and incubated overnight at 4°C. The next day, the plate was washed three times with PBST and blocked with 5% skim milk for 2 hours. After washing three times with PBST, gradient dilutions of each antibody and the positive control antibody Tab-1 (1 μg / mL, 3-fold gradient dilutions, 9 concentration points) 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 six times with PBST, dried, and developed with TMB for 15 minutes at 25°C. The reaction was stopped with 1M HCl, and the absorbance was read at OD450 using a microplate reader.

[0089] The results (Table 4) showed that both the antibodies obtained in this application and the antigen protein huCD112R exhibited excellent binding ability, and some antibodies exhibited superior binding ability to the antigen protein than the positive control antibody Tab-1.

[0090] [Table 4]

[0091] 6.2 FACS-based detection of antibody binding to huCD112R-CHO K1 cells In this example, the binding activity of human CD112R-overexpressing cells huCD112R-CHO K1 to antibodies was evaluated.

[0092] The specific method is as follows: huCD112R-CHO K1 cells in the logarithmic growth phase were prepared into a single cell suspension and grown at a density of 2 × 10 6The solution was adjusted to cells / mL and added at 50 μL per well to a 96-well round-bottom plate. The mixture was centrifuged at 300 g at 4°C and the supernatant was removed. The detection antibody and positive control antibody Tab-1 were added to each well, mixed well, and incubated at 4°C for 40 minutes. The incubated cell mixture was washed three times, and 100 μL of diluted secondary goat F(ab')2 anti-human IgG-Fc (Abcam, ab98596) was added. The mixture was incubated at 4°C in the dark for 30 minutes, washed three times, and then detected by flow cytometry, and the fluorescence intensity (MFI) was read.

[0093] Conclusion: In huCD112R-CHO K1 cells, the antibody of the present invention had the ability to bind to CD112R-overexpressing cells.

[0094] Example 7: Detection of antibody species and cross-reactivity of cognate antibodies (ELISA method) In this example, we examined the cross-reactivity of each antibody obtained in this application with human and monkey species. Binding assays were performed using the antibodies prepared in Example 4, a monkey antigen protein (Uniprot ID: A0A2K5WVV8), and the monkey CD112R-expressing cell line cynoCD112R-CHO K1. For specific procedures, see Example 6.1.

[0095] The results (Table 5) show that all of the antibodies obtained in the present invention can bind to monkey antigen proteins and cell lines overexpressing monkey proteins, indicating good cross-reactivity with humans and monkeys. Therefore, the antibodies obtained in the present invention can be widely applied in experiments and tests based on monkey models.

[0096] All of the antibodies of the present invention exhibited excellent cross-reactivity between human and monkey species.

[0097] [Table 5]

[0098] Example 8: Antibody affinity kinetics (Biacore) analysis In this example, the affinity of the resulting antibody or the positive control antibody Tab-1 to the antigen protein huCD112R-His was detected using a Biacore instrument. Anti-CD112R antibody samples were diluted to 10 μg / mL using running buffer HBS-EP+ (10 mM HEPES, 150 mM NaCl, 3 mM EDTA, 0.05% P20, pH 7.4) (BR100826, GE). Human CD112R antigen protein huCD112R-His (Acro Biosystems, PVG-H52H4) was diluted in a 2-fold gradient using HBS-EP+ buffer to concentrations of 0.03125 nM to 2 nM. Anti-CD112R antibodies were captured using a Protein A biosensor chip (BR100354, GE) at a capture time of 60 s and a flow rate of 30 μL / min. Next, human CD112R samples diluted to different concentrations were loaded sequentially from 0 to the highest concentration with an association time of 120 s, a dissociation time of 360 s, and a flow rate of 30 μL / min. The reaction signal was detected in real time using a Biacore X100 instrument, and binding and dissociation curves were acquired. After the dissociation period of each experimental cycle was completed, the Protein A biosensor chip was washed and regenerated with 10 mM glycine-HCl (pH 1.5) (Product Code: 29127558, GE). The regeneration time was 30 s and the flow rate was 30 μL / min. Parameter fitting: Experiments were performed in single-cycle mode, and analysis was performed with time on the horizontal axis and response values ​​on the vertical axis. Double reference subtraction was performed on the obtained data, followed by fitting using the BIAcore X100 (GE) analysis software. A 1:1 Langmuir binding model was used for fitting, and affinity indices such as binding dissociation constants were determined. The results showed that the affinity of the antibodies of the present invention was better than or comparable to the positive control Tab-1.

[0099] [Table 6]

[0100] Example 9: Detection of antibody-mediated inhibition of CD112R and CD112 binding signal transduction pathway (reporter gene method) The reporter gene method consists of two genetically engineered cell lines: the GS-J2C / CD112R effector cell line, which expresses human CD112R and a luciferase reporter gene driven by the NFAT-RE; and the GS-C2 / CD112 target cell line, which expresses human CD112 in an engineered cell surface protein to activate the homologous TCR in an antigen-independent manner. When the GS-J2C / CD112R effector cell line was cocultured with the GS-C2 / CD112 target cell line, the CD112R / CD112 interaction inhibited activation of the TCR signaling pathway, thereby inhibiting NFAT-driven luciferase expression, resulting in a relatively low corresponding fluorescent signal. Addition of a CD112R therapeutic antibody blocked the CD112R / CD112 interaction, restoring the TCR signaling pathway and increasing the fluorescent signal.

[0101] First, we constructed GS-2 / CD112 target cells. A full-length human CD112 DNA fragment (NP_001036189.1) was inserted into a lentiviral expression vector (blasticidin-resistant), mixed with a helper plasmid, and transfected into 293T cells. The resulting vector was packaged as a CD112-blasticidin recombinant lentivirus. CHO-K1 / APC cells were infected with the recombinant lentivirus (designated GS-C2) and screened with 10 μg / ml blasticidin to obtain a pool of cells successfully infected with CD112. GS-C2 / CD112 monoclonal cells were selected by limiting dilution.

[0102] Construction of GS-J2C / CD112R effector cells. The full-length human CD112R DNA fragment (XP_011514877.1) was inserted into a puromycin-resistant lentiviral expression vector, mixed with a helper plasmid, and transfected into 293T cells. The vector was packaged as a CD112-puromycin recombinant lentivirus. Jurkat-Luc reporter cells were infected with the lentivirus (designated GS-J2C) and screened with 1 μg / ml puromycin to obtain a pool of cells successfully infected with CD112R. GS-J2C / PVRIG monoclonal cells were selected by limiting dilution.

[0103] Target cells were collected by centrifugation and resuspended in their respective complete medium (10% FBS F-12K). The target cell density was adjusted and seeded into experimental plates. The experimental plates were transferred to a cell incubator (37°C / 5% CO2) and incubated for approximately 16 hours. Effector cells were collected by centrifugation and then resuspended in assay buffer (1.25% FBS RPMI 1640) to adjust the cell density. The plate containing the incubated target cells was removed from the cell incubator, and the medium was removed. The control and test sample working solutions and the effector cell suspension were transferred, in order, to the experiment board. The experimental plate was transferred to a cell incubator (37°C / 5% CO2) and incubated for 6 hours. The incubated experimental plate was removed from the cell incubator, and the luciferase detection reagent working solution was transferred to the corresponding wells of the experimental plate and incubated at room temperature for 3-5 minutes. Chemiluminescence values ​​were read using a PHERA star and the data were recorded.

[0104] The results showed that the antibodies of the present invention effectively blocked the binding of CD112R to CD112.

[0105] [Table 7]

[0106] Example 10: Blocking CD112R and CD112 binding by antibodies enhances antigen-specific CD8 T cell activation (primary immune cell method) antigen-specific CD8 + Antibody activation of T cells was measured. PBMC cells of a specific genotype (HLA-A*0201) were collected by centrifugation and resuspended in RPMI 1640 medium (Gibco) supplemented with 10% FBS (Gibco). The pp65(495-503) polypeptide (CEF20, cytomegalovirus, CMV pp65(495-503), GenScript) and cytokines (IL-2 Human and IL-7 Human, GenScript) were added to stimulate antigen-specific CD8 T cells. + After 11 days of culture, PBMC cells were collected by centrifugation and transfected with human CD8 T cells. + CD8 T cell isolation kit (17953, STEMCELL) was used. + T cells were obtained. 5 × 10 4 25 × 10 target cells (Ksaumi-1 and Colo-205) were added to a 96-well bottom plate, and the pp65(495-503) polypeptide working solution was added to each well and incubated in a cell culture incubator for 1 hour. 4 CD8 + T cells were added to each 96-well plate. Then, the antibody to be measured was added to the corresponding well depending on the detection concentration. The 96-well plate was incubated in a cell culture incubator (37°C / 5% CO2) for 18–22 hours. After incubation, the 96-well plate was removed and centrifuged at 2000 rpm for 5 minutes, and the supernatant was transferred to a new 96-well plate. The cytokine interferon-α (IFN-α) was measured according to the instructions of the cytokine detection kit (62HIFNGPEH, Cisbio).

[0107] [Table 8]

[0108] The results showed that the antibodies of the present invention effectively blocked the binding of CD112R to CD112, promoting the activation of antigen-specific CD8 T cells and the secretion of the cytokine interferon-γ (IFN-γ).

[0109] Modifications of the present invention in addition to those described herein are intended to be within the scope of the following claims in light of the foregoing. Each reference cited in this application (including all patents, patent applications, journal articles, books, and other publications) is hereby incorporated by reference in its entirety.

[0110] [Table 9-1] [Table 9-2] [Table 9-3] [Table 9-4] [Table 9-5] [Table 9-6] [Table 9-7] [Table 9-8] Table 9-9 Table 9-10 Table 9-11 Table 9-12 Table 9-13 Table 9-14 Table 9-15 Table 9-16 Table 9-17

Claims

1. Anti-CD112R antibodies or antigen-binding fragments thereof that specifically bind to CD112R, including: 1) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 430 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 431; 2) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 432 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 433; 3) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 434 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 435; 4) three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 436 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 437; 5) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 438 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 439; 6) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 438 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 440; 7) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 441 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 442; 8) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 443 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 444; 9) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region shown in SEQ ID NO: 445 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region shown in SEQ ID NO: 446; 10) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 447 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 448; 11) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 449 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 450; 12) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 451 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 452; 13) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 453 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 454; 14) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 455 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 456; 15) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 457 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 458; 16) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 459 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 460; 17) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 461 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 462; 18) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 463 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 464; 19) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 465 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 466; 20) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 467 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 468; 21) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 469 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 470; 22) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 471 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 472; 23) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 473 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 474; 24) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 475 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 476; 25) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 477 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 478; 26) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 479 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 480; 27) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 481 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 482; 28) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 483 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 484; 29) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 485 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 486; 30) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 487 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 456; 31) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 488 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 489; 32) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 490 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 491; 33) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 492 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 489; 34) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 493 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 494; 35) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 493 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 495; 36) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 496 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 497; 37) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 498 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 497; 38) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 499 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 500; 39) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 501 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 503; 40) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 502 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 503; 41) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 504 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 505; 42) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 499 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 506; 43) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 507 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 503; 44) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 508 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 509; 45) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 510 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 511; 46) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 512 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 513; 47) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 514 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 515; 48) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 501 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 516; 49) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 517 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 518; 50) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 519 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 520; 51) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 521 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 522; 52) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 523 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 524; 53) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 525 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 486; 54) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 526 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 527; 55) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 528 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 529; 56) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 530 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 531; 57) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 530 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 533; 58) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 532 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 531; 59) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 532 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 533; 60) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 534 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 535; 61) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 536 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 537; 62) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 538 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 539; 63) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 540 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 541; 64) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 540 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 542; 65) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 543 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 544; 66) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 545 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 546; 67) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 547 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 548; 68) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 549 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 550; 69) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 551 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 552; 70) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 553 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 554; 71) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 555 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 556; 72) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 557 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 558; 73) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 559 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 560; 74) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 561 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 554; 75) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 562 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 563; 76) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 564 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 565; 77) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 566 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 567; 78) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 568 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 569; 79) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 570 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 571; 80) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 572 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 573; 81) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 574 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 575; 82) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 576 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 578; 83) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 577 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 578; 84) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 579 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 580; 85) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 581 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 582; 86) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 583 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 584; 87) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 585 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 586; 88) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 587 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 588; 89) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 587 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 589; 90) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 590 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 591; 91) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 592 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 593; 92) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 592 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 594; 93) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 595 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 596; 94) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 595 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 594; 95) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 597 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 598; 96) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 597 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 594; 97) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 599 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 600; 98) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 601 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 602; 99) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 603 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 604; 100) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 605 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 606; 101) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 607 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 608; 102) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 609 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 610; 103) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 611 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 612; 104) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 613 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 614; 105) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 615 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 616; 106) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 617 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 618; 107) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 619 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 620; 108) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 621 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 622; 109) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 623 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 624; 110) Three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 625 and three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 626; 111) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 627 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 628; 112) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 629 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 630; 113) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 631 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 632; 114) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 617 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 633; 115) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 634 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 635; 116) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 636 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 637; 117) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 638 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 639; 118) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 640 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 641; 119) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 642 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 643; 120) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 644 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 645; 121) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 646 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 647; 122) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 648 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 649; 123) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 650 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 651; 124) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region represented by SEQ ID NO: 652 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region represented by SEQ ID NO: 653; 125) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region set forth in SEQ ID NO: 654 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region set forth in SEQ ID NO: 655; or 126) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region set forth in SEQ ID NO: 656 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region set forth in SEQ ID NO:

653.

2. Anti-CD112R antibodies or antigen-binding fragments thereof that specifically bind to CD112R, including: 1) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 1, 64 and 162, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 307 and 357, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 2) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 65 and 162, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308 and 358, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 3) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 3, 66, 163, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 240, 309, 359, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 4) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 4, 67, 164, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 310, 360, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 5) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 68, 165, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 361, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 6) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 68, 165, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 242, 312, 362, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 7) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 6, 69, 166, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 243, 313, 363, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 8) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 7, 70, 167, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 244, 314, 364, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 9) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 8, 71, 168, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 245, 313, 365, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 10) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 3, 72, 163, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 359, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 11) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 9, 73, 168, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 245, 313, 363, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 12) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 3, 74, 163, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 246, 311, 359, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 13) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 10, 75, 169, respectively, or sequences containing one or more and one or less than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 315, 366, respectively, or sequences containing one or more and one or less than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 14) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 10, 75, 170, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 315, 366, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 15) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 9, 76, 168, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 243, 313, 363, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 16) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 9, 77, 168, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 248, 313, 363, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 17) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 8, 77, 168, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 243, 313, 365, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 18) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 7, 78, 167, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 244, 314, 364, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 19) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 11, 79, 171, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 249, 316, 367, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 20) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 80, 162, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 317, 368, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 21) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 12, 81, 172, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 250, 315, 369, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 22) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 10, 82, 169, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 315, 370, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 23) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 83, 173, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 242, 312, 371, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 24) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 13, 84, 173, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 242, 312, 372, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 25) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 85, 174, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 251, 318, 373, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 26) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 14, 86, 175, respectively, or sequences containing one or more and one or less than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 252, 319, 374, respectively, or sequences containing one or more and one or less than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 27) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 15, 87, 176, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 253, 320, 375, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 28) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 16, 88, 177, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 254, 321, 376, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 29) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 89, 178, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 377, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 30) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 17, 75, 169, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 315, 366, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 31) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 18, 85, 162, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 322, 378, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 32) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 90, 162, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 255, 308, 368, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 33) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 19, 91, 179, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 322, 378, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 34) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 85, 180, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 323, 379, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 35) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 2, 85, 180, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 380, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 36) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 20, 92, 181, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 257, 324, 381, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 37) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 21, 93, 182, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 258, 325, 382, ​​respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 38) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 22, 94, 183, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 259, 323, 383, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 39) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 23, 94, 183, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 259, 323, 383, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 40) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 24, 95, 184, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 326, 384, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 41) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 21, 93, 182, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 326, 385, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 42) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 22, 94, 183, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 259, 323, 383, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 43) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 25, 96, 185, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 260, 327, 386, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 44) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 26, 97, 186, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 261, 328, 387, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 45) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 27, 98, 187, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 262, 328, 388, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 46) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 28, 99, 188, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 263, 328, 388, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 47) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 22, 94, 183, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 389, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 48) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 100, 189, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 264, 329, 390, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 49) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 24, 101, 190, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 326, 385, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 50) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 28, 102, 191, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 265, 328, 391, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 51) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 28, 103, 192, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 266, 328, 388, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 52) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 29, 104, 163, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 377, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 53) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 30, 105, 193, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 267, 330, 392, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 54) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 106, 194, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 268, 331, 393, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 55) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 31, 107, 195, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 318, 392, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 56) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 31, 107, 195, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 269, 332, 394, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 57) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 32, 108, 196, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 318, 392, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 58) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 32, 108, 196, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 269, 332, 394, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 59) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 29, 109, 197, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 395, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 60) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 33, 110, 198, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 270, 333, 396, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 61) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 111, 199, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 318, 397, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 62) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 34, 112, 200, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 269, 334, 398, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 63) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 34, 112, 200, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 271, 335, 399, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 64) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 35, 113, 201, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 400, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 65) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 36, 114, 202, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 272, 336, 401, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 66) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 29, 115, 203, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 402, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 67) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 37, 116, 204, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 273, 337, 403, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 68) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 117, 205, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 274, 338, 404, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 69) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 38, 110, 198, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 270, 333, 405, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 70) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 39, 118, 204, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 275, 337, 406, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 71) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 119, 206, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 276, 338, 407, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 72) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 29, 109, 197, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 395, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 73) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 38, 110, 198, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 270, 333, 405, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 74) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 120, 205, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 277, 338, 407, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 75) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 121, 207, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 278, 338, 404, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 76) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 35, 122, 201, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 279, 311, 408, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 77) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 35, 123, 208, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 280, 311, 400, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 78) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 5, 124, 209, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 281, 338, 407, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 79) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 40, 125, 210, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 282, 339, 409, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 80) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 41, 126, 211, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 245, 333, 410, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 81) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 10, 127, 212, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 411, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 82) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 40, 125, 213, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 411, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 83) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 42, 128, 214, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 283, 324, 412, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 84) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 43, 129, 215, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 284, 339, 409, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 85) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 42, 130, 216, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 285, 340, 409, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 86) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 131, 217, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 286, 341, 413, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 87) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 132, 218, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 282, 341, 414, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 88) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 132, 218, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 287, 342, 415, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 89) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 45, 133, 219, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 288, 343, 416, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 90) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 46, 134, 220, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 289, 324, 417, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 91) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 46, 134, 220, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 290, 344, 418, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 92) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 47, 135, 221, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 291, 345, 407, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 93) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 47, 135, 221, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 290, 344, 418, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 94) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 48, 136, 222, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 292, 346, 409, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 95) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 48, 136, 222, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 290, 344, 418, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 96) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 49, 137, 163, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 240, 347, 419, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 97) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 45, 138, 223, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 288, 343, 416, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 98) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 50, 139, 224, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 249, 348, 420, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 99) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 51, 140, 225, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 256, 349, 421, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 100) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 47, 141, 221, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 293, 345, 407, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 101) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 52, 142, 226, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 294, 350, 422, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 102) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 53, 143, 178, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 295, 311, 423, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 103) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 53, 144, 178, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 361, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 104) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 53, 145, 227, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 361, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 105) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 54, 146, 228, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 296, 328, 391, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 106) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 55, 147, 228, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 266, 328, 391, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 107) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 50, 148, 229, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 297, 351, 424, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 108) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 56, 149, 230, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 298, 323, 425, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 109) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 57, 150, 231, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 299, 338, 407, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 110) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 58, 151, 232, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 300, 352, 426, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 111) HCDR1, HCDR2, and HCDR3 comprising the sequences set forth in SEQ ID NOs: 59, 152, and 233, respectively, or sequences containing one or more and one or less than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, and LCDR3 comprising the sequences set forth in SEQ ID NOs: 301, 328, and 388, respectively, or sequences containing one or more and one or less than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 112) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 60, 153, 234, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 239, 308, 360, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 113) HCDR1, HCDR2, and HCDR3 comprising the sequences set forth in SEQ ID NOs: 54, 146, and 228, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, and LCDR3 comprising the sequences set forth in SEQ ID NOs: 302, 328, and 391, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 114) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 61, 154, 235, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 241, 311, 361, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 115) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 40, 125, 210, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 282, 353, 409, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; 116) HCDR1, HCDR2, and HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 155, and 236, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, and LCDR3 comprising the sequences set forth in SEQ ID NOs: 303, 324, and 409, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 117) HCDR1, HCDR2, and HCDR3 comprising the sequences set forth in SEQ ID NOs: 44, 156, and 217, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, and LCDR3 comprising the sequences set forth in SEQ ID NOs: 282, 341, and 414, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 118) HCDR1, HCDR2, and HCDR3 comprising the sequences set forth in SEQ ID NOs: 62, 157, and 237, respectively, or sequences containing one or more and one or less than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, and LCDR3 comprising the sequences set forth in SEQ ID NOs: 304, 332, and 427, respectively, or sequences containing one or more and one or less than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 119) HCDR1, HCDR2, and HCDR3 comprising the sequences set forth in SEQ ID NOs: 24, 158, and 184, respectively, or sequences containing one or more and one or less than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, and LCDR3 comprising the sequences set forth in SEQ ID NOs: 247, 326, and 428, respectively, or sequences containing one or more and one or less than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 120) HCDR1, HCDR2, and HCDR3 comprising the sequences set forth in SEQ ID NOs: 3, 159, and 189, respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, and LCDR3 comprising the sequences set forth in SEQ ID NOs: 249, 354, and 382, ​​respectively, or sequences containing one or more and not more than three amino acid amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 121) HCDR1, HCDR2, and HCDR3 comprising the sequences set forth in SEQ ID NOs: 63, 160, and 238, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, and LCDR3 comprising the sequences set forth in SEQ ID NOs: 305, 355, and 429, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; or 122) HCDR1, HCDR2 and HCDR3 comprising the sequences set forth in SEQ ID NOs: 42, 161, 214, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 comprising the sequences set forth in SEQ ID NOs: 306, 356, 409, respectively, or sequences containing one or more and not more than three amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said 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 a Fab, Fab'-SH, Fv (e.g., scFv) or (Fab')2 fragment.

4. The anti-CD112R antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, 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 set forth in SEQ ID NO: 659 and the light chain constant region comprises the amino acid sequence set forth in SEQ ID NO:

660.

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

7. 7. An expression vector comprising the nucleotide molecule of claim 6, wherein preferably the expression vector is a eukaryotic expression vector.

8. A host cell comprising the expression vector of claim 7 or the polynucleotide molecule of claim 6.

9. A pharmaceutical composition comprising: (1) an anti-CD112R antibody or antigen-binding fragment thereof described in any one of claims 1 to 5, or a polynucleotide molecule described in claim 6, or an expression vector described in claim 7, or a host cell described in 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 prophylactically or therapeutically effective amount of the antibody or antigen-binding fragment thereof described in any one of claims 1 to 5, or the polynucleotide molecule described in claim 6, or the expression vector described in claim 7, or the host cell described in claim 8, or the pharmaceutical composition described in claim 9.

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

12. The method according to claim 10 or the use according to claim 11, wherein the CD112R-mediated disease or disorder is a CD112R-associated cancer, preferably selected from melanoma, kidney 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.

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