CD112R targeting antibody or antigen binding fragment thereof and application thereof

Abstract

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

Description

[0001] This application is a divisional application of Chinese Patent Application No. 202380090088.8, filed on December 4, 2023, entitled "An antibody targeting CD112R or an antigen-binding fragment thereof and its application". Technical Field

[0002] This application relates to antibodies that specifically recognize CD112R or their antigen-binding fragments, their preparation methods, and their uses. Background Technology

[0003] CD112R, also known as the protein containing the poliovirus receptor-associated immunoglobulin domain, Q6DKI7, or C7orf15, is a 326-amino acid transmembrane domain protein with a signal peptide (spanning amino acids 1 to 40), an extracellular domain (spanning amino acids 41 to 171), a transmembrane domain (spanning amino acids 172 to 190), and a cytoplasmic domain (spanning amino acids 191 to 326). CD112R binds to poliovirus receptor-associated protein 2 (PVLR2, also known as nectin2, CD112, or herpesvirus invasion mediator B (HVEB), human plasma membrane glycoprotein), which is the binding partner of CD112R.

[0004] Administration of anti-CD112R immunotherapy offers an opportunity to increase, enhance, and maintain the immune response. CD112R is an inhibitory receptor primarily expressed by T cells and NK cells and competes with the activation receptor CD226 for binding to CD112. The interaction between CD112 and CD112R has a higher affinity than that with CD226, thereby effectively modulating CD226-mediated cell activation. Anti-CD112R antibodies that block the interaction with CD112 directly restrict the downstream of the inhibitory signaling pathway of CD112R, while simultaneously promoting greater immune cell activation by increasing the interaction between CD226 and CD112. Treatment with anti-CD112R antibodies provides an opportunity to downregulate inhibitory signals that may occur when CD112R-expressing immune cells bind to CD112 on tumor cells and / or myeloid cells within the tumor microenvironment, and may enhance, increase, and maintain the anti-tumor immune response.

[0005] Although there are publicly available anti-CD112R antibodies under development, there is still an urgent need to develop high-quality anti-CD112R antibodies. Summary of the Invention

[0006] In a first aspect, the present invention provides an antibody targeting human CD112R, which has the following advantages: (1) It binds to human / cynomolgus monkey CD112R protein with high affinity; (2) Inhibit or block 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.

[0007] In one embodiment, the present invention provides an anti-CD112R antibody that specifically binds to CD112R and its antigen-binding fragment, comprising: 1) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 430, and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 431; 2) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:432 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:433; 3) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 434 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 435; 4) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 436 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 437; 5) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 438 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 439; 6) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 438 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 440; 7) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 441 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 442; 8) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 443 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 444; 9) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 445 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 446; 10) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 447 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 448; 11) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 449 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 450; 12) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 451 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 452; 13) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 453 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 454; 14) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 455 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 456; 15) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 457 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 458. 16) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 459 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 460; 17) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 461 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 462; 18) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:463 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:464; 19) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:465 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:466; 20) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 467 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 468; 21) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 469 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 470; 22) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 471 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 472; 23) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 473 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 474; 24) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:475 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:476; 25) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 477 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 478; 26) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:479 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:480; 27) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 481 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 482; 28) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 483 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 484; 29) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 485 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 486. 30) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 487 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 456; 31) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 488 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 489; 32) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 490 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 491; 33) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 492 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 489; 34) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 493 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 494; 35) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 493 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 495; 36) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 496 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 497; 37) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 498 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 497; 38) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 499 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 500; 39) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 501 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 503; 40) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 502 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 503; 41) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:504 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:505; 42) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 499 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 506; 43) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 507 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 503; 44) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 508 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 509; 45) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 510 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 511. 46) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 512 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 513. 47) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 514 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 515. 48) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:501 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:516. 49) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 517 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 518. 50) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 519 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 520; 51) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 521 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 522; 52) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 523 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 524; 53) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 525 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 486; 54) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 526 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 527. 55) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 528 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 529. 56) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 530 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 531; 57) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 530 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 533; 58) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 532 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 531; 59) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 532 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 533; 60) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 534 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 535; 61) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:536 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:537. 62) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 538 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 539; 63) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 540 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 541; 64) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 540 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 542; 65) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 543 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 544. 66) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 545 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 546; 67) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 547 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 548. 68) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:549 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:550. 69) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 551 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 552. 70) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 553 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 554; 71) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 555 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 556. 72) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 557 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 558; 73) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:559 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:560; 74) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 561 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 554. 75) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 562 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 563. 76) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 564 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 565; 77) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 566 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 567. 78) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 568 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 569; 79) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 570 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 571. 80) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 572 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 573; 81) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:574 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:575; 82) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 576 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 578. 83) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 577 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 578; 84) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 579 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 580; 85) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 581 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 582; 86) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 583 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 584; 87) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 585 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 586; 88) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:587 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:588; 89) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 587 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 589; 90) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 590 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 591; 91) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 592 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 593; 92) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 592 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 594; 93) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:595 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:596; 94) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 595 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 594. 95) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 597 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 598; 96) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 597 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 594. 97) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 599 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 600; 98) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 601 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 602; 99) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 603 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 604; 100) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:605 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:606. 101) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:607 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:608; 102) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 609 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 610; 103) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 611 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 612; 104) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:613 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:614; 105) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 615 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 616; 106) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 617 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 618; 107) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 619 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 620; 108) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:621 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:622; 109) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 623 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 624; 110) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 625 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 626; 111) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:627 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:628; 112) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 629 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 630; 113) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 631 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 632; 114) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 617 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 633; 115) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 634 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 635; 116) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 636 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 637; 117) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 638 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 639; 118) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:640 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:641; 119) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 642 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 643; 120) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 644 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 645; 121) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:646 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:647. 122) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 648 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 649; 123) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 650 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 651; 124) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO:652 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:653; 125) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 654 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 655; 126) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 656 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 653.

[0008] In one embodiment, the present invention provides an anti-CD112R antibody that specifically binds to CD112R and its antigen-binding fragment, comprising: 1) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 1, 64, and 162, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 239, 307, and 357, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 2) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 2, 65, and 162, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 239, 308, and 358, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 3) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 3, 66, 163, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 240, 309, 359, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 4) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 4, 67, 164, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 239, 310, 360, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 5) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 5, 68, 165, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 241, 311, 361, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 6) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 5, 68, 165, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 242, 312, 362, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 7) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 6, 69, 166, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 243, 313, 363, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 8) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 7, 70, 167, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 244, 314, 364, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 9) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 8, 71, 168, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 245, 313, 365, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 10) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 3, 72, 163, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 241, 311, 359, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 11) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 9, 73, 168, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 245, 313, 363, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 12) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO:3, 74, 163, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO:246, 311, 359, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 13) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 10, 75, 169, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 247, 315, 366, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 14) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 10, 75, 170, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 247, 315, 366, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 15) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 9, 76, 168, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 243, 313, 363, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 16) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 9, 77, 168, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 248, 313, 363, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 17) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 8, 77, 168, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 243, 313, 365, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 18) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 7, 78, 167, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 244, 314, 364, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 19) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 11, 79, 171, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 249, 316, 367, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 20) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO:2, 80, 162, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO:239, 317, 368, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 21) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 12, 81, 172, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 250, 315, 369, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 22) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 10, 82, 169, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 247, 315, 370, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 23) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 2, 83, 173, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 242, 312, 371, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 24) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 13, 84, 173, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 242, 312, 372, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 25) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 2, 85, 174, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 251, 318, 373, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 26) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 14, 86, 175, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 252, 319, 374, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 27) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 15, 87, 176, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 253, 320, 375, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 28) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 16, 88, 177, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 254, 321, 376, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 29) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO:2, 89, 178, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO:241, 311, 377, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 30) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 17, 75, 169, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 247, 315, 366, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 31) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 18, 85, 162, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 239, 322, 378, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 32) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 2, 90, 162, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 255, 308, 368, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 33) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 19, 91, 179, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 239, 322, 378, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 34) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO:2, 85, 180, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO:256, 323, 379, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 35) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 2, 85, 180, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 239, 308, 380, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 36) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 20, 92, 181, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 257, 324, 381, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 37) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO:21, 93, 182, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO:258, 325, 382, ​​or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 38) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 22, 94, 183, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 259, 323, 383, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 39) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 23, 94, 183, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 259, 323, 383, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 40) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 24, 95, 184, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 247, 326, 384, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 41) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 21, 93, 182, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 247, 326, 385, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 42) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 22, 94, 183, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 259, 323, 383, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 43) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 25, 96, 185, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 260, 327, 386, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 44) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 26, 97, 186, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 261, 328, 387, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 45) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 27, 98, 187, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 262, 328, 388, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 46) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 28, 99, 188, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 263, 328, 388, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 47) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 22, 94, 183, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 239, 308, 389, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 48) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 5, 100, 189, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 264, 329, 390, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 49) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 24, 101, 190, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 247, 326, 385, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 50) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO:28, 102, 191, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO:265, 328, 391, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 51) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 28, 103, 192, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 266, 328, 388, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 52) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 29, 104, 163, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 241, 311, 377, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 53) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO:30, 105, 193, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO:267, 330, 392, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 54) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 5, 106, 194, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 268, 331, 393, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 55) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 31, 107, 195, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 256, 318, 392, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 56) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 31, 107, 195, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 269, 332, 394, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 57) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 32, 108, 196, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 256, 318, 392, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 58) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 32, 108, 196, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 269, 332, 394, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 59) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 29, 109, 197, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 241, 311, 395, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 60) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 33, 110, 198, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 270, 333, 396, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 61) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 5, 111, 199, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 256, 318, 397, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 62) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 34, 112, 200, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 269, 334, 398, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 63) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 34, 112, 200, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 271, 335, 399, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 64) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 35, 113, 201, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 241, 311, 400, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 65) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 36, 114, 202, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 272, 336, 401, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 66) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 29, 115, 203, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 241, 311, 402, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 67) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO:37, 116, 204, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO:273, 337, 403, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 68) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 5, 117, 205, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 274, 338, 404, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 69) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 38, 110, 198, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 270, 333, 405, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 70) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 39, 118, 204, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 275, 337, 406, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 71) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 5, 119, 206, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 276, 338, 407, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 72) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 29, 109, 197, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 241, 311, 395, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 73) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 38, 110, 198, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 270, 333, 405, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 74) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 5, 120, 205, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 277, 338, 407, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 75) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 5, 121, 207, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 278, 338, 404, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 76) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 35, 122, 201, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 279, 311, 408, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 77) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 35, 123, 208, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 280, 311, 400, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 78) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 5, 124, 209, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 281, 338, 407, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 79) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 40, 125, 210, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 282, 339, 409, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 80) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO:41, 126, 211, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO:245, 333, 410, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 81) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 10, 127, 212, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 239, 308, 411, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 82) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 40, 125, 213, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 239, 308, 411, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 83) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO:42, 128, 214, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO:283, 324, 412, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 84) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 43, 129, 215, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 284, 339, 409, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 85) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 42, 130, 216, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 285, 340, 409, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 86) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 44, 131, 217, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 286, 341, 413, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 87) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 44, 132, 218, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 282, 341, 414, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 88) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 44, 132, 218, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 287, 342, 415, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 89) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 45, 133, 219, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 288, 343, 416, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 90) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 46, 134, 220, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 289, 324, 417, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 91) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 46, 134, 220, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 290, 344, 418, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 92) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 47, 135, 221, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 291, 345, 407, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 93) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 47, 135, 221, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 290, 344, 418, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 94) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO:48, 136, 222, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO:292, 346, 409, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 95) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 48, 136, 222, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 290, 344, 418, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 96) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 49, 137, 163, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 240, 347, 419, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 97) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO:45, 138, 223, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO:288, 343, 416, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 98) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 50, 139, 224, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 249, 348, 420, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 99) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 51, 140, 225, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 256, 349, 421, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 100) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 47, 141, 221, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 293, 345, 407, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 101) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 52, 142, 226, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 294, 350, 422, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 102) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 53, 143, 178, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 295, 311, 423, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 103) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 53, 144, 178, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 241, 311, 361, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 104) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 53, 145, 227, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 241, 311, 361, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 105) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 54, 146, 228, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 296, 328, 391, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 106) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 55, 147, 228, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 266, 328, 391, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 107) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 50, 148, 229, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 297, 351, 424, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 108) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 56, 149, 230, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 298, 323, 425, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 109) HCDR1, HCDR2, HCDR3 comprising the sequences shown in SEQ ID NO: 57, 150, 231, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising the sequences shown in SEQ ID NO: 299, 338, 407, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 110) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO:58, 151, 232, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO:300, 352, 426, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 111) HCDR1, HCDR2, HCDR3 containing sequences as shown in SEQ ID NO: 59, 152, 233, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 containing sequences as shown in SEQ ID NO: 301, 328, 388, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 112) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 60, 153, 234, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 239, 308, 360, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 113) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO:54, 146, 228, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO:302, 328, 391, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 114) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 61, 154, 235, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 241, 311, 361, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 115) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 40, 125, 210, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 282, 353, 409, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 116) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 44, 155, 236, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 303, 324, 409, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 117) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 44, 156, 217, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 282, 341, 414, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 118) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 62, 157, 237, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 304, 332, 427, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 119) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 24, 158, 184, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 247, 326, 428, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 120) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO:3, 159, 189, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO:249, 354, 382, ​​or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; 121) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 63, 160, 238, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 305, 355, 429, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; or 122) HCDR1, HCDR2, HCDR3 comprising sequences as shown in SEQ ID NO: 42, 161, 214, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, LCDR3 comprising sequences as shown in SEQ ID NO: 306, 356, 409, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences.

[0009] In one embodiment, the present invention provides an anti-CD112R antibody that specifically binds to CD112R and its antigen-binding fragment, comprising a heavy chain variable region, wherein: 1) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 430, or is composed of SEQ ID NO: 430. 2) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 432, or is composed of SEQ ID NO: 432. 3) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 434, or is composed of SEQ ID NO: 434. 4) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 436, or is composed of SEQ ID NO: 436. 5) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 438, or is composed of SEQ ID NO: 438. 6) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 441, or is composed of SEQ ID NO: 441. 7) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 443, or is composed of SEQ ID NO: 443. 8) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 445, or is composed of SEQ ID NO: 445. 9) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 447, or is composed of SEQ ID NO: 447. 10) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 449, or is composed of SEQ ID NO: 449. 11) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 451, or is composed of SEQ ID NO: 451. 12) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 453, or is composed of SEQ ID NO: 453. 13) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 455, or is composed of SEQ ID NO: 455. 14) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 457, or is composed of SEQ ID NO: 457. 15) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 459, or is composed of SEQ ID NO: 459. 16) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 461, or is composed of SEQ ID NO: 461. 17) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 463, or is composed of SEQ ID NO: 463. 18) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 465, or is composed of SEQ ID NO: 465. 19) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 467, or is composed of SEQ ID NO: 467. 20) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 469, or is composed of SEQ ID NO: 469. 21) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 471, or is composed of SEQ ID NO: 471. 22) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 473, or is composed of SEQ ID NO: 473. 23) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 475, or is composed of SEQ ID NO: 475. 24) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 477, or is composed of SEQ ID NO: 477. 25) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 479, or is composed of SEQ ID NO: 479. 26) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 481, or is composed of SEQ ID NO: 481. 27) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 483, or is composed of SEQ ID NO: 483. 28) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 485, or is composed of SEQ ID NO: 485. 29) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 487, or is composed of SEQ ID NO: 487. 30) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 488, or is composed of SEQ ID NO: 488. 31) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 490, or is composed of SEQ ID NO: 490. 32) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 492, or is composed of SEQ ID NO: 492. 33) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 493, or is composed of SEQ ID NO: 493. 34) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 496, or is composed of SEQ ID NO: 496. 35) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 498, or is composed of SEQ ID NO: 498. 36) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 499, or is composed of SEQ ID NO: 499. 37) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 501, or is composed of SEQ ID NO: 501. 38) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 502, or is composed of SEQ ID NO: 502. 39) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 504, or is composed of SEQ ID NO: 504. 40) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 507, or is composed of SEQ ID NO: 507. 41) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 508, or is composed of SEQ ID NO: 508. 42) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 510, or is composed of SEQ ID NO: 510. 43) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 512, or is composed of SEQ ID NO: 512. 44) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 514, or is composed of SEQ ID NO: 514. 45) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 517, or is composed of SEQ ID NO: 517. 46) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 519, or is composed of SEQ ID NO: 519. 47) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 521, or is composed of SEQ ID NO: 521. 48) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 523, or is composed of SEQ ID NO: 523. 49) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 525, or is composed of SEQ ID NO: 525. 50) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 526, or is composed of SEQ ID NO: 526. 51) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 528, or is composed of SEQ ID NO: 528. 52) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 530, or is composed of SEQ ID NO: 530. 53) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 532, or is composed of SEQ ID NO: 532. 54) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 534, or is composed of SEQ ID NO: 534. 55) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 536, or is composed of SEQ ID NO: 536. 56) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 538, or is composed of SEQ ID NO: 538. 57) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 540, or is composed of SEQ ID NO: 540. 58) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 543, or is composed of SEQ ID NO: 543. 59) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 545, or is composed of SEQ ID NO: 545. 60) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 547, or is composed of SEQ ID NO: 547. 61) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 549, or is composed of SEQ ID NO: 549. 62) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 551, or is composed of SEQ ID NO: 551. 63) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 553, or is composed of SEQ ID NO: 553. 64) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 555, or is composed of SEQ ID NO: 555. 65) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 557, or is composed of SEQ ID NO: 557. 66) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 559, or is composed of SEQ ID NO: 559. 67) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 561, or is composed of SEQ ID NO: 561. 68) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 562, or is composed of SEQ ID NO: 562. 69) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 564, or is composed of SEQ ID NO: 564. 70) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 566, or is composed of SEQ ID NO: 566. 71) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 568, or is composed of SEQ ID NO: 568. 72) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 570, or is composed of SEQ ID NO: 570. 73) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 572, or is composed of SEQ ID NO: 572. 74) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 574, or is composed of SEQ ID NO: 574. 75) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 576, or is composed of SEQ ID NO: 576. 76) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 577, or is composed of SEQ ID NO: 577. 77) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 579, or is composed of SEQ ID NO: 579. 78) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 581, or is composed of SEQ ID NO: 581. 79) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 583, or is composed of SEQ ID NO: 583. 80) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 585, or is composed of SEQ ID NO: 585. 81) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 587, or is composed of SEQ ID NO: 587. 82) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 590, or is composed of SEQ ID NO: 590. 83) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 592, or is composed of SEQ ID NO: 592. 84) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 595, or is composed of SEQ ID NO: 595. 85) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 597, or is composed of SEQ ID NO: 597. 86) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 599, or is composed of SEQ ID NO: 599. 87) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 601, or is composed of SEQ ID NO: 601. 88) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 603, or is composed of SEQ ID NO: 603. 89) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 605, or is composed of SEQ ID NO: 605. 90) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 607, or is composed of SEQ ID NO: 607. 91) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 609, or is composed of SEQ ID NO: 609. 92) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 611, or is composed of SEQ ID NO: 611. 93) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 613, or is composed of SEQ ID NO: 613. 94) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 615, or is composed of SEQ ID NO: 615. 95) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 617, or is composed of SEQ ID NO: 617. 96) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 619, or is composed of SEQ ID NO: 619. 97) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 621, or is composed of SEQ ID NO: 621. 98) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 623, or is composed of SEQ ID NO: 623. 99) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 625, or is composed of SEQ ID NO: 625. 100) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 627, or is composed of SEQ ID NO: 627. 101) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 629, or is composed of SEQ ID NO: 629. 102) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 631, or is composed of SEQ ID NO: 631. 103) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 634, or is composed of SEQ ID NO: 634. 104) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 636, or is composed of SEQ ID NO: 636. 105) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 638, or is composed of SEQ ID NO: 638. 106) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 640, or is composed of SEQ ID NO: 640. 107) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 642, or is composed of SEQ ID NO: 642. 108) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 644, or is composed of SEQ ID NO: 644. 109) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 646, or is composed of SEQ ID NO: 646. 110) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 648, or is composed of SEQ ID NO: 648. 111) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 650, or is composed of SEQ ID NO: 650. 112) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 652, or is composed of SEQ ID NO: 652. 113) The heavy chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 654, or is composed of SEQ ID NO: 654; or 114) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 656, or is composed of SEQ ID NO: 656.

[0010] In one embodiment, the present invention provides an anti-CD112R antibody that specifically binds to CD112R and its antigen-binding fragment, comprising a light chain variable region, wherein: 1) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 431, or is composed of SEQ ID NO: 431; 2) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 433, or is composed of SEQ ID NO: 433. 3) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 435, or is composed of SEQ ID NO: 435. 4) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 437, or is composed of SEQ ID NO: 437. 5) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 439, or is composed of SEQ ID NO: 439. 6) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 440, or is composed of SEQ ID NO: 440. 7) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 442, or is composed of SEQ ID NO: 442. 8) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 444, or is composed of SEQ ID NO: 444. 9) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 446, or is composed of SEQ ID NO: 446. 10) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 448, or is composed of SEQ ID NO: 448. 11) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 450, or is composed of SEQ ID NO: 450. 12) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 452, or is composed of SEQ ID NO: 452. 13) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 454, or is composed of SEQ ID NO: 454. 14) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 456, or is composed of SEQ ID NO: 456. 15) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 458, or is composed of SEQ ID NO: 458. 16) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 460, or is composed of SEQ ID NO: 460. 17) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 462, or is composed of SEQ ID NO: 462. 18) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 464, or is composed of SEQ ID NO: 464. 19) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 466, or is composed of SEQ ID NO: 466. 20) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 468, or is composed of SEQ ID NO: 468. 21) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 470, or is composed of SEQ ID NO: 470. 22) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 472, or is composed of SEQ ID NO: 472. 23) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 474, or is composed of SEQ ID NO: 474. 24) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 476, or is composed of SEQ ID NO: 476. 25) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 478, or is composed of SEQ ID NO: 478. 26) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 480, or is composed of SEQ ID NO: 480. 27) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 482, or is composed of SEQ ID NO: 482. 28) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 484, or is composed of SEQ ID NO: 484. 29) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 486, or is composed of SEQ ID NO: 486. 30) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 489, or is composed of SEQ ID NO: 489. 31) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 491, or is composed of SEQ ID NO: 491. 32) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 494, or is composed of SEQ ID NO: 494. 33) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 495, or is composed of SEQ ID NO: 495. 34) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 497, or is composed of SEQ ID NO: 497. 35) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 500, or is composed of SEQ ID NO: 500. 36) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 503, or is composed of SEQ ID NO: 503. 37) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 505, or is composed of SEQ ID NO: 505. 38) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 506, or is composed of SEQ ID NO: 506. 39) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 509, or is composed of SEQ ID NO: 509. 40) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 511, or is composed of SEQ ID NO: 511. 41) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 513, or is composed of SEQ ID NO: 513. 42) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 515, or is composed of SEQ ID NO: 515. 43) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 516, or is composed of SEQ ID NO: 516. 44) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 518, or is composed of SEQ ID NO: 518. 45) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 520, or is composed of SEQ ID NO: 520. 46) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 522, or is composed of SEQ ID NO: 522. 47) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 524, or is composed of SEQ ID NO: 524. 48) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 527, or is composed of SEQ ID NO: 527. 49) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 529, or is composed of SEQ ID NO: 529. 50) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 531, or is composed of SEQ ID NO: 531. 51) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 533, or is composed of SEQ ID NO: 533. 52) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 535, or is composed of SEQ ID NO: 535. 53) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 537, or is composed of SEQ ID NO: 537. 54) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 539, or is composed of SEQ ID NO: 539. 55) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 541, or is composed of SEQ ID NO: 541. 56) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 542, or is composed of SEQ ID NO: 542. 57) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 544, or is composed of SEQ ID NO: 544. 58) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 546, or is composed of SEQ ID NO: 546. 59) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 548, or is composed of SEQ ID NO: 548. 60) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 550, or is composed of SEQ ID NO: 550. 61) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 552, or is composed of SEQ ID NO: 552. 62) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 554, or is composed of SEQ ID NO: 554. 63) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 556, or is composed of SEQ ID NO: 556. 64) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 558, or is composed of SEQ ID NO: 558. 65) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 560, or is composed of SEQ ID NO: 560. 66) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 563, or is composed of SEQ ID NO: 563. 67) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 565, or is composed of SEQ ID NO: 565. 68) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 567, or is composed of SEQ ID NO: 567. 69) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 569, or is composed of SEQ ID NO: 569. 70) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 571, or is composed of SEQ ID NO: 571. 71) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 573, or is composed of SEQ ID NO: 573. 72) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 575, or is composed of SEQ ID NO: 575. 73) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 578, or is composed of SEQ ID NO: 578. 74) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 580, or is composed of SEQ ID NO: 580. 75) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 582, or is composed of SEQ ID NO: 582. 76) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 584, or is composed of SEQ ID NO: 584. 77) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 586, or is composed of SEQ ID NO: 586. 78) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 588, or is composed of SEQ ID NO: 588. 79) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 589, or is composed of SEQ ID NO: 589. 80) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 591, or is composed of SEQ ID NO: 591. 81) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 593, or is composed of SEQ ID NO: 593. 82) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 594, or is composed of SEQ ID NO: 594. 83) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 596, or is composed of SEQ ID NO: 596. 84) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 598, or is composed of SEQ ID NO: 598. 85) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 600, or is composed of SEQ ID NO: 600. 86) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 602, or is composed of SEQ ID NO: 602. 87) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 604, or is composed of SEQ ID NO: 604. 88) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 606, or is composed of SEQ ID NO: 606. 89) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 608, or is composed of SEQ ID NO: 608. 90) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 610, or is composed of SEQ ID NO: 610. 91) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 612, or is composed of SEQ ID NO: 612. 92) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 614, or is composed of SEQ ID NO: 614. 93) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 616, or is composed of SEQ ID NO: 616. 94) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 618, or is composed of SEQ ID NO: 618. 95) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 620, or is composed of SEQ ID NO: 620. 96) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 622, or is composed of SEQ ID NO: 622. 97) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 624, or is composed of SEQ ID NO: 624. 98) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 626, or is composed of SEQ ID NO: 626. 99) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 628, or is composed of SEQ ID NO: 628. 100) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 630, or is composed of SEQ ID NO: 630. 101) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 632, or is composed of SEQ ID NO: 632. 102) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 633, or is composed of SEQ ID NO: 633. 103) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 635, or is composed of SEQ ID NO: 635. 104) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 637, or is composed of SEQ ID NO: 637. 105) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 639, or is composed of SEQ ID NO: 639. 106) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 641, or is composed of SEQ ID NO: 641. 107) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 643, or is composed of SEQ ID NO: 643. 108) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 645, or is composed of SEQ ID NO: 645. 109) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 647, or is composed of SEQ ID NO: 647. 110) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 649, or is composed of SEQ ID NO: 649. 111) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 651, or is composed of SEQ ID NO: 651. 112) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 653, or is composed of SEQ ID NO: 653; or 113) The light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 655, or is composed of SEQ ID NO: 655.

[0011] In another embodiment, the present invention provides an anti-CD112R antibody that specifically binds to CD112R and its antigen-binding fragment, comprising a heavy chain variable region and a light chain variable region, wherein: 1) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 430, or is composed of SEQ ID NO: 430; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 431, or is composed of SEQ ID NO: 431; 2) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 432, or is composed of SEQ ID NO: 432; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 433, or is composed of SEQ ID NO: 433; 3) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 434, or is composed of SEQ ID NO: 434; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 435, or is composed of SEQ ID NO: 435; 4) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 436, or is composed of SEQ ID NO: 436; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 437, or is composed of SEQ ID NO: 437. 5) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 438, or is composed of SEQ ID NO: 438; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 439, or is composed of SEQ ID NO: 439; 6) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 438, or is composed of SEQ ID NO: 438; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 440, or is composed of SEQ ID NO: 440; 7) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 441, or is composed of SEQ ID NO: 441; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 442, or is composed of SEQ ID NO: 442; 8) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 443, or is composed of SEQ ID NO: 443; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 444, or is composed of SEQ ID NO: 444. 9) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 445, or is composed of SEQ ID NO: 445; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 446, or is composed of SEQ ID NO: 446; 10) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 447, or is composed of SEQ ID NO: 447; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 448, or is composed of SEQ ID NO: 448; 11) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 449, or is composed of SEQ ID NO: 449; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 450, or is composed of SEQ ID NO: 450; 12) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 451, or is composed of SEQ ID NO: 451; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 452, or is composed of SEQ ID NO: 452; 13) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 453, or is composed of SEQ ID NO: 453; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 454, or is composed of SEQ ID NO: 454; 14) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 455, or is composed of SEQ ID NO: 455; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 456, or is composed of SEQ ID NO: 456; 15) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 457, or is composed of SEQ ID NO: 457; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 458, or is composed of SEQ ID NO: 458; 16) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 459, or is composed of SEQ ID NO: 459; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 460, or is composed of SEQ ID NO: 460; 17) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 461, or is composed of SEQ ID NO: 461; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 462, or is composed of SEQ ID NO: 462; 18) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 463, or is composed of SEQ ID NO: 463; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 464, or is composed of SEQ ID NO: 464; 19) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 465, or is composed of SEQ ID NO: 465; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 466, or is composed of SEQ ID NO: 466; 20) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 467, or is composed of SEQ ID NO: 467; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 468, or is composed of SEQ ID NO: 468; 21) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 469, or is composed of SEQ ID NO: 469; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 470, or is composed of SEQ ID NO: 470; 22) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 471, or is composed of SEQ ID NO: 471; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 472, or is composed of SEQ ID NO: 472; 23) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 473, or is composed of SEQ ID NO: 473; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 474, or is composed of SEQ ID NO: 474; 24) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 475, or is composed of SEQ ID NO: 475; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 476, or is composed of SEQ ID NO: 476; 25) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 477, or is composed of SEQ ID NO: 477; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 478, or is composed of SEQ ID NO: 478; 26) The heavy chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 479, or is composed of SEQ ID NO: 479; the light chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 480, or is composed of SEQ ID NO: 480; or 27) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 481, or is composed of SEQ ID NO: 481; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 482, or is composed of SEQ ID NO: 482.

[0012] 28) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 483, or is composed of SEQ ID NO: 483; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 484, or is composed of SEQ ID NO: 484; 29) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 485, or is composed of SEQ ID NO: 485; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 486, or is composed of SEQ ID NO: 486; 30) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 487, or is composed of SEQ ID NO: 487; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 456, or is composed of SEQ ID NO: 456; 31) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 488, or is composed of SEQ ID NO: 488; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 489, or is composed of SEQ ID NO: 489; 32) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 490, or is composed of SEQ ID NO: 490; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 491, or is composed of SEQ ID NO: 491; 33) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 492, or is composed of SEQ ID NO: 492; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 489, or is composed of SEQ ID NO: 489; 34) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 493, or is composed of SEQ ID NO: 493; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 494, or is composed of SEQ ID NO: 494; 35) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 493, or is composed of SEQ ID NO: 493; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 495, or is composed of SEQ ID NO: 495; 36) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 496, or is composed of SEQ ID NO: 496; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 497, or is composed of SEQ ID NO: 497; 37) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 498, or is composed of SEQ ID NO: 498; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 497, or is composed of SEQ ID NO: 497; 38) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 499, or is composed of SEQ ID NO: 499; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 500, or is composed of SEQ ID NO: 500; 39) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 501, or is composed of SEQ ID NO: 501; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 503, or is composed of SEQ ID NO: 503; 40) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 502, or is composed of SEQ ID NO: 502; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 503, or is composed of SEQ ID NO: 503; 41) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 504, or is composed of SEQ ID NO: 504; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 505, or is composed of SEQ ID NO: 505; 42) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 499, or is composed of SEQ ID NO: 499; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 506, or is composed of SEQ ID NO: 506; 43) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 507, or is composed of SEQ ID NO: 507; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 503, or is composed of SEQ ID NO: 503; 44) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 508, or is composed of SEQ ID NO: 508; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 509, or is composed of SEQ ID NO: 509; 45) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 510, or is composed of SEQ ID NO: 510; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 511, or is composed of SEQ ID NO: 511; 46) The heavy chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 512, or is composed of SEQ ID NO: 512; the light chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 513, or is composed of SEQ ID NO: 513; or 47) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 514, or is composed of SEQ ID NO: 514; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 515, or is composed of SEQ ID NO: 515.

[0013] 48) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 501, or is composed of SEQ ID NO: 501; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 516, or is composed of SEQ ID NO: 516; 49) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 517, or is composed of SEQ ID NO: 517; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 518, or is composed of SEQ ID NO: 518; 50) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 519, or is composed of SEQ ID NO: 519; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 520, or is composed of SEQ ID NO: 520; 51) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 521, or is composed of SEQ ID NO: 521; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 522, or is composed of SEQ ID NO: 522. 52) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 523, or is composed of SEQ ID NO: 523; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 524, or is composed of SEQ ID NO: 524; 53) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 525, or is composed of SEQ ID NO: 525; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 486, or is composed of SEQ ID NO: 486; 54) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 526, or is composed of SEQ ID NO: 526; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 527, or is composed of SEQ ID NO: 527; 55) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 528, or is composed of SEQ ID NO: 528; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 529, or is composed of SEQ ID NO: 529; 56) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 530, or is composed of SEQ ID NO: 530; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 531, or is composed of SEQ ID NO: 531; 57) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 530, or is composed of SEQ ID NO: 530; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 533, or is composed of SEQ ID NO: 533; 58) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 532, or is composed of SEQ ID NO: 532; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 531, or is composed of SEQ ID NO: 531; 59) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 532, or is composed of SEQ ID NO: 532; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 533, or is composed of SEQ ID NO: 533; 60) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 534, or is composed of SEQ ID NO: 534; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 535, or is composed of SEQ ID NO: 535; 61) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 536, or is composed of SEQ ID NO: 536; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 537, or is composed of SEQ ID NO: 537; 62) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 538, or is composed of SEQ ID NO: 538; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 539, or is composed of SEQ ID NO: 539; 63) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 540, or is composed of SEQ ID NO: 540; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 541, or is composed of SEQ ID NO: 541; 64) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 540, or is composed of SEQ ID NO: 540; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 542, or is composed of SEQ ID NO: 542; 65) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 543, or is composed of SEQ ID NO: 543; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 544, or is composed of SEQ ID NO: 544; 66) The heavy chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 545, or is composed of SEQ ID NO: 545; the light chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 546, or is composed of SEQ ID NO: 546; or 67) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 547, or is composed of SEQ ID NO: 547; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 548, or is composed of SEQ ID NO: 548.

[0014] 68) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 549, or is composed of SEQ ID NO: 549; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 550, or is composed of SEQ ID NO: 550; 69) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 551, or is composed of SEQ ID NO: 551; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 552, or is composed of SEQ ID NO: 552; 70) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 553, or is composed of SEQ ID NO: 553; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 554, or is composed of SEQ ID NO: 554; 71) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 555, or is composed of SEQ ID NO: 555; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 556, or is composed of SEQ ID NO: 556; 72) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 557, or is composed of SEQ ID NO: 557; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 558, or is composed of SEQ ID NO: 558; 73) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 559, or is composed of SEQ ID NO: 559; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 560, or is composed of SEQ ID NO: 560; 74) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 561, or is composed of SEQ ID NO: 561; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 554, or is composed of SEQ ID NO: 554; 75) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 562, or is composed of SEQ ID NO: 562; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 563, or is composed of SEQ ID NO: 563; 76) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 564, or is composed of SEQ ID NO: 564; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 565, or is composed of SEQ ID NO: 565; 77) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 566, or is composed of SEQ ID NO: 566; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 567, or is composed of SEQ ID NO: 567; 78) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 568, or is composed of SEQ ID NO: 568; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 569, or is composed of SEQ ID NO: 569; 79) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 570, or is composed of SEQ ID NO: 570; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 571, or is composed of SEQ ID NO: 571; 80) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 572, or is composed of SEQ ID NO: 572; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 573, or is composed of SEQ ID NO: 573; 81) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 574, or is composed of SEQ ID NO: 574; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 575, or is composed of SEQ ID NO: 575; 82) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 576, or is composed of SEQ ID NO: 576; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 578, or is composed of SEQ ID NO: 578; 83) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 577, or is composed of SEQ ID NO: 577; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 578, or is composed of SEQ ID NO: 578; 84) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 579, or is composed of SEQ ID NO: 579; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 580, or is composed of SEQ ID NO: 580; 85) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 581, or is composed of SEQ ID NO: 581; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 582, or is composed of SEQ ID NO: 582; 86) The heavy chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 583, or is composed of SEQ ID NO: 583; the light chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 584, or is composed of SEQ ID NO: 584; or 87) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 585, or is composed of SEQ ID NO: 585; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 586, or is composed of SEQ ID NO: 586.

[0015] 88) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 587, or is composed of SEQ ID NO: 587; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 588, or is composed of SEQ ID NO: 588; 89) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 587, or is composed of SEQ ID NO: 587; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 589, or is composed of SEQ ID NO: 589; 90) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 590, or is composed of SEQ ID NO: 590; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 591, or is composed of SEQ ID NO: 591; 91) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 592, or is composed of SEQ ID NO: 592; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 593, or is composed of SEQ ID NO: 593; 92) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 592, or is composed of SEQ ID NO: 592; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 594, or is composed of SEQ ID NO: 594; 93) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 595, or is composed of SEQ ID NO: 595; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 596, or is composed of SEQ ID NO: 596; 94) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 595, or is composed of SEQ ID NO: 595; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 594, or is composed of SEQ ID NO: 594; 95) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 597, or is composed of SEQ ID NO: 597; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 598, or is composed of SEQ ID NO: 598; 96) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 597, or is composed of SEQ ID NO: 597; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 594, or is composed of SEQ ID NO: 594; 97) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 599, or is composed of SEQ ID NO: 599; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 600, or is composed of SEQ ID NO: 600; 98) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 601, or is composed of SEQ ID NO: 601; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 602, or is composed of SEQ ID NO: 602; 99) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 603, or is composed of SEQ ID NO: 603; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 604, or is composed of SEQ ID NO: 604; 100) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 605, or is composed of SEQ ID NO: 605; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 606, or is composed of SEQ ID NO: 606; 101) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 607, or is composed of SEQ ID NO: 607; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 608, or is composed of SEQ ID NO: 608; 102) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 609, or is composed of SEQ ID NO: 609; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 610, or is composed of SEQ ID NO: 610; 103) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 611, or is composed of SEQ ID NO: 611; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 612, or is composed of SEQ ID NO: 612; 104) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 613, or is composed of SEQ ID NO: 613; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 614, or is composed of SEQ ID NO: 614; 105) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 615, or is composed of SEQ ID NO: 615; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 616, or is composed of SEQ ID NO: 616; 106) The heavy chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 617, or is composed of SEQ ID NO: 617; the light chain variable region comprises the amino acid sequence shown 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 with the amino acid sequence of SEQ ID NO: 618, or is composed of SEQ ID NO: 618; or 107) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 619, or is composed of SEQ ID NO: 619; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 620, or is composed of SEQ ID NO: 620.

[0016] 108) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 621, or is composed of SEQ ID NO: 621; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 622, or is composed of SEQ ID NO: 622; 109) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 623, or is composed of SEQ ID NO: 623; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 624, or is composed of SEQ ID NO: 624; 110) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 625, or is composed of SEQ ID NO: 625; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 626, or is composed of SEQ ID NO: 626; 111) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 627, or is composed of SEQ ID NO: 627; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 628, or is composed of SEQ ID NO: 628; 112) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 629, or is composed of SEQ ID NO: 629; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 630, or is composed of SEQ ID NO: 630; 113) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 631, or is composed of SEQ ID NO: 631; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 632, or is composed of SEQ ID NO: 632; 114) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 617, or is composed of SEQ ID NO: 617; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 633, or is composed of SEQ ID NO: 633; 115) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 634, or is composed of SEQ ID NO: 634; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 635, or is composed of SEQ ID NO: 635; 116) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 636, or is composed of SEQ ID NO: 636; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 637, or is composed of SEQ ID NO: 637; 117) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 638, or is composed of SEQ ID NO: 638; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 639, or is composed of SEQ ID NO: 639; 118) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 640, or is composed of SEQ ID NO: 640; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 641, or is composed of SEQ ID NO: 641; 119) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 642, or is composed of SEQ ID NO: 642; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 643, or is composed of SEQ ID NO: 643; 120) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 644, or is composed of SEQ ID NO: 644; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 645, or is composed of SEQ ID NO: 645; 121) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 646, or is composed of SEQ ID NO: 646; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 647, or is composed of SEQ ID NO: 647; 122) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 648, or is composed of SEQ ID NO: 648; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 649, or is composed of SEQ ID NO: 649; 123) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 650, or is composed of SEQ ID NO: 650; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 651, or is composed of SEQ ID NO: 651; 124) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 652, or is composed of SEQ ID NO: 652; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 653, or is composed of SEQ ID NO: 653; 125) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 654, or is composed of SEQ ID NO: 654; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 655, or is composed of SEQ ID NO: 655; 126) The heavy chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 656, or is composed of SEQ ID NO: 656; the light chain variable region comprises an amino acid sequence as shown 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 with the amino acid sequence of SEQ ID NO: 653, or is composed of SEQ ID NO: 653.

[0017] In some embodiments, the antibody or its antigen-binding fragment further comprises a heavy chain and / or light chain constant region sequence derived from a human antibody germline common sequence. The light chain constant region is preferably a human κ or λ chain constant region. The heavy chain constant region can be a γ, μ, α, δ, or ε chain, and in some embodiments, the heavy chain constant region is preferably derived from the constant region sequence of human IgG1, IgG2, IgG3, or IgG4. In one embodiment, the light chain constant region comprises or is composed of the sequence shown in SEQ ID NO: 660. In another embodiment, the heavy chain constant region comprises the Fc sequence shown in SEQ ID NO: 661. In yet another embodiment, the heavy chain constant region comprises or is composed of the sequence shown in SEQ ID NO: 659.

[0018] It should be understood that sequence variants of these constant region structural domains may also be used, for example, to contain one or more amino acid modifications, wherein the amino acid sites are identified by the EU indexing system of Kabat et al. (1991).

[0019] In some embodiments of the antibody described above, the antibody is a monoclonal antibody.

[0020] In some embodiments of the antibody mentioned above, the antibody is a full-length antibody.

[0021] In one embodiment, the anti-CD112R antibody of the present invention is a complete antibody, such as IgG1, IgG2, IgG3, or IgG4 antibody. In another embodiment, the anti-CD112R antibody of the present invention covers only its antigen-binding portion, such as Fab, Fab'-SH, Fv, scFv, or (Fab')2 fragment.

[0022] In a second aspect, the present invention provides isolated polynucleotide molecules that encode any of the antibodies or antigen-binding fragments described in the first aspect.

[0023] Thirdly, the present invention provides an expression vector comprising the nucleotide molecule of the second aspect. In one embodiment, the vector is a eukaryotic expression vector.

[0024] Fourthly, the present invention provides a host cell comprising the carrier of the third aspect or the nucleotide molecule of the second aspect. In some embodiments, the host cell is prokaryotic, such as *Escherichia coli*. In other embodiments, the host cell is eukaryotic, such as 293 cells, CHO cells, yeast cells, or plant cells.

[0025] Fifthly, the present invention provides a pharmaceutical composition comprising (1) an antibody or an antigen-binding fragment thereof (as described in the first aspect), a polynucleotide molecule (as described in the second aspect), an expression vector (as described in the third aspect), or a host cell (as described in the fourth aspect), and (2) a pharmaceutically acceptable carrier or excipient.

[0026] In a sixth aspect, the present invention provides a method for preparing the anti-CD112R antibody or an antigen-binding fragment thereof as described herein, the method comprising expressing the antibody or an antigen-binding fragment thereof in a host cell as described herein under conditions suitable for expression of the antibody or an antigen-binding fragment thereof, and recovering the expressed antibody or an antigen-binding fragment thereof from the host cell.

[0027] In a seventh aspect, the antibodies or antigen-binding fragments or pharmaceutical compositions of the present invention can also be administered in combination with one or more other therapies, such as treatment methods and / or other therapeutic agents, for the purposes described herein, such as for the prevention and / or treatment of the related diseases or conditions mentioned herein.

[0028] In an eighth aspect, the present invention provides a pharmaceutical combination comprising an antibody or antigen-binding fragment thereof as described herein, or a pharmaceutical composition thereof, and one or more additional therapeutic agents.

[0029] Ninthly, the present invention provides a method for preventing or treating CD112R-mediated diseases in a subject in need, comprising administering to the subject a preventively effective amount or a therapeutically effective amount of an antibody of the present invention or an antigen-binding fragment thereof, a polynucleotide molecule described herein, an expression vector described herein, a host cell described herein, a pharmaceutical composition described herein, or a combination of pharmaceuticals described herein, preferably the disease or condition being a CD112R-related cancer, more preferably the cancer being selected from melanoma, renal cell carcinoma, 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 a tenth aspect, the present invention provides the use of the antibodies or antigen-binding fragments thereof described herein, the polynucleotide molecules described herein, the expression vectors described herein, the host cells described herein, the pharmaceutical compositions described herein, or the pharmaceutical combinations described herein in the preparation of a medicament for treating and / or preventing CD112R-mediated diseases or conditions, preferably said diseases or conditions being CD112R-related cancers, more preferably said cancers being selected from melanoma, renal cell carcinoma, 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 one aspect, the present invention provides antibodies or antigen-binding fragments thereof described herein, polynucleotide molecules described herein, expression vectors described herein, host cells described herein, pharmaceutical compositions described herein, or combinations of pharmaceuticals described herein, for the treatment and / or prevention of CD112R-mediated diseases or conditions, preferably said diseases or conditions being cancer, more preferably said cancers being selected from melanoma, renal cancer, prostate cancer, breast cancer, colon cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, uterine cancer, ovarian cancer, and rectal cancer.

[0032] In a twelfth aspect, the present invention also provides a kit comprising the anti-CD112R antibody of the present invention or an antigen-binding fragment thereof, the polynucleotide molecule of the present invention, the expression vector of the present invention, the host cell of the present invention, the pharmaceutical composition of the present invention, or a combination of pharmaceuticals of the present invention, or a pharmaceutical composition, and instructions for use. The kit may also comprise a suitable container. In some embodiments, the kit further comprises a device for administration. The kit generally includes a label indicating the intended use and / or method of use of the kit contents. The term "label" includes any written or recorded material provided on or with the kit or otherwise accompanied by the kit.

[0033] On the other hand, the present invention provides a method for detecting the presence of CD112R in a sample using the antibody or antigen-binding fragment thereof described in the present invention or a detection composition containing the antibody or antigen-binding fragment thereof. Invention Details Before describing the invention in detail, it should be understood that the invention is not limited to the specific methods and experimental conditions described herein, as these methods and conditions can be modified. Furthermore, the terminology used herein is for illustrative purposes only and is not intended to be restrictive.

[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 the purposes of this invention, the following terms are defined below.

[0035] The term “about” when used in conjunction with a numeric value means to cover a range of numeric values ​​that have a lower limit of 10% less than the specified numeric value and an upper limit of 10% greater than the specified numeric value.

[0036] When the term “and / or” is used to connect two or more options, it should be understood to mean any one of the options or any two or more of the options.

[0037] As used herein, the terms “comprising” or “including” mean to include the stated elements, integers, or steps, but do not exclude any other elements, integers, or steps. In this document, when the terms “comprising” or “including” are used, unless otherwise specified, they also cover situations consisting of the mentioned elements, integers, or steps. For example, when referring to an antibody variable region “comprising” a specific sequence, it is also intended to cover the antibody variable region consisting of that specific sequence.

[0038] The terms “CD112R,” “PVR-associated immunoglobulin domain,” “CD112 receptor,” “poliovirus receptor-associated immunoglobulin domain,” “Nectin2 receptor,” “C7orfl5,” and “transmembrane protein PVRIG” are used interchangeably and include variants, subtypes, species homologs, or other species’ CD112R and analogs having at least one common epitope of CD112R, unless otherwise stated. This term includes untreated full-length CD112R and any form of CD112R produced by cellular processing. The term covers “full-length” unprocessed CD112R and any form of CD112R or any fragment thereof produced by intracellular processing, such as splice variants or allelic variants. The variants or homologs maintain, for example, at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% of the activity of CD112R. The variant or homologue has at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% amino acid sequence identity with the naturally occurring CD112R protein in its complete or partial sequence (e.g., 50, 100, 150, or 200 consecutive amino acid segments).

[0039] The term "antibody" is used in the broadest sense herein and encompasses a variety of antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, provided they exhibit the desired antigen-binding activity. A complete antibody will typically contain at least two full-length heavy chains and two full-length light chains, but in some cases may include fewer chains; for example, naturally occurring antibodies in camels may contain only heavy chains.

[0040] The term "antibody fragment" refers to a molecule distinct from the intact antibody, which contains a portion of the intact antibody and is capable of binding to the antigen bound by the intact antibody. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2; biantibodies; 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 a domain of the antibody heavy or light chain involved in antibody-antigen binding. The variable domains of the heavy and light chains of natural antibodies typically have similar structures, with each domain containing four conserved framework regions (FRs) and three complementarity-determining regions (CDRs) (see, for example, Kindt et al., Kuby Immunology, 6th ed., WH Freeman and Co., p. 91 (2007)). A single VH or VL domain is sufficient to provide antigen-binding specificity.

[0042] The complementarity-determining region (CDR) or CDR is a region within the variable domain of an antibody that is highly variable in sequence and forms a structurally defined loop ("hypervariant loop") and / or contains antigen contact residues ("antigen contact sites"). The CDR is primarily responsible for binding to antigen epitopes. CDRs within the variable domain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially starting from the N-terminus. In a given variable region amino acid sequence, the precise amino acid sequence boundaries of each CDR can be determined using any of a number of known antibody CDR assignment systems or combinations thereof, including, for example: Chothia (Chothia et al. (1989) Nature 342: 877-883, Al-Lazikani et al., “Standard conformations for the canonical structures of immunoglobulins”, Journal of Molecular Biology, 273, 927-948 (1997)) based on antibody sequence variability; Kabat (Kabat et al., Sequences of Proteins of Immunological Interest, 4th edition, US Department of Health and Human Services, National Institutes of Health (1987)) based on antibody sequence variability; AbM (University of Bath); Contact (University College London); and the International ImMunoGeneTics database (IMGT). (http: / / imgt.cines.fr / ), and the North CDR definition based on affinity propagation clustering using a large number of crystal structures.

[0043] Unless otherwise stated, in this invention, the term "CDR" or "CDR sequence" covers a CDR sequence determined in any of the above-described manner.

[0044] The CDR can also be determined based on having the same AbM numbering position as a reference CDR sequence (e.g., any of the CDRs in the examples of this invention). In one embodiment, the CDR of the antibody of this invention is located according to the AbM numbering scheme.

[0045] Unless otherwise stated, in this invention, when referring to the position of residues in the antibody variable region and CDR (including heavy chain variable region residues), it means the numbering position according to the AbM numbering system.

[0046] "Humanized antibody" refers to a chimeric antibody comprising amino acid residues from a non-human CDR and amino acid residues from a human FR. In some embodiments, all or substantially all of the CDRs (e.g., CDRs) in the humanized antibody correspond to those in the non-human antibody, and all or substantially all of the FRs correspond to those in the human antibody. The humanized antibody may optionally contain at least a portion of an antibody constant region derived from a human antibody. The "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 "binding" or "specific binding" mean that the binding is selective for the antigen and can be distinguished from unwanted or nonspecific interactions. The ability of an antigen-binding site to bind to a specific antigen can be determined by methods such as enzyme-linked immunosorbent assay (ELISA).

[0048] The term "half-maximum effective concentration (EC50)" 50 "" refers to the concentration of a drug, antibody, or toxicant that induces a 50% response between baseline and maximum after a specific exposure time.

[0049] The term "therapeutic agent" as used herein encompasses any substance effective in preventing or treating tumors, such as cancer, including chemotherapeutic agents, cytokines, angiogenesis inhibitors, cytotoxic agents, other antibodies, small molecule drugs, or immunomodulators (such as immunosuppressants).

[0050] The term "treatment" refers to slowing, interrupting, blocking, alleviating, stopping, reducing, or reversing the progression or severity of existing symptoms, conditions, ailments, or diseases. Desired 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 mitigating the disease state, and alleviating or improving prognosis. In some embodiments, the antibodies of this invention are used to delay disease development or to slow disease progression.

[0051] The term "prevention" includes the suppression of the occurrence or development of a disease or condition, or symptoms of a particular disease or condition. In some implementations, subjects with a family history of cancer are candidates for preventative programs. Generally, in the context of cancer, the term "prevention" refers to the administration of a drug prior to the onset of signs or symptoms of cancer, particularly in subjects at risk of cancer.

[0052] The term "effective amount" refers to the amount or dose of the antibody, conjugate, or composition of the present invention, which, when administered to a patient in a single or multiple doses, produces the intended effect in a patient requiring treatment or prevention. The effective amount can be readily determined by a physician skilled in the art by considering a variety of factors, such as: the species of the mammal; weight, age, and general health condition; the specific disease involved; the degree or severity of the disease; the individual patient's response; the specific antibody administered; the administration modality; the bioavailability characteristics of the administered formulation; the chosen dosing regimen; and the use of any concomitant therapies.

[0053] The term "therapeutic effective amount" refers to the amount that, at the required dose and for the required duration, effectively achieves the desired therapeutic outcome. Therapeutic effective amounts of antibodies or antibody fragments, or their conjugates or compositions, can vary depending on various factors such as disease state, individual age, sex, weight, and the ability of the antibody or antibody moiety to elicit the desired response in the individual. A therapeutic effective amount is also a amount in which any toxic or harmful effects of the antibody or antibody fragment, or its conjugates or compositions, are less than the beneficial therapeutic effect. Relative to untreated subjects, a "therapeutic effective amount" preferably inhibits measurable parameters (e.g., tumor growth rate, tumor volume, etc.) by at least about 20%, more preferably at least about 40%, even more preferably at least about 50%, 60%, or 70%, and still more preferably at least about 80% or 90%. The ability of a compound to inhibit measurable parameters (e.g., cancer) can be evaluated in animal model systems that predict efficacy in human tumors.

[0054] The term "preventive effective dose" refers to the amount of medication administered at the required dose for the required duration to effectively achieve the desired preventive outcome. Typically, because the prophylactic dose is administered to the subject before or at an early stage of the disease, the preventive effective dose will be less than the therapeutic effective dose.

[0055] The term "pharmaceutical composition" refers to a composition which is present in a form that allows the biological activity of the active ingredient contained therein to be effective, and which does not contain any additional ingredients that would have unacceptable toxicity to a subject administering the composition.

[0056] II. The Composition of the Invention In some embodiments, the present invention provides compositions comprising any anti-CD112R antibody described herein and its antigen-binding fragment, preferably pharmaceutical compositions. In one embodiment, the composition further comprises pharmaceutical excipients, such as pharmaceutical carriers, pharmaceutical excipients, including buffers, known in the art. In one embodiment, the composition (e.g., a pharmaceutical composition) comprises the anti-CD112R antibody of the present invention and its antigen-binding fragment, and a combination of one or more other therapeutic agents.

[0057] As used in this article, “pharmaceutical carrier” includes any and all physiologically compatible solvents, dispersion media, isotonic agents, and absorption delay agents.

[0058] For information on the use and applications of pharmaceutical excipients, see also “Handbook of Pharmaceutical Excipients”, 8th edition, RCRowe, PJSeskey and SC Owen, Pharmaceutical Press, London, Chicago.

[0059] The compositions of the present invention can be in a variety of forms. These forms include, for example, liquid, semi-solid, and solid dosage forms, such as liquid solutions (e.g., injectable and infusionable solutions), powders or suspensions, liposomes, and suppositories. Preferred forms depend on the intended administration method and therapeutic use.

[0060] The compositions of the present invention can be administered by known methods, such as orally, intravenously, intraperitoneally, intracerebral (internal parenchyma), intraventricularly, intramuscularly, intraocularly, intraarterially, intraportally, or intralesionally; via a continuous release system or via an implanted device. In some embodiments, the compositions can be administered by bolus injection, continuous infusion, or via an implanted device.

[0061] The subject may be a mammal, such as a primate, preferably a higher primate, such as a human (e.g., an individual suffering from or at risk of suffering from the diseases described herein). In one embodiment, the subject suffers from or is at risk of suffering from the diseases described herein (e.g., cancer). In some embodiments, the subject has received or has received other treatments, such as chemotherapy and / or radiation therapy. In some embodiments, the subject has previously received or is currently receiving immunotherapy.

[0062] A drug comprising the antibody described herein can be prepared by mixing the anti-CD112R antibody of the present invention, having the desired purity, and its antigen-binding fragment with one or more optional pharmaceutical excipients, preferably in the form of a lyophilized formulation or an aqueous solution.

[0063] The pharmaceutical compositions or formulations of the present invention may also comprise more than one active ingredient, said active ingredient being required for a specific indication to be treated, preferably those active ingredients having complementary activities that do not adversely affect each other. For example, it is desirable to also 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), etc. The active ingredients are suitably combined in amounts effective for the intended use.

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

[0065] To recombinantly generate the anti-CD112R antibody of the present invention, the nucleic acid encoding the anti-CD112R antibody of the present invention is first isolated, and said nucleic acid is inserted into a vector for further cloning and / or expression in host cells. Such nucleic acids are easily isolated and sequenced using conventional procedures, for example, by using oligonucleotide probes capable of specifically binding to the nucleic acid encoding the anti-CD112R antibody of the present invention.

[0066] The anti-CD112R antibody of the present invention, prepared as described herein, can be purified using 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 specific protein also depend on factors such as net charge, hydrophobicity, and hydrophilicity, which are obvious to those skilled in the art.

[0067] Example The following embodiments further illustrate the present invention; however, it should be understood that the embodiments are described in an illustrative rather than limiting manner, and various modifications can be made by those skilled in the art. The present disclosure is further described in detail below with reference to specific embodiments, but these embodiments are not intended to limit the scope of the invention. Experimental methods in the embodiments of this disclosure that do not specify specific conditions are generally under conventional conditions or according to the conditions recommended by the raw material or product manufacturer; reagents whose source is not specified are generally commercially available conventional reagents.

[0068] Unless otherwise expressly indicated, the present invention will be practiced using conventional chemical, biochemical, organic chemical, molecular biological, microbiological, recombinant DNA technology, genetic, immunological and cell biological methods within the art.

[0069] Example 1: Raw material preparation and identification 1.1 Preparation and identification of CD112R control antibody Preparation of CD112R control antibody: This application uses the anti-CD112R antibody CHA.7.518 (hereinafter referred to as Tab-1) as a positive control antibody. Based on the sequence disclosed in WO / 2016 / 134333, the gene was synthesized by GenScript Biotech, and an expression plasmid was constructed. The specific VH and VL sequences of Tab-1 are shown in SEQ ID NO: 657 and 658. After transient transfection of Expi293F cells and culturing for 6 days, the supernatant was collected, and antibody affinity purification was performed using Protein A Magnetic Beads (GenScript Biotech). 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. Elution buffer (0.1 M citrate buffer, pH 3.0) was added to Protein A Magnetic Beads for elution. The eluent was collected, and 1 / 10 volume of neutralizing buffer (0.1 M Tris, pH 9.0) was added to adjust the pH to neutral. After elution, Protein A Magnetic Beads were equilibrated with binding buffer for 10 column volumes. The eluted and neutralized antibody was transferred to a dialysis bag and dialyzed against Dialysis buffer (PBS, pH 7.4) for 2 hours at room temperature. The Dialysis buffer was then replaced, and the antibody was dialyzed against the buffer 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] CD112R control antibody identification: The activity of the prepared positive control antibody Tab-1 was detected using the purchased CD112R-His antigen protein (Acro Biosysterm, PVG-H52H4). The specific method is as follows: CD112R-His (0.5 μg / mL, 100 μL / well) was coated on a 96-well ELISA plate at 37°C for 1 hour; 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 diluted serially with PBS was added and incubated at room temperature for 1 hour; after washing, the secondary antibody (Peroxidase-Affini Pure Goat Anti-Mouse IgG, Fcγ Fragment Specific) diluted 1:6000 in PBS was added and incubated at 37°C for 0.5 hours; after washing three times, TMB was added for color development for 5-20 min; after stopping the color development, the data was read by OD450 of the microplate reader. The results showed that the expressed control antibody Tab-1 could bind to the CD112R protein, and the OD450 reading decreased with decreasing antibody concentration, indicating that the control antibody had normal anti-CD112R activity.

[0071] Example 2: Construction and identification of cell lines overexpressing human and monkey CD112R Construction of CHOK1 cell lines overexpressing human and monkey CD112R (hereinafter referred to as huCD112R-CHO K1; cynoCD112R-CHO K1): The coding nucleic acid sequences of full-length human (Uniprot ID: Q6DKI7) and monkey CD112R (Uniprot ID: A0A2K5WVV8) were constructed into a lentiviral vector. Then, the lentiviral plasmid was transfected into HEK293T cells for viral packaging. After 4 days of culture, the cell culture supernatant was collected. The harvested lentiviral supernatant was used to transfect CHO-K1 cells, and Puromycin was used as the selection pressure. After 3 days of selection, antigen expression in the cell pool was screened by flow cytometry. After obtaining a positive cell pool, single-cell clones were selected from the positive cell pool using limiting dilution or flow cytometry sorting. After single-clone selection, the cells were cultured for another week for antigen expression identification.

[0072] Flow cytometry identification of antigen expression in cell lines: Cells in the logarithmic growth phase were digested and plated into 96-well plates. After washing with FACS buffer (1×PBS buffer containing 2% FBS), the primary antibody Mouse anti-human PVRIG antibody (GenScript Probio, Cat. No.: C523UGG270-2D) serially diluted with PBS was added, and the cells were incubated at 4°C for 30 min. After washing, the prepared fluorescent secondary antibody PE Goat anti-mouse IgG antibody (BioLegend, Cat. No. 405307) was added, and the cells were incubated at 4°C for 30 min. Finally, the cells were detected by flow cytometry (Beckman, CytoFLEXAOO-1-1102). The results showed that huCD112R-CHO K1 and cynoCD112R-CHO K1 cell lines with high expression of human and monkey CD112R were obtained.

[0073] Example 3: Animal Immunization and Construction of an Immune Bank 3.1 Immunization regimen Mice of different species (Balb / c, SJL, A / J) were immunized using CD112R-His or CD112R-mFc protein antigens (Acro Biosysterm, PVG-H5259); CD112R expression plasmid-DNA antigens; and multiple immunogens of CD112R overexpressing CHO cells, either alone or alternately. Mice were immunized subcutaneously / intraperitoneally or via gene gun injection, depending on the selected antigen, every two weeks for a total of 3-5 immunizations. One week after the last immunization, blood was collected from the mice for immunotiter testing. Finally, a booster immunization was administered using the same antigens.

[0074] Table 1. Summary of Immune Methods Used in This Example

[0075] 3.2 Detection of serum antibody titers in mice after immunization Dilute the antigen to 0.5 µg / mL with coating buffer (PBS, pH 7.4), mix well, and add 100 µL / well to the ELISA strips. Incubate overnight at 4°C for 16 h. Discard the coating buffer, wash the plate once, and blot dry. Add 150 µL of blocking buffer (3% BSA solution) to each well and incubate at 37°C for 1 h. Remove the ELISA plate and discard the blocking buffer. Serially dilute mouse serum and add 100 µL / well to the plate. Incubate at 37°C for 1 h. Remove the ELISA plate, discard the liquid, and wash the plate three times. Add 100 µL of diluted enzyme-labeled secondary antibody Peroxidase-Affini Pure Goat Anti-Mouse IgG, FcγFragment Specific (min X Hu, Bov, Hrs Sr Prot) to each well and incubate at 37°C for 0.5 h. Remove the ELISA plate, discard the liquid in the plate, wash the plate three times, blot dry the plate, add 100 μl of chromogenic solution, and incubate at 25°C for 15 minutes. Stop the reaction by adding 50 μL of 1M HCl, and read the OD450 value on the ELISA reader. Select mice with an immunotiter greater than 512000 (dilution factor) for hybridoma fusion.

[0076] 3.3 Hybridoma cell fusion Prepare a suspension of myeloma cells (SP2 / 0) and calculate the total number of SP2 / 0 cells using a hemocytometer. Prepare a suspension of spleen cells and count the total number of cells using a hemocytometer. Mix myeloma cells and spleen cells at a 1:2 ratio and perform cell electrofusion. After cell fusion, mix the fused cells in HAT selective medium to prepare a cell suspension, and then use a multichannel pipette to seed the cells into 96-well cell culture plates. Place the fused 96-well cell culture plates in a 5.5% CO2 incubator and incubate at 37°C. After hybridoma cell culture, collect the supernatant for maternal clone screening. Screen the cell culture supernatant for antigen-binding ability at both the protein and cellular levels to obtain maternal clone cell lines capable of binding antigens.

[0077] 3.4 Hybridoma subcloning screening Select the mother clone cell lines obtained through step 3.3, and gently pipette the cells from the wells to be subcloned to mix them thoroughly. Add 20 µl of the cell suspension to 20 µl of trypan blue solution and mix well. Count the cells using a hemocytometer. Using the limiting dilution method, plate the cells in 96-well cell culture plates with 1×HT instead of feeder culture medium, label the wells, and incubate in a CO2 incubator. Incubate the subcloned 96-well plates at 37°C with 5.5% CO2. After 7 days of culture, collect the supernatant for single-clone selection.

[0078] After subcloning, the obtained antibodies were selected for sequencing. The CDR sequences of the antibodies are shown in Tables 2 and 3 below. The CDR sequence was determined using the AbM definition method.

[0079] Table 2. Heavy chain CDR sequence of anti-CD112R antibody

[0080] Table 3. Light chain CDR sequence of anti-CD112R antibody

[0081] Example 4: Antibody Construction, Expression and Purification 4.1 Plasmid Construction The VH coding sequence from the Fab sequence of the selected monoclonal antibody was ligated to the coding sequence of the heavy chain constant region (SEQ ID NO: 659) of human IgG1 to obtain the heavy chain coding sequence of the human-mouse chimeric antibody. The VL coding sequence from the Fab sequence was ligated to the coding sequence of the Kappa type (SEQ ID NO: 660) of the light chain constant region (CL) of human to obtain the light chain coding sequence of the human-mouse chimeric antibody. The coding sequences of the antibody heavy and light chains were inserted separately into eukaryotic expression vector plasmids, transformed into *E. coli* DH5α (Shanghai Sangon Biotech), and cultured overnight at 37°C. Endotoxin-free plasmid extraction was performed using an endotoxin-free plasmid extraction kit (Qiagen) to obtain endotoxin-free antibody plasmids for eukaryotic expression.

[0082] 4.2 Antibody Expression and Purification The obtained full-length antibody sequence was expressed using the Expi293F transient expression system (Thermo Fisher, A14635) or the ExpiCHO transient expression system (Thermo Fisher, A29133). For specific methods, please refer to the corresponding kit operation guide from the supplier. The antibody isolation and purification were performed according to the antibody purification steps in Example 1.

[0083] Example 5: Detection of the physicochemical properties of antibodies 5.1 Antibody SDS-PAGE Identification Preparation of non-reducing solution: Add 3 µg of each obtained antibody to 2×SDS loading buffer and 40 mM iodoacetamide respectively, heat in a dry bath at 75℃ for 10 min, cool to room temperature, centrifuge at 12000 rpm for 5 min and collect the supernatant.

[0084] Preparation of reducing solution: 3 µg of each obtained antibody was added to 2×SDS loading buffer and 5 mM DTT, respectively. The mixture was heated in a 99°C dry bath for 5 min, cooled to room temperature, and then briefly centrifuged. The supernatant was added to a Bis-tris 4-15% gradient gel (GenScript Biotech) for gel electrophoresis, and the protein bands were visualized by Coomassie Brilliant Blue staining.

[0085] The Odyssey 9140 dual-color infrared laser imaging system was used to image protein gels with chromogenic protein bands (decolorized with decolorizing solution until the gel background was transparent), and the purity of reduced and non-reduced bands was calculated using the built-in software.

[0086] The experimental results showed that the bands of each antibody on the non-reducing gel were around 150 kD, while the bands on the reducing gel were around 55 kD and 25 kD, respectively, which were in line with the expected sizes.

[0087] Example 6: Detection of Antibody Antigen Binding Activity In this embodiment, the binding of the expressed antibody to the human CD112R antigen protein huCD112R-His was detected using the ELISA method, and the binding of the expressed antibody to the human CD112R overexpressing cell huCD112R-CHOK1 was detected using the FACS method.

[0088] 6.1 ELISA-based detection of antibody binding affinity to antigen protein huCD112R-His 96-well ELISA plates were coated with 0.5 μg / mL human CD112R antigen protein huCD112R-His (Acro Biosysterm, PVG-H52H4) (30 μL / well) and incubated overnight at 4°C. The next day, the plates were washed three times with PBST, blocked with 5% skim milk for 2 h, washed three times with PBST, and then serially diluted (1 μg / mL, 3-fold serial dilution, 9 concentration points) of each antibody and positive control antibody Tab-1 were added and incubated for 1 h. After washing three times with PBST, secondary antibody Goat-anti-human Fc-HRP (Abcam, ab97225) was added and incubated for 30 min. After incubation, the plates were washed six times with PBST, dried, and then TMB was added for color development at 25°C for 15 min. The reaction was terminated by adding 1M HCl, and the absorbance was read at OD450 using a microplate reader.

[0089] The results (Table 4) show that the antibody and antigen protein huCD112R obtained in this application have good binding ability, and some antibodies have better binding ability to the antigen protein than the positive control antibody Tab-1.

[0090] Table 4: EC50 values ​​of antibodies and human antigen proteins

[0091] 6.2 Detection of antibody binding ability to huCD112R-CHO K1 cells based on FACS In this embodiment, the antibody binding activity was evaluated using human CD112R overexpressing cells huCD112R-CHO K1.

[0092] The specific method is as follows: huCD112R-CHO K1 cells in the logarithmic growth phase were prepared into a single-cell suspension, and the density was adjusted to 2 × 10⁻⁶ cells / cells. 6 Cells / mL were added at a rate of 50 μL to each well of a 96-well round-bottom plate. The plates were centrifuged at 300 g at 4 °C and the supernatant was removed. The detection antibody and positive control antibody (Tab-1) were added to the corresponding wells, mixed, and incubated at 4 °C for 40 min. After washing the incubated cell mixture three times, 100 μL of diluted secondary antibody Goat F(ab')2 Anti-Human IgG-Fc (Abcam, ab98596) was added, and the mixture was incubated at 4 °C in the dark for 30 min. After washing three times, the cells were analyzed by flow cytometry, and the fluorescence intensity (MFI) was recorded.

[0093] Conclusion: On huCD112R-CHO K1 cells, the antibody of the present invention has the ability to bind to CD112R over-antigen-expressing cells.

[0094] Example 7: Detection of antibody species and homologous cross-activity (ELISA method) This embodiment tested the cross-reactivity of the various antibodies obtained in this application in human and monkey species. The binding ability of the antibody prepared in Example 4 with monkey antigen protein (Uniprot ID: A0A2K5WVV8) and the cynoCD112R-CHO K1 cell line expressing monkey CD112R was determined. The specific operation method is as described in Example 6.1.

[0095] The results (Table 5) show that all the antibodies obtained in this application can bind to monkey antigen proteins and cell lines overexpressing monkey proteins, demonstrating good human-monkey cross-activity. Therefore, the antibodies obtained in this application have wide applications in monkey-based experiments and tests.

[0096] The antibodies of this invention all exhibit good cross-species activity between humans and monkeys.

[0097] Table 5: EC50 values ​​of antibody and monkey antigen protein

[0098] Example 8: Antibody affinity kinetics (Biacore) analysis In this embodiment, the affinity of the antibody obtained in this application and the positive control antibody Tab-1 for the antigen protein huCD112R-His was detected using a Biacore device. The anti-CD112R antibody sample was diluted to 10 μg / mL using running buffer HBS-EP+ (10 mM HEPES, 150 mM NaCl, 3 mM EDTA and 0.05% P2O, pH 7.4) (BR100826, GE). The human CD112R antigen protein huCD112R-His (Acro Biosysterm, PVG-H52H4) was serially diluted 2-fold with HBS-EP+ buffer to between 0.03125 nM and 2 nM. The anti-CD112R antibody was affinity-captured using a Protein A biosensor chip (BR100354, GE) with a capture time of 60 s and a flow rate of 30 μL / min. Human CD112R samples diluted to different concentrations were injected sequentially from zero to the highest concentration, with a binding time of 120 s, a dissociation time of 360 s, and a flow rate of 30 μL / min. Binding and dissociation curves were obtained by real-time monitoring of the reaction signals using a Biacore X100 instrument. After dissociation in each experimental cycle, the Protein A biosensor chip was washed and regenerated with 10 mM Glycine-HCl (pH 1.5) (29127558, GE), with a regeneration time of 30 s and a flow rate of 30 μL / min. Parameter fitting: The experiment was run in single-cycle mode, with analysis time as the x-axis and response value as the y-axis. After dual-reference subtraction, the obtained data were fitted using BIAcore X100 (GE) analysis software. The fitting model used was a 1:1 Langmuir binding model to determine affinity indices such as binding and dissociation constants. The results showed that the affinity of the antibody of this invention was superior to or comparable to that of Tab-1.

[0099] Table 6: KD values ​​of antibody binding to antigen protein huCD112R-His

[0100] Example 9: Detection of antibody-mediated blockade of the CD112R-CD112 binding signaling pathway (reporter gene assay) The reporter gene assay consists of two genetically engineered cell lines: the GS-J2C / CD112R effector cell line, expressing human CD112R and an NFAT-RE-driven luciferase reporter gene; and the GS-C2 / CD112 target cell line, expressing human CD112 in an engineered cell surface protein, designed to activate homologous TCRs in an antigen-independent manner. When the GS-J2C / CD112R effector cell line and the GS-C2 / CD112 target cell line are co-cultured, the CD112R / CD112 interaction inhibits TCR signaling pathway activation, thereby suppressing NFAT-driven luciferase expression, resulting in a relatively low fluorescence signal. The addition of a CD112R therapeutic antibody blocks the CD112R / CD112 interaction, thereby restoring the TCR signaling pathway and increasing the fluorescence signal value.

[0101] First, GS-2 / CD112 target cells were constructed. 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 to package a CD112-Blasticidin recombinant lentivirus. This recombinant lentivirus was used to infect CHO-K1 / APC cells (named GS-C2), and a cell pool successfully infected with CD112 was obtained by selection using 10 μg / ml Blasticidin. GS-C2 / CD112 monoclonal cells were selected using a limiting dilution method.

[0102] GS-J2C / CD112R effector cells were constructed. The full-length human CD112R DNA fragment (XP_011514877.1) was inserted into a lentiviral expression vector containing Puromycin resistance. This vector was mixed with a helper plasmid and transfected into 293T cells to package a CD112-Puromycin recombinant lentivirus. This lentivirus was used to infect Jurkat-Luc Reporter cells (named GS-J2C), and cell pools successfully infected with CD112R were obtained by selection using 1 μg / ml Puromycin. GS-J2C / PVRIG monoclonal cells were selected using a limiting dilution method.

[0103] Centrifuge to collect target cells and resuspend them in their corresponding complete medium (10% FBS F-12K). Adjust the target cell density, seed them in experimental plates, and transfer the plates to a cell culture incubator (37℃ / 5% CO2) for approximately 16 hours. Centrifuge to collect effector cells, resuspend them in experimental buffer (1.25% FBS RPMI 1640), and adjust the cell density. Remove the experimental plates containing target cells from the cell culture incubator and remove the medium. Transfer the working solutions of the control and test samples, along with the effector cell suspension, sequentially to the experimental plates. Transfer the experimental plates to a cell culture incubator (37℃ / 5% CO2) for 6 hours. Remove the incubated experimental plates from the cell culture incubator, transfer the luciferase assay working solution to the corresponding wells of the experimental plates, and incubate at room temperature for 3-5 minutes. Use a Pherastar to read the chemiluminescence values ​​and record the data.

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

[0105] Table 7: Blocking effect of antibodies

[0106] Implementation 10: Antibody blocking of CD112R binding to CD112 enhances antigen-specific CD8 T cell activation (primary immune cell method) Detection of antigen-specific CD8 of the test antibody + T cell activation. PBMCs of a specific genotype (HLA-A*0201) were collected by centrifugation and resuspended in RPMI-1640 medium (Gibco) with 10% FBS (Gibco). A certain volume of pp65 (495–503) peptide (CEF20, Cytomegalovirus, CMV pp65 (495–503), GenScript) and cytokines (IL-2 Human and IL-7 Human, GenScript) were added to the PBMC cell suspension to induce the production of antigen-specific CD8. + T cells. After 11 days of culture, PBMCs were collected by centrifugation and processed using human CD8+. + T-cell isolation kit (17953, STEMCELL) yields CD8 + T cells. 5 × 10 4 Target cells (Ksaumi-1 and Colo-205) were added to 96-well plates, followed by pp65 (495–503) peptide working solution to each well. The plates were then incubated in a cell culture incubator for 1 hour. 25 × 10⁻⁶ cells were added to each well. 4 CD8 +T cells were added to the corresponding 96-well plates. Then, the test antibody was added to the corresponding wells according to the detection concentration. The 96-well plates were incubated in a cell culture incubator (37℃ / 5% CO2) for 18–22 hours. After incubation, the 96-well plates were removed, centrifuged at 2000 rpm for 5 min, and the supernatant was transferred to new 96-well plates. Interferon-γ (IFN-γ) was detected according to the instructions of the cytokine kit (62HIFNGPEH, Cisbio).

[0107] Table 8

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

[0109] In addition to those described herein, various modifications of the invention are also intended to fall within the scope of the appended claims, based on the foregoing description. All references cited in this application (including all patents, patent applications, journal articles, books, and any other disclosures) are incorporated herein by reference in their entirety.

[0110] sequence list

Claims

1. An anti-CD112R antibody that specifically binds to CD112R, or an antigen-binding fragment thereof, comprising: (1) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 459 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 460; (2) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 430 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 431; (3) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 432 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 433; (4) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 434 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 435; (5) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 438 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 439; (6) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 441 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 442; (7) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 447 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 448; (8) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 449 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 450; (9) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 451 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 452; (10) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 453 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 454; (11) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 457 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 458; (12) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 461 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 462; (13) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 469 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO: 470; or (14) The three heavy chain CDRs (HCDR1, HCDR2, HCDR3) contained in the heavy chain variable region as shown in SEQ ID NO: 485 and the three light chain CDRs (LCDR1, LCDR2, LCDR3) contained in the light chain variable region as shown in SEQ ID NO:

486.

2. An anti-CD112R antibody that specifically binds to CD112R or its antigen-binding fragment, comprising: (1) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 9, 77 and 168, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 248, 313 and 363, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (2) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 1, 64 and 162, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 239, 307 and 357, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (3) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 2, 65 and 162, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 239, 308 and 358, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (4) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 3, 66 and 163, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 240, 309 and 359, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (5) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 5, 68 and 165, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 241, 311 and 361, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (6) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 6, 69 and 166, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 243, 313 and 363, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (7) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 3, 72 and 163, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 241, 311 and 359, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (8) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 9, 73 and 168, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 245, 313 and 363, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (9) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 3, 74 and 163, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 246, 311 and 359, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (10) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 10, 75 and 169, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 247, 315 and 366, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (11) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 9, 76 and 168, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 243, 313 and 363, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (12) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 8, 77 and 168, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 243, 313 and 365, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; (13) HCDR1, HCDR2, and HCDR3 respectively, as shown in SEQ ID NO: 12, 81, and 172, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; and LCDR1, LCDR2, and LCDR3 respectively, as shown in SEQ ID NO: 250, 315, and 369, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions, or insertions relative to said sequences; or (14) HCDR1, HCDR2 and HCDR3 respectively, as shown in SEQ ID NO: 2, 89 and 178, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences; and LCDR1, LCDR2 and LCDR3 respectively, as shown in SEQ ID NO: 241, 311 and 377, or sequences containing one or more amino acid substitutions (e.g., conservative substitutions), deletions or insertions relative to said sequences.

3. The anti-CD112R antibody of claim 1 or 2, or its antigen-binding fragment, comprising: (1) The heavy chain variable region as shown in SEQ ID NO: 459 and the light chain variable region as shown in SEQ ID NO: 460; (2) The heavy chain variable region as shown in SEQ ID NO: 430 and the light chain variable region as shown in SEQ ID NO: 431; (3) The heavy chain variable region as shown in SEQ ID NO: 432 and the light chain variable region as shown in SEQ ID NO: 433; (4) The heavy chain variable region as shown in SEQ ID NO: 434 and the light chain variable region as shown in SEQ ID NO: 435; (5) The heavy chain variable region as shown in SEQ ID NO: 438 and the light chain variable region as shown in SEQ ID NO: 439; (6) The heavy chain variable region as shown in SEQ ID NO: 441 and the light chain variable region as shown in SEQ ID NO: 442; (7) The heavy chain variable region as shown in SEQ ID NO: 447 and the light chain variable region as shown in SEQ ID NO: 448; (8) The heavy chain variable region as shown in SEQ ID NO: 449 and the light chain variable region as shown in SEQ ID NO: 450; (9) The heavy chain variable region as shown in SEQ ID NO: 451 and the light chain variable region as shown in SEQ ID NO: 452; (10) The heavy chain variable region as shown in SEQ ID NO: 453 and the light chain variable region as shown in SEQ ID NO: 454; (11) The heavy chain variable region as shown in SEQ ID NO: 457 and the light chain variable region as shown in SEQ ID NO: 458; (12) The heavy chain variable region as shown in SEQ ID NO: 461 and the light chain variable region as shown in SEQ ID NO: 462; (13) The heavy chain variable region as shown in SEQ ID NO: 469 and the light chain variable region as shown in SEQ ID NO: 470; or (14) The heavy chain variable region as shown in SEQ ID NO: 485 and the light chain variable region as shown in SEQ ID NO:

486.

4. The anti-CD112R antibody of any one of claims 1-3 or the antigen-binding fragment thereof, wherein the antigen-binding fragment is selected from Fab, Fab'-SH, Fv (e.g., scFv) or (Fab')2 fragment.

5. The anti-CD112R antibody or antigen-binding fragment thereof of any one of claims 1-4, comprising a constant region sequence, wherein at least a portion of the constant region sequence is a human common constant region sequence.

6. The anti-CD112R antibody or its antigen-binding fragment according to any one of claims 1-5, wherein the heavy chain constant region of the antibody comprises the amino acid sequence shown in SEQ ID NO: 659, and the light chain constant region comprises the amino acid sequence shown in SEQ ID NO:

660.

7. An isolated polynucleotide molecule encoding an anti-CD112R antibody or an antigen-binding fragment thereof as described in any one of claims 1-6.

8. An expression vector comprising the nucleotide molecule of claim 7, preferably, the expression vector being a eukaryotic expression vector.

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

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

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

12. Use of the anti-CD112R antibody or antigen-binding fragment thereof as described in any one of claims 1-6, or the polynucleotide molecule as described in claim 7, or the expression vector as described in claim 8, or the host cell as described in claim 9, or the pharmaceutical composition as described in claim 10 in the preparation of a medicament for treating and / or preventing CD112R-mediated diseases or conditions.

13. The method of claim 11 or the use of claim 12, wherein the CD112R-mediated disease or condition is a CD112R-related 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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