Antibody molecules to TIM-3 and uses thereof
Antibody molecules that specifically bind to TIM-3 are disclosed. The anti-TIM-3 antibody molecules can be used to treat, prevent and/or diagnose immune, cancerous, or infectious conditions and/or disorders.
1. A nucleic acid molecule comprising a nucleotide sequence selected from: a nucleotide sequence that encodes a heavy chain variable region (VH), a nucleotide sequence that encodes a light chain variable region (VL), or a nucleotide sequence that encodes both a VH and a VL of an antibody molecule that binds to human T-cell immunoglobulin domain and mucin domain 3 (TIM-3), wherein the antibody molecule comprises:
(a) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 9; a VHCDR2 amino acid sequence of SEQ ID NO: 10; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 12, a VLCDR2 amino acid sequence of SEQ ID NO: 13, and a VLCDR3 amino acid sequence of SEQ ID NO: 14;
(b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 3; a VHCDR2 amino acid sequence of SEQ ID NO: 4; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 6, a VLCDR2 amino acid sequence of SEQ ID NO: 7, and a VLCDR3 amino acid sequence of SEQ ID NO: 8;
(c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 9; a VHCDR2 amino acid sequence of SEQ ID NO: 25; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 12, a VLCDR2 amino acid sequence of SEQ ID NO: 13, and a VLCDR3 amino acid sequence of SEQ ID NO: 14;
(d) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 3; a VHCDR2 amino acid sequence of SEQ ID NO: 24; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 6, a VLCDR2 amino acid sequence of SEQ ID NO: 7, and a VLCDR3 amino acid sequence of SEQ ID NO: 8;
(e) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 9; a VHCDR2 amino acid sequence of SEQ ID NO: 31; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 12, a VLCDR2 amino acid sequence of SEQ ID NO: 13, and a VLCDR3 amino acid sequence of SEQ ID NO: 14; or
(f) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 3; a VHCDR2 amino acid sequence of SEQ ID NO: 30; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 6, a VLCDR2 amino acid sequence of SEQ ID NO: 7, and a VLCDR3 amino acid sequence of SEQ ID NO: 8.
2. The nucleic acid molecule of claim 1 , wherein the nucleotide sequences encoding the VH and VL of the antibody molecule are in the same nucleic acid molecule.
3. The nucleic acid molecule of claim 1 , wherein the nucleotide sequences encoding the VH and VL of the antibody molecule are in separate nucleic acid molecules.
4. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 9; a VHCDR2 amino acid sequence of SEQ ID NO: 10; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 12, a VLCDR2 amino acid sequence of SEQ ID NO: 13, and a VLCDR3 amino acid sequence of SEQ ID NO: 14.
5. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 3; a VHCDR2 amino acid sequence of SEQ ID NO: 4; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 6, a VLCDR2 amino acid sequence of SEQ ID NO: 7, and a VLCDR3 amino acid sequence of SEQ ID NO: 8.
6. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 9; a VHCDR2 amino acid sequence of SEQ ID NO: 25; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 12, a VLCDR2 amino acid sequence of SEQ ID NO: 13, and a VLCDR3 amino acid sequence of SEQ ID NO: 14.
7. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprising a VH comprising a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 3; a VHCDR2 amino acid sequence of SEQ ID NO: 24; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 6, a VLCDR2 amino acid sequence of SEQ ID NO: 7, and a VLCDR3 amino acid sequence of SEQ ID NO: 8.
8. The nucleic acid molecule of claim 1 wherein the antibody molecule comprising a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 9; a VHCDR2 amino acid sequence of SEQ ID NO: 31; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 12, a VLCDR2 amino acid sequence of SEQ ID NO: 13, and a VLCDR3 amino acid sequence of SEQ ID NO: 14.
9. The nucleic acid molecule of claim 1 , wherein the antibody molecule comprises a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO: 3; a VHCDR2 amino acid sequence of SEQ ID NO: 30; and a VHCDR3 amino acid sequence of SEQ ID NO: 5; and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO: 6, a VLCDR2 amino acid sequence of SEQ ID NO: 7, and a VLCDR3 amino acid sequence of SEQ ID NO: 8.
10. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes a VH comprising an amino acid sequence at least 85% identical to any of SEQ ID NOs: 1, 16, 26, 32, 36, 44, 48, 52, 60, 68, 72, 76, 80, 84, 92, or 100.
11. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes a VH comprising the amino acid sequence of SEQ ID NO: 1, 16, 26, 32, 36, 44, 48, 52, 60, 68, 72, 76, 80, 84, 92, or 100.
12. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes a VL comprising an amino acid sequence at least 85% identical to any of SEQ ID NOs: 2, 20, 40, 56, 64, 88, 96, or 104.
13. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes a VL comprising the amino acid sequence of SEQ ID NO: 2, 20, 40, 56, 64, 88, 96, or 104.
14. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence comprises a nucleotide sequence at least 85% identical to any of SEQ ID NOs: 11, 17, 29, 33, 37, 45, 49, 53, 61, 69, 73, 77, 81, 85, 93, 101, 115, or 120.
15. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 11, 17, 29, 33, 37, 45, 49, 53, 61, 69, 73, 77, 81, 85, 93, 101, 115, or 120.
16. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence comprises a nucleotide sequence at least 85% identical to any of SEQ ID NOs: 15, 21, 41, 57, 65, 89, 97, 105, 118, 123, 125, or 127.
17. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 15, 21, 41, 57, 65, 89, 97, 105, 118, 123, 125, or 127.
18. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes:
(a) a VH comprising the amino acid sequence of SEQ ID NO: 1 and a VL comprising the amino acid sequence of SEQ ID NO: 2;
(b) a VH comprising the amino acid sequence of SEQ ID NO: 16 and a VL comprising the amino acid sequence of SEQ ID NO: 20;
(c) a VH comprising the amino acid sequence of SEQ ID NO: 26 and a VL comprising the amino acid sequence of SEQ ID NO: 20;
(d) a VH comprising the amino acid sequence of SEQ ID NO: 32 and a VL comprising the amino acid sequence of SEQ ID NO: 20;
(e) a VH comprising the amino acid sequence of SEQ ID NO: 36 and a VL comprising the amino acid sequence of SEQ ID NO: 40;
(f) a VH comprising the amino acid sequence of SEQ ID NO: 44 and a VL comprising the amino acid sequence of SEQ ID NO: 40;
(g) a VH comprising the amino acid sequence of SEQ ID NO: 48 and a VL comprising the amino acid sequence of SEQ ID NO: 40;
(h) a VH comprising the amino acid sequence of SEQ ID NO: 36 and a VL comprising the amino acid sequence of SEQ ID NO: 20;
(i) a VH comprising the amino acid sequence of SEQ ID NO: 16 and a VL comprising the amino acid sequence of SEQ ID NO: 40;
(j) a VH comprising the amino acid sequence of SEQ ID NO: 52 and a VL comprising the amino acid sequence of SEQ ID NO: 56;
(k) a VH comprising the amino acid sequence of SEQ ID NO: 60 and a VL comprising the amino acid sequence of SEQ ID NO: 56;
(l) a VH comprising the amino acid sequence of SEQ ID NO: 52 and a VL comprising the amino acid sequence of SEQ ID NO: 64;
(m) a VH comprising the amino acid sequence of SEQ ID NO: 60 and a VL comprising the amino acid sequence of SEQ ID NO: 64;
(n) a VH comprising the amino acid sequence of SEQ ID NO: 68 and a VL comprising the amino acid sequence of SEQ ID NO: 64;
(o) a VH comprising the amino acid sequence of SEQ ID NO: 72 and a VL comprising the amino acid sequence of SEQ ID NO: 64;
(p) a VH comprising the amino acid sequence of SEQ ID NO: 76 and a VL comprising the amino acid sequence of SEQ ID NO: 56;
(q) a VH comprising the amino acid sequence of SEQ ID NO: 80 and a VL comprising the amino acid sequence of SEQ ID NO: 56;
(r) a VH comprising the amino acid sequence of SEQ ID NO: 68 and a VL comprising the amino acid sequence of SEQ ID NO: 56;
(s) a VH comprising the amino acid sequence of SEQ ID NO: 72 and a VL comprising the amino acid sequence of SEQ ID NO: 56;
(t) a VH comprising the amino acid sequence of SEQ ID NO: 76 and a VL comprising the amino acid sequence of SEQ ID NO: 64;
(u) a VH comprising the amino acid sequence of SEQ ID NO: 80 and a VL comprising the amino acid sequence of SEQ ID NO: 64;
(v) a VH comprising the amino acid sequence of SEQ ID NO: 84 and a VL comprising the amino acid sequence of SEQ ID NO: 88;
(w) a VH comprising the amino acid sequence of SEQ ID NO: 92 and a VL comprising the amino acid sequence of SEQ ID NO: 96; or
(x) a VH comprising the amino acid sequence of SEQ ID NO: 100 and a VL comprising the amino acid sequence of SEQ ID NO: 104.
19. The nucleic acid molecule of claim 1 , which comprises:
(a) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 11 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 15;
(b) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 17 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 21;
(c) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 27 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 21;
(d) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 33 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 21;
(e) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 37 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 41;
(f) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 45 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 41;
(g) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 49 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 41;
(h) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 115 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 118;
(i) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 120 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 123;
(j) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 53 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 57;
(k) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 61 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 57;
(l) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 53 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 65;
(m) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 61 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 65;
(n) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 69 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 125;
(o) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 73 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 125;
(p) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 77 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 127;
(q) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 81 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 127;
(r) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 69 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 127;
(s) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 73 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 127;
(t) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 77 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 125;
(u) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 81 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 125;
(v) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 85 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 89;
(w) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 93 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 97; or
(x) a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 101 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 105.
20. The nucleic acid molecule of claim 1 , which encodes a heavy chain comprising an amino acid sequence at least 85% identical to any of SEQ ID NOs: 18, 28, 34, 38, 46, 50, 54, 62, 70, 74, 78, 82, 86, 94, 102, 116, or 121.
21. The nucleic acid molecule of claim 1 , which encodes a heavy chain comprising the amino acid sequence of SEQ ID NO: 18, 28, 34, 38, 46, 50, 54, 62, 70, 74, 78, 82, 86, 94, 102, 116, or 121.
22. The nucleic acid molecule of claim 1 , which encodes a light chain comprising an amino acid sequence at least 85% identical to any of SEQ ID NOs: 22, 42, 58, 66, 90, 98, or 106.
23. The nucleic acid molecule of claim 1 , which encodes a light chain comprising the amino acid sequence of SEQ ID NO: 22, 42, 58, 66, 90, 98, or 106.
24. The nucleic acid molecule of claim 1 , which comprises a heavy chain nucleotide sequence at least 85% identical to any of SEQ ID NOs: 19, 29, 35, 39, 47, 51, 55, 63, 71, 75, 79, 83, 87, 95, 103, 117, or 122.
25. The nucleic acid molecule of claim 1 , which comprises a heavy chain nucleotide sequence of SEQ ID NO: 19, 29, 35, 39, 47, 51, 55, 63, 71, 75, 79, 83, 87, 95, 103, 117, or 1227.
26. The nucleic acid molecule of claim 1 , which comprises a light chain nucleotide sequence at least 85% identical to any of SEQ ID NOs: 23, 43, 59, 67, 91, 99, 107, 119, 124, 126, or 128.
27. The nucleic acid molecule of claim 1 , which comprises a light chain nucleotide sequence of SEQ ID NO: 23, 43, 59, 67, 91, 99, 107, 119, 124, 126, or 128.
28. The nucleic acid molecule of claim 1 , which encodes:
(a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 18 and a light chain comprising the amino acid sequence of SEQ ID NO: 22;
(b) a heavy chain comprising the amino acid sequence of SEQ ID NO: 28 and a light chain comprising the amino acid sequence of SEQ ID NO: 22;
(c) a heavy chain comprising the amino acid sequence of SEQ ID NO: 34 and a light chain comprising the amino acid sequence of SEQ ID NO: 22;
(d) a heavy chain comprising the amino acid sequence of SEQ ID NO: 38 and a light chain comprising the amino acid sequence of SEQ ID NO: 42;
(e) a heavy chain comprising the amino acid sequence of SEQ ID NO: 46 and a light chain comprising the amino acid sequence of SEQ ID NO: 42;
(f) a heavy chain comprising the amino acid sequence of SEQ ID NO: 50 and a light chain comprising the amino acid sequence of SEQ ID NO: 42;
(g) a heavy chain comprising the amino acid sequence of SEQ ID NO: 116 and a light chain comprising the amino acid sequence of SEQ ID NO: 22;
(h) a heavy chain comprising the amino acid sequence of SEQ ID NO: 121 and a light chain comprising the amino acid sequence of SEQ ID NO: 42;
(i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 54 and a light chain comprising the amino acid sequence of SEQ ID NO: 58;
(j) a heavy chain comprising the amino acid sequence of SEQ ID NO: 62 and a light chain comprising the amino acid sequence of SEQ ID NO: 58;
(k) a heavy chain comprising the amino acid sequence of SEQ ID NO: 54 and a light chain comprising the amino acid sequence of SEQ ID NO: 66;
(l) a heavy chain comprising the amino acid sequence of SEQ ID NO: 62 and a light chain comprising the amino acid sequence of SEQ ID NO: 66;
(m) a heavy chain comprising the amino acid sequence of SEQ ID NO: 70 and a light chain comprising the amino acid sequence of SEQ ID NO: 66;
(n) a heavy chain comprising the amino acid sequence of SEQ ID NO: 74 and a light chain comprising the amino acid sequence of SEQ ID NO: 66;
(o) a heavy chain comprising the amino acid sequence of SEQ ID NO: 78 and a light chain comprising the amino acid sequence of SEQ ID NO: 58;
(p) a heavy chain comprising the amino acid sequence of SEQ ID NO: 82 and a light chain comprising the amino acid sequence of SEQ ID NO: 58;
(q) a heavy chain comprising the amino acid sequence of SEQ ID NO: 70 and a light chain comprising the amino acid sequence of SEQ ID NO: 58;
(r) a heavy chain comprising the amino acid sequence of SEQ ID NO: 74 and a light chain comprising the amino acid sequence of SEQ ID NO: 58;
(s) a heavy chain comprising the amino acid sequence of SEQ ID NO: 78 and a light chain comprising the amino acid sequence of SEQ ID NO: 66;
(t) a heavy chain comprising the amino acid sequence of SEQ ID NO: 82 and a light chain comprising the amino acid sequence of SEQ ID NO: 66;
(u) a heavy chain comprising the amino acid sequence of SEQ ID NO: 86 and a light chain comprising the amino acid sequence of SEQ ID NO: 90;
(v) a heavy chain comprising the amino acid sequence of SEQ ID NO: 94 and a light chain comprising the amino acid sequence of SEQ ID NO: 98; or
(w) a heavy chain comprising the amino acid sequence of SEQ ID NO: 102 and a light chain comprising the amino acid sequence of SEQ ID NO: 106.
29. The nucleic acid molecule of claim 1 , which comprises:
(a) a heavy chain nucleotide sequence of SEQ ID NO: 19 and a light chain nucleotide sequence of SEQ ID NO: 23;
(b) a heavy chain nucleotide sequence of SEQ ID NO: 29 and a light chain nucleotide sequence of SEQ ID NO: 23;
(c) a heavy chain nucleotide sequence of SEQ ID NO: 35 and a light chain nucleotide sequence of SEQ ID NO: 23;
(d) a heavy chain nucleotide sequence of SEQ ID NO: 39 and a light chain nucleotide sequence of SEQ ID NO: 43;
(e) a heavy chain nucleotide sequence of SEQ ID NO: 47 and a light chain nucleotide sequence of SEQ ID NO: 43;
(f) a heavy chain nucleotide sequence of SEQ ID NO: 51 and a light chain nucleotide sequence of SEQ ID NO: 43;
(g) a heavy chain nucleotide sequence of SEQ ID NO: 117 and a light chain nucleotide sequence of SEQ ID NO: 119;
(h) a heavy chain nucleotide sequence of SEQ ID NO: 122 and a light chain nucleotide sequence of SEQ ID NO: 124;
(i) a heavy chain nucleotide sequence of SEQ ID NO: 55 and a light chain nucleotide sequence of SEQ ID NO: 59;
(j) a heavy chain nucleotide sequence of SEQ ID NO: 63 and a light chain nucleotide sequence of SEQ ID NO: 59;
(k) a heavy chain nucleotide sequence of SEQ ID NO: 55 and a light chain nucleotide sequence of SEQ ID NO: 67;
(l) a heavy chain nucleotide sequence of SEQ ID NO: 63 and a light chain nucleotide sequence of SEQ ID NO: 67;
(m) a heavy chain nucleotide sequence of SEQ ID NO: 71 and a light chain nucleotide sequence of SEQ ID NO: 126;
(n) a heavy chain nucleotide sequence of SEQ ID NO: 75 and a light chain nucleotide sequence of SEQ ID NO: 126;
(o) a heavy chain nucleotide sequence of SEQ ID NO: 79 and a light chain nucleotide sequence of SEQ ID NO: 128;
(p) a heavy chain nucleotide sequence of SEQ ID NO: 83 and a light chain nucleotide sequence of SEQ ID NO: 128;
(q) a heavy chain nucleotide sequence of SEQ ID NO: 71 and a light chain nucleotide sequence of SEQ ID NO: 128;
(r) a heavy chain nucleotide sequence of SEQ ID NO: 75 and a light chain nucleotide sequence of SEQ ID NO: 128;
(s) a heavy chain nucleotide sequence of SEQ ID NO: 79 and a light chain nucleotide sequence of SEQ ID NO: 126;
(t) a heavy chain nucleotide sequence of SEQ ID NO: 83 and a light chain nucleotide sequence of SEQ ID NO: 126;
(u) a heavy chain nucleotide sequence of SEQ ID NO: 87 and a light chain nucleotide sequence of SEQ ID NO: 91;
(v) a heavy chain nucleotide sequence of SEQ ID NO: 95 and a light chain nucleotide sequence of SEQ ID NO: 99; or
(w) a heavy chain nucleotide sequence of SEQ ID NO: 103 and a light chain nucleotide sequence of SEQ ID NO: 107.
30. The nucleic acid molecule of claim 1 , which encodes a Fab, F(ab′)2, Fv, or a single chain Fv fragment (scFv).
31. The nucleic acid molecule of claim 1 , further comprising a nucleotide sequence encoding a heavy chain constant region of IgG1, IgG2, IgG3, or IgG4.
32. The nucleic acid molecule of claim 1 , further comprising a nucleotide sequence encoding a light chain constant region of kappa or lambda.
33. The nucleic acid molecule of claim 1 , further comprising a nucleotide sequence encoding a human IgG4 heavy chain constant region with a Serine to Proline mutation at position 108 of SEQ ID NO: 108 or 110 and a nucleotide sequence encoding a kappa light chain constant region.
34. The nucleic acid molecule of claim 1 , further comprising a nucleotide sequence encoding a human IgG1 heavy chain constant region with an Asparagine to Alanine mutation at position 180 of SEQ ID NO: 112 and a nucleotide sequence encoding a kappa light chain constant region.
35. The nucleic acid molecule of claim 1 , further comprising a nucleotide sequence encoding a human IgG1 heavy chain constant region with an Aspartate to Alanine mutation at position 148 of SEQ ID NO: 113 and Proline to Alanine mutation at position 212 of SEQ ID NO: 113, and a nucleotide sequence encoding a kappa light chain constant region.
36. The nucleic acid molecule of claim 1 , further comprising a nucleotide sequence encoding a human IgG1 heavy chain constant region with a Leucine to Alanine mutation at position 117 of SEQ ID NO: 114 and Leucine to Alanine mutation at position 118 of SEQ ID NO: 114, and a nucleotide sequence encoding a kappa light chain constant region.
37. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes a VH comprising the amino acid sequence of SEQ ID NO: 32 and a VL comprising the amino acid sequence of SEQ ID NO: 20.
38. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes a VH comprising the amino acid sequence of SEQ ID NO: 52 and a VL comprising the amino acid sequence of SEQ ID NO: 64.
39. The nucleic acid molecule of claim 1 , comprising the nucleotide sequence of SEQ ID NO: 33 and SEQ ID NO: 21.
40. The nucleic acid molecule of claim 1 , comprising the nucleotide sequence of SEQ ID NO: 53 and SEQ ID NO: 65.
41. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes a heavy chain comprising the amino acid sequence of SEQ ID NO: 34 and a light chain comprising the amino acid sequence of SEQ ID NO: 22.
42. The nucleic acid molecule of claim 1 , wherein the nucleotide sequence encodes a heavy chain comprising the amino acid sequence of SEQ ID NO: 54 and a light chain comprising the amino acid sequence of SEQ ID NO: 66.
43. The nucleic acid molecule of claim 1 , comprising a heavy chain nucleotide sequence of SEQ ID NO: 35 and a light chain nucleotide sequence of SEQ ID NO: 23.
44. The nucleic acid molecule of claim 1 , comprising a heavy chain nucleotide sequence of SEQ ID NO: 55 and a light chain nucleotide sequence of SEQ ID NO: 67.
45. An expression vector comprising the nucleic acid molecule of claim 1 .
46. An isolated host cell comprising the nucleic acid molecule of claim 1 .
47. A method of producing an antibody molecule, comprising culturing the host cell of claim 46 under conditions suitable for gene expression.
48. A nucleic acid molecule comprising a first nucleotide sequence encoding a VH and a second nucleotide sequence encoding a VL, of an antibody molecule that binds to human TIM-3, wherein the VH comprises the amino acid sequence of SEQ ID NO: 32 and the VL comprises the amino acid sequence of SEQ ID NO: 20.
49. An expression vector comprising the nucleic acid molecule of claim 48 .
50. An isolated host cell comprising the nucleic acid molecule of claim 48 .
51. A method of producing an antibody molecule or fragment thereof, comprising culturing the host cell of claim 50 under conditions suitable for gene expression, thereby producing the antibody molecule or fragment thereof.
52. A nucleic acid molecule comprising a first nucleotide sequence encoding a VH and a second nucleotide sequence encoding a VL, of an antibody molecule that binds to human TIM-3, wherein the VH comprises the amino acid sequence of SEQ ID NO: 52 and the VL comprises the amino acid sequence of SEQ ID NO: 64.
53. An expression vector comprising the nucleic acid molecule of claim 52 .
54. An isolated host cell comprising the nucleic acid molecule of claim 52 .
55. A method of producing an antibody molecule or fragment thereof, comprising culturing the host cell of claim 54 under conditions suitable for gene expression, thereby producing the antibody molecule or fragment thereof.
56. A nucleic acid molecule comprising a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 33 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 21.
57. A nucleic acid molecule comprising a first nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 53 and a second nucleotide sequence comprising the nucleotide sequence of SEQ ID NO: 65.