Specific binding agents to hepatocyte growth factor
Specific binding agents that interact with hepatocyte growth factor (HGF) are described. Methods of treating cancer by administering a pharmaceutically effective amount of a specific binding agent to HGF are described. Methods of detecting the amount of HGF in a sample using a specific binding agent to HGF are described.
1. An isolated antibody that binds human hepatocyte growth factor (HGF), wherein the antibody is selected from the group consisting of:
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:24 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 25 from residue 20 to residue 141;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:26 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 27 from residue 20 to residue 137;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:28 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 29 from residue 20 to residue 139;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:30 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 31 from residue 20 to residue 148;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:32 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 33 from residue 20 to residue 139;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:34 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 35 from residue 20 to residue 144;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:36 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 from residue 20 to residue 142;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:38 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 39 from residue 20 to residue 139;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:40 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 41 from residue 20 to residue 140; and
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:42 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 43 from residue 20 to residue 139.
2. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 24 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 25 from residue 20 to residue 141.
3. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 26 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 27 from residue 20 to residue 137.
4. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 28 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 29 from residue 20 to residue 139.
5. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 30 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 31 from residue 20 to residue 148.
6. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 32 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 33 from residue 20 to residue 139.
7. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 34 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 35 from residue 20 to residue 144.
8. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 36 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 from residue 20 to residue 142.
9. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 38 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 39 from residue 20 to residue 139.
10. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 40 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 41 from residue 20 to residue 140.
11. The antibody of claim 1 , wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 42 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 43 from residue 20 to residue 139.
12. An isolated antibody that binds human hepatocyte growth factor (HGF), wherein the antibody is selected from the group consisting of:
an antibody comprising a light chain comprising SEQ ID NOs: 60, 70, and 80, and a heavy chain comprising SEQ ID NOs: 90, 100, and 110;
an antibody comprising a light chain comprising SEQ ID NOs: 61, 71, and 81, and a heavy chain comprising SEQ ID NOs: 91, 101, and 111;
an antibody comprising a light chain comprising SEQ ID NOs: 62, 72, and 82, and a heavy chain comprising SEQ ID NOs: 92, 102, and 112;
an antibody comprising a light chain comprising SEQ ID NOs: 63, 73, and 83, and a heavy chain comprising SEQ ID NOs: 93, 103, and 113;
an antibody comprising a light chain comprising SEQ ID NOs: 64, 74, and 84, and a heavy chain comprising SEQ ID NOs: 94, 104, and 114;
an antibody comprising a light chain comprising SEQ ID NOs: 65, 75, and 85, and a heavy chain comprising SEQ ID NOs: 95, 105, and 115;
an antibody comprising a light chain comprising SEQ ID NOs: 66, 76, and 86, and a heavy chain comprising SEQ ID NOs: 96, 106, and 116;
an antibody comprising a light chain comprising SEQ ID NOs: 67, 77, and 87, and a heavy chain comprising SEQ ID NOs: 97, 107, and 117;
an antibody comprising a light chain comprising SEQ ID NOs: 68, 78, and 88, and a heavy chain comprising SEQ ID NOs: 98, 108, and 118; and
an antibody comprising a light chain comprising SEQ ID NOs: 69, 79, and 89, and a heavy chain comprising SEQ ID NOs: 99, 109, and 119.
13. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 60, 70, and 80, and a heavy chain comprising SEQ ID NOs: 90, 100, and 110.
14. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 61, 71, and 81, and a heavy chain comprising SEQ ID NOs: 91, 101, and 111.
15. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 62, 72, and 82, and a heavy chain comprising SEQ ID NOs: 92, 102, and 112.
16. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 63, 73, and 83, and a heavy chain comprising SEQ ID NOs: 93, 103, and 113.
17. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 64, 74, and 84, and a heavy chain comprising SEQ ID NOs: 94, 104, and 114.
18. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 65, 75, and 85, and a heavy chain comprising SEQ ID NOs: 95, 105, and 115.
19. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 66, 76, and 86, and a heavy chain comprising SEQ ID NOs: 96, 106, and 116.
20. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 67, 77, and 87, and a heavy chain comprising SEQ ID NOs: 97, 107, and 117.
21. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 68, 78, and 88, and a heavy chain comprising SEQ ID NOs: 98, 108, and 118.
22. The antibody of claim 12 , wherein the antibody comprises a light chain comprising SEQ ID NOs: 69, 79, and 89, and a heavy chain comprising SEQ ID NOs: 99, 109, and 119.
23. The antibody of claim 9 , wherein the light chain further comprises the amino acid sequence of SEQ ID NO: 44 and the heavy chain further comprises the amino acid sequence of SEQ ID NO: 46.
24. An isolated fully human antibody that binds human hepatocyte growth factor comprising a light chain and a heavy chain, wherein the light chain comprises SEQ ID NOs. 67, 77, and 87 and the heavy chain comprises SEQ ID NOs: 97, 107, and 117.
25. The antibody of claim 24 , wherein the light chain further comprises the amino acid sequence of SEQ ID NO: 44 and the heavy chain further comprises the amino acid sequence of SEQ ID NO: 46.
26. An isolated fully human antibody that binds human hepatocyte growth factor (HGF) comprising a light chain and a heavy chain, wherein the light chain comprises the amino acid sequence of SEQ ID NO: 38 from residue 21 to residue 128 and the heavy chain comprises the amino acid sequence of SEQ ID NO: 39 from residue 20 to residue 139.
27. The antibody of claim 26 , wherein the light chain further comprises the amino acid sequence of SEQ ID NO: 44 and the heavy chain further comprises the amino acid sequence of SEQ ID NO: 46.
28. A polypeptide consisting of at least one amino acid sequence selected from SEQ ID NO: 164 and 165.
29. An isolated antibody or antigen binding domain which is capable of binding at least one amino acid sequence consisting of SEQ ID NO: 164 or SEQ ID NO: 165, wherein the antibody or antigen binding domain is humanized or fully human.
30. A method of obtaining an antibody capable of binding hepatocyte growth factor (HGF) comprising administering at least one polypeptide consisting of SEQ ID NO: 164 or 165 to a non-human animal and obtaining the antibody from the animal.
31. A method of producing a humanized antibody capable of binding hepatocyte growth factor (HGF) comprising administering at least one polypeptide consisting of SEQ ID NO: 164 or 165 to a non-human animal, obtaining an antibody capable of binding HGF from the animal, designing a humanized antibody capable of binding HGF based on the antibody obtained from the animal, and producing the humanized antibody.
32. An antibody of any one of claim 1 , 29 , 12 , or 20 , wherein the antibody neutralizes binding of HGF to c-MET.
33. An antibody of any one of claim 1 - 11 , or 12 - 22 , wherein the antibody is an immunologically functional immunoglobulin fragment that binds human hepatocyte growth factor.
34. A composition comprising an antibody of any one of claim 1 , 12 , or 23 and a pharmaceutically acceptable carrier.
35. A composition comprising the antibody of claim 24 and a pharmaceutically acceptable carrier.
36. A composition comprising the antibody of claim 26 and a pharmaceutically acceptable carrier.