Antibodies against the MUC18 antigen
The present invention relates generally to the generation and characterization of anti-MUC18 monoclonal antibodies. The invention further relates to the use of such anti-MUC18 antibodies in the diagnosis and treatment of disorders associated with increased activity of MUC18, in particular, tumors, such as melanomas.
1. An isolated monoclonal antibody comprising a heavy chain polypeptide, wherein said polypeptide has an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 5, 9, 13, 17, 21, 25, 29, 33 and 37, and wherein said monoclonal antibody binds to MUC18.
2. The antibody of claim 1 , wherein said antibody is a fully human antibody.
3. The antibody of claim 1 , wherein the antibody further comprises a light chain polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 6, 10, 14, 18, 22, 26, 30, 34 and 38.
4. The monoclonal antibody of claim 1 , wherein said antibody is in a therapeutically acceptable carrier.
5. The monoclonal antibody of claim 1 , wherein said antibody is conjugated to a therapeutic or cytotoxic agent.
6. The monoclonal antibody of claim 5 wherein the cytotoxic agent is ricin.
7. The monoclonal antibody of claim 5 wherein the therapeutic agent is a radioisotope.
8. A monoclonal antibody comprising a heavy chain variable domain encoded by a nucleic acid molecule having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 3, 7, 11, 15, 19, 23, 27, 31, 35 and 39, and wherein said monoclonal antibody binds to MUC18.
9. The monoclonal antibody of claim 8 , wherein said antibody comprises a light chain variable domain encoded by a nucleic acid molecule having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40.
10. The monoclonal antibody of claim 8 , wherein said antibody is a fully human antibody.
11. The monoclonal antibody of claim 8 , wherein said antibody is in a therapeutically acceptable carrier.
12. The monoclonal antibody of claim 8 , wherein said antibody is conjugated to a therapeutic or cytotoxic agent.
13. The monoclonal antibody of claim 12 wherein the cytotoxic agent is ricin.
14. The monoclonal antibody of claim 12 wherein the therapeutic agent is a radioisotope.
15. An isolated monoclonal antibody comprising a heavy chain polypeptide, wherein said polypeptide has an amino acid sequence of SEQ ID NO: 1, and wherein said monoclonal antibody binds to MUC18.
16. The antibody of claim 15 , wherein said antibody is a fully human antibody.
17. The antibody of claim 15 , wherein the antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 2.
18. The monoclonal antibody of claim 15 , wherein said antibody is in a therapeutically acceptable carrier.
19. The monoclonal antibody of claim 15 , wherein said antibody is conjugated to a therapeutic or cytotoxic agent.
20. The monoclonal antibody of claim 19 , wherein the cytotoxic agent is ricin.
21. The monoclonal antibody of claim 19 , wherein the therapeutic agent is a radioisotope.
22. A monoclonal antibody comprising a heavy chain variable domain encoded by a nucleic acid molecule having a nucleotide sequence of SEQ ID NO: 3, and wherein said monoclonal antibody binds to MUC18.
23. The monoclonal antibody of claim 22 , wherein said antibody comprises a light chain variable domain encoded by a nucleic acid molecule having a nucleotide sequence of SEQ ID NO: 4.
24. The monoclonal antibody of claim 22 , wherein said antibody is a fully human antibody.
25. The monoclonal antibody of claim 22 , wherein said antibody is in a therapeutically acceptable carrier.
26. The monoclonal antibody of claim 22 , wherein said antibody is conjugated to a therapeutic or cytotoxic agent.
27. The monoclonal antibody of claim 26 , wherein the cytotoxic agent is ricin.
28. The monoclonal antibody of claim 26 , wherein the therapeutic agent is a radioisotope.
29. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ ID NO: 1.
30. The monoclonal antibody of claim 29 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 2.
31. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ ID NO: 5.
32. The monoclonal antibody of claim 31 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 6.
33. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ ID NO: 9.
34. The monoclonal antibody of claim 33 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 10.
35. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ ID NO: 13.
36. The monoclonal antibody of claim 35 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 14.
37. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ ID NO: 17.
38. The monoclonal antibody of claim 37 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 18.
39. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ ID NO: 21.
40. The monoclonal antibody of claim 39 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 22.
41. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ ID NO: 25.
42. The monoclonal antibody of claim 41 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 26.
43. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ ID NO: 29.
44. The monoclonal antibody of claim 43 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 30.
45. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ II) NO: 33.
46. The monoclonal antibody of claim 45 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 34.
47. The monoclonal antibody of claim 1 , wherein the heavy chain polypeptide has an amino acid sequence of SEQ ID NO: 37.
48. The monoclonal antibody of claim 47 , wherein the monoclonal antibody further comprises a light chain polypeptide having an amino acid sequence of SEQ ID NO: 38.
49. A monoclonal antibody comprising a light chain polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 6, 10, 22, 26, 30, 34 and 38, wherein said monoclonal antibody binds to MUC18.
50. The monoclonal antibody of claim 49 , wherein said antibody has the amino acid sequence of SEQ ID NO: 2.
51. The monoclonal antibody of claim 49 , wherein said antibody has the amino acid sequence of SEQ ID NO: 6.
52. The monoclonal antibody of claim 49 , wherein said antibody has the amino acid sequence of SEQ ID NO: 10.
53. The monoclonal antibody of claim 49 , wherein said antibody has the amino acid sequence of SEQ ID NO: 22.
54. The monoclonal antibody of claim 49 , wherein said antibody has the amino acid sequence of SEQ ID NO: 26.
55. The monoclonal antibody of claim 49 , wherein said antibody has the amino acid sequence of SEQ ID NO: 30.
56. The monoclonal antibody of claim 49 , wherein said antibody has the amino acid sequence of SEQ ID NO: 34.
57. The monoclonal antibody of claim 49 , wherein said antibody has the amino acid sequence of SEQ ID NO: 38.