Generation and profiling of fully human gold-derived therapeutic antibodies specific for human CD38
The present invention provides novel antibodies and functional fragments thereof specific for CD38, and methods for using the same. These antibodies as well as the novel methods for using those antibodies can be used to treat, for example, hematological malignancies such as multiple myeloma.
1. An isolated antibody or antigen-binding fragment thereof that binds to CD38, which comprises the three variable heavy chain complementarity determining regions (H-CDRs) and the three variable light-chain complementarity determining regions (L-CDRs) that are in the variable heavy chain and variable light chain pairs selected from:
(i) SEQ ID NO: 18 and 48,
(ii) SEQ ID NO: 20 and 50,
(iii) SEQ ID NO: 21 and 51,
(iv) SEQ ID NO: 22 and 52, and
(v) SEQ ID NO: 25 and 55.
2. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises the three H-CDRs in SEQ ID NO: 18 and the three L-CDRs depicted in SEQ ID NO: 48.
3. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises the three H-CDRs in SEQ ID NO: 20 and the three L-CDRs depicted in SEQ ID NO: 50.
4. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises the three H-CDRs in SEQ ID NO: 21 and the three L-CDRs depicted in SEQ ID NO: 51.
5. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises the three H-CDRs in SEQ ID NO: 22 and the three L-CDRs depicted in SEQ ID NO: 52.
6. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises the three H-CDRs in SEQ ID NO: 25 and the three L-CDRs depicted in SEQ ID NO: 55.
7. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises a variable heavy chain at least eighty percent identical to that depicted in SEQ ID NO: 18, 20, 21, 22, or 25.
8. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 7 , which comprises a variable heavy chain at least ninety percent identical to that depicted in SEQ ID NO: 18, 20, 21, 22, or 25.
9. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 8 , which comprises a variable heavy chain depicted in SEQ ID NO: 18, 20, 21, 22, or 25.
10. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises a variable light chain at least eighty percent identical to that depicted in SEQ ID NO: 48, 50, 51, 52, or 55.
11. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 10 , which comprises a variable light chain at least ninety percent identical to that depicted in SEQ ID NO: 48, 50, 51, 52, or 55.
12. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 11 , which comprises a variable light chain depicted in SEQ ID NO: 48, 50, 51, 52, or 55.
13. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 4 , which comprises a variable heavy chain at least 80% identical to that depicted in SEQ ID NO: 21.
14. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 13 , which comprises a variable heavy chain at least 90% identical to that depicted in SEQ ID NO: 21.
15. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 14 , which comprises a variable heavy chain depicted in SEQ ID NO: 21.
16. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 15 , which comprises a variable heavy chain at least 80% identical to that depicted in SEQ ID NO: 22.
17. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 16 , which comprises a variable heavy chain at least 90% identical to that depicted in SEQ ID NO: 22.
18. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 17 , which comprises a variable heavy chain depicted in SEQ ID NO: 22.
19. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 4 , which comprises a variable light chain at least 80% identical to that depicted in SEQ ID NO: 51.
20. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 19 , which comprises a variable light chain at least 90% identical to that depicted in SEQ ID NO: 51.
21. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 20 , which comprises a variable light chain depicted in SEQ ID NO: 51.
22. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 5 , which comprises a variable light chain at least 80% identical to that depicted in SEQ ID NO: 52.
23. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 22 , which comprises a variable light chain at least 90% identical to that depicted in SEQ ID NO: 52.
24. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 23 , which comprises a variable light chain depicted in SEQ ID NO: 52.
25. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises a heavy and light chain pair that has at least eighty percent identity to those depicted in the heavy and light chain pairs selected from:
(i) SEQ ID NO: 18 and 48,
(ii) SEQ ID NO: 20 and 50,
(iii) SEQ ID NO: 21 and 51,
(iv) SEQ ID NO: 22 and 52, and
(v) SEQ ID NO: 25 and 55.
26. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises a heavy and light chain pair that has at least ninety percent identity to those depicted in the heavy and light chain pairs selected from:
(i) SEQ ID NO: 18 and 48,
(ii) SEQ ID NO: 20 and 50,
(iii) SEQ ID NO: 21 and 51,
(iv) SEQ ID NO: 22 and 52, and
(v) SEQ ID NO: 25 and 55.
27. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises a heavy chain depicted in SEQ ID NO: 18, and a light chain depicted in SEQ ID NO: 48.
28. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises a heavy chain depicted in SEQ ID NO: 20, and a light chain depicted in SEQ ID NO: 50.
29. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 25 , which comprises a heavy chain at least 80% identical to that depicted in SEQ ID NO: 21, and a light chain at least 80% identical to that depicted in SEQ ID NO: 51.
30. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 26 , which comprises a heavy chain at least 90% identical to that depicted in SEQ ID NO: 21, and a light chain at least 90% identical to that depicted in SEQ ID NO: 51.
31. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises a heavy chain depicted in SEQ ID NO: 21, and a light chain depicted in SEQ ID NO: 51.
32. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 25 , which comprises a heavy chain at least 80% identical to that depicted in SEQ ID NO: 22 and a light chain at least 80% identical to that depicted in SEQ ID NO: 52.
33. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 26 , which comprises a heavy chain at least 90% identical to that depicted in SEQ ID NO: 22 and a light chain at least 90% identical to that depicted in SEQ ID NO: 52.
34. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises a heavy chain depicted in SEQ ID NO: 22 and a light chain depicted in SEQ ID NO: 52.
35. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which comprises a heavy chain depicted in SEQ ID NO: 25 and a light chain depicted in SEQ ID NO: 55.
36. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which is an scFv, Fab or F(ab′) 2 fragment.
37. The isolated antibody or antigen binding fragment thereof that binds to CD38 according to claim 1 , which is an IgG.
38. The isolated antibody according to claim 37 , which is an IgG1.
39. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof that binds to CD38 according to claim 1 , and a pharmaceutically acceptable carrier or excipient therefor.
40. A diagnostic composition comprising an antibody or antigen-binding fragment thereof that binds to CD38 according to claim 1 , and an acceptable carrier or excipient therefor.