IP Library › Granted Patent US 7,718,776

Granted Patent B2

US 7,718,776 · App. 10/408,901 · Granted May 18, 2010

Human anti-OPGL neutralizing antibodies as selective OPGL pathway inhibitors

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Quick Facts

Patent No.: US 7,718,776
App. No.: 10/408,901
Granted: May 18, 2010
Kind: B2

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Abstract

Monoclonal antibodies and hybridomas producing them that interact with osteoprotegerin ligand (OPGL) are provided. Methods of treating osteopenic disorders by administering a pharmaceutically effective amount of antibodies to OPGL are also provided. Methods of detecting the amount of OPGL in a sample using antibodies to OPGL are further provided.

Claims (64)

1. An isolated antibody or an antigen-binding fragment thereof that specifically binds human osteoprotegerin ligand (OPGL), comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises any of SEQ ID NO: 6 SEQ ID NO: 14, SEQ ID NO: 22, or SEQ ID NO: 26.

2. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises any of SEQ ID NO: 10 or SEQ ID NO: 18.

3. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), comprising a heavy chain variable region and a light chain variable region, wherein the light chain variable region comprises any of SEQ ID NO: 8, SEQ ID NO: 16, SEQ ID NO: 24, or SEQ ID NO: 28.

4. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), comprising a heavy chain variable region and a light chain variable region, wherein the light chain variable region comprises any of SEQ ID NO: 12 or SEQ ID NO: 20.

5. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), comprising a heavy chain and a light chain, wherein the heavy chain comprises any of SEQ ID NO: 30, SEQ ID NO: 38, SEQ ID NO: 46, or SEQ ID NO: 50.

6. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), comprising a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 34 or SEQ ID NO: 42.

7. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), comprising a heavy chain and a light chain, wherein the light chain comprises any of SEQ ID NO: 32, SEQ ID NO: 40, SEQ ID NO: 48, or SEQ ID NO: 52.

8. The antibody of any of claims 1 , 3 , 5 , or 7 , wherein the antibody specifically binds the D-E loop region of human osteoprotegerin ligand (OPGL).

9. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), comprising a heavy chain and a light chain, wherein the light chain comprises SEQ ID NO: 36 or SEQ ID NO: 44.

10. The antibody of any of claims 2 , 4 , 6 , or 9 , wherein the antibody specifically binds to:

a. a region of human osteoprotegerin ligand (OPGL) that is outside the D-E loop region; or

b. both a region of human OPGL that is outside the D-E loop region and all or a portion of the D-E loop region.

11. The antibody of claim 10 , wherein binding to both a region of human OPGL that is outside the D-E loop region and all or a portion of the D-E loop region is consecutive or simultaneous.

12. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain variable region comprising SEQ ID NO: 6 and a light chain variable region comprising SEQ ID NO: 8, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 6 and CDR1, CDR2, and CDR3 of SEQ ID NO: 8.

13. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain variable region comprising SEQ ID NO: 14 and a light chain variable region comprising SEQ ID NO: 16, or wherein antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 14 and CDR1, CDR2, and CDR3 of SEQ ID NO: 16.

14. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain variable region comprising SEQ ID NO: 22 and a light chain variable region comprising SEQ ID NO: 24, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 22 and CDR1, CDR2, and CDR3 of SEQ ID NO: 24.

15. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain variable region comprising SEQ ID NO: 26 and a light chain variable region comprising SEQ ID NO: 28, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 26 and CDR1, CDR2, and CDR3 of SEQ ID NO: 28.

16. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 30 and the light chain comprises SEQ ID NO: 32, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 6 and CDR1, CDR2, and CDR3 of SEQ ID NO: 8.

17. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 38 and the light chain comprises SEQ ID NO: 40, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 14 and CDR1, CDR2, and CDR3 of SEQ ID NO: 16.

18. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 46 and the light chain comprises SEQ ID NO: 48, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 22 and CDR1, CDR2, and CDR3 of SEQ ID NO: 24.

19. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 50 and the light chain comprises SEQ ID NO: 52, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 26 and CDR1, CDR2, and CDR3 of SEQ ID NO: 28.

20. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain variable region comprising SEQ ID NO: 10 and a light chain variable region comprising SEQ ID NO: 12, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 10 and CDR1, CDR2, and CDR3 of SEQ ID NO: 12.

21. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain variable region comprising SEQ ID NO: 18 and a light chain variable region comprising SEQ ID NO: 20, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 18 and CDR1, CDR2, and CDR3 of SEQ ID NO: 20.

22. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 34 and the light chain comprises SEQ ID NO: 36, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 10 and CDR1, CDR2, and CDR3 of SEQ ID NO: 12.

23. An isolated antibody or an antigen-binding fragment thereof, that specifically binds human osteoprotegerin ligand (OPGL), wherein the antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 42 and the light chain comprises SEQ ID NO: 44, or wherein the antigen-binding fragment thereof comprises CDR1, CDR2, and CDR3 of SEQ ID NO: 18 and CDR1, CDR2, and CDR3 of SEQ ID NO: 20.

24. An isolated antibody or antigen-binding fragment thereof comprising:

(i) CDR1, CDR2, and CDR3 of SEQ ID NO: 6, and CDR1, CDR2, and CDR3 of SEQ ID NO: 8;

(ii) CDR1, CDR2, and CDR3 of SEQ ID NO: 14, and CDR1, CDR2, and CDR3 of SEQ ID NO: 16;

(iii) CDR1, CDR2, and CDR3 of SEQ ID NO: 22, and CDR1, CDR2, and CDR3 of SEQ ID NO: 24; or

(iv) CDR1, CDR2, and CDR3 of SEQ ID NO: 26, and CDR1, CDR2, and CDR3 of SEQ ID NO: 28;

wherein the antibody or antigen-binding fragment thereof specifically binds to human osteoprotegerin ligand (OPGL).

25. The antibody or antigen-binding fragment thereof of claim 24 , wherein the antibody or antigen-binding fragment thereof specifically binds the D-E loop region of human osteoprotegerin ligand (OPGL).

26. An isolated antibody or antigen-binding fragment thereof comprising:

(i) CDR1, CDR2, and CDR3 of SEQ ID NO: 10, and CDR1, CDR2, and CDR3 of SEQ ID NO: 12; or

(ii) CDR1, CDR2, and CDR3 of SEQ ID NO: 18, and CDR1, CDR2, and CDR3 of SEQ ID NO: 20;

wherein the antibody or antigen-binding fragment thereof specifically binds to human osteoprotegerin ligand (OPGL).

27. The antibody or antigen-binding fragment thereof of claim 26 , wherein the antibody or antigen-binding fragment thereof specifically binds to:

c. a region of human osteoprotegerin ligand (OPGL) that is outside the D-E loop region; or

d. both a region of human OPGL that is outside the D-E loop region and all or a portion of the D-E loop region, wherein binding is consecutive or simultaneous.

28. The antibody or antigen-binding fragment thereof of claim 27 , wherein binding to both a region of human OPGL that is outside the D-E loop region and all or a portion of the D-E loop region is consecutive or simultaneous.

29. The antibody of any of claims 12 , 13 , 14 , 15 , 16 , 17 , 18 , or 19 , wherein the antibody specifically binds the D-E loop region of human osteoprotegerin ligand (OPGL).

30. The antibody of any of claims 20 , 21 , 22 , or 23 , wherein the antibody specifically binds to:

a. a region of human osteoprotegerin ligand (OPGL) that is outside the D-E loop region; or

b. both a region of human OPGL that is outside the D-E loop region and all or a portion of the D-E loop region.

31. The antibody of claim 30 , wherein binding to both a region of OPGL that is outside the D-E loop region and all or a portion of the D-E loop region is consecutive or simultaneous.

32. The antibody or antigen-binding fragment thereof of any of claims 12 , 13 , 14 , 15 , 20 , 21 , 24 , or 26 , which is a single-chain antibody.

33. The antibody or antigen-binding fragment thereof of claim 32 , which is a single-chain Fv antibody.

34. The antigen-binding fragment of any of claims 12 , 13 , 14 , 15 , 20 , 21 , 24 , or 26 , which is a Fab antibody fragment.

35. The antigen-binding fragment of any of claims 12 , 13 , 14 , 15 , 20 , 21 , 24 , 26 , which is Fab′ antibody fragment.

36. The antigen-binding fragment of any of claims 12 , 13 , 14 , 15 , 20 , 21 , 24 , 26 , which is a (Fab′) 2 antibody fragment.

37. The antibody or antigen-binding fragment thereof of any of claims 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , or 26 wherein the antibody or antigen-binding fragment thereof inhibits binding of OPGL to an osteoclast differentiation and activation receptor (ODAR).

38. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 37 .

39. An isolated antibody comprising a heavy chain variable region comprising SEQ ID NO: 6, and a light chain variable region comprising SEQ ID NO: 8.

40. An isolated antibody comprising a heavy chain variable region comprising SEQ ID NO: 14, and a light chain variable region comprising SEQ ID NO: 16.

41. An isolated antibody comprising a heavy chain variable region comprising SEQ ID NO: 22, and a light chain variable region comprising SEQ ID NO: 24.

42. An isolated antibody comprising a heavy chain variable region comprising SEQ ID NO: 26, and a light chain variable region comprising SEQ ID NO: 28.

43. An isolated antibody comprising a heavy chain variable region comprising SEQ ID NO: 10, and a light chain variable region comprising SEQ ID NO: 12.

44. An isolated antibody comprising a heavy chain variable region comprising SEQ ID NO: 18, and a light chain variable region comprising SEQ ID NO: 20.

45. An isolated antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 30, and the light chain comprises SEQ ID NO: 32.

46. An isolated antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 34, and the light chain comprises SEQ ID NO: 36.

47. An isolated antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 38, and the light chain comprises SEQ ID NO: 40.

48. An isolated antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 42, and the light chain comprises SEQ ID NO: 44.

49. An isolated antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 46, and the light chain comprises SEQ ID NO: 48.

50. An isolated antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 50, and the light chain comprises SEQ ID NO: 52.

Assignments (2)

MERGER Recorded Jun 2, 2015

From: MEDAREX, L.L.C.

To: E. R. SQUIBB & SONS, L.L.C.

Reel/Frame 035767/0494 →

MERGER Recorded Aug 15, 2013

From: MEDAREX, INC.

To: MEDAREX, L.L.C.

Reel/Frame 031016/0678 →