BCMA antibodies and use of same to treat cancer and immunological disorders

Patent metadata

Field	Value
Publication number	US-11078291-B2
Application number	US-201916411867-A
Country	US
Kind code	B2
Filing date	May 14, 2019
Priority date	Feb 17, 2016
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

The invention provides humanized antibodies that specifically bind to BCMA. The antibodies are useful for treatment and diagnoses of various cancers and immune disorders as well as detecting BCMA.

First claim

What is claimed is:

1. An isolated antibody or a binding fragment thereof that binds to human B-cell maturation antigen (BCMA), wherein the antibody or binding fragment comprises a mature heavy chain variable region and a mature light chain variable region, wherein the mature heavy chain variable region comprises complementarity determining regions (CDRs) comprising the amino acid sequences of SEQ ID NOs: 60, 61 and 62, and the mature light chain variable region comprises CDRs comprising the amino acid sequences of SEQ ID NOs:90, 91 and 92.

2. The isolated antibody or binding fragment of claim 1 , wherein the antibody is a monoclonal antibody.

3. The isolated antibody or binding fragment of claim 1 , wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light chain variable region is fused to a light chain constant region.

4. The isolated antibody or binding fragment of claim 3 , wherein the heavy chain constant region is a mutant form of a natural human constant region and has reduced binding to an Fcγ receptor relative to the natural human constant region.

5. The isolated antibody or binding fragment of claim 3 , wherein the heavy chain constant region is of immunoglobulin G1 (IgG1) isotype.

6. The isolated antibody or binding fragment of claim 3 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:5 and the light chain constant region comprises the amino acid sequence of SEQ ID NO:3.

7. The isolated antibody or binding fragment of claim 3 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:7 (S293C) and the light chain constant region comprises the amino acid sequence of SEQ ID NO:3.

8. The isolated antibody or binding fragment of claim 3 , which is non-fucosylated.

9. The isolated antibody or binding fragment of claim 1 , which is an antibody binding fragment.

10. The isolated antibody or binding fragment of claim 9 , wherein the antibody binding fragment is selected from the group consisting of a Fab, a Fab′, and a F(ab′) 2 .

11. The isolated antibody or binding fragment of claim 1 , which is a humanized antibody.

12. The isolated antibody or binding fragment of claim 1 , which is a naked antibody or binding fragment.

13. The isolated antibody or binding fragment of claim 1 , which is conjugated to a cytotoxic or cytostatic agent.

14. The isolated antibody or binding fragment of claim 13 , which is conjugated to a cytotoxic agent.

15. The isolated antibody or binding fragment of claim 14 , wherein the cytotoxic agent is conjugated to the antibody or the binding fragment via an enzyme-cleavable linker.

16. The isolated antibody or binding fragment of claim 14 , wherein the cytotoxic agent is a DNA minor groove binder.

17. The isolated antibody or binding fragment of claim 16 , wherein the cytotoxic agent has the formula:

18. The isolated antibody or binding fragment of claim 14 , wherein the cytotoxic agent is monomethyl auristatin (MMAE) or monomethyl auristatin F (MMAF).

19. A bispecific antibody or binding fragment thereof that binds to human B-cell maturation antigen (BCMA), wherein the bispecific antibody or binding fragment comprises a mature heavy chain variable region and a mature light chain variable region, wherein the mature heavy chain variable region comprises complementarity determining regions (CDRs) comprising the amino acid sequences of SEQ ID NOs: 60, 61 and 62, and the mature light chain variable region comprises CDRs comprising the amino acid sequences of SEQ ID NOs:90, 91 and 92.

20. An isolated antibody or a binding fragment thereof that binds to human B-cell maturation antigen (BCMA), wherein the antibody or binding fragment comprises a mature heavy chain variable region comprising the amino acid sequence of SEQ ID NO:13, and a mature light chain variable region comprising the amino acid sequence of SEQ ID NO:19.

21. The isolated antibody or binding fragment of claim 20 , wherein the antibody is a monoclonal antibody.

22. The isolated antibody or binding fragment of claim 20 , wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light chain variable region is fused to a light chain constant region.

23. The isolated antibody or binding fragment of claim 22 , wherein the heavy chain constant region is a mutant form of a natural human constant region and has reduced binding to an Fcγ receptor relative to the natural human constant region.

24. The isolated antibody or binding fragment of claim 22 , wherein the heavy chain constant region is of immunoglobulin G1 (IgG1) isotype.

25. The isolated antibody or binding fragment of claim 22 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:5 and the light chain constant region comprises the amino acid sequence of SEQ ID NO:3.

26. The isolated antibody or binding fragment of claim 22 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:7 (S293C) and the light chain constant region comprises the amino acid sequence of SEQ ID NO:3.

27. The isolated antibody or binding fragment of claim 22 , which is non-fucosylated.

28. The isolated antibody or binding fragment of claim 20 , which is an antibody binding fragment.

29. The isolated antibody or binding fragment of claim 20 , which is a naked antibody or binding fragment.

30. The isolated antibody or binding fragment of claim 20 , wherein the antibody or binding fragment is conjugated to a cytotoxic or cytostatic agent.

31. The isolated antibody or binding fragment of claim 20 , which is conjugated to a cytotoxic agent.

32. The isolated antibody or binding fragment of claim 31 , wherein the cytotoxic agent is conjugated to the antibody or the binding fragment via an enzyme-cleavable linker.

33. The isolated antibody or binding fragment of claim 31 , wherein the cytotoxic agent is a DNA minor groove binder.

34. The isolated antibody or binding fragment of claim 33 , wherein the cytotoxic agent has the formula:

35. The antibody or binding fragment of claim 31 , wherein the cytotoxic agent is monomethyl auristatin (MMAE) or monomethyl auristatin F (MMAF).

36. A bispecific antibody or binding fragment thereof, wherein the bispecific antibody or binding fragment comprises a mature heavy chain variable region comprising the amino acid sequence of SEQ ID NO:13, and a mature light chain variable region comprising the amino acid sequence of SEQ ID NO:19 that bind to human B-cell maturation antigen (BCMA).

37. An isolated, monoclonal, immunoglobulin G1 (IgG1) antibody that binds to human B-cell maturation antigen (BCMA), wherein the antibody comprises a mature heavy chain variable region and a mature light chain variable region, wherein the mature heavy chain variable region comprises complementarity determining regions (CDRs) comprising the amino acid sequences of SEQ ID NOs: 60, 61 and 62, and the mature light chain variable region comprises CDRs c

Assignees

• Seagen Inc

Inventors

• Sussman Django
• Ryan Maureen
• Westendorf Lori
• Feldhaus Michael

Classifications

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61K47/6803

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title

• C07K2317/72

  Increased effector function due to an Fc-modification · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title