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

Patent metadata

Field	Value
Publication number	US-11767365-B2
Application number	US-202117358642-A
Country	US
Kind code	B2
Filing date	Jun 25, 2021
Priority date	Feb 17, 2016
Publication date	Sep 26, 2023
Grant date	Sep 26, 2023

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. A method for treating a subject with a cancer that expresses human B-cell maturation antigen (BCMA), the method comprising administering to the subject an effective amount of an antibody or a binding fragment thereof that binds to human 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 method 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.

3. The method of claim 2 , 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.

4. The method of claim 2 , wherein the heavy chain constant region is of immunoglobulin G1 (IgG1) isotype.

5. The method of claim 2 , 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.

6. The method of claim 1 , wherein the antibody or antibody binding fragment is non-fucosylated.

7. The method of claim 1 , wherein the antibody or antibody binding fragment is an antibody binding fragment.

8. The method of claim 7 , wherein the antibody binding fragment is selected from the group consisting of a Fab, a Fab′, and a F(ab′) 2 .

9. The method of claim 1 , wherein the antibody is a humanized antibody.

10. The method of claim 1 , wherein the cancer is a hematological cancer.

11. The method of claim 10 , wherein the hematological cancer is a myeloma, leukemia or a lymphoma.

12. The method of claim 10 , wherein the hematological cancer is multiple myeloma.

13. The method of claim 10 , wherein the hematological cancer is non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma.

14. The method of claim 10 , wherein the hematological cancer is myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS), Waldenström's macroglobulinemia or Burkett's lymphoma.

15. A method for treating a subject with a cancer that expresses human B-cell maturation antigen (BCMA), the method comprising administering to the subject an effective amount of an antibody or a binding fragment thereof that binds to human 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.

16. The method of claim 15 , 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.

17. The method of claim 16 , 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.

18. The method of claim 16 , wherein the heavy chain constant region is of immunoglobulin G1 (IgG1) isotype.

19. The method of claim 16 , 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.

20. The method of claim 15 , wherein the antibody or antibody binding fragment is non-fucosylated.

21. The method of claim 15 , wherein the antibody or antibody binding fragment is an antibody binding fragment.

22. The method of claim 15 , wherein the cancer is a hematological cancer.

23. The method of claim 22 , wherein the hematological cancer is a myeloma, leukemia or a lymphoma.

24. The method of claim 22 , wherein the hematological cancer is multiple myeloma.

25. The method of claim 22 , wherein the hematological cancer is non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma.

26. A method for treating a subject with a cancer that expresses human B-cell maturation antigen (BCMA), the method comprising administering to the subject an effective amount of an antibody that binds to human BCMA, wherein
(a) the antibody is a monoclonal, immunoglobulin G1 (IgG1) antibody; and
(b) 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 comprising the amino acid sequences of SEQ ID NOs:90, 91 and 92.

27. The method of claim 26 , wherein the cancer is a hematological cancer.

28. The method of claim 27 , wherein the hematological cancer is a myeloma, leukemia or a lymphoma.

29. The method of claim 27 , wherein the hematological cancer is multiple myeloma.

30. The method of claim 27 , wherein the hematological cancer is non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma.

31. A method for treating a subject with a cancer that expresses human B-cell maturation antigen (BCMA), the method comprising administering to the subject an effective amount of an antibody that binds to human BCMA, wherein
(a) the antibody is a monoclonal, immunoglobulin G1 (IgG1) antibody; and
(b) the antibody 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.

32. The method of claim 31 , wherein the cancer is a hematological cancer.

33. The method of claim 32 , wherein the hematological cancer is a myeloma, leukemia or a lymphoma.

34. The method of claim 32 , wherein the hematological cancer is multiple myeloma.

35. The method of claim 32 , wherein the hematological cancer is non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma.

36. A method for treating a subject with a cancer that expresses human B-cell maturation antigen (BCMA), the method comprising administering to the subject an effective amount of a monoclonal, non-fucosylated antibody that binds to human 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 comprising the amino acid sequences of SEQ ID NOs:90, 91 and 92.

37. The method of claim 36 , wherein the antibody is an immunoglobulin G1 (IgG1) antibody.

38. The method of claim 36 , 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, and wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:5 and the light chain constant region comprises

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