Anti-BCMA antibodies

• US 9,034,324 B2
• Filed: 03/10/2010
• Issued: 05/19/2015
• Est. Priority Date: 03/10/2009
• Status: Active Grant

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Inventors: Kalled, Susan L., Hsu, Yen-Ming
• Primary Examiner(s): Goddard, Laura B
• Assistant Examiner(s): Natarajan, Meera
• Application Number:
  US13/255,610
• Publication Number:
  US 20120082661A1
• Time in Patent Office: 1,896 Days
• Field of Search: None
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/54 : F(ab')2
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/732 : Antibody-dependent cellular cytotoxicity [ADCC]

Abstract

This invention provides antibodies that recognize the B Cell Maturation Antigen (BCMA) and that bind naïve B cells, plasma cells, and/or memory B cells. The invention further provides methods for depleting naïve B cells, plasma cells, and memory B cells, and for treating B cell-related disorders, including lymphomas and autoimmune diseases.

Claims

1. An isolated antibody or antigen binding fragment thereof that binds to the polypeptide of SEQ ID NO:

9, wherein the antibody or antigen binding fragment thereof comprises;

a) a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO;

1 and a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO;

2;

b) a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO;

3 and a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO;

4, SEQ ID NO;

11, or SEQ ID NO;

12;

c) a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO;

5 and a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO;

6;

or

d) a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO;

7 and a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO;

8.

2. The antibody of claim 1, wherein the heavy chain variable domain comprises SEQ ID NO:

5 and the light chain variable domain comprises SEQ ID NO;

6.

3. The antibody of claim 1, wherein the antibody is a chimeric, humanized, or single chain antibody.

4. The antibody of claim 1, wherein the antibody comprises a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO:

1 and a variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO;

2.

5. The antibody of claim 4, wherein the antibody comprises a variable domain of SEQ ID NO:

1 and a variable domain of SEQ ID NO;

2.

6. A hybridoma that produces the antibody of claim 1.

7. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

8. A polypeptide that binds to SEQ ID NO:

9 and comprises the antigen binding portion, Fab fragment, or F(ab′

)2 fragment of the antibody of claim 1.

9. A hybridoma that produces the antigen binding portion, Fab fragment, or F(ab′

)2 fragment of claim 8.

10. A pharmaceutical composition comprising the antigen binding portion, Fab fragment, or F(ab′

)2 fragment of claim 8 and a pharmaceutically acceptable carrier.

11. A method of depleting plasma cells which express BCMA, comprising administering the antibody of claim 1 or the polypeptide of claim 8 to a patient in need thereof.

12. A method of treating a B cell-related disorder associated with BCMA expression, comprising administering the antibody of claim 1 or the polypeptide of claim 8 to a patient in need thereof.

13. The method of claim 12, wherein the B-cell related disorder is plasmacytoma, Hodgkins'"'"' lymphoma, follicular lymphomas, small non-cleaved cell lymphomas, endemic Burkitt'"'"'s lymphoma, sporadic Burkitt'"'"'s lymphoma, marginal zone lymphoma, extranodal mucosa-associated lymphoid tissue lymphoma, nodal monocytoid B cell lymphoma, splenic lymphoma, mantle cell lymphoma, large cell lymphoma, diffuse mixed cell lymphoma, immunoblastic lymphoma, primary mediastinal B cell lymphoma, pulmonary B cell angiocentric lymphoma, small lymphocytic lymphoma, B cell proliferations of uncertain malignant potential, lymphomatoid granulomatosis, post-transplant lymphoproliferative disorder, an immunoregulatory disorder, rheumatoid arthritis, myasthenia gravis, idiopathic thrombocytopenia purpura, anti-phospholipid syndrome, Chagas'"'"' disease, Grave'"'"'s disease, Wegener'"'"'s granulomatosis, poly-arteritis nodosa, Sjogren'"'"'s syndrome, pemphigus vulgaris, scleroderma, multiple sclerosis, anti-phospholipid syndrome, ANCA associated vasculitis, Goodpasture'"'"'s disease, Kawasaki disease, autoimmune hemolytic anemia, and rapidly progressive glomerulonephritis, heavy-chain disease, primary or immunocyte-associated amyloidosis, or monoclonal gammopathy of undetermined significance.

14. The method of claim 13, wherein the B cell-related disorder is a B cell malignancy.

15. The method of claim 13, wherein the B cell-related disorder is a plasma cell malignancy.

16. The method of claim 15, wherein the plasma cell malignancy is multiple myeloma.

17. The method of claim 13, wherein the B cell-related disorder is an autoimmune disease.

18. The method of claim 17, wherein the autoimmune disease is systemic lupus erythematosus.

19. The method of claim 13, wherein the B-cell related disorder is rheumatoid arthritis.

20. The method of claim 13, wherein the B-cell related disorder is idiopathic thrombocytopenia purpura, or myasthenia gravis, or autoimmune hemolytic anemia.

21. The method of claim 11, further comprising administering rituximab.

22. A method of reducing the level of at least one autoantibody in a subject that expresses BCMA, comprising administering the antibody of claim 1 or the polypeptide of claim 8 to a patient in need thereof.