Anti-BCMA antibodies
View Patent ↗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.
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.