Anti-BCMA antibodies
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 polypeptide comprising an antigen binding fragment of an antibody that binds to the polypeptide of SEQ ID NO:9, wherein the antigen binding fragment of the antibody comprises:
a) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 1 and a light chain variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 2;
b) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 3 and a light chain 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 heavy chain variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 5 and a light chain variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 6; or
d) a heavy chain variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 7 and a light chain variable domain comprising CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 8.
2. The isolated polypeptide of claim 1 , wherein the heavy chain variable domain comprises SEQ ID NO: 1 and the light chain variable domain comprises SEQ ID NO: 2.
3. The isolated polypeptide of claim 1 , wherein the heavy chain variable domain comprises SEQ ID NO: 3 and the light chain variable domain comprises SEQ ID NO: 4, SEQ ID NO: 11, or SEQ ID NO: 12.
4. The isolated polypeptide 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.
5. The isolated polypeptide of claim 1 , wherein the heavy chain variable domain comprises SEQ ID NO: 7 and the light chain variable domain comprises SEQ ID NO: 8.
6. The isolated polypeptide of claim 1 , wherein the antigen binding fragment of the antibody is chimeric, humanized, or a single chain antigen binding fragment.
7. The isolated polypeptide of claim 1 , wherein the antigen binding fragment of the antibody is a Fab fragment, or a F(ab′)2 fragment.
8. An isolated polynucleotide encoding the isolated polypeptide of claim 1 .
9. A vector comprising the isolated polynucleotide of claim 8 .
10. A cell comprising the vector of claim 9 .
11. A method of treating a B cell-related disorder associated with BCMA expression, comprising administering the isolated polypeptide of claim 1 .
12. The method of claim 11 , 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.
13. The method of claim 11 , wherein the B cell-related disorder is a B cell malignancy.
14. The method of claim 11 , wherein the B cell-related disorder is a plasma cell malignancy.
15. The method of claim 14 , wherein the plasma cell malignancy is multiple myeloma.
16. An isolated polynucleotide encoding the isolated polypeptide of claim 6 .
17. A vector comprising the isolated polynucleotide of claim 16 .
18. A cell comprising the vector of claim 17 .