Anti-bcma antibodies

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.

1 . An isolated polypeptide comprising an antigen binding fragment of an antibody that binds to the polypeptide of SEQ ID NO:9, wherein antigen binding fragment of the antibody 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 NOs: 4, 11, or 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 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 NOs: 4, 11, or 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 vector comprising the vector of  claim 17 .