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

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.

What is claimed is: 
     
         1 . A humanized antibody the specifically binds to the human BCMA protein, the antibody comprising a mature heavy chain variable region having at least 90% sequence identity to hSG16.17 VH3 (SEQ ID NO: 13) and a mature light chain variable region having at least 90% sequence identity to hSG16.17 VK2 (SEQ ID NO: 19). 
     
     
         2 . The antibody of  claim 1 , comprising a mature heavy chain variable region having at least 95% sequence identity to hSG16.17 VH3 (SEQ ID NO: 13) and a mature light chain variable region having at least 95% sequence identity to hSG16.17 VK2 (SEQ ID NO: 19). 
     
     
         3 . The antibody of  claim 1 , comprising the three Kabat CDRs (SEQ ID NOs: 60-62) of hSG16.17 VH3 (SEQ ID NO: 13) and three Kabat CDRs (SEQ ID NOs: 90-92) of hSG16.17 VK2 (SEQ ID NO: 19) provided that position H58 can be occupied by N or K, position H60 can be occupied by A or N, position H61 can be occupied by Q or E, position H62 can be occupied by K or N, position H64 can be occupied by Q or K, position H65 can be occupied by G or T, position L24 can be occupied by R or L, and position L53 can be occupied by S or R. 
     
     
         4 . The antibody of  claim 1  comprising the three Kabat CDRs (SEQ ID NOs: 60-62) of hSG16.17 VH3 (SEQ ID NO: 13) and three Kabat CDRs (SEQ ID NOs: 90-92) of hSG16.17 VK2 (SEQ ID NO: 19). 
     
     
         5 . The antibody of  claim 1 , wherein positions H20, H48, H69, H71, H73, H76, H80, H88, H91 and H93 are occupied by L, I, M, A, K, N, V, A, F, and T respectively, and positions L46, L48 and L87 are occupied by V, V and F respectively. 
     
     
         6 . The antibody of  claim 1 , wherein the mature heavy chain variable has the sequence of hSG16.17 VH3 (SEQ ID NO: 13) and the mature light chain variable region has the sequence of hSG16.17 VK2 (SEQ ID NO: 19). 
     
     
         7 . The antibody 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. 
     
     
         8 . The antibody of  claim 6 , 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. 
     
     
         9 . A pharmaceutical composition comprising an antibody of  claim 8  and a pharmaceutically acceptable carrier. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein less than about 10% of the antibodies have core fucosylation by fucose or a fucose analogue. 
     
     
         11 . The pharmaceutical composition of  claim 9 , wherein less than about 5% of the antibodies have core fucosylation by fucose or a fucose analogue. 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein about 2% of the antibodies have core fucosylation by fucose or a fucose analogue. 
     
     
         13 . The antibody of  claim 1 , wherein the antibody is conjugated to a cytotoxic agent. 
     
     
         14 . The antibody of  claim 13 , wherein the cytotoxic agent is conjugated to the antibody via an enzyme cleavable linker. 
     
     
         15 . A humanized antibody the specifically binds to the human BCMA protein, the antibody comprising a mature heavy chain variable region of hSG16.17 VH3 (SEQ ID NO: 13) and a mature light chain variable region of hSG16.17 VK2 (SEQ ID NO: 19). 
     
     
         16 . The antibody 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 . A pharmaceutical composition comprising an antibody of  claim 16  and a pharmaceutically acceptable carrier. 
     
     
         18 . The pharmaceutical composition of  claim 17 , wherein less than about 10% of the antibodies have core fucosylation by fucose or a fucose analogue. 
     
     
         19 . The pharmaceutical composition of  claim 17 , wherein less than about 5% of the antibodies have core fucosylation by fucose or a fucose analogue. 
     
     
         20 . The pharmaceutical composition of  claim 17 , wherein less than about 2% of the antibodies have core fucosylation by fucose or a fucose analogue.