Antigen binding proteins

Abstract

The present invention concerns antigen binding proteins and fragments thereof which specifically bind B Cell Maturation Antigen (BCMA), particularly human BCMA (hBCMA) and which inhibit the binding of BAFF and APRIL to the BCMA receptor. Further disclosed are pharmaceutical compositions, screening and medical treatment methods.

1 . An immunoconjugate comprising an antibody and a cytotoxic agent wherein said antibody comprises a heavy chain variable region set forth in SEQ. ID. NO:23 and a light chain variable region set forth in SEQ. ID. NO:31 and wherein said cytotoxic agent is selected from monomethylauristatin E (MMAE) and monomethylauristatin F (MMAF). 
     
     
         2 . The immunoconjugate of  claim 1  wherein the antibody is an IgG1 isotype. 
     
     
         3 . The immunoconjugate of  claim 1  wherein the antibody binds BCMA with an affinity of stronger than 150 pM. 
     
     
         4 . The immunoconjugate  claim 1  wherein the cytotoxic agent is covalently bound to said antibody. 
     
     
         5 . The immunoconjugate  claim 1  wherein the cytotoxic agent is bound to said antibody via a linker. 
     
     
         6 . The immunoconjugate of  claim 5  wherein said linker is a cleavable linker. 
     
     
         7 . The immunoconjugate of  claim 5  wherein said linker is a non-cleavable linker. 
     
     
         8 . The immunoconjugate of  claim 5  wherein the linker is selected from 6-maleimidocaproyl (MC), maleimidopropanoyl (MP), valine-citrulline (val-cit), alanine-phenylalanine (ala-phe), p-aminobenzyloxycarbonyl (PAB), N-Succinimidyl 4-(2-pyridylthio)pentanoate (SPP), N-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1 carboxylate (SMCC), and N-Succinimidyl (4-iodo-acetyl) aminobenzoate (SIAB). 
     
     
         9 . The immunoconjugate of  claim 1  wherein said immunoconjugate is engulfed by a tumor cell when contacted with a tumor cell. 
     
     
         10 . The immunoconjugate of  claim 1  wherein said antibody is afucosylated. 
     
     
         11 . A pharmaceutical composition comprising the immunoconjugate of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         12 . A method of treating a human patient afflicted with a B cell lymphoma comprising administering to said human a therapeutically affective amount of the immunoconjugate of  claim 1 . 
     
     
         13 . The method of  claim 12  wherein the B cell lymphoma is selected from Multiple Myeloma (MM) and Chronic Lymphocytic Leukaemia (CLL). 
     
     
         14 . An immunoconjugate comprising an antibody and a cytoxic agent wherein said antibody comprises the heavy chain amino acid sequence set forth in SEQ ID NO:55 and the light chain amino acid sequence set forth in SEQ ID NO:63 and the cytotoxic agent is monomethylauristatin E (MMAE), wherein said MMAE is linked to said antibody via a valine-citrulline (val-cit) linker. 
     
     
         15 . An immunoconjugate comprising an antibody and a cytoxic agent wherein said antibody comprises the heavy chain amino acid sequence set forth in SEQ ID NO:55 and the light chain amino acid sequence set forth in SEQ ID NO:63 and the cytotoxic agent is monomethylauristatin F (MMAF), wherein said MMAF is linked to said antibody via a 6-maleimidocaproyl (mc) linker.