ANTIGEN BINDING PROTEINS
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.