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 anti-BCMA antibody and a cytotoxic agent, wherein the cytotoxic agent is a maytansinoid.
2 . The immunoconjugate of claim 1 , wherein the maytansinoid is DM-1 or DM-4.
3 . The immunoconjugate of claim 1 , wherein the antibody is conjugated to the cytotoxic agent via a linker.
4 . The immunoconjugate of claim 3 , wherein the linker is selected from the group consisting of 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”).
5 . The immunoconjugate of claim 3 , wherein the linker is N-Succinimidyl 4-(N-maleimidomethyl) cyclohexane-1 carboxylate (“SMCC”).
6 . The immunoconjugate of claim 1 , wherein the antibody is humanized.
7 . The immunoconjugate of claim 1 , wherein the antibody is human.
8 . The immunoconjugate of claim 1 , wherein the antibody is a monoclonal antibody.
9 . The immunoconjugate of claim 1 , wherein the antibody is a chimeric antibody.
10 . The immunoconjugate of claim 1 , wherein the antibody is an IgG1 antibody.
11 . The immunoconjugate of claim 1 , wherein the antibody inhibits the binding of BAFF and/or APRIL to BCMA.
12 . The immunoconjugate of claim 1 , wherein the antibody binds to human BCMA and neutralizes the binding of the ligands BAFF and/or APRIL to BCMA in a cell neutralization assay wherein the antibody has an IC 50 of between about 1 nM and about 500 nM.
13 . The immunoconjugate of claim 1 , wherein the antibody does not bind to Taci or BAFF-R.
14 . The immunoconjugate of claim 1 , wherein the antibody binds to human BCMA with an affinity of 5 nM or less, 1000 pM or less, 500 pM or less, 400 pM or less, 300 pM or less, or 150 pm or less.
15 . A pharmaceutical composition comprising the immunoconjugate of claim 1 and a pharmaceutically acceptable carrier.
16 . A method of treating a human patient afflicted with a B cell mediated disease or disorder comprising administering to a patient a therapeutically effective amount of the immunoconjugate of claim 1 .
17 . The method of claim 16 , wherein the B-cell mediated disease or disorder is B-cell lymphoma, non-hodgkins lymphoma (NHL), Multiple myeloma (MM), Chronic Lymphocytic Leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma.
18 . The method of claim 16 , wherein the B cell related disorder or disease is multiple myeloma.