Antagonists
The invention relates to Bone Morphogenetic Protein 6 (BMP6) antagonists, such as antibodies and fragments, as well as methods, uses and combinations.
1 . An antibody or antigen binding fragment thereof that specifically binds to Bone Morphogenetic Protein 6 (BMP6), wherein:
(a) (i) the antibody or antigen binding fragment thereof comprises a VH domain comprising heavy-chain complementarity determining region (CDR) sequences of SEQ ID NO: 111 (CDRH1), SEQ ID NO: 112 (CDRH2), and SEQ ID NO: 113 (CDRH3); and
(ii) the antibody or antigen binding fragment thereof comprises a VL domain comprising light-chain CDR sequences of SEQ ID NO: 120 (CDRL1), SEQ ID NO: 121 (CDRL2), and SEQ ID NO: 122 (CDRL3); or
(b) (i) the antibody or antigen binding fragment thereof comprises a VH domain comprising heavy-chain CDR sequences of SEQ ID NO: 291 (CDRH1), SEQ ID NO: 292 (CDRH2), and SEQ ID NO: 293 (CDRH3); and
(ii) the antibody or antigen binding fragment thereof comprises a VL domain comprising light-chain CDR sequences of SEQ ID NO: 300 (CDRL1), SEQ ID NO: 301 (CDRL2), and SEQ ID NO: 302 (CDRL3).
2 . The antibody or antigen binding fragment thereof according to claim 1 , wherein the VH domain is encoded by a nucleotide sequence that is derived from the recombination of a human VH gene segment, DH gene segment and JH gene segment, wherein:
(a) the VH gene segment is IGHV3-11;
(b) the DH gene segment is IGHD6-19; and/or
(c) the JH gene segment is IGHJ4.
3 . The antibody or antigen binding fragment thereof according to claim 1 ,
wherein the antibody or antigen binding fragment thereof comprises CDR sequences of SEQ ID NOs: 111, 112, 113, 120, 121, and 122,
wherein the VH domain comprises SEQ ID NO: 114 and the VL domain comprises SEQ ID NO: 123.
4 . The antibody or antigen binding fragment thereof according to claim 1 ,
wherein the antibody or antigen binding fragment thereof comprises CDR sequences of SEQ ID NOs: 111, 112, 113, 120, 121, and 122, and
wherein the VH domain comprises SEQ ID NO: 114 or an amino acid sequence that is at least 85% identical thereto.
5 . The antibody or antigen binding fragment thereof according to claim 1 , comprising first and second copies of said VH domain, and/or first and second copies of said VL domain.
6 . The antibody or antigen binding fragment thereof of claim 1 ,
wherein the VL domain is encoded by a nucleotide sequence that is derived from the recombination of a human VL gene segment and JL gene segment, wherein
(a) the VL gene segment is IGKV3-20; and/or
(b) the JL gene segment is IGKJ1.
7 . The antibody or antigen binding fragment thereof according to claim 1 ,
wherein the antibody or antigen binding fragment thereof comprises CDR sequences of SEQ ID NOs: 111, 112, 113, 120, 121, and 122, and
comprises a VL domain comprising SEQ ID NO: 123, or an amino acid sequence that is at least 85% identical thereto.
8 . The antibody or antigen binding fragment thereof according to claim 1 , wherein the antibody or antigen binding fragment thereof comprises CDR sequences of SEQ ID NOs: 111, 112, 113, 120, 121, and 122, and comprises:
(i) a heavy chain sequence comprising SEQ ID NO: 116 or an amino acid sequence that is at least 85% identical thereto; and/or
(ii) a light chain sequence comprising SEQ ID NO: 125 or an amino acid that is at least 85% identical thereto.
9 . The antibody or antigen binding fragment thereof according to claim 1 , wherein the antibody or antigen binding fragment thereof specifically binds to
(i) human BMP6 comprising SEQ ID NO: 562;
(ii) a cynomolgus BMP6 comprising SEQ ID NO: 564; and/or
(iii) a rat BMP6 comprising SEQ ID NO: 563.
10 . The antibody or antigen binding fragment thereof according to claim 1 , wherein the antibody or antigen binding fragment thereof comprise a heavy chain and/or a light chain comprising a human constant region.
11 . The antibody or antigen binding fragment thereof according to claim 10 , wherein the human constant region is an IgG4-PE constant region.
12 . The antibody or antigen binding fragment thereof according to claim 1 , further comprising an antigen-binding site that specifically binds another target antigen.
13 . A method of treating or preventing a BMP6-mediated disease or condition in a subject, the method comprising administering to said subject a therapeutically effective amount of the antibody or antigen binding fragment thereof of claim 1 , wherein the BMP6-mediated disease or condition is thereby treated or prevented.
14 . The method according to claim 13 , wherein the BMP6-mediated disease or condition is anaemia.
15 . A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable excipient, diluent, or carrier.
16 . A kit comprising the pharmaceutical composition according to claim 15 and a label or instructions for use to treat and/or prevent a BMP6-mediated disease or condition in a human.
17 . A nucleic acid that encodes the VH domain and/or the VL domain of the antibody or antigen binding fragment thereof of claim 1 .
18 . A vector comprising the nucleic acid of claim 17 .
19 . A host cell comprising the nucleic acid of claim 17 .
20 . The antibody or antigen binding fragment thereof according to claim 1 , wherein the antibody or antigen binding fragment thereof comprises CDR sequences of SEQ ID NOs: 291, 292, 293, 300, 301, and 302, wherein the VH domain comprises SEQ ID NO: 294 and the VL domain comprises SEQ ID NO: 303.
21 . The antibody or antigen binding fragment thereof according to claim 1 , wherein the antibody or antigen binding fragment thereof comprises CDR sequences of SEQ ID NOs: 291, 292, 293, 300, 301, and 302, wherein the VH domain comprises SEQ ID NO: 294 or an amino acid sequence that is at least 85% identical thereto.
22 . The antibody or antigen binding fragment thereof according to claim 1 , wherein the antibody or antigen binding fragment thereof comprises CDR sequences of SEQ ID NOs: 291, 292, 293, 300, 301, and 302, and comprises a VL domain comprising SEQ ID NO: 303, or an amino acid sequence that is at least 85% identical thereto.
23 . The antibody or antigen binding fragment thereof according to claim 1 , wherein the antibody or antigen binding fragment thereof comprises CDR sequences of SEQ ID NOs: 291, 292, 293, 300, 301, and 302, and comprises:
(i) a heavy chain sequence comprising SEQ ID NO: 296 or an amino acid sequence that is at least 85% identical thereto; and/or
(ii) a light chain sequence comprising SEQ ID NO: 305 or an amino acid that is at least 85% identical thereto.