Sclerostin binding antibodies
Compositions and methods relating to epitopes of sclerostin protein, and sclerostin binding agents, such as antibodies capable of binding to sclerostin, are provided.
1. An IgG antibody that binds sclerostin of SEQ ID NO: 1 and comprises CDRH-1, CDR-H2, CDR-H3, CDR-L1 CDR-L2 and CDR-L3 wherein CDR-H1 is SEQ ID NO:245, CDR-H2 is SEQ ID NO:246, CDR-H3 is SEQ ID NO:247, CDR-L1 is SEQ ID NO:78, CDR-L2 is SEQ ID NO:79 and CDR-L3 is SEQ ID NO:80.
2. An antibody that binds sclerostin of SEQ ID NO: 1 and comprises a heavy chain comprising a polypeptide having the sequence provided in SEQ ID NO:145 or 392, and a light chain comprising a polypeptide having the sequence provided in SEQ ID NO: 141.
3. A pharmaceutical composition comprising an antibody according to claim 2 in combination with one or more of a pharmaceutically acceptable excipient, diluent or carrier.
4. A pharmaceutical composition according to claim 3 , additionally comprising other active ingredients.
5. A method of increasing at least one of bone formation, bone mineral content, bone mass, bone mineral density, or bone strength in a mammalian subject comprising administering to the mammalian subject an antibody comprising a heavy chain comprising CDRs of SEQ ID NOs: 245, 246 and 247 and a light chain comprising CDRs of SEQ ID NOs: 78, 79 and 80, wherein the antibody demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1×10 −7 M.
6. The method of claim 5 , wherein the heavy chain of the antibody comprises SEQ ID NO: 378 and the light chain of the antibody comprises SEQ ID NO: 376.
7. The method of claim 5 , wherein the heavy chain of the antibody comprises SEQ ID NO: 141 and the light chain of the antibody comprises SEQ ID NO: 145 or SEQ ID NO: 392.
8. The antibody of claim 2 , which is an IgG antibody.
9. The method of claim 5 , wherein the antibody is a chimeric antibody or a humanized antibody.
10. The method of claim 5 , wherein the antibody is an IgG antibody.
11. The method of claim 5 , wherein the antibody is a monoclonal antibody.
12. The method of claim 5 , wherein the antibody demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1×10 −8 M.
13. The method of claim 5 , wherein the antibody demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1×10 −9 M.
14. The method of claim 5 , wherein the subject is a postmenopausal woman.
15. A method of treating osteoporosis or osteopenia comprising administering to a mammalian subject in need thereof an IgG antibody comprising heavy chain CDRs of SEQ ID NOs: 245, 246 and 247 and light chain CDRs of SEQ ID NOs: 78, 79 and 80, wherein the antibody demonstrates a binding affinity for sclerostin of SEQ ID NO: 1 of less than or equal to 1×10 −7 M.
16. The method of claim 15 , wherein the subject is a postmenopausal woman.