Crispr/cas-related methods and compositions for knocking out c5
US-2024415980-A1 · Dec 19, 2024 · US
US9296812B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9296812-B2 |
| Application number | US-201213691344-A |
| Country | US |
| Kind code | B2 |
| Filing date | Nov 30, 2012 |
| Priority date | May 3, 2005 |
| Publication date | Mar 29, 2016 |
| Grant date | Mar 29, 2016 |
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Compositions and methods relating to epitopes of sclerostin protein, and sclerostin binding agents, such as antibodies capable of binding to sclerostin, are provided.
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What is claimed is: 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.
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