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AssigneeCelltech R&D Limited
InventorsMary Brunkow, David Galas, Brian Kovacevich, John Mulligan, Bryan Paeper, Jeffrey Ness, David Winkler
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A novel class or family of TGF-β binding proteins is disclosed. Also disclosed are assays for selecting molecules for increasing bone mineralization and methods for utilizing such molecules. In particular, compositions and methods relating to antibodies that specifically bind to TGF-beta binding proteins are provided. These methods and compositions relate to altering bone mineral density by interfering with the interaction between a TGF-beta binding protein sclerostin and a TGF-beta superfamily member, particularly a bone morphogenic protein. Increasing bone mineral density has uses in diseases and conditions in which low bone mineral density typifies the condition, such as osteopenia, osteoporosis, and bone fractures.
An antibody, or an antigen-binding fragment thereof, that binds specifically to a sclerostin polypeptide, said sclerostin polypeptide comprising an amino acid sequence set forth in SEQ ID NO:2, wherein the antibody competitively inhibits binding of the sclerostin polypeptide to at least one of (i) a bone morphogenic protein (BMP) Type I Receptor binding site and (ii) a BMP Type II Receptor binding site, wherein the BMP Type I Receptor binding site is capable of binding to a BMP Type I Receptor polypeptide comprising an amino acid sequence set forth in a sequence of and wherein the BMP Type II Receptor binding site is capable of binding to a BMP Type II Receptor polypeptide comprising the amino acid sequence set forth in a sequence SEQ ID NO:114.
An antibody, or an antigen-binding fragment thereof, that binds specifically to a sclerostin polypeptide and that impairs formation of a sclerostin homodimer, wherein the sclerostin polypeptide comprises an amino acid sequence set forth in SEQ ID NO:
14-20. (canceled)
Dependencies are inferred from the claim text.