ANTIBODIES SPECIFIC FOR SCLEROSTIN AND METHODS FOR INCREASING BONE MINERALIZATION

摘要

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.

主权项

1. An isolated antibody, or an antigen-binding fragment thereof, that binds specifically to a SOST polypeptide, said SOST polypeptide comprising an amino acid sequence set forth in SEQ ID NO:1, 20, 58, 60, 62, or 68 wherein the antibody competitively inhibits binding of the SOST 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 selected from the group consisting of GenBank Acc. Nos. NM—004329 (SEQ ID NO:71); D89675 (SEQ ID NO:72); NM—001203 (SEQ ID NO:73); 575359 (SEQ ID NO:74); NM—030849 (SEQ ID NO:75); D38082 (SEQ ID NO:76); NP—001194 (SEQ ID NO:77); BAA19765 (SEQ ID NO:78); and AAB33865 (SEQ ID NO:79), 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 selected from the group consisting of GenBank Acc. NOs. U25110 (SEQ ID NO:80); NM—033346 (SEQ ID NO:81); Z48923 (SEQ ID NO:83); CAA88759 (SEQ ID NO:84); and NM—001204 (SEQ ID NO:82).