| 摘要 |
A method of treating an individual (i) having abnormal bone; or (ii) afflicted with a disease or disorder related to normal or abnormal FGF receptors or a skeletal disorder; or (iii) having dysplasic bone. The method includes administering to the individual a pharmaceutical composition comprising a therapeutically effective amount of a fibroblast growth factor 9 (FGF-9) variant comprising at least one amino acid substitution in the beta 8-beta 9 loop, wherein said FGF-9 variant incorporates one of the amino acid sequences set forth in SEQ ID NO: 11, 13, 14, 15, 16 or 17. |
| 主权项 |
1. A method of treating an individual that (i) has abnormal bone; or (ii) is afflicted with a disease or disorder related to normal or abnormal FGF receptors or a skeletal disorder; or (iii) has dysplasic bone, which method comprises administering to the individual a pharmaceutical composition comprising a therapeutically effective amount of a fibroblast growth factor 9 (FGF-9) variant comprising at least one amino acid substitution in the beta 8-beta 9 loop, wherein the FGF-9 variant is an antagonist; wherein the FGF-9 variant reduces proliferation of target cells having at least one FGF receptor subtype compared to the corresponding wild type FGF-9; wherein the FGF-9 variant has enhanced receptor specificity for the at least one receptor subtype compared to the corresponding wild type FGF-9 by decreasing the biological activity mediated by at least one receptor subtype while retaining the activity mediated through another receptor subtype; wherein the FGF-9 variant further comprises a truncation at the N-terminus, or at the C-terminus, or at both termini; and wherein the FGF-9 variant comprises an amino acid sequence selected from one of the sequences forth in SEQ ID NO: 11, 13, 14, 15, 16 and 17. |
