Active variants of FGF with improved specificity
First Claim
1. An active FGF-9 variant having at least one mutation in the beta 8 beta 9 loop of the core structure, wherein said FGF-9 variant has enhanced specificity for 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 at least one substitution is replacement of tryptophan at position 144 of FGF-9 or asparagine at position 143 of FGF-9.
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Abstract
The present invention provides active fibroblast growth factor variants demonstrating enhanced receptor subtype specificity. The preferred novel variants retain binding to FGF Receptor Type 3 (FGFR3) triggering intracellular downstream mechanisms leading to activation of a biological response. Methods of utilizing preferred FGF mutants in preparation of medicaments for the treatment of malignancies and skeletal disorders including osteoporosis and enhancing fracture healing and wound healing processes are provided.
113 Citations
22 Claims
- 1. An active FGF-9 variant having at least one mutation in the beta 8 beta 9 loop of the core structure, wherein said FGF-9 variant has enhanced specificity for 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 at least one substitution is replacement of tryptophan at position 144 of FGF-9 or asparagine at position 143 of FGF-9.
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19. An active FGF-9 variant wherein said variant is selected from the polypeptides having the amino acid sequence of SEQ ID NO:
- 5, SEQ ID NO;
6 or SEQ ID NO;
7. - View Dependent Claims (20, 21, 22)
- 5, SEQ ID NO;
Specification