The present invention provides novel Fibroblast Growth Factor-like (FGF-like) polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, antibodies and methods for producing FGF-like polypeptides. Also provided for are methods for the diagnosis and tr
The present invention provides novel Fibroblast Growth Factor-like (FGF-like) polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, antibodies and methods for producing FGF-like polypeptides. Also provided for are methods for the diagnosis and treatment of diseases associated with FGF-like polypeptides.
대표청구항▼
What is claimed is: 1. A polypeptide produced by a process comprising: (a) culturing a host cell containing a vector comprising a nucleic acid molecule having a nucleotide sequence: (i) as set forth in SEQ ID NO: 1; (ii) of the DNA insert in ATCC Deposit No. PTA-626; (iii) encoding the polypeptide
What is claimed is: 1. A polypeptide produced by a process comprising: (a) culturing a host cell containing a vector comprising a nucleic acid molecule having a nucleotide sequence: (i) as set forth in SEQ ID NO: 1; (ii) of the DNA insert in ATCC Deposit No. PTA-626; (iii) encoding the polypeptide of SEQ ID NO: 2; (iv) encoding the polypeptide of SEQ ID NO: 5; or (v) encoding the polypeptide of SEQ ID NO: 5 and an amino-terminal methionine; under conditions suitable to express the polypeptide; and optionally (b) isolating the polypeptide from the culture. 2. An isolated polypeptide comprising: (a) the amino acid sequence set forth in SEQ ID NO: 2; or (b) an amino acid sequence encoded by the DNA insert of ATCC Deposit No. PTA-626. 3. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 5, optionally further comprising an amino-terminal methionine. 4. An isolated polypeptide encoded by a nucleic acid molecule comprising a nucleotide sequence: (a) as set forth in SEQ ID NO: 1; (b) of the DNA insert in ATCC Deposit No. PTA-626; (c) encoding the polypeptide of SEQ ID NO: 2; (d) encoding the polypeptide of SEQ ID NO: 5; or (e) encoding the polypeptide of SEQ ID NO: 5 and an amino-terminal methionine. 5. A pharmaceutical composition comprising the polypeptide of any of claims 1, 2, 3 or 4 and a pharmaceutically acceptable formulation agent. 6. The pharmaceutical composition of claim 5, wherein the pharmaceutically acceptable formulation agent is a carrier, adjuvant, solubilizer, stabilizer, or anti-oxidant. 7. The pharmaceutical composition of claim 5, wherein the polypeptide comprises the mature amino acid sequence as set forth in SEQ ID NO: 5. 8. A fusion polypeptide comprising the polypeptide of any of claims 1, 2, 3, or 4 fused to a heterologous amino acid sequence. 9. The fusion polypeptide of claim 8, wherein the heterologous amino acid sequence is an IgG constant domain or fragment thereof. 10. The polypeptide of claim 1 wherein the host cell is a eukaryotic cell. 11. The polypeptide of claim 1 wherein the host cell is a prokaryotic cell. 12. The polypeptide of claim 9, wherein the IgG constant domain or fragment thereof is fused to the amino terminus of the polypeptide. 13. The polypeptide of claim 9, wherein the IgG constant domain or fragment thereof is fused to the carboxyl terminus of the polypeptide. 14. The polypeptide of claim 8, wherein the heterologous amino acid sequence is an IgG hinge, CH2, or CH3 region. 15. The polypeptide of claim 8, wherein the polypeptide is fused to a heterologous amino acid sequence via a linker. 16. The polypeptide of claim 15, wherein the linker is designed with a cleavage site to allow for cleavage of the polypeptide and the heterologous amino acid sequence. 17. The polypeptide of claim 1, 2, 3 or 4 that is chemically modified by linking the polypeptide to one or a plurality of polymers. 18. The polypeptide of claim 17, wherein at least one of the polymers is a water-soluble polymer. 19. The polypeptide of claim 18, wherein the water-soluble polymer is branched. 20. The polypeptide of claim 18, wherein the water-soluble polymer is unbranched. 21. The polypeptide of claim 18, wherein the water-soluble polymer is polyethylene glycol (PEG), monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, a propylene glycol homopolymer, a polypropylene oxide/ethylene oxide co-polymer, polyoxyethylated polyols, or polyvinyl alcohol. 22. The polypeptide of claim 21, wherein the water-soluble polymer is PEG. 23. The polypeptide of claim 22, wherein the polypeptide has a single PEG moiety at its amino terminus. 24. The polypeptide of claim 18, wherein the water-soluble polymer is a bifunctional PEG cross-linking molecule. 25. The polypeptide of claim 17, wherein the polypeptide is linked to more than one type of polymer. 26. The polypeptide of claim 25, wherein at least one of the polymers is a water-soluble polymer. 27. The polypeptide of claim 26, wherein the water-soluble polymer is branched. 28. The polypeptide of claim 26, wherein the water-soluble polymer is unbranched. 29. The polypeptide of claim 26, wherein the water-soluble polymer is polyethylene glycol (PEG), monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, a propylene glycol homopolymer, a polypropylene oxide/ethylene oxide co-polymer, polyoxyethylated polyols, or polyvinyl alcohol. 30. The polypeptide of claim 29, wherein the water-soluble polymer is PEG. 31. The polypeptide of claim 30, wherein the polypeptide has a single PEG moiety at its amino terminus. 32. The polypeptide of claim 29, wherein the water-soluble polymer is a bifunctional PEG cross-linking molecule. 33. A process for preparing a chemically modified FGF-21 polypeptide, comprising: (a) reacting a polypeptide comprising: (i) the amino acid sequence of SEQ ID NO: 2; (ii) the amino acid sequence of SEQ ID NO: 5; or (iii) the amino acid sequence of SEQ ID NO: 5 further comprising an amino-terminal methionine; with polyethylene glycol (PEG) under conditions whereby the polypeptide becomes attached to at least one PEG group; and (b) obtaining the reaction products. 34. A polypeptide produced by the process of claim 33.
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