FGF-21 mutants comprising polyethylene glycol and uses thereof
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/18
C07K-014/50
A61K-038/00
출원번호
US-0123205
(2009-10-08)
등록번호
US-9279013
(2016-03-08)
국제출원번호
PCT/US2009/060045
(2009-10-08)
§371/§102 date
20110407
(20110407)
국제공개번호
WO2010/042747
(2010-04-15)
발명자
/ 주소
Walker, Kenneth W.
Gegg, Jr., Colin V.
Hecht, Randy I.
Belouski, Edward J.
Li, Yue-Sheng
Michaels, Mark L.
Xu, Jing
Ellison, Murielle M.
출원인 / 주소
Amgen Inc.
인용정보
피인용 횟수 :
0인용 특허 :
75
초록▼
The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides comprising extended in vivos half-lives, pharmaceutical compositions comprising FGF21 mutant polypeptides having extended in vivos half lives, and methods for treating metabolic disorders usin
The invention provides nucleic acid molecules encoding FGF21 mutant polypeptides, FGF21 mutant polypeptides comprising extended in vivos half-lives, pharmaceutical compositions comprising FGF21 mutant polypeptides having extended in vivos half lives, and methods for treating metabolic disorders using such nucleic acids, polypeptides, or pharmaceutical compositions.
대표청구항▼
1. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide of SEQ ID NO: 4 having a lysine residue substitution at position 36 and at least one amino acid substitution that is: an arginine residue substitution at position 56, 59, 69, or 122; and wherein the isolated
1. An isolated nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide of SEQ ID NO: 4 having a lysine residue substitution at position 36 and at least one amino acid substitution that is: an arginine residue substitution at position 56, 59, 69, or 122; and wherein the isolated polypeptide comprises no more than five amino acid substitutions. 2. A vector comprising the nucleic acid molecule of claim 1. 3. A host cell comprising the vector of claim 2. 4. The host cell of claim 3 that is a eukaryotic cell. 5. The host cell of claim 3 that is a prokaryotic cell. 6. A process of producing a polypeptide encoded by the vector of claim 2 comprising culturing a host cell comprising the vector of claim 2 under suitable conditions to express the polypeptide, and optionally isolating the polypeptide. 7. A polypeptide produced by the process of claim 6. 8. The polypeptide of claim 7, further comprising a prolinc or glycinc residue added to the C-terminus of the polypeptide. 9. The isolated polypeptide of claim 7, wherein the polypeptide is covalently linked to one or more polymers. 10. The isolated polypeptide of claim 9, wherein the polypeptide is covalently linked to one polymer. 11. The isolated polypeptide of claim 10, wherein the polymer is a water-soluble polymer. 12. The isolated polypeptide of claim 11, wherein the water-soluble polymer is polyethylene glycol (PEG), monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, or polyvinyl alcohol. 13. The isolated polypeptide of claim 12, wherein the water-soluble polymer is PEG. 14. The isolated polypeptide of claim 9, wherein the polymer is a branched polymer. 15. The isolated polypeptide of claim 8, wherein the polypeptide has a PEG moiety covalently linked to its amino-terminus. 16. The isolated polypeptide of claim 8, wherein the polypeptide is covalently linked to two polymers. 17. The isolated polypeptide of claim 16, wherein one of the two polymers is a water-soluble polymer. 18. The isolated polypeptide of claim 17, wherein the water-soluble polymer is polyethylene glycol (PEG), monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, or polyvinyl alcohol. 19. The isolated polypeptide of claim 18, wherein the water-soluble polymer is PEG. 20. The isolated polypeptide of claim 16, wherein one of the polymers is branched. 21. The isolated polypeptide of claim 16, wherein both of the polymers are branched. 22. The isolated polypeptide of claim 8, wherein the polypeptide has a PEG moiety covalently linked to its amino-terminus. 23. A pharmaceutical composition comprising the isolated polypeptide of claim 8 and a pharmaceutically acceptable formulation agent. 24. The pharmaceutical composition of claim 23, wherein the pharmaceutically acceptable formulation agent is a carrier, adjuvant, solubilizer, stabilizer, or anti-oxidant. 25. A method for lowering blood glucose levels, lowering insulin levels, lowering triglyceride levels, lowering cholesterol levels, or reducing body weight comprising administering to a human in need thereof the pharmaceutical composition of claim 24. 26. The method of claim 25, wherein the human has diabetes. 27. The method of claim 25, wherein the human has obesity. 28. A composition comprising a first polypeptide comprising the amino acid sequence of SEQ ID NO: 4 having a lysine residue substitution at position 36 and having at least one amino acid substitution that is: an arginine residue substitution at position 56, 59, 69, or 122; and wherein the isolated polypeptide comprises no more than five amino acid substitutions, and wherein the isolated polypeptide is joined by a linker to a second polypeptide comprising the amino acid sequence of SEQ ID NO: 4 having a lysine residue substitution at position 36 and having at least one amino acid substitution that is an arginine residue substitution at position 56, 59, 69, or 122; and wherein the second polypeptide-comprises no more than five amino acid substitutions. 29. The polypeptide of claim 28, wherein the first, second or both polypeptides further comprise a proline or glycine residue added to the C-terminus of the polypeptide. 30. The composition of claim 28, wherein the linker is a peptide. 31. The composition of claim 28, wherein the linker is a water insoluble polymer. 32. The composition of claim 31, wherein the water-soluble polymer is polyethylene glycol (PEG), monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, or polyvinyl alcohol. 33. The composition of claim 32, wherein the water-soluble polymer is PEG. 34. The composition of claim 28, wherein the first, second or both polypeptides are further covalently linked to one polymer, in addition to the linker. 35. The composition of claim 34, wherein the polymer is a water-soluble polymer. 36. The composition of claim 35, wherein the water-soluble polymer is polyethylene glycol (PEG), monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, or polyvinyl alcohol. 37. The composition of claim 36, wherein the water-soluble polymer is PEG. 38. The composition of claim 31, wherein the polymer is branched. 39. The composition of claim 28, wherein the composition has a single PEG moiety covalently linked to its amino-terminus. 40. The composition of claim 28, wherein the composition is covalently linked to two polymers. 41. The composition of claim 40, wherein one if the two polymers is a water-soluble polymer. 42. The composition of claim 41, wherein the water-soluble polymer is polyethylene glycol (PEG), monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, or polyvinyl alcohol. 43. The composition of claim 42, wherein the water-soluble polymer is PEG. 44. The composition of claim 40, wherein both of the polymers are water soluble polymers. 45. The composition of claim 44, wherein the water-soluble polymers are independently polyethylene glycol (PEG), monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, or polyvinyl alcohol and combinations thereof. 46. The composition of claim 45, wherein both of the water soluble polymers are PEG. 47. The isolated polypeptide of claim 40, wherein one of the polymers is branched. 48. The isolated polypeptide of claim 40, wherein both of the polymers are branched. 49. A pharmaceutical composition comprising the composition of claim 28 and a pharmaceutically acceptable formulation agent. 50. The pharmaceutical composition of claim 49, wherein the pharmaceutically acceptable formulation agent is a carrier, adjuvant, solubilizer, stabilizer, or anti-oxidant. 51. A method for lowering blood glucose levels, lowering insulin levels, lowering triglyceride levels, lowering cholesterol levels, or reducing body weight comprising administering to a human in need thereof the pharmaceutical composition of claim 49. 52. The method of claim 51, wherein the human has diabetes. 53. The method of claim 51, wherein the human has obesity.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (75)
Bogin,Oren; Adar,Rivka; Yayon,Avner, Active variants of FGF with improved specificity.
Kim Jin-Seok (Salt Lake City UT) Maruyama Atsushi (Yokohama JPX) Akaike Toshihiro (Tokyo JPX) Kim Sung Wan (Salt Lake City UT), Cationic polymer and lipoprotein-containing system for gene delivery.
Keifer, Michael C.; Valenzuela, Pablo D. T.; Barr, Philip J., Compositions comprising polynucleotides encoding human fibroblast growth factor receptor and uses thereof.
Keifer Michael C. (Clayton CA) Valenzuela Pablo D. T. (Berkeley CA) Barr Philip J. (Oakland CA), Expression and use of human fibroblast growth factor receptor.
Bergonzoni Laura (Milan ITX) Mazue Guy (Milan ITX) Isacchi Antonella (Milan ITX) Roncucci Romeo (Milan ITX) Sarmientos Paolo (Milan ITX), Extracellular form of the human fibroblast growth factor receptor.
Imamura, Toru; Asada, Masahiro; Suzuki, Masashi, Heparin-binding protein modified with heparan sulfate sugar chains, process for producing the same and pharmaceutical compositions containing the same.
Queen Cary L. (Los Altos CA) Co Man Sung (Cupertino CA) Schneider William P. (Mountain View CA) Landolfi Nicholas F. (Milpitas CA) Coelingh Kathleen L. (San Francisco CA) Selick Harold E. (Belmont CA, Humanized immunoglobulins.
Aebischer Patrick (Providence RI) Galletti Pierre M. (Providence RI) Panol George (Warwick RI) Miracoli Luigi (Genoa ITX), Implantable delivery system for biological factors.
Aebischer Patrick (Providence RI) Winn Shelley R. (Providence RI) Galletti Pierre M. (Providence RI), In vivo delivery of neurotransmitters by implanted, encapsulated cells.
Sanford John C. (Geneva NY) Wolf Edward D. (Ithaca NY) Allen Nelson K. (Newfield NY), Method for transporting substances into living cells and tissues and apparatus therefor.
Aslam Muhammed (Rochester NY) Light William (Victor NY), Method of making a projection viewable transparency comprising an electrostatographic toner image.
Roninson Igor B. (818 S. Laflin St. Chicago IL 60607) Holzmayer Tatyana (1451 W. Flournoy St. ; Apt. 2E Chicago IL 60607) Choi Kyunghee (1121 Albion St. ; Apt. 806 Denver CO 80220), Methods and applications for efficient genetic suppressor elements.
Davis Frank F. (19 Farmingdale Rd. East Brunswick NJ 08816) Van Es Theodorus (313 Overbrook Rd. Piscataway NJ 08854) Palczuk Nicholas C. (45 W. Franklin St. Bound Brook NJ 08805), Non-immunogenic polypeptides.
Benjamin Howard ; Chai Ling ; Findeis Mark A. ; Goodwin William ; Hundal Arvind ; Israel David I. ; Kelley Michael ; Keough Martin P. ; Lu Kuanghui ; Natoli Farah ; Peticolas Alicia ; Signer Ethan R., Peptide compounds useful for modulating FGF receptor activity.
Surani Azim M. (Cambridge GB3) Neuberger Michael S. (Cambridge GB3) Bruggemann Marianne (Cambridge GB3), Production of antibodies from transgenic animals.
Vegeto Elisabetta (7707 Eads Ave. LaJolla CA 92037) McDonnell Donald P. (10382 Rue Riviere Verte San Diego CA 92131) O\Malley Bert W. (629 Ramblewood Houston TX 77079), Progesterone receptor having C. terminal hormone binding domain truncations.
Cabilly Shmuel (Monrovia CA) Heyneker Herbert L. (Burlingame CA) Holmes William E. (Pacifica CA) Riggs Arthur D. (La Verne CA) Wetzel Ronald B. (San Francisco CA), Recombinant immunoglobin preparations.
Bujard Hermann (Heidelberg DEX) Gossen Manfred (Heidelberg DEX) Salfeld Jochen G. (North Grafton MA) Voss Jeffrey W. (Framingham MA), Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.