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Truncated keratinocyte growth factor (KGF) having increased biological activity

Gospodarowicz, Denis J. ; Masiarz, Frank R.
2005
Online Patent

Titel:
Truncated keratinocyte growth factor (KGF) having increased biological activity
Autor/in / Beteiligte Person: Gospodarowicz, Denis J. ; Masiarz, Frank R.
Link:
Veröffentlichung: 2005
Medientyp: Patent
Sonstiges:
  • Nachgewiesen in: USPTO Patent Applications
  • Sprachen: English
  • Document Number: 20050090445
  • Publication Date: April 28, 2005
  • Appl. No: 10/998425
  • Application Filed: November 29, 2004
  • Claim: 1-23. (canceled)
  • Claim: 24. An isolated polypeptide, wherein said polypeptide is a fragment of mature, full-length, human KGF as depicted in FIG. 1 (amino acids 32-194 of SEQ ID NO:1) or an analog thereof, wherein said analog has the same number of amino acids as the fragment and has at least 80% sequence identity thereto and optionally further comprises a methionine residue at the N-terminus thereof, and further wherein said polypeptide exhibits an increase in bioactivity relative to said mature, full-length, human KGF as determined by the Balb/MK bioactivity assay.
  • Claim: 25. The polypeptide of claim 24, wherein said analog has at least 90% sequence identity to a fragment of the amino acid sequence of amino acids 1-163 of FIG. 1 (amino acids 32-194 of SEQ ID NO:1).
  • Claim: 26. The polypeptide of claim 24, wherein said analog has at least 95% sequence identity to a fragment of the amino acid sequence of amino acids 1-163 of FIG. 1 (amino acids 32-194 of SEQ ID NO:1).
  • Claim: 27. The polypeptide of claim 24, wherein said analog has at least 98% sequence identity to a fragment of the amino acid sequence of amino acids 1-163 of FIG. 1 (amino acids 32-194 of SEQ ID NO:1).
  • Claim: 28. A composition comprising the polypeptide of claim 24 and a pharmaceutically acceptable carrier.
  • Claim: 29. An isolated polypeptide, wherein said polypeptide is an analog of KGFdes1-23 or a fragment thereof, wherein said analog has at least 80% sequence identity to the contiguous amino acid sequence of amino acids 24-163 of FIG. 1 (amino acids 55-194 of SEQ ID NO:1) and optionally further comprises a methionine residue at the N-terminus thereof, and further wherein said polypeptide exhibits an increase in bioactivity relative to mature, full-length, human KGF as depicted in FIG. 1 (amino acids 32-194 of SEQ ID NO:1) as determined by the Balb/MK bioactivity assay.
  • Claim: 30. The polypeptide of claim 29, wherein said polypeptide has at least 90% sequence identity to amino acids 24-163 of FIG. 1 (amino acids 55-194 of SEQ ID NO:1).
  • Claim: 31. The polypeptide of claim 29, wherein said polypeptide has at least 95% sequence identity to amino acids 24-163 of FIG. 1 (amino acids 55-194 of SEQ ID NO:1).
  • Claim: 32. A composition comprising the polypeptide of claim 29 and a pharmaceutically acceptable carrier.
  • Claim: 33. An isolated polypeptide, wherein said polypeptide is a fragment of mature, full-length, human KGF having an amino acid sequence comprising at least amino acids 24-163 of FIG. 1 (amino acids 55-194 of SEQ ID NO:1) or an analog thereof, wherein said analog has the same number of amino acids as the fragment and has at least 80% sequence identity thereto and optionally further comprises a methionine residue at the N-terminus thereof, and further wherein said polypeptide exhibits an increase in bioactivity relative to mature, said full-length, human KGF as determined by the Balb/MK bioactivity assay and specifically stimulates epithelial cell proliferation.
  • Claim: 34. The polypeptide of claim 33, wherein said increase in bioactivity is at least about a 2-fold increase in bioactivity.
  • Claim: 35. The polypeptide of claim 33, wherein said increase in bioactivity is at least about a 2-fold to about a 10-fold increase in bioactivity.
  • Claim: 36. The polypeptide of claim 33, wherein said increase in bioactivity is at least about a 7-fold to about a 10-fold increase in bioactivity.
  • Claim: 37. The polypeptide of claim 33, wherein said increase in bioactivity is about a 10-fold increase in bioactivity.
  • Claim: 38. The polypeptide of claim 33, wherein said analog has at least 90% sequence identity to said fragment.
  • Claim: 39. The polypeptide of claim 33, wherein said analog has at least 95% sequence identity to said fragment.
  • Claim: 40. A composition comprising the polypeptide of claim 33 and a pharmaceutically acceptable carrier.
  • Claim: 41. An isolated polypeptide, wherein said polypeptide is (a) a fragment of mature, full-length, human KGF as depicted in FIG. 1 (amino acids 32-194 of SEQ ID NO:1), wherein the amino acid sequence of said fragment has an N-terminus at a position between amino acid 9 and amino acid 26, inclusive, and extends to amino acid 163, of mature, full-length, human KGF, numbered relative to FIG. 1, or (b) an analog of the fragment of (a) that has the same number of amino acids as the fragment and has at least 80% sequence identity thereto and optionally further comprises a methionine residue at the N-terminus thereof, and further wherein said polypeptide exhibits an increase in bioactivity relative to said mature, full-length, human KGF as determined by the Balb/MK bioactivity assay and specifically stimulates epithelial cell proliferation.
  • Claim: 42. The polypeptide of claim 41, wherein said increase in bioactivity is at least about a 2-fold increase in bioactivity.
  • Claim: 43. The polypeptide of claim 41, wherein said increase in bioactivity is about 2-fold to about a 10-fold increase in bioactivity.
  • Claim: 44. The polypeptide of claim 41, wherein said increase in bioactivity is about a 7-fold to about a 10-fold increase in bioactivity.
  • Claim: 45. The polypeptide of claim 41, wherein said increase in bioactivity is about a 10-fold increase in bioactivity.
  • Claim: 46. The polypeptide of claim 41, wherein said analog has at least 90% sequence identity to said fragment.
  • Claim: 47. The polypeptide of claim 41, wherein said analog has at least 95% sequence identity to said fragment.
  • Claim: 48. The polypeptide of claim 41, wherein said polypeptide is a fragment of said mature, full-length, human KGF, wherein the amino acid sequence of said fragment has an N-terminus at a position between amino acid 9 and amino acid 26, inclusive, and extends to amino acid 163, of mature, full-length, human KGF, numbered relative to FIG. 1.
  • Claim: 49. A composition comprising the polypeptide of claim 41 and a pharmaceutically acceptable carrier.
  • Claim: 50. A method of treating a gastrointestinal disorder comprising administering the composition of claim 28 to a subject in need thereof.
  • Claim: 51. A method of treating a gastrointestinal disorder comprising administering the composition of claim 32 to a subject in need thereof.
  • Claim: 52. A method of treating a gastrointestinal disorder comprising administering the composition of claim 40 to a subject in need thereof.
  • Claim: 53. A method of treating a gastrointestinal disorder comprising administering the composition of claim 49 to a subject in need thereof.
  • Claim: 54. A method for wound healing comprising administering the composition of claim 28 to a subject in need thereof.
  • Claim: 55. A method for wound healing comprising administering the composition of claim 32 to a subject in need thereof.
  • Claim: 56. A method for wound healing comprising administering the composition of claim 40 to a subject in need thereof.
  • Claim: 57. A method for wound healing comprising administering the composition of claim 49 to a subject in need thereof.
  • Claim: 58. An antibody selective for the polypeptide of claim 24.
  • Claim: 59. An antibody selective for the polypeptide of claim 29.
  • Claim: 60. An antibody selective for the polypeptide of claim 33.
  • Claim: 61. An antibody selective for the polypeptide of claim 41.
  • Claim: 62. An isolated polynucleotide comprising a coding sequence encoding the polypeptide of claim 24.
  • Claim: 63. An isolated polynucleotide comprising a coding sequence encoding the polypeptide of claim 29.
  • Claim: 64. An isolated polynucleotide comprising a coding sequence encoding the polypeptide of claim 33.
  • Claim: 65. An isolated polynucleotide comprising a coding sequence encoding the polypeptide of claim 41.
  • Claim: 66. A non-human host cell that expresses a polypeptide according to claim 24.
  • Claim: 67. A non-human host cell that expresses a polypeptide according to claim 29.
  • Claim: 68. A non-human host cell that expresses a polypeptide according to claim 33.
  • Claim: 69. A non-human host cell that expresses a polypeptide according to claim 41.
  • Claim: 70. The host cell of claim 66, wherein the host cell is a bacterial cell.
  • Claim: 71. The host cell of claim 67, wherein the host cell is a bacterial cell.
  • Claim: 72. The host cell of claim 68, wherein the host cell is a bacterial cell.
  • Claim: 73. The host cell of claim 69, wherein the host cell is a bacterial cell.
  • Claim: 74. The host cell of claim 70, wherein the host cell is E. coli.
  • Claim: 75. The host cell of claim 71, wherein the host cell is E. coli.
  • Claim: 76. The host cell of claim 72, wherein the host cell is E. coli.
  • Claim: 77. The host cell of claim 73, wherein the host cell is E. coli.
  • Claim: 78. A method of producing a recombinant polypeptide comprising culturing the host cell of claim 66 under conditions whereby the polypeptide is expressed.
  • Claim: 79. A method of producing a recombinant polypeptide comprising culturing the host cell of claim 67 under conditions whereby the polypeptide is expressed.
  • Claim: 80. A method of producing a recombinant polypeptide comprising culturing the host cell of claim 68 under conditions whereby the polypeptide is expressed.
  • Claim: 81. A method of producing a recombinant polypeptide comprising culturing the host cell of claim 69 under conditions whereby the polypeptide is expressed.
  • Current U.S. Class: 514012/000

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