Claims
- 1. A method of promoting blood flow within the vasculature of a mammal comprising administering to said mammal a therapeutically effective amount of an adipocyte complement related protein; in a pharmaceutically acceptable vehicle; whereby said adipocyte complement related protein reduces thrombogenic and complement activity within said vasculature.
- 2. A method according to claim 1 wherein said adipocyte complement related protein comprises a polypeptide comprising a sequence of amino acid residues that is at least 75% identical in amino acid sequence to residues 26-281 of SEQ ID NO:2, wherein said sequence comprises:
Gly-Xaa-Xaa or Gly-Xaa-Pro repeats forming a collagen domain, wherein Xaa is any amino acid, and a carboxy-terminal globular portion.
- 3. A method according to claim 2, wherein said polypeptide comprises a sequence of amino acid residues that is at least 90% identical in amino acid sequence to residues 22-281 of SEQ ID NO:2.
- 4. A method according to claim 2, wherein said polypeptide comprises an amino acid sequence that is at least 90% identical in amino acid sequence to residues 26-281 of SEQ ID NO:2.
- 5. A method according to claim 3, wherein any differences between said polypeptide and SEQ ID NO:2 are due to conservative amino acid substitutions.
- 6. A method according to claim 3, wherein said collagen domain consists of 13 Gly-Xaa-Xaa repeats and 1 Gly-Xaa-Pro repeat.
- 7. A method according to claim 3, wherein said globular domain consists of ten beta sheets.
- 8. A method according to claim 7, wherein said beta sheets are associated with amino acid residues corresponding to 147-151, 170-172, 178-181, 191-203, 207-214, 219-225, 227-239, 244-250, and 269-274 of SEQ ID NO:2.
- 9. A method according to claim 2, wherein said polypeptide comprises residues 1-281 of SEQ ID NO:2 or residues 1-281 of SEQ ID NO:44.
- 10. A method according to claim 2, wherein said polypeptide is complexed to a second polypeptide to form a oligomer.
- 11. A method according to claim 10, wherein said polypeptides are complexed by intermolecular disulfide bonds.
- 12. A method according to claim 11, wherein said oligomer is a trimer.
- 13. A method according to claim 11 wherein said oligomer is a hexamer.
- 14. A method according to claim 11 wherein said oligomer is an 18mer.
- 15. A method according to claim 1, wherein said polypeptide reduces thrombogenic and complement activity by inhibition of the complement pathway and inhibition collagen-mediated platelet adhesion, activation or aggregation.
- 16. A method according to claim 1, wherein said polypeptide reduces thrombogenic and complement activity by inhibition of the complement pathway.
- 17. A method according to claim 1, wherein said polypeptide reduces thrombogenic and complement activity by inhibition of collagen-mediated platelet adhesion, activation or accretion.
- 18. A method according to claim 1, wherein said polypeptide reduces thrombogenic and complement activity by inhibition of collagen-mediated platelet aggregation.
- 16. A method according to claim 1, wherein said polypeptide is administered prior to, during or following an acute vascular injury in said mammal.
- 17. A method according to claim 16, wherein said injury is due to vascular reconstruction.
- 18. A method according to claim 17, wherein said vascular reconstruction comprises angioplasty, coronary artery bypass graft, endarterectomy, microvascular repair or anastomosis of a vascular graft.
- 19. A method according to claim 18, wherein said injury is due to trauma, stroke or aneurysm.
- 20. A method of pacifying damaged collagenous tissues within a mammal comprising administering to said mammal a therapeutically effective amount of an adipocyte complement related protein; whereby said protein renders the damaged collagenous tissue inert towards complement activation, thrombotic activity or immune activation
- 21. A method according to claim 20, wherein said adipocyte complement related protein comprises a polypeptide comprising a sequence of amino acid residues that is at least 75% identical in amino acid sequence to residues 26-281 of SEQ ID NO:2, wherein said sequence comprises:
Gly-Xaa-Xaa or Gly-Xaa-Pro repeats forming a collagen domain, wherein Xaa is any amino acid, and a carboxy-terminal globular portion.
- 22. A method according to claim 21, wherein said polypeptide comprises a sequence of amino acid residues that is at least 90% identical in amino acid sequence to residues 22-281 of SEQ ID NO:2.
- 23. A method according to claim 21, wherein said polypeptide comprises an amino acid sequence that is at least 90% identical in amino acid sequence to residues 26-281 of SEQ ID NO:2.
- 24. A method according to claim 22, wherein any differences between said polypeptide and SEQ ID NO:2 are due to conservative amino acid substitutions.
- 25. A method according to claim 22, wherein said collagen domain consists of 13 Gly-Xaa-Xaa repeats and 1 Gly-Xaa-Pro repeat.
- 26. A method according to claim 22, wherein said globular domain consists of ten beta sheets.
- 27. A method according to claim 26, wherein said beta sheets are associated with amino acid residues corresponding to 147-151, 170-172, 178-181, 191-203, 207-214, 219-225, 227-239, 244-250, and 269-274 of SEQ ID NO:2.
- 28. A method according to claim 22, wherein said polypeptide comprises residues 1-281 of SEQ ID NO:2 or residues 1-281 of SEQ ID NO:44.
- 29. A method according to claim 22, wherein said polypeptide is complexed to a second polypeptide to form a oligomer.
- 30. A method according to claim 29, wherein said polypeptides are complexed by intermolecular disulfide bonds.
- 31. A method according to claim 29, wherein said oligomer is a trimer.
- 32. A method according to claim 29 wherein said oligomer is a hexamer.
- 33. A method according to claim 29 wherein said oligomer is an 18mer.
- 34. A method according to claim 20, wherein said damaged collagenous tissues are due to injury associated with ischemia and reperfusion.
- 35. A method according the claim 34, wherein said injury comprises trauma injury ischemia, intestinal strangulation, or injury associated with pre- and post-establishment of blood flow.
- 36. A method according to claim 20, wherein said polypeptide is administered to a mammal suffering from cardiopulmonary bypass ischemia and recesitation, myocardial infarction, or post-trauma vasospasm.
- 37. A method according to claim 36, wherein said post-trauma vasospasm comprises stroke, percutanious transluminal angioplasty, endarterectomy, accidental vascular trauma or surgical-induced vascular trauma.
- 38. A method of pacifying the surface of a prostatic biomaterial for use in association with a mammal comprising administering to said mammal a therapeutically effective amount of an adipocyte complement related protein;
whereby said polypeptide renders the surface of said prosthetic biomaterial inert towards complement activation, thrombotic activity or immune activation.
- 39. A method according to claim 38, wherein said adipocyte complement related protein comprises a polypeptide comprising a sequence of amino acid residues that is at least 75% identical in amino acid sequence to residues 26-281 of SEQ ID NO:2, wherein said sequence comprises:
Gly-Xaa-Xaa or Gly-Xaa-Pro repeats forming a collagen domain, wherein Xaa is any amino acid, and a carboxy-terminal globular portion.
- 40. A method according to claim 39, wherein said polypeptide comprises a sequence of amino acid residues that is at least 90% identical in amino acid sequence to residues 22-281 of SEQ ID NO:2.
- 41. A method according to claim 39, wherein said polypeptide comprises an amino acid sequence that is at least 90% identical in amino acid sequence to residues 26-281 of SEQ ID NO:2.
- 42. A method according to claim 40, wherein any differences between said polypeptide and SEQ ID NO:2 are due to conservative amino acid substitutions.
- 43. A method according to claim 40, wherein said collagen domain consists of 13 Gly-Xaa-Xaa repeats and 1 Gly-Xaa-Pro repeat.
- 44. A method according to claim 40, wherein said globular domain consists of ten beta sheets.
- 45. A method according to claim 44, wherein said beta sheets are associated with amino acid residues corresponding to 147-151, 170-172, 178-181, 191-203, 207-214, 219-225, 227-239, 244-250, and 269-274 of SEQ ID NO:2.
- 46. A method according to claim 40, wherein said polypeptide comprises residues 1-281 of SEQ ID NO:2 or residues 1-281 of SEQ ID NO:44.
- 47. A method according to claim 39, wherein said polypeptide is complexed to a second polypeptide to form a oligomer.
- 48. A method according to claim 47, wherein said polypeptides are complexed by intermolecular disulfide bonds.
- 49. A method according to claim 47, wherein said oligomer is a trimer.
- 50. A method according to claim 47 wherein said oligomer is a hexamer.
- 51. A method according to claim 47 wherein said oligomer is an 18mer.
- 52. A method of pacifying the surface of a prostatic biomaterial according to claim 38, wherein the surface of said prostatic biomaterial is coated with collagen or collagen fragments, gelatin, fibrin or fibronectin.
- 53. A method of mediating wound repair within a mammal comprising administering to said mammal a therapeutically effective amount of an adipocyte complement related protein; whereby said polypeptide enhances progression in wound healing.
- 54. A method according to claim 53, wherein said adipocyte complement related protein comprises a polypeptide comprising a sequence of amino acid residues that is at least 75% identical in amino acid sequence to residues 26-281 of SEQ ID NO:2, wherein said sequence comprises:
Gly-Xaa-Xaa or Gly-Xaa-Pro repeats forming a collagen domain, wherein Xaa is any amino acid, and a carboxy-terminal globular portion.
- 55. A method according to claim 54, wherein said polypeptide comprises a sequence of amino acid residues that is at least 90% identical in amino acid sequence to residues 22-281 of SEQ ID NO:2.
- 56. A method according to claim 54, wherein said polypeptide comprises an amino acid sequence that is at least 90% identical in amino acid sequence to residues 26-281 of SEQ ID NO:2.
- 57. A method according to claim 55, wherein any differences between said polypeptide and SEQ ID NO:2 are due to conservative amino acid substitutions.
- 58. A method according to claim 55, wherein said collagen domain consists of 13 Gly-Xaa-Xaa repeats and 1 Gly-Xaa-Pro repeat.
- 59. A method according to claim 55, wherein said globular domain consists of ten beta sheets.
- 60. A method according to claim 59, wherein said beta sheets are associated with amino acid residues corresponding to 147-151, 170-172, 178-181, 191-203, 207-214, 219-225, 227-239, 244-250, and 269-274 of SEQ ID NO:2.
- 61. A method according to claim 55, wherein said polypeptide comprises residues 1-281 of SEQ ID NO:2 or residues 1-281 of SEQ ID NO:44.
- 62. A method according to claim 55, wherein said polypeptide is complexed to a second polypeptide to form a oligomer.
- 63. A method according to claim 62, wherein said polypeptides are complexed by intermolecular disulfide bonds.
- 64. A method according to claim 62, wherein said oligomer is a trimer.
- 65. A method according to claim 62, wherein said oligomer is a hexamer.
- 66. A method according to claim 62, wherein said multimer is an 18mer.
- 67. A method according to claim 62, wherein progression in wound healing comprises reduction in inflammation, reduction in fibroblast recruitment, wound retraction, or reduction in infection.
- 68. A method for inhibiting platelet adhesion comprising administering to a patient in need of such inhibition a therapeutically effective amount of an adipocyte complement related protein in a pharmaceutical acceptable vehicle.
- 69. A method for inhibiting platelet activation comprising administering to a patient in need of such inhibition a therapeutically effective amount of an adipocyte complement related protein in a pharmaceutical acceptable vehicle.
- 70. A method for inhibiting platelet accretion comprising administering to a patient in need of such inhibition a therapeutically effective amount of an adipocyte complement related protein in a pharmaceutical acceptable vehicle.
- 71. A method for minimizing vascular occlusion by increasing patency time in a patient in need of such treatment comprising administering an adipocyte complement related protein in a pharmaceutically acceptable vehicle, wherein said adipocyte complement related protein promotes blood flow.
- 72. A method according to claim 71, wherein said adipocyte complement related protein is administered concurrently with, or within an effective time period before, an acute vascular injury.
- 73. A method according to claim 71 wherein said adipocyte complement related protein is administered following an acute vascular injury.
- 74. A method according to claim 71, wherein blood flow is increased by inhibition of platelet adhesion, activation or accretion.
- 75. A method for inducing vasodilation within the vasculature of a mammal comprising administrating to said mammal a therapeutically effective amount of an adipocyte complement related protein; in a pharmaceutically acceptable vehicle; whereby said adipocyte complement related protein elicits a vasorelaxant response.
- 76. A method for protecting ischemic myocardium from reperfusion injury comprising administering an adipocyte complement related protein to a patient in need of such protection, wherein said adipocyte complement related protein inhibits complement.
- 77. A method for mediating tumor metastasis comprising administering an adipocyte complement related protein to a patient in need of such inhibition, wherein said adipocyte complement related protein mediates tumor cell binding to collagen.
REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 09/506,855, filed on Feb. 17, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09/444,794, filed on Nov. 22, 1999, which is a continuation-in-part of U.S. patent application Ser. No. 09/253,604, filed on Feb. 19, 1999, all three of which applications are pending.
Divisions (1)
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Number |
Date |
Country |
Parent |
09619740 |
Jul 2000 |
US |
Child |
10180762 |
Jun 2002 |
US |
Continuation in Parts (3)
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Number |
Date |
Country |
Parent |
09506855 |
Feb 2000 |
US |
Child |
09619740 |
Jul 2000 |
US |
Parent |
09444794 |
Nov 1999 |
US |
Child |
09506855 |
Feb 2000 |
US |
Parent |
09253604 |
Feb 1999 |
US |
Child |
09444794 |
Nov 1999 |
US |