WO1998019701B1 - Methods for promoting wound healing and treating transplant-associated vasculopathy - Google Patents
Methods for promoting wound healing and treating transplant-associated vasculopathyInfo
- Publication number
- WO1998019701B1 WO1998019701B1 PCT/US1997/020388 US9720388W WO9819701B1 WO 1998019701 B1 WO1998019701 B1 WO 1998019701B1 US 9720388 W US9720388 W US 9720388W WO 9819701 B1 WO9819701 B1 WO 9819701B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- inos
- graft
- wound
- region
- cells
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract 22
- 230000001737 promoting effect Effects 0.000 title claims abstract 3
- 230000029663 wound healing Effects 0.000 title 1
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 claims abstract 36
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 claims abstract 36
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 13
- 239000000203 mixture Substances 0.000 claims 8
- 238000011200 topical administration Methods 0.000 claims 2
- 230000002255 enzymatic effect Effects 0.000 claims 1
- 206010052428 Wound Diseases 0.000 abstract 5
- 208000027418 Wounds and injury Diseases 0.000 abstract 5
Abstract
The present invention provides a method of promoting the closure of a wound in a patient. This method involves transferring exogenous iNOS to the region of the wound whereby a product of iNOS is produced in the region of the wound to promote the closure of the wound. The present invention also provides a method of transplanting a graft into a patient, which method involves transferring a vector comprising an iNOS expression cassette to cells associated with the graft and surgically incorporating the graft tissue into the patient. Upon expression of iNOS within the patient, a product of iNOS is produced in the region of the graft to attenuate vasculopathy in the region of the graft. To effectuate the inventive methods, the invention also provides pharmaceutical compositions for supplying iNOS and/or BH4 to cells associated with wounds or grafts.
Claims
1. A method of promoting the closure of a wound in a patient which comprises transferring exogenous iNOS to the region of said wound whereby a product of iNOS is produced in the region of said wound to promote the closure of said wound.
2. The method of claim 1, wherein exogenous iNOS is transferred to the region of said wound by topical administration of iNOS to the region of the wound.
3. The method of claim 1, wherein exogenous iNOS is transferred to the region of said wound by transferring to cells associated with said wound a vector, said vector comprising an iNOS expression cassette, whereby iNOS is expressed in said cells in the region of said wound.
4. A method of transplanting a graft into a patient comprising transferring to cells associated with said graft a vector, said vector comprising an iNOS expression cassette, and surgically incorporating said graft tissue into said patient such that said graft survives within said patient, whereby iNOS is expressed in said cells in the region of said wound.
5. The method of claim 4, wherein said cells associated with said graft are cells within the tissue comprising said graft.
6. The method of claim 4, wherein said cells associated with said graft are cells of the patient in the region of said graft.
7. The method of claim 4, wherein said cells associated with said graft are cells of the patient in the region of said graft.
8. The method of any of claims 4-7, wherein said cells associated with said graft are cells of the patient in the region of said graft.
9. The method of any of claims 4-8, wherein said vector is transferred to the region of said graft subsequent to surgically incorporating said graft tissue into said patient.
10. The method of any of claims 4-8, wherein said vector is transferred to the region of said graft prior to surgically incorporating said graft tissue into said patient.
11. The method of any of claims 1-10, wherein said patient is human.
12. The method of any of claim 1-11, which further comprises transferring exogenous BH* such that iNOS enzymatic activity is increased.
13. The method of claim 12, wherein said BEL4 is transferred by topical administration of BH4.
14. The method of claim 12, wherein said BHL* is transferred by transferring a vector comprising a GTPCH expression cassette to cells such that said cells produce BH^
15. The method of claim 14 and any of claims 3 or 4-10, wherein said iNOS expression cassette and said GTPCH expression cassette are co-transferred.
16. The method of claim 14 and any of claims 3 or 4-10 wherein said iNOS expression cassette and said GTPCH expression cassette are not co- transferred.
17. A pharmaceutical composition for transferring exogenous iNOS to cells in the region of a wound such that a product of iNOS is produced in the region of said wound to promote the closure of said wound, said composition comprising a source of iNOS and a pharmacologically-acceptable carrier.
18. A pharmaceutical composition for transferring exogenous iNOS to cells associated with a graft such that a product of iNOS is produced to attenuate vasculopathy in the region of said graft, said composition comprising a source of iNOS and a pharmacologically-acceptable carrier.
19. A pharmaceutical composition of claim 23 or 24 comprising a vector having an iNOS expression cassette.
20. A pharmaceutical composition for transferring exogenous BR} to cells associated with a graft or a wound, said composition comprising a source of BHt, and a pharmacologically-acceptable carrier.
21. A pharmaceutical composition of claim 26, which comprises a vector having a GTPCH expression cassette.
22. A pharmaceutical composition for transferring exogenous iNOS and exogenous BH4 to cells associated with a graft or a wound, said composition comprising a source of iNOS, a source of BH4, and a pharmacologically-acceptable carrier
23. The use of a pharmaceutical composition for transferring exogenous iNOS to cells in the region of a wound such that a product of iNOS is produced in the region of said wound to promote the closure of said wound, said composition comprising a source of iNOS and a pharmacologically-acceptable carrier.
24. The use of a pharmaceutical composition for transferring exogenous iNOS to cells associated with a graft such that a product of iNOS is produced to attenuate vasculopathy in the region of said graft, said composition comprising a source of iNOS and a pharmacologically-acceptable carrier.
25. The use of a pharmaceutical composition of claim 23 or 24 comprising a vector having an iNOS expression cassette.
26. The use of a pharmaceutical composition for transferring exogenous BH4 to cells associated with a graft or a wound, said composition comprising a source of BH*, and a pharmacologically-acceptable carrier.
27. The use of a pharmaceutical composition of claim 26, which comprises a vector having a GTPCH expression cassette.
28. The use of a pharmaceutical composition for transferring exogenous iNOS and exogenous BRj to cells associated with a graft or a wound, said composition comprising a source of iNOS, a source of BR}, and a pharmacologically-acceptable carrier. STATEMENT UNDER ARTICLE 19
By way of Amendment, Applicant has added new claims 23-28. The other claims have not been altered.
The new claims are fully supported by the Description filed with the application on 24 January 1997, and do not go beyond the original disclosure of the said application. Thus, no new matter has been added by way of the present amendments.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002270619A CA2270619A1 (en) | 1996-11-08 | 1997-11-07 | Methods for promoting wound healing and treating transplant-associated vasculopathy |
| EP97946907A EP0963204A1 (en) | 1996-11-08 | 1997-11-07 | Promoting wound healing and treating transplant-associated vasculopathy |
| JP52181598A JP2001503432A (en) | 1996-11-08 | 1997-11-07 | Methods for promoting wound healing and treating vasculopathy associated with transplantation |
| AU51992/98A AU5199298A (en) | 1996-11-08 | 1997-11-07 | Methods for promoting wound healing and treating transplant-associated vasculopathy |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/745,375 US5830461A (en) | 1992-11-25 | 1996-11-08 | Methods for promoting wound healing and treating transplant-associated vasculopathy |
| US08/745,375 | 1996-11-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1998019701A1 WO1998019701A1 (en) | 1998-05-14 |
| WO1998019701B1 true WO1998019701B1 (en) | 1998-07-23 |
Family
ID=24996422
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1997/020388 WO1998019701A1 (en) | 1996-11-08 | 1997-11-07 | Methods for promoting wound healing and treating transplant-associated vasculopathy |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US5830461A (en) |
| EP (1) | EP0963204A1 (en) |
| JP (1) | JP2001503432A (en) |
| AU (1) | AU5199298A (en) |
| CA (1) | CA2270619A1 (en) |
| WO (1) | WO1998019701A1 (en) |
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-
1996
- 1996-11-08 US US08/745,375 patent/US5830461A/en not_active Expired - Fee Related
-
1997
- 1997-11-07 AU AU51992/98A patent/AU5199298A/en not_active Abandoned
- 1997-11-07 CA CA002270619A patent/CA2270619A1/en not_active Abandoned
- 1997-11-07 WO PCT/US1997/020388 patent/WO1998019701A1/en not_active Application Discontinuation
- 1997-11-07 JP JP52181598A patent/JP2001503432A/en active Pending
- 1997-11-07 EP EP97946907A patent/EP0963204A1/en not_active Ceased
-
1998
- 1998-10-02 US US09/165,882 patent/US6103230A/en not_active Expired - Fee Related
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