US5336615A
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Genetically engineered endothelial cells exhibiting enhanced migration and plasminogen activator activity
Assignee: Yale University
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Filing: 1992-01-06
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Granted: 1994-08-09
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Expires: 2012-01-06
Abstract
Abstract Genetically engineered endothelial cells which exhibit enhanced cell migration and enhanced urokinase-type plasminogen activator (u-PA) activity are provided. The cells are modified by incorporation of the coding sequence for the c-src gene so that the cells express elevated levels of the tyrosine kinase protein, pp60c-src. The C-src gene is a naturally occurring gene which appears to be present in all animal species and is highly conserved. Because of their enhanced migration rates, the modified cells can be used to efficiently seed denuded segments of vessels or natural or synthetic grafts prior to implantation. Because of their enhanced u-PA activity, the cells can reduce the probability of thrombus formation at sites of vessel damage, such as that produced during such surgical procedures as coronary angioplasty and vessel reconstruction with grafts, stents, or the like.
Inventors
- 👤 Leonard Bell
- 👤 Joseph A. Madri
- 👤 Stephen L. Warren
- 👤 Daniel J. Luthringer
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 13:45
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/50; A61L27/507; A61L31/00; A61L31/005; C; C07; C07K; C07K14/00; C07K14/82; A61K; A61K38/00; Y; Y10; Y10S; Y10S623/00; Y10S623/924; Y10S623/925
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
77 words
An in vitro culture of endothelial cells, said cells containing a heterologous vector which comprises DNA coding for a c-src polypeptide, wherein the c-src DNA supplied by the heterologous vector effects, upon expression of the c-src polypeptide encoded thereby, enhanced migration or enhanced urokinase plasminogen activator activity or enhanced tyrosine kinase activity compared endothelial to cells which do not contain the heterologous vector, and said endothelial cells containing the heterologous vector retain the nontransformed endothelial cell phenotype.
Claim 2
Dependent Claim
77 words
An in vitro culture of endothelial cells, said cells containing a heterologous vector which comprises DNA coding for a c-src polypeptide, wherein the c-src DNA supplied by the heterologous vector effects, upon expression of the c-src polypeptide encoded thereby, enhanced migration or enhanced urokinase plasminogen activator activity or enhanced tyrosine kinase activity compared endothelial to cells which do not contain the heterologous vector, and said endothelial cells containing the heterologous vector retain the nontransformed endothelial cell phenotype.
Claim 3
Dependent Claim
19 words
The culture of claim 1 wherein the DNA coding for the c-src polypeptide is operably linked to a promoter.
Claim 4
Dependent Claim
12 words
The culture of claim 2 wherein the promoter is a heterologous promoter.
Claim 5
Dependent Claim
12 words
The culture of claim 1 wherein the cells are human endothelial cells.
Claim 6
Dependent Claim
61 words
An in vitro culture of endothelial cells, said cells containing a heterologous vector which comprises DNA coding for at least a fragment of a c-src polypeptide, wherein said fragment effects enhanced migration of said cells in comparison to endothelial cells which do not contain said heterologous vector, and said endothelial cells containing the heterologous vector retain the nontransformed endothelial cell phenotype.
Claim 7
Dependent Claim
61 words
An in vitro culture of endothelial cells, said cells containing a heterologous vector which comprises DNA coding for at least a fragment of a c-src polypeptide, wherein said fragment effects enhanced migration of said cells in comparison to endothelial cells which do not contain said heterologous vector, and said endothelial cells containing the heterologous vector retain the nontransformed endothelial cell phenotype.
Claim 8
Dependent Claim
64 words
An in vitro culture of endothelial cells, said cells containing a heterologous vector which comprises DNA coding for at least a fragment of a c-src polypeptide, wherein said fragment effects enhanced urokinase plasminogen activator activity by said cells in comparison to endothelial cells which do not contain said heterologous vector, and said endothelial cells containing the heterologous vector retain the nontransformed endothelial cell phenotype.
Claim 9
Dependent Claim
64 words
An in vitro culture of endothelial cells, said cells containing a heterologous vector which comprises DNA coding for at least a fragment of a c-src polypeptide, wherein said fragment effects enhanced urokinase plasminogen activator activity by said cells in comparison to endothelial cells which do not contain said heterologous vector, and said endothelial cells containing the heterologous vector retain the nontransformed endothelial cell phenotype.
Claim 10
Dependent Claim
25 words
A prosthesis to be implanted in the vascular system of an animal comprising a tubular support carrying endothelial cells from the culture of claim 1.
Claim 11
Dependent Claim
14 words
The prosthesis of claim 7 wherein the tubular support comprises an autologous vascular graft.
Claim 12
Dependent Claim
14 words
The prosthesis of claim 7 wherein the tubular support comprises a synthetic vascular graft.
Claim 13
Dependent Claim
12 words
The prosthesis of claim 7 wherein the tubular support comprises a stent.
Claim 14
Dependent Claim
28 words
The prosthesis of claim 7 wherein the endothelial cells containing the heterologous vector exhibit enhanced migration in comparison to endothelial cells which do not contain the heterologous vector.
Claim 15
Dependent Claim
31 words
The prosthesis of claim 7 wherein the endothelial cells containing the heterologous vector exhibit enhanced urokinase plasminogen activator activity in comparison to endothelial cells which do not contain the heterologous vector.
Claim 16
Dependent Claim
30 words
The prosthesis of claim 7 wherein the endothelial cells containing the heterologous vector exhibit enhanced tyrosine kinase activity in comparison to endothelial cells which do not contain the heterologous vector.
Claim 17
Dependent Claim
19 words
The prosthesis of claim 7 wherein the DNA coding for the c-src polypeptide is operably linked to a promoter.
Claim 18
Dependent Claim
12 words
The prosthesis of claim 14 wherein the promoter is a heterologous promoter.
Claim 19
Dependent Claim
13 words
The prosthesis of claim 7 wherein the endothelial cells are human endothelial cells.
Claim 20
Dependent Claim
25 words
A prosthesis to be implanted in the vascular system of an animal comprising a tubular support carrying endothelial cells from the culture of claim 5.
Claim 21
Dependent Claim
25 words
A prosthesis to be implanted in the vascular system of an animal comprising a tubular support carrying endothelial cells from the culture of claim 6.
Claim 22
Dependent Claim
46 words
The culture of claim 1 wherein the cells containing the heterologous vector exhibit at least a 25 percent enhancement in migration or exhibit at least a 25 percent enhancement in urokinase plasminogen activator activity in comparison to endothelial cells which do not contain the heterologous vector.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1997-08-08 | 1998-02-07 | 1998-08-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-08-08 | 2002-02-07 | 2002-08-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-08-08 | 2006-02-07 | 2006-08-09 | $7700.00 | Window Closed / Lapsed |