US5658565A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Inducible nitric oxide synthase gene for treatment of disease
Assignee: University of Pittsburgh
•
Filing: 1994-06-24
•
Granted: 1997-08-19
•
Expires: 2014-06-24
Abstract
Abstract The present invention discloses a full-length human hepatocyte iNOS cDNA clone and various gene therapy applications utilizing an iNOS DNA sequence. In preferred embodiments of the disclosed invention, iNOS-directed gene therapy involves specific targeting of a DNA sequence encoding a protein or protein fragment with iNOS biological activity for treating vascular diseases and disorders, antitumor applications and in response to certain microbial infections.
Inventors
- 👤 Timothy R. Billiar
- 👤 Edith Tzeng
- 👤 Andreas K. Nussler
- 👤 David A. Geller
- 👤 Richard L. Simmons
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 06:49
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/0004; C12N9/0071; A; A61; A61P; A61P9/00; A61P9/14; C12N15/00; C12N15/09; C12N15/63; C12N15/79; C12N15/85; C12N15/86; C12N9/0012; C12N9/0014; C12N9/0022; A61K; A61K38/00; A61K48/00; C12N2710/00; C12N2710/00011; C12N2710/10011; C12N2710/10311; C12N2710/10341; C12N2710/10343; C12N2740/00; C12N2740/00011; C12N2740/10011; C12N2740/13011; C12N2740/13041; C12N2740/13043; C12N2795/00; C12N2795/00011; C12N2795/10011; C12N2795/10211; C12N2795/10241; C12N2795/10243; C12N2840/00; C12N2840/20; C12N2840/203
Claims Analysis
Total Claims: 43
Claim 1
Independent Claim
95 words
A method of treating a vascular occlusion within a mammalian host which comprises transferring an isolated nucleic acid polymer inserted into a viral or plasmid vector to a population of mammalian cells at the site of said occlusion, said nucleic acid polymer encoding a biologically active nitric oxide synthase which has the enzymatic activity of the iNOS of SEQ ID NO:2 such that said nucleic acid polymer is expressed in said cells to effect increased amounts of nitric oxide (NO) via iNOS catalysis in amounts and for a time sufficient to reduce said vascular occlusion.
Claim 2
Independent Claim
95 words
A method of treating a vascular occlusion within a mammalian host which comprises transferring an isolated nucleic acid polymer inserted into a viral or plasmid vector to a population of mammalian cells at the site of said occlusion, said nucleic acid polymer encoding a biologically active nitric oxide synthase which has the enzymatic activity of the iNOS of SEQ ID NO:2 such that said nucleic acid polymer is expressed in said cells to effect increased amounts of nitric oxide (NO) via iNOS catalysis in amounts and for a time sufficient to reduce said vascular occlusion.
Claim 3
Dependent Claim
12 words
The method of claim 1 wherein said mammalian host is a human.
Claim 4
Dependent Claim
21 words
The method of claim 2 wherein said isolated nucleic acid polymer is an isolated human DNA sequence of SEQ ID NO:2.
Claim 5
Dependent Claim
29 words
The method of claim 1 wherein said population of mammalian cells are in situ mammalian cells selected from the group consisting of endothelial cells and vascular smooth muscle cells.
Claim 6
Dependent Claim
26 words
The method of claim 4 which further comprises clearing said occlusion by procedure selected from the group consisting of balloon angioplasty, mechanical endarterectomy and vascular endoscopy.
Claim 7
Dependent Claim
29 words
The method of claim 5 which further comprises utilizing a double balloon catheter to physically segregate the site of said occlusion and for delivering said vector to said cells.
Claim 8
Dependent Claim
13 words
The method of claim 6 wherein said vector is a recombinant viral vector.
Claim 9
Dependent Claim
13 words
The method of claim 6 wherein said vector is a recombinant viral vector.
Claim 10
Dependent Claim
15 words
The method of claim 7 wherein said recombinant vector is a recombinant MoMLV retroviral vector.
Claim 11
Dependent Claim
15 words
The method of claim 8 wherein said recombinant vector is a recombinant MoMLV retroviral vector.
Claim 12
Dependent Claim
12 words
The method of claim 9 wherein said recombinant MoMLV vector is MFG-iNOS.
Claim 13
Dependent Claim
12 words
The method of claim 9 wherein said recombinant MoMLV vector is DFG-iNOS-Neo.
Claim 14
Dependent Claim
12 words
The method of claim 10 wherein said recombinant MoMLV vector is MFG-iNOS.
Claim 15
Dependent Claim
12 words
The method of claim 10 wherein said recombinant MoMLV vector is DFG-iNOS-Neo.
Claim 16
Dependent Claim
14 words
The method of claim 1 wherein said vector is a recombinant plasmid DNA vector.
Claim 17
Dependent Claim
13 words
The method of claim 15 wherein said recombinant plasmid DNA vector is pCIS-iNOS.
Claim 18
Dependent Claim
14 words
The method of claim 7 wherein said recombinant viral vector is an adenovirus vector.
Claim 19
Dependent Claim
15 words
The method of claim 7 wherein said recombinant viral vector is an adeno-associated virus vector.
Claim 20
Independent Claim
115 words
A method of treating an occlusion of an arterial vessel which comprises: (a) clearing the site in said arterial vessel of occluding material; and (b) delivering an isolated nucleic acid polymer inserted into a viral or plasmid vector to a population of mammalian cells at the cleared occluded site in the arterial vessel, said nucleic acid polymer encoding a biologically active nitric oxide synthase which has the enzymatic activity of the iNOS of SEQ ID NO:2, such that said nucleic acid polymer is expressed in said cells at said cleared occluded site to effect an increased amount of nitric oxide (NO) via iNOS catalysis in amounts and for a time sufficient to attenuate vascular occlusion.
Claim 21
Independent Claim
115 words
A method of treating an occlusion of an arterial vessel which comprises: (a) clearing the site in said arterial vessel of occluding material; and (b) delivering an isolated nucleic acid polymer inserted into a viral or plasmid vector to a population of mammalian cells at the cleared occluded site in the arterial vessel, said nucleic acid polymer encoding a biologically active nitric oxide synthase which has the enzymatic activity of the iNOS of SEQ ID NO:2, such that said nucleic acid polymer is expressed in said cells at said cleared occluded site to effect an increased amount of nitric oxide (NO) via iNOS catalysis in amounts and for a time sufficient to attenuate vascular occlusion.
Claim 22
Dependent Claim
26 words
The method of claim 19 wherein step (a) is accomplished by a procedure selected from the group consisting of balloon angioplasty, mechanical endarcterectomy and vascular endoscopy.
Claim 23
Dependent Claim
21 words
The method of claim 20 wherein a double balloon catheter is used to physically segregate the cleared site of said artery.
Claim 24
Dependent Claim
13 words
The method of claim 19 wherein said vector is a recombinant viral vector.
Claim 25
Dependent Claim
15 words
The method of claim 22 wherein said recombinant vector is a recombinant MoMLV retroviral vector.
Claim 26
Dependent Claim
12 words
The method of claim 23 wherein said recombinant MoMLV vector is MFG-iNOS.
Claim 27
Dependent Claim
12 words
The method of claim 23 wherein said recombinant MoMLV vector is DFG-iNOS-Neo.
Claim 28
Dependent Claim
14 words
The method of claim 19 wherein said vector is a recombinant plasmid DNA vector.
Claim 29
Dependent Claim
13 words
The method of claim 26 wherein said recombinant plasmid DNA vector is pCIS-iNOS.
Claim 30
Dependent Claim
14 words
The method of claim 22 wherein said recombinant viral vector is an adenovirus vector.
Claim 31
Dependent Claim
15 words
The method of claim 22 wherein said recombinant viral vector is an adeno-associated virus vector.
Claim 32
Independent Claim
125 words
A method of treating a blood vessel occlusion which comprises: (a) forming a graft composed of a bypass vessel joined by proximal and distal anastomoses to bypass said occlusion; (b) isolating an anastomosis subsequent to graft suturing; and (c) delivering an isolated nucleic acid polymer inserted into a viral or plasmid vector to a population of mammalian cells at the site of said isolated anastomosis, said nucleic acid polymer encoding a biologically active nitric oxide synthase which has the enzymetic activity of the iNOS of SEQ ID NO:2, such that said nucleic acid polymer is expressed in said cells at said site to effect an increased amount of nitric oxide (NO) via iNOS catalysis in amounts and for a time sufficient to attenuate vascular occlusion.
Claim 33
Independent Claim
125 words
A method of treating a blood vessel occlusion which comprises: (a) forming a graft composed of a bypass vessel joined by proximal and distal anastomoses to bypass said occlusion; (b) isolating an anastomosis subsequent to graft suturing; and (c) delivering an isolated nucleic acid polymer inserted into a viral or plasmid vector to a population of mammalian cells at the site of said isolated anastomosis, said nucleic acid polymer encoding a biologically active nitric oxide synthase which has the enzymetic activity of the iNOS of SEQ ID NO:2, such that said nucleic acid polymer is expressed in said cells at said site to effect an increased amount of nitric oxide (NO) via iNOS catalysis in amounts and for a time sufficient to attenuate vascular occlusion.
Claim 34
Dependent Claim
15 words
The method of claim 30 wherein said anastomosis of step (b) is said distal anastomosis.
Claim 35
Dependent Claim
17 words
The method of claim 31 wherein a double balloon catheter is used to physically isolate said anastomosis.
Claim 36
Dependent Claim
13 words
The method of claim 31 wherein said vector is a recombinant viral vector.
Claim 37
Dependent Claim
15 words
The method of claim 33 wherein said recombinant vector is a recombinant MoMLV retroviral vector.
Claim 38
Dependent Claim
12 words
The method of claim 34 wherein said recombinant MoMLV vector is MFG-iNOS.
Claim 39
Dependent Claim
12 words
The method of claim 34 wherein said recombinant MoMLV vector is DFG-iNOS-Neo.
Claim 40
Dependent Claim
14 words
The method of claim 31 wherein said vector is a recombinant plasmid DNA vector.
Claim 41
Dependent Claim
12 words
The method of claim 37 wherein said recombinant DNA vector is pCIS-iNOS.
Claim 42
Dependent Claim
14 words
The method of claim 33 wherein said recombinant viral vector is an adenovirus vector.
Claim 43
Dependent Claim
15 words
The method of claim 33 wherein said recombinant viral vector is an adeno-associated virus vector.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-08-18 | 2001-02-17 | 2001-08-19 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-08-18 | 2005-02-17 | 2005-08-19 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-08-18 | 2009-02-17 | 2009-08-19 | $7700.00 | Window Closed / Lapsed |