Steven A Gross

US Patent:

6784178, Aug 31, 2004

Filed:

Oct 9, 2002

Appl. No.:

10/240729

Inventors:

Steven S. Gross - New York NY
Caroline L. Jones - Nottingham, GB

Assignee:

Cornell Research Foundation, Inc. - Ithaca NY

International Classification:

A61K 3150

US Classification:

514249, 514565, 514634

Abstract:

A patient with a disorder involving endothelial dysfunction associated with deficient nitric oxide bioactivity, e. g. , coronary artery disease, atherosclerosis, hypertension, diabetes or neurodegenerative condition stemming from ischemia and/or inflammation, is treated by administering nitric oxide bioactivity increasing hydroxyguanidine.

US Patent:

6967219, Nov 22, 2005

Filed:

Oct 10, 2002

Appl. No.:

10/268106

Inventors:

Steven S. Gross - New York NY, US
Michael S. Goligorsky - Stony Brook NY, US

Assignee:

Cornell Research Foundation, Inc. - Ithaca NY
The Research Foundation of the State University of New York - Albany NY

International Classification:

A61K031/195

US Classification:

514565, 514564

Abstract:

Premature vascular senescence is reversed or prevented in tissue or cells by contacting the tissue or cells with a hydroxyguanidine. This finds application in treatment of patients with a disorder associated with elevated levels of advanced glycation end products in blood or tissue, e. g. , patients with end stage renal disease or poorly controlled diabetes, and in contacting vascular tissue or cells ex vivo to prevent occurrence of premature senescence.

US Patent:

55020500, Mar 26, 1996

Filed:

Nov 29, 1993

Appl. No.:

8/158829

Inventors:

Steven S. Gross - New York NY

Assignee:

Cornell Research Foundation, Inc. - Ithaca NY

International Classification:

A61K 3154
A61K 31495
A61K 31525
A61K 3144

US Classification:

514241

Abstract:

Inhibitor of the use of tetrahydrobiopterin as a cofactor for nitric oxide synthase, e. g. , substituted 4-phenyl(hydropyridines) such as 1-methyl-4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine or, 4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine) or tetrahydropterin analog which does not replace tetrahydrobiopterin as a substrate for nitric oxide synthase such as (6R,S)-6,7-dimethyl-tetrahydropterin or (6R,S)-tetrahydrofolic acid or 2,4-diamino-, 2,6-diamino, or 4,6-diamino mono- or disubstituted pyrimidines or the corresponding pyrimidine-3-oxides such as 2,4-diamino-6-(diethylamino)pyrimidine, 2,4-diamino-6-piperidino-pyrimidine-3-oxide, 2,4-diamino-6-hydroxypyrimidine, 4,6-diamino-2-hydroxypyrimidine or 2,5-diamino-4,6-dihydroxypyrimidine is administered to inhibit nitric oxide synthesis from arginine in vascular cells in a subject in need of such inhibition (e. g. , for prophylaxis or treatment of cytokine- or endotoxin-induced hypotension (e. g. , septic shock).

US Patent:

58744339, Feb 23, 1999

Filed:

Dec 19, 1995

Appl. No.:

8/574654

Inventors:

Steven S. Gross - New York NY

Assignee:

Cornell Research Foundation, Inc. - Ithaca NY

International Classification:

A01N 4366
A61K 3153
A61K 31495

US Classification:

514241

Abstract:

Inhibitor of the use of tetrahydrobiopterin as a cofactor for nitric oxide synthase, e. g. , substituted 4-phenyl(hydropyridines) such as 1-methyl-4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine or, 4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine) or tetrahydropterin analog which does not replace tetrahydrobiopterin as a substrate for nitric oxide synthase such as (6R,S)-6,7-dimethyl-tetrahydropterin or (6R,S)-tetrahydrofolic acid or 2,4-diamino-, 2,6-diamino, or 4,6-diamino mono- or disubstituted pyrimidines or the corresponding pyrimidine-3-oxides such as 2,4-diamino-6-(diethylamino)pyrimidine, 2,4-diamino-6-piperidino-pyrimidine-3-oxide, 2,4-diamino-6-hydroxypyrimidine, 4,6-diamino-2-hydroxypyrimidine or 2,5-diamino-4,6-dihydroxypyrimidine is administered to inhibit nitric oxide synthesis from arginine in vascular cells in a subject in need of such inhibition (e. g. , for prophylaxis or treatment of cytokine- or endotoxin-induced hypotension (e. g. , septic shock).

US Patent:

62745816, Aug 14, 2001

Filed:

May 20, 1993

Appl. No.:

8/063067

Inventors:

Steven S. Gross - New York NY

Assignee:

Cornell Research Foundation, Inc. - Ithaca NY

International Classification:

A61K 31495
A61K 3150

US Classification:

514249

Abstract:

Guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist and/or pterin salvage pathway tetrahydrobiopterin synthesis antagonist are administered to inhibit nitric oxide synthesis from arginine in vascular smooth muscle cells in a subject in need of such inhibition (e. g. for prophylactic or curative effect for cytokine-induced hypotension or for restoration of vascular contractile sensitivity to pressor agents in the treatment of such hypotension).

US Patent:

61536156, Nov 28, 2000

Filed:

Jan 12, 1999

Appl. No.:

9/228977

Inventors:

Steven S. Gross - New York NY

Assignee:

Cornell Research Foundation, Inc. - Ithaca NY

International Classification:

A61K 31495
A61K 31405
A61K 31195

US Classification:

514253

Abstract:

Guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist and/or pterin salvage pathway tetrahydrobiopterin synthesis antagonists are administered to inhibit nitric oxide synthesis from arginine in vascular cells in a subject in need of such inhibition (e. g. , for prophylactic or curative effect for endotoxin- or cytokine-induced hypotension or for restoration of vascular contractile sensitivity to pressor agents in the treatment of such hypotension). The tetrahydrobiopterin synthesis antagonist may be administered with. alpha. sub. 1 -adrenergic agonist or with nitric oxide synthase inhibitor. The tetrahydrobiopterin synthesis antagonists are also administered to attenuate inflammation caused by induced nitric oxide production in immune cells. Unwanted counterproductive or side effects can be eliminated or ameliorated by administration additionally of levodopa with or without carbidopa and L-5-hydroxytryptophane.

US Patent:

58771760, Mar 2, 1999

Filed:

Nov 15, 1993

Appl. No.:

8/151889

Inventors:

Steven S. Gross - New York NY

Assignee:

Cornell Research Foundation, Inc. - Ithaca NY

International Classification:

A61K 31495
A61K 31405
A61K 31195

US Classification:

514253

Abstract:

Guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist and/or pterin salvage pathway tetrahydrobiopterin synthesis antagonists are administered to inhibit nitric oxide synthesis from arginine in vascular cells in a subject in need of such inhibition (e. g. , for prophylactic or curative effect for endotoxin- or cytokine-induced hypotension or for restoration of vascular contractile sensitivity to pressor agents in the treatment of such hypotension). The tetrahydrobiopterin synthesis antagonist may be administered with. alpha. sub. 1 -adrenergic agonist or with nitric oxide synthase inhibitor. The tetrahydrobiopterin synthesis antagonists are also administered to attenuate inflammation caused by induced nitric oxide production in immune cells. Unwanted counterproductive or side effects can be eliminated or ameliorated by administration additionally of levodopa with or without carbidopa and L-5-hydroxytryptophane.

US Patent:

57234485, Mar 3, 1998

Filed:

Mar 20, 1996

Appl. No.:

8/618810

Inventors:

Steven S. Gross - New York NY
Owen W. Griffith - Milwaukee WI

Assignee:

The Medical College of Wisconsin Research Foundation - Milwaukee WI

International Classification:

A61K 3170
A61K 31195
C07C24100

US Classification:

514 33

Abstract:

Administration of argininosuccinate synthetase activity reducing agents, e. g. , argininosuccinate synthetase induction blocking agents (e. g. , antibiotics that bind to DNA sequences present in the upstream regulatory region of the argininosuccinate synthetase gene, such as mithramycin) and argininosuccinate synthetase inhibitors (e. g. , L-citrulline antagonists such as methyl citrulline and L-aspartate antagonists such as D-aspartate) is useful to prevent or treat sepsis or cytokine-induced systemic hypotension, is useful in the treatment of sepsis or cytokine-induced systemic hypotension to restore vascular sensitivity to the effects of. alpha. sub. 1 -adrenergic agonists, and is useful to suppress an immune response, e. g. , in treating inflammation. In one embodiment, certain argininosuccinate synthetase activity reducing agents are used together with arginine antagonists to treat sepsis or cytokine induced hypotension.