Patents by Inventor Owen W. Griffith
Owen W. Griffith has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
-
Patent number: 5523084Abstract: L-amino acid oxidase is utilized to reduce plasma level of large neutral amino acids to allow the opportunity of increased melphalan transport into tumors and melphalan is administered when the plasma level of L-amino acid oxidase is sufficiently low so the gain from increased transport outweighs the loss from L-amino acid oxidase-mediated metabolism of melphalan. Preferably anti L-amino acid oxidase antibody is administered intermediate the L-amino acid oxidase and melphalan administrations to deplete L-amino acid oxidase activity once the L-amino acid oxidase has caused the melphalan transport improving plasma level reduction of large neutral amino acids thereby to reduce or eliminate degrading of melphalan by L-amino acid oxidase.Type: GrantFiled: September 7, 1994Date of Patent: June 4, 1996Assignees: Cornell Research Foundation, Inc., Duke UniversityInventors: Darell D. Bigner, Henry S. Friedman, Owen W. Griffith
-
Patent number: 5476871Abstract: Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of .alpha..sub.1 -adrenergic agonists are physiologically active compounds including N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties or monoalkyl carbon-substituted N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is alkyl having 1 to 5 carbon atoms, and physiologically acceptable acid addition salts thereof.Type: GrantFiled: September 12, 1994Date of Patent: December 19, 1995Assignee: The Medical College of Wisconsin Research Foundation, Inc.Inventors: Owen W. Griffith, Krishnaswamy Narayanan
-
Patent number: 5464858Abstract: Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of .alpha..sub.1 adrenergic agonists are physiologically active compounds including N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties or monoalkyl carbon-substituted N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is a heme binding moiety and/or a sulfur-containing binding moiety and Q' is --NH.sub.2 when there is a double bond between the omega carbon and Q and Q' is .dbd.Type: GrantFiled: December 12, 1994Date of Patent: November 7, 1995Assignee: The Medical College of Wisconsin Research Foundation, Inc.Inventors: Owen W. Griffith, Krishnaswamy Narayanan
-
Patent number: 5453441Abstract: Guanidino substituted arginines or homoarginines based on monoalkyl carbon-substituted ornithines or lysines, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and Q is an alkyl group containing from 1 to 6 carbon atoms or NH.sub.2 or NO.sub.2, and only one of R, R' and R" providing an alkyl substituent on the ornithine or lysine moiety. Preferred compounds are .alpha.-methyl-N.sup..omega. -methyl-DL-arginine, RS-.beta.-methyl-N.sup..omega. -methyl-DL-arginine, RS-.gamma.-methyl-N.sup..omega. -methyl-DL-arginine, .alpha.-methyl-N.sup..omega. -amino-DL-arginine, RS-.beta.-methyl-N.sup..omega. -amino-DL-arginine, RS-.gamma.-methyl-N.sup..omega. -amino-DL-arginine, .alpha.-methyl-N.sup..omega. -nitro-DL-arginine, RS-.beta.-methyl-N.sup..omega. -nitro-DL-arginine, and RS-.gamma.-methyl-N.sup..omega. -nitro-DL-arginine.Type: GrantFiled: October 24, 1994Date of Patent: September 26, 1995Assignee: Cornell Research Foundation, Inc.Inventor: Owen W. Griffith
-
Patent number: 5436271Abstract: Physiologically active N.sup.6 -(hydrazinoiminomethyl)lysine or pharmaceutically acceptable acid addition salt thereof is administered in a nitric oxide synthesis inhibiting amount to a subject in need of such inhibition (e.g., a subject with low blood pressure, e.g., due to sepsis or to therapeutic administration of cytokines, or needing immunosuppressive effect) or is added to a medium containing isolated organs, intact cells, cell homogenates or tissue homogenates in an amount sufficient to inhibit nitric oxide formation to elucide or control the biosynthesis, metabolism or physiological role of nitric oxide. Compared to known nitric oxide synthesis inhibitors, N.sup.6 -(hydrazinoiminomethyl)lysine and its acid addition salts show a greater relative activity toward inducible isoform of nitric oxide synthase than toward constitutive isoform of nitric oxide synthase. N.sup.6 -(hydrazinoiminomethyl)lysine and its pharmaceutically acceptable acid addition salts are substantially less toxic than are N.sup.Type: GrantFiled: May 4, 1993Date of Patent: July 25, 1995Assignee: Cornell Research Foundation, Inc.Inventor: Owen W. Griffith
-
Patent number: 5424447Abstract: Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of .alpha..sub.1 adrenergic agonists are physiologically active compounds including N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties or monoalkyl carbon-substituted N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H) (CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H) (CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is a heme binding moiety and/or a sulfur-containing binding moiety and Q' is --NH.sub.2 when there is a double bond between the omega carbon and Q and Q' is .dbd.Type: GrantFiled: July 7, 1993Date of Patent: June 13, 1995Assignee: The Medical College of Wisconsin Research Foundation, Inc.Inventors: Owen W. Griffith, Krishnaswamy Narayanan
-
Patent number: 5419901Abstract: Reducing plasma levels of endogenous arginine by parenteral administration of arginine depleting agent reduces nitric oxide levels and results in blood pressure increase. Preferably arginase is administered intravenously to raise blood pressure. The arginase can be administered in conjunction with arginine antagonists to potentiate the effect of these. Duration of action and avoidance of antigenicity may be obtained by use in conjunction with a carrier or modifier.Type: GrantFiled: February 22, 1993Date of Patent: May 30, 1995Assignee: Cornell Research Foundation, Inc.Inventor: Owen W. Griffith
-
Patent number: 5407672Abstract: L-amino acid oxidase is utilized to reduce plasma level of large neutral amino acids to allow the opportunity of increased melphalan transport into tumors and melphalan is administered when the plasma level of L-amino acid oxidase is sufficiently low so the gain from increased transport outweighs the loss from L-amino acid oxidase-mediated metabolism of melphalan.Type: GrantFiled: April 8, 1993Date of Patent: April 18, 1995Assignees: Cornell Research Foundation, Inc., Duke UniversityInventors: Owen W. Griffith, Henry S. Friedman
-
Patent number: 5395612Abstract: Reducing plasma levels of endogenous arginine by parenteral administration of arginine depleting agent limits nitric oxide formation and results in blood pressure increase. Preferably arginase is administered intravenously to raise blood pressure. The arginine depleting agent can be administered in conjunction with arginine antagonists to potentiate the effect of these. The arginine depleting agent can be used concurrently with .alpha..sub.1 adrenergic agonists in treating systemic hypotension caused by induced production of nitric oxide, to restore vascular contractile sensitivity to the effect of the .alpha..sub.1 adrenergic agonists. Duration of action and avoidance of antigenicity may be obtained by use in conjunction with a carrier or modifier.Type: GrantFiled: December 31, 1991Date of Patent: March 7, 1995Assignee: Cornell Research Foundation, Inc.Inventors: Owen W. Griffith, Steven S. Gross, Roberto Levi
-
Patent number: 5374651Abstract: Methods and compositions for treating and inhibiting hypotension are provided. A therapeutic regimen useful in the present invention includes an arginine-free parenteral formulation administered concurrently with or followed by an arginine analog. The combination therapy provides an augmentation of the anti-hypotensive effect found by the present inventors with arginine analogs, such as N.sup..omega. -methyl-L-arginine, N.sup..omega. -amino-L-arginine or N.sup..omega. -nitro-L-arginine. These arginine analogs, otherwise described as nitric oxide synthase inhibitors, provide for a decrease in nitric oxide concentrations, and are demonstrated to elicit an increase in blood pressure in vivo, particularly in animals with cytokine and/or endotoxin induced hypotension. The parenteral formulation of the therapeutic regimen and methods of the invention are arginine-free and provide a decrease in plasma arginine levels.Type: GrantFiled: June 23, 1992Date of Patent: December 20, 1994Assignee: Board of Regents, The University of Texas SystemInventors: Robert G. Kilbourn, Owen W. Griffith, Steven S. Gross
-
Patent number: 5364881Abstract: Inhibitors of nitric oxide formation from arginine useful for treating hypotension, inflammation, stroke and to restore vascular contractile sensitivity to the effects of .alpha..sub.1 -adrenergic agonists are physiologically active compounds including N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties or monoalkyl carbon-substituted N.sup..delta. -substituted ornithine or N.sup..epsilon. -substituted lysine moieties, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and wherein none or only one of R, R' and R" provides an alkyl substituent on ornithine or lysine moiety, and wherein Q is alkyl having 1 to 5 carbon atoms, and physiologically acceptable acid addition salts thereof.Type: GrantFiled: November 15, 1993Date of Patent: November 15, 1994Assignee: The Medical College of Wisconsin Research Foundation, Inc.Inventors: Owen W. Griffith, Krishnaswamy Narayanan
-
Patent number: 5334380Abstract: Methods and compositions for treating and inhibiting hypotension related to both endotoxin and cytokine-induced shock are provided. A therapeutic regimen useful in the present invention includes an arginine-free parenteral formulation administered with or followed by the administration of an anti-endotoxin antibody, an interleukin-1 or interleukin-2 receptor antagonist, an anti-tumor necrosis factor antibody or a combination thereof. Most preferably, the administration of an arginine-free parenteral formulation augments the anti-hypotensive effect of the various antibodies and antagonist described so as to provide an effective treatment for various forms of hypotension. The therapeutic regimens of the invention are proposed to provide for a decrease in nitric oxide synthase, and thereby an increase in blood pressure in vivo, particularly in animals with cytokine- and/or endotoxin-induced hypotension.Type: GrantFiled: June 30, 1992Date of Patent: August 2, 1994Assignee: Board of Regents, The University of Texas SystemInventors: Robert G. Kilbourn, Owen W. Griffith, Steven S. Gross
-
Patent number: 5312835Abstract: The present invention involves a method for prophylaxis or treatment of an animal for systemic hypotension induced by endotoxin and/or a biological response modifier such as the cytokines, IFN, TNF, IL-1 or IL-2 and the like. Said method involves administering, preferably intravascularly, a therapeutically effective amount of dobutamine and an inhibitor of nitric oxide formation from arginine. Although preferable administration is intravascular, it is contemplated that other parenteral administration routes such as intraperitoneal, intramuscular or subdermal injection, for example, may prove useful. Enteral or topical administration of arginine analogs may also prove beneficial under certain clinical conditions.Type: GrantFiled: May 29, 1992Date of Patent: May 17, 1994Assignees: Board of Regents, the University of Texas System, Cornell Research Foundation, Inc.Inventors: Robert G. Kilbourn, Steven S. Gross, Owen W. Griffith
-
Patent number: 5294736Abstract: The pure isomers L-buthionine-S-sulfoximine and L-buthionine-R-sulfoximine are provided. The L-S-isomer has utility, for example, in causing the depletion of glutathione, a major protectant molecule in tumors and certain parasites. The L-R-isomer has utility as a compound decreasing further uptake and thus effect of the L-S-isomer and for causing glutathione depletion specific to the kidney. The isolation of pure isomers from L-buthionine-SR-sulfoximine enables treatment at lower dosages without cross effects.The pure L-buthionine-S-sulfoximine isomer is obtained from L-buthionine-SR-sulfoximine by recrystallization preferably by forming a solution of L-buthionine-SR-sulfoximine in water at a concentration of 0.Type: GrantFiled: May 5, 1993Date of Patent: March 15, 1994Assignee: Cornell Research Foundation, Inc.Inventor: Owen W. Griffith
-
Patent number: 5286739Abstract: An anti-hypotensive formulation comprising an essentially arginine-free or low arginine (less than about 0.1%, most preferably, about 0.01%) containing mixture of amino acids is provided. The invention in particular embodiments of the anti-hypotensive formulation includes ornithine, citrulline or both. A method for prophylaxis and treatment of systemic hypotension in an animal is provided. Most particularly, a method for treating hypotension caused by nitric oxide synthesis through administering a low or essentially arginine-free parenteral formulation to an animal, so as to reduce or eliminate nitric oxide synthesis is described. A method for treating an animal in septic shock is also disclosed, comprising administering to the animal an anti-hypotensive formulation comprising a mixture of amino acids, which is essentially arginine free.Type: GrantFiled: September 27, 1991Date of Patent: February 15, 1994Assignee: Board of Regents, University of Texas SystemInventors: Robert G. Kilbourn, Owen W. Griffith, Steven S. Gross
-
Patent number: 5281627Abstract: Guanidino substituted arginines or homoarginines based on monoalkyl carbon-substituted ornithines or lysines, having the formula ##STR1## wherein R is (CH.sub.2).sub.y CH.sub.3 or H, R' is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, and R" is CH.sub.2 or C(H)(CH.sub.2).sub.y CH.sub.3, with y ranging from 0 to 5, and x is 0 or 1 and Q is an alkyl group containing from 1 to 6 carbon atoms or NH.sub.2 or NO.sub.2, and only one of R, R' and R" providing an alkyl substituent on the ornithine or lysine moiety. PreThis invention was made at least in part with Government support under Grant DK 37116 from National Institutes of Health.Type: GrantFiled: May 28, 1992Date of Patent: January 25, 1994Assignee: Cornell Research Foundation, Inc.Inventor: Owen W. Griffith
-
Patent number: 5273875Abstract: Physiologically active N.sup.6 -(hydrazinoiminomethyl)lysine or pharmaceutically acceptable acid addition salt thereof is administered in a nitric oxide synthesis inhibiting amount to a subject in need of such inhibition (e.g., a subject with low blood pressure, e.g., due to sepsis or to therapeutic administration of cytokines, or needing immunosuppressive effect) or is added to a medium containing isolated organs, intact cells, cell homogenates or tissue homogenates in an amount sufficient to inhibit nitric oxide formation to elucide or control the biosynthesis, metabolism or physiological role of nitric oxide. CompThis invention was made at least in part with Government support under National Institutes of Health grant number DK 37116. The Government has certain rights in the invention.Type: GrantFiled: April 8, 1992Date of Patent: December 28, 1993Assignee: Cornell Research Foundation, Inc.Inventor: Owen W. Griffith
-
Patent number: 5245077Abstract: The pure isomers L-buthionine-S-sulfoximine and L-buthionine-R-sulfoximine are provided. The L-S-isomer has utility, for example, in causing the depletion of glutathione, a major protectant molecule in tumors and certain parasites. The L-R-isomer has utility as a compound decreasing further uptake and thus effect of the L-S-isomer and for causing glutathione depletion specific to the kidney. The isolation of pure isomers from L-buthionine-SR-sulfoximine enables treatment at lower dosages without cross effects.The pure L-buthionine-S-sulfoximine isomer is obtained from L-buthionine-SR-sulfoximine by recrystallization preferably by forming a solution of L-buthionine-SR-sulfoximine in water at a concentration of 0.Type: GrantFiled: July 2, 1992Date of Patent: September 14, 1993Assignee: Cornell Research Foundation Inc.Inventor: Owen W. Griffith
-
Patent number: 5196195Abstract: Reducing plasma levels of endogenous arginine by parenteral administration of arginine depleting agent reduces nitric oxide levels and results in blood pressure increase. Preferably arginase is administered intravenously to raise blood pressure. The arginase can be administered in conjunction with arginine antagonists to potentiate the effect of these. Duration of action and avoidance of antigenicity may be obtained by use in conjunction with a carrier or modifier.Type: GrantFiled: March 27, 1990Date of Patent: March 23, 1993Assignee: Cornell Research Foundation, Inc.Inventor: Owen W. Griffith
-
Patent number: 5171885Abstract: The pure isomers L-buthionine-S-sulfoximine and L-buthionine-R-sulfoximine are provided. The L-S-isomer has utility, for example, in causing the depletion of glutathione, a major protectant molecule in tumors and certain parasites. The L-R-isomer has utility as a compound decreasing further uptake and thus effect of the L-S-isomer and for causing glutathione depletion specific to the kidney. The isolation of pure isomers from L-buthionine-SR-sulfoximine enables treatment at lower dosages without cross effects.The pure L-buthionine-S-sulfoximine isomer is obtained from L-buthionine-SR-sulfoximine by recrystallization preferably by forming a solution of L-buthionine-SR-sulfoximine in water at a concentration of 0.Type: GrantFiled: June 19, 1991Date of Patent: December 15, 1992Assignee: Cornell Research Foundation, Inc.Inventor: Owen W. Griffith