Richard Earl

7396829, Jul 8, 2008

Feb 24, 2006

11/360599

David S. Garvey - Dover MA, US
L. Gordon Letts - Dover MA, US
Richard A. Earl - Westford MA, US
Maiko Ezawa - San Diego CA, US
Xinqin Fang - Lexington MA, US
Ricky D. Gaston - Malden MA, US
Subhash P. Khanapure - Littleton MA, US
Chia-En Lin - Concord MA, US
Ramani R. Ranatunge - Lexington MA, US
Cheri A. Stevenson - Haverhill MA, US

Nitromed, Inc. - Lexington MA

C07D 417/02
A61K 31/549

5142232, 544 48

The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

7442802, Oct 28, 2008

May 5, 2006

11/418187

Upul K. Bandarage - Lexington MA, US
Richard A. Earl - Westford MA, US
Maiko Ezawa - Acton MA, US
Xinqin Fang - Lexington MA, US
David S. Garvey - Dover MA, US
Subhash P. Khanapure - Clinton MA, US
Ramani R. Ranatunge - Lexington MA, US
Stewart K. Richardson - Tolland CT, US
Joseph D. Schroeder - Minneapolis MA, US
Cheri A. Stevenson - Haverhill MA, US

NitroMed, Inc. - Lexington MA

A61K 31/415
C07D 231/12

5483751, 514406

The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

6462044, Oct 8, 2002

Aug 30, 2001

09/941691

David S. Garvey - Dover MA
Inigo Saenz de Tejada - Madrid, ES
Richard A. Earl - Westford MA
Subhash P. Khanapure - Clinton MA

NitroMed, Inc. - Bedford MA

A61K 31519

514246, 514250, 51425216, 5142581, 5142633, 5142664, 514267, 514292, 514307, 514404, 514619, 514655, 514676, 514716, 514728, 544237, 544251, 544254, 544265, 544280, 544293, 544343, 546111, 546149, 5483677, 564163, 564384, 568306, 568584, 568588, 568716, 568744

The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions containing at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one phosphodiesterase inhibitor, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3â,5â-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e. g. , postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, glucoma, and diseases characterized by disorders of gut motility, e. g.

7595313, Sep 29, 2009

Jun 10, 2008

12/136531

David S. Garvey - Dover MA, US
L. Gordon Letts - Dover MA, US
Richard A. Earl - Westford MA, US
Maiko Ezawa - Acton MA, US
Xinqin Fang - Lexington MA, US
Ricky D. Gaston - Malden MA, US
Subhash P. Khanapure - Clinton MA, US
Chia-En Lin - Concord MA, US
Ramani R. Ranatunge - Lexington MA, US
Cheri A. Stevenson - Haverhill MA, US

NicOx, S.A.

C07D 285/24
C07D 417/04
C07D 513/10
A61K 31/549

5142232, 544 6

The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

7754772, Jul 13, 2010

May 23, 2005

11/134358

Richard A. Earl - Westford MA, US
Maiko Ezawa - Acton MA, US
Xinqin Fang - Lexington MA, US
David S. Garvey - Dover MA, US
Ricky D. Gaston - Malden MA, US
Subhash P. Khanapure - Clinton MA, US
L. Gordon Letts - Dover MA, US
Chia-En Lin - Burlington MA, US
Ramani R. Ranatunge - Lexington MA, US
Stewart K. Richardson - Tolland CT, US
Joseph D. Schroeder - Minneapolis MN, US
Cheri A. Stevenson - Haverhill MA, US

NicOx, S.A.

A61K 31/135
C07C 203/04

514658, 558484

The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

6706724, Mar 16, 2004

Dec 21, 2001

10/024046

Subhash P. Khanapure - Clinton MA
David S. Garvey - Dover MA
Richard A. Earl - Westford MA
Maiko Ezawa - Acton MA
Xinqin Fang - Lexington MA
Ricky D. Gaston - Malden MA

NitroMed, Inc. - Bedford MA

A61K 31435

514277, 514336, 514340, 514342, 514365, 514374, 514443, 514469, 546 1, 546114, 546115, 546208, 548146, 548152, 548153, 548217, 549229, 549396, 549398, 549430, 549462, 549469, 549472

The invention describes novel substituted aryl compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or, optionally, at least one therapeutic agent, such as, steroids, nonsterodal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B (LTB ) receptor antagonists, leukotriene A (LTA ) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H antagonists, antineoplastic agents, antiplatelet agents, thrombin inhibitors, thromboxane inhibitors, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated.

7883714, Feb 8, 2011

Dec 11, 2009

12/636306

Richard A. Earl - Westford MA, US
Maiko Ezawa - Acton MA, US
Xinqin Fang - Lexington MA, US
David S. Garvey - Dover MA, US
Ricky D. Gaston - Malden MA, US
Subhash P. Khanapure - Clinton MA, US
L. Gordon Letts - Dover MA, US
Chia-En Lin - Concord MA, US
Ramani R. Ranatunge - Lexington MA, US
Stewart K. Richardson - Tolland CT, US
Joseph D. Schroeder - Minneapolis MN, US
Cheri A. Stevenson - Haverhill MA, US

NicOx S.A.

A61K 9/00
A61K 31/21
C07C 203/04

424400, 514509, 514510, 558480, 558482

The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

8088762, Jan 3, 2012

Dec 11, 2009

12/636316

Richard A. Earl - Westford MA, US
Maiko Ezawa - Acton MA, US
Xinqin Fang - Lexington MA, US
David S. Garvey - Dover MA, US
Ricky D. Gaston - Malden MA, US
Subhash P. Khanapure - Clinton MA, US
L. Gordon Letts - Dover MA, US
Chia-En Lin - Concord MA, US
Ramani R. Ranatunge - Lexington MA, US
Stewart K. Richardson - Tolland CT, US
Joseph D. Schroeder - Minneapolis MN, US
Cheri A. Stevenson - Haverhill MA, US

NiCox S.A. - Sophia Antipolis

A61K 31/54
A61K 31/44
A61K 31/425
C07D 498/02
C07D 295/02
C07D 333/22

5142248, 514300, 514302, 514365, 544386, 548224, 549 72

The invention describes novel nitrosated nonsteroidal anti-inflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.