Mitchell P Fink, 763967 Marcasel Ave, Los Angeles, CA 90066

6846842, Jan 25, 2005

Apr 4, 2002

10/116707

Alfred M. Ajami - Brookline MA, US
Carrie A. Sims - Boston MA, US
Mitchell P. Fink - Pittsburgh PA, US

Beth Israel Deconess Medical Center, Inc. - Boston MA
Xanthus Life Sciences, Inc. - Montreal

A61K 31231
A61K 3119

514547, 514557

A therapeutic composition comprising an alkyl, aralkyl, alkoxyalkyl or carboxyalkyl ester of 2-ketoalkanoic acid and a component for inducing and stabilizing the enol resonance form of the ester at physiological pH values is disclosed. The composition of the invention further comprises a pharmceutically acceptable carier vehicle in which the enol resonance form of the ester is stabilized at physiological pH values. Formulations containing the compositions of the invention permit the successful use of 2-ketoalkanoic acid esters, e. g. , pyruvic acid esters, to treat, e. g. , ischemic events, shock, organ reanimation, resuscitation and other recognized pyruvate-effective treatments. The compositions of the inventions are also useful in a process for preserving organ parts, organs or limbs removed from a living mammal and in need of preservation, e. g. , for later transplantation to an organ recipient.

6943190, Sep 13, 2005

Sep 15, 2003

10/662975

Mitchell P. Fink - Pittsburgh PA, US
Luis Ulloa - Jackson Heights NY, US
Kevin J. Tracey - Old Greenwich CT, US
Russell L. Delude - Pittsburgh PA, US

University of Pittsburgh-of the Commonwealth System of Higher Education - Pittsburgh PA
North Shore-Long Island Jewish Research Institute - Great Neck NY

A61K031/22

514456

This invention is directed to a method of using a therapeutic composition comprising a compound of an alpha-ketoalkanoic acid (pyruvate) and/or its derivatives for the treatment of cytokine-mediated inflammatory conditions. The compound is an alpha-ketoalkanoic acid, a physiologically acceptable salt of an alpha-ketoalkanoic acid, an ester of an alpha-ketoalkanoic acid, or an amide of an alpha-ketoalkanoic acid. A component for inducing and stabilizing the enol resonance form of the ester at physiological pH values is also disclosed. The cytokine-mediated inflammatory conditions are mediated by, for example, an “early” (Tumor Necrosis Factor (TNF), interleukin-1β (IL-1β)) or “late” (high mobility group B-1 (HMGB-1)) mediator of inflammation. Exemplary cytokine-mediated inflammatory conditions include, but are not limited to, local and systemic inflammation, inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatoid arthritis, asthma (including status asthmaticus), sepsis or septic shock, also including inflammatory skin conditions, for example, psoriasis and eczema.

7304034, Dec 4, 2007

Nov 20, 2002

10/300072

Kevin J. Tracey - Old Greenwich CT, US
Huan Yang - Douglaston NY, US
Mitchell P. Fink - Pittsburgh PA, US

The Feinstein Institute for Medical Research - Manhasset NY
The General Hospital Corporation - Boston MA
University of Pittsburgh-Of the Commonwealth System of Higher Education - Pittsburgh PA

A61K 38/00
C07K 14/00

514 12, 514 2, 530300, 530324, 5303871, 536 231, 4353201, 4352523, 435325, 435 71, 424 91

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise a vertebrate HMGB A box, and an antibody preparation that specifically binds to a vertebrate HMGB B box. The methods comprise treating a cell or a patient with sufficient amounts of the composition to inhibit the release of the proinflammatory cytokine, or to inhibit the inflammatory cytokine cascade.

7332479, Feb 19, 2008

Sep 10, 2003

10/659063

Mitchell P. Fink - Pittsburgh PA, US
Russell L. Delude - Pittsburgh PA, US
Xianonan Han - Pittsburgh PA, US

University of Pittsburgh - of the Commonwealth System of Higher Education - Pittsburgh PA

A61K 31/70
A61K 31/7076
C07H 19/167

514 46, 514 47, 514886, 514921, 536 261

A method of prophylaxis or treatment of inflammatory conditions, including, but not limited to, intestinal epithelial inflammation due to intestine-specific conditions (e. g. , Crohn's disease or ulcerative colitis) or systemic causes of inflammation (e. g. , endotoxemia, sepsis, hemorrhagic shock/resuscitation or pancreatitis) is disclosed. In the method of the invention, an affected patient is administered a therapeutically effective amount of a composition including an NAD-related compound, in a form that is accessible to a receptor molecule, conveyed in a pharmaceutically acceptable carrier vehicle. NAD-related compounds include nicotinamide adenine dinucleotide (NAD), cyclic adenosine diphosphate ribose (cADPR), or functionally equivalent analogues, derivatives, metabolites or agonists thereof or prodrugs therefor. Also disclosed are ex vivo and in vivo assay methods to test candidate compounds for activity, kits for carrying out the therapeutic methods or the assay methods of the invention and articles of manufacture that include compositions for use in the methods of the invention and instructions for the use thereof.

7528174, May 5, 2009

Aug 17, 2006

11/465162

Peter Wipf - Pittsburgh PA, US
Jingbo Xiao - Pittsburgh PA, US
Mitchell P. Fink - Pittsburgh PA, US
Valerian E. Kagan - Pittsburgh PA, US
Yulia Y. Tyurina - Pittsburgh PA, US

University of Pittsburgh-Of The Commonwealth System of Higher Education - Pittsburgh PA

A61K 38/05
A61K 38/06
A61K 38/08
A61K 31/00

514645, 514 17, 514 18, 514 19

Compositions and methods are disclosed for treating an illness that is caused or associated with cellular damage or dysfunction which is caused by excessive mitochondrial production of reaction oxygen species (ROS). Compositions which act as mitochondria-selective targeting agents using specific structural signaling features recognizable by cells as mitochondrial targeting sequences are discussed. A method for delivering these agents effectively into cells and mitochondria where they act as electron scavengers by way of certain targeting sequences is also disclosed. Mitochondria dysfunction and cell death by way of apoptosis is inhibited as a result of the ROS-scavenging activity, thereby increasing the survival rate of the patient. In a preferred embodiment, the compositions and methods may be administered therapeutically in the field to patients with profound hemorrhagic shock so that survival could be prolonged until it is feasible to obtain surgical control of the bleeding vessels.

7718603, May 18, 2010

Dec 1, 2006

11/565779

Peter Wipf - Pittsburgh PA, US
Jingbo Xiao - Pittsburgh PA, US
Mitchell P. Fink - Pittsburgh PA, US
Valerian E. Kagan - Pittsburgh PA, US
Yulia Y. Tyurina - Pittsburgh PA, US
Anthony J. Kanai - Pittsburgh PA, US

University of Pittsburgh-Of the Commonwealth System of Higher Education - Pittsburgh PA

A61K 38/00

514 2

The present invention provides a composition and related methods for delivering cargo to a mitochondria which includes (a) a membrane active peptidyl fragment having a high affinity with the mitochondria and (b) cargo. The cargo may be selected from a wide variety of desired cargos which are to be delivered to the mitochondria for a specific purpose. Compositions and methods are disclosed for treating an illness that is caused or associated with cellular damage or dysfunction which is caused by excessive mitochondrial production of reaction oxygen species (ROS). Compositions which act as mitochondria-selective targeting agents using the structural signaling of the β-turn recognizable by cells as mitochondria) targeting sequences are discussed. Mitochondria and cell death by way of apoptosis is inhibited as a result of the ROS-scavenging activity, thereby increasing the survival rate of the patient. In a preferred embodiment, the compositions and methods may be administered therapeutically in the field to patients with profound hemorrhagic shock so that survival could be prolonged until it is feasible to obtain surgical control of the bleeding vessels.

7749959, Jul 6, 2010

Sep 19, 2007

11/901880

Kevin J. Tracey - Old Greenwich CT, US
Huan Yang - Douglaston NY, US
Mitchell P. Fink - Pittsburgh PA, US

The Feinstein Institute for Medical Research - Manhasset NY
The General Hospital Corporation - Boston MA
University of Pittsburgh-of the Commonwealth System of Higher Education - Pittsburgh PA

A61K 38/00
C07K 14/00

514 2, 514 12, 530300, 530324, 424 91, 435 71, 435 697

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise a vertebrate HMGB A box, and an antibody preparation that specifically binds to a vertebrate HMGB B box. The methods comprise treating a cell or a patient with sufficient amounts of the composition to inhibit the release of the proinflammatory cytokine, or to inhibit the inflammatory cytokine cascade.

7829097, Nov 9, 2010

Feb 6, 2007

11/671932

Allan Tsung - Pittsburgh PA, US
Timothy R. Billiar - Presto PA, US
Mitchell P. Fink - Pittsburgh PA, US
Kevin J. Tracey - Old Greenwich CT, US

University of Pittsburgh - Of the Commonwealth System of Higher Education - Pittsburgh PA
The Feinstein Institute for Medical Research - Manhasset NY

A61K 38/18

4241851

Methods and compositions are disclosed for protecting an organ or tissue from inflammation and organ injury following ischemia, reperfusion, and trauma through the administration of an HMGB protein within a time period sufficient to protect the organ or tissue from injury.