Signature Therapeutics, Inc.

Theravance, Inc.

Elysium Therapeutics, Inc.

Axys Pharmaceuticals, Inc.

Advanced Medicine, Inc.

University of California

Other

Arris Pharmaceutical Corporation

Singature Therapeutics, Inc.

Pharmacofore, Inc.

Thomas E Jenkins

Craig Husfeld

Yu-Hua Ji

Sabine Axt

Timothy J Church

Jonathan W Wray

Julie D Seroogy

Jennifer Bolton

John R Jacobsen

John H Griffin

J Kevin Judice

James M Clark

Robert M Stroud

Bradley A Katz

Huiwei Wu

Martin Sheringham Linsell

Maya Natarajan

Witold Hruzewicz

Seok-Ki Choi

Daniel Marquess

Aleksandr Kolesnikov

William R Moore

Kyle C Elrod

David Beattie

Scott Armstrong

Paul Ross Fatheree

Michael Robert Leadbetter

Wendy B Young

Sean Gary Trapp

Kenneth D Rice

Joane Litvak

Erik Joel Verner

Jeffrey R Spencer

Anthony R Gangloff

David C Green

Qi-Qi Chen

Witold N Hruzewicz

Neil Scott Cutshall

Vivian R Wang

Craig O Husfeld

Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise an amphetamine prodrug that provides enzymatically-controlled release of amphetamine or an amphetamine analog. The composition can further comprise an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of amphetamine or the amphetamine analog from the amphetamine prodrug so as to attenuate enzymatic cleavage of the amphetamine prodrug.

Compositions comprising enzyme-cleavable amphetamine prodrugs and inhibitors thereof

The present invention provides a composition comprising an opioid agonist, and a polymer-antagonist conjugate. The polymer-antagonist conjugate preferably does not hydrolyze upon administration to a patient, and does not bind to the opioid receptors. The covalent bond between the polymer and the antagonist in the conjugate is broken over a defined period of time to release the antagonist into the formulation. The released antagonist attenuates the liking of the agonist, thereby eliminating the incentive to the diversion of the medicines.

Diversion-resistant opioid formulations

The invention provides compositions and methods for the treatment or prevention of pain. Compositions provided are resistant to overdose and abuse. Compositions provided comprise two or more different molecules, where each molecule comprises at least one GI enzyme-labile opioid agonist releasing subunit comprising an opioid agonist that is covalently linked to at least one GI enzyme inhibitor subunit.

Polysubunit opioid prodrugs resistant to overdose and abuse

The invention provides pharmaceutical compositions comprising macromolecular gastrointestinal enzyme-labile opioid prodrugs, co-formulated with small-molecule and/or macromolecular gastrointestinal enzyme inhibitors. The macromolecular constructs are minimally absorbed from the GI tract, and can produce non-linear pharmacokinetic profiles of the delivered opioid agonist following oral ingestion. An optional macromolecular opioid antagonist may also be present in compositions of the invention to discourage tampering by potential abusers.

Opioid compositions resistant to overdose and abuse

The invention provides compositions and methods for the treatment or prevention of pain. The invention provides constructs whereby hydrolysis of the construct by a specified gastrointestinal enzyme directly, or indirectly, releases an opioid when taken orally as prescribed. The gastrointestinal enzyme mediated release of opioid from constructs of the invention is designed to be attenuated in vivo via a saturation or inhibition mechanism when overdoses are ingested. The invention further provides constructs that are highly resistant to oral overdose, chemical tampering, and abuse via non-oral routes of administration.

A method of providing a patient with controlled release of ketone-containing opioid using a prodrug capable, upon enzymatic activation and intramolecular cyclization, of releasing the ketone-containing opioid is disclosed. The disclosure also provides such prodrug compounds and pharmaceutical compositions comprising such compounds. Such pharmaceutical compositions can optionally include an enzyme inhibitor that interacts with the enzyme(s) to mediate the enzymatically-controlled release of the ketone-containing opioid from the prodrug so as to modify enzymatic cleavage of the prodrug. Also included are methods to use such compounds and pharmaceutical compositions.

Compositions comprising enzyme-cleavable ketone-modified opioid prodrugs and optional inhibitors thereof

Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise an opioid prodrug that provides enzymatically-controlled release of an opioid, and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the opioid from the opioid prodrug so as to attenuate enzymatic cleavage of the opioid prodrug.

Compositions comprising enzyme-cleavable opioid prodrugs and inhibitors thereof

Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise a phenolic opioid prodrug that provides enzymatically-controlled release of a phenolic opioid, and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the phenolic opioid from the prodrug so as to attenuate enzymatic cleavage of the prodrug.

Pharmaceutical compositions with attenuated release of phenolic opioids

The embodiments provide Compound KC-8, N-1-[3-(oxycodone-6-enol-carbonyl-methyl-amino)-2,2-dimethyl-propylamine]-arginine-glycine-malonic acid, or acceptable salts, solvates, and hydrates thereof. The present disclosure also provides compositions, and their methods of use, where the compositions comprise a prodrug, Compound KC-8, that provides controlled release of oxycodone. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of oxycodone from the prodrug so as to attenuate enzymatic cleavage of the prodrug.

Compositions comprising enzyme-cleavable oxycodone prodrug

Growing community of inventors

Half Moon Bay, CA, United States of America

Thomas E Jenkins