Duke University

Mountain View Pharmaceuticals, Inc.

Other

Savient Pharmaceuticals, Inc.

Horizon Pharma Rheumatology LLC

Michael S Hershfield

Susan J Kelly

L David Williams

Mark G P Saifer

Merry R Sherman

Ashutosh Chilkoti

Yizhi Qi

Nancy J Ganson

Mark G Saifer

Jacob R Hartman

Simona Mendelovitz

Angus Hucknall

Daniel Joh

Claudia D Rehrig

William Huang

L David Williams Williams

Mark Gp Saifer

Disclosed herein are compositions and methods for reducing the antigenicity of molecules. The antigenicity of a molecule may be reduced or eliminated by conjugating at least one branched polymer to the molecule to form a molecule-polymer conjugate. The branched polymer may include a backbone and a plurality of side chains, each side chain covalently attached to the backbone.

Surfaces having reduced non-specific binding and antigenicity

Disclosed herein are compositions and methods for reducing the antigenicity of molecules, wherein the molecule comprises a uricase. The antigenicity of a molecule may be reduced or eliminated by conjugating at least one branched polymer to the molecule to form a molecule-polymer conjugate. The branched polymer may include a backbone and a plurality of side chains, each side chain covalently attached to the backbone.

Polymer conjugates having reduced antigenicity and methods of using the same

A naturally occurring or recombinant urate oxidase (uricase) covalently coupled to poly(ethylene glycol) or poly(ethylene oxide) (both referred to as PEG), wherein an average of 2 to 10 strands of PEG are conjugated to each uricase subunit and the PEG has an average molecular weight between about 5 kDa and 100 kDa. The resulting PEG-uricase conjugates are substantially non-immunogenic and retain at least 75% of the uricolytic activity of the unmodified enzyme.

PEG-urate oxidase conjugates and use thereof

A naturally occurring or recombinant protein, especially a mutein of porcine urate oxidase (uricase), that is essentially free of large aggregates can be rendered substantially non-immunogenic by conjugation with a sufficiently small number of strands of polymer such that the bioactivity of the protein is essentially retained in the conjugate. Such conjugates are unusually well suited for treatment of chronic conditions because they are less likely to induce the formation of antibodies and/or accelerated clearance than are similar conjugates prepared from protein preparations containing traces of large aggregates.

Method for purifying urate oxidase tetramers and octamers

A method for lowering elevated uric acid levels in patients is disclosed and consists of administering to the patients an intravenous injection of PEG-uricase having a dosage from about 4 to about 12 mg.

Methods for lowering elevated uric acid levels using intravenous injections of PEG-uricase

Aggregate-free urate oxidase for preparation of non-immunogenic polymer conjugates

The present invention relates, in general, to urate oxidase (uricase) proteins and nucleic acid molecules encoding same. In particular, the invention relates to uricase proteins which are particularly useful as, for example, intermediates for making improved modified uricase proteins with reduced immunogenicity and increased bioavailability.

Urate oxidase

Growing community of inventors

Durham, NC, United States of America

Michael S Hershfield