PEG-urate oxidase conjugates and use thereof
AssigneesMountain View Pharmaceuticals, Inc., Duke University
InventorsL. David Williams, Michael S. Hershfield, Susan J. Kelly, Mark G. P. Saifer, Merry R. Sherman
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Abstract
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.
Claims53
A conjugate of uricase that retains at least about 75% of the uricolytic activity of unconjugated uricase and is substantially non-immunogenic, comprising a purified uricase comprising subunits in which each subunit of the uricase is covalently linked to an average of 2 to 10 strands of PEG, wherein each molecule of PEG has a molecular weight between about 5 kDa and 100 kDa.
A method for lowering elevated uric acid levels in a body fluid or tissue of a mammal, comprising the step of administering to said mammal an effective uric acid-lowering amount of PEG-uricase, said PEG-uricase comprising a purified uricase comprising at least two subunits in which each subunit is covalently linked to an average of 2 to 10 strands of PEG, wherein each molecule of PEG has a molecular weight between about 5 kDa and 100 kDa, in a pharmaceutically acceptable carrier.
A method for isolating a tetrameric form of uricase from a solution of uricase, said solution comprising tetrameric uricase and uricase aggregates, comprising the steps of:
- applying said solution to at least one separation column at a pH between about 9 and 10.5;
- and
- recovering from said column one or more fractions that contain isolated tetrameric uricase, wherein said one or more fractions are substantially free of uricase aggregates.
A method for isolating a tetrameric form of uricase from a solution of uricase, said solution comprising tetrameric uricase and uricase aggregates, comprising the steps of:
- applying said solution to at least one separation column at a pH between about 9 and 10.5;
- and
- recovering from said column one or more fractions that contain isolated tetrameric uricase, wherein said one or more fractions are substantially free of uricase aggregates.
Dependencies are inferred from the claim text.