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.
Claims8
An isolated recombinant tetrameric mammalian uricase, wherein said uricase is in a substantially tetrameric form, wherein less than 10% of said uricase is in a non-tetrameric aggregated form, and wherein said uricase is chimeric.
An isolated recombinant tetrameric mammalian uricase, wherein said uricase is recombinant porcine uricase containing lysine in place of arginine at residue number 291 in SEQ ID NO:1 and serine in place of threonine at residue number 301 in SEQ ID NO:1.
An isolated recombinant tetrameric mammalian uricase, wherein said uricase has the sequence of baboon liver uricase in which tyrosine 97 in SEQ ID NO:2 has been replaced by histidine.
Dependencies are inferred from the claim text.