PEG-urate oxidase conjugates and use thereof
First Claim
1. A conjugate of urate oxidase (uricase) that retains uricolytic activity and has a prolonged half-life in vivo compared to an unconjugated uricase, said conjugate comprising a purified recombinant mammalian uricase conjugated to poly(ethylene glycol) (PEG), wherein greater than 90% of said uricase is in a tetrameric form, and wherein said PEG has an average molecular weight of about 10 kDa to about 60 kDa.
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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.
55 Citations
23 Claims
- 1. A conjugate of urate oxidase (uricase) that retains uricolytic activity and has a prolonged half-life in vivo compared to an unconjugated uricase, said conjugate comprising a purified recombinant mammalian uricase conjugated to poly(ethylene glycol) (PEG), wherein greater than 90% of said uricase is in a tetrameric form, and wherein said PEG has an average molecular weight of about 10 kDa to about 60 kDa.
- 9. A conjugate of urate oxidase (uricase) that retains uricolytic activity and has a prolonged half-life in vivo compared to an unconjugated uricase, said conjugate comprising a purified recombinant uricase conjugated to poly(ethylene glycol) (PEG), wherein greater than 90% of said uricase is in a tetrameric form, wherein said uricase contains a portion of at least one of a porcine, bovine, ovine or baboon liver uricase, and wherein said PEG has an average molecular weight of about 10 kDa to about 60 kDa.
- 22. A pharmaceutical composition for lowering uric acid levels in a body fluid or tissue, comprising a purified recombinant uricase conjugated to poly(ethylene glycol) (PEG) and a pharmaceutically acceptable carrier, wherein greater than 90% of said uricase is in a tetrameric form, wherein said uricase contains a portion of at least one of a porcine, bovine, ovine or baboon liver uricase, and wherein said PEG has an average molecular weight of about 10 kDa to about 60 kDa.
Specification