Novel uricase variants and methods of use thereof
AssigneeInsmed Incorporated
InventorsChris BAILEY-KELLOGG, Karl GRISWOLD, Claire GODBERSEN-PALMER, Hao CHENG, Yongliang FANG, Matthew MILLER, Adam PLAUNT, Sasha ROSE
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Abstract
The present disclosure relates to chimeric pig-baboon uricase variants, Arthrobacter globiformis uricase variants, Aspergillus flavus uricase variants, and Candida utilis uricase variants, and methods of using the same to treat gout, tumor lysis syndrome, and other diseases associated with elevated uric acid levels in body fluids, including blood. Methods of producing the uricase variants disclosed herein are also provided.
Claims63
A uricase variant comprising a plurality of amino acid substitutions relative to the chimeric pig-baboon uricase of SEQ ID NO:5, wherein the plurality of amino acid substitutions is selected from the group consisting of (i), (ii), (iii) and (iv):
- (i) F75Q;
- K79E;
- T83Q;
- E90H;
- F96H;
- I100H;
- Y105D;
- V119K;
- Y127H;
- F172Y;
- and L260N;
- (ii) F75Q;
- K79E;
- T83Q;
- E90H;
- F96H;
- I100H;
- Y105D;
- V119K;
- Y127H;
- K155N;
- F172Y;
- and L260N;
- (iii) F75Q;
- K76N;
- K79N;
- T83Q;
- E90H;
- F96H;
- I100E;
- Y105D;
- V119K;
- F172Y;
- L260N;
- and I262T;
- and
- (iv) F75Q;
- K76N;
- K79N;
- T83Q;
- E90H;
- F96H;
- I100E;
- Y105D;
- V119K;
- K155N;
- F172Y;
- L260N;
- and I262T.
A uricase variant comprising an amino acid sequence selected from SEQ ID NOs:
- 197-273.
A uricase variant comprising an amino acid sequence selected from SEQ ID NOs:
- 12-196.
A uricase variant comprising an amino acid sequence selected from SEQ ID NOs:
- 274-341.
Dependencies are inferred from the claim text.