Provided herein are methods and compositions related to the administration of uricase compositions and compositions comprising synthetic nanocarriers comprising an immunosuppressant for the treatment of subjects, including subjects with hyperuricemia, gout or a condition associated with gout.

A mutant-type uricase, PEG modified mutant-type uricase, and application thereof. The mutant-type uricase has a cysteine residue introduced by recombination, the cysteine residue is located at an inactive region of the uricase, and one or more PEGs are coupled to the mutant-type uricase. The resulting PEGylated mutant-type uricase has characteristics of a half-life extension, product uniformity, and stable enzyme activity. Therefore, the present invention has a wide future application range.

The present invention relates to a conjugate capable of controlling in vivo half-life, which comprises urate oxidase; a pharmaceutical composition with increased in vivo half-life for preventing or treating gout, which comprises the conjugate or a pharmaceutically acceptable salt thereof; and a method for preventing or treating gout using the same.

It was found that the conjugate of the present invention has a very important role in the extension of in vivo serum half-life by controlling its binding competition with a neonatal Fc receptor (FcRn) for serum albumin (SA) based on the length of its linker, and this finding has significance with respect to its application as an agent for gout treatment and extension of application of fatty acid (FA) conjugation to therapeutic proteins having a high molecular weight.

Genetically modified proteins with uricolytic activity are described. Proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidase are described.

Zwitterionic phosphatidylserione (ZPS) monomers, ZPS polymers and ZPS copolymers, methods for making the ZPS monomers, ZPS polymers, and ZPS copolymers, compositions and materials that include ZPS polymers and ZPS copolymers, and methods for using the ZPS monomers, ZPS polymers, and ZPS copolymers.

A modified uricase is described herein, as well as a method of reducing a level of uric acid by contacting a medium with the modified uricase. The modified uricase comprises a uricase polypeptide crosslinked by at least one bifunctional linking moiety that comprises a poly(alkylene glycol) moiety. A molecular weight of the bifunctional linking moiety is from about 1.5 kDa to about 4 kDa, and/or the modified uricase comprises a plurality of polypeptides having the amino acid sequence SEQ ID NO: 2. Further described is a polypeptide having the amino acid sequence SEQ ID NO: 2. A process of preparing the modified uricase is also described, comprising contacting the polypeptide with a crosslinking agent that comprises a poly(alkylene glycol) moiety and at least two aldehyde groups, to obtain a conjugate; and contacting the conjugate with a reducing agent.

Provided herein are methods and compositions and kits related to identification and/or treatment of subjects, including subjects with hyperuricemia, gout or a condition associated with gout, and for preventing gout flare.

The disclosure provides methods of treating gout in patients comprising administering a PEGylated uricase. Also provided are methods of treating gout in patients comprising co-administering a PEGylated uricase and MMF. Also provided are methods of reducing intolerance to a PEGylated uricase and prolonging the urate lowering effect comprising co-administration of the PEGylated uricase and MMF.

Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response during intravenous PEGylated uricase therapy in gout patients is provided. Routine SUA monitoring can be used to identify patients receiving PEGylated uricase who may no longer benefit from treatment and who are at greater risk for infusion reactions.

Disclosed are recombinant mutant Candida utilis uricase enzymes with improved pancreatin stability and/or activity, compositions containing such uricase enzymes, which can be used, among other things, to treat diseases or disorders associated with an elevated amount of uric acid, including, for example, hyperuricemia, hyperuricosuria, and gout.