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.

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.

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.

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.

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.

The subject invention provides a method for purifying a target protein from a mixture comprising the target protein and contaminating protein, comprising the steps of exposing the mixture to an effective amount of a cationic surfactant such that the contaminating protein is preferentially precipitated and recovering the target protein. Proteins purified according to the method of the invention are also provided.

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.

The subject invention provides a method for purifying a target protein from a mixture comprising the target protein and contaminating protein, comprising the steps of exposing the mixture to an effective amount of a cationic surfactant such that the contaminating protein is preferentially precipitated and recovering the target protein. Proteins purified according to the method of the invention are also provided.