The present disclosure is directed to a drug delivery system in which urate oxidase and metal-based nanoparticles for hydrogen peroxide degradation are loaded in a temperature-sensitive nanocarrier, and a pharmaceutical composition for treating hyperuricemia-related disease comprising the drug delivery system. In the drug delivery system of the present disclosure, urate oxidase and metal-based nanoparticles for hydrogen peroxide degradation are positioned close to each other, thereby effectively removing the toxic substance hydrogen peroxide (H.sub.2O.sub.2) generated during uric acid degradation. The drug delivery system of the present disclosure may be developed as an active ingredient of a drug for preventing or treating hyperuricemia-related disease.

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 present invention relates to conjugates of a protein drug and two or more P/A peptides, and pharmaceutical compositions comprising them. The conjugates of the invention exhibit an advantageously reduced immunogenicity as compared to the respective unmasked protein drugs as well as a favorable safety and tolerability profile, which render them particularly suitable for therapeutic use. The conjugates further show an enhanced plasma half-life and, thus, a prolonged duration of action as compared to the respective unmasked protein drugs, which allows for a reduction in the dosing frequency and, thus, side-effect burden. The invention also provides processes of preparing such conjugates as well as activated P/A peptides that are useful as synthetic intermediates in the preparation of the conjugates.

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 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.

An aqueous composition having increased protein stability is obtained by: a. determining a pH at which the protein has stability at the desired temperature; b. adding to the composition at least one displacement buffer wherein the displacement buffer has a pK.sub.a that is at least 1 unit greater or less than the pH of step (a); and c. adjusting the pH of the composition to the pH of step (a); wherein the aqueous composition does not comprise a conventional buffer at a concentration greater than about 2 mM and wherein the conventional buffer has a pK.sub.a that is within 1 unit of the pH of step (a).

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.

A composition for uric acid decomposition using gold nanoparticles is disclosed. The composition for uric acid decomposition in accordance with an exemplary embodiment of the present invention is characterized by including urate oxidase (UOX), gold nanoparticles and a buffer.

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.