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 disclosure provides methods of treating gout in renal transplant recipients comprising administering pegloticase as described herein. Also provided are methods of reducing immunogenicity of pegloticase and prolonging the urate lowering effect comprising administration of pegloticase. Also provided are methods of preserving kidney function as a result of administration of the pegloticase.

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 methotrexate (MTX). Also provided are methods of reducing immunogenicity of a PEGylated uricase and prolonging the urate lowering effect comprising co-administration of the PEGylated uricase and MTX.

Provided are an improved uricase, a method for treating hyperuricemia using the same, and a corresponding pharmaceutical composition. The improved uricase comprises an amino acid sequence having at least about 90% identity with SEQ ID NO: 1, wherein the sequence is not SEQ ID NO: 1.

Provided herein are methods and compositions, such as kits, related to compositions comprising synthetic nanocarriers comprising an immunosuppressant and compositions comprising an uricase and a composition comprising an anti-inflammatory therapeutic. Also provided herein are methods and compositions for the treatment of subjects in need of administration or treatment with the uricase.

Compositions and kits comprising a tyrosine hydroxylase inhibitor and an anticancer agent that is chemically bonded to, or physically associated with, the tyrosine hydroxylase inhibitor are provided. Also provided are methods for reducing cell proliferation in a subject comprising administering to a subject in need thereof a composition comprising a tyrosine hydroxylase inhibitor and an anticancer agent that is chemically bonded to, or physically associated with, the tyrosine hydroxylase inhibitor.

The present disclosure provides recombinant bacterial cells that have been engineered with genetic circuitry which allow the recombinant bacterial cells to sense a patient's internal environment and respond by turning an engineered metabolic pathway on or off. When turned on, the recombinant bacterial cells complete all of the steps in a metabolic pathway to achieve a therapeutic effect in a host subject. These recombinant bacterial cells are designed to drive therapeutic effects throughout the body of a host from a point of origin of the microbiome. Specifically, the present disclosure provides recombinant bacterial cells that comprise a uric acid catabolism enzyme, e.g., a uric acid degrading enzyme, for the treatment of diseases and disorders associated with uric acid, including hyperuricemia and gout, in a subject. The disclosure further provides pharmaceutical compositions and methods of treating disorders associated with uric acid, such as hyperuricemia.

The present specification discloses a urate oxidase-albumin conjugate, a preparation method thereof, a urate oxidase variant contained in the urate oxidase-albumin conjugate, and a preparation method thereof. The urate oxidase-albumin conjugate is characterized in that three or more albumins are conjugated to the urate oxidase variant through a linker, thereby improving half-life and reducing immunogenicity. In addition, the urate oxidase-albumin conjugate can be used to prevent or treat various diseases, disorders and/or indications caused by uric acid.

This invention relates to formulations of uric acid lowering agent(s) (UALA) designed to inhibit xanthine oxidase and/or decrease serum or tissue uric acid concentration for the treatment and prevention of morbidities and mortality during viral infection. For example, acute kidney injury due to coronavirus infection by administering a therapeutically effective amount of an agent capable of inhibiting xanthine oxidase and/or decreasing uric acid levels in a patient in need of such treatment. Additionally, the scope of the invention includes a method of treating and preventing acute kidney injury and health consequences due to coronavirus infection.

The present disclosure provides a polyethylene glycol-modified urate oxidase. At least 11 of the following amino acid sites in the urate oxidase have a PEG modification: T.sup.1, K.sup.3, K.sup.4, K.sup.30, K.sup.35, K.sup.76, K.sup.79, K.sup.97, K.sup.112, K.sup.116, K.sup.120, K.sup.152, K.sup.179, K.sup.222, K.sup.231, K.sup.266, K.sup.272, K.sup.285, K.sup.291, and K.sup.293.