The present disclosure relates to engineered microbial cells that have been engineered to include a uricase, a uric acid transporter, or both a uricase and a uric acid transporter. The engineered microbial cells of the present disclosure are useful in degrading uric acid inside the engineered microbial cell. The engineered microbial cells of the present disclosure are useful in methods of treating hyperuricemia. The engineered microbial cells of the present disclosure are also useful in methods of treating gout, and in particular chronic refractory gout.

The present invention relates to a novel peptide or a partial sequence thereof for enhancing expression efficiency of a target protein, and a fusion protein comprising the same. The novel peptide according to the present invention can enhance expression efficiency of a target protein, and furthermore, the peptide can also be applied to a solubility-enhancing fusion protein in order to enhance solubility of the target protein, so that solubility as well as expression efficiency of the target protein is enhanced, which allows such a peptide to be usefully used for production of a recombinant target protein.

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.

The present application relates to a method of preparing urate oxidase (Uox) including a non-nature amino acid (NNAA) and Uox prepared thereby. The present application showed that the method of preparing Uox including an NNAA may be effectively used to prolong the half-life of a protein which is difficult to be linked to a carrier.

In addition, the Uox produced by the method may be effectively used for various biopharmaceuticals since its efficacy is maintained and drug persistency increases due to site-specific conjugation of a carrier, a risk of an immune response is reduced, and it is easily separated due to formation of uniform conjugate.

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.

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.

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.

Described herein are methods for reducing an antibody response to uricase therapy, improving the treatment of gout, reducing uric acid levels, and preventing and/or delaying infusion reactions. The methods may include administration of a uricase and a steroid as described herein.

The present invention provides compositions comprising one or more active pharmaceutical ingredients, wherein the compositions are in the form of high solids concentration pastes capable of being injected in relatively low volumes into an animal using standard commercially available syringes. The invention also provides methods of making such compositions, particularly those compositions comprising high molecular weight active ingredients (e.g., antibodies, enzymes and other proteins and peptides) at relatively high therapeutic concentrations in the high solids concentration pastes. The invention further provides methods of using such formulations in treating, preventing and/or ameliorating certain diseases and physical disorders in animals, including humans, in need thereof. The invention also provides kits comprising the formulations of the invention and a suitable syringe, which in some aspects may be pre-loaded or pre-filled with a composition of the invention.

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.