Patent Issued for Variant Forms of Urate Oxidase and Use
The following quote was obtained by the news editors from the background information supplied by the inventors: "The terms urate oxidase and uricase are used herein interchangeably. Urate oxidases (uricases; E.C. 22.214.171.124) are enzymes which catalyze the oxidation of uric acid to a more soluble product, allantoin, a purine metabolite that is more readily excreted. Humans do not produce enzymatically active uricase, as a result of several mutations in the gene for uricase acquired during the evolution of higher primates. Wu, X, et al., (1992) J Mol Evol 34:78-84, incorporated herein by reference in its entirety. As a consequence, in susceptible individuals, excessive concentrations of uric acid in the blood (hyperuricemia) can lead to painful arthritis (gout), disfiguring urate deposits (tophi) and renal failure. In some affected individuals, available drugs such as allopurinol (an inhibitor of uric acid synthesis) produce treatment-limiting adverse effects or do not relieve these conditions adequately. Hande, K R, et al., (1984) Am J Med 76:47-56; Fam, A G, (1990) Bailliere's Clin Rheumatol 4:177-192, each incorporated herein by reference in its entirety. Injections of uricase can decrease hyperuricemia and hyperuricosuria, at least transiently. Since uricase is a foreign protein in humans, even the first injection of the unmodified protein from Aspergillus flavus has induced anaphylactic reactions in several percent of treated patients (Pui, C--H, et al., (1997) Leukemia 11:1813-1816, incorporated herein by reference in its entirety), and immunologic responses limit its utility for chronic or intermittent treatment. Donadio, D, et al., (1981) Nouv Presse Med 10:711-712; Leaustic, M, et al., (1983) Rev Rhum Mal Osteoartic 50:553-554, each incorporated herein by reference in its entirety.
Enzymes based on the deduced amino acid sequences of uricases from mammals, including pig and baboon, or from insects... more on the hispanicbusiness site...
The present invention is related to mutant recombinant uricase proteins having truncations and enhanced structural stability."
"In another embodiment, the present invention to provides a means for metabolizing uric acid comprising a novel recombinant uricase protein having uricolytic activity. Uricolytic activity is used herein to refer to the enzymatic conversion of uric acid to allantoin.
"The subject invention further provides a host cell with the capacity for producing a uricase that has been truncated by 1-20 amino acids, and has mutated amino acids and retains uricolytic activity.
Also provided are pharmaceutical compositions comprising the uricase of the invention, including the polyethylene glycol-uricase conjugate. In an embodiment, the pharmaceutical composition is suitable for repeated administration.
Thx again everybody but I have a hard time processing all the various excerpts from different articles from various dates. Need the dates so I can keep this in a chronological perspective... I do confess though I haven't had time to read all the new extracts...