Patent Issued for Variant Forms of Urate Oxidase and Use
I found below a news column about this new and very interesting patent. This is cut and paste from HispanicBusiness.
"Japanese Patent No. 3-148298 to A Sano, et al., incorporated herein by reference in its entirety, discloses modified proteins, including uricase, derivatized with PEG having a molecular weight of 1-12 kDa that show reduced antigenicity and 'improved prolonged' action, and methods of making such derivatized peptides. However, there are no disclosures regarding strand counts, enzyme assays, biological tests or the meaning of 'improved prolonged.' Japanese Patents 55-99189 and 62-55079, each incorporated herein by reference in its entirety, both to Y Inada, disclose uricase conjugates prepared with PEG-triazine or bis-PEG-triazine (denoted as PEG.sub.2), respectively. See Nishimura, et al., (1979 and 1981). In the first type of conjugate, the molecular weights of the PEGs are 2 kDa and 5 kDa, while in the second, only 5 kDa PEG is used. Nishimura, et al., (1979) reported the recovery of 15% of the uricolytic activity after modification of 43% of the available lysines with linear 5 kDa PEG, while Nishimura, et al., (1981) reported the recovery of 31% or 45% of the uricolytic activity after modification of 46% or 36% of the lysines, respectively, with PEG.sub.2."
"Previously studied uricase proteins were either natural or recombinant proteins. However, studies using SDS-PAGE and/or Western techniques revealed the presence of unexpected low molecular weight peptides which appear to be degradation products and increase in frequency over time. The present invention is related to mutant recombinant uricase proteins having truncations and enhanced structural stability."
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"In addition to the background information obtained for this patent, NewsRx journalists also obtained the inventors' summary information for this patent: "The present invention provides novel recombinant uricase proteins. In one embodiment, the proteins of the invention contemplated are truncated and have mutated amino acids relative to naturally occurring uricase proteins. In particular embodiments, the mutations are at or around the areas of amino acids 7, 46, 291, and 301. Conservative mutations anywhere in the peptide are also contemplated as a part of the invention.
"The subject invention provides a mutant recombinant uricase, wherein the uricase has been truncated by 1-20 amino acids and retains the uricolytic activity of the naturally occurring uricase. The truncations are at or around the sequence termini such that the protein may contain the ultimate amino acids. These mutations and truncations may enhance stability of the protein comprising such mutations.
"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."
Transcript Call Date 03/19/2013
Kenneth M. Bahrt, M.D. - SVP and Chief Medical Officer: Thank you, John, and good morning. I'd like to bring you up to date on the clinical and medical events since the last call. On the clinical side as Lou mentioned, the trial of KRYSTEXXA in dialysis patients has completed. We will be developing a manuscript for publication as soon as the data has been finalized and will be presenting the final data at an appropriate scientific meeting later in the year.
We are completing the planning process for the immunogenicity trial, due to begin in the third quarter. This trial will test a new dosing schedule designed to induce a high zone tolerance. We believe that it will further reduce the incidents of infusion reactions and increase the number of patients who maintain their response to KRYSTEXXA over the longer term. As you know, in the Phase III development program 42% of the patients maintain their response to KRYSTEXXA over the six months of the trial. Many of the patients who discontinued from these trials lost their therapeutic response due to the development of high-titer antibodies. If the immunogenicity trial is successful, we believe fewer patients will develop high-titer antibodies and thereby better able to maintain their therapeutic response over a longer period of time. Because this trial may result in a different dosing schedule for KRYSTEXXA and higher response rates. We decided to push back to start of the induction maintenance trials until the data from the immunogenicity trial is available.
This will allow us to conduct the induction maintenance trial with fewer patients and at less cost, while further lessening the risk of infusion reactions for the patients. The U.S. observational trial continues to enroll patients and we continue to believe that we will meet study timelines.