PEG-Urate Oxidase Conjugates and Use Thereof

• US 20100323423A1
• Filed: 04/28/2010
• Published: 12/23/2010
• Est. Priority Date: 08/06/1998
• Status: Abandoned Application

• Current Assignee: Horizon Therapeutics USA, Inc. (Amgen Inc.), Duke University
• Original Assignee: Horizon Therapeutics USA, Inc. (Amgen Inc.)
• Inventors: Herschfield, Michael S., WILLIAMS, L. David, Sherman, Merry R., Kelly, Susan J., Saifer, Mark G.P.
• Application Number:
  US12/769,572
• Publication Number:
  US 20100323423A1
• Time in Patent Office: Days
• US Class Current: 435/191
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: C12N 9/0046 with oxygen as acceptor (1.7.3)
• CPC Class Codes: C12N 9/0048 Uricase (1.7.3.3)
• CPC Class Codes: C12N 9/0093 acting on CH or CH2 groups (1.17)
• CPC Class Codes: C12N 9/96 Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
• CPC Class Codes: C12Y 107/03003 Factor-independent urate hydroxylase (1.7.3.3), i.e. uricase

Abstract

A naturally occurring or recombinant urate oxidase (uricase) covalently coupled to poly(ethylene glycol) or poly(ethylene oxide) (both referred to as PEG), wherein an average of 2 to 10 strands of PEG are conjugated to each uricase subunit and the PEG has an average molecular weight between about 5 kDa and 100 kDa. The resulting PEG-uricase conjugates are substantially non-immunogenic and retain at least 75% of the uricolytic activity of the unmodified enzyme.

Claims

1-41. -41. (canceled)

42. An isolated tetrameric mammalian uricase, wherein said tetrameric uricase is substantially free of uricase aggregates.

43. The isolated tetrameric uricase of claim 42, wherein the uricase is a porcine liver, a bovine liver or an ovine liver uricase.

44. The isolated tetrameric uricase of claim 42, wherein the uricase is recombinant.

45. The isolated tetrameric uricase of claim 44, wherein the uricase has substantially the sequence of a porcine, a bovine, an ovine or a baboon liver uricase.