Variant form of urate oxidase and use thereof

• US 8,178,334 B2
• Filed: 09/07/2011
• Issued: 05/15/2012
• Est. Priority Date: 04/11/2005
• Status: Active Grant

• Current Assignee: Horizon Therapeutics USA, Inc. (Amgen Inc.)
• Original Assignee: Savient Pharmaceuticals Incorporated (Amgen Inc.)
• Inventors: Hartman, Jacob, Mendelovitz, Simona
• Primary Examiner(s): Nashed, Nashaat
• Application Number:
  US13/226,891
• Publication Number:
  US 20120070876A1
• Time in Patent Office: 251 Days
• Field of Search: None
• US Class Current: 435/189
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• 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 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 9/0046 with oxygen as acceptor (1.7.3)
• CPC Class Codes: C12Y 107/03003 Factor-independent urate hydroxylase (1.7.3.3), i.e. uricase

Abstract

The present invention relates to genetically modified proteins with uricolytic activity. More specifically, the invention relates to proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidases.

Claims

1. An isolated nucleic acid comprising a nucleic acid sequence which encodes a uricase selected from the group consisting of:

a uricase comprising the amino acid sequence of position 8 through position 287 of SEQ ID NO. 12;

a uricase comprising the amino acid sequence of position 8 through position 287 of SEQ ID NO. 13;

a uricase comprising the amino acid sequence of position 8 through position 287 of SEQ ID NO. 12 further comprising an amino terminal amino acid, wherein the amino terminal amino acid is alanine, glycine, proline, serine, or threonine; and

a uricase comprising the amino acid sequence of position 8 through position 287 of SEQ ID NO. 12 further comprising an amino terminal amino acid, wherein the amino terminal amino acid is methionine.

2. The isolated nucleic acid of claim 1, wherein the nucleic acid sequence is operatively linked to a heterologous promoter.

3. The nucleic acid of claim 2, wherein the promoter is the osmB promoter.

4. A nucleic acid vector comprising the nucleic acid of claim 2.

5. A host cell comprising the vector of claim 4.

6. A method for producing a uricase comprising the steps of culturing the host cell of claim 5 under conditions such that the nucleic acid sequence is expressed by the host cell and isolating the expressed uricase.