Variant form of urate oxidase and use thereof

• US 8,465,735 B2
• Filed: 09/20/2012
• Issued: 06/18/2013
• 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 T
• Application Number:
  US13/623,512
• Publication Number:
  US 20130084273A1
• Time in Patent Office: 271 Days
• Field of Search: None
• US Class Current: 424/94.4
• 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. A method for lowering elevated uric acid levels in a patient comprising administering to said patient an intravenous injection of PEG-uricase having a dosage from about 0.5 to about 24 mg of uricase, the uricase comprising the amino acid sequence of SEQ ID NO:

7, wherein said administration takes place from about every 2 to 4 weeks.

2. The method of claim 1, wherein said dosage is between 4 and 8 mg of uricase.

3. The method of claim 1, wherein said dosage is between 8 and 12 mg of uricase.

4. The method of claim 1, wherein said dosage is about 4 mg of uricase.

5. The method of claim 1, wherein said dosage is about 8 mg of uricase.

6. The method of claim 1, wherein said dosage is about 12 mg of uricase.

7. The method of claim 2, wherein the about 4 mg of uricase is administered every two weeks.

8. The method of claim 5, wherein the about 8 mg of uricase is administered every two weeks.

9. The method of claim 5, wherein the about 8 mg of uricase is administered every four weeks.

10. The method of claim 6, wherein about 12 mg of uricase is administered every four weeks.

11. The method of claim 1, wherein the uric acid levels are lowered to 6.8 mg/dL or less.

12. The method of claim 11, wherein the uric acid levels are lowered to 6 mg/dL or less.

13. The method of claim 1, wherein said patient is suffering from hyperuricemia, gout or hyperuricemia and gout.

14. The method of claim 1, wherein said patient has a plasma level of uric acid (PUA) of more than about 6 mg/dL before said administration.

15. A method for lowering elevated uric acid levels in a patient comprising administering to said patient an intravenous injection of PEG-uricase having a dosage from about 4 to about 12 mg of uricase, the uricase consisting of the amino acid sequence of SEQ ID NO:

7, wherein the PEG-uricase administration takes place from about every 2 to 4 weeks.

16. The method of claim 15, wherein said dosage is between 4 and 8 mg of uricase.

17. The method of claim 15, wherein said dosage is between 8 and 12 mg of uricase.

18. The method of claim 15, wherein said dosage is about 4 mg of uricase.

19. The method of claim 15, wherein said dosage is about 8 mg of uricase.

20. The method of claim 15, wherein said dosage is about 12 mg of uricase.

21. The method of claim 18, wherein the about 4 mg of uricase is administered every two weeks.

22. The method of claim 19, wherein the about 8 mg of uricase is administered every two weeks.

23. The method of claim 19, wherein the about 8 mg of uricase is administered every four weeks.

24. The method of claim 20, wherein about 12 mg of uricase is administered every four weeks.

25. The method of claim 15, wherein the uric acid levels are lowered to 6.8 mg/dL or less.

26. The method of claim 25, wherein the uric acid levels are lowered to 6 mg/dL or less.

27. The method of claim 15, wherein said patient is suffering from hyperuricemia, gout or hyperuricemia and gout.

28. The method of claim 15, wherein said patient has a plasma level of uric acid (PUA) of more than about 6 mg/dL before said administration.