Methods for lowering elevated uric acid levels using intravenous injections of PEG-uricase

• US 8,148,123 B2
• Filed: 10/06/2006
• Issued: 04/03/2012
• Est. Priority Date: 04/11/2005
• Status: Active Grant

• Current Assignee: Horizon Therapeutics USA, Inc. (Amgen Inc.), Duke University
• Original Assignee: Savient Pharmaceuticals Incorporated (Amgen Inc.)
• Inventors: Hartman, Jacob, Rehrig, Claudia D., Huang, William, Hershfield, Michael, Mendelovitz, Simona
• Primary Examiner(s): DAVIS, RUTH A
• Application Number:
  US11/539,475
• Publication Number:
  US 20070274977A1
• Time in Patent Office: 2,006 Days
• Field of Search: 424/94.1, 424/94.4, 435/181, 435/189
• 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 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: C12Y 107/03003 Factor-independent urate hydroxylase (1.7.3.3), i.e. uricase

Abstract

A method for lowering elevated uric acid levels in patients is disclosed and consists of administering to the patients an intravenous injection of PEG-uricase having a dosage from about 4 to about 12 mg.

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 4 to about 12 mg of uricase, the uricase consisting of the amino acid sequence of SEQ ID NO:

8, wherein said administration takes place from about every 2 to 4 weeks, wherein a plasma uricase activity level is undetectable in the patient prior to a first intravenous injection of PEG-uricase, and wherein the plasma uricase activity level is detectable about 21 days after the intravenous injection.

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 patient is suffering from gout.

6. The method of claim 5, wherein said gout is refractory.

7. The method of claim 5, wherein said gout is chronic or tophaceous.

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

9. The method of claim 1, wherein the plasma uricase activity level is detectable in the patient from about 26 mU/mL to about 6.5 mU/mL about 21 days after the intravenous injection.

10. 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 12 mg of uricase, the uricase consisting of the amino acid sequence of SEQ ID NO:

8, wherein said administration takes place from about every 2 to 4 weeks, and wherein a plasma uricase activity level is undetectable in the patient prior to a first intravenous injection of PEG-uricase, and wherein the plasma uricase activity level is detectable about 21 days after the intravenous injection.

11. The method of claim 10, wherein said dosage is between 4 and 8 mg of uricase.

12. The method of claim 10, wherein said dosage is between 8 and 12 mg of uricase.

13. The method of claim 10, wherein said dosage is about 4 mg of uricase.

14. The method of claim 10, wherein said patient is suffering from gout.

15. The method of claim 14, wherein said gout is refractory.

16. The method of claim 14, wherein said gout is chronic or tophaceous.

17. The method of claim 10, wherein said patient has a plasma level of uric acid (pUAc) of more than about 6 mg/dL before said administration.

18. The method of claim 10, wherein the plasma uricase activity level is detectable in the patient from about 26 mU/mL to about 6.5 mU/mL about 21 days after the intravenous injection.