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Claims for Patent: 7,662,365

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Claims for Patent: 7,662,365

Title:Polymer conjugates of opioid antagonists
Abstract: The invention provides polymer conjugates of opioid antagonists comprising a polymer, such as poly(ethylene glycol), covalently attached to an opioid antagonist. The linkage between the polymer and the opioid antagonist is preferably hydrolytically stable. The invention also includes a method of treating one or more side effects associated with the use of opioid analgesics, such as constipation, nausea, or pruritus, by administering a polymer conjugate of the invention.
Inventor(s): Bentley; Michael David (Huntsville, AL), Roberts; Michael James (Williamsburg, VA), Shen; Xiaoming (Madison, AL), Cheng; Lin (Huntsville, AL)
Assignee: Nektar Therapeutics (San Carlos, CA)
Application Number:11/332,964
Patent Claims: 1. A polymer conjugate according to the formula: ##STR00009## or pharmaceutically acceptable salt thereof, wherein: Y is allyl; Z is OH; X is amide, amine, carbamate, sulfide, ether, thioether or urea; and POLY is methoxy poly(ethylene glycol), wherein POLY has a molecular weight of from about 100 Da to about 2,000 Da.

2. The polymer conjugate of claim 1, wherein POLY has the formula CH.sub.3O--(CH.sub.2CH.sub.2O).sub.n--CH.sub.2CH.sub.2-- wherein n is from 2 to 45.

3. The polymer conjugate of claim 2, wherein n is from 2 to 20.

4. The polymer conjugate of claim 1, wherein POLY has a molecular weight of from about 100 Da to about 500 Da.

5. The polymer conjugate of claim 1, wherein X is amide.

6. The polymer conjugate of claim 1, wherein X is amine.

7. The polymer conjugate of claim 1, wherein X is carbamate.

8. The polymer conjugate of claim 1, wherein X is sulfide.

9. The polymer conjugate of claim 1, wherein X is ether.

10. The polymer conjugate of claim 1, wherein X is thioether.

11. The polymer conjugate of claim 1, wherein X is urea.

12. A pharmaceutical composition comprising a polymer conjugate and a pharmaceutically acceptable carrier wherein the polymer conjugate has the formula: ##STR00010## or pharmaceutically acceptable salt thereof, wherein: Y is allyl; Z is OH; X is amide, amine, carbamate, sulfide, ether, thioether or urea; and POLY is methoxy poly(ethylene glycol), wherein POLY has a molecular weight of from about 100 Da to about 2,000 Da.

13. The pharmaceutical composition of claim 12, wherein POLY has the formula CH.sub.3O--(CH.sub.2CH.sub.2O).sub.nCH.sub.2CH.sub.2-- wherein n is from 2 to 45.

14. The pharmaceutical composition of claim 12, wherein n is from 2 to 20.

15. The pharmaceutical composition of claim 12, wherein POLY has a molecular weight of from about 100 Da to about 500 Da.

16. The pharmaceutical composition of claim 12, wherein X is amide.

17. The pharmaceutical composition of claim 12, wherein X is amine.

18. The pharmaceutical composition of claim 12, wherein X is carbamate.

19. The pharmaceutical composition of claim 12, wherein X is sulfide.

20. The pharmaceutical composition of claim 12, wherein X is ether.

21. The pharmaceutical composition of claim 12, wherein X is thioether.

22. The pharmaceutical composition of claim 12, wherein X is urea.
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