Compositions comprising two different populations of polymer-active agent conjugates

Patent metadata

Field	Value
Publication number	US-9539337-B2
Application number	US-930404-A
Country	US
Kind code	B2
Filing date	Dec 10, 2004
Priority date	Dec 10, 2003
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

Compositions comprising two different populations of polymer-active agent conjugates, wherein the weight average molecular weight of the polymers associated with each population is different, are provided. Also provided are methods preparing such compositions and methods for administering such compositions.

First claim

What is claimed is:

1. A composition comprising:
a first population of polymer-active agent conjugates, wherein each polymer in the first population of polymer-active agent conjugates has a weight average molecular weight; and
a second population of polymer-active agent conjugates, wherein each polymer in the second population of polymer-active agent conjugates has a weight average molecular weight,
wherein the weight average molecular weight of each polymer in the first population is in the range of from about 100 Daltons to less than 20,000 Daltons, and the weight average molecular weight of each polymer in the second population is in the range of from greater than 100 Daltons to about 120,000 Daltons, wherein the weight average molecular weight of each polymer in the first population is different from the weight average molecular weight of each polymer in the second population.

2. The composition of claim 1 , wherein the weight average molecular weight of each polymer in the first population is in the range of from about 100 Daltons to less than 20,000 Daltons, and the weight average molecular weight of each population in the second population is in the range of from greater than 20,000 Daltons to about 100,000 Daltons.

3. The composition of claim 2 , wherein the weight average molecular weight of each polymer in the first population is in the range of from about 1,000 Daltons to about 15,000 Daltons, and the weight average molecular weight of each polymer in the second population is in the range of from greater than about 25,000 Daltons to about 50,000 Daltons.

4. The composition of claim 3 , wherein the weight average molecular weight of each polymer in the first population is in the range of from about 2,500 Daltons to about 10,000 Daltons, and the weight average molecular weight of each polymer in the second population is in the range of greater than 30,000 Daltons to about 40,000 Daltons.

5. The composition of claim 4 , wherein the weight average molecular weight of each polymer in the first population is about 5,000 Daltons, and the weight average molecular weight of each polymer in the second population is in the range of from about 30,000 Daltons to about 40,000 Daltons.

6. The composition of claim 1 , wherein the absolute difference between the weight average molecular weight of each polymer in the first population and the weight average molecular weight of each polymer in the second population is from about 500 Daltons to about 100,000 Daltons.

7. The composition of claim 1 , wherein the absolute difference between the weight average molecular weight of each polymer in the first population and the weight average molecular weight of each polymer in the second population is from about 2,000 Daltons to about 100,000 Daltons.

8. The composition of claim 1 , wherein the absolute difference between the weight average molecular weight of each polymer in the first population and the weight average molecular weight of each polymer in the second population is from about 10,000 Daltons to about 100,000 Daltons.

9. The composition of claim 1 , wherein the absolute difference between the weight average molecular weight of each polymer in the first population and the weight average molecular weight of each polymer in the second population is from about 20,000 Daltons to about 100,000 Daltons.

10. The composition of claim 1 , wherein the absolute difference between the weight average molecular weight of each polymer in the first population and the weight average molecular weight of each polymer in the second population is from about 30,000 Daltons to about 100,000 Daltons.

11. The composition of claim 1 , wherein the absolute difference between the weight average molecular weight of each polymer in the first population and the weight average molecular weight of each polymer in the second population is from about 20,000 Daltons to about 40,000 Daltons.

12. The composition of claim 1 , wherein the absolute difference between the weight average molecular weight of each polymer in the first population and the weight average molecular weight of each polymer in the second population is from about 25,000 Daltons to about 35,000 Daltons.

13. The composition of claim 1 , wherein the first and second populations of polymer-active agent conjugates has a molar ratio between them of from about 1000:1 to about 100:1.

14. The composition of claim 1 , wherein the first and second populations of polymer-active agent conjugates has a molar ratio between them of from about 100:1 to about 10:1.

15. The composition of claim 1 , wherein the first and second populations of polymer-active agent conjugates has a molar ratio between them of from about 10:1 to about 1:1.

16. The composition of claim 1 , wherein the first and second populations of polymer-active agent conjugates has a molar ratio between them of from about 1:1 to about 1:10.

17. The composition of claim 1 , wherein the first and second populations of polymer-active agent conjugates has a molar ratio between them of from about 1:10 to about 1:100.

18. The composition of claim 1 , wherein the first and second populations of polymer-active agent conjugates has a molar ratio between them of from about 1:100 to about 1:1000.

19. The composition of claim 1 , wherein each polymer in the first and second populations of polymer-active agent conjugates is independently selected from the group consisting of a poly(alkylene oxide), poly(vinyl pyrrolidone), poly(vinyl alcohol), polyoxazoline, poly(acryloylmorpholine), and poly(oxyethylated polyols).

20. The composition of claim 1 , wherein each polymer is a poly(ethylene glycol).

21. The composition of claim 20 , wherein each poly(ethylene glycol) is terminally capped with an end-capping moiety.

22. The composition of claim 21 , wherein each end-capping moiety is independently selected from the group consisting alkyloxy, substituted alkyloxy, alkenyloxy, substituted alkenyloxy, alkynyloxy, substituted alkynyloxy, aryloxy, substituted aryloxy, and hydroxy.

23. The composition of claim 22 , wherein the end-capping moiety is hydroxy.

24. The composition of claim 22 , wherein each end-capping moiety is alkoxy.

25. The composition of claim 24 , wherein each alkoxy is methoxy.

26. The composition of claim 1 , wherein each polymer in the first and second populations of polymer-active agent conjugates independently has a structure selected from the group consisting of homopolymer, alternating copolymer, random copolymer, block copolymer, alternating tripolymer, random tripolymer, and block tripolymer.

27. The composition of claim 1 , wherein each of the polymer-active agent conjugates in the first population comprises a single polymer attached to a single active agent.

28. The composition of claim 1 , wherein each of the polymer-active agent conjugates in the second population comprises a single polymer attached to a single active agent.

29. The composition of claim 28 , wherein the poly(ethylene glycol) is linear.

30. The composition of claim 1 , wherein each of the polymer-active agent conjugates in both the first and second populations comprises a single polymer attached to a single active agent.

31. The composition of claim 30 , wherein the polymer is a poly(ethylene glycol).

32. The composition of claim 1 , wherein th

Assignees

• Bossard Mary J
• Nektar Therapeutics

Inventors

• Bossard Mary J

Classifications

• A61K47/48176 Primary

  Human Necessities · mapped topic

• A61K47/48215

  Human Necessities · mapped topic

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K47/58 Primary

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin · CPC title

• A61K31/74

  Synthetic polymeric materials · CPC title