Compositions comprising an RNA polymerase inhibitor and cyclodextrin for treating viral infections

Patent metadata

Field	Value
Publication number	US-11975017-B2
Application number	US-202217585651-A
Country	US
Kind code	B2
Filing date	Jan 27, 2022
Priority date	Jul 11, 2017
Publication date	May 7, 2024
Grant date	May 7, 2024

Abstract

The present disclosure provides a composition comprising Compound 1, or a pharmaceutically acceptable salt thereof, cyclodextrin, and, optionally, pH adjusting agents.

First claim

What is claimed is:

1. A composition comprising Compound 1

or a pharmaceutically acceptable salt thereof, and
cyclodextrin;
wherein the composition is a lyophilized composition,
wherein the composition comprises less than about 1% of impurity via HPLC following
storage for 18 months at a temperature of 25° C. (±1° C.) and a relative humidity of 60% (±1%).

2. The composition of claim 1 , wherein the cyclodextrin is a beta-cyclodextrin.

3. The composition of claim 2 , wherein the beta-cyclodextrin is sulfobutylalkyl ether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.

4. The composition of claim 2 , wherein the beta-cyclodextrin is betadex-sulfobutylether sodium.

5. The composition of claim 1 , comprising less than about 0.5% of impurity via HPLC.

6. The composition of claim 1 , further comprising a pH adjusting agent.

7. The composition of claim 6 , wherein the pH adjusting agent comprises HCl, NaOH, or a combination thereof.

8. The composition of claim 6 , wherein the pH adjusting agent is HCl.

9. The composition of claim 6 , wherein the pH adjusting agent is NaOH.

10. The composition of claim 1 , wherein the composition has a pH of about 3 to about 4.

11. The composition of claim 6 , comprising
Compound 1 in an amount from 1% to 10% w/w; and
cyclodextrin in an amount from 90% to 99% w/w.

12. The composition of claim 6 , comprising
Compound 1 in an amount from 1% to 5% w/w; and
cyclodextrin in an amount from 95% to 99% w/w.

13. The composition of claim 6 , comprising
Compound 1 in an amount from 2% to 4% w/w; and
cyclodextrin in an amount from 96% to 98% w/w.

14. The composition of claim 6 , comprising
Compound 1 in an amount from 3% to 3.5% w/w; and
cyclodextrin in an amount from 96.5% to 97% w/w.

15. The composition of claim 6 , comprising
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.

16. The composition of claim 6 , consisting essentially of
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.

17. A composition comprising Compound 1

or a pharmaceutically acceptable salt thereof, and
cyclodextrin;
wherein the composition is a lyophilized composition;
wherein the composition comprises less than about 1% of impurity via HPLC following
storage for 18 months at a temperature of 30° C. (±1° C.) and a relative humidity of 75% (±1%).

18. The composition of claim 17 , wherein the cyclodextrin is a beta-cyclodextrin.

19. The composition of claim 18 , wherein the beta-cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.

20. The composition of claim 18 , wherein the beta-cyclodextrin is betadex-sulfobutylether sodium.

21. The composition of claim 17 , comprising less than about 0.5% of impurity via HPLC.

22. The composition of claim 17 , further comprising a pH adjusting agent.

23. The composition of claim 22 , wherein the pH adjusting agent comprises HCl, NaOH, or a combination thereof.

24. The composition of claim 22 , wherein the pH adjusting agent is HCl.

25. The composition of claim 22 , wherein the pH adjusting agent is NaOH.

26. The composition of claim 17 , wherein the composition has a pH of about 3 to about 4.

27. The composition of claim 22 , comprising
Compound 1 in an amount from 1% to 10% w/w; and
cyclodextrin in an amount from 90% to 99% w/w.

28. The composition of claim 22 , comprising
Compound 1 in an amount from 1% to 5% w/w; and
cyclodextrin in an amount from 95% to 99% w/w.

29. The composition of claim 22 , comprising
Compound 1 in an amount from 2% to 4% w/w; and
cyclodextrin in an amount from 96% to 98% w/w.

30. The composition of claim 22 , comprising
Compound 1 in an amount from 3% to 3.5% w/w; and
cyclodextrin in an amount from 96.5% to 97% w/w.

31. The composition of claim 22 , comprising
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.

32. The composition of claim 22 , consisting essentially of
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.

33. A composition comprising Compound 1

or a pharmaceutically acceptable salt thereof, and
cyclodextrin;
wherein the composition is a lyophilized composition;
wherein the composition comprises less than about 1% of impurity via HPLC following
storage for 6 months at a temperature of 40° C. (±1° C.) and a relative humidity of 75% (±1%).

34. The composition of claim 33 , wherein the cyclodextrin is a beta-cyclodextrin.

35. The composition of claim 34 , wherein the beta-cyclodextrin is sulfobutylalkylether-beta-cyclodextrin, betadex-sulfobutylether sodium, or hydroxypropyl-beta-cyclodextrin.

36. The composition of claim 34 , wherein the beta-cyclodextrin is betadex-sulfobutylether sodium.

37. The composition of claim 33 , comprising less than about 0.5% of impurity via HPLC.

38. The composition of claim 33 , further comprising a pH adjusting agent.

39. The composition of claim 38 , wherein the pH adjusting agent comprises HCl, NaOH, or a combination thereof.

40. The composition of claim 38 , wherein the pH adjusting agent is HCl.

41. The composition of claim 38 , wherein the pH adjusting agent is NaOH.

42. The composition of claim 33 , wherein the composition has a pH of about 3 to about 4.

43. The composition of claim 38 , comprising
Compound 1 in an amount from 1% to 10% w/w; and
cyclodextrin in an amount from 90% to 99% w/w.

44. The composition of claim 38 , comprising
Compound 1 in an amount from 1% to 5% w/w; and
cyclodextrin in an amount from 95% to 99% w/w.

45. The composition of claim 38 , comprising
Compound 1 in an amount from 2% to 4% w/w; and
cyclodextrin in an amount from 96% to 98% w/w.

46. The composition of claim 38 , comprising
Compound 1 in an amount from 3% to 3.5% w/w; and
cyclodextrin in an amount from 96.5% to 97% w/w.

47. The composition of claim 38 , comprising
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.

48. The composition of claim 38 , consisting essentially of
Compound 1 in an amount of about 3.2% w/w; and
betadex-sulfobutylether sodium in an amount of about 96.8% w/w.

Assignees

• Gilead Sciences Inc

Inventors

• Larson Nate
• Strickley Robert G

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K31/683

  Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols · CPC title