IP Library › Granted Patent US 9,469,600
Granted Patent B2
US 9,469,600 · App. 14/523,538 · Granted Oct 18, 2016

Prostacyclin compounds, compositions and methods of use thereof

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Quick Facts
Patent No.
US 9,469,600
App. No.
14/523,538
Granted
Oct 18, 2016
Kind
B2
Abstract

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C 5 -C 18 alkyl, branched C 5 -C 18 alkyl, linear C 2 -C 18 alkenyl, branched C 3 -C 18 alkenyl, aryl, aryl-C 1 -C 18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

Claims (50)

1. A composition comprising a PEGylated lipid and a prostacyclin compound of Formula (II), or a pharmaceutically acceptable salt thereof:

wherein R 1 is O;

R 2 is tetradecyl, pentadecyl, hexadecyl, heptadecyl, or octadecyl; and

n is an integer from 0 to 5.

2. The composition of claim 1 , wherein n is 0 or 1.

3. The composition of claim 1 , wherein n is 0.

4. The composition of claim 1 , wherein n is 1.

5. The composition of claim 1 , wherein R 2 is hexadecyl and n is 1.

6. The composition of claim 1 , wherein the PEGylated lipid comprises PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000 or PEG5000.

7. The composition of claim 1 , wherein the PEGylated lipid comprises PEG2000.

8. The composition of claim 1 , wherein the PEGylated lipid comprises cholesterol.

9. The composition of claim 1 , wherein the PEGylated lipid comprises a phospholipid.

10. The composition of claim 1 , wherein the PEGylated lipid comprises phosphatidylethanolamine (DSPE), dirnyristoyl phosphoethanolamine (DMPE) or distearoyl glycerol (DSG).

11. The composition of claim 1 , wherein the PEGylated lipid is cholesterol-PEG2000, DSPE-PEG1000 or DSG-PEG2000.

12. The composition of claim 1 , further comprising a hydrophobic additive.

13. The composition of claim 12 , wherein the hydrophobic additive is a hydrocarbon, a terpene or a hydrophobic lipid, alkyl ester, cholesteryl ester or an alkyl-glyceride.

14. The composition of claim 13 , wherein the hydrophobic additive is a terpene.

15. The composition of claim 14 , wherein the terpene is squalane.

16. The composition of claim 4 , wherein the PEGylated lipid comprises PEG400, PEG500, PEG1000, PEG2000, PEG3000, PEG4000 or PEG5000.

17. The composition of claim 4 , wherein the PEGylated lipid comprises PEG2000.

18. The composition of claim 4 , wherein the PEGylated lipid comprises cholesterol.

19. The composition of claim 4 , wherein the PEGylated lipid comprises a phospholipid.

20. The composition of claim 4 , wherein the PEGylated lipid comprises phosphatidylethanolamine (DSPE), dimyristoyl phosphoethanolamine (DMPE) or distearoyl glycerol (DSG).

21. The composition of claim 4 , PEGylated lipid is cholesterol-PEG2000, DSPE-PEG1000 or DSG-PEG2000.

22. The composition of claim 4 , further comprising a hydrophobic additive.

23. The composition of claim 22 , wherein the hydrophobic additive is a hydrocarbon, a terpene or a hydrophobic lipid, alkyl ester, cholesteryl ester or an alkyl-glyceride.

24. The composition of claim 23 , wherein the hydrophobic additive is a terpene.

25. The composition of claim 24 , wherein terpene is squalane.

26. The composition of claim 25 , wherein the PEGylated lipid is cholesterol-PEG2000.

27. The composition of claim 25 , wherein the PEGylated lipid is DSPE-PEG1000.

28. The composition of claim 25 , wherein the PEGylated lipid is DSG-PEG2000.

29. The composition of claim 10 , wherein R 2 is hexadecyl.

30. The composition of claim 11 , wherein R 2 is hexadecyl.

31. The composition of claim 12 , wherein R 2 is hexadecyl.

32. The composition of claim 13 , wherein R 2 is hexadecyl.

33. The composition of claim 14 , wherein R 2 is hexadecyl.

34. The composition of claim 15 , wherein R 2 is hexadecyl.

35. The composition of claim 16 , wherein R 2 is hexadecyl.

36. The composition of claim 17 , wherein R 2 is hexadecyl.

37. The composition of claim 18 , wherein R 2 is hexadecyl.

38. The composition of claim 19 , wherein R 2 is hexadecyl.

39. The composition of claim 20 , wherein R 2 is hexadecyl.

40. The composition of claim 21 , wherein R 2 is hexadecyl.

41. The composition of claim 22 , wherein R 2 is hexadecyl.

42. The composition of claim 23 , wherein R 2 is hexadecyl.

43. The composition of claim 24 , wherein R 2 is hexadecyl.

44. The composition of claim 25 , wherein R 2 is hexadecyl.

45. The composition of claim 26 , wherein R 2 is hexadecyl.

46. The composition of claim 27 , wherein R 2 is hexadecyl.

47. The composition of claim 28 , wherein R 2 is hexadecyl.

Assignments (4)
PATENT SECURITY AGREEMENT Recorded Oct 20, 2022
From: INSMED INCORPORATED
To: BIOPHARMA CREDIT PLC
Reel/Frame 061735/0875 →
SECOND LIEN PATENT SECURITY AGREEMENT Recorded Oct 19, 2022
From: INSMED INCORPORATED
To: ORBIMED ROYALTY & CREDIT OPPORTUNITIES IV, LP
Reel/Frame 061727/0039 →
CONFIRMATORY ASSIGNMENT Recorded Aug 25, 2016
From: MALININ, VLADIMIR
To: INSMED INCORPORATED
Reel/Frame 039813/0450 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 6, 2015
From: MALININ, VLADIMIR; PERKINS, WALTER; LEIFER, FRANZISKA; KONICEK, DONNA M.; LI, ZHILI; PLAUNT, ADAM
To: INSMED INCORPORATED
Reel/Frame 034907/0304 →