Heterocyclic compounds and their uses

Patent metadata

Field	Value
Publication number	US-12275704-B2
Application number	US-202318531424-A
Country	US
Kind code	B2
Filing date	Dec 6, 2023
Priority date	Mar 14, 2013
Publication date	Apr 15, 2025
Grant date	Apr 15, 2025

Abstract

Provided are certain pharmaceutical formulations of omecamtiv mecarbil and methods for their preparation and use.

First claim

What is claimed is:

1. A pharmaceutical formulation comprising:
omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof;
a control release agent comprising hydroxypropylmethylcellulose;
a pH modifying agent comprising fumaric acid;
a filler; and
a lubricant.

2. The pharmaceutical formulation of claim 1 , wherein the omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof is crystalline.

3. The pharmaceutical formulation of claim 2 , wherein the omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof has an x-ray powder diffraction pattern (XRPD) comprising peaks at 6.6±0.2, 14.9±0.2, 20.1±0.2, 21.4±0.2, and 26.8±0.2° 2θ using Cu Kα radiation.

4. The pharmaceutical formulation of claim 3 , wherein the XRPD pattern further comprises peaks at 8.4±0.2, 24.2±0.2, 26.0±0.2, and 33.3±0.2° 2θ using Cu Kα radiation.

5. The pharmaceutical formulation of claim 2 , wherein the omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof has an x-ray powder diffraction pattern (XRPD) comprising peaks at 6.6±0.2, 8.4±0.2, 14.9±0.2, 15.4±0.2, and 26.8±0.2° 2θ using Cu Kα radiation.

6. The pharmaceutical formulation of claim 5 , wherein the XRPD pattern further comprises peaks at 16.3±0.2, 19.5±0.2, 21.8±0.2, 22.8±0.2, 27.7±0.2, and 28.4±0.2° 2θ using Cu Kα radiation.

7. The pharmaceutical formulation of claim 2 , wherein the omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof has an x-ray powder diffraction pattern (XRPD) comprising peaks at 6.6±0.2, 14.9±0.2, 16.3±0.2, 19.5±0.2, and 26.8±0.2° 2θ using Cu Kα radiation.

8. The pharmaceutical formulation of claim 7 , wherein the XRPD pattern further comprises peaks at 21.8±0.2, 22.8±0.2, 27.7±0.2, and 28.4±0.2° 2θ using Cu Kα radiation.

9. The pharmaceutical formulation of claim 1 , comprising 3-30% w/w omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof.

10. The pharmaceutical formulation of claim 9 , comprising 12-25% w/w omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof.

11. The pharmaceutical formulation of claim 9 , comprising 3-10% w/w omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof.

12. The pharmaceutical formulation of claim 11 , comprising 5-7% w/w omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof.

13. The pharmaceutical formulation of claim 1 , comprising 15-35% w/w control release agent.

14. The pharmaceutical formulation of claim 1 , comprising 4-11% w/w fumaric acid.

15. The pharmaceutical formulation of claim 1 , comprising 12-25% w/w fumaric acid.

16. The pharmaceutical formulation of claim 1 , comprising a weight ratio of fumaric acid to omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate thereof of less than 2:1 to 1:1.

17. The pharmaceutical formulation of claim 16 , wherein the weight ratio of fumaric acid to omecamtiv mecarbil dihydrochloride salt or a pharmaceutically acceptable hydrate is about 1:1.

Assignees

• Cytokinetics Inc

Inventors

• Bi Mingda
• Kuehl Robert

Classifications

• A61K47/38

  Cellulose; Derivatives thereof · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title

• A61K9/2013

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title