Granted Patent B2

US 12,409,180 · App. 18/946,234 · Granted Sep 9, 2025

Inventors: Peter Lionel Spargo (Canterbury, GB); Phillip A. Haywood (Buntingford, GB); Edward James French (Canterbury, GB)

Assignee: Verona Pharma PLC

A61K31/519A61K9/0075A61K9/1682

Abstract

Claims (28)

1. A sterile liquid pharmaceutical composition comprising sterile ensifentrine particles suitable for administration by inhalation, wherein the composition is produced by a method comprising:

(a) dry heating ensifentrine particles as a dry powder at a temperature of from 145° C. to 175° C. for 45 minutes to 160 minutes to obtain the sterile ensifentrine particles, and

(b) combining the sterile ensifentrine particles with a sterile liquid vehicle to produce the sterile liquid pharmaceutical composition suitable for administration by inhalation;

wherein the dry heating produces less than a 0.5% w/w increase in total impurities.

2. The composition of claim 1 , wherein the dry heating is performed at a temperature of 155° C. to 165° C. for 110 minutes to 130 minutes.

3. The composition of claim 1 , wherein the sterile ensifentrine particles comprise at least 95% by weight of ensifentrine or a pharmaceutically acceptable salt thereof relative to a total weight of the sterile ensifentrine particles.

4. The composition of claim 1 , wherein the sterile ensifentrine particles comprise at least 95% by weight of ensifentrine free base relative to a total weight of the sterile ensifentrine particles.

5. The composition of claim 1 , wherein the sterile ensifentrine particles have a particle size distribution with a Dv10 of from 0.1 μm to 1.0 μm.

6. The composition of claim 1 , wherein the sterile ensifentrine particles have a particle size distribution with a Dv50 of from 0.5 μm to 5.0 μm.

7. The composition of claim 1 , wherein the sterile ensifentrine particles have a particle size distribution with a Dv90 of from 2.5 μm to 6 μm.

8. The composition of claim 1 , wherein the method further comprises subjecting a liquid vehicle to aseptic filtration to produce the sterile liquid vehicle.

9. The composition of claim 1 , wherein the sterile liquid vehicle comprises a diluent and optionally one or more additional excipients selected from surfactants, buffers, and tonicity adjusters.

10. The composition of claim 9 comprising

(a) sterile ensifentrine particles at a concentration of from 0.5 mg/mL to 6 mg/ml;

(b) one or more surfactants at a concentration of from 0.01 mg/mL to 2 mg/ml;

(c) a buffer at a concentration of from 0.6 mg/mL to 4 mg/mL;

(d) a tonicity adjuster at a concentration of from 5 mg/mL to 12 mg/mL.

11. The composition of claim 10 , wherein the sterile liquid vehicle comprises water, sodium chloride, sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate dihydrate, polysorbate 20, or sorbitan laurate.

12. The composition of claim 11 , comprising

(a) sterile ensifentrine particles at a concentration of from 0.5 mg/mL to 6 mg/ml;

(b) polysorbate 20 at a concentration of from 0.1 mg/mL to 1.5 mg/ml;

(c) sorbitan monolaurate at a concentration of from 0.01 mg/mL to 0.5 mg/ml;

(d) sodium dihydrogen phosphate dihydrate at a concentration of from 0.3 mg/mL to 2 mg/mL;

(e) disodium hydrogen phosphate dihydrate at a concentration of from 0.3 mg/mL to 2 mg/mL; and

(f) sodium chloride at a concentration of from 5 mg/mL to 12 mg/mL,

wherein a total weight of ensifentrine in the sterile liquid pharmaceutical composition is from 2.7 to 3.3 mg.

13. The composition of claim 1 , wherein the sterile liquid pharmaceutical composition comprises the sterile ensifentrine particles at a concentration of from 0.1 mg/mL to 5 mg/mL.

14. The composition of claim 13 , wherein the sterile liquid pharmaceutical composition comprises the sterile ensifentrine particles at a concentration of from 1 mg/mL to 2 mg/mL.

Assignments (1)

Priority Claims (1)

Continuity (3)

References Cited (305)