Granted Patent B2

US 11,691,948 · App. 17/301,820 · Granted Jul 4, 2023

Inventor: Grahame Woollam (Basel, CH)

Assignee: Theravance Biopharma R&D IP, LLC

C07D211/62A61K9/124A61K9/1623A61K31/4545A61K45/06C07D401/12C07B2200/13

Abstract

Claims (21)

1. A pharmaceutical composition useful for treating chronic obstructive pulmonary disease in a human patient, produced by the following step: dissolving a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{1[4-(4-carbamoylpiperidin-1-ylmethyl) benzoyl]methylamino}-ethyl)piperidin-4-yl ester in a solvent to form a solution; wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 20 values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1; and wherein the pharmaceutical composition has a pH of about 5.

2. The pharmaceutical composition of claim 1 , wherein the solution is combined with an aqueous pharmaceutical carrier.

3. The pharmaceutical composition of claim 1 , wherein the solvent is an aqueous pharmaceutical carrier.

4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1, and further characterized by having five or more additional diffraction peaks at 2θ values selected from 8.8±0.1, 10.1±0.1, 11.4±0.1, 11.6±0.1, 14.8±0.1, 15.2±0.1, 16.1±0.1, 16.4±0.1, 16.9±0.1, 17.5±0.1, 18.2±0.1, 19.3±0.1, 19.9±0.1, 20.8±0.1, 21.1±0.1, 21.7±0.1, and 22.3±0.1; and wherein crystalline freebase is dissolved in a solvent and then combined with the pharmaceutically acceptable carrier; and wherein the pharmaceutical composition has a pH of about 5.

5. The pharmaceutical composition of claim 4 , wherein the crystalline freebase is further characterized by a melting point of about 125° C.

6. A pharmaceutical composition comprising: a dissolved crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl) benzoyl]methylamino}-ethyl)piperidin-4-yl ester and an aqueous pharmaceutical carrier; wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1; and wherein the pharmaceutical composition has a pH of about 5.

7. The pharmaceutical composition of claim 4 , wherein the pharmaceutical composition is isotonic.

8. The pharmaceutical composition of claim 4 , wherein the pharmaceutical composition is buffered with citrate buffer to a pH of about 5.

9. The pharmaceutical composition of claim 4 , wherein the pharmaceutical composition contains about 0.05m/mL to about 10 mg/mL of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino }ethyl)piperidin-4-yl ester.

10. The pharmaceutical composition of claim 4 , wherein the pharmaceutical composition is administered by inhalation using a nebulizer inhaler.

11. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is isotonic.

12. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is buffered with citrate buffer to a pH of about 5.

13. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition contains about 0.05 μm/mL to about 10 mg/mL of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester.

14. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is administered by inhalation using a nebulizer inhaler.

15. A pharmaceutical composition comprising: a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester in a solution; wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1.

16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1, and further characterized by having five or more additional diffraction peaks at 20 values selected from 8.8±0.1, 10.1±0.1, 11.4±0.1, 11.6±0.1, 14.8±0.1, 15.2±0.1, 16.1±0.1, 16.4±0.1, 16.9±0.1, 17.5±0.1, 18.2±0.1, 19.3±0.1, 19.9±0.1, 20.8±0.1, 21.1±0.1, 21.7±0.1, and 22.3±0.1, wherein the crystalline freebase is in solution with the pharmaceutically acceptable carrier.

17. A pharmaceutical composition comprising a solution of a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester characterized by (i) a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1 or (ii) a melting point of about 125° C.

18. A pharmaceutical composition comprising a solution comprising a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester; wherein the crystalline freebase is characterized by a melting point of about 125° C.

19. A pharmaceutical composition comprising a solution comprising a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester; wherein the crystalline freebase is characterized by a powder x-ray diffraction comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1.

20. A solution comprising a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester; wherein the crystalline freebase is characterized by a melting point of about 125° C.

21. A solution comprising a crystalline freebase of biphenyl- 2 -ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester; wherein the crystalline freebase is characterized by a powder x-ray diffraction comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1.

Assignments (1)

Continuity (10)