Claims for Patent: 11,858,898

Summary for Patent: 11,858,898

Title:	Crystalline freebase forms of a biphenyl compound
Abstract:	The invention provides two crystalline freebase forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester. The invention also provides pharmaceutical compositions comprising the crystalline freebase or prepared using the crystalline freebases; processes and intermediates for preparing the crystalline freebases; and methods of using the crystalline freebases to treat a pulmonary disorder.
Inventor(s):	Grahame Woollam
Assignee:	Theravance Biopharma R&D IP LLC
Application Number:	US18/199,812
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,858,898
Patent Claims:	1. A method for treating chronic obstructive pulmonary disease in a human patient, the method comprising: administering 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; wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1 and 20.2±0.1. 2. The method of claim 1, wherein the crystalline freebase is further characterized by a melting point of about 125° C. 3. The method of claim 1, wherein the crystalline freebase is further characterized by a differential scanning calorimetry thermograph which shows an onset of endothermic heat flow at about 123° C. 4. The method of claim 1, wherein the pharmaceutical composition is isotonic. 5. The method of claim 1, wherein the pharmaceutical composition has a pH of about 4-6. 6. The method of claim 1, wherein the pharmaceutical composition is buffered with citrate buffer to a pH of about 5. 7. The method of claim 1, wherein the pharmaceutical composition contains about 0.05 μg/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. 8. The method of claim 1, wherein the pharmaceutical composition is administered to the human patient using a nebulizer. 9. A crystalline form of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 20 values of 11.4±0.1 and 11.6±0.1. 10. The crystalline form of claim 9, wherein the crystalline form is characterized by a DSC thermograph which shows an onset of endothermic heat flow at about 123° C. 11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a crystalline form of claim 9. 12. A crystalline form of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, wherein the crystalline form is characterized by a differential scanning calorimetry thermograph which shows an onset of endothermic heat flow at about 123° C. 13. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a crystalline form of claim 12. 14. A method for treating chronic obstructive pulmonary disease in a human patient, the method comprising: administering the pharmaceutical composition of claim 11. 15. The method of claim 14, wherein the pharmaceutical composition is isotonic. 16. The method of claim 14, wherein the pharmaceutical composition has a pH of about 4-6. 17. The method of claim 14, wherein the pharmaceutical composition is buffered with citrate buffer to a pH of about 5. 18. The method of claim 14, wherein the pharmaceutical composition contains about 0.05 μg/mL to about 10 mg/mL of biphenyl-2-ylcarbamic acid -(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester. 19. The method of claim 14, wherein the pharmaceutical composition is administered to the human patient using a nebulizer. 20. A method for treating chronic obstructive pulmonary disease in a human patient, the method comprising: administering the pharmaceutical composition of claim 13. 21. The method of claim 20, wherein the pharmaceutical composition is isotonic. 22. The method of claim 20, wherein the pharmaceutical composition has a pH of about 4-6. 23. The method of claim 20, wherein the pharmaceutical composition is buffered with citrate buffer to a pH of about 5. 24. The method of claim 20, wherein the pharmaceutical composition contains about 0.05 μg/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. 25. The method of claim 20, wherein the pharmaceutical composition is administered to the human patient using a nebulizer. 26. A pharmaceutical composition prepared from a crystalline form of claim 9 by adding a pharmaceutically acceptable carrier. 27. A pharmaceutical composition prepared from a crystalline form of claim 12 by adding a pharmaceutically acceptable carrier.