Claims for Patent: 11,008,289

Summary for Patent: 11,008,289

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)piper- idin-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):	Woollam; Grahame (Basel, CH)
Assignee:	THERAVANCE BIOPHARMA R&D IP, LLC (South San Francisco, CA)
Application Number:	16/715,225
Patent Claims:	1. A method for treating chronic obstructive pulmonary disease in a human patient, the method comprising: (a) preparing a pharmaceutical composition by dissolving a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl- )piperidin-4-yl ester in an aqueous pharmaceutical carrier; 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 (b) administering the pharmaceutical composition to the human patient using a nebulizer. 2. The method of claim 1, wherein the crystalline freebase is further characterized by 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. 3. The method of claim 1, wherein the crystalline freebase is further characterized by a powder x-ray diffraction pattern having peak positions in accordance with the peak positions shown in FIG. 1. 4. The method of claim 1, wherein the crystalline freebase is further characterized by a melting point of about 125.degree. C. 5. The method of claim 1, wherein the crystalline freebase is further characterized by a differential scanning calorimetry thermogram in accordance with that shown in FIG. 4. 6. The method of any one of claims 1 to 5, wherein the pharmaceutical composition is isotonic. 7. The method of any one of claims 1 to 5, wherein the pharmaceutical composition has a pH of about 4-6. 8. The method of any one of claims 1 to 5, wherein the pharmaceutical composition is buffered with citrate buffer to a pH of about 5. 9. The method of any one of claims 1 to 5, wherein the pharmaceutical composition contains about 0.05 .mu.g/mL to about 10 mg/mL of biphenyl-2-ylcarbamic acid 1424 [4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-- 4-yl ester.