US010752634B2 ( 12 ) United States Patent ( 10 ) Patent No .: US 10,752,634 B2 Purro et al . ( 45 ) Date of Patent : * Aug . 25 , 2020 ( 54 ) CRYSTALLINE FORMS OF A BRUTONS ( 52 ) U.S. CI . TYROSINE KINASE INHIBITOR CPC CO7D 487/04 ( 2013.01 ) ; A61J 1/035 ( 2013.01 ) ; A61K 9/0053 ( 2013.01 ) ; A61K ( 71 ) Applicant: Pharmacyclics LLC , Sunnyvale, CA 9/2013 ( 2013.01 ) ; A61K 9/2018 ( 2013.01 ) ; ( US ) A61K 9/2054 ( 2013.01 ) ; A61K 9/4825 ( 2013.01 ) ; A61K 9/4858 ( 2013.01 ) ; A61K ( 72 ) Inventors : Norbert Purro , Los Gatos, CA ( US ); 9/4866 ( 2013.01 ) ; A61K 31/519 ( 2013.01 ) ; Mark S. Smyth , Granite Bay , CA ( US ) ; A61K 45/06 ( 2013.01 ) ; B65D 75/36 ( 2013.01 ) ; Erick Goldman , Concord , CA (US ); C07B 2200/13 ( 2013.01 ) David D. Wirth , Oak Ridge, NC (US ) ( 58 ) Field of Classification Search CPC A61K 31/519 ; C07D 487/04 ( 73 ) Assignee : Pharmacyclics LLC , Sunnyvale , CA USPC 514 / 262.1 ; 544/262 ( US ) See application file for complete search history. ( * ) Notice: Subject to any disclaimer , the term of this patent is extended or adjusted under 35 ( 56 ) References Cited U.S.C. 154 ( b ) by 0 days. U.S. PATENT DOCUMENTS This patent is subject to a terminal dis 4,824,982 A 4/1989 Vahlensieck et al . claimer . 5,033,252 A 7/1991 Carter 5,052,558 A 10/1991 Carter ( 21 ) Appl . No .: 16 /837,665 5,145,684 A 9/1992 Liversidge et al . 5,323,907 A 6/1994 Kalvelage 5,397,787 A 3/1995 Buzzetti et al . ( 22 ) Filed : Apr. 1 , 2020 5,593,997 A 1/1997 Dow et al . 6,160,010 A 12/2000 Uckun et al . ( 65 ) Prior Publication Data 6,221,900 B1 4/2001 Uckun et al . 6,303,652 B1 10/2001 Uckun et al . US 2020/0223856 A1 Jul . 16 , 2020 6,306,897 B1 10/2001 Uckun et al . 6,326,469 B1 12/2001 Ullrich et al . 6,342,247 B1 1/2002 Ku et al . 6,410,054 B1 6/2002 Thosar et al . Related U.S. Application Data 6,506,769 B2 1/2003 Snow et al . ( 60 ) Continuation of application No. 16 / 690,788 , filed on 6,607,747 B2 8/2003 Ullah et al . Nov. 21 , 2019 , which is a continuation of application ( Continued ) No. 16 / 393,775 , filed on Apr. 24 , 2019 , now abandoned , which is a continuation of application No. FOREIGN PATENT DOCUMENTS 16 / 111,014 , filed on Aug. 23 , 2018 , now Pat . No. CN 101610676 A 12/2009 10,294,232 , which is a continuation of application CN 103121999 A 5/2013 No. 15 / 900,660 , filed on Feb. 20 , 2018 , now Pat . No. 10,106,548 , which is a continuation of application (Continued ) No. 15 / 887,744 , filed on Feb. 2 , 2018 , now abandoned , which is a continuation of application No. OTHER PUBLICATIONS 15 / 645,319 , filed on Jul. 10 , 2017 , now abandoned , US 10,085,944 B2 , 10/2018 , Chong et al . (withdrawn ) which is a continuation of application No. 15 / 497,896 , filed on Apr. 26 , 2017 , now Pat . No. ( Continued ) 9,725,455 , which is a continuation of application No. 15 / 386,118 , filed on Dec. 21 , 2016 , now Pat . No. Primary Examiner — Jeffrey H Murray 9,713,617 , which is a division of application No. ( 74 ) Attorney, Agent, or Firm — Foley Hoag LLP 14 / 405,317 , filed as application No. PCT /US2013 / 043888 on Jun . 3 , 2013 , now Pat . No. 9,540,382 . ( 57 ) ABSTRACT Described herein is the Bruton's tyrosine kinase ( Btk ) inhibitor 1 - ( (R )-3- ( 4 - amino - 3- ( 4 - phenoxyphenyl) -1H -pyra ( 60 ) Provisional application No. 61 / 655,381 , filed on Jun . zolo [ 3,4 - d ]pyrimidin - 1 -yl ) piperidin - 1 - yl ) prop - 2 - en - 1 - one , 4 , 2012 . including crystalline forms, solvates and pharmaceutically ( 51 ) Int. Cl . acceptable salts thereof . Also disclosed are pharmaceutical A61K 31/519 ( 2006.01 ) compositions that include the Btk inhibitor, as well as CO7D 487/04 ( 2006.01 ) methods of using the Btk inhibitor, alone or in combination A61K 45/06 ( 2006.01 ) with other therapeutic agents, for the treatment of autoim A61K 9/20 ( 2006.01 ) mune diseases or conditions , heteroimmune diseases or A61K 9/48 ( 2006.01 ) conditions , cancer , including lymphoma, and inflammatory A61 ) 1/03 ( 2006.01 ) diseases or conditions . A61K 9/00 ( 2006.01 ) B65D 75/36 ( 2006.01 ) 28 Claims , 16 Drawing Sheets US 10,752,634 B2 Page 2 ( 56 ) References Cited 9,545,407 B2 1/2017 Shu et al . 9,655,857 B2 5/2017 Chong et al . 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