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(12) United States Patent (10) Patent No.: US 9,642,796 B2 Packhaeuser Et Al

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(12) United States Patent (10) Patent No.: US 9,642,796 B2 Packhaeuser Et Al USOO9642796 B2 (12) United States Patent (10) Patent No.: US 9,642,796 B2 Packhaeuser et al. (45) Date of Patent: May 9, 2017 (54) PHARMACEUTICAL DOSAGE FORM FOR 8, 168,784 B2 5/2012 Franczyk, II et al. ORAL ADMINISTRATION OF ABCL 2 8,377,952 B2 2/2013 Rosenberg et al. 8,927,009 B2 1/2015 Tong et al. FAMILY INHIBITOR 2002/0055631 A1 5/2002 Augeri et al. 2005/0101628 A1 5/2005 Jiao et al. (75) Inventors: Claudia Packhaeuser, Mannheim 2005, 0163835 A1 7/2005 Gellert et al. (DE); Norbert Steiger, Lingenfield 2005/0208082 A1 9/2005 Papas et al. 2005/0236236 A1 10/2005 Farooq (DE); Bernd Liepold, Dossenheim 2006/0177430 A1 8, 2006 Bhushan et al. (DE); Drazen Kostelac, Roemerberg 2006/0183776 A9 8, 2006 Pratt (DE); Martin Knobloch, Neuhofen 2007/0027135 A1 2/2007 Bruncko et al. (DE) 2007/OO72860 A1 3/2007 Bruncko et al. 2007/O104780 A1 5/2007 Lipari et al. (73) Assignee: AbbVie Inc., North Chicago, IL (US) 2007, 0161681 A1 7/2007 Marfat et al. 2007,024.3257 A1 10, 2007 Bedos et al. 2008.0004286 A1 1/2008 Wang et al. (*) Notice: Subject to any disclaimer, the term of this 2008/0085313 A1 4/2008 Given et al. patent is extended or adjusted under 35 2008. O182845 A1 7/2008 Bardwell et al. U.S.C. 154(b) by 128 days. 2009, O149461 A1 6/2009 Krivoshik 2010. 0233251 A1 9/2010 Von Andrian et al. Appl. No.: 12/796,000 2010/0278.905 A1 11/2010 Catron et al. (21) 2010/0278921 A1 11/2010 Fischer et al. 2010/0280031 A1 11/2010 David et al. (22) Filed: Jun. 8, 2010 2010/0297 194 A1 11/2010 Catron et al. 2010/03051 22 A1 12/2010 Bruncko et al. (65) Prior Publication Data 2010/0305125 A1 12/2010 Borchardt et al. 2010/0311751 A1 12/2010 Schmitt et al. US 2010/0310648 A1 Dec. 9, 2010 2010.0323020 A1 12/2010 Gokhale et al. (Continued) Related U.S. Application Data FOREIGN PATENT DOCUMENTS (60) Provisional application No. 61/185.130, filed on Jun. 8, 2009. CN 1561.201 A 1, 2005 CN 1706371 A 12/2005 (51) Int. C. (Continued) A6 IK 9/48 (2006.01) A6 IK 9/00 (2006.01) OTHER PUBLICATIONS A6 IK 9/14 (2006.01) A6 IK3I/635 (2006.01) Tse et al. 2008. ABT-263: A potent and orally bioavailable bcl-2 U.S. C. family inhibitor. Cancer Res; 68(9): 3421-3428.* (52) Sharma D.K., et al., “Solubility Enhancement Strategies for Poorly CPC ............ A61K 9/0053 (2013.01); A61K 9/146 Water-Soluble Drugs in Solid Dispersions: A Review”. Asian Jour (2013.01); A61 K3I/635 (2013.01) nal of Pharmaceutics, 2007, vol. 1 (1), pp. 9-19. (58) Field of Classification Search Park C.M., et al. “Discovery of an Orally Bioavailable Small CPC ...... A61K 9/10; A61K 31/427; A61K 3 1/505; Molecule Inhibitor of ProSurvival B-Cell Lymphoma 2 Proteins.” A61K 3 1/513; A61K 3 1/635; A61 K Journal of Medicinal Chemistry, 2008, vol. 51 (21), pp. 6902-6915. 47/14: A61K 47/22: A61 K9/0053: A61 K Brandrup J. et al., “Polymer Handbook,” 1975, 2, John Wiley & 9/146; C07D 239/49; C07D 239/69 Sons, Inc. See application file for complete search history. (Continued) (56) References Cited Primary Examiner — David Browe U.S. PATENT DOCUMENTS 5,536,729 A 7, 1996 Waranis et al. (57) ABSTRACT 5,538,737 A 7, 1996 Leonard et al. 5,559,121 A 9, 1996 Harrison et al. 5,635,187 A 6, 1997 Bathurst et al. The invention relates to a pharmaceutical dosage form 5,645,856 A 7/1997 Lacy et al. which comprises a solid dispersion product comprising 5,665,379 A 9, 1997 Herslöf et al. N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1- 5,707,648 A 1, 1998 Yv 5,891,469 A 4/1999 AmSelem pholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3- 6,004,973 A 12/1999 Guitard et al. 6,267,985 B1 7/2001 Chen et al. ((trifluoromethyl)sulfonyl)benzenesulfonamide or a salt, 6,309.663 B1 10/2001 Patel et al. hydrate or Solvate thereof, at least one pharmaceutically 6,451,339 B2 9, 2002 Patel et al. acceptable polymer, and at least one pharmaceutically 6,464,987 B1 10/2002 Fanara et al. acceptable solubilizer. The invention is further directed to 6,964,946 B1 1 1/2005 Gutierrez-Rocca et al. processes for preparing the pharmaceutical dosage form and 7,151,188 B1 12/2006 Simandan et al. 7,390,799 B2 6, 2008 Bruncko et al. to use of the dosage form for treating proliferative disorders. 7,459,283 B2 12/2008 Wertz et al. 7,842,681 B2 11/2010 Elmore et al. 7,973,161 B2 7/2011 Bruncko et al. 22 Claims, 4 Drawing Sheets US 9,642,796 B2 Page 2 (56) References Cited Extended European Search Report issued for EP 2515883 on Jun. 17, 2013, pp. 7. U.S. PATENT DOCUMENTS Gould, “Salt selection for basic drugs.” International Journal of Pharmaceutics, Nov. 1986, 33(1-3):201-217. 2011 (0071151 A1 3/2011 Zhang et al. International Search Report for Application No. PCT/IB2010/ 2015, 0021339 A1 1/2015 Felts et al. 00.1659, mailed on Dec. 13, 2010, pp. 12. Lessene et al., “BLC-2 family antagonists for cancer therapy,' FOREIGN PATENT DOCUMENTS Nature Reviews / Drug Discovery, Dec. 2008, vol. 7, pp.989-1000, CN 1.01175738 A 5, 2008 Macmillan Publishers Limited. CN 101.22O008 A T 2008 Paolini et al., Global mapping of pharamacological space, Jul. 2006, CN 101325944 A 12/2008 vol. 24. No. 24, pp. 805-815, Nature Biotechnology. CN 101798292 A 8, 2010 SkypePharma, DissoCubesonline), 2010 retrived on Nov. 17. CN 102131792 A T/2011 2012. 1 page, Retrieved from the Internet: <URL:http//www. EP 1880 715 A1 * 1, 2008 ............... A61K 9,20 skyepharma.com/Technology/Oral Technology Particle Engi RU 2008123798 A 12/2009 WO 97.03654 A2 2, 1997 neering Technologies/DissoCubes/Default.aspx?id=81. 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WO WO2009073835 A1 6, 2009 Crowley, M. et al.; “Pharmaceutical Applications of Hot-Melt WO 2009 155386 A1 12/2009 Extrusion: Part 1'; Drug Development and Industrial Pharmacy, WO 2010 127190 A1 11 2010 vol. 33, 2007, pp. 909-926. WO 2010 127198 A1 11 2010 Design and Evaluation of Oral Administration Drugs, 1995, pp. WO 2010O127.193 A1 11, 2010 172-179. WO 2010 143074 A2 12/2010 Holzelova, E. et al.; “Autoimmune Lymphoproliferative Syndrome WO 2011034934 A1 3, 2011 with Somatic Fas Mutations'. The New England Journal of Medi cine, vol. 351, 2004, pp. 1409-1418. OTHER PUBLICATIONS Kibbe et al., Handbook of Pharmaceutical Excipients, 2000, 3rd Bruncko M., et al. “Studies leading to potent, dual inhibitors of Edition, Table of Contents, 4 pages. Bcl-2 and Bcl-XL” Journal of Medicinal Chemistry, 2007, 50 (4), Klein, C. et al., “The Tablet Formulation of Lopinavir/Ritonavir 641-662. Provides Similar Bioavailability to the Soft-Gelatin Capsule For Fiedler H. B. 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