US009314465B2 (12) United States Patent (10) Patent No.: US 9,314.465 B2 Brew et al. (45) Date of Patent: *Apr. 19, 2016 (54) DRUG COMBINATIONS AND USES IN 2008.0003280 A1 1/2008 Levine et al. ................. 424/456 TREATING A COUGHING CONDITION 2008/O176955 A1 7/2008 Hecket al. 2008, 0220078 A1 9, 2008 Morton et al. (71) Applicant: Infirst Healthcare Limited 2009, O136427 A1 5/2009 Croft et al. 2009, O220594 A1 9, 2009 Field (72) Inventors: John Brew, London (GB); Robin Mark 2012/O128738 A1 5, 2012 Brew et al. Bannister, London (GB) 2012fO252824 A1 10/2012 Brew et al. (73) Assignee: Infirst Healthcare Limited, London FOREIGN PATENT DOCUMENTS (GB) CN 1593451 3, 2005 CN 101024.014 A 8, 2007 (*) Notice: Subject to any disclaimer, the term of this CN 101112383 B 5, 2010 patent is extended or adjusted under 35 DE 4420708 A1 12, 1995 U.S.C. 154(b) by 0 days. EP 2050435 B1 4/2009 GB 2114001 A 8, 1983 This patent is Subject to a terminal dis GB 2284761 A 6, 1995 claimer. 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Chung, et PCT/GB2010/051896, filed on Nov. 12, 2010, and a al., 2003). continuation-in-part of application No. Forsberg, et al., Selective Inhibition of Cough and Bronchoconstric tion in Conscious Guinea Pigs, Respiration 59: 72-76 (1992). PCT/GB2010/050997, filed on Jun. 15, 2010. Levine, A Novel Treatment of Chronic Unexplained Cough, Chest J. (51) Int. Cl. 134(4 Meeting Abstracts): s 17003 (2008). A6 IK3I/522 (2006.01) Murao, et al., Intoxication with Over-the-Counter Antitussive Medi A6 IK3I/485 (2006.01) cation Containing Dihydrocodeine and Chlorpheniramine Causes A6 IK 45/06 (2006.01) Generalized Convulsion and Mixed Acidosis, Inter. Med. 47: 1013 (52) U.S. Cl. 1015 (2008). CPC ............. A6 IK3I/522 (2013.01); A61 K3I/485 (Continued) (2013.01); A61K 45/06 (2013.01) (58) Field of Classification Search USPC ..................................................... 51.4/263.34 Primary Examiner — Kathrien Cruz See application file for complete search history. (74) Attorney, Agent, or Firm — One3 IP Management, P.C.; Dean G. Stathakis; Peter D. Weinstein (56) References Cited U.S. PATENT DOCUMENTS (57) ABSTRACT 6,348,470 B1 2, 2002 Korbonits et al. 6,417,206 B1 7/2002 Leflein et al. The present specification discloses compositions comprising 2002fOO52312 A1 5, 2002 Reiss et al. a plurality of therapeutic compound having antitussive activ 2003/0206942 A1 11/2003 Kulkarni et al. ity and methods and uses for treating a coughing condition 2004/0202677 A1 10/2004 Hopkins et al. 2004/0204440 A1 10, 2004 Staniforth et al. with Such compositions. 2005/022O897 A1 10/2005 Hacket al. 2006, O148837 A1 7/2006 Giordano et al. 2007, 0160689 A1 7/2007 Giordano et al. 10 Claims, No Drawings US 9,314.465 B2 Page 2 (56) References Cited Database WPI, Week 200343, Thomson Scientific, London, GB, AN 2003-451953 & JP 2003-055258 (Rohto) Feb. 26, 2003. Dicpinigaitis, et al., Currently Available Antitussives. 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Database WPI, Week 200308, Thomson Scientific, London, GB, AN 2003-078587 & JP 2002-193839 (Meiji) Jul 10, 2002. * cited by examiner US 9,314,465 B2 1. 2 DRUG COMBINATIONS AND USES IN complications are common and include abdominal or pelvic TREATING ACOUGHING CONDITION hernias, fatigue fractures of lower ribs and costochondritis. Even though cough medicines are a common an over-the This continuation-in-part application claims priority pur counter remedy for individuals seeking outpatient medical suant to 35 U.S.C. S 120 to U.S. patent application Ser. No. attention, their effectiveness as a treatment for a cough is 13/446.217, filed Apr. 13, 2012, a continuation-in-part appli doubtful. In 2006, the American College of Chest Physicians cation of International patent Application PCT/GB2011/ issued guidelines stating that “most over the counter cough 051610, filed Aug. 25, 2011, which claims priority to GB medications are ineffective’, and several research reports Provisional 1014391.5, filed Aug. 27, 2010; International seem to confirm this conclusion. For example, the non-opiate patent Application PCT/GB2010/052085, filed Dec. 14, 10 antitussive drug Dextromethorphan is marketed as a cough 2010, which claims priority to GB Provisional 092.1805.8. filed Dec. 14, 2009; International patent Application PCT/ therapy. However, its efficacy and suitability as a treatment GB2010/052086, filed Dec. 14, 2010, which claims priority for cough is questionable, since its apparent Success as a to GB Provisional 092.1803.3, filed Dec. 14, 2009: Interna clinical treatment was attributed to a placebo effect: Dex tional patent Application PCT/GB2010/051895, filed Nov. 15 tromethorphan itself had no efficacy in treating cough. (Ram 12, 2010, which claims priority to GB Provisional 09 19889.6 sey et al., Br. J. Clin. Pharmacol.) Similarly, the decongestant filed Nov. 13, 2009; International patent Application PCT/ pseudoephedrine has been to shown to have very limited GB2010/051896, filed Nov.