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(12) Patent (10) Patent No.: US 9,504,640 B2 Oberegger et al. (45) Date of Patent: Nov. 29, 2016

(54) MODIFIED RELEASE FORMULATIONS OF 3,845,770 A 1 1/1974 Theeuwes et al. A BUPROPION SALT 3,916,899 A 11/1975 Theeuwes et al. 4,008,719 A 2f1977 Theeuwes et al. 4,021,492 A 5, 1977 Linder et al. (71) Applicant: VALEANT PHARMACEUTICALS 4,177.291. A 12/1979 Lindberg et al. LUXEMBOURG S.A.R.L., 4,308.400 A 12/1981 Felder et al. Luxembourg (LU) 4,347,257 A 8, 1982 Stern 4,393,078 A 7, 1983 Peck (72) Inventors: Werner Oberegger, Mississauga (CA); 2. A RE: St. Fang Zhou, Centreville, VA (US); Paul 4507333 A 3, 1985 SE Maes, Toronto (CA); Stefano 4,536,518 A 8/1985 Welch, Jr. et al. Turchetta, Rome (IT); Graham 4,576,944 A 3, 1986 Lafon Jackson, County Kildare (IE); Pietro 4,687,660 A 8, 1987 Baker et al. Massardo, Rome (IT); Mohammad 2. A 23. Past et al. Ashty Saleh, Oakville (CA) 4,851.22s. A 7/1989 Zentner et al. 4,886,668 A 12/1989 Haslam et al. (73) Assignee: Valeant Pharmaceuticals Luxembourg 4,980,377. A 12/1990 Lafon S.A.R.L., Luxembourg (LU) RE33,994 E 7, 1992 Baker et al. 5,260,068 A 11, 1993 Chen (*) Notice: Subject to any disclaimer, the term of this 33.5% A 1992 SE al. patent is extended or adjusted under 35 5.427.79s A 6/1995 Ludwig et al. U.S.C. 154(b) by 0 days. 5,508,040 A 4/1996 Chen 5,541,231 A 7, 1996 Ruff et al. (21) Appl. No.: 14/474,580 5,648,096 A 7/1997 Gander et al. Continued (22) Filed: Sep. 2, 2014 ( ) FOREIGN PATENT DOCUMENTS (65) Prior Publication Data EP O118036 A1 9, 1984 US 2015/0202147 A1 Jul. 23, 2015 EP O147479 A1 7, 1985 Continued Related U.S. Application Data ( ) (63) Continuation of application No. 1 1/762.343, filed on OTHER PUBLICATIONS Jun. 13, 2007, now Pat. No. 8,932,628, which is a continuation of application No. 1 1/751,768, filed on Badio, B., et al., “: a potent noncompetitive blocker of May 22, 2007, now Pat. No. 7,569,610, which is a ganglionic/neuronal nicotinic receptors.” Molecular pharmacology continuation of application No. 1 1/475.252, filed on 51(1):1-5, American Society for Pharmacology and Experimental Jun. 27, 2006, now Pat. No. 7,241,805. Therapeutics, United States (1997). Bastin, R.J., et al., “Salt Selection and Optimisation Procedures for (60) gyal application No. 60/693,906, filed on Jun. Pharmaceutical New Chemical Entities.” Organic Process Research s and Development 4(5):427-435, American Chemical Society, United States (2000). (51) Int. Cl. Berge, S.M., et al., “Pharmaceutical salts,” Journal of pharmaceu CD7C 225/6 (2006.01) tical sciences 66(1):1-19, Wiley-Liss, United States (1977). A6 IK 9/28 (2006.01) Bupropion. A review of the Scientific literature on bupropion, a A6 IK3I/35 3.08: novel , (C) Aug. 1990 by PJB Publications Ltd. A6 IK3I/37 2006.O1 A6 IK 9/00 (2006.01) (Continued)Continued A6 IK 9/20 (2006.01) (52) U.S.CPC Cl...... A61K 9/0004 (2013.01); A61K 9/2027 Primary Examiner Paul A Zucker (2013.01); A61K 9/28 (2013.01); A61K 9/2846 (74) Attorney, Agent, or Firm — John E. Thomas, Esq.; (2013.01); A61K 9/2866 (2013.01); A61 K Andrew J. Anderson, Esq.; Harter Secrest & Emery LLP 9/2886 (2013.01); A61K 31/135 (2013.01); A6IK3I/137(2013.01); C07B(2013.01); 2200/13 C07C (2013.01) 225/16 (57) ABSTRACT (58) Field of Classification Search The present invention relates to pharmaceutical composi CPC opli------... .filefo A.0004: R. 225/16 tions, formulations and medicaments comprising a bupro See application file for complete search history. pion salt, in particular, modified-release tablets comprising an effective amount of bupropion hydrobromide, and the use (56) References Cited of the bupropion salt to propprepare ya medicament to treat a U.S. PATENT DOCUMENTS condition. 3,117,967 A 1/1964 Anderson et al. 3,819,706 A 6, 1974 Mehta 11 Claims, 71 Drawing Sheets US 9,504640 B2 Page 2

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Tutka, P. et al., "Bupropion-induced convulsions: preclinical evalu Popik, P. et al., "Nmda antagonist properties of the putative ation of antiepileptic drugs.” Epilepsy research 64(1-2): 13-22, antiaddictive drug, ibogaine.” The Journal of pharmacology and Elsevier Science Publishers, Netherlands (2005). experimental therapeutics 275(2):753-760, American Society for Tutka, P. et al., " and anticonvulsant effects of Pharmacology and Experimental Therapeutics, United States bupropion in mice.” European journal of pharmacology 499(1- (1995). 2): 117-120, Elsevier Science, Netherlands (2004). Pulvirenti, L., et al., “Dextromethorphan reduces intravenous WikipediaR i Wikimedia Foundation, Inc. http://en.wikipedia.org/ cocaine self-administration in the rat.” European journal of phar wiki/13upropionhillistory 20:57, Apr. 8, 2007. macology 321(3):279-283, Elsevier Science, Netherlands (1997). Zyban (C) (bupropion hydrochloride) Sustained-Release Tablets Quick, M.W., et al., “Alpha3beta4 subunit-containing nicotinic Prescribing Information, pp. 1-32, Jun. 2007. receptors dominate function in rat medial habenula neurons.” Van Wyck Fleet, J., et al., “Overview of clinically significant Neuropharmacology 38(6):769-783, Pergamon Press, England adverse reactions to bupropion.” The Journal of clinical psychiatry (1999). 44(5 Pt 2):191-196, Physicians Postgraduate Press, United States Reid, M.S., et al., "A nicotine antagonist, mecamylamine, reduces (1983). cue-induced cocaine craving in cocaine-dependent subjects.” Verbeeck, R.K., et al., "Generic substitution: the use of medicinal Neuropsychopharmacology 2003):297-307. Nature Publishing products containing different salts and implications for safety and Group, England (1999). efficacy.” European journal of pharmaceutical sciences 28(1-2): 1-6, Remington's Pharmaceutical Sciences, Edition 17, pp. 1418, 1985. Elsevier Science B.V. Netherlands (2006). Rezvani, A.H., et al., "Attenuation of consumption by a Wacks, I., et al., "Spurious hyperchloremia and novel nontoxic ibogaine analogue (18-methoxycoronaridine) in hyperbicarbonatemia in a patient receiving pyridostigmine bromide alcohol-preferring rats.” Pharmacology, biochemistry, and behavior therapy for myasthenia gravis.” American journal of kidney dis 58(2):615-619, Elsevier, United States (1997). eases 16(1):76-79, W.B. Saunders, United States (1990). Russian Office Action Issued Jul. 3, 2012 in Patent Application No. Welch, R.M., et al., "Pharmacological significance of the species 2010116863/15(024001) (with English translation). differences in bupropion metabolism.” Xenobiotica 17(3):287-298, Russian Office Action issued May 11, 2012 in corresponding Informa Healthcare, England (1987). Russian Application No. 2010/07843/15(0.11034), filed on Aug. 6, Wellbutrin SR (bupropion bydrochloride) Tablets-Prescribing 2008 (with an English Translation). 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