US009765043B2 (12 ) United States Patent (10 ) Patent No. : US 9 ,765 ,043 B2 Cowen et al. ( 45 ) Date of Patent : Sep. 19, 2017 ( 54 ) SALTS OF POTASSIUM ATP CHANNEL 2004 / 0058009 Al 3 / 2004 Ruddy et al. 2004 /0072216 A1 4 / 2004 Johnson et al. OPENERS AND USES THEREOF 2004 /0204472 Al 10 /2004 Briggs et al . 2009 / 0062264 Al 3 /2009 Cowen et al. (71 ) Applicant: Essentialis , Inc. , Carlsbad , CA (US ) 2009 /0149451 A1 6 / 2009 Cowen ( 72 ) Inventors : Neil M . Cowen , Carlsbad , CA (US ) ; 2012 /0238554 AL 9 / 2012 Cowen et al . Richard C . Pasternak, New York , NY FOREIGN PATENT DOCUMENTS (US ) GB 982072 A 2 / 1965 @(73 ) Assignee : Essentialls , Inc. , Redwood City , CA WO WO 98 / 10786 A1 3 / 1998 (US ) OTHER PUBLICATIONS ( * ) Notice : Subject to any disclaimer , the term of this patent is extended or adjusted under 35 Standridge et al . “ Diazoxide down - regulates leptin and lipid U . S . C . 154 (b ) by 161 days . metabolizing enzymes in adipose tissue of Zucker rats ” The FASEB Journal, Aug . 2016 , vol. 14 , No. 3 , pp . 455 -460 . * Coskun et al. “ Treatment of hypertriglyceridemia - induced acute (21 ) Appl. No. : 14 /466 ,852 pancreatitis with insulin ” Przeglad Gastroenterologiczny, 2015 , vol. 10 , No ., pp . 18 -22 . * ( 22 ) Filed : Aug . 22 , 2014 J. G . Cannon Chapter Nineteen in Burgers Medicinal Chemistry and Drug Discovery , Fifth Edition , vol . I : Principles and Practice , (65 ) Prior Publication Data Wiley - Interscience 1995 , pp . 783 - 802, 784 . * US 2014 /0364425 A1 Dec . 11, 2014 Drug Delivery Technologies online article Dong et al , “ L - ORSOR SOFTCAPSTM for controlled Release of Non - Aqueous Liquid For mulations ." Related U . S . Application Data Remington : The Science and Practice of Pharmacy , Remington ' s (63 ) Continuation of application No. Pharmaceutical Sciences , 19th ed . , Mack Publishing Co . , Eason , PA , vol . 2 , p . 1457 , ( 1995 ) . PCT/ US2013 / 027676 , filed on Feb . 25 , 2013. U . S . Pharmacopeia , Chapter 711 Dissolution /Physical Tests , p . (60 ) Provisional application No . 61/ 603 ,923 , filed on Feb . 2412 - 2414 ( 2005 ) . 27 , 2012 Aguilar - Bryan et al ., “ Toward Understanding the Assembly and Structure of KATP Channels ” , Aguilar - Bryan , et al. , Physiological (51 ) Int. Cl. Reviews, vol . 78 , No . 1 , Jan . 1998 , 227 - 245 . Aizawa et al ., " Prophylaxis of genetically determined diabetes by A6IK 31/ 549 ( 2006 .01 ) diazoxide : a study in rat model of naturally occurring obese diabe C07D 285 /24 ( 2006 .01 ) tes .” , Aizawa et al ., Prophylaxis of genetically determined diabetes A61K 45 / 06 ( 2006 .01 ) by diazoxide : a study in rat model of naturally occurring obese A61K 31 / 14 ( 2006 .01 ) diabetes , The Journal of Pharmacology and Experimental Thera A61K 31 / 192 ( 2006 .01 ) peutics, 1995 , vol. 275 , No . 1 , pp . 194 - 199 . A6IK 31/ 202 ( 2006 .01 ) Alemzadeh et al. , “ Beneficial Effect of Diazoxide in Obese A61K 31 /655 ( 2006 .01 ) Hyperinsulinemic Adults ” , Journal of Clinical Endocrinology and A61K 31/ 44 ( 2006 . 01 ) Metabolism , vol. 83 , No. 6 , 1998 , pp . 1911 - 1915 . (52 ) U . S . CI. Alemzadeh et al. , “ Chronic suppression of insulin by diazoxide ???CPC . .. .. .. .. .. CO7D 285 /24 ( 2013 .01 ) ; A61K 31/ 14 alters the activities of key enzymes regulating hepatic ( 2013 .01 ) ; A61K 31/ 192 ( 2013 .01 ) ; A61K gluconeogenesis in Zucker rats , ” European Journal of Endocrinol 31/ 202 (2013 .01 ) ; A61K 31/ 44 ( 2013. 01 ) ; ogy , 2002 , vol. 146 , pp . 871- 879 . A61K 31 /549 ( 2013 .01 ) ; A61K 31 /655 (Continued ) ( 2013 .01 ) ; A61K 45 / 06 ( 2013 .01 ) ( 58 ) Field of Classification Search Primary Examiner — Kendra D Carter CPC .. .. .. A61K 31/ 549; CO7D 285/ 24 See application file for complete search history. ( 57 ) ABSTRACT ( 56 ) References Cited Provided are immediate or prolonged administration of U . S . PATENT DOCUMENTS certain salts of Karp channel openers such as diazoxide to a subject to achieve novel pharmacodynamic , pharmacoki 2 , 986 , 573 A 5 / 1961 Topliss et al. netic , therapeutic , physiological, metabolic and composi 4 ,880 ,830 A 11/ 1989 Rhodes et al. 5 ,284 , 845 A 2 / 1994 Paulsen tional outcomes in the treatment of diseases or conditions 5 , 399 ,359 A 3 / 1995 Baichwal involving Kftp channels . Also provided are pharmaceutical 5 ,415 , 871 A 5 / 1995 Pankhania et al. formulations , methods of administration and dosing of the 5 ,629 , 045 A 5 / 1997 Veech et al . salts that achieve these outcomes and reduce the incidence 5 , 656 ,667 A 8 / 1997 Breivik et al. 6 ,022 , 562 A 2 / 2000 Autant et al. of adverse effects in treated individuals . 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