|HAI LALA A US009737508B2MARA UNNAMIN (12 ) United States Patent ( 10 ) Patent No. : US 9 , 737 ,508 B2 Zhang et al . (45 ) Date of Patent: * Aug. 22 , 2017 ( 54) USE OF NK - 1 RECEPTOR ANTAGONISTS IN ( 56 ) References Cited PRURITUS U . S . PATENT DOCUMENTS (71 ) Applicant: MENLO THERAPEUTICS INC ., 5 ,077 , 142 A 12 / 1991 Sakon et al . Menlo Park , CA (US ) 5 , 334 ,606 A 8 / 1994 MacLeod (72 ) Inventors : Xiaoming Zhang , Sunnyvale , CA (US ) ; 5 ,521 , 183 A 5 / 1996 Woodward et al. 5 ,629 , 327 A 5 / 1997 D ' Amato Edward F . Schnipper, Redwood City , 5 ,679 , 360 A 10 / 1997 De Lacharriere et al . CA (US ) ; Andrew J . Perlman , 5 , 869 ,521 A 2 / 1999 Farrar et al. Stanford , CA (US ) ; James W . Larrick , 5 , 981, 513 A 11 / 1999 Kruse et al . Sunnyvale , CA (US ) 6 ,054 , 445 A 4 / 2000 Zhang et al. 6 ,221 , 880 B1 4 / 2001 Shih (73 ) Assignee : MENLO THERAPEUTICS INC . , 6 , 476 , 063 B2 11/ 2002 Zhang et al. 6 , 743 , 793 B2 6 / 2004 Torisu et al . Menlo Park , CA (US ) 7 ,153 , 852 B2 12 /2006 Torisu et al. ( * ) Notice : Subject to any disclaimer , the term of this 7 , 217 , 731 B2 5 /2007 Bunda et al . 7 , 345 , 083 B2 3 / 2008 Bunda et al . patent is extended or adjusted under 35 7 , 435 , 745 B2 10 / 2008 D ' Amato U .S . C . 154 (b ) by 0 days. 7 , 511 , 072 B2 3 / 2009 Man et al . 7 , 544 , 815 B2 6 / 2009 Kuethe et al. This patent is subject to a terminal dis 7 , 645 , 790 B2 1 /2010 Bunda et al. claimer . 7 , 683 , 068 B2 3 / 2010 Jiang et al. 7 , 732 , 479 B2 6 /2010 Gazit et al. ( 21) Appl. No. : 15 / 271, 103 7 ,740 , 959 B2 6 / 2010 Yagi 7 , 893 , 091 B2 2 /2011 Gottesdiener et al . ( 22 ) Filed : Sep . 20 , 2016 8 , 008, 479 B2 8 / 2011 Portman 8 , 039 , 488 B2 10 / 2011 D 'Amato (65 ) Prior Publication Data 8 , 124, 633 B2 2 / 2012 DeVita et al . US 2017 / 0065558 A1 Mar. 9 , 2017 8 , 143, 283 B1 3 / 2012 D ' Amato 8 , 153 , 682 B2 4 / 2012 Branum et al . 8 ,263 ,636 B2 9 / 2012 Ansorge et al . Related U . S . Application Data (Continued ) (60 ) Continuation of application No. 15 / 175 ,358 , filed on FOREIGN PATENT DOCUMENTS Jun . 7 , 2016 , now Pat. No . 9 ,474 , 741 , which is a continuation of application No. 14 /922 ,684 , filed on EP 0717997 A1 6 / 1996 Oct . 26 , 2015 , now Pat . No . 9 , 381, 188 , which is a EP 1711465 Al 10 / 2006 division of application No. 14 /312 , 942 , filed on Jun . (Continued ) 24 , 2014 , now Pat . No . 9 , 198 ,898 , which is a continuation - in - part of application No . 13 / 925 , 509, OTHER PUBLICATIONS filed on Jun . 24 , 2013 , now Pat. No . 8 , 906 ,951 . Aitken , “ Section ofMeasurement in Medicine ” , Proc Roy Soc Med , vol. 62, pp . 989 - 993 ( Oct. 1969 ) . London , UK : Royal Society of (60 ) Provisional application No . 61/ 838 , 784, filed on Jun . Medicine. 24 , 2013 . Akiyama, et al. , “ Roles for substance P and gastrin - releasing peptide as neurotransmitters released by primary afferent pruricep (51 ) Int. Ci. tors ” , J Neurophysiol, vol. 109 , Issue 3 , pp . 742 -748 (Feb . 2013 ) . A61K 31 / 403 ( 2006 .01 ) Bethesda , MD : American Physiological Society . A61K 45 /06 ( 2006 .01 ) Akiyama, et al. , Abstract of “ Roles for substance P and gastrin A61K 31 /4035 ( 2006 .01 ) releasing peptide as neurotransmitters released by primary afferent A61K 9 / 00 ( 2006 .01 ) pruriceptors ” , J Neurophysiol, (2012 ). A61K 47 / 10 ( 2017 .01 ) Ally et al. , “ The use of aprepitant in brachioradial pruritus” , Dept. A61K 9 / 06 ( 2006 . 01 ) of Dermatology , Stanford University , School of medicine , pp . 1 - 7 A61K 9 / 20 ( 2006 . 01 ) ( Dec . 13 , 2012 ) . A61K 9 / 48 ( 2006 . 01 ) (Continued ) (52 ) U . S . Cl. Primary Examiner — Kristin Vajda CPC .. .. .. .. .. A61K 31/ 403 ( 2013 . 01 ) ; A61K 9 /0014 (74 ) Attorney , Agent, or Firm — Morrison & Foerster ( 2013 .01 ) ; A61K 9 /0053 (2013 .01 ) ; A61K 9 / 06 LLP (2013 .01 ) ; A61K 9 / 2009 ( 2013 .01 ) ; A61K 9 / 2013 ( 2013 .01 ) ; A61K 9 / 2018 ( 2013 . 01 ) ; (57 ) ABSTRACT A61K 9 / 2054 ( 2013 .01 ) ; A61K 9 / 4808 The invention relates to methods for treating pruritus with ( 2013 .01 ) ; A61K 9 /4858 ( 2013 .01 ) ; A61K NK - 1 receptor antagonists such as serlopitant. The invention 31/ 4035 (2013 . 01 ) ; A61K 45 /06 ( 2013 .01 ) ; further relates to pharmaceutical compositions comprising A61K 47 / 10 ( 2013 .01 ) NK - 1 receptor antagonists such as serlopitant. In addition , (58 ) Field of Classification Search the invention encompasses treatment of a pruritus - associ CPC .. A61K 31/ 4035 ; A61K 9 /0053 ; A61K ated condition with serlopitant and an additional antipruritic 9 /0014 ; A61K 45 / 06 ; A61K 31/ 403 agent, and the use of serlopitant as a sleep aid , optionally in USPC . .. .. .. .. 514 / 171, 416 combination with an additional sleep - aiding agent . See application file for complete search history . 31 Claims, 5 Drawing Sheets US 9 ,737 , 508 B2 Page 2 (56 ) References Cited WO WO 2014 /093907 A1 6 / 2014 WO WO 2014 / 107794 A1 7 /2014 U . S . PATENT DOCUMENTS WO WO 2014 /209962 A112 / 2014 8 ,455 ,638 B26 / 2013 Bittner et al . 8 , 809 , 327 B28 / 2014 Branum et al. OTHER PUBLICATIONS 8 , 889 , 729 B2 11/ 2014 Gazit et al . 8 , 901, 307 B2 12 / 2014 Dakin et al . Amatya , et al. , “ Responses to intradermal injections of substance P 8 , 906 , 951 B1 12 / 2014 Zhang et al. in psoriasis patients with pruritus” , Skin Pharmacol Physiol, vol. 23 , 9 , 198 , 898 B2 12 / 2015 Zhang et al . Issue 3 , pp . 133 - 138 (2010 ) . Basel , Switzerland : S . Karger AG . 9 , 381 ,188 B2 7 / 2016 Zhang et al . American Medical Association , “ Statement on a Nonproprietary 2003 / 0100565 A1 5 / 2003 Ohmura et al. 2006 / 0149076 Al 7 / 2006 Hicks Name Adopted by the USAN Council ” , www .ama - assn .org / re 2009 / 0209556 A1 8 / 2009 Bittner et al . sources/ doc /usan /serlopltant . pdf , p . 1 of 1 . 2009 / 0270477 AL 10 / 2009 Kuethe et al . Andersson , et al ., “ Current pharmacotherapy of lower urinary tract 2010 /0113469 Al 5 / 2010 Frenkl et al. symptoms” , Surgery , vol. 29 , Issue 6 (Renal and Urology III ) , pp . 2010 /0209496 A1 8 / 2010 Dokou et al . 260 -264 , (2011 ) . St . Louis , MO : Mosby . 2011/ 0224204 Al 9 / 2011 Chesworth et al. Andoh et al ., " Substance P induction of Itch -Associated Response 2011/ 0262442 Al 10 / 2011 Hamilton et al . Mediation by Cutaneous NK1 Tachykinin Receptors in Mice " , The 2012 / 0035168 A1 2 / 2012 Brandl et al . 2012 /0077803 AL 3 / 2012 Stuetz et al . Journal of Pharmacology and Experimental Therapeutics , vol . 286 , 2012 / 0225904 AL 9 / 2012 Bosch et al. No . 3 , pp . 1140 - 1145 ( 1998 ) . 2013 /0266645 A1 10 / 2013 Becker et al . Antiga E , et al. , “ A further case of subacute prurigo - like linear IgA 2013 / 0303497 A1 11/ 2013 Hansen et al. bullous dermatosis : growing evidence of a new subset ," Int J 2014 / 0378521 A112 / 2014 Zhang et al . Dermatol ., vol . 51, No. 12 , pp . 1500 - 1501 (Dec . 2012 ) . Oxford , UK : 2015 /0057255 AL 2 / 2015 Zhang et al. Blackwell Science . 2016 /0038462 A1 2 /2016 Zhang et al. Beauregard , et al ., “ A survey of skin problems and skin care 2016 /0143882 A15 / 2016 Zhang et al. regimens in the elderly ” , Arch Dermatol, vol . 12 , No. 12 , pp . 1638 - 1643 ( Dec . 1987) . Chicago , IL : American Medical Associa FOREIGN PATENT DOCUMENTS tion . RU 2370265 Ci 10 / 2009 Bergasa, et al ., “ Gabapentin in patients with the pruritus of WO WO 94 / 20085 Al 9 / 1994 cholestasis : a double- blind , randomized , placebo -controlled trial” , WO WO 96 / 06601 3 / 1996 Hepatology , vol . 44 , No . 5 , pp . 1317 - 1323 ( Nov. 2006 ) . Hoboken , WO WO 97 / 14671 4 / 1997 NJ : Wiley WO WO 98 / 19649 A2 5 / 1998 Booken , et al ., " Oral aprepitant in the therapy of refractory pruritus WO WO 98 / 19649 A3 5 / 1998 in erythrodermic cutaneous T -cell lymphoma” [ Correspondence ], W0 WO 99 / 02510 A1 1 / 1999 WO WO 00 / 56812 A1 9 / 2000 Br J Dermatol , vol . 164 , No. 3 , pp . 665 -667 (Mar . 2011 ) . Oxford , WO WO 03 /026658 A1 4 / 2003 UK : Wiley - Blackwell . WO WO 2004 /013072 A2 2 / 2004 Brown , et al. , “ PET [ C ]DASB imaging of serotonin transporters wo WO 2004 /013072 A3 2 / 2004 in patients with alcoholism ” , Alcohol Clin Exp Res, vol. 31, No . 1 , WO WO 2005 / 032464 A2 4 / 2005 pp . 28 - 32 ( Jan . 2007 ) . Baltimore , MD : Research Society on Alco WO WO 2005 / 034940 A3 4 / 2005 holism & Blackwell Publishing . W0 WO 2005 /073191 A1 8 / 2005 Carmel , et al ., “ Management of refractory overactive bladder ” , WO WO 2005 /090333 Al 9 / 2005 Expert Rev Obstet Gynecol , vol. 7 , No . 6 , pp . 605 -613 (Nov . 2012 ) . WO WO 2006 /018850 A2 2 / 2006 WO WO 2006 /018850 A3 2 / 2006 London , UK : Informa Healthcare . WO WO 2007 /002457 A2 1 / 2007 Chopra , et al ., “ Neoteric pharmacotherapeutic targets in WO WO 2007 /002457 A3 1 / 2007 fibromyalgia ” , Expert Opin Ther Targets ,vol . 15 , No . 11, pp . 1267 WO WO 2007 /008564 A1 1 / 2007 1281 (Nov . 2011 ) . London , UK : Informa Healthcare . W0 WO 2007 /044296 A2 4 / 2007 Costa , et al . , Abstract of " How important are NK1 receptors for WO WO 2007 /044296 A3 4 / 2007 influencing microvascular inflammation and itch in the skin ? Stud WO WO 2007 / 118651 Al 10 / 2007 ies using Phoneutria nigriventer venom ” , Vascul Pharmacol , vol . 45 , WO WO 2007 / 146224 A2 12 / 2007 No.