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( 12 ) United States Patent THAT US009737507B2 (12 ) United States Patent ( 10 ) Patent No. : US 9 , 737 ,507 B2 Zhang et al . (45 ) Date of Patent: * Aug. 22 , 2017 ( 54 ) USE OF NK - 1 RECEPTOR ANTAGONIST ( 56 ) References Cited SERLOPITANT IN 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 5 ,521 , 183 A 5 / 1996 Woodward et al. (72 ) Inventors: Xiaoming Zhang , Sunnyvale , CA (US ) ; 5 ,629 , 327 A 5 / 1997 D ' Amato 5 ,679 , 360 A 10 / 1997 De Lacharriere et al . Edward F . Schnipper , Redwood City , 5 , 869 ,521 A 2 / 1999 Farrar et al. CA (US ) ; Andrew J . Perlman , 5 , 981, 513 A 11 / 1999 Kruse et al . Stanford , CA (US ) ; James W . Larrick , 6 ,054 , 445 A 4 / 2000 Zhang et al. Sunnyvale , CA (US ) 6 ,221 , 880 B1 4 / 2001 Shih 6 , 476 , 063 B2 11/ 2002 Zhang et al. 6 , 743 , 793 B2 6 / 2004 Torisu et al . ( 73 ) Assignee : MENLO THERAPEUTICS INC ., 7 ,153 , 852 B2 12 /2006 Torisu et al. Menlo Park , CA (US ) 7 , 217 , 731 B2 5 /2007 Bunda et al . 7 , 345 , 083 B2 3 / 2008 Bunda et al . 7 , 435 , 745 B2 10 / 2008 D ' Amato ( * ) Notice: Subject to any disclaimer, the term of this 7 , 511 , 072 B2 3 / 2009 Man et al . patent is extended or adjusted under 35 7 , 544 , 815 B2 6 / 2009 Kuethe et al. U . S .C . 154 ( b ) by 0 days . 7 , 645 , 790 B2 1 /2010 Bunda et al. 7 , 683 , 068 B2 3 / 2010 Jiang et al. This patent is subject to a terminal dis 7 , 732 , 479 B2 6 /2010 Gazit et al. claimer . 7 ,740 , 959 B2 6 / 2010 Yagi 7 , 893 , 091 B2 2 /2011 Gottesdiener et al . 8 , 008, 479 B2 8 / 2011 Portman ( 21) Appl. No. : 15 / 269, 792 8 , 039 , 488 B2 10 / 2011 D 'Amato 8 , 124, 633 B2 2 / 2012 DeVita et al. ( 22 ) Filed : Sep . 19 , 2016 8 , 143 , 283 B1 3 / 2012 D 'Amato 8 ,153 ,682 B2 4 / 2012 Branum et al. (65 ) Prior Publication Data 8 , 263 , 636 B2 9 / 2012 Ansorge et al. 8 , 455 , 638 B2 6 / 2013 Bittner et al . US 2017 /0065557 A1 Mar. 9 , 2017 8 , 809 , 327 B2 8 / 2014 Branum et al. 8 . 889 . 729 B2 11/ 2014 Gazit et al. 8 , 901 ,307 B2 12 /2014 Dakin et al . 8 , 906 , 951 B1 12 / 2014 Zhang et al . Related U . S . Application Data (Continued ) (63 ) Continuation of application No . 14 /899 , 255 , filed as application No . PCT/ US2014 /043811 on Jun . 24 , FOREIGN PATENT DOCUMENTS 2014 , now Pat. No. 9 ,486 ,439 , which is a EP 0717997A 6 / 1996 continuation - in - part of application No . 13 /925 ,509 , EP 1711465 Al 10 / 2006 filed on Jun . 24 , 2013 , now Pat. No . 8 , 906 , 951 . (Continued ) (60 ) Provisional application No. 61 /838 , 784 , filed on Jun . OTHER PUBLICATIONS 24 , 2013 . Aitken , “ Section ofMeasurement in Medicine” , Proc Roy Soc Med , (51 ) Int. CI. vol . 62, pp . 989 - 993 ( Oct. 1969) . London , UK : Royal Society of A61K 31/ 403 ( 2006 .01 ) Medicine . A61K 45 / 06 ( 2006 .01 ) (Continued ) A61K 31 /4035 ( 2006 . 01 ) A61K 9 / 06 ( 2006 .01 ) Primary Examiner — Kristin Vajda A61K 47 / 10 ( 2017 .01 ) (74 ) Attorney , Agent, or Firm — Morrison & Foerster A61K 9 / 20 ( 2006 .01 ) LLP A61K 9 / 48 ( 2006 . 01 ) A61K 9 / 00 ( 2006 .01 ) (52 ) U . S . CI. (57 ) ABSTRACT CPC . .. .. A61K 31 /403 ( 2013 .01 ) ; A61K 9 /0014 The invention relates to methods for treating pruritus with (2013 . 01 ) ; A61K 9 / 0053 (2013 . 01 ) ; A61K 9 / 06 NK - 1 receptor antagonists such as serlopitant. The invention ( 2013 .01 ) ; A61K 9 /2054 ( 2013 .01 ) ; A61K further relates to pharmaceutical compositions comprising 9 /4858 ( 2013 .01 ) ; A61K 9 /4883 (2013 .01 ) ; NK - 1 receptor antagonists such as serlopitant. In addition , A61K 31/ 4035 (2013 . 01 ) ; A61K 45 / 06 the invention encompasses treatment of a pruritus -associ ( 2013 .01 ) ; A61K 47/ 10 ( 2013 .01 ) ated condition with serlopitant and an additional antipruritic (58 ) Field of Classification Search agent, and the use of serlopitant as a sleep aid , optionally in CPC .. A61K 31 /4035 ; A61K 9 /0053 ; A61K 9 /0014 ; A61K 45 / 06 ; A61K 31 /403 combination with an additional sleep - aiding agent. USPC . .. .. 514 / 171, 416 See application file for complete search history . 31 Claims, 5 Drawing Sheets US 9 ,737 ,507 B2 Page 2 (56 ) References Cited OTHER PUBLICATIONS U . S . PATENT DOCUMENTS Akiyama, et al. , “ Roles for substance P and gastrin -releasing peptide as neurotransmitters released by primary afferent pruricep 9 , 198 ,898 B2 12 / 2015 Zhang et al. 9 , 381 , 188 B2 7 / 2016 Zhang et al. tors ” , J Neurophysiol, vol. 109 , Issue 3 , pp . 742 -748 (Feb . 2013 ) . 2003 Al 5 / 2003 Ohmura et al. Bethesda , MD : American Physiological Society . 2006 /0149076 A1 7 / 2006 Hicks Akiyama, et al . , Abstract of “ Roles for substance P and gastrin 2009 /0209556 Al 8 / 2009 Bittner et al . releasing peptide as neurotransmitters released by primary afferent 2009 /0270477 Al 10 / 2009 Keuthe et al . pruriceptors ” , J Neurophysiol, ( 2012 ) . 2010 /0113469 AL 5 / 2010 Frenkl et al . Ally et al ., “ The use of aprepitant in brachioradial pruritus” , Dept. 2010 /0209496 AL 8 / 2010 Dokou et al . of Dermatology, Stanford University , School of medicine, pp . 1 - 7 2011/ 0224204 AL 9 / 2011 Chesworth et al. ( Dec . 13, 2012 ). 2011/ 0262442 Al 10 /2011 Hamilton et al . Amatya , et al . , “ Responses to intradermal injections of substance P 2012 / 0035168 A1 2 / 2012 Brandl et al . in psoriasis patients with pruritus” , Skin Pharmacol Physiol , vol. 23 , 2012 /0077803 A1 3 / 2012 Stuetz et al . Issue 3 , pp . 133 -138 (2010 ) . Basel , Switzerland : S . Karger AG . 2012 /0225904 AL 9 / 2012 Bosch et al. American Medical Association , “ Statement on a Nonproprietary 2013 /0266645 Al 10 / 2013 Becker et al. Name Adopted by the USAN Council” , www .ama - assn .org / re 2013 /0303497 A1 11/ 2013 Hansen et al . sources/ doc /usan /serlopltant . pdf , p . 1 of 1 . 2014 / 0378521 Al 12 / 2014 Zhang et al. Andersson , et al. , " Current pharmacotherapy of lower urinary tract 2015/ 0057255 AL 2 / 2015 Zhang et al. symptoms” , Surgery , vol . 29 , Issue 6 (Renal and Urology III ) , pp . 2016 / 0038462 A1 2 / 2016 Zhang et al. 260 - 264 , (2011 ) . St. Louis , MO : Mosby . 2016 /0143882 A15 / 2016 Zhang et al. Andoh et al ., " Substance P induction of Itch -Associated Response Mediation by Cutaneous NK1 Tachykinin Receptors in Mice " , The FOREIGN PATENT DOCUMENTS Journal of Pharmacology and Experimental Therapeutics , vol . 286 , RU 2370265 Ci 10 / 2009 No . 3 , pp . 1140 - 1145 ( 1998 ) . WO WO 94 / 20085 AL 9 / 1994 Antiga E , et al. , “ A further case of subacute prurigo - like linear IgA WO WO 96 / 06601 3 / 1996 bullous dermatosis : growing evidence of a new subset, ” Int J WO WO 97 / 14671 4 / 1997 Dermatol. , vol. 51, No . 12 , pp . 1500 - 1501 (Dec . 2012 ) . Oxford ,UK : WO WO 98 / 19649 A2 5 / 1998 Blackwell Science . WO WO 98 / 19649 A3 5 / 1998 Beauregard , et al ., “ A survey of skin problems and skin care WO WO 99 / 02510 A1 1 / 1999 regimens in the elderly " , Arch Dermatol, vol . 12 , No . 12 , pp . WO WO 00 / 56812 A1 9 / 2000 WO WO 03 / 026658 A1 4 / 2003 1638 - 1643 (Dec . 1987 ) . Chicago , IL : American Medical Associa WO WO 2004 /013072 A2 2 / 2004 tion . W0 WO 2004 /013072 A3 2 / 2004 Bergasa, et al ., “ Gabapentin in patients with the pruritus of WO WO 2005 /032464 A2 4 / 2005 cholestasis : a double -blind , randomized , placebo -controlled trial” , WO WO 2005 / 034940 A3 4 / 2005 Hepatology, vol . 44 , No. 5 , pp . 1317 - 1323 ( Nov . 2006 ) . Hoboken , WO WO 2005 / 073191 A1 8 / 2005 NJ: Wiley. wo WO 2005 /090333 A1 9 / 2005 Booken , et al ., “ Oral aprepitant in the therapy of refractory pruritus WO WO 2006 /018850 A2 2 / 2006 W0 WO 2006 /018850 A3 2 /2006 in erythrodermic cutaneous T -cell lymphoma” [ Correspondence ) , WO WO 2007 /002457 A2 1 / 2007 Br J Dermatol , vol. 164 , No. 3 , pp . 665 -667 (Mar . 2011) . Oxford , WO WO 2007 /002457 A3 1 / 2007 UK : Wiley - Blackwell . WO WO 2007 /008564 Al 1 / 2007 Brown, et al ., “ PET [ C ]DASB imaging of serotonin transporters WO WO 2007 /044296 A2 4 / 2007 in patients with alcoholism ” , Alcohol Clin Exp Res , vol. 31, No . 1 , WO WO 2007 /044296 A3 4 / 2007 pp . 28 - 32 ( Jan . 2007 ) . Baltimore , MD : Research Society on Alco WO WO 2007 / 118651 A1 10 / 2007 holism & Blackwell Publishing . 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