IP Library › Granted Patent US 12,558,317
Granted Patent B2
US 12,558,317 · App. 18/392,891 · Granted Feb 24, 2026

Compositions and methods for treating disorders ameliorated by muscarinic receptor activation

Inventors: Aimesther Betancourt (Montreal, CA); Bruce Rehlaender (Lake Oswego, OR); Roch Thibert (Mont-Royal, CA)
Assignee: Karuna Therapeutics, Inc.
A61K9/1652A61K9/0053A61K9/1611A61K9/485A61K9/4858A61K9/4866A61K31/439A61K31/454
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,558,317
App. No.
18/392,891
Granted
Feb 24, 2026
Kind
B2
Abstract

Provided herein is an oral pharmaceutical composition, comprising a plurality of xanomeline beads having a core comprising xanomeline or a salt thereof; and a plurality of trospium beads having a core comprising a salt of trospium.

Claims (76)

1 . A pharmaceutical composition comprising xanomeline or a pharmaceutically acceptable salt thereof; trospium chloride; and 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium.

2 . The pharmaceutical composition of claim 1 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.25 wt. % of the pharmaceutical composition.

3 . The pharmaceutical composition of claim 1 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

4 . The pharmaceutical composition of claim 1 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2wt. % of the pharmaceutical composition.

5 . The pharmaceutical composition of claim 1 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

6 . The pharmaceutical composition of claim 2 , wherein the xanomeline or a pharmaceutically acceptable salt thereof is formulated as a first component, and the trospium chloride is formulated as a second component.

7 . The pharmaceutical composition of claim 6 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

8 . The pharmaceutical composition of claim 6 , wherein the 3- [(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2wt. % of the pharmaceutical composition.

9 . The pharmaceutical composition of claim 6 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

10 . The pharmaceutical composition of claim 6 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity.

11 . The pharmaceutical composition of claim 10 , wherein the xanomeline is xanomeline tartrate.

12 . The pharmaceutical composition of claim 6 , wherein the first component further comprises a first excipient, and the second component further comprises a second excipient.

13 . The pharmaceutical composition of claim 12 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

14 . The pharmaceutical composition of claim 12 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2wt. % of the pharmaceutical composition.

15 . The pharmaceutical composition of claim 12 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

16 . The pharmaceutical composition of claim 12 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3months at 40°° C. and 75% relative humidity.

17 . The pharmaceutical composition of claim 16 , wherein the xanomeline is xanomeline tartrate.

18 . The pharmaceutical composition of claim 6 , wherein the first component further comprises microcrystalline cellulose; and the second component further comprises microcrystalline cellulose, lactose, or a combination thereof.

19 . The pharmaceutical composition of claim 18 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

20 . The pharmaceutical composition of claim 18 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition.

21 . The pharmaceutical composition of claim 18 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

22 . The pharmaceutical composition of claim 18 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity.

23 . The pharmaceutical composition of claim 22 , wherein the xanomeline is xanomeline tartrate.

24 . The pharmaceutical composition of claim 12 , wherein the first component is a first plurality of beads, and the second component is a second plurality of beads.

25 . The pharmaceutical composition of claim 24 , wherein the 3-[(4-hexyloxy)-1,2,5 -thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

26 . The pharmaceutical composition of claim 24 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition.

27 . The pharmaceutical composition of claim 24 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

28 . The pharmaceutical composition of claim 24 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity.

29 . The pharmaceutical composition of claim 28 , wherein the xanomeline is xanomeline tartrate.

30 . The pharmaceutical composition of claim 29 , wherein the first plurality of beads and the second plurality of beads have a dissolution rate of more than about 80% within the first 30 minutes following entry of the pharmaceutical composition into a 0.1 N HCI solution.

31 . The pharmaceutical composition of claim 24 , wherein the first excipient comprises microcrystalline cellulose; and the second excipient comprises microcrystalline cellulose, lactose, or a combination thereof.

32 . The pharmaceutical composition of claim 31 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

33 . The pharmaceutical composition of claim 31 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition.

34 . The pharmaceutical composition of claim 31 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

35 . The pharmaceutical composition of claim 31 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity.

36 . The pharmaceutical composition of claim 35 , wherein the xanomeline is xanomeline tartrate.

37 . The pharmaceutical composition of claim 36 , wherein the first plurality of beads and the second plurality of beads have a dissolution rate of more than about 80% within the first 30 minutes following entry of the pharmaceutical composition into a 0.1 N HCl solution.

38 . The pharmaceutical composition of claim 1 , further comprising an antioxidant.

39 . The pharmaceutical composition of claim 38 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.25 wt. % of the pharmaceutical composition.

40 . The pharmaceutical composition of claim 39 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

41 . The pharmaceutical composition of claim 39 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition.

42 . The pharmaceutical composition of claim 39 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

43 . The pharmaceutical composition of claim 39 , wherein the antioxidant and the xanomeline or a pharmaceutically acceptable salt thereof are formulated as a first component, and the trospium chloride is formulated as a second component.

44 . The pharmaceutical composition of claim 43 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity.

45 . The pharmaceutical composition of claim 44 , wherein the antioxidant is ascorbic acid.

46 . The pharmaceutical composition of claim 45 , wherein the xanomeline is xanomeline tartrate.

47 . The pharmaceutical composition of claim 43 , wherein the first component further comprises a first excipient, and the second component further comprises a second excipient.

48 . The pharmaceutical composition of claim 47 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

49 . The pharmaceutical composition of claim 47 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition.

50 . The pharmaceutical composition of claim 47 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

51 . The pharmaceutical composition of claim 47 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity.

52 . The pharmaceutical composition of claim 48 , wherein the antioxidant is ascorbic acid.

53 . The pharmaceutical composition of claim 52 , wherein the xanomeline is xanomeline tartrate.

54 . The pharmaceutical composition of claim 43 , wherein the first component further comprises microcrystalline cellulose; and the second component further comprises microcrystalline cellulose, lactose, or a combination thereof.

55 . The pharmaceutical composition of claim 54 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

56 . The pharmaceutical composition of claim 54 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition.

57 . The pharmaceutical composition of claim 54 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

58 . The pharmaceutical composition of claim 54 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity.

59 . The pharmaceutical composition of claim 58 , wherein the antioxidant is ascorbic acid.

60 . The pharmaceutical composition of claim 59 , wherein the xanomeline is xanomeline tartrate.

61 . The pharmaceutical composition of claim 47 , wherein the first component is a first plurality of beads, and the second component is a second plurality of beads.

62 . The pharmaceutical composition of claim 61 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

63 . The pharmaceutical composition of claim 61 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition.

64 . The pharmaceutical composition of claim 61 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

65 . The pharmaceutical composition of claim 61 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity.

66 . The pharmaceutical composition of claim 65 , wherein the antioxidant is ascorbic acid.

67 . The pharmaceutical composition of claim 66 , wherein the xanomeline is xanomeline tartrate.

68 . The pharmaceutical composition of claim 67 , wherein the first plurality of beads and the second plurality of beads have a dissolution rate of more than about 80% within the first 30 minutes following entry of the pharmaceutical composition into a 0.1 N HCl solution.

69 . The pharmaceutical composition of claim 61 , wherein the first excipient comprises microcrystalline cellulose; and the second excipient comprises microcrystalline cellulose, lactose, or a combination thereof.

70 . The pharmaceutical composition of claim 69 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.25 wt. % of the pharmaceutical composition.

71 . The pharmaceutical composition of claim 69 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.2 wt. % of the pharmaceutical composition.

72 . The pharmaceutical composition of claim 69 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount between 0.1 wt. % and 0.2 wt. % of the pharmaceutical composition.

73 . The pharmaceutical composition of claim 69 , wherein the 3-[(4-hexyloxy)-1,2,5-thiadiazol-3-yl]-5-hydroxyl-1-methylpyridin-1-ium is present in an amount of less than 0.5 wt. % of the pharmaceutical composition after the pharmaceutical composition is stored for 3 months at 40° C. and 75% relative humidity.

74 . The pharmaceutical composition of claim 73 , wherein the antioxidant is ascorbic acid.

75 . The pharmaceutical composition of claim 74 , wherein the xanomeline is xanomeline tartrate.

76 . The pharmaceutical composition of claim 75 , wherein the first plurality of beads and the second plurality of beads have a dissolution rate of more than about 80% within the first 30 minutes following entry of the pharmaceutical composition into a 0.1 N HCl solution.

Assignments (6)
CERTIFICATE OF CHANGE OF ASSIGNEE PRINCIPAL BUSINESS ADDRESS Recorded Oct 22, 2024
From: KARUNA THERAPEUTICS, INC.
To: KARUNA THERAPEUTICS, INC.
Reel/Frame 069205/0476 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2024
From: BETANCOURT, AIMESTHER
To: COREALIS PHARMA
Reel/Frame 068959/0979 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2024
From: THIBERT, ROCH
To: COREALIS PHARMA
Reel/Frame 068960/0062 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2024
From: COREALIS PHARMA
To: KARUNA THERAPEUTICS, INC.
Reel/Frame 068960/0168 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2024
From: REHLAENDER, BRUCE
To: PHARMADIRECTIONS, INC.
Reel/Frame 068960/0221 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2024
From: PHARMADIRECTIONS, INC.
To: KARUNA THERAPEUTICS, INC.
Reel/Frame 068960/0259 →
Continuity (6)
Continuation 17822872 · Aug 29, 2022
Continuation 17649826 · Feb 3, 2022
Continuation 17143904 · Jan 7, 2021
Continuation 16585532 · Sep 27, 2019
Provisional Application 62738333 · Sep 28, 2018
Related Publication 20240238205A1 · Jul 18, 2024
References Cited (322)
US 4647580A · Roszkowski · 1987 [cited by applicant]
US 5043345A · Sauerberg · 1991 [cited by applicant]
US 5480651A · Callaway · 1996 [cited by applicant]
US 5744476A · Locke · 1998 [cited by applicant]
US 5852029A · Fisher · 1998 [cited by applicant]
US 6423842B1 · Grewal · 2002 [cited by applicant]
US 6862890B2 · Williams, III · 2005 [cited by applicant]
US 7049321B2 · Fisher · 2006 [cited by applicant]
US 7410978B2 · Kidane · 2008 [cited by applicant]
US 7491715B2 · Ek · 2009 [cited by applicant]
US 7517871B2 · Ek · 2009 [cited by applicant]
US 7524965B2 · Colson · 2009 [cited by applicant]
US 7550454B2 · Ek · 2009 [cited by applicant]
US 7622461B2 · Ek · 2009 [cited by applicant]
US 7666894B2 · Paborji · 2010 [cited by applicant]
US 7678821B2 · Paborji · 2010 [cited by applicant]
US 7781472B2 · Paborji · 2010 [cited by applicant]
US 7786166B2 · Frey, II · 2010 [cited by applicant]
US 7790905B2 · Tawa · 2010 [cited by applicant]
US 8404701B2 · Chase · 2013 [cited by applicant]
US 9561218B2 · Clarence-Smith · 2017 [cited by applicant]
US 9671678B2 · Tokura · 2017 [cited by applicant]
US 10238643B2 · Elenko · 2019 [cited by applicant]
US 10265311B2 · Elenko · 2019 [cited by applicant]
US 10369143B2 · Elenko · 2019 [cited by applicant]
US 10369144B2 · Elenko · 2019 [cited by applicant]
US 10695339B2 · Elenko · 2020 [cited by applicant]
US 10925832B2 · Betancourt · 2021 [cited by applicant]
US 10933020B2 · Betancourt · 2021 [cited by applicant]
US 11452692B2 · Betancourt · 2022 [cited by applicant]
US 11471413B2 · Betancourt · 2022 [cited by applicant]
US 11890378B2 · Betancourt · 2024 [cited by applicant]
US 20020010216A1 · Rogosky · 2002 [cited by applicant]
US 20030068365A1 · Suvanprakorn · 2003 [cited by applicant]
US 20040023951A1 · Bymaster · 2004 [cited by applicant]
US 20040058914A1 · Doi · 2004 [cited by applicant]
US 20040224012A1 · Suvanprakorn · 2004 [cited by applicant]
US 20050085463A1 · Weiner · 2005 [cited by applicant]
US 20050250767A1 · Weiner · 2005 [cited by applicant]
US 20050267078A1 · Gras Escardo · 2005 [cited by applicant]
US 20060018933A1 · Vaya · 2006 [cited by applicant]
US 20060189651A1 · Gras Escardo · 2006 [cited by applicant]
US 20060197831A1 · Takeuchi · 2006 [cited by applicant]
US 20060287294A1 · Zhu · 2006 [cited by applicant]
US 20060293356A1 · Aberg · 2006 [cited by applicant]
US 20070027160A1 · Asselin · 2007 [cited by applicant]
US 20070049576A1 · Barlow · 2007 [cited by applicant]
US 20070053995A1 · Paborji · 2007 [cited by applicant]
US 20070116729A1 · Palepu · 2007 [cited by applicant]
US 20080045565A1 · Gras Escardo · 2008 [cited by applicant]
US 20080114014A1 · Rich · 2008 [cited by applicant]
US 20090005722A1 · Jennlngs-Spring · 2009 [cited by applicant]
US 20090017111A1 · Van Den Heuvel · 2009 [cited by applicant]
US 20090082388A1 · Hacksell · 2009 [cited by applicant]
US 20090275629A1 · Paborji · 2009 [cited by applicant]
US 20090318522A1 · Paborji · 2009 [cited by applicant]
US 20100137392A1 · Paborji · 2010 [cited by applicant]
US 20100152263A1 · Paborji · 2010 [cited by applicant]
US 20100226943A1 · Brennan · 2010 [cited by applicant]
US 20110020423A1 · Elenko · 2011 [cited by applicant]
US 20110263613A1 · Hendrickson · 2011 [cited by applicant]
US 20120201894A1 · Paborji · 2012 [cited by applicant]
US 20160375001A1 · Chase · 2016 [cited by applicant]
US 20170056347A1 · Glick · 2017 [cited by applicant]
US 20170095465A1 · Elenko · 2017 [cited by applicant]
US 20170112820A1 · Elenko · 2017 [cited by applicant]
US 20170313687A1 · Hendrickson · 2017 [cited by applicant]
US 20180193311A1 · Benjamin · 2018 [cited by applicant]
US 20190167658A1 · Elenko · 2019 [cited by applicant]
US 20190192500A1 · Elenko · 2019 [cited by applicant]
US 20190307739A1 · Elenko · 2019 [cited by applicant]
US 20190314354A1 · Chase · 2019 [cited by applicant]
US 20200101018A1 · Betancourt · 2020 [cited by applicant]
US 20200182850A1 · Kimura · 2020 [cited by applicant]
US 20200289419A1 · Betancourt · 2020 [cited by applicant]
US 20200323839A1 · Elenko · 2020 [cited by applicant]
US 20210145004A1 · Ucar · 2021 [cited by applicant]
US 20210145804A1 · Brannan · 2021 [cited by applicant]
US 20210154146A1 · Betancourt · 2021 [cited by applicant]
US 20210177762A1 · Betancourt et al. · 2021 [cited by applicant]
US 20220151933A1 · Betancourt et al. · 2022 [cited by applicant]
US 20220370454A1 · Felder · 2022 [cited by applicant]
AU 2003299453 · 2004 [cited by applicant]
CA 2804215 · 2011 [cited by applicant]
CL 199600120 · 1996 [cited by applicant]
CL 199600157 · 1996 [cited by applicant]
CL 201800559 · 2018 [cited by applicant]
CL 202100622 · 2021 [cited by applicant]
DE 19612504 · 1997 [cited by applicant]
EP 0734259 · 1996 [cited by applicant]
EP 0813870 · 1997 [cited by applicant]
EP 0813870A1 · 1997 [cited by applicant]
EP 2002843 · 2008 [cited by applicant]
EP 2002844 · 2008 [cited by applicant]
JP H09501658A · 1997 [cited by applicant]
JP H10059848 · 1998 [cited by applicant]
JP 2000515213 · 2000 [cited by applicant]
JP 2000516213 · 2000 [cited by applicant]
JP 2004502655 · 2004 [cited by applicant]
JP 2004517699A · 2004 [cited by applicant]
JP 2005530742 · 2005 [cited by applicant]
JP 20050530742 · 2005 [cited by applicant]
JP 2007509970A · 2007 [cited by applicant]
JP 2007510656 · 2007 [cited by applicant]
JP 2009507021 · 2009 [cited by applicant]
JP 2012533621A · 2012 [cited by applicant]
JP 2013516497A · 2013 [cited by applicant]
JP 2021530572A · 2021 [cited by applicant]
JP 2022065045A · 2022 [cited by applicant]
KR 1020140045379A · 2014 [cited by applicant]
RU 2191580C2 · 2002 [cited by applicant]
WO 1995005174 · 1995 [cited by applicant]
WO 1998005207 · 1998 [cited by applicant]
WO 1998005208 · 1998 [cited by applicant]
WO 1998005291 · 1998 [cited by applicant]
WO 1998005324 · 1998 [cited by applicant]
WO 1998005325 · 1998 [cited by applicant]
WO 1998005326 · 1998 [cited by applicant]
WO 1998030243 · 1998 [cited by applicant]
WO 2002060411 · 2002 [cited by applicant]
WO 2003030818 · 2003 [cited by applicant]
WO 2003092580 · 2003 [cited by applicant]
WO 2004060347 · 2004 [cited by applicant]
WO 2004087161 · 2004 [cited by applicant]
WO 2005044262 · 2005 [cited by applicant]
WO 2005046684 · 2005 [cited by applicant]
WO 2006067494 · 2006 [cited by applicant]
WO 2006067496 · 2006 [cited by applicant]
WO 2006086698 · 2006 [cited by applicant]
WO 2007027675 · 2007 [cited by applicant]
WO 2007049098 · 2007 [cited by applicant]
WO 2008076287 · 2007 [cited by applicant]
WO 2007125287 · 2007 [cited by applicant]
WO 2007125290 · 2007 [cited by applicant]
WO 2007125293 · 2007 [cited by applicant]
WO 2007127196 · 2007 [cited by applicant]
WO 2007128674 · 2007 [cited by applicant]
WO 2008096111 · 2008 [cited by applicant]
WO 2008096121 · 2008 [cited by applicant]
WO 2008096126 · 2008 [cited by applicant]
WO 2008096136 · 2008 [cited by applicant]
WO 2008103351 · 2008 [cited by applicant]
WO 2008104776 · 2008 [cited by applicant]
WO 2008121268 · 2008 [cited by applicant]
WO 2009036243 · 2009 [cited by applicant]
WO 2009037503 · 2009 [cited by applicant]
WO 2009039460 · 2009 [cited by applicant]
WO 2009092601 · 2009 [cited by applicant]
WO 2009132239 · 2009 [cited by applicant]
WO 2010024870 · 2010 [cited by applicant]
WO 2010064047 · 2010 [cited by applicant]
WO 2010102218 · 2010 [cited by applicant]
WO 2011011060 · 2011 [cited by applicant]
WO 2011085406 · 2011 [cited by applicant]
WO 2011123836 · 2011 [cited by applicant]
WO 2012033956 · 2012 [cited by applicant]
WO 2012170676 · 2012 [cited by applicant]
WO 2014176460 · 2014 [cited by applicant]
WO 2016144727 · 2016 [cited by applicant]
WO 2016144749 · 2016 [cited by applicant]
WO 2017040864 · 2017 [cited by applicant]
WO 2017044714 · 2017 [cited by applicant]
WO 2017127073 · 2017 [cited by applicant]
WO 2017147104 · 2017 [cited by applicant]
WO 2020069301 · 2020 [cited by applicant]
WO 2021101875 · 2021 [cited by applicant]
WO 2022182733 · 2022 [cited by applicant]
WO 2023196952 · 2023 [cited by applicant]
Arehart-Treichel, J., “GABA Targeted for Study in Schizophrenia”, Psych News, 40(9):29 & 52, (2005). [cited by applicant]
Bai, Y. et al., “Therapeutic Effect of of Pirenzepine for Clozapine-Induced Hypersalivation: A Randomized, Double-Blind, Placebo Controlled, Cross-Over Study”, J Clin Psychopharmacol., 21(6):608-11, (2001). [cited by applicant]
Barak, S. et al., “The M1/M4 Preferring Agonist Xanomeline Reverses Amphetamine-, MK801- and Scopolamine-Induced Abnormalities of Latent Inhibition: Putative Efficacy Against Positive, Negative and Cognitive Symptoms in… [cited by applicant]
Bender, A. et al., “Classics in Chemical Neuroscience: Xanomeline”, ACS Chem Neurosci., 8(3):435-43, (2017). [cited by applicant]
Bewley, B. et al., “Discovery of a Novel, CNS Penetrant M4 PAM Chemotype Based on a 6+-Fluoro-4-(piperidin-1-yl)quinolone-3-Carbonite Core”, Bioorg Med Chem Lett., 27(18):4274-9, (2017). [cited by applicant]
Bodick, N. et al., “Effects of Xanomeline, a Selective Muscarinic Receptor Agonist, on Cognitive Function and Behavioral Symptoms in Alzheimer Disease”, Arch Neurol., 54(4):465-73, (1997). [cited by applicant]
Bolbecker, A. et al., “Muscarinic agonists and antagonists in schizophrenia: recent therapeutic advances and future directions”, Handb Exp Pharmacol., 208:167-90, (2012). [cited by applicant]
Bonifazi, A. et al., “Synthesis and Biological Evaluation of a Novel Series of Heterobivalent Muscarinic Ligands Based on Xanomeline and 1-[3-(4-Butylpiperin-1-yl)propyl]-1,2,3,4-Tetrahydroquinolin-2-one (77-LH-28-1)”, … [cited by applicant]
Bradley, S. et al., “AC-260584, an Orally Bioavailable M1 Muscarinic Receptor Allosteric Agonist Improves Cognitive Performance in an Animal Model”, Neuropharmacology, 58(2):365-73, (2010). [cited by applicant]
Brannan, S. (Oct. 5, 2018-Oct. 26, 2020) A Study to Assess Safety and Efficacy of KarXT in Adult Patients With Schizophrenia (Emergent-1). Identifier NCT03697252. [cited by applicant]
Brannan, S. et al., “Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia”, N Engl J Med., 384(8):717-26, (2021). [cited by applicant]
Brown, S. et al., “Causes of the Excess Mortality of Schizophrenia”, Br J Psychiatry, 177:212-7, (2000). [cited by applicant]
Bymaster, F. et al., “Neurochemical Effects of the M1 Muscarinic Agonist Xanomeline (LY246708/NNC11-0232)”, J Pharmacol Exp Ther., 269(1):282-9, (1994). [cited by applicant]
Bymaster, F. et al., “Role of the Cholinergic Muscarinic System in Bipolar Disorder and Related Mechanism of Action of Antipsychotic Agents”, Mol Psychiatry, 7(Suppl 1):S57-63, (2000). [cited by applicant]
Bymaster, F. et al., “Xanomeline compared to other muscarinic agents on stimulation of phosphoinositide hydrolysis in vivo and other cholinomimetic effects”, Brain Res., 795(1-2):179-90, (1998). [cited by applicant]
Carey, G. et al., “SCH 57790, A Selective Muscarinic M2 Receptor Antagonist, Releases Acetylcholine and Produces Cognitive Enhancement in Laboratory Animals”, Eur J Pharmacol., 431(2):189-200, (2001). [cited by applicant]
Carnicella, S. et al., “Cholinergic Effects on Fear Conditioning II: Nicotinic and Muscarinic Modulations of Atropine-Induced Disruption of the Degraded Contingency Effect”, Psychopharmacology (Berl), 178(4):533-41, (20… [cited by applicant]
Caulfield, M. et al., “International Union of Pharmacology. XVII. Classification of Muscarinic Acetylcholine Receptors”, Pharmacol Rev., 50(2):279-90, (1998). [cited by applicant]
ClinicalTrials.gov, “Pilot Study Comparing the Effects of Xanomeline Alone to Xanomeline Plus Tropsium”, U.S. Nat'l Lib of Med., accessed online at <https://clinicaltraials.gov/ct2/show/NCT02831231> on Nov. 24, 2021, (2… [cited by applicant]
Coward, D., “General Pharmacology of Clozapine”, Br J Psychiatry Suppl., (17):5-11, (1992). [cited by applicant]
Croissant, B. et al., “Reduction of Side Effects by Combining Clozapine with Amisulpride: Case Report and Short Review of Clozapine-Induced Hypersalivation”, Pharmacopsychiatry, 38(1):38-9, (2005). [cited by applicant]
Cutler, N. et al., “Scientific and Ethical Concerns in Clinical Trials in Alzheimers Patients: The Bridging Study”, Eur J Clin Pharmacol., 48(6):421-8, (1995). [cited by applicant]
Davydov, L. et al., “Clozapine-Induced Hypersalivation”, Ann Pharmacother., 34(5):662-5, (2000). [cited by applicant]
Dawe, G. et al., “Pathophysiology and Animal Models of Schizophrenia”, Ann Acad Med Singapore, 38(5):425-30, (2009). [cited by applicant]
Dean, B. et al., “The Density of Muscarinic M1 Receptors is Decreased in the Caudate-Putamen of Subjects with Schizophrenia”, Mol Psychiatry, 1(1):54-8, (1996). [cited by applicant]
Desbonnet, L. et al., “Mutant Models for Genes Associated with Schizophenia”, Biochem Soc Trans., 37(pt 1):308-12, (2009). [cited by applicant]
Detrol® tolterodine tartrate tablets (Product Label) Prescribing Information, LAB-0329-4.0, Pharmacia & Upjohn, a division of Pfizer Inc., issued Apr. 2009; 17 pages. [cited by applicant]
Dixit, R. et al., “Oral Strip Technology: Overview and Future Potential”, J Control Release, 139(2):94-107, (2009). [cited by applicant]
Eglen, R., “Muscarinic Receptor Subtypes in Neuronal and Non-Neuronal Cholinergic Function”, Auton Autacoid Pharmacol., 26(3):219-33, (2006). [cited by applicant]
Ellis, J. et al., “Muscarinic and Nicotinic Receptors Synergistically Modulate Working Memory and Attention in Humans”, Int J Neuropsychopharmacol., 9(2):175-89, (2006). [cited by applicant]
Enablex® darifenacin (Product Label) Prescribing Information, reference ID: 3102220, Warner Chilcott (US), LLC, Mar. 2012, 18 pages. [cited by applicant]
EP Patent Application No. 10802549; Supplementary European Search Report, dated Sep. 30, 2013; 3 pages. [cited by applicant]
Fogueri, L. et al., “Smart Polymers for Controlled Delivery of Proteins and Peptides: A Review of Patents”, Recent Pat Drug Deliv Formul., 3(1):40-8, (2009). [cited by applicant]
Gao, T. et al., “Pharmaceutics”, Yanbian University Press, 1st edition, 1st print, pp. 108-110, (2017). [cited by applicant]
Geyer, M., “Developing Translational Animal Models for Symptoms of Schizophrenia or Bipolar Manina”, Neurotox Res., 14(1):71-8, (2008). [cited by applicant]
Gralewicz, S. et al., “Interaction of Chlorphenvinphos with Cholinergic Receptors in the Rabbit Hypothalamus”, Neurotoxicol Teratol., 17(3):289-95, (1995). [cited by applicant]
Houthoofd, S. et al., “Cognitive and psychomotor effects of risperidone in schizophrenia and schizoaffective disorder”, Clin Ther., 30(9):1565-89, (2008). [cited by applicant]
Iconomopoulou, S. et al., “Incorporation of Small Molecular Weight Active Agents into Polymeric Components”, Recent Pat Drug Deliv Formul., 2(2):94-107, (2008). [cited by applicant]
International Application No. PCT/US2010/002044; International Preliminary Report on Patentability, date of issuance, Jan. 24, 2012; 5 pages. [cited by applicant]
International Application No. PCT/US2010/002044; International Search Report and Written Opinion of the International Searching Authority, date of mailing, Sep. 2, 2010; 6 pages. [cited by applicant]
International Application No. PCT/US2019/053429; International Search Report and Written Opinion of the International Searching Authority, date of mailing Dec. 4, 2019; 14 pages. [cited by applicant]
International Application No. PCT/US2020/060859; International Preliminary Report on Patentability, date of issuance Jun. 2, 2022; 6 pages. [cited by applicant]
International Application No. PCT/US2020/060859; International Search Report and Written Opinion of the International Searching Authority, date of mailing Feb. 26, 2021; 8 pages. [cited by applicant]
International Application No. PCT/US2022/017485; International Preliminary Report on Patentability, date of issuance Sep. 7, 2023; 8 pages. [cited by applicant]
International Application No. PCT/US2022/017485; International Search Report and Written Opinion of the International Searching Authority, date of mailing May 3, 2022; 10 pages. [cited by applicant]
International Application No. PCT/US2022/017485; International Search Report and Written Opinion of the International Searching Authority, date of mailing May 3, 2023; 10 pages. [cited by applicant]
International Application No. PCT/US2023/065498; International Search Report and Written Opinion of the International Searching Authority, date of mailing Oct. 19, 2023; 10 pages. [cited by applicant]
Iwanaga, K. et al., “Carbachol Induces Ca2+-Dependent Contraction via Muscarinic M2 and M3 Receptors in Rat Intestinal Subepithelial Myofibroblasts”, J Pharmacol Sci., 110(3):306-14, (2009). [cited by applicant]
Jones, C. et al., “Novel Selective Allosteric Activator of the M1 Muscarinic Acetylcholine Receptor Regulates Amyloid Processing and Produces Antipsychotic-Like Activity in Rats”, J Neurosci., 28(41):10422-33, (2008). [cited by applicant]
Kahl, K. et al., “Therapie der Clozapin-Induzierten Hypersalivations Mit Botulinum-Toxin B”, Nervenarzt, 76(2):205-8, (2005). [cited by applicant]
Kalantzi, L. et al., “Recent Advances in Oral Pulsatile Drug Delivery”, Recent Pat Drug Deliv Formul., 3(1):49-63, (2009). [cited by applicant]
Karuna Therapeutics, Inc., Corporate Presentation, Aug. 2020; 40 pages. [cited by applicant]
Kreinin, A. et al., “Sulpiride Addition for the Treatment of Clozapine-Induced Hypersalivation: Preliminary Study”, Isr J Pysch Relat Sci., 42(1):61-3, (2005). [cited by applicant]
Kurimoto, E. et al., “An Approach to Discovering Novel Muscarinic M1 Receptor Positive Allosteric Modulators with Potent Cognitive Improvement and Minimized Gastrointestinal Dysfunction”, J Pharmacol Exp Ther., doi: 10.… [cited by applicant]
Langmead, C. et al., “Muscarinic Acetylcholine Receptors as CNS Drug Targets”, Pharmacol Ther., 117(2):232-43, (2008). [cited by applicant]
Li, Z. et al., “Effect of Muscarinic Receptor Agonists Xanomeline and Sabcomeline on Acetylcholine and Dopamine Efflux in the Rat Brain; Comparison with Effects of 4-[3-(4-butylpiperidin-1-yl)-propyl]-7 fluoro-4H-benzo[… [cited by applicant]
Li, Z. et al., “Xanomeline Derivative EUK1001 Attenuates Alzheimer's Disease Pathology in Triple Transgenic Mouse Model”, Mol Med Rep., 16(5):7835-40, (2017). [cited by applicant]
Liu, B. et al., “Design and Synthesis of N-[6-(Substituted Aminoethylideneamino)-2-Hydroxyindan-1-yl]arylamides as Selective and Potent Muscarinic M1 Agaonists”, Bioorg Med Chem Lett., 25(19):4153-63, (2015). [cited by applicant]
Long, M. et al., “Discovery of a Novel 2,4-Dimethylquinoline-6-Carboxmide M4 Positive Allosteric Modulator (PAM) Chemotype via Scaffold Hopping”, Bioorg Med Chem Lett., 27(22):4999-5001, (2017). [cited by applicant]
Luo, X. et al., “CHRM2 Gene Predisposes to Alcohol Dependence, Drug Dependence and Affective Disorders: Results From an Extended Case-Control Structured Association Study”, Hum Mol Genet., 14(16):2421-34, (2005). [cited by applicant]
Material Safety Data Sheet—Lethal Nerve Agent Sarin, Appendix to the Riegle Report: US Chemical and Biological Warfare-Related Dual Use Exports to Iraq and Their Possible Impact on the Health Consequences of the Gulf Wa… [cited by applicant]
McKinzie, D. et al., “Xanomeline's Activity in Rodent Models of Psychosis: Role of Central Muscarinic Receptors and Augmentation by Risperidone and Aripiprazole”, Karuna Therapeutics, 1 page, (2021). [cited by applicant]
Medina, A. et al., “Effects of Central Muscarinic-1 Receptor Stimulation on Blood Pressure Regulation”, Hypertension, 29(3):828-34, (1997). [cited by applicant]
Messer Jr., W. et al., “Design and Development of Selective Muscarinic Agonists for the Treatment of Alzheimer's Disease: Characterization of Tetrahydropyrimidine Derivatives and Development of New Approaches for Improv… [cited by applicant]
Miller, A. et al., “Xanomeline Plus Tropsium: A Novel Strategy to Enhance Pro-Muscarinic Efficacy and Mitigate Peripheral Side Effects”, Neuropsychopharmacology, 41:S230, (2016). [cited by applicant]
Mirza, N. et al., “Xanomeline and the antipsychotic potential of muscarinic receptor subtype selective agonists”, CNS Drug Rev., 9(2):159-86, (2003). [cited by applicant]
Mizrahi, B. et al., “Mucoadhesive Polymers for Delivery of Drugs to the Oral Cavity”, Recent Pat Drug Deliv Formul., 2(2):108-19, (2008). [cited by applicant]
Mobascher, A. et al., “Association of a Variant in the Muscarinic Acetylcholine Receptor 2 Gene (CHRM2) with Nicotine Addiction”, Am J Med Genet B Neuropsychiatr Genet., 153B(2):684-90, (2010). [cited by applicant]
Mortimer, A. et al., “Syptoms Rating Scales and Outcome in Schizophrenia”, Br J Pysch., 191(Suppl 50):s7-14, (2007). [cited by applicant]
Mouradian, M. et al., “No Response to High-Dose Muscarinic Agonist Therapy in Alzheimer's Disease”, Neurology, 34(8):606-8, (1988). [cited by applicant]
Nathan, P. et al., “The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction”, Int J Neuropsychopharmacol., 16(4):721-31, (2013). [cited by applicant]
National Library of Medicine (U.S.). (Dec. 2020-) A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (Emergent-2). Identifier NCT04659161. https://clinical… [cited by applicant]
National Library of Medicine (U.S.). (Dec. 2020-)An Extension Study to Assess Long-term Safety, Tolerability, and Efficacy of KarXT in Adult Patients With Schizophrenia (Emergent-4). Identifier NCT04659174. https://clin… [cited by applicant]
National Library of Medicine (U.S.). (Dec. 2021-) A Study to Assess Efficacy and Safety of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia (Arise). Identifier NCT05145413. https://cli… [cited by applicant]
National Library of Medicine (U.S.). (Feb. 2021-) A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (Emergent-3). Identifier NCT04738123. https://clinical… [cited by applicant]
National Library of Medicine (U.S.). (Mar. 2021-) An Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of KarXT in Adult Patients With Schizophrenia (Emergent-5). Identifier NCT04820309. https:… [cited by applicant]
National Library of Medicine (U.S.). (Mar. 2022-) An Extension Study to Assess Long-Term Safety and Tolerability of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia. Identifier NCT0530… [cited by applicant]
Nikam, S. et al., “Evolution of Schizophrenia Drugs: A Focus on Dopaminergic Systems”, Curr Opin Investig Drugs, 9(1):37-46, (2008). [cited by applicant]
Paños, I. et al., “New Drug Delivery Systems Based on Chitosan”, Curr Drug Discov Technol., 5(4):333-41, (2008). [cited by applicant]
Patel, A. et al., “Prediction of Relapse After Discontinuation of Antipsychotic Treatment in Alzheimer's Disease: The Role of Hallucinations”, Am J Psychiatry, 174(4):362-9, (2017). [cited by applicant]
Paul, S. et al., “Muscarinic Acetylcholine Receptor Agonists as Novel Treatments for Schizophrenia”, Am J Psychiatry, 179(9):611-27, (2022). [cited by applicant]
Praharaj, S. et al., “Is Clonidine Useful for Treatment of Clozpine-Induced Sialorrhea?”, J Psychopharmacol., 19(5):426-8, (2005). [cited by applicant]
Raedler, T. et al., “In Vivo Determination of Muscarinic Acetylcholine Receptor Availability in Schizophrenia”, Am J Psychiatry, 160(1):118-27, (2003). [cited by applicant]
Rogers, D. et al., “Therapeutic Options in the Treatment of Clozapine-Induced Sialorrhea”, Pharmacother., 20(9):1092-5, (2000). [cited by applicant]
Sanctura® trospium chloride (Product Label) Prescribing Information, reference ID: 3163014, Allergan, Inc., Jul. 2012, 17 pages. [cited by applicant]
Sauder, C. et al., “Effectiveness of KarXT (xanomeline-trospium) for cognitive impairment in schizophrenia: post hoc analyses from a randomised, double-blind, placebo-controlled phase 2 study”, Transl Psychiatry, 12(1):… [cited by applicant]
Schneider, B. et al., “Reduction of Clozapine-Induced Hypersalivation by Pirenzepine is Safe”, Pharmacopsychiatry, 37(2):43-5, (2004). [cited by applicant]
Schultz, S. et al., “Schizophrenia: A Review”, Am Fam Physician, 75(12):1821-9, (2007). [cited by applicant]
Shannon, H. et al., “Xanomeline, an M1/M4 Preferring Muscarinic Cholinergic Receptor Agonist, Produces Antipsychotic-Like Activity in Rats and Mice”, Schizophrenia Res., 42(3):249-59, (2000). [cited by applicant]
Shekhar, A. et al., “Selective Muscarinic Receptor Agonist Xanomeline as a Novel Treatment Approach for Schizophrenia”, Am J Psychiatry, 165(8):1033-9, (2008). [cited by applicant]
Shirey, J. et al., “An Allosteric Potentiator of M4 mAChR Modulates Hippocampal Synaptic Transmission”, Nature Chem Biol., 4(1):42-50, (2008). [cited by applicant]
Si, W. et al., “A Novel Derivative of Xanomeline Improves Fear Cognition in Aged Mice”, Neurosci Lett., 473(2):115-9, (2010). [cited by applicant]
Soukup, O. et al., “Acetylcholinesterase Inhibitors and Drugs Acting on Muscarinic Receptors—Potential Crosstalk of Cholinergic Mechanisms During Pharmacological Treatment”, Curr Neuropharmacol., 15(4):637-53, (2017). [cited by applicant]
Sramek, J. et al., “The Safety and Tolerance of Xenomeline Tartrate in Patients with Alzheimer's Disease”, J Clin Pharmacol., 35(8):800-6, (1995). [cited by applicant]
Syed, R. et al., “Pharmacological Inventions for Clozapine-Induced Hypersalivation”, Cochrane Database Sys Rev., 3:1-62, (2008). [cited by applicant]
Tarr, J. et al., “Challenges in the Development of an M4 PAM Preclinical Candidate: The Discovery, SAR, and In Vivo Characterization of a Series of 3-Aminoazetidine-Derived Amides”, Bioorg Med Chem Lett., 27(13):2990-5,… [cited by applicant]
U.S. Appl. No. 14/534,698; Non-Final Office Action, dated Nov. 24, 2015; 11 pages. [cited by applicant]
U.S. Appl. No. 15/378,796; Applicant-Initiated Interview Summary, dated Jul. 17, 2018, 3 pages. [cited by applicant]
U.S. Appl. No. 15/378,796; Applicant-Initiated Interview Summary, dated Jun. 5, 2018; 4 pages. [cited by applicant]
U.S. Appl. No. 15/378,796; Final Office Action, dated Jan. 4, 2018; 14 pages. [cited by applicant]
U.S. Appl. No. 15/378,796; Non-Final Office Action, dated May 24, 2017; 11 pages. [cited by applicant]
U.S. Appl. No. 15/400,108; Applicant-Initiated Interview Summary, dated Jun. 5, 2018; 3 pages. [cited by applicant]
U.S. Appl. No. 15/400,108; Applicant-Initiated Interview Summary, dated Oct. 9, 2018; 3 pages. [cited by applicant]
U.S. Appl. No. 15/400,108; Final Office Action, dated Jul. 18, 2017; 14 pages. [cited by applicant]
U.S. Appl. No. 15/400,108; Non-Final Office Action, dated Feb. 24, 2017; 11 pages. [cited by applicant]
U.S. Appl. No. 15/400,108; Non-Final Office Action, dated Sep. 7, 2018; 43 pages. [cited by applicant]
U.S. Appl. No. 15/400,108; Notice of Allowance, dated Nov. 8, 2018; 23 pages. [cited by applicant]
U.S. Appl. No. 15/400,108; Notice of Appeal, dated Jan. 17, 2018; 1 page. [cited by applicant]
U.S. Appl. No. 15/738,796; Applicant-Initiated Interview Summary, dated Apr. 2, 2019; 3 pages. [cited by applicant]
U.S. Appl. No. 15/738,796; Applicant-Initiated Interview Summary, dated Mar. 4, 2019; 3 pages. [cited by applicant]
U.S. Appl. No. 15/738,796; Notice of Allowance, dated Sep. 6, 2018; 15 pages. [cited by applicant]
U.S. Appl. No. 16/270,206; Applicant-Initiated Interview Summary, dated May 9, 2019; 7 pages. [cited by applicant]
U.S. Appl. No. 16/270,206; Applicant-Initiated Interview Summary, dated May 24, 2019; 3 pages. [cited by applicant]
U.S. Appl. No. 16/270,206; Non-Final Office Action, dated Apr. 16, 2019; 28 pages. [cited by applicant]
U.S. Appl. No. 16/270,206; Notice of Allowance, dated Jun. 12, 2019; 28 pages. [cited by applicant]
U.S. Appl. No. 16/289,165; Applicant-Initiated Interview Summary, dated Apr. 2, 2019; 3 pages. [cited by applicant]
U.S. Appl. No. 16/289,165; Applicant-Initiated Interview Summary, dated May 9, 2019; 6 pages. [cited by applicant]
U.S. Appl. No. 16/289,165; Applicant-Initiated Interview Summary, dated May 24, 2019; 4 pages. [cited by applicant]
U.S. Appl. No. 16/289,165; Non-Final Office Action, dated Apr. 11, 2019; 29 pages. [cited by applicant]
U.S. Appl. No. 16/289,165; Notice of Allowance, dated Jun. 13, 2019; 27 pages. [cited by applicant]
U.S. Appl. No. 16/444,206; Non-Final Office Action, dated Nov. 8, 2019; 22 pages. [cited by applicant]
U.S. Appl. No. 16/444,206; Notice of Allowance, dated Feb. 27, 2020; 13 pages. [cited by applicant]
U.S. Appl. No. 16/585,532; Non-Final Office Action, dated Aug. 5, 2020; 39 pages. [cited by applicant]
U.S. Appl. No. 16/585,532; Non-Final Office Action, dated Oct. 6, 2020; 7 pages. [cited by applicant]
U.S. Appl. No. 16/585,532; Notice of Allowance, dated Jan. 7, 2021; 10 pages. [cited by applicant]
U.S. Appl. No. 16/880,600; Non-Final Office Action, dated Aug. 5, 2020; 20 pages. [cited by applicant]
U.S. Appl. No. 16/880,600; Non-Final Office Action, dated Nov. 5, 2020; 13 pages. [cited by applicant]
U.S. Appl. No. 16/880,600; Notice of Allowance, dated Jan. 12, 2021; 9 pages. [cited by applicant]
U.S. Appl. No. 16/880,634; Applicant-Initiated Interview Summary, Date Jan. 19, 2022; 2 pages. [cited by applicant]
U.S. Appl. No. 16/880,634; Final Office Action, dated May 27, 2021; 30 pages. [cited by applicant]
U.S. Appl. No. 16/880,634; Final Office Action, dated Sep. 21, 2022; 17 pages. [cited by applicant]
U.S. Appl. No. 16/880,634; Non-Final Office Action, dated Jan. 1, 2021; 39 pages. [cited by applicant]
U.S. Appl. No. 16/880,634; Non-Final Office Action, dated Mar. 8, 2023; 13 pages. [cited by applicant]
U.S. Appl. No. 16/880,634; Non-Final Office Action, dated Nov. 18, 2021; 27 pages. [cited by applicant]
U.S. Appl. No. 16/950,203; Final Office Action, dated Aug. 24, 2022; 16 pages. [cited by applicant]
U.S. Appl. No. 16/950,203; Final Office Action, dated Sep. 14, 2023; 18 pages. [cited by applicant]
U.S. Appl. No. 16/950,203; Non-Final Office Action, dated Feb. 16, 2022; 31 pages. [cited by applicant]
U.S. Appl. No. 16/950,203; Non-Final Office Action, dated Mar. 16, 2023; 17 pages. [cited by applicant]
U.S. Appl. No. 17/143,904; Non-Final Office Action, dated Feb. 17, 2022; 23 pages. [cited by applicant]
U.S. Appl. No. 17/143,904; Notice of Allowance, dated Jun. 30, 2022; 8 pages. [cited by applicant]
U.S. Appl. No. 17/167,714; Final Office Action, dated Apr. 26, 2022; 12 pages. [cited by applicant]
U.S. Appl. No. 17/167,714; Non-Final Office Action, dated Apr. 15, 2021; 23 pages. [cited by applicant]
U.S. Appl. No. 17/649,826; Notice of Allowance, dated Aug. 4, 2022; 20 pages. [cited by applicant]
U.S. Appl. No. 17/663,760; Non-Final Office Action, dated May 12, 2023; 26 pages. [cited by applicant]
U.S. Appl. No. 17/822,872; Non-Final Office Action, dated Apr. 11, 2023; 18 pages. [cited by applicant]
U.S. Appl. No. 17/822,872; Notice of Allowance, dated Sep. 28, 2023; 8 pages. [cited by applicant]
Vardigan, J. et al., “Improved Cognition Without Adverse Effects: Novel M1 Muscarinic Potentiator Compares Favorably to Donepezil and Xanomeline in Rhesus Monkey”, Psychopharmacol., 232(11):1859-66, (2015). [cited by applicant]
Wan, W. et al., “Use of Degradable and Nondegradable Nanomaterials for Controlled Release”, Nanomed., 2(4):483-509, (2007). [cited by applicant]
Witte, L. et al., “Muscarinic Receptor Antoagonists for Overactive Bladder Treatment: Does One Fit All?”, Curr Opin Urol., 19(1):13-9, (2009). [cited by applicant]
Wood, M. et al., “Discovery of VU0467485/AZ13713945: An M4 PAM Evaluated as a Preclinical Candidate for the Treatment of Schizophrenia”, ACS Med Chem Lett., 8(2):233-8, (2017). [cited by applicant]
Yohn, S. et al., “Muscarinic acetylcholine receptors for psychotic disorders: bench-side to clinic”, Trends Pharmacol Sci., 43(12):1098-112, (2022). [cited by applicant]
Yohn, S. et al., “Positive allosteric modulation of M1 and M4 muscarinic receptors as potential therapeutic treatments for schizophrenia”, Neuropharmacology, 136(Pt C):438-48, (2018). [cited by applicant]
Third Party Observation with English Translation against CN201980064585.4 issued on Jan. 18, 2025, 17 pages. [cited by applicant]
Zhou, W. (2017) “Exploration of the Technology and Development of Pharmaceutical Preparations”, Science, Technology Literature Press, 1st Edition, 96-98. [cited by applicant]