IP Library › Granted Patent US 12,414,948
Granted Patent B2
US 12,414,948 · App. 18/518,436 · Granted Sep 16, 2025

Methods

Inventors: Sophie Dutheil (Stamford, CT); Gretchen Snyder (New York, NY); Peng Li (New Milford, NJ); Robert E. Davis (San Diego, CA)
Assignee: INTRA-CELLULAR THERAPIES, INC.
A61K31/4985A61P25/18A61P25/22A61P25/24A61P29/00
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Quick Facts
Patent No.
US 12,414,948
App. No.
18/518,436
Granted
Sep 16, 2025
Kind
B2
Abstract

The disclosure provides methods the treatment of psychiatric disorders caused by viral, bacterial, or autoimmune encephalitis, and for treatment of psychiatric symptoms of viral, bacterial, and autoimmune encephalitis, and for protecting or reinforcing the blood-brain barrier, comprising administering to a patient in need thereof, a therapeutically effective amount of a 5-HT 2A .

Claims (45)

1. A method for the treatment of psychiatric disorders caused by viral, bacterial, or autoimmune encephalitis, and for treatment of psychiatric symptoms of viral, bacterial, and autoimmune encephalitis comprising administering to a patient in need thereof a Compound of Formula I:

wherein:

X is —N(CH 3 )—; and

Y is —C(═O)—;

in free base, or pharmaceutically acceptable salt form;

wherein the patient has elevated levels of one or more biomarkers indicative of peripheral inflammation in the blood, plasma, serum, peripheral blood mononuclear cells (PBMC), or urine; and

wherein the psychiatric disorder and/or the psychiatric symptom is depression, anxiety, psychosis, anhedonia, memory loss, impairment of executive functioning, difficulty concentrating, seizures, difficulty sleeping, hallucination, change in personality, or any combination thereof.

2. The method according to claim 1 , wherein the Compound of Formula I is in the form of a tosylate salt.

3. The method according to claim 1 , wherein the method comprises once daily administration of a unit dosage for oral administration, comprising the compound of Formula I in free base or in tosylate salt form, in an amount equivalent 1 to 100 mg of free base, and a pharmaceutically acceptable diluent or carrier.

4. The method according to claim 1 , wherein the method comprises once daily administration of a unit dosage for oral transmucosal administration selected from a sublingual or buccal orally disintegrating tablet, wafer, or film, comprising the compound of Formula I in free base or in tosylate salt form, in an amount equivalent to 0.5 to 30 mg of free base, and a pharmaceutically acceptable diluent or carrier.

5. The method according to claim 1 , wherein the compound of Formula I is administered in the form of a long-acting injectable (LAI) composition.

6. The method according to claim 1 , wherein the encephalitis is viral encephalitis.

7. The method according to claim 6 , wherein the encephalitis is caused by, or suspected to be caused by, Herpes simplex Virus 1, Herpes Simplex Virus 2, West Nile Virus, Nipah Virus, human immunodeficiency virus, rabies virus, Epstein-Barr Virus, cytomegalovirus, coronavirus, or influenza virus.

8. The method according to claim 1 , wherein the encephalitis is bacterial encephalitis.

9. The method according to claim 8 , wherein the encephalitis is caused by, or believed to be caused by, toxoplasmosis, Rickettsia, Mycoplasma, Borrelia (e.g., Lyme disease), or malaria.

10. The method according to claim 1 , wherein the encephalitis is autoimmune encephalitis.

11. The method according to claim 10 , wherein the encephalitis is caused by, or believed to be caused by, autoantibodies against the NMDA receptor, the AMPA receptor, the voltage-gated potassium, channel (VGKC), the LGL1 protein, the GABA receptor, the glycine receptor, the glutamate receptor, or the CASPR2 receptor.

12. The method according to claim 1 , wherein the psychiatric disorder and/or the psychiatric symptom is acute depression, depression of MDD, depression of bipolar disorder, acute anxiety, schizophrenia, anhedonia, or any combination thereof.

13. The method according to claim 1 , wherein the method protects or reinforces the blood-brain barrier.

14. The method according to claim 1 , wherein the patient has elevated levels of pro-inflammatory cytokines in the CNS, or elevated levels of C-reactive protein (CRP) of Csf1, and/or depressed levels of anti-inflammatory cytokines in the CNS.

15. The method according to claim 1 , wherein the compound of Formula I is administered intra-nasally subcutaneously, intramuscularly, intravenously, orally, sub-lingually, intra-peritoneally, or buccally.

16. The method according to claim 1 , wherein the patient has not responded to, or has not responded adequately to, or who suffers undesirable side effects from, treatment with another antidepressant agent.

17. A method for protecting or reinforcing the blood-brain barrier, comprising administering to a patient in need thereof, a therapeutically effective amount of a Compound of Formula I:

wherein:

X is —N(CH 3 )—; and

Y is —C(═O)—;

in free base, or pharmaceutically acceptable salt form;

wherein the patient has elevated levels of one or more biomarkers indicative of peripheral inflammation in the blood, plasma, serum, peripheral blood mononuclear cells (PBMC), or urine.

18. A method for the treatment of psychiatric disorders in a patient in need thereof, wherein the psychiatric disorder and/or the psychiatric symptom is depression, anxiety, psychosis, anhedonia, memory loss, impairment of executive functioning, difficulty concentrating, seizures, difficulty sleeping, hallucination, change in personality, or any combination thereof;

wherein the patient has elevated levels of one or more biomarkers indicative of peripheral inflammation in the blood, plasma, serum, peripheral blood mononuclear cells (PBMC), or urine; and

wherein the patient has elevated levels of pro-inflammatory cytokines in the CNS, or elevated levels of C-reactive protein (CRP), or Csf1, and/or depressed levels of anti-inflammatory cytokines in the CNS, the method comprising administering a therapeutically effective amount of a Compound of Formula I:

wherein:

X is —N(CH 3 )—; and

Y is —C(═O)—;

in free base, or pharmaceutically acceptable salt form,

to the patient.

19. The method according to claim 1 , wherein the one or more biomarkers indicative of peripheral inflammation are selected from the group consisting of interferon-alpha, interferon-beta, interferon-delta, and combinations thereof.

20. The method according to claim 1 , wherein after treatment with the Compound of Formula I, the patient has a reduced level of the one or more biomarkers indicative of peripheral inflammation.

21. The method according to claim 1 , wherein the patient has peripheral serotonin deficiency.

22. The method according to claim 17 , wherein the one or more biomarkers indicative of peripheral inflammation are selected from the group consisting of interferon-alpha, interferon-beta, interferon-delta, and combinations thereof.

23. The method according to claim 17 , wherein after treatment with the Compound of Formula I, the patient has a reduced level of the one or more biomarkers indicative of peripheral inflammation.

24. The method according to claim 17 , wherein the patient has peripheral serotonin deficiency.

25. The method according to claim 18 , wherein the one or more biomarkers indicative of peripheral inflammation are selected from the group consisting of interferon-alpha, interferon-beta, interferon-delta, and combinations thereof.

26. The method according to claim 18 , wherein after treatment with the Compound of Formula I, the patient has a reduced level of the one or more biomarkers indicative of peripheral inflammation.

27. The method according to claim 18 , wherein the patient has peripheral serotonin deficiency.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 18, 2024
From: DUTHEIL, SOPHIE; SNYDER, GRETCHEN; LI, PENG; DAVIS, ROBERT E.
To: INTRA-CELLULAR THERAPIES, INC.
Reel/Frame 067155/0744 →
Continuity (3)
Continuation In Part 18320173 · May 18, 2023
Provisional Application 63343192 · May 18, 2022
Related Publication 20240122924A1 · Apr 18, 2024
References Cited (400)
US 2490813A · Hughes et al. · 1949 [cited by applicant]
US 3299078A · Pachter · 1967 [cited by applicant]
US 3813392A · Sellstedt et al. · 1974 [cited by applicant]
US 3914421A · Rajagopalan · 1975 [cited by applicant]
US 4001263A · Plattner et al. · 1977 [cited by applicant]
US 4115577A · Rajagopalan · 1978 [cited by applicant]
US 4136145A · Fuchs et al. · 1979 [cited by applicant]
US 4183936A · Rajagopalan · 1980 [cited by applicant]
US 4219550A · Rajagopalan · 1980 [cited by applicant]
US 4238607A · Rajagopalan · 1980 [cited by applicant]
US 4389330A · Tice et al. · 1983 [cited by applicant]
US 4522944A · Doria et al. · 1985 [cited by applicant]
US 4530840A · Tice et al. · 1985 [cited by applicant]
US 4767628A · Hutchinson · 1988 [cited by applicant]
US 4849246A · Schmidt · 1989 [cited by applicant]
US 4971971A · Tokunaga et al. · 1990 [cited by applicant]
US 4985432A · Tokunaga et al. · 1991 [cited by applicant]
US 5004602A · Hutchinson · 1991 [cited by applicant]
US 5114976A · Norden · 1992 [cited by applicant]
US 5151419A · Perenyi et al. · 1992 [cited by applicant]
US 5538739A · Bodmer et al. · 1996 [cited by applicant]
US 5629003A · Horstmann et al. · 1997 [cited by applicant]
US 5648539A · Goodbrand et al. · 1997 [cited by applicant]
US 5648542A · Goodbrand et al. · 1997 [cited by applicant]
US 5654482A · Goodbrand et al. · 1997 [cited by applicant]
US 5688801A · Mesens et al. · 1997 [cited by applicant]
US 5705697A · Goodbrand et al. · 1998 [cited by applicant]
US 5723669A · Goodbrand et al. · 1998 [cited by applicant]
US 5723671A · Goodbrand et al. · 1998 [cited by applicant]
US 5763476A · Delbressine et al. · 1998 [cited by applicant]
US 5779231A · Okazaki et al. · 1998 [cited by applicant]
US 5834493A · Gil Quintero et al. · 1998 [cited by applicant]
US 5847166A · Buchwald et al. · 1998 [cited by applicant]
US 5902901A · Goodbrand et al. · 1999 [cited by applicant]
US 5922338A · Brich et al. · 1999 [cited by applicant]
US 5922682A · Brich et al. · 1999 [cited by applicant]
US 5948430A · Zerbe et al. · 1999 [cited by applicant]
US 5965168A · Mesens et al. · 1999 [cited by applicant]
US 6043370A · Kubo et al. · 2000 [cited by applicant]
US 6110921A · Mesens et al. · 2000 [cited by applicant]
US 6221335B1 · Foster · 2001 [cited by applicant]
US 6307087B1 · Buchwald et al. · 2001 [cited by applicant]
US 6323366B1 · Wolfe et al. · 2001 [cited by applicant]
US 6368632B1 · Mesens et al. · 2002 [cited by applicant]
US 6407092B1 · Hester et al. · 2002 [cited by applicant]
US 6419952B2 · Wong et al. · 2002 [cited by applicant]
US 6440710B1 · Keinan et al. · 2002 [cited by applicant]
US 6541639B2 · Zhou et al. · 2003 [cited by applicant]
US 6544599B1 · Mesens et al. · 2003 [cited by applicant]
US 6548493B1 · Robichaud et al. · 2003 [cited by applicant]
US 6552017B1 · Robichaud et al. · 2003 [cited by applicant]
US 6552024B1 · Chen et al. · 2003 [cited by applicant]
US 6579881B2 · Kitazawa et al. · 2003 [cited by applicant]
US 6603008B1 · Ando et al. · 2003 [cited by applicant]
US 6699852B2 · Robichaud et al. · 2004 [cited by applicant]
US 6713471B1 · Robichaud et al. · 2004 [cited by applicant]
US 6762329B2 · Marcoux et al. · 2004 [cited by applicant]
US 6803055B2 · Mesens et al. · 2004 [cited by applicant]
US 6828091B2 · Kasibhatla et al. · 2004 [cited by applicant]
US 6849619B2 · Robichaud et al. · 2005 [cited by applicant]
US 6849640B2 · Ennis et al. · 2005 [cited by applicant]
US 6884429B2 · Koziak et al. · 2005 [cited by applicant]
US 6929803B2 · Wong et al. · 2005 [cited by applicant]
US 7071186B2 · Robichaud et al. · 2006 [cited by applicant]
US 7071201B2 · Kitazawa et al. · 2006 [cited by applicant]
US 7081455B2 · Robichaud et al. · 2006 [cited by applicant]
US 7109339B2 · Lee et al. · 2006 [cited by applicant]
US 7118763B2 · Mesens et al. · 2006 [cited by applicant]
US 7183282B2 · Robichaud et al. · 2007 [cited by applicant]
US 7223870B2 · Ghosh et al. · 2007 [cited by applicant]
US RE39679E · Robichaud et al. · 2007 [cited by applicant]
US RE39680E · Robichaud et al. · 2007 [cited by applicant]
US 7238690B2 · Robichaud et al. · 2007 [cited by applicant]
US 7244734B2 · Iwema Bakker et al. · 2007 [cited by applicant]
US 7375226B2 · Jolidon et al. · 2008 [cited by applicant]
US 7462641B2 · Igo et al. · 2008 [cited by applicant]
US 7517990B2 · Ito et al. · 2009 [cited by applicant]
US 7547452B2 · Mesens et al. · 2009 [cited by applicant]
US 7592454B2 · Lee et al. · 2009 [cited by applicant]
US 7598273B2 · Gant et al. · 2009 [cited by applicant]
US 7601740B2 · Weiner et al. · 2009 [cited by applicant]
US 7614727B2 · Hori · 2009 [cited by applicant]
US 7645752B2 · McDevitt et al. · 2010 [cited by applicant]
US 7659285B2 · Weiner et al. · 2010 [cited by applicant]
US 7713995B2 · Weiner et al. · 2010 [cited by applicant]
US 7732462B2 · Weiner et al. · 2010 [cited by applicant]
US 7750168B2 · Potyen et al. · 2010 [cited by applicant]
US 7968538B2 · Becker et al. · 2011 [cited by applicant]
US 7994193B2 · Weiner et al. · 2011 [cited by applicant]
US 7998971B2 · Barlow et al. · 2011 [cited by applicant]
US 8008323B2 · Weiner et al. · 2011 [cited by applicant]
US 8227487B2 · Weiner et al. · 2012 [cited by applicant]
US 8309722B2 · Tomesch et al. · 2012 [cited by applicant]
US 8309772B2 · Weiner et al. · 2012 [cited by applicant]
US 8377959B2 · Weiner et al. · 2013 [cited by applicant]
US 8414922B2 · Bryson et al. · 2013 [cited by applicant]
US 8461148B2 · Hollander · 2013 [cited by applicant]
US 8475793B2 · De Waal Malefyt et al. · 2013 [cited by applicant]
US 8598119B2 · Mates et al. · 2013 [cited by applicant]
US 8603514B2 · Yang et al. · 2013 [cited by applicant]
US 8604021B2 · Becker et al. · 2013 [cited by applicant]
US 8618130B2 · Weiner et al. · 2013 [cited by applicant]
US 8648077B2 · Tomesch et al. · 2014 [cited by applicant]
US 8652378B1 · Yang et al. · 2014 [cited by applicant]
US 8697700B2 · Surman et al. · 2014 [cited by applicant]
US 8778893B2 · Gong et al. · 2014 [cited by applicant]
US 8779139B2 · Tomesch et al. · 2014 [cited by applicant]
US 8791138B2 · Seeman et al. · 2014 [cited by applicant]
US 8835459B2 · Kottayil et al. · 2014 [cited by applicant]
US 8900497B2 · Yang et al. · 2014 [cited by applicant]
US 8900498B2 · Yang et al. · 2014 [cited by applicant]
US 8906277B2 · Yang et al. · 2014 [cited by applicant]
US 8921393B2 · Weiner et al. · 2014 [cited by applicant]
US 8993572B2 · Mates et al. · 2015 [cited by applicant]
US 9108340B2 · Yang et al. · 2015 [cited by applicant]
US 9168258B2 · Mates et al. · 2015 [cited by applicant]
US 9199995B2 · Tomesch et al. · 2015 [cited by applicant]
US 9211289B2 · Weiner et al. · 2015 [cited by applicant]
US 9216175B2 · Amancha et al. · 2015 [cited by applicant]
US 9315504B2 · Tomesch et al. · 2016 [cited by applicant]
US 9371324B2 · Mates et al. · 2016 [cited by applicant]
US 9393192B2 · Yam et al. · 2016 [cited by applicant]
US 9427412B2 · Bryson et al. · 2016 [cited by applicant]
US 9428506B2 · Mates et al. · 2016 [cited by applicant]
US 9566271B2 · Weiner et al. · 2017 [cited by applicant]
US 9567327B2 · Xiong et al. · 2017 [cited by applicant]
US 9586960B2 · Tomesch et al. · 2017 [cited by applicant]
US 9616061B2 · Mates et al. · 2017 [cited by applicant]
US 9708322B2 · Li et al. · 2017 [cited by applicant]
US 9745300B2 · Mates et al. · 2017 [cited by applicant]
US 9751883B2 · Tomesch et al. · 2017 [cited by applicant]
US 9956227B2 · Vanover et al. · 2018 [cited by applicant]
US 10028944B2 · Weiner et al. · 2018 [cited by applicant]
US 10072010B2 · Li et al. · 2018 [cited by applicant]
US 10077267B2 · Mates et al. · 2018 [cited by applicant]
US 10117867B2 · Mates et al. · 2018 [cited by applicant]
US 10118926B2 · Koolman et al. · 2018 [cited by applicant]
US 10179776B2 · Davis et al. · 2019 [cited by applicant]
US 10221176B2 · Tomesch et al. · 2019 [cited by applicant]
US 10245260B2 · Yao et al. · 2019 [cited by applicant]
US 10322134B2 · Vanover et al. · 2019 [cited by applicant]
US 10464938B2 · Tomesch et al. · 2019 [cited by applicant]
US 10472359B2 · Li et al. · 2019 [cited by applicant]
US 10525046B2 · Weiner et al. · 2020 [cited by applicant]
US 10597394B2 · Mates et al. · 2020 [cited by applicant]
US 10597395B2 · Tomesch et al. · 2020 [cited by applicant]
US 10654854B2 · Li et al. · 2020 [cited by applicant]
US 10682354B2 · Wennogle · 2020 [cited by applicant]
US 10688097B2 · Yao et al. · 2020 [cited by applicant]
US 10695345B2 · Li et al. · 2020 [cited by applicant]
US 10702522B2 · Mates et al. · 2020 [cited by applicant]
US 10716786B2 · Li et al. · 2020 [cited by applicant]
US 10799500B2 · Yao et al. · 2020 [cited by applicant]
US 10844061B2 · Li et al. · 2020 [cited by applicant]
US 10899762B2 · Mates et al. · 2021 [cited by applicant]
US 10906906B2 · Li et al. · 2021 [cited by applicant]
US 10960009B2 · Vanover et al. · 2021 [cited by applicant]
US 10960010B2 · Vanover et al. · 2021 [cited by applicant]
US 10961245B2 · Li et al. · 2021 [cited by applicant]
US 11014925B2 · Li et al. · 2021 [cited by applicant]
US 11026951B2 · Vanover et al. · 2021 [cited by applicant]
US 11052083B2 · Li et al. · 2021 [cited by applicant]
US 11053245B2 · Mates et al. · 2021 [cited by applicant]
US 11066407B2 · Tomesch et al. · 2021 [cited by applicant]
US 11096944B2 · Yao et al. · 2021 [cited by applicant]
US 11124514B2 · Mates et al. · 2021 [cited by applicant]
US RE48825E · Tomesch et al. · 2021 [cited by applicant]
US RE48839E · Mates et al. · 2021 [cited by applicant]
US 11311536B2 · Li et al. · 2022 [cited by applicant]
US 11331316B2 · Li et al. · 2022 [cited by applicant]
US 11376249B2 · Li et al. · 2022 [cited by applicant]
US 11407751B2 · Tomesch et al. · 2022 [cited by applicant]
US 11427587B2 · Li et al. · 2022 [cited by applicant]
US 11440911B2 · Wennogle et al. · 2022 [cited by applicant]
US 11453670B2 · Li et al. · 2022 [cited by applicant]
US 11560382B2 · Mates et al. · 2023 [cited by applicant]
US 11680065B2 · Li et al. · 2023 [cited by applicant]
US 11690842B2 · Li et al. · 2023 [cited by applicant]
US 11723909B2 · Li et al. · 2023 [cited by applicant]
US 11753419B2 · Li et al. · 2023 [cited by applicant]
US 11806347B2 · Li et al. · 2023 [cited by applicant]
US 11806348B2 · Li et al. · 2023 [cited by applicant]
US 11957791B2 · Li et al. · 2024 [cited by applicant]
US 11980617B2 · Snyder et al. · 2024 [cited by applicant]
US 12023331B2 · Snyder et al. · 2024 [cited by applicant]
US 12070459B2 · Li et al. · 2024 [cited by applicant]
US 12090155B2 · Mates et al. · 2024 [cited by applicant]
US 12122792B2 · Li et al. · 2024 [cited by applicant]
US 12128043B2 · Li et al. · 2024 [cited by applicant]
US 12144808B2 · Li et al. · 2024 [cited by applicant]
US 12194044B2 · Yao et al. · 2025 [cited by applicant]
US 20030144319A1 · Bigge et al. · 2003 [cited by applicant]
US 20040009970A1 · Ramamoorthy · 2004 [cited by applicant]
US 20040034015A1 · Robichaud et al. · 2004 [cited by applicant]
US 20040092534A1 · Yam et al. · 2004 [cited by applicant]
US 20040127482A1 · Robichaud et al. · 2004 [cited by applicant]
US 20040142970A1 · Chung et al. · 2004 [cited by applicant]
US 20040186136A1 · Alken et al. · 2004 [cited by applicant]
US 20050166771A1 · Gygi et al. · 2005 [cited by applicant]
US 20050182749A1 · Matsui · 2005 [cited by applicant]
US 20050222209A1 · Zeldis et al. · 2005 [cited by applicant]
US 20050222238A1 · Alken · 2005 [cited by applicant]
US 20060178362A1 · Robichaud et al. · 2006 [cited by applicant]
US 20060205787A1 · Muller et al. · 2006 [cited by applicant]
US 20080069885A1 · Mesens et al. · 2008 [cited by applicant]
US 20080132552A1 · Kleinman et al. · 2008 [cited by applicant]
US 20080280941A1 · Lourtie · 2008 [cited by applicant]
US 20080287450A1 · Cid-Nunez et al. · 2008 [cited by applicant]
US 20090076159A1 · Czarnik · 2009 [cited by applicant]
US 20090209608A1 · Czarnik · 2009 [cited by applicant]
US 20100159033A1 · Gant et al. · 2010 [cited by applicant]
US 20100204470A1 · Wieser et al. · 2010 [cited by applicant]
US 20110071080A1 · Mates et al. · 2011 [cited by applicant]
US 20110269777A1 · Bachurin et al. · 2011 [cited by applicant]
US 20140080816A1 · Koolman et al. · 2014 [cited by applicant]
US 20140210117A1 · Friesen et al. · 2014 [cited by applicant]
US 20150004237A1 · Edgar et al. · 2015 [cited by applicant]
US 20150031804A1 · Shiramizu et al. · 2015 [cited by applicant]
US 20150072964A1 · Mates et al. · 2015 [cited by applicant]
US 20150079172A1 · Mates et al. · 2015 [cited by applicant]
US 20150080404A1 · Mates et al. · 2015 [cited by applicant]
US 20150374684A1 · Javitt et al. · 2015 [cited by applicant]
US 20160235720A1 · Foster et al. · 2016 [cited by applicant]
US 20160310502A1 · Vanover et al. · 2016 [cited by applicant]
US 20160354315A1 · Li · 2016 [cited by applicant]
US 20170114037A1 · Davis et al. · 2017 [cited by applicant]
US 20170183350A1 · Mates et al. · 2017 [cited by applicant]
US 20170319580A1 · Yao et al. · 2017 [cited by applicant]
US 20180044337A1 · Tomesch et al. · 2018 [cited by applicant]
US 20180200256A1 · Vanover et al. · 2018 [cited by applicant]
US 20190071445A1 · Li et al. · 2019 [cited by applicant]
US 20190183888A1 · Mates et al. · 2019 [cited by applicant]
US 20190192511A1 · Li et al. · 2019 [cited by applicant]
US 20190211015A1 · Mittleman et al. · 2019 [cited by applicant]
US 20190231780A1 · Yao et al. · 2019 [cited by applicant]
US 20190290655A1 · Vanover et al. · 2019 [cited by applicant]
US 20190298730A1 · Vanover et al. · 2019 [cited by applicant]
US 20190328692A1 · Doller et al. · 2019 [cited by applicant]
US 20190328745A1 · Vanover et al. · 2019 [cited by applicant]
US 20190388418A1 · Li et al. · 2019 [cited by applicant]
US 20200087305A1 · Tomesch et al. · 2020 [cited by applicant]
US 20200102304A1 · Li et al. · 2020 [cited by applicant]
US 20200148683A1 · Peddy et al. · 2020 [cited by applicant]
US 20200157100A1 · Li · 2020 [cited by applicant]
US 20200392135A1 · Wennogle et al. · 2020 [cited by applicant]
US 20200405713A1 · Mates et al. · 2020 [cited by applicant]
US 20200407362A1 · Mates et al. · 2020 [cited by applicant]
US 20210002280A1 · Mates · 2021 [cited by applicant]
US 20210008065A1 · Li et al. · 2021 [cited by applicant]
US 20210009592A1 · Li et al. · 2021 [cited by applicant]
US 20210032247A1 · Li et al. · 2021 [cited by applicant]
US 20210060009A1 · Synder et al. · 2021 [cited by applicant]
US 20210070755A1 · Zrt et al. · 2021 [cited by applicant]
US 20210093634A1 · Snyder et al. · 2021 [cited by applicant]
US 20210145829A1 · Li et al. · 2021 [cited by applicant]
US 20210163481A1 · Li et al. · 2021 [cited by applicant]
US 20210186962A1 · Davis et al. · 2021 [cited by applicant]
US 20210322433A1 · Vanover et al. · 2021 [cited by applicant]
US 20220024924A1 · Janton et al. · 2022 [cited by applicant]
US 20220041600A1 · Li et al. · 2022 [cited by applicant]
US 20220056031A1 · Li et al. · 2022 [cited by applicant]
US 20230312573A1 · Li et al. · 2023 [cited by applicant]
US 20230372336A1 · Dutheil et al. · 2023 [cited by applicant]
CN 109867674A · 2019 [cited by applicant]
EP 0058481A1 · 1982 [cited by applicant]
EP 0856508A1 · 1998 [cited by applicant]
EP 0976732A1 · 2000 [cited by applicant]
EP 1539115A1 · 2005 [cited by applicant]
EP 1564671A1 · 2005 [cited by applicant]
GB 1476087A · 1977 [cited by applicant]
GB 2145422A · 1985 [cited by applicant]
RU 2465267C2 · 2012 [cited by applicant]
WO WO94024125A1 · 1994 [cited by applicant]
WO WO95013814A1 · 1995 [cited by applicant]
WO WO95026325A2 · 1995 [cited by applicant]
WO WO1995026325A2 · 1995 [cited by applicant]
WO WO98043956A1 · 1998 [cited by applicant]
WO WO2000035419A2 · 2000 [cited by applicant]
WO WO2000048610A1 · 2000 [cited by applicant]
WO WO2000064899A1 · 2000 [cited by applicant]
WO WO2000077001A1 · 2000 [cited by applicant]
WO WO2000077002A1 · 2000 [cited by applicant]
WO WO2000077010A2 · 2000 [cited by applicant]
WO WO2002059129A2 · 2002 [cited by applicant]
WO WO2003014118A1 · 2003 [cited by applicant]
WO WO2004010981A1 · 2004 [cited by applicant]
WO WO2004039788A1 · 2004 [cited by applicant]
WO WO2004045668A1 · 2004 [cited by applicant]
WO WO2004056324A2 · 2004 [cited by applicant]
WO WO2004064738A2 · 2004 [cited by applicant]
WO WO2005030214A1 · 2005 [cited by applicant]
WO WO2006034187A2 · 2006 [cited by applicant]
WO WO2006081251A2 · 2006 [cited by applicant]
WO WO2006081332A1 · 2006 [cited by applicant]
WO WO2007084841A2 · 2007 [cited by applicant]
WO WO2008112280A1 · 2008 [cited by applicant]
WO WO2009017836A1 · 2009 [cited by applicant]
WO WO2009100324A1 · 2009 [cited by applicant]
WO WO2017117514A1 · 2017 [cited by applicant]
WO WO2017120012A1 · 2017 [cited by examiner]
WO WO2018031535A1 · 2018 [cited by applicant]
WO WO2018106916A1 · 2018 [cited by applicant]
WO WO2019102240A1 · 2019 [cited by applicant]
WO WO2019178484A1 · 2019 [cited by applicant]
WO WO2020112941A2 · 2020 [cited by applicant]
WO WO2020182978A1 · 2020 [cited by applicant]
WO WO2022199708A1 · 2022 [cited by applicant]
WO WO2022261633A1 · 2022 [cited by applicant]
Snyder et al., Psychopharmacology (Heidelberg, Germany) (2015), 232(3), 605-621. [cited by examiner]
Davis et al., Psychopharmacology (Heidelberg, Germany) (2015), 232(15), 2863-2872. [cited by examiner]
Mazza et al, CNS § Neurological Disorders-Drug Targets, (2020), 19, 243-247. [cited by examiner]
Corponi et al., European Neuropsychopharmacology, (2019), 29, 971-985. [cited by examiner]
Jairo et al., Neuroscience and Biobehavioral reviews 83 (2017), 97-108. [cited by examiner]
Galea et al., Cellular & Molecular Immunology, 18, (2021), 2489-2501. [cited by examiner]
Dutheil et al., The journal of Neurosicence, Feb. 1, 2023, 43(5), 863-877. [cited by examiner]
U.S. Appl. No. 61/911,416, filed Dec. 3, 2013, Vanover et al. [cited by applicant]
U.S. Appl. No. 61/925,607, filed Jan. 9, 2014, Vanover et al. [cited by applicant]
U.S. Appl. No. 61/975,502, filed Apr. 4, 2014, Mates et al. [cited by applicant]
U.S. Appl. No. 61/975,610, filed Apr. 4, 2014, Mates et al. [cited by applicant]
U.S. Appl. No. 61/975,702, filed Apr. 4, 2014, Mates et al. [cited by applicant]
U.S. Appl. No. 62/009,849, filed Jun. 9, 2014, Davis et al. [cited by applicant]
U.S. Appl. No. 62/015,120, filed Jun. 20, 2014, Mates et al. [cited by applicant]
“Clinical Trial Evaluating ITI-007 (Lumateperone) as a Monotherapy for the Treatment of Bipolar Depression,” ClinicalTrials.gov, 5 pages, Nov. 9, 2015. [cited by applicant]
“Clinical Trial Evaluating ITI-007 (Lumateperone) as a Monotherapy for the Treatment of Bipolar,” ClinicalTrials.gov (Identifier: NCT02600494), 5 pages, (2015). [cited by applicant]
“Clinical Trial Evaluating ITI-007 as an Adjunctive Therapy to Lithium or Valproate for the Treatment of Bipolar Depression,” ClinicalTrials.gov, 6 pages, Nov. 9, 2015. [cited by applicant]
“Study of a Novel Antipsychotic ITI-007 in Schizophrenia,” Clinical Trials.gov, 6 pages, Dec. 26, 2011. [cited by applicant]
Aiken, C., “An Overview of Atypical Antipsychotics for Bipolar Depression,” published on Jan. 3, 2020 at https://www.psychiatrictimes.com/view/overview-atypical-antipsychotics-bipolar-depression, 11 pages. [cited by applicant]
Angst et al. “Prevalence and Characteristics of Undiagnosed Bipolar Disorders in Patients With a Major Depressive Episode”, Arch Gen Psychiatry, vol. 68, No. 8, pp. 701-709, (2011). [cited by applicant]
Balbach, et al. “Pharmaceutical evaluation of early development candidates ‘the 100 mg-approach’, ” International Journal of Pharmaceutics, vol. 275, pp. 1-12 (2004). [cited by applicant]
Barman et al., “Newer Antipsychotics: Brexpiprazole, Cariprazine, and Lumateperone: A Pledge or Another Unkept Promise?,” World J. Psychiatr., vol. 11, No. 12, pp. 1228-1238 (2021). [cited by applicant]
Barry et al. “Schizophrenia,” Clinical Evidence, vol. 6, No. 1007, pp. 1-170, (2012). [cited by applicant]
Bastin et al., “Salt Selection and Optimized Procedures for Pharmaceutical New Chemical Entities,” Organic Process and Research Development, vol. 4, No. 5, pp. 427-435 (2000). [cited by applicant]
Bavin, M, “Polymorphism in Process Development,” Chemistry & Industry, pp. 527-529 (1989). [cited by applicant]
Bechtold, D.A., et al. “Circadian Dysfunction in Disease,” Trends in Pharmacological Sciences, vol. 31, No. 5, pp. 191-198, (2010); DOI: 10.1016/j.tips.2010.01.002. [cited by applicant]
Bennett, J.C., et al., “Cecil Textbook of Medicine,” 20th Edition, vol. 1, pp. 1004-1010, (1996). [cited by applicant]
Berge, S. et al., “Pharmaceutical Salts,” J. Pharm. Sci., vol. 66, No. 1, pp. 1-19, (1977). [cited by applicant]
Bharate, S.S., “Recent Developments in Pharmaceutical Salts: FDA Approvals From 2015 to 2019,” Drug Discovery Today, vol. 26, No. 2, pp. 384-398, (2021). [cited by applicant]
Bobo, W. V., et al. “Fluoxetine and olanzapine combination therapy in treatment-resistant major depression: review of efficacy and safety data,” Expert Opinion on Pharmacotherapy, vol. 10, No. 13, pp. 2145-2159, (2009). [cited by applicant]
Bowers, K.M., et al. “Neuroinfections: Presentation, Diagnosis, and Treatment of Meningitis and Encephalitis,” Neurology, pp. 93-102, (2020). [cited by applicant]
Bremner et al., “Neuroimaging of Posttraumatic Stress Disorder,” Psychiatric Annals Journal, vol. 28, No. 8, pp. 445-450, (1998). [cited by applicant]
Brittain et al., “Chapter 5: Generation of Polymorphs, Hydrates, Solvates, and Amorphous Solids,” Polymorphism in Pharmaceutical Solids, 25 pages, (1999). [cited by applicant]
Bryan-Lluka et al., “Potencies of Haloperidol Metabolites as Inhibitors of the Human Noradrenaline, Dopamine and Serotonin Transporters in Transfected COS-7 Cells,” Naunyn-Shemiedeberg's Arch Pharmacol, vol. 360, pp. 10… [cited by applicant]
Byrn, “Pharmaceutical Solids: A Strategic Approach to Regulatory Considerations,” vol. 12, No. 7, pp. 945-954 (1995). [cited by applicant]
Calabrese et al., “Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated with Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial,” American Journal of Psychiatry, vol.… [cited by applicant]
Chang, C-C., et al. “Melatonin inhibits matrix metalloproteinase-9 (MMP-9) activation in the lipopolysaccharide (LPS)-stimulated RAW 264.7 and BV2 cells and a mouse model of meningitis,” J. Pineal Res., vol. 53, pp. 188… [cited by applicant]
Correll et al., “Efficacy and Safety of Lumateperone for Treatment of Schizophrenia A Randomized Clinical Trial,” JAMA Psychiatry, vol. 77, No. 4, pp. 349-358 (2020). [cited by applicant]
Coyle et al., “Beyond the dopamine receptor: novel therapeutic targets for treating schizophrenia,” Dialogues Clin Neurosci., vol. 12, No. 3, p. 359-382, (2010). [cited by applicant]
Darmani et al., “Do Functional Relationships Exist Between 5-HT1A and 5-HT2 Receptors?” Pharmacology and Biochemistry & Behavior, vol. 36, pp. 901-906, (1990). [cited by applicant]
Davis et al., “ITI-007 demonstrates brain occupancy at serotonin 5-HT2A and dopamine D2 receptors and serotonin transporters using positron emission tomography in healthy volunteers,” Psychopharmacology, vol. 232, pp. 2… [cited by applicant]
Davis et al., “ITI-007: A Novel Treatment for Behavioral Disturbances Associated with Dementia and Related Disorders,” Clinical Trials in Alzheimer's Disease (CTAD) Congress 2014 (2014) (poster presentation). [cited by applicant]
Davis et al., “Rationale for the Development of Low Doses of ITI-007 for the Treatment of Behavioral Disturbances Associated with Dementia,” The Journal of Prevention of Alzheimer's Disease, 2(4):302 (2015) (Clinical Tr… [cited by applicant]
Davis, et al., “ITI-007 in the treatment of schizophrenia: from novel pharmacology to clinical outcomes,” Expert Review of Neurotherapeutics, vol. 16, No. 6, pp. 601-614 (2016). [cited by applicant]
Davis, et al., “Lumateperone (ITI-007), A Novel Drug in Development for the Treatment of Agitation in Patients with Dementia, including Alzheimer's Disease: Rationale and Clinical Design,” The Journal of Prevention of A… [cited by applicant]
De Sousa, A.K., et al. “SARS-CoV-2-mediated encephalitis: Role of AT2R receptors in the blood-brain barrier,” Medical Hypotheses, vol. 144, pp. 1-4, (2020). [cited by applicant]
Del-Monte et al., “Nonverbal expressive behaviour in schizophrenia and social phobia,” Psychiatry Res., vol. 210, p. 29-35, (2013). [cited by applicant]
Docherty et al., “Effect of aripiprazole versus haloperidol on PANSS Prosocial items in early-episode patients with schizophrenia,” Schizophrenia Res., vol. 120, pp. 199-203, (2010). [cited by applicant]
Dutheil, S., et al. “Lumateperone Normalizes Pathological Levels of Acute Inflammation through Important Pathways Known to Be Involved in Mood Regulation,” The Journal of Neuroscience, vol. 43, No. 5, pp. 863-877, (2023… [cited by applicant]
Edinoff et al., “Lumateperone for the Treatment of Schizophrenia,” Psychopharmacology Bulletin, vol. 50, No. 4, pp. 32-59 (2020). [cited by applicant]
Ellenbroeck et al. “Animal Models for the Negative Symptoms of Schizophrenia, ” Behavioural Pharmacology, vol. 11, pp. 223-233, (2000). [cited by applicant]
Fletcher, P., et al. “Perceiving is Believing: Perceiving is Bayesian approach to explaining the positive symptoms of schizophrenia,” Nature Reviews/Neuroscience, vol. 10, pp. 48-58, (2009). [cited by applicant]
Foster et al. “Emerging Approaches for Treatment of Schizophrenia: Modulation of Cholinergic Signaling,” Discov Med., vol. 14, No. 79, pp. 413-420, (2012). [cited by applicant]
Gadade, et al., “Pharmaceutical Cocrystals: Regulatory and Strategic Aspects, Design and Development,” Adv Pharm Bull, vol. 6, No. 4, pp. 479-494, (2016). [cited by applicant]
Gramigna, J, “Lumateperone Safe, Effective for Depressive Symptoms Among Patients with Bipolar Disorders,” American Society of Clinical Psychopharmacology Annual Meeting, Jun. 2, 2020, 3 pages. [cited by applicant]
Grant, D., “Theory and Origin and Polymorphism,” Polymorphism in Pharmaceutical Solids, Chapter 1, pp. 1-10, (1999). [cited by applicant]
Guillory, “Generation of Polymorphs, Hydrates, Solvates, and Amorphous Solids”, Polymorphism in Pharmaceutical Solids, Chapter 5, pp. 183-226 (1999). [cited by applicant]
Hackam, D., et al. “Translation of Research Evidence from Animals to Humans,” JAMA, vol. 296, No. 14, pp. 1731-1732, (2006). [cited by applicant]
Harbert et al., “Neuroleptic Activity in 5-Aryltetrahydro-y-carbolines,” J. Med. Chem., vol. 23, pp. 635-643, (1980). [cited by applicant]
Harvey et al., “Lumateperone Improves Negative Symptoms Related to Emotional Experience (Avolition) in Patient with Schizophrenia,” Abstract presented at the American Society of Clinical Psychopharmacology (ASCP) Annual… [cited by applicant]
Harvey, B.H., et al. “Serotonin and Stress: Protective or Malevolent Actions in the Biobehavioral Response to Repeated Trauma?,” Annals of the New York Academy of Sciences, vol. 1032, pp. 267-272, (2004). [cited by applicant]
Harvey, P.D., “Ziprasidone and Cognition: The Evolving Story,” J Clin Psychiatry, vol. 64, Suppl. 19, pp. 33-39, (2003). [cited by applicant]
Haynes et al., “Occurrence of Pharmaceutically Acceptable Anions and Cations in the Cambridge Database,” Journal of Pharmaceutical Sciences, vol. 94, No. 10, pp. 2111-2120, (2005). [cited by applicant]
Helfer et al., “Efficacy and Safety of Antidepressants Added to Antipsychotics for Schizophrenia: A Systematic Review and Meta-Analysis,” Am J Psychiatry, vol. 173, No. 9, pp. 876-886, (2016). [cited by applicant]
Hlavinka, E., “Schizophrenia Tx Eases Depression in Bipolar Disorder: Lumateperone Offers Greater Rate of Response, Remission versus Placebo,” Medpage Today, 7 pages, (2020); https://www.medpagetoday.com/meetingcoverage… [cited by applicant]
Howes et al., “Glutamate and dopamine in schizophrenia: An update for the 21st century,” J Psychopharmacol., vol. 29, No. 2, p. 97-115, (2015). [cited by applicant]
International Search Report issued in International Application No. PCT/US2020/041063, mailed Oct. 8, 2020, 3 pages. [cited by applicant]
Intra-Cellular Therapies, Inc., “Corporate Presentation” (Jun. 30, 2019). [cited by applicant]
Intra-Cellular Therapies, Inc., “Corporate Presentation” (Sep. 24, 2019), downloaded from https://ir.intracellulartherapies.com/static-files/93b08960-f01c-4864-aa22-8cadb3539753 (last accessed Mar. 13, 2023). [cited by applicant]
Izrayelit, L. “Schizoaffective Disorder and PTSD Successfully Treated With Olanzapine and Supportive Psychotherapy,” Psychiatric Annals journal, vol. 28, No. 8, pp. 424-426, (1998). [cited by applicant]
Jain, et al., “Polymorphism in Pharmacy”, Indian Drugs, vol. 23, No. 6, pp. 315-316 (1986). [cited by applicant]
Johnson, O., et al. “Serotonin receptor activity is necessary for olfactory learning and memory in [cited by applicant]
Jozwiakowski, MJ, Liu, R (Ed.), “Alteration of the Solid State of the Drug Substance: Polymorphs, Solvates, and Amorphous Forms,” Water-Insoluble Drug Formulation, Interpharm Press, pp. 525, 557-561 (2000). [cited by applicant]
Kahn, A.Y., et al. “Residual symptoms of schizophrenia: What are realistic treatment goals? Lingering symptoms require you to evaluate pharmacotherapy and offer psychosocial interventions,” Current Psychiatry, vol. 16, … [cited by applicant]
Kantrowitz, J.T., “The Potential Role of Lumateperone-Something Borrowed? Something New?,” JAMA Psychiatry, vol. 77, No. 4, p. 343-344, (2020); Abstract Only. [cited by applicant]
Kay et al., “The Positive an negative Syndrome Scale (PANSS) for Schizophrenia,” Schizophrenia Bulletin, vol. 13, No. 2, pp. 261-276, (1987). [cited by applicant]
Kendrick, T. “The Newer, ‘Atypical’ Antipsychotic Drugs—Their Development and Current Therapeutic Use,” British J. General Practice, vol. 49, p. 745-749 (1999). [cited by applicant]
Kessler et al., “Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication,” Arch Gen Psychiatry, vol. 62, pp. 593-602, (2005). [cited by applicant]
Khorana, N., et al., “Gamma-Carbolines: Binding at 5-HT5A Serotonin Receptors”, Bioorganic & Medicinal Chemistry, vol. 11, DD. 717-722, p. 718 Table 1, (2003). [cited by applicant]
Kumar et al., “Lumateperone: A New Treatment Approach for Neuropsychiatric Disorders,” Drugs of Today, vol. 54, No. 12, pp. 713-719, (2018). [cited by applicant]
Lammers et al., “Risperidone Long-acting Injection in Schizophrenia Spectrum Illnesses Compared to First Generation Depot Antipsychotics in an Outpatient Setting in Canada,” BMC Psychiatry, vol. 13, No. 155, 9 pages, (2… [cited by applicant]
Lee, et al., “Novel, Highly Potent, Selective 5-HT2A/D2 Receptor Antagonists as Potential Atypical Antipsychotics,” Bioorg. Med. Chem. Lett., vol. 13, p. 767-770, (2003). [cited by applicant]
Li et al., “Discovery of a Tetracyclic Quinoxaline Derivative as a Potent and Orally Active Multifunctional Drug Candidate for the Treatment of Neuropsychiatric and Neurological Disorders”, Journal of Medicinal Chemistr… [cited by applicant]
Liebermann et al., “ITI-007 for the Treatment of Schizophrenia: A 4-Week Randomized, Double-Blind, Controlled Trial,” Biological Psychiatry, vol. 79, pp. 952-961, (2016). [cited by applicant]
Lin et al., “Dosage and duration of antipsychotic treatment in demented outpatients with agitation or psychosis,” Journal of the Formosan Medical Association, vol. 114, pp. 147-153, (2015). [cited by applicant]
Lindstrom et al., “Principal component analysis of the Swedish version of the Positive and Negative Syndrome Scale for schizophrenia,” Nord J Psychiatry, vol. 47, No. 4, p. 257-263, (1993). [cited by applicant]
Lipschitz, D.S., et al. “Childhood Posttraumatic Stress Disorder: A Review of Neurobiologic Sequelae,” Psychiatric Annals Journal, vol. 28, No. 8, pp. 452-457, (1998). [cited by applicant]
Lustig, S., et al. “Viral Neuroinvasion and Encephalitis Induced by Lipopolysaccharide and its Mediators,” J. Exp. Med., vol. 176, pp. 707-712, (1992). [cited by applicant]
Makadia et al., “Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier,” Polymers (Basel), vol. 3, No. 3, pp. 1377-1397, (2011). [cited by applicant]
Marek, et al., “Synergistic Action of 5-HT2A Antagonists and Selective Serotonin Reuptake Inhibitors in Neuropsychiatric Disorders,” Neuropsychopharmacology, vol. 28, pp. 402-412 (2003). [cited by applicant]
Mass et al., “Psychopathological Syndromes of Schizophrenia: Evaluation of the Dimensional Structure of the Positive and Negative Syndrome Scale,” Schizophrenia Bull., vol. 26, No. 1, p. 167-177, (2000). [cited by applicant]
McIntyre et al., “Rapid-acting Antidepressants in Psychiatry: Psychedelics, Episodic Treatments, Innovation, and Clarion Call for Methodologic Rigor in Drug Development,” Expert Opinion on Drug Safety, vol. 21, No. 6, p… [cited by applicant]