IP Library Granted Patent US 12,264,160
Granted Patent B2
US 12,264,160 · App. 18/327,607 · Granted Apr 1, 2025

Pharmaceutical compositions comprising 4-((6bR, 10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-1-(4-fluorophenyl)butan-1-one for treating central nervous system disorders

Inventors: Peng Li (New Milford, NJ); Qiang Zhang (Plainsboro, NJ); Robert Davis (San Diego, CA); Lawrence P. Wennogle (Steamboat Springs, CO)
Assignee: INTRA-CELLULAR THERAPIES, INC.
C07D471/16A61K9/4825A61K9/4891A61K9/5031A61K31/4985A61K47/34A61K47/38C07D471/14
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Quick Facts
Patent No.
US 12,264,160
App. No.
18/327,607
Granted
Apr 1, 2025
Kind
B2
Abstract

The invention relates to pharmaceutical compositions comprising compounds of Formula Q: wherein W is —N(CH 3 )—, and Y is —C(O)—, in free base or pharmaceutically acceptable salt form, and methods of use in the treatment of diseases involving 5-HT 2A receptor, serotonin transporter (SERT) pathway and/or the dopamine D 2 receptor pathway, and methods of treating conditions of the central nervous system therewith.

Claims (47)

1. A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier in admixture with:

(i) a compound of Formula Q:

wherein:

W is —N(CH 3 )—; and

Y is —C(O)—;

in free base or pharmaceutically acceptable salt form; and

(ii) a polymeric matrix;

wherein:

(a) the compound of Formula Q is dissolved or dispersed in the pharmaceutical composition;

(b) the pharmaceutical composition is formulated as a sustained-release injectable composition or a delayed-release injectable composition;

(c) wherein the pharmaceutically acceptable diluent or carrier is an organic solvent; and

(d) wherein the pharmaceutical composition is non-aqueous.

2. The pharmaceutical composition according to claim 1 , wherein the compound of Formula Q is in free base form.

3. The pharmaceutical composition according to claim 1 , wherein the compound of Formula Q is in pharmaceutically acceptable salt form.

4. The pharmaceutical composition according to claim 3 , wherein the pharmaceutically acceptable salt form is a toluenesulfonic acid addition salt form.

5. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises at least one polymer selected from the group consisting of a poly(acetal) polymer, an alkyl α-cyanoacrylate polymer, a poly(alkylene oxalate) polymer, a poly(aliphatic carboxylic acid) polymer, a poly(amino acid) polymer, a poly(β-hydroxybutyric acid acid) polymer, a poly(caprolactone) polymer, a poly(carbonate) polymer, a poly(citric acid) polymer, a poly(dioxanone) polymer, a poly(glycolic acid) polymer, an ester of a hyaluronic acid polymer, a poly(lactic acid) polymer, a poly(lactide-co-glycolide) polymer, a poly(malic acid) polymer, a poly(orthocarbonate) polymer, a poly(orthoester) polymer, a copoly(oxalate) polymer, a 2-hydroxybutyric acid-glycolic acid copolymer, a poly(glycolic acid-caprolactone) copolymer, a poly(glycolic acid-ethylene glycol) copolymer, a poly(lactic acid-caprolactone) copolymer, a poly(lactic acid-ethylene glycol) copolymer, and a lactic acid-glycolic acid copolymer.

6. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises at least one polymer selected from the group consisting of a poly(glycolic acid) polymer, a poly(lactic acid) polymer, and a poly(D,L-lactide-co-glycolide) polymer.

7. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises a poly(D,L-lactide-co-glycolide) polymer.

8. The pharmaceutical composition according to claim 7 , wherein the polymeric matrix is a microspheric polymeric matrix comprising the poly(D,L-lactide-co-glycolide) polymer and the compound of Formula Q.

9. The pharmaceutical composition according to claim 7 , wherein:

(a) the polymeric matrix is a liquid polymeric matrix comprising the poly(D,L-lactide-co-glycolide) polymer and the compound of Formula Q in a liquid form; and

(b) the pharmaceutical composition does not comprise microparticles.

10. The pharmaceutical composition according to claim 1 , wherein the organic solvent is a water-miscible organic solvent.

11. The pharmaceutical composition according to claim 1 , wherein:

(a) the compound of Formula Q is in free base form;

(b) the polymeric matrix comprises a poly(D,L-lactide-co-glycolide) polymer; and

(c) the organic solvent is a water-miscible organic solvent.

12. The pharmaceutical composition according to claim 1 , wherein:

(a) the compound of Formula Q is in toluenesulfonic acid addition salt form;

(b) the polymeric matrix comprises a poly(D,L-lactide-co-glycolide) polymer; and

(c) the organic solvent is a water-miscible organic solvent.

13. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is formulated for controlled-release or sustained-release of the compound of Formula Q over a period of 7 days, 14 days, 30 days, 60 days, or 90 days.

14. A method for inhibiting serotonin 5-hydroxytryptamine-2A receptor activity in a patient, wherein the method comprises administering to the patient in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 1 .

15. The method according to claim 14 , wherein the patient has a disorder involving the serotonin 5-hydroxytryptamine-2A receptor pathway selected from the group consisting of anxiety, depression, psychosis, and schizophrenia.

16. The method according to claim 15 , wherein the disorder is depression.

17. The method according to claim 16 , wherein the depression is bipolar depression.

18. The method according to claim 15 , wherein the disorder is schizophrenia.

19. A method for inhibiting serotonin 5-hydroxytryptamine-2A receptor activity in a patient, wherein the method comprises administering to the patient in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 11 .

20. The method according to claim 19 , wherein the patient has a disorder involving the serotonin 5-hydroxytryptamine-2A receptor pathway selected from the group consisting of anxiety, depression, psychosis, and schizophrenia.

21. The method according to claim 20 , wherein the disorder is depression.

22. The method according to claim 21 , wherein the depression is bipolar depression.

23. The method according to claim 20 , wherein the disorder is schizophrenia.

24. A method for inhibiting serotonin 5-hydroxytryptamine-2A receptor activity in a patient, wherein the method comprises administering to the patient in need thereof a therapeutically effective amount of the pharmaceutical composition according to claim 12 .

25. The method according to claim 24 , wherein the patient has a disorder involving the serotonin 5-hydroxytryptamine-2A receptor pathway selected from the group consisting of anxiety, depression, psychosis, and schizophrenia.

26. The method according to claim 25 , wherein the disorder is depression.

27. The method according to claim 26 , wherein the depression is bipolar depression.

28. The method according to claim 25 , wherein the disorder is schizophrenia.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 1, 2023
From: LI, PENG; ZHANG, QIANG; DAVIS, ROBERT; WENNOGLE, LAWRENCE P.
To: INTRA-CELLULAR THERAPIES, INC.
Reel/Frame 063834/0806 →
Continuity (8)
Continuation 18314785 · May 9, 2023
Continuation 17072933 · Oct 16, 2020
Division 16591178 · Oct 2, 2019
Continuation 16056143 · Aug 6, 2018
Continuation 15629481 · Jun 21, 2017
Continuation 14777466
Provisional Application 61799405 · Mar 15, 2013
Related Publication 20230339951A1 · Oct 26, 2023
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