# US 11,998,524 B2 · Forms of aticaprant

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- Number: US 11,998,524 B2
- Document ID: US11998524B2
- Status: Granted
- Kind: B2
- Application number: 18/178,961
- Filed: 2023-03-06
- Published: 2023-09-07
- Granted: 2024-06-04
- Earliest claimed: 2022-03-07
- Assignees: Janssen Pharmaceuticals, Inc.
- Applicants: Janssen Pharmaceuticals, Inc.
- Inventors: Philippe Fernandes; Mark Schmidt; Vanina Popova; Adam Savitz; Rama Melkote; Wayne C. Drevets; Srihari Gopal; Darrel Pemberton; Chakradhar Lagishetty; Iva Kezic
- Web page: https://patentgrep.com/patent/US11998524B2

## CPC

- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/24: Antidepressants
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The disclosure provides crystalline and amorphous forms of aticaprant. Also provided by the disclosure are pharmaceutical compositions comprising the amorphous or crystalline forms, methods of treating major depressive disorder using the amorphous or crystalline forms of aticaprant, amorphous or crystalline forms of aticaprant for use in the treatment of major depressive disorder in a human patient having anhedonia, uses of the amorphous or crystalline forms of aticaprant in the manufacture of a medicament for the treatment of major depressive disorder, and packages or pharmaceutical products comprising (i) amorphous or crystalline forms of aticaprant and (ii) instructions for treating major depressive disorder. In some aspects, the human patient treated as described herein has anhedonia.

## Claims

### Claim 1

A method of treating major depressive disorder in a human patient, comprising administering an effective amount of crystalline aticaprant of Form I, II, or III to the human patient, wherein the patient had a previous inadequate response to other antidepressant therapy, wherein:
crystalline Form I is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 4.6°, 17.3°, 17.4°, 18.0°, and 24.0°,
crystalline Form II is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 3.1°, 19.0°, 24.0°, 24.3°, and 26.2°,
crystalline Form III is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 4.1°, 9.0°, 17.6°, 18.0°, and 21.4°,
wherein aticaprant has the following structure:

### Claim 2 (depends on 1)

The method of claim 1, wherein the crystalline aticaprant is crystalline Form I of aticaprant that is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 4.6°, 17.3°, 17.4°, 18.0°, and 24.0°.

### Claim 3 (depends on 2)

The method of claim 2, wherein the crystalline aticaprant is crystalline Form I of aticaprant that is characterized by an x-ray powder diffraction pattern that corresponds to FIG. 6.

### Claim 4 (depends on 2)

The method of claim 2, wherein the crystalline Form I of aticaprant is characterized by a differential scanning calorimetry thermogram comprising one endotherm at about 92.9° C.

### Claim 5 (depends on 2)

The method of claim 2, wherein the crystalline Form I of aticaprant is characterized by a differential scanning calorimetry thermogram that corresponds to FIG. 7.

### Claim 6 (depends on 1)

The method of claim 1, wherein the crystalline aticaprant is a crystalline Form II of aticaprant that is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 3.1°, 19.0°, 24.0°, 24.3°, and 26.2°.

### Claim 7 (depends on 6)

The method of claim 6, wherein the crystalline Form II of aticaprant is characterized by an x-ray powder diffraction pattern that corresponds to FIG. 8.

### Claim 8 (depends on 6)

The method of claim 6, wherein the crystalline Form II of aticaprant is characterized by a differential scanning calorimetry thermogram comprising one or both endotherms at about 74.7° C. and about 96.2° C.

### Claim 9 (depends on 6)

The method of claim 6, wherein the crystalline Form II of aticaprant is characterized by a differential scanning calorimetry thermogram that corresponds to FIG. 9.

### Claim 10 (depends on 1)

The method of claim 1, wherein the crystalline aticaprant is a crystalline Form III of aticaprant that is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 4.1°, 9.0°, 17.6°, 18.0°, and 21.4°.

### Claim 11 (depends on 10)

The method of claim 10, wherein the crystalline Form III of aticaprant is characterized by an x-ray powder diffraction pattern that corresponds to FIG. 1.

### Claim 12 (depends on 10)

The method of claim 10, wherein the crystalline Form III of aticaprant is characterized by a peak temperature (Tm) at about 121° C.

### Claim 13 (depends on 10)

The method of claim 10, wherein the crystalline Form III of aticaprant is characterized by a differential scanning calorimetry thermogram that corresponds to FIG. 4.

### Claim 14 (depends on 1)

The method of claim 1, wherein the crystalline form of aticaprant is anhydrous.

### Claim 15 (depends on 1)

The method of claim 1, wherein the other antidepressant therapy is a selective serotonin reuptake inhibitor, or serotonin-norepinephrine reuptake inhibitor, or a combination thereof.

### Claim 16 (depends on 1)

The method of claim 1, further comprising adjunctive treatment with an effective amount of one or more antidepressants.

### Claim 17 (depends on 16)

The method of claim 16, wherein the one or more antidepressants is a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, or a combination thereof.

### Claim 18 (depends on 1)

The method of claim 1, wherein the effective amount of the crystalline Form I, II, or III of aticaprant is between about 2 mg and about 35 mg, between about 5 mg and about 10 mg, about 5 mg, or about 10 mg.

### Claim 19 (depends on 1)

The method of claim 1, wherein the crystalline Form I, II, or III of aticaprant is administered orally once daily.

### Claim 20 (depends on 1)

The method of claim 1, wherein the patient has anhedonia.

### Claim 21

A method of treating major depressive disorder in a human patient, comprising administering an effective amount of crystalline S-aticaprant of Form I, II, or III to the human patient, wherein the patient had a previous inadequate response to other antidepressant therapy, wherein:
crystalline Form I of S-aticaprant is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 4.6°, 17.3°, 17.4°, 18.0°, and 24.0°;
crystalline Form II of S-aticaprant is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 3.1°, 19.0°, 24.0°, 24.3°, and 26.2°; and
crystalline Form III of S-aticaprant is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 4.1°, 9.0°, 17.6°, 18.0°, and 21.4°;
wherein S-aticaprant has the following structure:

### Claim 22 (depends on 21)

The method of claim 21, wherein the crystalline S-aticaprant is crystalline Form I of S-aticaprant that is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 4.6°, 17.3º, 17.4°, 18.0°, and 24.0°.

### Claim 23 (depends on 22)

The method of claim 22, wherein the crystalline S-aticaprant is crystalline Form I of S-aticaprant that is characterized by an x-ray powder diffraction pattern that corresponds to FIG. 6.

### Claim 24 (depends on 22)

The method of claim 22, wherein the crystalline Form I of S-aticaprant is characterized by a differential scanning calorimetry thermogram comprising one endotherm at about 92.9°C.

### Claim 25 (depends on 22)

The method of claim 22, wherein the crystalline Form I of S-aticaprant is characterized by a differential scanning calorimetry thermogram that corresponds to FIG. 7.

### Claim 26 (depends on 21)

The method of claim 21, wherein the crystalline S-aticaprant is a crystalline Form II of S-aticaprant that is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 3.1°, 19.0°, 24.0°, 24.3°, and 26.2°.

### Claim 27 (depends on 26)

The method of claim 26, wherein the crystalline Form II of S-aticaprant is characterized by an x-ray powder diffraction pattern that corresponds to FIG. 8.

### Claim 28 (depends on 26)

The method of claim 26, wherein the crystalline Form II of S-aticaprant is characterized by a differential scanning calorimetry thermogram comprising one or both endotherms at about 74.7° C. and about 96.2° C.

### Claim 29 (depends on 26)

The method of claim 26, wherein the crystalline Form II of S-aticaprant is characterized by a differential scanning calorimetry thermogram that corresponds to FIG. 9.

### Claim 30 (depends on 21)

The method of claim 21, wherein the crystalline S-aticaprant is a crystalline Form III of S-aticaprant that is characterized by four or more x-ray diffraction pattern peaks at 2θ (±0.2) of 4.1°, 9.0°, 17.6°, 18.0°, and 21.4°.

### Claim 31 (depends on 30)

The method of claim 30, wherein the crystalline Form III of S-aticaprant is characterized by an x-ray powder diffraction pattern that corresponds to FIG. 1.

### Claim 32 (depends on 30)

The method of claim 30, wherein the crystalline Form III of S-aticaprant is characterized by a peak temperature (Tm) at about 121° C.

### Claim 33 (depends on 30)

The method of claim 30, wherein the crystalline Form III of S-aticaprant is characterized by a differential scanning calorimetry thermogram that corresponds to FIG. 4.

### Claim 34 (depends on 21)

The method of claim 21, wherein the crystalline form of S-aticaprant is anhydrous.

### Claim 35 (depends on 21)

The method of claim 21, wherein the other antidepressant therapy is a selective serotonin reuptake inhibitor, or serotonin-norepinephrine reuptake inhibitor, or a combination thereof.

### Claim 36 (depends on 21)

The method of claim 21, further comprising adjunctive treatment with an effective amount of one or more antidepressants.

### Claim 37 (depends on 36)

The method of claim 36, wherein the one or more antidepressants is a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, or a combination thereof.

### Claim 38 (depends on 21)

The method of claim 21, wherein the effective amount of the crystalline Form I, II, or III of S-aticaprant is between about 2 mg and about 35 mg, between about 5 mg and about 10mg, about 5 mg, or about 10 mg.

### Claim 39 (depends on 21)

The method of claim 21, wherein the crystalline Form I, II, or III of S-aticaprant is administered orally once daily.

### Claim 40 (depends on 21)

The method of claim 21, wherein the patient has anhedonia.

### Claim 41 (depends on 30)

The method of claim 30, wherein about 10 mg of the crystalline Form III is administered orally once daily.

### Claim 42 (depends on 41)

The method of claim 41, further comprising adjunctive treatment with an effective amount of one or more antidepressants.

### Claim 43 (depends on 42)

The method of claim 42, wherein the one or more antidepressants is a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, or a combination thereof.

### Claim 44 (depends on 30)

The method of claim 30, wherein the patient has anhedonia.