# US 12,589,083 B2 · Abuse-deterrent dosage forms containing esketamine

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- Number: US 12,589,083 B2
- Document ID: US12589083B2
- Status: Granted
- Kind: B2
- Application number: 17/523,193
- Filed: 2021-11-10
- Published: 2022-03-03
- Granted: 2026-03-31
- Earliest claimed: 2019-05-07
- Assignees: Clexio Biosciences Ltd.
- Applicants: Clexio Biosciences Ltd.
- Inventors: Derek Moe; Randal Seburg; Sagar Rane
- Web page: https://patentgrep.com/patent/US12589083B2

## CPC

- A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2081: {with microcapsules or coated microparticles according to A61K9/50}
- A61K 9/2095: {Tabletting processes}
- A61P 25/00: Drugs for disorders of the nervous system
- A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5078: {with drug-free core}
- G01N 2030/027: {Liquid chromatography}
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Disclosed herein are immediate release oral dosage forms that contain abuse-deterrent and abuse-resistant features. In particular, the disclosed dosage forms can provide deterrence of abuse by ingestion of multiple individual doses. The disclosed dosage forms can likewise provide protection from overdose in the event of accidental or intentional ingestion of multiple individual doses. The dosage forms may also exhibit abuse resistant properties when physically manipulated, and also when physically manipulated and then administered in a manner not consistent with oral dosing. The dosage forms may also exhibit abuse resistant properties when administered in a manner intended to result in administration of the esketamine in a higher than therapeutic dose.

## Claims

### Claim 1

A method of treating depression comprising orally administering to a subject in need thereof, an immediate release tablet comprising esketamine or a pharmaceutically acceptable salt thereof, sodium bicarbonate in an amount of no more than 2.2 wt % and 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one in an amount that is no more than 5.5 wt % after storage in accelerated conditions for at least 6 months.

### Claim 2 (depends on 1)

The method of claim 1, wherein the immediate release tablet comprises between 5 and 100 mg of esketamine or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the immediate release tablet comprises 40 mg base equivalent of esketamine.

### Claim 4 (depends on 1)

The method of claim 1, wherein the immediate release tablet comprises between 20 mg and 100 mg of esketamine.

### Claim 5 (depends on 4)

The method of claim 4, wherein prior to the administration, the immediate release tablet has been exposed to a storage period of six months;
after the storage period, the area under a peak corresponding to 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one present in the tablet is measured by high performance liquid chromatography (HPLC); and
the total amount of 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one present in the tablet is determined to be no more than 5.5 wt. %;
wherein the peak corresponding to 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one appears at a relative retention time of about 1.3 minutes when using C18, 100×3.0 mm, 3.5 μm HPLC column at a temperature of 45° C. and a sample temperature of 4° C., with a mobile phase comprising 0.050% trifluoroacetic acid (TFA) in water and 0.0025% TFA in acetonitrile and UV detection at 215 nm.

### Claim 6 (depends on 5)

The method of claim 5, wherein the tablet is exposed to 40° C.±2° C. and 75%±5% relative humidity for the six month storage period.

### Claim 7 (depends on 5)

The method of claim 5, wherein the tablet comprises 40-60 mg of esketamine.

### Claim 8 (depends on 5)

The method of claim 5, wherein the tablet comprises 60 mg of esketamine.

### Claim 9 (depends on 5)

The method of claim 5, wherein the 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one is measured in an amount of no more than 0.2 wt % after the storage period.

### Claim 10 (depends on 5)

The method of claim 5, wherein the 2-(2-chlorophenyl)-2-(methylamino)-6-methylidenecyclohexan-1-one is measured in a non-detectable amount after the storage period.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the immediate release tablet comprises sodium bicarbonate in an amount of no more than 2 wt %.