# US 12,599,585 B2 · Use of [(1R)-1-(2-chlorophenyl)-2-(tetrazol-2-yl)ethyl] carbamate in combination therapy

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- Number: US 12,599,585 B2
- Document ID: US12599585B2
- Status: Granted
- Kind: B2
- Application number: 18/134,203
- Filed: 2023-04-13
- Published: 2023-09-21
- Granted: 2026-04-14
- Earliest claimed: 2018-03-21
- Assignees: SK Biopharmaceuticals Co., Ltd.
- Applicants: SK Biopharmaceuticals Co., Ltd.
- Inventors: Marc Kamin; Laurent Vernillet
- Web page: https://patentgrep.com/patent/US12599585B2

## CPC

- A61K 31/41: having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K 31/4166: having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
- A61K 31/515: Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
- A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495})
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- 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

## Abstract

The present disclosure provides combination therapy using [(1R)-1-(2-chlorophenyl)-2-(tetrazol-2-yl)ethyl] carbamate (cenobamate) and one or more antiepileptic drugs for the prevention or treatment of a neurological disorder such as epilepsy.

## Claims

### Claim 1

A method for treating a patient who is suffering from epilepsy with co-administering a therapeutically effective amount of (i) [(1R)-1-(2-chlorophenyl)-2-(tetrazol-2-ylethyl] carbamate (cenobamate) or a pharmaceutically acceptable salt thereof and (ii) one or two antiepileptic drugs, said method comprising:
modifying the therapeutically effective amount of the antiepileptic drug to adjust AUC of the antiepileptic drug obtained after the co-administration having at least 5% difference to the level of AUC obtained after the administration of antiepileptic drug to the patient without cenobamate or a pharmaceutically acceptable salt thereof,
wherein the antiepileptic drug is selected from the group consisting of phenobarbital and phenytoin, and
wherein the therapeutically effective amount of cenobamate is achieved by the following titration method:
(1) administering cenobamate to the patient about 12.5 mg once daily for about two weeks;
(2) then administering cenobamate to the patient about 25 mg once daily for two weeks;
(3) then administering cenobamate to the patient about 50 mg once daily for about two weeks; and
(4) then increasing the dose in about bi-weekly increments by no more than about 50 mg once daily to a therapeutically effective amount.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the therapeutically effective amount of cenobamate is achieved by the following titration method:
(1) administering cenobamate to the patient about 12.5 mg once daily for weeks 1 and 2;
(2) then administering cenobamate to the patient about 25 mg once daily for weeks 3 and 4;
(3) then administering cenobamate to the patient about 50 mg once daily for weeks 5 and 6;
(4) then administering cenobamate to the patient about 100 mg once daily for weeks 7 and 8;
(5) then optionally administering cenobamate to the patient about 150 mg once daily for weeks 9 and 10; and
(6) then optionally administering cenobamate to the patient about 200 mg once daily for week 11 and thereafter.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the therapeutically effective amount of cenobamate is achieved by the following titration method:
(1) administering cenobamate to the patient about 12.5 mg once daily for weeks 1 and 2;
(2) then administering cenobamate to the patient about 25 mg once daily for weeks 3 and 4;
(3) then administering cenobamate to the patient about 50 mg once daily for weeks 5 and 6;
(4) then administering cenobamate to the patient about 100 mg once daily for weeks 7 and 8;
(5) then administering cenobamate to the patient about 150 mg once daily for weeks 9 and 10; and
(6) then administering cenobamate to the patient about 200 mg once daily for week 11 and thereafter.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the therapeutically effective amount of cenobamate is achieved by the following titration method:
(1) administering cenobamate to the patient about 50 mg once daily for about two weeks; and
(2) then increasing the dose in about bi-weekly increments by about 50 mg once daily to about 200 mg/day once daily,
wherein cenobamate is administered for about 6 weeks and the therapeutically effective amount of cenobamate is about 200 mg/day.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the therapeutically effective amount of cenobamate is achieved by the following titration method:
(1) administering cenobamate to the patient about 50 mg once daily which is increased with 50 mg once daily per week to about 100 mg/day;
(2) optionally increasing the dose in about weekly increments by about 50 mg once daily per week to about 200 mg/day; and
(3) optionally increasing the dose in about weekly increments by about 100 mg/day per week to about 400 mg/day,
wherein cenobamate is administered for about 2 weeks, 4 weeks, or 6 weeks depending on therapeutically effective amount of cenobamate which is required and the therapeutically effective amount of cenobamate is about 100 mg/day, about 200 mg/day or about 400 mg/day.