# US 10,441,563 B2 · A19-144, A2-73 and certain anticholinesterase inhibitor compositions and method for anti-seizure therapy

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- Number: US 10,441,563 B2
- Document ID: US10441563B2
- Status: Granted
- Kind: B2
- Application number: 15/571,877
- Filed: 2015-10-19
- Published: 2018-06-28
- Granted: 2019-10-15
- Earliest claimed: 2014-10-20
- Assignees: Anavex Life Sciences Corp.
- Applicants: Anavex Life Sciences Corp.
- Inventors: Missling U. Christopher; Durrant Cameron
- Web page: https://patentgrep.com/patent/US10441563B2

## CPC

- A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K 31/27: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
- A61K 31/4015: having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/08: Antiepileptics; Anticonvulsants
- C07D 307/14: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

This invention concerns a dosage form comprising a therapeutically effective amount of A19-144 or A2-73 and a therapeutically effective amount of at least one AED. This invention further encompasses a method of treating a subject in need of such treatment comprising administering a therapeutically effective amount of A19-144 or A2-73 in conjunction with an therapeutically effective amount of an AED.

## Claims

### Claim 1

A dosage form comprising a therapeutically effective amount of an anti-seizure drug selected from A19-144 and a combination of A19-144 and A2-73, and a sub-MED amount of at least one anti-epilepsy drug (AED), wherein the sub-MED dose and the at least one AED are selected from the group consisting of:
less than about 8 mg/day of acetazolamide; less than about 1.5 mg/day of Clonazepam for an adult, less than about 0.01 mg/kg/day of Clonezepam for a child up to 10 years of age or 30 kg of body weight;
less than about 30 (mg) of Clorazepate; less than about 0.1 mg/kg of Lorazepam;
less than about 0.2 mg/kg of Midazolam; less than about 7.5 mg/day of Carbamazepine;
less than about 0.2 mg/kg of Diazepam;
less than about 30 mg/day of Chlordiazepoxide;
less than about 5 mg/day for body weight 30 kg or less, and less than about 10 mg/day for body weight 30 kg or more, of Clobazam;
less than about 5 mg/kg/day of Hydrocortisone;
less than about 800 mg/day of Eslicarbazepine/Eslicarbazepine acetate;
less than about 250 mg daily every 4-7 days of Ethosuximide; less than about 2 g daily of Ethotoin;
less than about 1200 mg/day for adults, for children 2-14 yrs, less than about 15 mg/kg/day of Felbamate;
less than about 50 mg twice daily of Lacosamide;
less than about 25 mg/day of Lamotrigine;
less than about 1000 mg/day of Levetiracetam;
less than about 200 mg/day of Mephyntoin;
less than about 400 mg/day of Mephobarbitol;
less than about 250 mg daily every 4-7 days of Methsuxamide;
less than about 600 mg/day of Oxcarbazepine;
less than about 150 mg/day of Paramethadione;
less than about 2 mg/day of Perampanel (Fycompa);
less than about 500 milligrams three times a day of Phenacemide;
establish a serum level of less than about 10 μg/mL of Phenobarbital;
less than about 0.5 g b.i.d of Phensuxamide;
less than about 100 mg a day of Phenytoin;
less than about 75 mg 2 times a day of Pregabalin;
a dose of less than about 10 mg/kg/day of Primidone;
daily dose of less than about 2100 mg of Progabide;
less than about 400 mg/day of Rufinamide;
less than about 250 mg twice a day of Stiripentol;
less than about 100 mg/day of Sulthiame;
less than about 4 mg/day of Tiagabine;
less than about 25 mg/day of Topiramate; less than about 900 mg/day of Tremethadione;
less than about 10 mg/kg of Valproate;
less than about 50 mg/kg/day of Vigabatrin and, less than about 100 mg once a day of Zonisamide.

### Claim 2 (depends on 1)

The dosage form of claim 1 wherein the therapeutically effective amount of A19-144 or of A19-144 and A2-73 in combination is from about 0.01 to about 100 mg/daily.

### Claim 3 (depends on 1)

The dosage form of claim 1 wherein said dosage form is a unit dosage form.

### Claim 4

A method of treating seizures in a subject in need of such treatment comprising administering an therapeutically effective amount of A19-144 or a combination of A19-144 and A2-73 in conjunction with a sub-MED amount of an AED, wherein the sub-MED dose and the at least one AED are selected from the group consisting of:
less than about 8 mg/day of acetazolamide; less than about 1.5 mg/day of Clonazepam for an adult, less than about 0.01 mg/kg/day of Clonezepam for a child up to 10 years of age or 30 kg of body weight;
less than about 30 (mg) of Clorazepate; less than about 0.1 mg/kg of Lorazepam;
less than about 0.2 mg/kg of Midazolam; less than about 7.5 mg/day of Carbamazepine;
less than about 0.2 mg/kg of Diazepam;
less than about 30 mg/day of Chlordiazepoxide;
less than about 5 mg/day for body weight 30 kg or less, and less than about 10 mg/day for body weight 30 kg or more, of Clobazam;
less than about 5 mg/kg/day of Hydrocortisone;
less than about 800 mg/day of Eslicarbazepine/Eslicarbazepine acetate;
less than about 250 mg daily every 4-7 days of Ethosuximide; less than about 2 g daily of Ethotoin;
less than about 1200 mg/day for adults, for children 2-14 yrs, less than about 15mg/kg/day of Felbamate;
less than about 50 mg twice daily of Lacosamide;
less than about 25 mg/day of Lamotrigine;
less than about 1000 mg/day of Levetiracetam;
less than about 200 mg/day of Mephyntoin;
less than about 400 mg/day of Mephobarbitol;
less than about 250 mg daily every 4-7 days of Methsuxamide;
less than about 600 mg/day of Oxcarbazepine;
less than about 150 mg/day of Paramethadione;
less than about 2 mg/day of Perampanel (Fycompa);
less than about 500 milligrams three times a day of Phenacemide;
establish a serum level of less than about 10 μg/mL of Phenobarbital;
less than about 0.5 g b.i.d of Phensuxamide;
less than about 100 mg a day of Phenytoin;
less than about 75 mg 2 times a day of Pregabalin;
a dose of less than about 10 mg/kg/day of Primidone;
daily dose of less than about 2100 mg of Progabide;
less than about 400 mg/day of Rufinamide;
less than about 250 mg twice a day of Stiripentol;
less than about 100 mg/day of Sulthiame;
less than about 4 mg/day of Tiagabine;
less than about 25 mg/day of Topiramate; less than about 900 mg/day of Tremethadione;
less than about 10 mg/kg of Valproate;
less than about 50 mg/kg/day of Vigabatrin and, less than about 100 mg once a day of Zonisamide.

### Claim 5 (depends on 4)

The method of claim 4 wherein said administering of A19-144 or the combination of A19-144 and A2-73 in conjunction with a sub-MED amount of an AED is co-timely.

### Claim 6 (depends on 4)

The method of claim 4 wherein said administering of A19-144 or the combination of A19-144 and A2-73 in conjunction with a sub-MED amount of an AED is coordinated.