# US 11,439,649 B2 · Combination therapy with apilimod and glutamatergic agents

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- Number: US 11,439,649 B2
- Document ID: US11439649B2
- Status: Granted
- Kind: B2
- Application number: 16/987,542
- Filed: 2020-08-07
- Published: 2021-03-18
- Granted: 2022-09-13
- Earliest claimed: 2018-02-21
- Assignees: AI Therapeutics, Inc.
- Applicants: AI Therapeutics, Inc.
- Inventors: Henri Lichenstein; Sean Landrette; Peter R. Young; Jonathan M. Rothberg
- Web page: https://patentgrep.com/patent/US11439649B2

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 31/428: condensed with carbocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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

Provided are compositions and methods related to the use of apilimod in combination with glutamatergic agents for treating neurological diseases and disorders, and for the treatment of cancer.

## Claims

### Claim 1

A method for treating a neurological disease or disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising apilimod, or a pharmaceutically acceptable salt thereof, in combination with an antioxidant.

### Claim 2 (depends on 1)

The method of claim 1, wherein the apilimod is apilimod dimesylate.

### Claim 3 (depends on 2)

The method of claim 2, wherein the antioxidant is edaravone.

### Claim 4 (depends on 3)

The method of claim 3, wherein the apilimod and the antioxidant are administered as part of a therapeutic regimen comprising administration of a glutamatergic agent.

### Claim 5 (depends on 4)

The method of claim 4, wherein the glutamatergic agent is selected from a glutamate transporter modulating agent and a glutamate receptor antagonist.

### Claim 6 (depends on 5)

The method of claim 5, wherein the glutamatergic agent is a glutamate transporter modulating agent selected from an excitatory amino acid reuptake inhibitor.

### Claim 7 (depends on 5)

The method of claim 5, wherein the glutamatergic agent is a glutamate receptor antagonist selected from an N-methyl-D-aspartate (NMDA) receptor antagonist.

### Claim 8 (depends on 5)

The method of claim 5, wherein the glutamatergic agent is a glutamate receptor antagonist selected from the group consisting of AP5 (R-2-amino-5-phosphonopentanoate), AP7 (2-amino-7-phosphonoheptanoic acid), CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), CPPene (3-[(R)-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid), NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione), and selfotel (CGS-19755).

### Claim 9 (depends on 5)

The method of claim 5, wherein the glutamatergic agent is a glutamate receptor antagonist selected from the group consisting of amantadine, atomoxetine, AZD6765, agmatine, gacyclidine, ketamine, memantine, eliprodil, delucemin.

### Claim 10 (depends on 5)

The method of claim 5, wherein the glutamatergic agent is selected from BHV-5000, lamotrigine, lanicemine, riluzole, trigriluzole, and topiramate.

### Claim 11 (depends on 10)

The method of claim 10, wherein the glutamatergic agent is riluzole or trigriluzole.

### Claim 12 (depends on 1)

The method of claim 1, wherein the pharmaceutical composition is an oral dosage form or a sublingual dosage form.

### Claim 13 (depends on 1)

The method of claim 1, wherein the antioxidant is administered in the same or a different dosage form as the apilimod.

### Claim 14 (depends on 1)

The method of claim 1, wherein the neurological disease or disorder is selected from Alzheimer's disease, amyotrophic lateral sclerosis (ALS), attention deficit hyperactivity disorder, autism, cerebellar ataxia, Charcot-Marie-Tooth disease, Creutzfeldt-Jakob disease, dementia, epilepsy, Friedreich's ataxia, Huntington's disease, multiple sclerosis, obsessive compulsive disorder (OCD), Parkinson's disease, Rett syndrome, senile chorea, spinal ataxia, spinal cord injury, supranuclear palsy, traumatic brain injury.

### Claim 15 (depends on 14)

The method of claim 14, wherein the neurological disease or disorder is dementia.

### Claim 16 (depends on 15)

The method of claim 15, wherein the dementia is selected from AIDS dementia complex (ADC), dementia associated with Alzheimer's disease (AD), dementia pugilistica, diffuse Lewy body disease, frontotemporal dementia, mixed dementia, senile dementia of Lewy body type, and vascular dementia.

### Claim 17 (depends on 14)

The method of claim 14, wherein the neurological disease or disorder is amyotrophic lateral sclerosis (ALS).

### Claim 18 (depends on 1)

The method of claim 1, wherein the subject is human.

### Claim 19

A method for treating amyotrophic lateral sclerosis (ALS) in a human subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising apilimod, or a pharmaceutically acceptable salt thereof, in combination with edaravone.

### Claim 20 (depends on 19)

The method of claim 19, further comprising administering to the subject a glutamatergic agent selected from riluzole or trigriluzole.

### Claim 21 (depends on 19)

The method of claim 19, wherein the apilimod is apilimod dimesylate.