# US 9,872,865 B2 · Compositions for improving cell viability and methods of use thereof

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- Number: US 9,872,865 B2
- Document ID: US9872865B2
- Status: Granted
- Kind: B2
- Application number: 14/140,083
- Filed: 2013-12-24
- Published: 2014-09-25
- Granted: 2018-01-23
- Earliest claimed: 2013-03-24
- Assignees: Amylyx Pharmaceuticals Inc.
- Applicants: Amylyx Pharmaceuticals Inc.
- Inventors: Joshua Cohen; Justin Klee
- Web page: https://patentgrep.com/patent/US9872865B2

## CPC

- A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- 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

This invention relates to methods and compositions for use improving cell viability, particularly neural cell viability, and more particularly to methods and compositions for use improving cell viability by reducing reactive oxygen metabolite-mediated oxidative damage in a cell, regulating redox homeostasis in a cell, or reducing mitochondrial dysfunction in a cell. The invention further relates to the administration of the bile acid tauroursodeoxycholic acid (TUDCA) in combination with phenylbutyric Acid (PBA) to improve cell viability, and treat at least one symptom associated with, prevent the time of onset of, or slow the development of a disease related to oxidative stress.

## Claims

### Claim 1

A method of treating a neurodegenerative disease, the method comprising administering to a subject
about 10 mg/kg to about 50 mg/kg of body weight of tauroursodeoxycholic acid (TUDCA), or a pharmaceutically acceptable salt thereof; and
about 10 mg/kg to about 400 mg/kg of body weight of 4-phenylbutyric acid (4-PBA), or a pharmaceutically acceptable salt thereof,
wherein the TUDCA and 4-PBA are administered in an amount sufficient to treat the neurodegenerative disease.

### Claim 2 (depends on 1)

The method of claim 1, wherein in the subject is a mammal.

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

The method of claim 1, wherein the neurodegenerative disease is selected from the group consisting of Multiple Sclerosis (MS), Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), stroke, Pick's Disease, Multi-Infarct Dementia, Creutzfeldt-Jakob's Disease, Dementia with Lewy bodies, Mixed dementia and Frontotemporal dementia.

### Claim 5 (depends on 1)

The method of claim 1, comprising administering to a subject about 10 mg/kg to about 30 mg/kg of body weight of tauroursodeoxycholic acid (TUDCA).

### Claim 6 (depends on 1)

The method of claim 1, comprising administering to a subject about 10 mg/kg to about 100 mg/kg of body weight 4-PBA.

### Claim 7 (depends on 1)

The method of claim 1, comprising administering to a subject about 30 mg/kg to about 100 mg/kg of body weight 4-PBA.

### Claim 8 (depends on 1)

The method of claim 1, wherein the tauroursodeoxycholic acid (TUDCA) and 4-PBA are administered separately.

### Claim 9 (depends on 1)

The method of claim 1, wherein the tauroursodeoxycholic acid (TUDCA) and 4-PBA are administered once a day, twice a day, or three times a day.

### Claim 10 (depends on 1)

The method of claim 1, wherein the neurodegenerative disease is caused by oxidative stress or mitochondrial dysfunction.

### Claim 11 (depends on 1)

The method of claim 1, wherein the TUDCA and 4-PBA are administered in an amount sufficient to reduce reactive oxygen metabolite-mediated oxidative damage in a cell of the subject.

### Claim 12 (depends on 11)

The method of claim 11, wherein the reactive oxygen metabolite-mediated oxidative damage is hydrogen peroxide (H2O2) mediated damage.

### Claim 13 (depends on 1)

The method of claim 1, wherein the TUDCA and 4-PBA are administered in an amount sufficient to promote redox homeostasis in a cell of the subject.

### Claim 14 (depends on 1)

The method of claim 1, wherein the TUDCA and 4-PBA are administered in an amount sufficient to reduce mitochondrial dysfunction in a cell of the subject.