# US 10,765,664 B2 · Treatment of infectious diseases

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- Number: US 10,765,664 B2
- Document ID: US10765664B2
- Status: Granted
- Kind: B2
- Application number: 16/392,492
- Filed: 2019-04-23
- Published: 2019-08-15
- Granted: 2020-09-08
- Earliest claimed: 2015-01-26
- Assignees: Children's Medical Center Corporation
- Applicants: Children's Medical Center Corporation
- Inventors: Anne Goldfeld; Luke Jasenosky; Viraga Haridas; Shahin Ranjbar
- Web page: https://patentgrep.com/patent/US10765664B2

## CPC

- A61K 31/426: 1,3-Thiazoles
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/18: for HIV
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Disclosed herein are methods for treating or preventing a disease comprising administering a pharmaceutical composition comprising a therapeutically-effective amount of nitazoxanide to a subject having the disease, wherein the disease is causally linked to infection by one or more pathogens selected from the group consisting of members of the genus Ebolavirus, members of the genus Marburgvirus, members of the species dengue virus, human immunodeficiency viruses 1 and 2, and members of the species Mycobacterium tuberculosis.

## Claims

### Claim 1

A method of increasing an anti-viral response in a cell, the method consisting essentially of contacting the cell with nitazoxanide, wherein the anti-viral response is an anti-viral stress response.

### Claim 2 (depends on 1)

The method of claim 1, wherein the anti-viral response comprises an increase in the expression level of a protein in a cell selected from the group consisting of an interferon-induced transmembrane (IFITM) protein, protein kinase R (PKR), retinoic acid-inducible gene 1 (RIG-I), and growth arrest and DNA damage-inducible protein (GADD34).

### Claim 3 (depends on 2)

The method of claim 2, wherein the IFITM protein is selected from the group consisting of IFITM1, IFITM2, IFITM3, and IFITM5.

### Claim 4 (depends on 1)

The method of claim 1, wherein the anti-viral response is an increase of phosphorylation of eIF2α.

### Claim 5 (depends on 1)

The method of claim 1, wherein the contacting is in vitro.

### Claim 6 (depends on 1)

The method of claim 1, wherein the contacting is in vivo.

### Claim 7 (depends on 6)

The method of claim 6, wherein the in vivo contacting is done in a mammal.

### Claim 8 (depends on 7)

The method of claim 7, wherein the mammal is a human.

### Claim 9 (depends on 1)

The method of claim 1, wherein the nitazoxanide is the sole anti-viral therapeutic.

### Claim 10

A method of measuring an anti-viral response in a patient who has been administered nitazoxanide as a first anti-viral therapeutic, the method comprising
measuring an expression level of interferon-induced transmembrane (IFITM) protein, protein kinase R (PKR), retinoic acid-inducible gene 1 (RIG-I), and growth arrest or DNA damage-inducible protein (GADD34).

### Claim 11 (depends on 10)

The method of claim 10, further comprising administering nitazoxanide and/or a second anti-viral therapeutic.

### Claim 12

A method of measuring an anti-viral response following administration of nitazoxanide, the method comprising
a. measuring a first expression level of interferon-induced transmembrane (IFITM) protein, protein kinase R (PKR), retinoic acid-inducible gene 1 (RIG-I), and growth arrest or DNA damage-inducible protein (GADD34) in a subject;
b. administering nitazoxanide to the subject;
c. measuring a second expression level of interferon-induced transmembrane (IFITM) protein, protein kinase R (PKR), retinoic acid-inducible gene 1 (RIG-I), and growth arrest or DNA damage-inducible protein (GADD34) in a subject.

### Claim 13

A method of increasing an anti-viral response in a cell, the method consisting essentially of contacting the cell with nitazoxanide, wherein the anti-viral response comprises formation of stress granules and/or increase in cellular acidity.

### Claim 14

A method of increasing an anti-viral stress response in a cell, the method consisting essentially of contacting a cell with nitazoxanide in vivo, thereby increasing an anti-viral stress response in the cell.