# US 10,864,210 B2 · Composition and combined medication method for treating enterovirus infection

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- Number: US 10,864,210 B2
- Document ID: US10864210B2
- Status: Granted
- Kind: B2
- Application number: 16/073,487
- Filed: 2017-01-11
- Published: 2019-01-31
- Granted: 2020-12-15
- Earliest claimed: 2016-01-29
- Assignees: Institut Pasteur of Shanghai, Chinese Academy of Sciences
- Applicants: Institut Pasteur of Shanghai, Chinese Academy of Sciences
- Inventors: Gang Zou; Ralf Altmeyer; Yizhuo Wang
- Web page: https://patentgrep.com/patent/US10864210B2

## CPC

- A61K 31/4965: Non-condensed pyrazines
- A61K 31/185: Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327)
- A61K 31/422: not condensed and containing further heterocyclic rings
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/14: for RNA viruses
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- G01N 33/56983: {Viruses}
- C12N 2770/00021: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- G01N 2333/085: Picornaviridae, e.g. coxsackie virus, echovirus, enterovirus
- G01N 2500/04: Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention provides a composition and a combined medication method for treating an enterovirus infection. In particular, the present invention provides a composition for inhibiting enteroviruses, wherein the composition at least contains an inhibitor of a 3D virus protein and an inhibitor of a capsid protein, or a combination of an inhibitor of a 3C protein and an inhibitor of a 3A protein.

## Claims

### Claim 1

A composition for inhibiting enterovirus, wherein the composition includes a first active ingredient and a second active ingredient,
wherein the first active ingredient is an inhibitor of 3C protein of enterovirus (eg, EV71);
the second active ingredient is an inhibitor of 3A protein of enterovirus (eg, EV71);
wherein the inhibitor of 3C protein of enterovirus (eg, EV71) is rupintrivir, an analog thereof, or a pharmaceutically acceptable salt thereof; and
the inhibitor of 3A protein of enterovirus (eg, EV71) is itraconazole, an analog thereof, or a pharmaceutically acceptable salt thereof, and
wherein a molar ratio of the first active ingredient to the second active ingredient is about 1-20:10-100.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the first active ingredient specifically binds to an amino acid residue at position 121 of 3D protein of enterovirus, wherein the amino acid residue is numbered based on SEQ ID NO: 1.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the analog of rupintrivir includes a substance which acts on the same target of enterovirus as rupintrivir (eg, AG7404); and/or
the analog of itraconazole includes a substance which acts on the same target of enterovirus as itraconazole.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the molar ratio of the first active ingredient to the second active ingredient is about 1-10:10-100.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the molar ratio of the first active ingredient to the second active ingredient is 1-5:10-100.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the dosage form of the pharmaceutical composition is a tablet, granule, capsule, pill, injection, or oral solution.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the composition is a unit dosage form, and the content of the first active ingredient and the second active ingredient in each unit dosage form is 0.1-1 of a daily dose, wherein the daily dose is 20-100 mg.

### Claim 8 (depends on 2)

The composition of claim 2, wherein the amino acid residue is a serine residue.