# US 10,478,431 B2 · Methods for treating a cytomegalovirus infection

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- Number: US 10,478,431 B2
- Document ID: US10478431B2
- Status: Granted
- Kind: B2
- Application number: 15/527,662
- Filed: 2015-11-24
- Published: 2017-12-21
- Granted: 2019-11-19
- Earliest claimed: 2014-11-26
- Assignees: The J. David Gladstone Institutes
- Applicants: The J. David Gladstone Institutes
- Inventors: Leor S. Weinberger
- Web page: https://patentgrep.com/patent/US10478431B2

## CPC

- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A01N 1/124: Disinfecting agents, e.g. antimicrobials
- A61K 31/522: having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
- A61K 31/662: Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/7056: containing five-membered rings with nitrogen as a ring hetero atom
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/20: for DNA viruses
- 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)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure provides a method for inhibiting cytomegalovirus (CMV) replication in a cell infected with CMV, the method comprising contacting the cell with a bisbenzimidazole compound. The present disclosure provides a method of treating a CMV infection in an individual, the method comprising administering to the individual an effective amount of a bisbenzimidazole compound.

## Claims

### Claim 1

A method for inhibiting cytomegalovirus (CMV) replication in a cell infected with CMV, the method comprising contacting the cell with an effective amount of a bisbenzimidazole compound to inhibit CMV replication in the cell, wherein the bisbenzimidazole compound has the structure of formula (I)
wherein:
R is OH, —O—CH2CH3 or N(CH3)2.

### Claim 2 (depends on 1)

The method of claim 1, wherein the bisbenzimidazole compound is 2′-(4-hydroxyphenyl)-5-(4-methyl-1-piperazinyl)-2,5′-bi-1H-benzimidazole trihydrochloride hydrate.

### Claim 3 (depends on 1)

The method of claim 1, wherein the bisbenzimidazole compound has the structure of formula (II)

### Claim 4

A method of treating a cytomegalovirus (CMV) infection in an individual, the method comprising administering to the individual an effective amount of a bisbenzimidazole compound to treat the CMV infection, wherein the bisbenzimidazole compound has the structure of formula (I)
wherein:
R is OH, —O—CH2CH3 or N(CH3)2.

### Claim 5 (depends on 4)

The method of claim 4, wherein the bisbenzimidazole compound is 2′-(4-hydroxyphenyl)-5-(4-methyl-1-piperazinyl)-2,5′-bi-1H-benzimidazole trihydrochloride hydrate.

### Claim 6 (depends on 4)

The method of claim 4, wherein the bisbenzimidazole compound has the structure of formula (II)

### Claim 7 (depends on 4)

The method of claim 4, wherein the bisbenzimidazole compound is administered orally or intravenously.

### Claim 8 (depends on 4)

The method of claim 4, wherein the bisbenzimidazole compound is administered at a dose of from 5 mg/m2/day to 50 mg/m2/day.

### Claim 9 (depends on 4)

The method of claim 4, wherein the individual is a human.

### Claim 10 (depends on 4)

The method of claim 4, comprising administering at least a second therapeutic agent.

### Claim 11 (depends on 10)

The method of claim 10, wherein the second therapeutic agent is ganciclovir, foscarnet, cidofovir, maribavir, or valganciclovir.

### Claim 12 (depends on 10)

The method of claim 10, wherein the second therapeutic agent is a histone deacetylase (HDAC) inhibitor.

### Claim 13 (depends on 10)

The method of claim 10, wherein the second therapeutic agent is a transcriptional transactivator.

### Claim 14 (depends on 4)

The method of claim 4, wherein the individual is an organ transplant recipient.

### Claim 15 (depends on 4)

The method of claim 4, wherein the individual is a bone marrow transplant recipient.

### Claim 16 (depends on 4)

The method of claim 4, wherein the individual does not have a CMV infection, and is an organ transplant recipient.

### Claim 17 (depends on 4)

The method of claim 4, wherein the individual does not have a CMV infection, and is a bone marrow transplant recipient.

### Claim 18 (depends on 4)

The method of claim 4, wherein the individual is a pregnant female.

### Claim 19 (depends on 4)

The method of claim 4, wherein the individual is a neonate.

### Claim 20

A method of inhibiting cytomegalovirus (CMV) replication in an organ or tissue, the method comprising contacting the organ or tissue in vitro or ex vivo with an effective amount of a bisbenzimidazole compound to inhibit CMV replication in the organ or tissue, wherein the bisbenzimidazole compound has the structure of formula (I)
wherein:
R is OH, —O—CH2CH3 or N(CH3)2.
