# US 10,117,911 B2 · Compositions and methods to treat herpes simplex virus infections

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- Number: US 10,117,911 B2
- Document ID: US10117911B2
- Status: Granted
- Kind: B2
- Application number: 15/167,204
- Filed: 2016-05-27
- Published: 2016-12-01
- Granted: 2018-11-06
- Earliest claimed: 2015-05-29
- Assignees: Agenovir Corporation
- Applicants: Agenovir Corporation
- Inventors: Stephen R. Quake; Jianbin Wang
- Web page: https://patentgrep.com/patent/US10117911B2

## CPC

- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- C12N 9/16: acting on ester bonds (3.1)
- C12N 15/1133: {against herpetoviridae, e.g. HSV}
- C12Y 301/00: Hydrolases acting on ester bonds (3.1)
- C12N 2310/20: involving clustered regularly interspaced short palindromic repeats [CRISPR]
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

Herpes simplex virus (HSV) including herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are a persistent cause of human disease with no known cure. Guided nuclease systems target specific regions of the HSV-1 and HSV-2 genomes, disrupting the virus' nucleic acid and rendering even latent viruses incapacitated.

## Claims

### Claim 1

A composition for treatment of a herpes simplex virus (HSV) infection, the composition comprising a vector encoding:
a Cas9 endonuclease; and
a guide RNA having a portion complementary to an origin of replication S (oriS) region of HSV nucleic acid, the guide RNA capable of directing the Cas9 endonuclease to the region of HSV nucleic acid.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the composition is configured to be administered transdermally.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the composition comprises a topical solution.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the composition is packaged for delivery to a human patient.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the portion of the guide RNA complementary to the origin of replication S (oriS) region of HSV nucleic acid has no match >60% within a human genome.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the vector comprises one selected from the group consisting of: retrovirus, lentivirus, adenovirus, herpesvirus, poxvirus, alphavirus, vaccinia virus, adeno-associated viruses, a plasmid, a nanoparticle, a cationic lipid, a cationic polymer, metallic nanoparticle, a nanorod, a liposome, microbubbles, a cell-penetrating peptide, and a liposphere.

### Claim 7

A method for treating a herpes simplex virus (HSV) infection, the method comprising:
introducing into a cell of a host,
(i) a vector encoding a Cas9 endonuclease and a guide RNA having a portion complementary to an origin of replication S (oriS) region of HSV nucleic acid, or
(ii) a ribonucleoprotein that includes the Cas9 endonuclease and a guide RNA having a portion complementary to an origin of replication S (oriS) region of HSV nucleic acid, wherein the guide RNA is capable of directing the Cas9 endonuclease to the region of HSV nucleic acid.

### Claim 8 (depends on 7)

The method of claim 7, further comprising transdermally administering the vector or ribonucleoprotein to the host.

### Claim 9 (depends on 8)

The method of claim 8, wherein the transdermal administration comprises applying a topical solution comprising the vector or ribonucleoprotein.

### Claim 10 (depends on 7)

The method of claim 7, wherein the host is a living human subject and the method is performed in vivo.

### Claim 11 (depends on 7)

The method of claim 7, wherein the portion of the guide RNA complementary to the origin of replication S (oriS) region of HSV nucleic acid has no match >60% within a human genome.

### Claim 12 (depends on 7)

The method of claim 7, wherein the vector comprises one selected from the group consisting of: retrovirus, lentivirus, adenovirus, herpesvirus, poxvirus, alphavirus, vaccinia virus, adeno-associated viruses, a plasmid, a nanoparticle, a cationic lipid, a cationic polymer, metallic nanoparticle, a nanorod, a liposome, microbubbles, a cell-penetrating peptide, and a liposphere.

### Claim 13

A composition for treatment of a herpes simplex virus (HSV) infection, the composition comprising a ribonucleoprotein, wherein the ribonucleoprotein comprises:
a Cas9 endonuclease; and
a guide RNA having a portion complementary to an origin of replication S (oriS) region of HSV nucleic acid, the guide RNA capable of directing the Cas9 endonuclease to the region of HSV nucleic acid.

### Claim 14 (depends on 13)

The composition of claim 13, wherein the composition is configured to be administered transdermally.

### Claim 15 (depends on 13)

The composition of claim 13, further comprising a pharmaceutically acceptable carrier for topical application to infected tissue.

### Claim 16 (depends on 13)

The composition of claim 13, wherein the portion of the guide RNA complementary to the origin of replication S (oriS) region of HSV nucleic acid has no match >60% within a human genome.

### Claim 17

A composition for treatment of a herpes simplex virus (HSV) infection, the composition comprising:
an mRNA encoding a Cas9 endonuclease; and
a guide RNA having a portion complementary to an origin of replication S (oriS) region of HSV nucleic acid, the guide RNA capable of directing the Cas9endonuclease to the region of HSV nucleic acid.

### Claim 18 (depends on 17)

The composition of claim 17, wherein the mRNA and the guide RNA are encapsulated in or complexed with a lipid nanoparticle.

### Claim 19 (depends on 17)

The composition of claim 17, wherein the composition comprises a topical solution.

### Claim 20 (depends on 17)

The composition of claim 17, wherein the portion of the guide RNA complementary to the origin of replication S (oriS) region of HSV nucleic acid has no match >60% within a human genome.

### Claim 21 (depends on 17)

The composition of claim 17, wherein the mRNA and the guide RNA are encapsulated in or complexed with a lipid nanoparticle.
