# US 2026/0091069 A1 · Transcriptional and translational dual regulated oncolytic herpes simplex virus vectors

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- Number: US 2026/0091069 A1
- Document ID: US20260091069A1
- Status: Published application
- Kind: A1
- Application number: 18/283,654
- Filed: 2022-03-24
- Published: 2026-04-02
- Earliest claimed: 2021-03-24
- Assignees: Virogin Biotech Canada Ltd
- Applicants: Virogin Biotech Canada Ltd
- Inventors: William Wei-Guo Jia; Dmitry V. Chouljenko; I-Fang Lee; Yanal M. Murad; Xiaohu Liu; Guoyu Liu; Xuexian Bu; Zahid Delwar; Jun Ding
- Web page: https://patentgrep.com/patent/US20260091069A1

## CPC

- A61K 35/763: Herpes virus
- A61K 38/208: {IL-12}
- A61K 38/2086: {IL-13 to IL-16}
- A61P 35/00: Antineoplastic agents
- C07K 14/5434: {IL-12}
- C07K 14/5443: {IL-15}
- C07K 14/7155: {for interleukins [IL]}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/86: Viral vectors
- C12N 2710/16032: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2710/16071: Demonstrated in vivo effect
- C12N 2710/16632: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2710/16643: viral genome or elements thereof as genetic vector
- C12N 2710/16662: by genetic engineering
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A herpes virus vector is provided with both transcriptional and translational control. Within various embodiments the herpes virus vector is based upon a modified herpes virus and has both ICP27 and ICP34.5 under control of a CEA promoter and miRNA-124/143, respectively, and deletion of at least one copy of terminal repeat long region is provided to increase safety without sacrificing efficacy. The herpes virus vector can also incorporate a virus-expressed cytokine cassette encoding IL-12, IL-15/IL-15RA under the control of CXCR4 promoter.

## Claims

### Claim 1

A recombinant herpes virus comprising a modified oncolytic herpes virus genome, wherein the modified herpes virus genome comprises at least one miRNA target sequence operably linked to a first copy of an ICP34.5 gene, and a second copy of the ICP34.5 gene comprises an inactivating mutation, wherein the mutation is deletion of at least one terminal repeat long region of the viral genome.

### Claim 2

(canceled)

### Claim 3 (depends on 1)

The recombinant herpes virus of claim 1, wherein the herpes virus is a herpes simplex virus, and further comprising from two to ten miRNA target sequences operably linked to the first copy of the ICP34.5 gene, wherein the miRNA target sequences are inserted into a 3′ untranslated region of the first copy of the ICP34.5 gene.

### Claim 4

(canceled)

### Claim 5 (depends on 3)

The recombinant herpes simplex virus of claim 3, wherein the from two to ten miRNA target sequences bind at least two different miRNAs, wherein the miRNA target sequence targets an miRNA selected from the group consisting of miR-124, miR-124*, and miR-143.

### Claim 6

(canceled)

### Claim 7 (depends on 1)

The recombinant herpes virus of claim 1, wherein the herpes virus is herpes simplex virus and the modified herpes virus genome comprises additional mutations or modifications in viral genes ICP4 and/or ICP27.

### Claim 8 (depends on 1)

The recombinant herpes virus of claim 1, wherein said virus is modified by replacing a native viral promoter with a tumor specific promoter.

### Claim 9 (depends on 1)

The recombinant herpes virus of claim 1, wherein the herpes virus is a herpes simplex virus and the modification is replacement of the entire promoter-regulatory region of ICP 4 or ICP27 with a tumor specific promoter.

### Claim 10 (depends on 9)

The recombinant herpes simplex virus of claim 9, wherein the ICP27 promoter is replaced with a hCEA promoter.

### Claim 11 (depends on 1)

The recombinant herpes virus of claim 1, further comprising at least one nucleic acid encoding a non-viral protein selected from the group consisting of immunostimulatory factors, antibodies, and checkpoint blocking peptides, wherein the at least one nucleic acid is operably linked to a generic or a tumor-specific promoter.

### Claim 12 (depends on 11)

The recombinant herpes virus of claim 11, wherein the non-viral protein is selected from the group consisting of IL12, IL15, IL15 receptor alpha subunit.

### Claim 13 (depends on 12)

The recombinant herpes virus of claim 12, wherein the tumor-specific promoter is CXCR4 promoter.

### Claim 14 (depends on 1)

The recombinant herpes virus of claim 1, wherein the herpes virus is herpes simplex virus, and further comprising a nucleic acid sequence encoding a fusogenic form of glycoprotein B, wherein the glycoprotein B can be truncated with a deletion occurring after amino acid 876.

### Claim 15

(canceled)

### Claim 16 (depends on 1)

The recombinant herpes virus of claim 1, wherein the oncolytic herpes virus is HSV-1.

### Claim 17 (depends on 1)

A method for inhibiting tumor cells, comprising providing a therapeutically effective amount of recombinant herpes virus according to claim 1.

### Claim 18 (depends on 1)

A therapeutic composition comprising the recombinant herpes virus according to claim 1 and a pharmaceutically acceptable carrier.

### Claim 19 (depends on 18)

A method for treating cancer in a subject suffering therefrom, comprising the step of administering a therapeutically effective amount of the composition of claim 18.

### Claim 20 (depends on 19)

The method according to claim 19 wherein said cancer expresses a high level of a biomarker.

### Claim 21 (depends on 19)

The method according to claim 19 wherein said cancer is selected from the group consisting of cancers of the cervix, esophagus, lung, colorectum, liver, stomach, cholangiocarcinoma and pancreas.

### Claim 22 (depends on 19)

The method according to claim 19 wherein said cancer is a leukemia or a lymphoma.

### Claim 23 (depends on 22)

The method according to claim 22 wherein said cancer is an acute myeloid leukemia (AML) or a B cell lymphoma.

### Claim 24 (depends on 19)

The method according to claim 19 wherein said step of administering a therapeutically effective amount of the composition comprises intravenous (i.v.) or intratumoral administration.