# US 2019/0169253 A1 · Oncolytic herpes simplex virus vectors expressing immune system-stimulatory molecules

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- Number: US 2019/0169253 A1
- Document ID: US20190169253A1
- Status: Published application
- Kind: A1
- Application number: 16/322,903
- Filed: 2017-08-01
- Published: 2019-06-06
- Earliest claimed: 2016-08-01
- Assignees: Virogin Biotech Canada Ltd
- Applicants: Virogin Biotech Canada Ltd
- Inventors: William Jia; Guoyu Liu; Erica Lee; Dmitry Chouljenko; Jun Ding
- Web page: https://patentgrep.com/patent/US20190169253A1

## CPC

- C07K 14/5443: {IL-15}
- A61K 35/763: Herpes virus
- A61P 35/00: Antineoplastic agents
- C07K 14/035: Herpes simplex virus I or II
- C07K 14/5434: {IL-12}
- C07K 14/7155: {for interleukins [IL]}
- C12N 15/00: Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor (mutants or genetically engineered microorganisms, per se C12N1/00, C12N5/00, C12N7/00; new plants per se A01H; plant reproduction by tissue culture techniques A01H4/00; new animals per se A01K67/00; use of medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases, gene therapy A61K48/00)
- C12N 15/625: {containing a sequence coding for a signal sequence}
- C12N 15/85: for animal cells
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C12N 15/8695: {Herpes simplex virus-based vectors}
- 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
- 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)
- 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)

## Abstract

An HSV vector comprising an expression cassette for one or more of IL12, IL15, and hIL15Receptor alpha subunit is provided.

## Claims

### Claim 1

An HSV vector comprising an expression cassette for one or more of IL12, IL15, and IL15Receptor alpha subunit.

### Claim 2 (depends on 1)

The HSV vector of claim 1, wherein nucleic acid sequence encoding a self-cleaving 2A peptide is located in-frame between coding sequences for IL12, IL15, and/or an IL15Receptor alpha subunit.

### Claim 3 (depends on 2)

The HSV vector of claim 2, wherein the nucleic acid sequence encodes a self-cleaving 2A peptide selected from the group consisting of VKQTLNFDLLKLAGDVESNPGP, QCTNYALLKLAGDVESNPGP, ATNF-SLLKQAGDVEENPGP, HYAGYFADLLIHDIETNPGP, GIFN-AHYAGYFADLLIHDIETNPGP, KAVRGYHADYYKQRLIHDVEMNPGP, GATNF-SLLKLAGDVELNPGP, EGRGSLLTCGDVEENPGP, AARQMLLLLSGDVETNPGP, FLRKRTQLLMSGDVESNPGP, GSWTDILLLLSGDVETNPGP, TRAEUEDELIRAGIESNPGP, AKFQIDKILISGDVELNPGP, SKFQIDKILISGDIELNPGP, SSIIRTKMLVSGDVEENPGP and CDAQRQKLLLSGDIEQNPGP.

### Claim 4 (depends on 1)

The HSV vector of claim 1, wherein one or more IRES sequences is located between the coding sequences for IL12, IL15, and/or an IL15Receptor alpha subunit.

### Claim 5

(canceled)

### Claim 6 (depends on 1)

The HSV vector of claim 1, wherein one or more of IL12, IL15 and an IL15Receptor alpha subunit are expressed by a bi-directional promoter.

### Claim 7

(canceled)

### Claim 8

(canceled)

### Claim 9 (depends on 1)

The HSV vector of claim 1, wherein the hIL15Receptor alpha subunit is selected from the group consisting of variant 1, variant 2, variant 3 and variant 4.

### Claim 10 (depends on 1)

The HSV vector of claim 1, which expresses IL-12, IL-15 and a PD-L1 blocking peptide.

### Claim 11 (depends on 10)

The HSV vector of claim 10, further comprising sequence encoding a peptide linker between multiple PD-L1 blocking peptides.

### Claim 12

(canceled)

### Claim 13 (depends on 10)

The HSV vector of claim 10, further comprising sequence encoding an Fc domain linked to the 3′-end of the PD-L1 blocking peptide.

### Claim 14 (depends on 1)

The HSV vector of claim 1, where an expression cassette is inserted either in an internal repeat region, a terminal repeat region, between the US1 and US2 genes, the UL3 and UL4 viral genes, or the UL50 and UL51 genes.

### Claim 15

(canceled)

### Claim 16 (depends on 1)

The HSV vector of claim 1, further comprising an NFkB and an OCT4/SOX2 enhancing element in ICP4 or ICP27 regulatory regions.

### Claim 17 (depends on 1)

The HSV vector of claim 1, wherein the ICP34.5 genes are deleted.

### Claim 18

(canceled)

### Claim 19 (depends on 1)

The HSV vector of claim 1, wherein the expression cassette comprises a CMV promoter or an EF-1alpha promoter.

### Claim 20

(canceled)

### Claim 21 (depends on 1)

The HSV vector of claim 1, wherein the HSV is either HSV-1 or HSV-2.

### Claim 22 (depends on 1)

The HSV vector of claim 1, wherein the ICP34.5 gene is regulated by a 3′UTR containing target sequences of miRNAs that are under-expressed in tumor cells.

### Claim 23 (depends on 1)

A pharmaceutical composition, comprising a HSV vector according to claim 1, and a pharmaceutically acceptable carrier.

### Claim 24 (depends on 1, 23)

A method of treating cancer, comprising administering to a patient a HSV vector according to claim 1, or a pharmaceutical composition according to claim 23.

### Claim 25 (depends on 24)

The method according to claim 24 wherein said cancer is selected from the group consisting of carcinomas, leukemia's, lymphomas, myelomas and sarcomas.