# US 6,719,982 B1 · Mutant herpes simplex viruses and uses thereof

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- Number: US 6,719,982 B1
- Document ID: US6719982B1
- Status: Granted
- Kind: B1
- Application number: 09/601,102
- Filed: 2001-02-20
- Granted: 2004-04-13
- Earliest claimed: 1998-01-29
- Assignees: Biovex Limited
- Inventors: Robert S. Coffin; David S. Latchman; Nicholas J. Finnie
- Web page: https://patentgrep.com/patent/US6719982B1

## CPC

- C07K 14/005: from viruses
- A61P 25/00: Drugs for disorders of the nervous system
- 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 2710/16622: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The present invention provides a herpes simplex virus strain having a functional ICP27 gene and lacking at lease a functional ICP4 gene and a functional ICP34.5 gene. It also provides the use of a herpes simplex virus strain which lacks at least a functional ICP4 gene and a functional ICP34.5 gene in the treatment of disorders of, or injuries to, the nervous system of a mammal.

## Claims

### Claim 1

A herpes simplex virus having a functional ICP27 gene and which lacks functional ICP4 and functional ICP34.5 genes, a functional vhs gene and a functional VMW65 gene due to a mutation in said VMW65 gene which abolishes its transcriptional-activation activity.

### Claim 2 (depends on 1)

A virus according to claim 1 which is selected from the group consisting of an HSV1 strain, an HSV2 strains and an intertype recombinant containing DNA from an HSV1 strain and an HSV2 strain.

### Claim 3 (depends on 2)

A virus according to claim 2 which is an HSV1 strain.

### Claim 4 (depends on 1)

A virus according to claim 1 which carries at least one heterologous gene.

### Claim 5 (depends on 4)

A virus according to claim 4 wherein said heterologous gene is operably linked to a control sequence permitting expression of said heterologous gene in mammalian cells.

### Claim 6 (depends on 5)

A virus according to claim 5 wherein said mammalian cell is a cell of the central or peripheral nervous system of a mammal.

### Claim 7 (depends on 5)

A virus according to claim 5 wherein said mammalian cell is a cell of the eye, heart or skeletal muscle of a mammal.

### Claim 8 (depends on 5)

A virus according to claim 5 wherein said gene encodes a polypeptide which is cytotoxic.

### Claim 9 (depends on 5)

A virus according to claim 5 wherein said gene encodes a polypeptide which converts a precursor prodrug into a cytotoxic compound.

### Claim 10 (depends on 5)

A virus according to claim 5 wherein the heterologous gene is selected from the group consisting of genes encoding proteins involved in the regulation of cell division, enzymes involves in metabolic pathways, transcription factors, and heat shock proteins.

### Claim 11 (depends on 5)

A composition comprising an HSV strain according to claim 5 together with a carrier or diluent.

### Claim 12 (depends on 1)

A method for studying the function of a heterologous gene in a mammalian cell, which method comprises:
(a) introducing said heterologous gene into a herpes simplex virus according to claim 1;
(b) introducing the resulting herpes simplex virus into said mammalian cell such that said heterologous gene is expressed in said cell; and
(c) determining the effect on said cell of expression of said heterologous gene in said mammalian cell to determine the function of said heterologous gene.

### Claim 13 (depends on 12)

A method according to claim 12, wherein said heterologous gene is a gene implicated in causing disease.

### Claim 14 (depends on 12)

A method according to claim 12 wherein said mammalian cell is dysfunctional in a particular cellular function, said heterologous gene is wild-type and the effect of expression of said heterologous gene is determined by an assay for said cellular function, to determine whether said gene restores said function to said mammalian cell.

### Claim 15 (depends on 12)

A method according to claim 12 wherein said mammalian cell has one or more endogenous genes inactivated by mutation.
