# US 2019/0167784 A1 · Recombinant virus with diminished latency and methods of using same

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- Number: US 2019/0167784 A1
- Document ID: US20190167784A1
- Status: Published application
- Kind: A1
- Application number: 16/195,247
- Filed: 2018-11-19
- Published: 2019-06-06
- Earliest claimed: 2006-11-09
- Assignees: The U.S.A., as represented by the Secretary, Department of Health and Human Services
- Applicants: The U.S.A., as represented by the Secretary, Department of Health and Human Services
- Inventors: Jeffrey I. Cohen; Lesley Pesnicak
- Web page: https://patentgrep.com/patent/US20190167784A1

## CPC

- A61K 39/25: Varicella-zoster virus
- A61K 39/12: Viral antigens
- A61K 39/245: Herpetoviridae, e.g. herpes simplex virus
- C07K 14/005: from viruses
- 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
- A61K 2039/5254: {avirulent or attenuated}
- C12N 2710/16022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2710/16722: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2710/16734: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2710/16743: viral genome or elements thereof as genetic vector
- C12N 2710/16761: Methods of inactivation or attenuation
- 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)
- 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

The disclosure provides recombinant herpes virus with diminished latency. In embodiments, the recombinant herpes virus comprises a latency gene or transcript linked to an altered or heterologous promoter. The disclosure also provides compositions and methods for inducing immunity in animals using the recombinant herpes viruses.

## Claims

### Claim 1

A method for making an attenuated live virus having an impaired ability to establish latency, comprising:
introducing a recombinant virus comprising all or a portion of a herpes virus genome into a host cell to produce an amount of the virus suitable for a vaccine, wherein the genome comprises a promoter for a latency gene or transcript that is altered or modified; and
recovering the virus from the host cell.

### Claim 2 (depends on 1)

The method of claim 1, wherein the herpes virus is selected from the group consisting of herpes simplex virus, varicella-zoster virus (VZV), Marek's disease virus, pseudorabies virus and cytomegalovirus.

### Claim 3 (depends on 1)

The method of claim 1, wherein the promoter for the latency gene or transcript is replaced by a heterologous promoter.

### Claim 4 (depends on 1)

The method of claim 1, wherein the genome comprises a deletion in a latency gene or transcript at its native location, and the latency gene or transcript is located at a different location in the viral genome and is expressed from a heterologous promoter.

### Claim 5 (depends on 1)

The method of claim 1, wherein the latency gene is a VZV gene selected from the group consisting of ORF4, ORF21, ORF29, ORF62, ORF63 and ORF66.

### Claim 6 (depends on 5)

The method of claim 5, wherein the latency gene is the VZV ORF29 gene and encodes a major DNA binding protein.

### Claim 7 (depends on 1)

The method of claim 1, wherein the virus substantially lacks a DNA binding protein encoding gene at its native location, the gene being encoded by a nucleic acid sequence that hybridizes to a nucleic acid sequence that encodes a ORF29 protein of VZV.

### Claim 8 (depends on 7)

The method of claim 7, wherein the nucleic acid encoding the major DNA binding protein has a deletion of a nucleic acid that encodes at least 10 amino acids.

### Claim 9 (depends on 8)

The method of claim 8, wherein amino acids corresponding to amino acids 22-957 of an ORF29 having the amino acid sequence of SEQ ID NO: 3 are deleted.

### Claim 10

A method for making an attenuated live virus having an impaired ability to establish latency, comprising:
introducing a recombinant virus comprising all or a portion of a herpes virus genome into a host cell to produce an amount of the virus suitable for a vaccine, wherein the genome comprises a latency gene or transcript; and
recovering the virus from the host cell.

### Claim 11 (depends on 10)

The method of claim 10, wherein the latency gene or transcript is at a different location in the genome relative to its native location and comprises at least one mutation.

### Claim 12 (depends on 11)

The method of claim 11, wherein the latency gene is VZV ORF29 and the mutation is a deletion or substitution in the nuclear localization sequence that impairs the ability of ORF29 to translocate to the nucleus.

### Claim 13 (depends on 11)

The method of claim 11, wherein the latency gene is located in a position corresponding to that between ORF65 and ORF66 of VZV.

### Claim 14

A method of inhibiting latent viral infection, comprising administering to a subject in need thereof a recombinant virus comprising all or a portion of a herpes virus genome, wherein the genome has a promoter for a latency gene or transcript altered or modified so that the gene or transcript is expressed during virus replication.

### Claim 15 (depends on 14)

The method of claim 14, wherein the viral infection is from a virus selected from the group consisting of herpes simplex virus, varicella-zoster virus, Marek's disease virus, pseudorabies virus and cytomegalovirus.

### Claim 16 (depends on 14)

The method of claim 14, wherein the promoter for the latency gene or transcript is replaced by a heterologous promoter.

### Claim 17 (depends on 14)

The method of claim 14, wherein the genome comprises a deletion in a latency gene or transcript at its native location, and the latency gene or transcript is located at a different location in the viral genome and is expressed from a heterologous promoter.

### Claim 18 (depends on 14)

The method of claim 14, wherein the latency gene is a VZV gene selected from the group consisting of ORF4, ORF21, ORF29, ORF62, ORF63 and ORF66.

### Claim 19 (depends on 14)

The method of claim 14, wherein the latency gene or transcript is at a different location in the genome relative to its native location and comprises at least one mutation.

### Claim 20 (depends on 20)

The method of claim 20, wherein the latency gene is VZV ORF29 and the mutation is a deletion or substitution in the nuclear localization sequence that impairs the ability of ORF29 to translocate to the nucleus.