# US 2013/0280299 A1 · Viral vectors and their use in therapeutic methods

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- Number: US 2013/0280299 A1
- Document ID: US20130280299A1
- Status: Published application
- Kind: A1
- Application number: 13/924,936
- Filed: 2013-06-24
- Published: 2013-10-24
- Earliest claimed: 2001-03-27
- Assignees: Catherex, Inc.; Georgetown University; The General Hospital Corporation
- Applicants: Catherex, Inc.; Georgetown University; The General Hospital Corporation
- Inventors: Paul JOHNSON; Robert L. Martuza; Samuel D. Rabkin; Tomoki Todo
- Web page: https://patentgrep.com/patent/US20130280299A1

## CPC

- A61K 39/245: Herpetoviridae, e.g. herpes simplex virus
- A61K 35/763: Herpes virus
- A61K 35/768: Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
- A61K 38/162: {from virus}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- 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 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/585: {wherein the target is cancer}
- C12N 2710/16632: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2710/16634: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2710/16643: viral genome or elements thereof as genetic vector
- C12N 2710/16662: by genetic engineering
- C12N 2710/16671: Demonstrated in vivo effect
- 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

The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

## Claims

### Claim 1

A herpes simplex virus comprising a mutation within the BstEII-EcoNI fragment of the BamHI x fragment of said virus.

### Claim 2 (depends on 1)

The virus of claim 1, further comprising an inactivating mutation in the γ34.5 neurovirulence locus of said virus.

### Claim 3 (depends on 1)

The virus of claim 1, further comprising an inactivating mutation in the γ34.5 neurovirulence locus of said virus and an inactivating mutation in the ICP6 locus of said virus.

### Claim 4

A herpes simplex virus comprising an inactivating mutation in the ICP47 locus of said virus, in the absence of an inactivating mutation in the γ34.5 neurovirulence locus of said virus.

### Claim 5 (depends on 1, 4)

The virus of claim 1 or 4, further comprising an inactivating mutation in the ICP6 locus of said virus.

### Claim 6

A method of inducing a systemic immune response to cancer in a patient, said method comprising administering to said patient a herpes virus comprising an inactivating mutation in the ICP47 locus of said herpes virus.

### Claim 7 (depends on 6)

The method of claim 6, wherein said herpes virus is administered to a tumor of said patient.

### Claim 8 (depends on 6)

The method of claim 6, wherein said patient has or is at risk of developing metastatic cancer.

### Claim 9 (depends on 6)

The method of claim 6, wherein said inactivating mutation in the ICP47 locus of said herpes virus is in the BstEII-EcoNI fragment of the BamHI x fragment of said virus.

### Claim 10 (depends on 6)

The method of claim 6, wherein said herpes virus further comprises an inactivating mutation in the γ34.5 neurovirulence locus of said herpes virus.

### Claim 11 (depends on 6)

The method of claim 6, wherein said herpes virus further comprises an inactivating mutation in the ICP6 locus of said herpes virus.

### Claim 12 (depends on 6)

The method of claim 6, wherein said herpes virus further comprises an inactivating mutation in the γ34.5 neurovirulence locus of said herpes virus and an inactivating mutation in the ICP6 locus of said herpes virus.

### Claim 13

A herpes virus comprising a first mutation that inactivates the γ34.5 neurovirulence locus of said virus and a second mutation that results in early expression of US11, in the absence of an ICP47-inactivating mutation in the BamHI x fragment of said virus.

### Claim 14 (depends on 13)

The virus of claim 13, wherein said virus comprises a promoter inserted upstream from said US11 gene, resulting in said early expression.

### Claim 15 (depends on 13)

The virus of claim 13, wherein said virus comprises a US11 gene under the control of an early-expressing promoter inserted into the genome of said virus.

### Claim 16 (depends on 13)

The virus of claim 13, wherein said virus comprises a mutation that results in downregulation of ICP47 expression, in the absence of a mutation in the BamHI x fragment of said vector.

### Claim 17 (depends on 16)

The virus of claim 16, wherein said downregulation of ICP47 expression is due to a deletion in, or inactivation of, the ICP47 promoter.

### Claim 18 (depends on 16)

The virus of claim 16, wherein said virus encodes ICP47 that is fused with a peptide that prevents functional expression of ICP47.

### Claim 19

A herpes virus comprising a first mutation that inactivates the γ34.5 neurovirulence locus of said virus and a second mutation that results in downregulation of ICP47 expression, in the absence of a mutation in the BamHI x fragment of said virus.

### Claim 20 (depends on 19)

The virus of claim 19, wherein said downregulation of ICP47 expression is due to a deletion in, or inactivation of, the ICP47 promoter.

### Claim 21 (depends on 19)

The virus of claim 19, wherein said virus encodes ICP47 that is fused with a peptide that prevents functional expression of ICP47.

### Claim 22 (depends on 13, 19)

The virus of claim 13 or 19, further comprising an additional mutation to prevent reversion to wild type.

### Claim 23 (depends on 22)

The virus of claim 22, wherein said additional mutation is in the ICP6 locus.

### Claim 24 (depends on 1, 4, 13)

The virus of claim 1, 4, 13, or 19, further comprising sequences encoding a heterologous gene product.

### Claim 25 (depends on 24)

The virus of claim 24, wherein said heterologous gene product comprises a vaccine antigen or an immunomodulatory protein.

### Claim 26 (depends on 13, 19)

The virus of claim 13 or 19, wherein said virus is a herpes simplex virus.

### Claim 27 (depends on 1, 4)

The virus of claim 1, 4, or 26, wherein said virus is a herpes simplex-1 virus.

### Claim 28 (depends on 1, 4, 13)

A pharmaceutical composition comprising the virus of claim 1, 4, 13, or 19 and a pharmaceutically acceptable carrier, adjuvant, or diluent.

### Claim 29 (depends on 28)

A method of treating cancer in a patient, said method comprising administering the pharmaceutical composition of claim 28 to said patient.

### Claim 30 (depends on 28)

A method of immunizing a patient against an infectious disease, cancer, or an autoimmune disease, said method comprising administering the pharmaceutical composition of claim 28 to said patient.