# US 11,298,420 B2 · Armed oncolytic viruses

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,298,420 B2
- Document ID: US11298420B2
- Status: Granted
- Kind: B2
- Application number: 15/843,603
- Filed: 2017-12-15
- Published: 2018-06-21
- Granted: 2022-04-12
- Earliest claimed: 2016-12-21
- Assignees: MEMGen Corporation
- Applicants: Memgen, LLC
- Inventors: Mark J. Cantwell
- Web page: https://patentgrep.com/patent/US11298420B2

## CPC

- A61K 39/42: viral
- A61K 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)}
- A61P 35/00: Antineoplastic agents
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- A61K 2039/5256: {expressing foreign proteins}
- C12N 2710/16032: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Disclosed are oncolytic viruses comprising chimeric human/mouse CD40 ligands. The chimeric human/mouse CD40 ligand may be MEM40. The oncolytic virus may be replication competent. The oncolytic virus may be an oncolytic herpes simplex virus. Also disclosed are methods comprising administering an oncolytic virus armed with at least one chimeric human/mouse CD40 ligand, for example MEM40, to a patient suffering from cancer.

## Claims

### Claim 1

A composition, comprising:
an oncolytic virus comprising a heterologous nucleic acid inserted into the oncolytic virus genome, said nucleic acid comprising a sequence encoding a chimeric human/mouse CD40 ligand operatively linked to a transcriptional control element, wherein the oncolytic virus further comprises one heterologous gene encoding a therapeutic protein, wherein the heterologous gene is selected from the group consisting of genes encoding antibodies, genes encoding pro-drug converting enzymes, and genes encoding checkpoint inhibitors, wherein the chimeric human/mouse CD40 ligand and the therapeutic protein encoded by the one heterologous gene are the only heterologous amino acid sequences expressed by the oncolytic virus.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the oncolytic virus is replication competent.

### Claim 3 (depends on 2)

The composition of claim 2, wherein the replication competent oncolytic virus is selected from herpes simplex virus (HSV), adenovirus, vaccinia virus, poxvirus, coxsackievirus, poliovirus, measles virus, parvovirus, reovirus, Seneca valley virus, Newcastle disease virus, retrovirus, vesicular stomatitis virus, reovirus, paramyxovirus, Sindbis virus, myxoma virus, Maraba virus, influenza virus, measles virus, mumps virus, arenavirus, and Semliki Forest virus.

### Claim 4 (depends on 3)

The composition of claim 3, wherein the replication competent oncolytic virus is a herpes simplex virus.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the replication competent oncolytic herpes simplex virus is selected from the group consisting of herpes simplex virus 1 and herpes simplex virus 2.

### Claim 6 (depends on 4)

The composition of claim 4, wherein the replication competent oncolytic herpes simplex virus lacks a functional ICP34.5 encoding gene.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the nucleic acid comprising a sequence encoding a CD40 agonist operatively linked to a transcriptional control element is inserted in the ICP34.5 encoding gene region.

### Claim 8 (depends on 4)

The composition of claim 4, wherein the replication competent oncolytic herpes simplex virus lacks a functional ICP47 encoding gene.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the at least one chimeric human/mouse CD40 ligand is selected from the group consisting of ISF30 (SEQ ID NO:1), ISF31 (SEQ ID NO:2), ISF32 (SEQ ID NO:3), ISF33 (SEQ ID NO:4), ISF34 (SEQ ID NO:5), ISF35 (MEM40) (SEQ ID NO:6), ISF36 (SEQ ID NO:7), ISF37 (SEQ ID NO:8), ISF38 (SEQ ID NO:9), ISF39 (SEQ ID NO:10), ISF40 (SEQ ID NO:11), and ISF41 (SEQ ID NO:12).

### Claim 10 (depends on 9)

The composition of claim 9, wherein the at least one chimeric human/mouse CD40 ligand is MEM40 (SEQ ID NO:6).

### Claim 11 (depends on 1)

The composition of claim 1, wherein the at least one chimeric human/mouse CD40 ligand has at least 90% identity with a ligand selected from the group consisting of ISF30 (SEQ ID NO:1), ISF31 (SEQ ID NO:2), ISF32 (SEQ ID NO:3), ISF33 (SEQ ID NO:4), ISF34 (SEQ ID NO:5), ISF35 (MEM40) (SEQ ID NO:6), ISF36 (SEQ ID NO:7), ISF37 (SEQ ID NO:8), ISF38 (SEQ ID NO:9), ISF39 (SEQ ID NO:10), ISF40 (SEQ ID NO:11), and ISF41 (SEQ ID NO:12).

### Claim 12 (depends on 1)

The composition of claim 1, wherein the transcriptional control element operatively linked to the sequence encoding the CD40 agonist is a transcriptional promoter.

### Claim 13 (depends on 12)

The composition of claim 12, wherein the transcriptional promoter is a cytomegalovirus (CMV) promoter.

### Claim 14 (depends on 4)

The composition of claim 4, wherein the replication competent oncolytic herpes simplex virus is a non-laboratory virus strain.

### Claim 15 (depends on 14)

The composition of claim 14, wherein the replication competent oncolytic herpes simplex virus is derived from an HSV JS1 strain.

### Claim 16 (depends on 1)

The composition of claim 1, further comprising a pharmaceutically-acceptable carrier.

### Claim 17

A method, comprising:
administering to a patient suffering from a tumor, an oncolytic virus comprising a heterologous nucleic acid inserted into the oncolytic virus genome, said nucleic acid comprising a sequence encoding a chimeric human/mouse CD40 ligand operatively linked to a transcriptional control element, wherein the oncolytic virus further comprises one heterologous gene encoding a therapeutic protein, wherein the heterologous gene is selected from the group consisting of genes encoding antibodies, genes encoding pro-drug converting enzymes, and genes encoding checkpoint inhibitors, wherein the chimeric human/mouse CD40 ligand and the therapeutic protein encoded by the one heterologous gene are the only heterologous amino acid sequences expressed by the oncolytic virus.

### Claim 18 (depends on 17)

The method of claim 17, wherein the oncolytic virus is replication competent.

### Claim 19 (depends on 18)

The method of claim 18, wherein the replication competent oncolytic virus is selected from herpes simplex virus (HSV), adenovirus, vaccinia virus, poxvirus, coxsackievirus, poliovirus, measles virus, parvovirus, reovirus, Seneca valley virus, Newcastle disease virus, retrovirus, vesicular stomatitis virus, reovirus, paramyxovirus, Sindbis virus, myxoma virus, Maraba virus, influenza virus, measles virus, mumps virus, arenavirus, and Semliki Forest virus.

### Claim 20 (depends on 19)

The method of claim 19, wherein the replication competent oncolytic virus is a herpes simplex virus.

### Claim 21 (depends on 20)

The method of claim 20, wherein the replication competent oncolytic herpes simplex virus is selected from the group consisting of herpes simplex virus 1 and herpes simplex virus 2.

### Claim 22 (depends on 20)

The method of claim 20, wherein the replication competent oncolytic herpes simplex virus lacks a functional ICP34.5 encoding gene.

### Claim 23 (depends on 22)

The method of claim 22, wherein the nucleic acid comprising a sequence encoding a CD40 agonist operatively linked to a transcriptional control element is inserted in the ICP34.5 encoding gene region.

### Claim 24 (depends on 20)

The method of claim 20, wherein the replication competent oncolytic herpes simplex virus lacks a functional ICP47 encoding gene.

### Claim 25 (depends on 17)

The method of claim 17, wherein the at least one chimeric human/mouse CD40 ligand is selected from the group consisting of ISF30 (SEQ ID NO:1), ISF31 (SEQ ID NO:2), ISF32 (SEQ ID NO:3), ISF33 (SEQ ID NO:4), ISF34 (SEQ ID NO:5), ISF35 (MEMA40) (SEQ ID NO:6), ISF36 (SEQ ID NO:7), ISF37 (SEQ ID NO:8), ISF38 (SEQ ID NO:9), ISF39 (SEQ ID NO:10), ISF40 (SEQ ID NO:11), and ISF41 (SEQ ID NO:12).

### Claim 26 (depends on 25)

The method of claim 25, wherein the at least one chimeric human/mouse CD40 ligand is MEM40 (SEQ ID NO:6).

### Claim 27 (depends on 17)

The method of claim 17, wherein the at least one chimeric human/mouse CD40 ligand has at least 90% identity to a ligand selected from the group consisting of ISF30 (SEQ ID NO: 1), ISF31 (SEQ ID NO: 2), ISF32 (SEQ ID NO: 3), ISF33 (SEQ ID NO: 4), ISF34 (SEQ ID NO: 5), ISF35 (MEM40) (SEQ ID NO: 6), ISF36 (SEQ ID NO: 7), ISF37 (SEQ ID NO: 8), ISF38 (SEQ ID NO: 9), ISF39 (SEQ ID NO: 10), ISF40 (SEQ ID NO: 11), and ISF41 (SEQ ID NO: 12).

### Claim 28 (depends on 17)

The method of claim 17, wherein the transcriptional control element operatively linked to the sequence encoding the CD40 ligand is a transcriptional promoter.

### Claim 29 (depends on 28)

The method of claim 28, wherein the transcriptional promoter is a cytomegalovirus (CMV) promoter.

### Claim 30 (depends on 20)

The method of claim 20, wherein the replication competent oncolytic herpes simplex virus is a non-laboratory virus strain.

### Claim 31 (depends on 30)

The method of claim 30, wherein the replication competent oncolytic herpes simplex virus is derived from an HSV JS1 strain.

### Claim 32 (depends on 17)

The method of claim 17, wherein the patient has a cancer selected from primary or metastatic cancer.

### Claim 33 (depends on 17)

The method of claim 17, wherein the oncolytic virus is administered intratumorally, intravenously, intraperitoneally, intratracheally, intramuscularly, intracranially, endoscopically, intralesionally, percutaneously, subcutaneously, regionally, or by direct injection or perfusion.

### Claim 34 (depends on 17)

The method of claim 17, wherein the oncolytic virus is administered once or multiple times.

### Claim 35 (depends on 17)

The method of claim 17, further comprising:
administering at least one additional therapeutic agent.

### Claim 36 (depends on 35)

The method of claim 35, wherein the at least one additional therapeutic agent is chemotherapy, immunotherapy, surgery, radiotherapy, viral therapy, or biotherapy.

### Claim 37 (depends on 35)

The method of claim 35, wherein the at least one additional therapeutic agent is a nonreplicating adenovirus encoding MEM40.

### Claim 38 (depends on 35)

The method of claim 35, wherein the at least one additional therapeutic agent is administered to the patient before administration of the oncolytic virus.

### Claim 39 (depends on 35)

The method of claim 35, wherein the at least one additional therapeutic agent is administered to the patient at the same time as administration of the oncolytic virus.

### Claim 40 (depends on 35)

The method of claim 35, wherein the at least one additional therapeutic agent is administered to the patient after administration of the oncolytic virus.

### Claim 41 (depends on 17)

The method of claim 17, wherein the patient is a human.

### Claim 42 (depends on 1)

The composition of claim 1, wherein the heterologous gene is a gene encoding a checkpoint inhibitor.

### Claim 43 (depends on 42)

The composition of claim 42, wherein the checkpoint inhibitor is selected from the group consisting of anti-PD-1, anti-CDTA4, and anti-PD-L1.