# US 12,128,099 B2 · Myxoma virus compositions and methods of use

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- Number: US 12,128,099 B2
- Document ID: US12128099B2
- Status: Granted
- Kind: B2
- Application number: 17/058,765
- Filed: 2019-05-24
- Published: 2021-07-08
- Granted: 2024-10-29
- Earliest claimed: 2018-05-25
- Assignees: BioVentures, LLC
- Applicants: Bioventures, LLC
- Inventors: Jia Liu; Martin Cannon
- Web page: https://patentgrep.com/patent/US12128099B2

## CPC

- A61K 39/12: Viral antigens
- A61K 39/275: Poxviridae, e.g. avipoxvirus
- A61K 39/0011: {Cancer antigens}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 40/19: Dendritic cells
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/42: Cancer antigens
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- A61K 35/768: Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/585: {wherein the target is cancer}
- A61K 2039/892: {Reproductive system [uterus, ovaries, cervix, testes]}
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C12N 2710/24021: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2710/24034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- 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)
- 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)

## Abstract

Mutant Myxoma viruses are provided herein and methods of using these viruses to treat cancer or elicit an interferon response in a subject are also provided. The mutant Myxoma virus is modified to reduce or eliminate the activity or expression of Myxoma virus protein M62 as compared to a control virus. The mutant virus is capable of stimulating an interferon response in subjects after administration and can also lead to inhibition, reduction or elimination of the CD14+ tumor associated macrophage inhibition of CD4+ T cells in a subject having cancer and lead to a change in the tumor microenvironment to treat the cancer or work in combination with other cancer therapeutics to treat the cancer as described herein.

## Claims

### Claim 1

A method of treating cancer in a subject comprising administering a therapeutically effective amount of a myxoma virus, wherein the myxoma virus has been genetically modified to lack the Myxoma virus M62R gene.

### Claim 2 (depends on 1)

The method of claim 1, further comprising administering to the subject a therapeutically effective amount of an anti-cancer therapeutic agent.

### Claim 3 (depends on 2)

The method of claim 2, wherein the myxoma virus is administered at least 24 hours after the anti-cancer therapeutic agent.

### Claim 4 (depends on 2)

The method of claim 2, wherein the myxoma virus is administered at least 24 hours before the anti-cancer therapeutic agent.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cancer comprises ovarian cancer or pancreatic cancer.

### Claim 6 (depends on 1)

The method of claim 1, wherein the anti-cancer therapeutic agent is selected from the group consisting of a chemotherapeutic agent, a cancer vaccine, and a combination thereof.

### Claim 7 (depends on 6)

The method of claim 6, wherein the anti-cancer therapeutic agent comprises an agent selected from the group consisting of a platinum-based chemotherapeutic agent, a PARP inhibitor and a dendritic cell (DC) vaccine.

### Claim 8 (depends on 2)

The method of claim 2, wherein the cancer is ovarian cancer, wherein the subject is a human subject, and wherein the
anti-cancer therapeutic agent is administered to the human subject, and
subsequently the myxoma virus is administered to the human subject.

### Claim 9 (depends on 8)

The method of claim 8, wherein the myxoma virus is administered at least 24 hours after the anti-cancer therapeutic agent.

### Claim 10 (depends on 8)

The method of claim 8, wherein the anti-cancer therapeutic agent comprises an agent selected from the group consisting of a platinum-based chemotherapeutic agent, and a PARP inhibitor.

### Claim 11 (depends on 8)

The method of claim 8, wherein the method comprises administering both an anti-cancer therapeutic agent and a cancer vaccine.

### Claim 12 (depends on 2)

The method of claim 2, wherein the cancer is ovarian cancer, wherein the subject is a human subject, and wherein
the myxoma virus genetically modified to lack the Myxoma virus M62R gene is administered to the human subject, and
subsequently a cancer vaccine is administered to the human subject.

### Claim 13 (depends on 12)

The method of claim 12, wherein the myxoma virus is administered at least 24 hours before the cancer vaccine.

### Claim 14 (depends on 12)

The method of claim 12, wherein the cancer vaccine comprises a dendritic cell (DC) vaccine.

### Claim 15

A method of eliciting an interferon response in a subject having cancer, the method comprising administering to the subject a therapeutically effective amount of a Myxoma virus genetically modified to lack Myxoma virus M62R gene to elicit an interferon response in the subject.

### Claim 16 (depends on 15)

The method of claim 15, wherein the interferon response comprises an increase in IFN-β and IFN-I in a subject.

### Claim 17 (depends on 15)

The method of claim 15, wherein the cancer subject has been treated with an anti-cancer therapeutic agent prior to eliciting the interferon response.

### Claim 18 (depends on 15)

The method of claim 15, wherein the subject has been treated with an anti-cancer therapeutic agent or a cancer vaccine prior to administering the myxoma virus.

### Claim 19 (depends on 15)

The method of claim 15, wherein the anti-cancer therapeutic agent is a chemotherapeutic agent, PARP inhibitor or checkpoint inhibitor.

### Claim 20

A method of inhibiting, reducing or eliminating a CD14+tumor associated macrophage (TAM) inhibition of CD4+ T cells in a subject having cancer, the method comprising administering a therapeutically effective amount of a Myxoma virus genetically modified to lack Myxoma virus M62R gene to increase the CD4+ T cell response in a subject.

### Claim 21 (depends on 20)

The method of claim 20, wherein the subject has been treated with an anti-cancer therapeutic agent prior to administering the myxoma virus.
