# US 11,401,511 B2 · Mumps virus as a potential oncolytic agent

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- Number: US 11,401,511 B2
- Document ID: US11401511B2
- Status: Granted
- Kind: B2
- Application number: 16/747,782
- Filed: 2020-01-21
- Published: 2020-07-16
- Granted: 2022-08-02
- Earliest claimed: 2015-06-12
- Assignees: Mayo Foundation for Medical Education and Research
- Applicants: Mayo Foundation for Medical Education and Research
- Inventors: Mark J. Federspiel; Arun Ammayappan; Gennett Pike; Stephen James Russell
- Web page: https://patentgrep.com/patent/US11401511B2

## CPC

- 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 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 39/12: Viral antigens
- A61K 39/165: Mumps or measles virus
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61K 2039/525: {Virus}
- C12N 2760/18721: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2760/18734: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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

## Abstract

This document relates to methods and materials for virotherapy. For example, this document provides methods and materials for treating cancer using a recombinant mumps virus as an oncolytic agent.

## Claims

### Claim 1

A recombinant mumps virus (MuV) having oncolytic anti-cancer activity, wherein said recombinant MuV comprises nucleic acid selected from the group consisting of nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, nucleic acid encoding a modified matrix (M) protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, nucleic acid encoding a modified fusion (F) protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and nucleic acid encoding a modified hemagglutinin-neuraminidase (HN) protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9.

### Claim 2 (depends on 1)

The recombinant MuV of claim 1, wherein said recombinant MuV is a replication competent MuV.

### Claim 3 (depends on 1)

The recombinant MuV of claim 1, wherein said recombinant MuV comprises nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, and wherein said modification in a V protein coding sequence comprises a C to T substitution at nucleotide 2585 as numbered in SEQ ID NO:1.

### Claim 4 (depends on 1)

The recombinant MuV of claim 1, wherein said recombinant MuV comprises nucleic acid encoding a modified M protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, and wherein said modification in a M protein coding sequence comprises a C to A substitution at nucleotide 4275 as numbered in SEQ ID NO:1.

### Claim 5 (depends on 1)

The recombinant MuV of claim 1, wherein said recombinant MuV comprises nucleic acid encoding a modified F protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and wherein said modification in a F protein coding sequence comprises a A to C substitution at nucleotide 5834 as numbered in SEQ ID NO:1.

### Claim 6 (depends on 1)

The recombinant MuV of claim 1, wherein said recombinant MuV comprises nucleic acid encoding a modified HN protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9, and wherein said modification in a HN protein coding sequence comprises a C to A substitution at nucleotide 8177 as numbered in SEQ ID NO:1.

### Claim 7 (depends on 1)

The recombinant MuV of claim 1, wherein said recombinant MuV comprises nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, nucleic acid encoding a modified M protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, nucleic acid encoding a modified F protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and nucleic acid encoding a modified HN protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9.

### Claim 8

A method for treating a patient having cancer, the method comprising:
administering to the patient a recombinant mumps virus (MuV) having oncolytic anticancer activity, wherein said recombinant MuV comprises nucleic acid selected from the group consisting of nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, nucleic acid encoding a modified matrix (M) protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, nucleic acid encoding a modified fusion (F) protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and nucleic acid encoding a modified hemagglutinin-neuraminidase (HN) protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9.

### Claim 9 (depends on 8)

The method of claim 8, wherein the cancer is a blood cancer selected from leukemia, lymphoma, or myeloma.

### Claim 10 (depends on 9)

The method claim 9, wherein the blood cancer is myeloma.

### Claim 11 (depends on 8)

The method of claim 8, wherein the cancer is a carcinoma selected from prostate cancer, breast cancer, hepatocellular carcinoma, lung cancer, or colorectal carcinoma.

### Claim 12 (depends on 11)

The method of claim 11, wherein the carcinoma is colorectal carcinoma.

### Claim 13 (depends on 8)

The method of claim 8, wherein said recombinant MuV is a replication competent MuV.

### Claim 14 (depends on 8)

The method of claim 8, wherein said recombinant MuV comprises nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, and wherein said modification in a V protein coding sequence comprises a C to T substitution at nucleotide 2585 as numbered in SEQ ID NO:1.

### Claim 15 (depends on 8)

The method of claim 8, wherein said recombinant MuV comprises nucleic acid encoding a modified M protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, and wherein said modification in a M protein coding sequence comprises a C to A substitution at nucleotide 4275 as numbered in SEQ ID NO:1.

### Claim 16 (depends on 8)

The method of claim 8, wherein said recombinant MuV comprises nucleic acid encoding a modified F protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and wherein said modification in a F protein coding sequence comprises a A to C substitution at nucleotide 5834 as numbered in SEQ ID NO:1.

### Claim 17 (depends on 8)

The method of claim 8, wherein said recombinant MuV comprises nucleic acid encoding a modified HN protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9, and wherein said modification in a HN protein coding sequence comprises a C to A substitution at nucleotide 8177 as numbered in SEQ ID NO:1.

### Claim 18 (depends on 8)

The method of claim 8, wherein said recombinant MuV comprises nucleic acid encoding a modified V protein comprising a H to Y substitution at amino acid 203 as numbered in SEQ ID NO: 4, nucleic acid encoding a modified M protein comprising a L to O substitution at amino acid 338 as numbered in SEQ ID NO:6, nucleic acid encoding a modified F protein comprising a Y to S substitution at amino acid 430 as numbered in SEQ ID NO:7, and nucleic acid encoding a modified HN protein comprising a L to I substitution at amino acid 522 as numbered in SEQ ID NO:9.

### Claim 19 (depends on 8)

The method of claim 8, further comprising administering ruxolitinib.