# US 7,608,257 B2 · Sensitization of chemotherapeutic agent resistant neoplastic cells with a virus

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- Number: US 7,608,257 B2
- Document ID: US7608257B2
- Status: Granted
- Kind: B2
- Application number: 11/809,293
- Filed: 2007-05-31
- Published: 2008-02-07
- Granted: 2009-10-27
- Earliest claimed: 2001-02-20
- Assignees: Oncolytics Biotech Inc.
- Inventors: Matthew C. Coffey; Bradley G. Thompson
- Web page: https://patentgrep.com/patent/US7608257B2

## CPC

- A61K 33/243: Platinum; Compounds thereof
- A61K 35/765: Reovirus; Rotavirus
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/08: of the prostate
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 2720/12232: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- 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 present invention relates to a method of increasing the sensitivity of neoplastic cells to chemotherapeutic agents by using a virus, a method of treating proliferative disorders with a virus and chemotherapeutic agents, and a method for preventing a neoplasm from developing drug resistance to chemotherapeutic agents. The virus is preferably a reovirus.

## Claims

### Claim 1

A method of treating ras-activated neoplastic cells in a subject, comprising:
(a) infecting the neoplastic cells in the subject with a reovirus by administering an effective amount of the reovirus to the subject under conditions that result in infection of the neoplastic cells; and
(b) administering an effective amount of a first chemotherapeutic agent to the subject, wherein the ras-activated neoplastic cells were previously determined to be refractory to the first chemotherapeutic agent in the absence of the reovirus.

### Claim 2 (depends on 1)

The method of claim 1, wherein the reovirus is administered prior to the administration of the first chemotherapeutic agent.

### Claim 3 (depends on 1)

The method of claim 1, wherein the reovirus and the first chemotherapeutic agent are concurrently administered.

### Claim 4 (depends on 1)

The method of claim 1, wherein the reovirus is administered in multiple doses.

### Claim 5 (depends on 1)

The method of claim 1, wherein the reovirus is administered in multiple doses prior to administration of the first chemotherapeutic agent.

### Claim 6 (depends on 1)

The method of claim 1, further comprising administering a second chemotherapeutic agent to the subject.

### Claim 7 (depends on 1)

The method of claim 1, wherein the subject is a mammal.

### Claim 8 (depends on 1)

The method of claim 1, wherein the subject has a solid tumor, a hematopoietic tumor, or a metastatic tumor.

### Claim 9 (depends on 8)

The method of claim 8, wherein the subject has lung cancer, prostate cancer, colorectal cancer, thyroid cancer, renal cancer, adrenal cancer, liver cancer, pancreatic cancer, breast cancer, central and peripheral nervous system cancer, a lymphoma, or a leukemia.

### Claim 10 (depends on 8)

The method of claim 8, wherein the reovirus is administered into or near the solid tumor.

### Claim 11 (depends on 8)

The method of claim 8, wherein the reovirus is administered systemically.

### Claim 12 (depends on 8)

The method of claim 8, wherein the first chemotherapeutic agent is selected from the group consisting of 5-fluorouracil, mitomycin C, methotrexate, hydroxyurea, cyclophosphamide, dacarbazine, mitoxantrone, anthracyclins, carboplatin, cisplatin, taxol, taxotere, tamoxifen, anti-estrogens, and interferons.

### Claim 13 (depends on 1)

The method of claim 1, wherein reovirus infection of the ras-activated neoplastic cells prevents the neoplastic cells from becoming refractory to a second chemotherapeutic agent.