# US 9,364,532 B2 · Compositions and methods for glioblastoma treatment

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- Number: US 9,364,532 B2
- Document ID: US9364532B2
- Status: Granted
- Kind: B2
- Application number: 14/123,057
- Filed: 2012-06-07
- Published: 2014-04-03
- Granted: 2016-06-14
- Earliest claimed: 2011-06-08
- Assignees: Children's Hospital of Eastern Ontario Research Institute Inc.
- Applicants: David F. Stojdl
- Inventors: David F. Stojdl
- Web page: https://patentgrep.com/patent/US9364532B2

## CPC

- A61K 39/205: Rhabdoviridae, e.g. rabies virus
- A61K 35/766: Rhabdovirus, e.g. vesicular stomatitis virus
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- C07K 14/005: from viruses
- 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 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/572: {cytotoxic response}
- A61K 2039/585: {wherein the target is cancer}
- C12N 2760/00032: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2760/20021: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2760/20022: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/20023: Virus like particles [VLP]
- C12N 2760/20032: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2760/20043: viral genome or elements thereof as genetic vector
- 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)

## Abstract

The present disclosure concerns an oncolytic virus for the treatment of cancer, such as in brain cancer, for example glioblastoma. The oncolytic virus may exhibit reduced levels of neurotoxicity. The oncolytic virus may be an isolated viral particle capable of producing a cDNA polynucleotide that includes a sequence according to SEQ ID NO: 1 when the virus is in a host cell. The oncolytic virus may be an isolated viral particle that includes an RNA polynucleotide that includes a sequence according to SEQ ID NO: 2. The oncolytic virus may be an isolated viral particle having a genome that includes open reading frames that encode: proteins having sequences comprising SEQ ID NOs: 3, 4, 5, 6 and 7; or variants thereof.

## Claims

### Claim 1

A method for inducing an immunogenic response in a patient, the method comprising administering to the patient an isolated viral particle having a genome comprising open reading frames that encode:
a protein comprising SEQ ID NO: 3;
a protein comprising SEQ ID NO: 4;
a protein comprising SEQ ID NO: 5;
a protein comprising SEQ ID NO: 6;
and a protein comprising SEQ ID NO: 7.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the isolated viral particle is administered directly to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the isolated viral particle is administered to the patient intrathecally, intravenously or via intracranial injection.

### Claim 4 (depends on 1)

The method according to claim 1, wherein a cell is infected with the isolated viral particle and the infected cell is administered to the patient.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the infected cell is administered directly to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the infected cell is administered to the patient intrathecally, intravenously or via intracranial injection.

### Claim 7 (depends on 1)

The method according to claim 1, wherein inducing an immunogenic response is against a malignant glioma in the brain of the patient, and wherein the method comprises administration of the isolated viral particle inside the blood/brain barrier.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the malignant glioma is a glioblastoma or medulloblastoma.