# US 2014/0093527 A1 · Compositions and methods for glioblastoma treatment

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- Number: US 2014/0093527 A1
- Document ID: US20140093527A1
- Status: Published application
- Kind: A1
- Application number: 14/123,057
- Filed: 2012-06-07
- Published: 2014-04-03
- Earliest claimed: 2011-06-08
- Assignees: Children's Hopital of Eastern Ontario Research Institute Inc.
- Inventors: David F. Stojdl
- Web page: https://patentgrep.com/patent/US20140093527A1

## 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

An isolated viral particle having a genome comprising open reading frames that encode:
a protein having a sequence comprising SEQ ID NO: 3, or a variant thereof;
a protein having a sequence comprising SEQ ID NO: 4, or a variant thereof;
a protein having a sequence comprising SEQ ID NO: 5, or a variant thereof;
a protein having a sequence comprising SEQ ID NO: 6, or a variant thereof; and
a protein having a sequence comprising SEQ ID NO: 7, or a variant thereof.

### Claim 2 (depends on 1)

The isolated viral particle according to claim 1 wherein the variant of a reference protein is a protein having a sequence which is at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to the sequence of the reference protein, and the variant protein maintains the same biological function as the reference protein.

### Claim 3 (depends on 1)

The isolated viral particle according to claim 1, wherein at least one of the open reading frames encodes a protein having a sequence consisting of a sequence selected from the group consisting of SEQ ID NOs: 3, 4, 5, 6, and 7.

### Claim 4 (depends on 3)

The isolated viral particle according to claim 3 wherein the variant of a reference protein is a protein having a sequence which is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to the sequence of the reference protein, and the variant protein maintains the same biological function as the reference protein.

### Claim 5 (depends on 1)

The isolated viral particle according to claim 1, wherein the viral genome comprises open reading frames that encode:
a protein having a sequence comprising SEQ ID NO: 3;
a protein having a sequence comprising SEQ ID NO: 4;
a protein having a sequence comprising SEQ ID NO: 5;
a protein having a sequence comprising SEQ ID NO: 6; and
a protein having a sequence comprising SEQ ID NO: 7.

### Claim 6 (depends on 1)

The isolated viral particle according to claim 1 further comprising at least one additional open reading frame for encoding at least one additional protein.

### Claim 7 (depends on 6)

The isolated viral particle according to claim 6 wherein the additional protein is an immunogenic protein.

### Claim 8

An isolated viral particle capable of producing a cDNA polynucleotide when the virus is in a host cell, the cDNA polynucleotide having a sequence comprising:
SEQ ID NO: 8, or a conservative variant thereof;
SEQ ID NO: 9, or a conservative variant thereof;
SEQ ID NO: 10, or a conservative variant thereof;
SEQ ID NO: 11, or a conservative variant thereof;
SEQ ID NO: 12, or a conservative variant thereof; and
promoters thereof.

### Claim 9 (depends on 8)

The isolated viral particle according to claim 8 wherein a conservative variant of a sequence of nucleotides is a sequence that is at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to the reference sequence of nucleotides.

### Claim 10 (depends on 8)

The isolated viral particle according to claim 8 wherein a conservative variant is a sequence comprising one or more silent substitutions.

### Claim 11

An isolated viral particle capable of producing a cDNA polynucleotide comprising a sequence according to SEQ ID NO: 1 when the virus is in a host cell.

### Claim 12

An isolated viral particle comprising an RNA polynucleotide comprising a sequence according to SEQ ID NO: 2.

### Claim 13

(canceled)

### Claim 14

(canceled)

### Claim 15

(canceled)

### Claim 16

(canceled)

### Claim 17

(canceled)

### Claim 18

(canceled)

### Claim 19

(canceled)

### Claim 20

(canceled)

### Claim 21

(canceled)

### Claim 22

(canceled)

### Claim 23

(canceled)

### Claim 24

(canceled)

### Claim 25

(canceled)

### Claim 26

(canceled)

### Claim 27

(canceled)

### Claim 28

(canceled)

### Claim 29

(canceled)

### Claim 30

(canceled)

### Claim 31

(canceled)

### Claim 32

(canceled)

### Claim 33 (depends on 1)

A method for inducing an immunogenic response in a patient, the method comprising administering an isolated viral particle according to claim 1 to the patient.

### Claim 34 (depends on 33)

The method according to claim 33 wherein the isolated viral particle is administered to the patient directly.

### Claim 35 (depends on 34)

The method according to claim 34 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 36 (depends on 35)

The method according to claim 35 wherein the isolated viral particle is administered to the patient intrathecally, intravenously or via intracranial injection.

### Claim 37 (depends on 33)

The method according to claim 33 wherein a cell is infected with the isolated viral particle and the infected cell is administered to the patient.

### Claim 38 (depends on 37)

The method according to claim 37 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 39 (depends on 38)

The method according to claim 38 wherein the infected cell is administered to the patient intrathecally, intravenously or via intracranial injection.

### Claim 40 (depends on 1)

A kit for the treatment of cancer in a patient, the kit comprising;
the isolated viral particle according to claim 1; and
instructions for administration of the isolated viral particle to the patient.

### Claim 41

(canceled)

### Claim 42

(canceled)

### Claim 43

(canceled)

### Claim 44

(canceled)

### Claim 45

(canceled)

### Claim 46

(canceled)