# US 10,369,196 B2 · Compositions and methods for treating glioblastoma GBM

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,369,196 B2
- Document ID: US10369196B2
- Status: Granted
- Kind: B2
- Application number: 13/826,303
- Filed: 2013-03-14
- Published: 2013-11-14
- Granted: 2019-08-06
- Earliest claimed: 2010-01-05
- Assignees: Vascular Biogenics Ltd.
- Applicants: Vascular Biogenics Ltd.
- Inventors: Yael Cohen; Livnat Bangio; Andrew J. Brenner; Eyal Breitbart
- Web page: https://patentgrep.com/patent/US10369196B2

## CPC

- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 38/162: {from virus}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61N 5/1001: {using radiation sources introduced into or applied onto the body; brachytherapy}
- A61N 5/1077: {Beam delivery systems}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 35/00: Antineoplastic agents
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- A61K 2039/5258: {Virus-like particles}
- A61N 2005/1087: {Ions; Protons}
- C12N 2799/022: where the vector is derived from an adenovirus
- Y02E 60/36: Hydrogen production from non-carbon containing sources, e.g. by water electrolysis
- 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)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- 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)
- Y02E: REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION

## Abstract

Methods of treating a malignant glioma in a subject are disclosed. The methods comprise administering to the subject a therapeutically effective amount of a viral vector comprising: (i) a first polynucleotide sequence encoding a Fas-chimera (Fas-c), said first polynucleotide sequence comprising SEQ ID NOs: 2 and 3; and (ii) a second polynucleotide sequence encoding an endothelial cell-specific promoter or a periendothelial cell-specific promoter.

## Claims

### Claim 1

A method of treating a malignant glioma in a subject in need thereof, the method comprising administering directly into the malignant glioma or intravenously to the subject a therapeutically effective amount of a non-replicating adenovirus serotype 5 vector (Ad5), wherein said adenoviral vector comprises:
(i) a first nucleotide sequence comprising the nucleotide sequence of the extracellular region of TNFR1 as set forth in SEQ ID NO:2 fused to the trans-membrane and intracellular regions of Fas as set forth in SEQ ID NO:3 encoding a Fas-chimera (Fas-c); and
(ii) a second nucleotide sequence of an endothelial cell-specific promoter comprising the nucleotide sequence as set forth in SEQ ID NO:6, or the complementary sequence thereof,
wherein said second nucleotide sequence is operably linked to and is upstream of said first nucleotide sequence for expression of said Fas-chimera in endothelial cells, and
wherein growth of the malignant glioma is inhibited.

### Claim 2 (depends on 1)

The method of claim 1, wherein said promoter comprises at least two copies of the nucleotide sequence as set forth in SEQ ID NO: 6, or the complementary sequence thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein said promoter further comprises the nucleotide sequence as set forth in SEQ ID NO: 8, or the complementary sequence thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein said promoter comprises the nucleotide sequence as set forth in SEQ ID NO: 7, or a complementary sequence thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein said promoter further comprises the hypoxia response element (HRE) as set forth in SEQ ID NO: 5.

### Claim 6 (depends on 1)

The method of claim 1, wherein the malignant glioma is selected from the group consisting of glioblastoma, astrocytoma, oligodendroglioma, ependymoma, and juvenile pilocystic astrocytoma.

### Claim 7 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount of said adenoviral vector is 1013 virus particles.

### Claim 8 (depends on 1)

The method of claim 1, wherein said administering comprises intravenous administration.

### Claim 9 (depends on 1)

The method of claim 1, wherein said administering is in at least two doses of said adenoviral vector.

### Claim 10 (depends on 1)

The method of claim 1, wherein said administering is at least three doses of said adenoviral vector.

### Claim 11 (depends on 1)

The method of claim 1, wherein the adenoviral vector is administered as a single unit dose.

### Claim 12 (depends on 1)

The method of claim 1, further comprising administering to the subject an anti-cancer drug.

### Claim 13 (depends on 12)

The method of claim 12, wherein said anti-cancer drug is bevacizumab.

### Claim 14 (depends on 1)

The method of claim 1, further comprising administering a therapy selected from the group consisting of chemotherapy, radiotherapy, phototherapy, photodynamic therapy, surgery, nutritional therapy, ablative therapy, brachiotherapy, proton beam therapy, immunotherapy, cellular therapy and photon beam radiosurgical therapy.

### Claim 15 (depends on 14)

The method of claim 14, wherein said therapy is immunotherapy.

### Claim 16 (depends on 1)

The method of claim 1, wherein said administering comprises intravenous administration, and wherein the malignant glioma is a glioblastoma.

### Claim 17 (depends on 16)

The method of claim 16, wherein the therapeutically effective amount of said adenoviral vector is 1013 virus particles.