# US 11,998,540 B2 · Compositions and methods for treating drug-tolerant glioblastoma

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- Number: US 11,998,540 B2
- Document ID: US11998540B2
- Status: Granted
- Kind: B2
- Application number: 16/060,852
- Filed: 2016-03-24
- Published: 2019-01-03
- Granted: 2024-06-04
- Earliest claimed: 2015-12-11
- Assignees: The General Hospital Corporation
- Applicants: The General Hospital Corporation
- Inventors: Brian B. Liau; Anoop P. Patel; Cem Sievers; Bradley E. Bernstein
- Web page: https://patentgrep.com/patent/US11998540B2

## CPC

- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 31/5513: 1,4-Benzodiazepines, e.g. diazepam {or clozapine}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- 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

The present invention provides compositions and methods for the treatment of drug-tolerant glioblastoma, and in particular glioblastoma stem cells. Specifically, the methods comprise contacting a glioblastoma stem cell with a platelet-derived growth factor receptor alpha inhibitor and one or more of a histone lysine demethylase inhibitor and a Notch inhibitor.

## Claims

### Claim 1

A method of increasing cell death in a glioblastoma stem cell population comprising measuring expression in the glioblastoma stem cell population of one or more biomarkers selected from the group consisting of SALL2, DLX2, ZFHX4, HEY1, HES5, and FABP7 in the glioblastoma stem cell population;
contacting the glioblastoma stem cell population with dasatinib, crenolanib, or a combination thereof,
wherein dasatinib has the following structure:
and crenolanib has the following structure:
measuring expression of said one or more biomarkers in in the glioblastoma stem cell population after said contacting with dasatinib, crenolanib, or a combination thereof; and
contacting the glioblastoma stem cell persister population with GSKJ4 if there is increased expression of said one or more biomarkers after said contacting with dasatinib, crenolanib, or a combination thereof as compared to the first measuring step, wherein,
GSKJ4 has the following structure: