# US 9,872,857 B2 · Methods of using propentofylline to treat glioma and glioblastoma

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- Number: US 9,872,857 B2
- Document ID: US9872857B2
- Status: Granted
- Kind: B2
- Application number: 15/068,890
- Filed: 2016-03-14
- Published: 2016-08-04
- Granted: 2018-01-23
- Earliest claimed: 2009-10-23
- Assignees: The Translational Genomics Research Institutet; Mayo Foundation for Medical Education and Research
- Applicants: The Translational Genomics Research Institute; Mayo Foundation for Medical Education and Research
- Inventors: Nhan Tran; Joseph C. Loftus; Harshil Dhruv
- Web page: https://patentgrep.com/patent/US9872857B2

## CPC

- A61K 31/522: having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/495: having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53})
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/5755: of the uterine cervix, uterine corpus or endometrium
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/158: Expression markers
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N 2800/54: Determining the risk of relapse
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention encompasses methods of treating a patient with cancer, such as glioblastoma. The methods may include the administration of one or more pharmaceutical compositions that are capable of inhibiting TROY to treat the patient with cancer.

## Claims

### Claim 1

A method of sensitizing a patient with glioma to radiation therapy and/or chemotherapy, the method comprising
administering to the patient with glioma propentofylline or a pharmaceutically acceptable salt thereof in an amount sufficient to inhibit TROY expression, but the amount is less than sufficient to substantially reduce viability of glioma cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the glioma is glioblastoma.

### Claim 3 (depends on 2)

The method of claim 2, wherein the glioma is invasive glioblastoma.

### Claim 4 (depends on 1)

The method of claim 1, wherein the propentofylline is in a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers.

### Claim 5 (depends on 1)

The method of claim 1 further comprising administering to the patient with glioma a second pharmaceutical composition.

### Claim 6 (depends on 5)

The method of claim 5, wherein the second pharmaceutical composition comprises at least one of the following: an antibody against TROY that inhibits TROY, Pyk2 shRNA, Rac1 siRNA, Dock180 siRNA, Dock7 siRNA, temozolomide and bevacizumab.

### Claim 7 (depends on 6)

The method of claim 6, wherein the second pharmaceutical composition comprises temozolomide.

### Claim 8 (depends on 5)

The method of claim 5, wherein the propentofylline and the second pharmaceutical composition are co-administered to the patient.

### Claim 9 (depends on 1)

The method of claim 1 further comprising administering a therapeutically effective amount of radiation to the patient with glioma.

### Claim 10

A method of sensitizing glioblastoma cells in a subject, the method comprising the steps of contacting the glioblastoma cells with a therapeutically effective amount of propentofylline or a pharmaceutically acceptable salt thereof in an amount sufficient to inhibit TROY expression, but the amount is less than sufficient to substantially reduce viability of glioblastoma cells, and further contacting the glioblastoma cells with another pharmaceutical composition.

### Claim 11 (depends on 10)

The method of claim 10, wherein the glioblastoma comprises invasive glioblastoma.

### Claim 12 (depends on 10)

The method of claim 10, wherein the pharmaceutical composition comprises the administration of one or more compounds selected from the group consisting of Pyk2 shRNA, Rac1 siRNA, Dock180 siRNA, Dock7 siRNA, temozolomide and bevacizumab.

### Claim 13 (depends on 12)

The method of claim 12, wherein pharmaceutical composition comprises temozolomide.

### Claim 14 (depends on 10)

The method of claim 10, wherein the pharmaceutical composition comprises a therapeutically effective amount of radiation.

### Claim 15 (depends on 10)

The method of claim 10, wherein the glioblastoma cells are sequentially contacted with the therapeutically effective amount of propentofylline or a pharmaceutically acceptable salt thereof and the another pharmaceutical composition.

### Claim 16 (depends on 10)

The method of claim 10, wherein the glioblastoma cells are substantially simultaneously contacted with the therapeutically effective amount of propentofylline or a pharmaceutically acceptable salt thereof and the another pharmaceutical composition.