# US 10,119,137 B2 · Methods used to treat cancer

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- Number: US 10,119,137 B2
- Document ID: US10119137B2
- Status: Granted
- Kind: B2
- Application number: 15/204,969
- Filed: 2016-07-07
- Published: 2017-01-12
- Granted: 2018-11-06
- Earliest claimed: 2015-07-09
- Assignees: The Translational Genomics Research Institute
- Applicants: The Translational Genomics Research Institute
- Inventors: Nhan Tran
- Web page: https://patentgrep.com/patent/US10119137B2

## CPC

- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- 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 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C12N 15/1135: {against oncogenes or tumor suppressor genes}
- C12N 2310/122: Hairpin
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/531: Stem-loop; Hairpin
- C12N 2320/31: Combination therapy
- C12N 2320/35: based on a specific dosage / administration regimen
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)

## Abstract

The invention encompasses methods used in the sensitization and treatment of cancer based upon the expression of SGEF.

## Claims

### Claim 1

A method of sensitizing a patient with glioblastoma to a radiation therapy and/or chemotherapy, the method comprising the steps of:
administering to the patient with glioblastoma an src-homology 3 domain containing guanine nucleotide exchange factor (SGEF) inhibitor, wherein the SGEF inhibitor sensitizes the glioblastoma to the radiation therapy and/or chemotherapy, and wherein the SGEF inhibitor is a small hairpin RNA targeting the nucleic acid encoding for SGEF.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 2)

The method of claim 2, wherein the SGEF inhibitor converts the invasive glioblastoma to a non-migratory phenotype.

### Claim 4 (depends on 1)

The method of claim 1, and further comprising administering a therapeutically effective amount of the radiation therapy and/or chemotherapy to the patient with glioblastoma.

### Claim 5 (depends on 4)

The method of claim 4, wherein the radiation therapy and/or chemotherapy comprises the administration of one or more compounds selected from the group consisting of TROY inhibitors, Pyk2 inhibitors, Rac1 inhibitors, Dock180 inhibitors, Dock7 inhibitors, TWEAK inhibitors, Fn14 inhibitors, BAD inhibitors, and PI3k inhibitors, TRAIL, camptothecin, temozolomide and bevacizumab.

### Claim 6

A method of treating a patient with invasive glioblastoma, the method comprising the steps of:
a. sensitizing the patient with invasive glioblastoma by reducing an expression level of Src-homology 3 domain containing guanine nucleotide exchange factor (SGEF) using an SGEF inhibitor, wherein the SGEF inhibitor is a small hairpin RNA targeting the nucleic acid encoding for SGEF; and
b. administering a therapeutically effective amount of a radiation therapy and/or chemotherapy to the patient with invasive glioblastoma.

### Claim 7 (depends on 6)

The method of claim 6, wherein the radiation therapy and/or chemotherapy comprises the administration of one or more compounds selected from the group consisting of TROY inhibitors, Pyk2 inhibitors, Rac1 inhibitors, Dock180 inhibitors, Dock7 inhibitors, TWEAK inhibitors, Fn14 inhibitors, BAD inhibitors, and PI3k inhibitors, TRAIL, camptothecin, temozolomide and bevacizumab.

### Claim 8 (depends on 6)

The method of claim 6, wherein the SGEF inhibitor converts the invasive glioblastoma to a non-migratory phenotype.

### Claim 9 (depends on 6)

The method of claim 6, wherein the chemotherapy comprises administering a therapeutically effective amount of temozolomide.

### Claim 10 (depends on 6)

The method of claim 6, wherein the radiation therapy comprises the administration of a therapeutically effective amount of radiation.

### Claim 11

A method of treating a patient with glioblastoma, the method comprising the steps of:
a. sensitizing the patient with glioblastoma by reducing an expression level of Src-homology 3 domain containing guanine nucleotide exchange factor (SGEF) by administering to the patient a small hairpin RNA targeting SGEF; and
b. administering a therapeutically effective amount of a radiation therapy and/or chemotherapy to the patient with glioblastoma.

### Claim 12 (depends on 11)

The method of claim 11, wherein the radiation therapy and/or chemotherapy comprises the administration of one or more compounds selected from the group consisting of TROY inhibitors, Pyk2 inhibitors, Rac1 inhibitors, Dock180 inhibitors, Dock7 inhibitors, TWEAK inhibitors, Fn14 inhibitors, BAD inhibitors, and PI3k inhibitors, TRAIL, camptothecin, temozolomide and bevacizumab.

### Claim 13 (depends on 11)

The method of claim 11, wherein the radiation therapy comprises the administration of a therapeutically effective amount of radiation.