# US 10,765,675 B2 · Compositions and methods for treating Ewing family tumors

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

- Number: US 10,765,675 B2
- Document ID: US10765675B2
- Status: Granted
- Kind: B2
- Application number: 15/755,258
- Filed: 2016-08-22
- Published: 2018-08-30
- Granted: 2020-09-08
- Earliest claimed: 2015-08-24
- Assignees: The Methodist Hospital
- Applicants: The Methodist Hospital
- Inventors: Hong Zhao; Stephen T. C. Wong
- Web page: https://patentgrep.com/patent/US10765675B2

## CPC

- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/155: Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- C12Q 2600/158: Expression markers
- 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
- 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

## Abstract

A method for treating a sarcoma by administering a tyrosine kinase inhibitor and a biguanide compound. Also described is a method for treating a tumor of the Ewing Sarcoma family by obtaining a tumor sample; determining in the sample gene expression levels of ACTB, B2M, MLH1, PRKDC, XPC, APEX1, ERCC5, MMS19, or RAD23; and administering a tyrosine kinase inhibitor and a biguanide compound. Furthermore, a pharmaceutical composition for treating a Ewing family tumor is disclosed. The composition contains a tyrosine kinase inhibitor, a biguanide compound, and a pharmaceutically acceptable excipient.

## Claims

### Claim 1

A method for treating a sarcoma, the method comprising administering to a subject having a sarcoma an effective amount of imatinib and metformin.

### Claim 2 (depends on 1)

The method of claim 1, further comprising administering a tyrosine kinase inhibitor different from imatinib or a biguanide compound different from metformin.

### Claim 3 (depends on 1)

The method of claim 1, further comprising administering a chemotherapy agent selected from the group consisting of cyclophosphamide, doxorubicin, 5-fluorouracil, docetaxel, paclitaxel, trastuzumab, methotrexate, epirubicin, cisplatin, carboplatin, vinorelbine, capecitabine, gemcitabine, mitoxantrone, isabepilone, eribulin, lapatinib, carmustine, a nitrogen mustard, a sulfur mustard, a platin tetranitrate, vinblastine, etoposide, camptothecin, a topoisomerase inhibitor, and a combination thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cancer is a Ewing Sarcoma family tumor.

### Claim 5

A method for treating a Ewing family tumor, the method comprising:
obtaining a tissue sample from a Ewing family tumor in a subject;
determining in the sample a level of expression of a gene selected from ACTB, B2M, MLH1, PRKDC, XPC, APEX1, ERCC5, MMS19, and RAD23A; and
administering to the subject an effective amount of imatinib and metformin if the level of expression of the gene is elevated as compared to a predetermined level of expression of the gene.

### Claim 6 (depends on 5)

The method of claim 5, further comprising administering a tyrosine kinase inhibitor different from imatinib or a biguanide compound different from metformin.

### Claim 7 (depends on 5)

The method of claim 5, further comprising administering a chemotherapy agent selected from the group consisting of cyclophosphamide, doxorubicin, 5-fluorouracil, docetaxel, paclitaxel, trastuzumab, methotrexate, epirubicin, cisplatin, carboplatin, vinorelbine, capecitabine, gemcitabine, mitoxantrone, isabepilone, eribulin, lapatinib, carmustine, a nitrogen mustard, a sulfur mustard, a platin tetranitrate, vinblastine, etoposide, camptothecin, a topoisomerase inhibitor, or a combination thereof.

### Claim 8 (depends on 5)

The method of claim 5, wherein the determining step is carried out by quantitative reverse-transcription polymerase chain reaction.