# US 10,480,032 B2 · Use of EI24 gene

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- Number: US 10,480,032 B2
- Document ID: US10480032B2
- Status: Granted
- Kind: B2
- Application number: 15/458,676
- Filed: 2017-03-14
- Published: 2017-09-21
- Granted: 2019-11-19
- Earliest claimed: 2016-03-15
- Assignees: University-Industry Foundation, Yonsei University
- Applicants: University-Industry Foundation, Yonsei University
- Inventors: Han Woong Lee; Jung-Min Choi; Byoung Chul Cho; Yu-Ra Choi; Ji-Young Jang; Hye Ryun Kim
- Web page: https://patentgrep.com/patent/US10480032B2

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- A61K 31/277: having a ring, e.g. verapamil
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/47: Quinolines; Isoquinolines
- A61K 31/4706: 4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
- A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 38/1709: {from mammals}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- G01N 33/57595: {involving intracellular compounds}
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/158: Expression markers
- G01N 33/5752: of the lungs
- 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
- 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)
- 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 present disclosure relates to a novel use of EI24, and provides a novel use of EI24 involved in the improvement of EGFR-TKI drug resistance by inhibiting IGF-1R signaling. According to the present disclosure, the presence or absence of resistance to anti-cancer drugs may be determined by detecting an expression level of EI24. In addition, resistance to anti-cancer drugs may be inhibited, delayed, or improved using EI24 or an activating agent thereof. Moreover, by regulating a pathway of EI24-mediated resistance to anti-cancer drugs, the efficacy of existing anti-cancer drugs may be enhanced, and resistance to anti-cancer drugs may be inhibited, delayed, or improved.

## Claims

### Claim 1

A method of diagnosing and treating EGFR-TKI drug resistance in an EGFR-TKI drug-administered patient, the method comprising:
contacting a biological sample from an EGFR-TKI drug-administered patient with an antibody specifically binding to an EI24 protein and an antibody specifically binding to an insulin growth factor-1 (IGF-1) protein and detecting an expression level of the EI24 protein and the IGF-1 protein in the biological sample by detecting the antibody binding to the EI24 protein and to the IGF-1 protein;
diagnosing the EGFR-TKI drug-administered patient as having EGFR-TKI drug resistance when the expression level of the EI24 protein is 5 times to 20 times lower than that of a control sample obtained from an EGFR-TKI drug resistance-free control group and the expression level of the IGF-1 protein is greater than that of a control sample obtained from an EGFR-TKI drug resistance-free control group; and
administering an effective amount of EI24 and at least one selected from the group consisting of EGFR-TKI and an insulin growth factor-1 receptor (IGF-1R) inhibitor to the patient diagnosed as having EGFR-TKI drug resistance.

### Claim 2 (depends on 1)

The method of claim 1, wherein the EGFR-TKI comprises at least one selected from the group consisting of erlotinib, lapatinib, apatinib, neratinib, poziotinib, and gefitinib.

### Claim 3 (depends on 1)

The method of claim 1, wherein the IGF-1R inhibitor comprises at least one selected from the group consisting of OSI-906, NVP-AEW541, GSK1904529A, NVP-ADW742, BMS-536924, NT157, AG-1024, GSK1838705A, BMS-754807, PQ401, and picropodophyllin.