# US 11,999,956 B2 · Targeted therapy composition and its use for suppressing breast cancer cell proliferation, migration or invasion

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- Number: US 11,999,956 B2
- Document ID: US11999956B2
- Status: Granted
- Kind: B2
- Application number: 17/930,136
- Filed: 2022-09-07
- Published: 2023-03-23
- Granted: 2024-06-04
- Earliest claimed: 2021-09-13
- Assignees: National Cheng Kung University
- Applicants: National Cheng Kung University
- Inventors: Nan-Haw Chow; Yi-Wen Wang; Yih-Lin Tuan; Yao-Lung Kuo
- Web page: https://patentgrep.com/patent/US11999956B2

## CPC

- C12N 15/1135: {against oncogenes or tumor suppressor genes}
- 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 31/713: Double-stranded nucleic acids or oligonucleotides
- A61P 35/00: Antineoplastic agents
- C12N 15/1138: {against receptors or cell surface proteins}
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/31: Combination therapy
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention discloses a targeted therapy composition and a method for suppressing breast cancer cell proliferation, migration or invasion by administrating the targeted therapy composition to a subject in need thereof. The composition comprises a type 3 epithelial membrane proteins (EMP3) targeted inhibitor. The breast cancer cells are characterized by upregulation of EMP3, EGFR, HER2, HER3, HR, or downregulation of HER4 gene expression. EMP3-targeting oligonucleotide or nuclease is administrated upon the breast cancer cells so as to degrade EMP3-coding DNA or mRNA, and to suppress breast cancer cell proliferation, migration or invasion.

## Claims

### Claim 1

A method for suppressing breast cancer cell proliferation, migration or invasion, comprising administrating a targeted therapy composition comprising an effective dosage of EMP3-targeting inhibitor to a subject in need thereof;
wherein the EMP3-targeting inhibitor comprises RNA interference comprising a small interfering RNA, short hairpin RNA, microRNA or a combination thereof, and the RNA interference hybridizes with EMP3 coding DNA or mRNA by complementary base pairing;
wherein the RNA interference comprises a complementary sequence including SEQ NO: 1 or SEQ NO: 2.

### Claim 2 (depends on 1)

The method as claimed in claim 1, comprising sequentially or separately administrating the targeted therapy composition and Metformin to the subject in need, wherein the targeted therapy composition is administrated to the subject in need when Metformin is completely excreted, or the targeted therapy composition is administrated to the subject in need at 24 hours post Metformin administration.

### Claim 3 (depends on 2)

The method as claimed in claim 2, wherein the subject in need is human (Homo sapiens) having diabetes.

### Claim 4 (depends on 1)

The method as claimed in claim 1, wherein the breast cancer cell is selected from a group consisting of hormone receptor (HR) positive breast cancer cell, human epidermal growth factor receptor 2 (HER2) positive breast cancer cell and triple negative breast cancer cell.

### Claim 5 (depends on 1)

The method as claimed in claim 1, wherein the complementary sequence hybridizes to a nucleotide sequence of 61st to 180th or 241st to 360th base pairs of the mRNA by complementary base pairing, wherein the mRNA consists of SEQ NO: 5.

### Claim 6

A method for suppressing breast cancer cell proliferation, migration or invasion, comprising administrating a targeted therapy composition comprising an effective dosage of EMP3-targeting inhibitor to a subject in need thereof;
wherein the EMP3-targeting inhibitor comprises a plasmid DNA fragment carried by a vector comprising a promoter upstream the plasmid DNA fragment so as to amplify productions of a RNA interference, and the RNA interference hybridizes with EMP3 coding DNA or mRNA by complementary base pairing;
wherein the plasmid DNA fragment comprises SEQ NO: 3 or SEQ NO: 4.

### Claim 7 (depends on 5)

The method as claimed in claim 5, wherein the RNA interference comprises a complementary sequence, and the complementary sequence hybridizes to a nucleotide sequence of 61st to 180th or 241st to 360th base pairs of the mRNA by complementary base pairing, wherein the mRNA consists of SEQ NO: 5.

### Claim 8 (depends on 6)

The method as claimed in claim 6, wherein the RNA interference comprises a small interfering RNA, short hairpin RNA, microRNA or a combination thereof, and wherein the complementary sequence comprises SEQ NO: 1 or SEQ NO: 2.

### Claim 9 (depends on 6)

The method as claimed in claim 6, comprising sequentially or separately administrating the targeted therapy composition and Metformin to the subject in need, wherein the targeted therapy composition is administrated to the subject in need when Metformin is completely excreted, or the targeted therapy composition is administrated to the subject in need at 24 hours post Metformin administration.

### Claim 10 (depends on 6)

The method as claimed in claim 6, wherein the subject in need is human (Homo sapiens) having diabetes.

### Claim 11 (depends on 10)

The method as claimed in claim 10, wherein the breast cancer cell is selected from a group consisting of hormone receptor (HR) positive breast cancer cell, human epidermal growth factor receptor 2 (HER2) positive breast cancer cell and triple negative breast cancer cell.