Aptamer for periostin and anti-cancer composition including same

Patent metadata

Field	Value
Publication number	US-9650638-B2
Application number	US-201214411176-A
Country	US
Kind code	B2
Filing date	Nov 12, 2012
Priority date	Jul 2, 2012
Publication date	May 16, 2017
Grant date	May 16, 2017

Abstract

This disclosure relates to DNA aptamer specifically binding to periostin, which is cancer-related protein, a composition for inhibiting cancer and/or cancer metastasis and/or a composition for diagnosis of cancer and/or cancer metastasis, comprising the same as an active ingredient, wherein the aptamer has different binding mechanism from the existing antibodies, and thus, may inhibit and diagnose cancer/cancer metastasis more effectively.

First claim

The invention claimed is:

1. A periostin aptamer that specifically binds to periostin and is in a length of 25 to 100 bases comprising 5 to 20 modified bases that are substituted with a hydrophobic functional group selected from the group consisting of a naphthyl group, a benzyl group, a pyrrole benzyl group, and tryptophan at 5-position of dU (deoxyuracil),
wherein the nucleotide sequence of the periostin aptamer is selected from the group consisting of SEQ ID NO: 5 to SEQ ID NO: 40, where n in the nucleotide sequence is a modified base substituted at 5-position of dU (deoxyuracil) with a hydrophobic functional group selected from the group consisting of a naphthyl group, a benzyl group, a pyrrole benzyl group, and tryptophan.

2. The periostin aptamer according to claim 1 , wherein the periostin aptamer further comprises an additional nucleotide sequence at the 5′-terminal, 3′-terminal or both terminals selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 4.

3. The periostin aptamer according to claim 2 , wherein the periostin aptamer is represented by the following nucleotide sequence of SEQ ID NO: 45 or SEQ ID NO: 46:

(SEQ ID NO: 45)

5′-ACGAG-[N]-AACAA-3′

or

(SEQ ID NO: 46)

5′-GATGTGAGTGTGTGACGAG-[N]-AACAACAGAACAAGGAAAGG-3′,

in the nucleotide sequence, ‘N’ consists of 25 to 80 bases, each base is independently selected from the group consisting of A, C, G, deoxy forms of A, C, and G, and a modified base that is substituted at 5-position of dU (deoxyuracil) with a naphthyl group, a benzyl group, a pyrrole benzyl group, and tryptophan, and the number of modified base is 5 to 20.

4. The periostin aptamer according to claim 3 , wherein the ‘N’ is a nucleotide sequence selected from the group consisting of SEQ ID NO: 5 to SEQ ID NO: 40.

5. The periostin aptamer according to claim 4 , wherein the periostin aptamer is represented by the nucleotide sequence selected from the group consisting of SEQ ID NO: 41 to SEQ ID NO: 44.

6. The periostin aptamer according to claim 1 , wherein the periostin aptamer comprises an additional nucleotide sequence consisting of 3 to 25 bases at 5′-terminal, 3′-terminal, or both terminals, and consists of total 30 to 120 bases.

7. The periostin aptamer according to claim 1 , wherein the periostin aptamer is modified by binding of at least one selected from the group consisting of PEG (polyethylene glycol), idT (inverted deoxythymidine), LNA (Locked Nucleic Acid), 2′-methoxy nucleoside, 2′-amino nucleoside, 2′F-nucleoside, amine linker, thiol linker and cholesterol, to the 5′-terminal, 3′-terminal, or both terminals of the periostin aptamer.

8. A pharmaceutical composition comprising the periostin aptamer of claim 1 as an active ingredient.

9. The pharmaceutical composition according to claim 8 , wherein the periostin aptamer is modified by binding of at least one selected from the group consisting of PEG (polyethylene glycol), idT (inverted deoxythymidine), LNA (Locked Nucleic Acid), 2′-methoxy nucleoside, 2′-amino nucleoside, 2′F-nucleoside, amine linker, thiol linker and cholesterol, to the 5′-terminal, 3′-terminal, or both terminals of the periostin aptamer.

10. A method for treating cancer or inhibiting cancer metastasis, comprising administering a pharmaceutically effective amount of the periostin aptamer of claim 1 to a subject in need of treatment of cancer or inhibition of cancer metastasis.

11. The method according to claim 10 , wherein the periostin aptamer is modified by binding of at least one selected from the group consisting of PEG (polyethylene glycol), idT (inverted deoxythymidine), LNA (Locked Nucleic Acid), 2′-methoxy nucleoside, 2′-amino nucleoside, 2′F-nucleoside, amine linker, thiol linker and cholesterol, to the 5′-terminal, 3′-terminal, or both terminals of the periostin aptamer.

12. The method according to claim 10 , wherein the cancer is at least one selected from the group consisting of breast cancer, colorectal cancer, lung cancer, gallbladder cancer, pancreatic cancer, stomach cancer, uterine cancer, head and neck squamous cell carcinoma, prostate cancer, and glioblastoma.

Assignees

• Unist Academy-Industry Res Corp
• Postech Academy-Industry Found
• Unist (Ulsan Nat Inst Of Science And Technology)

Inventors

• Suh Pann-Ghill
• Kim Ii Shin
• Lee Yu Jin
• Kim Youn Dong
• Chae Young Chan
• Im Jong Hun
• Ryu Sung Ho

Classifications

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title

• G01N2333/705

  Assays involving receptors, cell surface antigens or cell surface determinants · CPC title

• C12N15/115 Primary

  Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith {; Nucleic acids binding to non-nucleic acids, e.g. aptamers} · CPC title

• C12N2310/335

  Modified T or U · CPC title

• C12N2320/30

  Special therapeutic applications · CPC title