IP Library Granted Patent US 9,731,032
Granted Patent B2
US 9,731,032 · App. 14/763,283 · Granted Aug 15, 2017

Aptamers for tumor initiating cells

Inventors: Jeremy N. Rich (Cleveland, OH); Youngmi Kim (Cleveland, OH); Anita B. Hjelmeland (Cleveland, OH)
Assignee: The Cleveland Clinic Foundation
A61K47/48907A61K47/10A61K47/48092A61K47/48915A61K49/0002C12N15/115G01N33/57407C12N2310/16C12N2310/3517C12N2320/30
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Quick Facts
Patent No.
US 9,731,032
App. No.
14/763,283
Granted
Aug 15, 2017
Kind
B2
Abstract

Aptamers consisting of a single stranded nucleic acids having 100 nucleotides or less that specifically binds to tumor initiating cancer cells are described. The aptamers can be identified by screening a large pool of randomly generated aptamers to obtain a discrete set of aptamers that specifically bind to tumor initiating cancer cells, such as those found in brain cancer or glioblastoma. The aptamers can also be linked or complexed with anticancer agents or imaging agents for use in therapy or diagnosis.

Claims (29)

1. An aptamer consisting of a single stranded nucleic acid having 100 nucleotides or less and comprising a sequence selected from the group consisting of SEQ ID NOS. 1-9 or an analog thereof that specifically binds to tumor initiating cancer cells.

2. The aptamer of claim 1 , wherein the nucleic acid has 50 nucleotides or less.

3. The aptamer of claim 1 , wherein the tumor initiating cancer cells are brain cancer cells.

4. The aptamer of claim 1 , wherein the tumor initiating cancer cells are glioblastoma cells.

5. The aptamer of claim 1 , wherein the nucleic acid is DNA.

6. The aptamer of claim 1 , wherein the nucleic acid is complexed or linked to an imaging agent or an anticancer agent.

7. The aptamer of claim 1 , wherein the aptamer comprises a sequence selected from the group consisting of SEQ ID NOS. 1-3 or an analog thereof.

8. A method of imaging tumor initiating cancer cells in a subject, comprising administering an effective amount of an aptamer consisting of a single stranded nucleic acid having 100 nucleotides or less and comprising a sequence selected from the group consisting of SEQ ID NOS. 1-9 or an analog thereof that specifically binds to tumor initiating cancer cells, the aptamer being complexed or linked to an imaging agent, to the subject and detecting the aptamers with an imaging apparatus.

9. The method of claim 8 , wherein the aptamer is detected in vivo.

10. The method of claim 8 , wherein the aptamer is detected ex vivo.

11. The method of claim 8 , wherein the aptamer specifically binds to tumor initiating brain cancer cells.

12. The method of claim 8 , wherein the aptamer specifically binds to tumor initiating glioblastoma cells.

13. The method of claim 8 , wherein the aptamer comprises a sequence selected from the group consisting of SEQ ID NOS. 1-9, or analog thereof.

14. The method of claim 8 , wherein the aptamer comprises a sequence selected from the group consisting of SEQ ID NOS. 1-3, or analog thereof.

15. A method of treating brain cancer in a subject, comprising administering an effective amount of an aptamer consisting of a single stranded nucleic acid having 100 nucleotides or less and comprising a sequence selected from the group consisting of SEQ ID NOS. 1-9 or an analog thereof that specifically binds to brain cancer cells, the aptamer being complexed or linked to an anticancer agent, to the subject.

16. The method of claim 15 , wherein the brain cancer is glioblastoma and the aptamer specifically binds to glioblastoma cells.

17. The method of claim 15 , wherein the aptamer specifically binds to brain tumor initiating cells.

18. The method of claim 15 , wherein the aptamer comprises a sequence selected from the group consisting of SEQ ID NOS. 1-9, or analog thereof.

19. The method of claim 15 , wherein the aptamer comprises a sequence selected from the group consisting of SEQ ID NOS. 1-3, or analog thereof.

20. The aptamer of claim 1 , wherein the aptamer comprises SEQ ID NO. 1 or an analog thereof.

21. The aptamer of claim 1 , wherein the aptamer comprises SEQ ID NO. 2 or an analog thereof.

22. The aptamer of claim 1 , wherein the aptamer comprises SEQ ID NO. 3 or an analog thereof.

23. The aptamer of claim 1 , wherein the aptamer comprises SEQ ID NO. 4 or an analog thereof.

24. The aptamer of claim 1 , wherein the aptamer comprises SEQ ID NO. 5 or an analog thereof.

25. The aptamer of claim 1 , wherein the aptamer comprises SEQ ID NO. 6 or an analog thereof.

26. The aptamer of claim 1 , wherein the aptamer comprises SEQ ID NO. 7 or an analog thereof.

27. The aptamer of claim 1 , wherein the aptamer comprises SEQ ID NO. 8 or an analog thereof.

28. The aptamer of claim 1 , wherein the aptamer comprises SEQ ID NO. 9 or an analog thereof.

29. The aptamer of claim 1 , wherein the nucleic acid has 35 nucleotides or less.

Assignments (2)
CONFIRMATORY LICENSE Recorded Apr 6, 2017
From: CLEVELAND CLINIC FOUNDATION
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 042171/0369 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 9, 2016
From: RICH, JEREMY N.; KIM, YOUNGMI; HJELMELAND, ANITA B.
To: THE CLEVELAND CLINIC FOUNDATION
Reel/Frame 040961/0336 →
Continuity (3)
Provisional Application 61760376 · Feb 4, 2013
Related Publication 20150366996A1 · Dec 24, 2015
Related Publication 20170165376A9 · Jun 15, 2017