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Last Updated: March 29, 2024

Claims for Patent: 6,831,171


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Summary for Patent: 6,831,171
Title: Nucleic acid catalysts with endonuclease activity
Abstract:The present invention relates to novel Nucleic acid catalysts, methods of synthesis, and uses thereof.
Inventor(s): Breaker; Ronald (Guilford, CT), Beigelman; Leonid (Longmont, CO)
Assignee: Yale University (New Haven, CT) Sirna Therapeutics, Inc. (Boulder, CO)
Application Number:09/780,929
Patent Claims:1. A nucleic acid molecule with endonuclease activity having the formula II:3'--X--Z--Y--5' wherein, X and Y are independently oligonucleotides of length sufficient to stably interact with a target nucleic acid molecule; Z is an oligonucleotide having a nucleotide sequence selected from the group consisting of 5'-AGAUAACGUGAAGAU-3' SEQ ID NO:97) and 5'-AAUGGCCUAUCGGUGCGA-3' (SEQ ID NO: 98).

2. The nucleic acid molecule with endonuclease activity of claim 1, wherein said chemical linkage is independently or in combination selected from the group consisting of phosphate ester amide, phosphorothioate, phosphorodithioate, arabino, and arabinofluoro linkages.

3. The nucleic acid molecule with endonuclease activity of claim 1, wherein said nucleic acid molecule is chemically synthesized.

4. The nucleic acid molecule with endonuclease activity of claim 1, wherein said nucleic acid molecule comprises at least one sugar modification.

5. The nucleic acid molecule with endonuclease activity of claim, wherein said nucleic acid molecule comprises at least one nucleic acid base modification.

6. The nucleic acid molecule with endonuclease activity of claim 1, wherein said nucleic acid molecule comprises at least one phosphate backbone modification.

7. The nucleic acid molecule with endonuclease activity of claim 4, wherein said sugar modification is selected from the group consisting of 2'-H, 2'-O-methyl, 2'-O-allyl, 2'-C-allyl, 2'-deoxy-2'-fluoro, and 2'-deoxy-2'-amino modifications.

8. The nucleic acid molecule with endonuclease activity of claim 6, wherein said phosphate backbone modification is selected from the group consisting of phosphorothioate, phosphorodithioate, and amide modifications.

9. The nucleic acid molecule with endonuclease activity of claim 1, wherein said nucleic acid molecule comprises a 5'-cap, a 3'-cap, or both a 5'-cap and a 3'-cap.

10. The nucleic acid molecule with endonuclease activity of claim 9, wherein said 5'-cap is a phosphorothioate modification of at least one 5'-terminal nucleotide in said nucleic acid molecule.

11. The nucleic acid molecule with endonuclease activity of claim 9, wherein said 5'-cap is a phosphorothioate modification of at least two 5'-terminal nucleotides in said nucleic acid molecule.

12. The nucleic acid molecule with endonuclease activity of claim 9, wherein said 5'-cap is a phosphorothioate modification of at least three 5'-terminal nucleotides in said nucleic acid molecule.

13. The nucleic acid molecule with endonuclease activity of claim 9, wherein said 5'-cap is a phosphorothioate modification of at least four 5'-terminal nucleotides in said nucleic acid molecule.

14. The nucleic acid molecule with endonuclease activity of claim 9, wherein said 3'-cap is a 3'-3' inverted riboabasic moiety.

15. The nucleic acid molecule with endonuclease activity of claim 9, wherein said 3'-cap is a 3'-3' inverted deoxyriboabasic moiety.

16. The nucleic acid molecule with endonuclease activity of claim 1, wherein said nucleic acid cleaves a separate nucleic acid molecule.

17. The nucleic acid molecule with endonuclease activity of claim 16, wherein said separate nucleic acid molecule is RNA.

18. The nucleic acid molecule with endonuclease activity of claim 16, wherein said nucleic acid comprises between 12 and 100 bases complementary to said separate nucleic acid molecule.

19. The nucleic acid molecule with endonuclease activity of claim 16, wherein said nucleic acid comprises between 14 and 24 bases complementary to said separate nucleic acid molecule.

20. The nucleic acid molecule with endonuclease activity of claims 1, wherein said X and Y are independently of length selected from the group consisting of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, and 20 nucleotides.

21. The nucleic acid molecule with endonuclease activity of claim 1, wherein the length of X is equal to the length of Y.

22. The nucleic acid molecule with endonuclease activity of claim 1, wherein the length of X is not equal to the length of Y.

23. An isolated cell including the nucleic acid molecule with endonuclease activity of claim 1.

24. The isolated cell of claim 23, wherein said cell is a mammalian cell.

25. The isolated cell of claim 24, wherein said cell is a human cell.

26. An expression vector comprising a nucleic acid sequence encoding the nucleic acid molecule with endonuclease activity of claim 1, in a manner which allows expression of the nucleic acid molecule with endonuclease activity.

27. An isolated cell including the expression vector of claim 26.

28. The isolated cell of claim 27, wherein said cell is a mammalian cell.

29. The isolated cell of claim 28, wherein said cell is a human cell.

30. A composition comprising the nucleic acid molecule with endonuclease activity of claim 1 and a phamaceutically acceptable diluent.

31. The expression vector of claim 26, wherein said vector comprises: a) a transcription initiation region; b) a transcription termination region; c) a nucleic acid sequence encoding the nucleic acid molecule with endonuclease activity of claim 2; and wherein said nucleic acid sequence is operably linked to said initiation region and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.

32. The expression vector of claim 26, wherein said vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an open reading frame; d) a nucleic acid sequence encoding the nucleic acid molecule with endonuclease activity of claim 2, wherein said sequence is operably linked to the 3'-end of said open reading frame; and wherein said nucleic acid sequence is operably linked to said initiation region, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.

33. The expression vector of claim 26, wherein said vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) a nucleic acid sequence encoding the nucleic acid molecule with endonuclease activity of claim 2; and wherein said nucleic acid sequence is operably linked to said initiation region, said intron and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.

34. The expression vector of claim 26, wherein said vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) an open reading frame; e) a nucleic acid sequence encoding the nucleic acid molecule with endonuclease activity of claim 2, wherein said sequence is operably linked to the 3'-end of said open reading frame; and wherein said nucleic acid sequence is operably linked to said initiation region, said intron, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.

Details for Patent 6,831,171

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 06/04/1986 ⤷  Try a Trial 2020-02-08
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Try a Trial 2020-02-08
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b Injection 103132 ⤷  Try a Trial 2020-02-08
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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