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Last Updated: March 28, 2024

Claims for Patent: 6,057,156


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Summary for Patent: 6,057,156
Title: Enzymatic nucleic acid treatment of diseases or conditions related to levels of epidermal growth factor receptors
Abstract:Enzymatic nucleic acid molecules which cleave EGFR RNA.
Inventor(s): Akhtar; Saghir (Birmingham, GB), Fell; Patricia (Wythall, GB), McSwiggen; James A. (Boulder, CO)
Assignee: Robozyme Pharmaceuticals, Inc. (Boulder, CO)
Application Number:08/985,162
Patent Claims:1. An enzymatic nucleic acid molecule which specifically cleaves RNA derived from an epidermal growth factor receptor (EGFR) gene encoding an EGFR with a functional extracellular domain and a functional intracellular domain.

2. The enzymatic nucleic acid molecule of claim 1, wherein said nucleic acid molecule is in a hairpin motif.

3. The enzymatic nucleic acid molecule of claim 1, wherein said nucleic acid molecule is in a hammerhead motif.

4. The enzymatic nucleic acid molecule of claim 3, wherein said nucleic acid molecule comprises a stem II region of length greater than or equal to 2 base pairs.

5. The enzymatic nucleic acid molecule of claim 3, wherein the binding arms of said nucleic acid molecule comprises sequences complementary to any of SEQ ID NOs 1-823.

6. The enzymatic nucleic molecule of claim 2, wherein the binding arms of said nucleic acid molecule comprises sequences complementary to any of SEQ ID NOs 1759-1870.

7. The enzymatic nucleic acid molecule of claim 2, wherein said nucleic haipin motif consists essentially of any ribozyme sequence shown as SEQ ID NOs 1647-1758.

8. The enzymatic nucleic molecule of claim 3, wherein said nucleic hammerhead motif consists essentially of any ribozyme sequence shown as SEQ ID NOs 824-1646.

9. The enzymatic nucleic acid molecule of claim 1, wherein said nucleic acid molecule is in a hepatitis delta virus, VS nucleic acid, group I intron, Group II intron, or RNase P nucleic acid motif.

10. The enzymatic nucleic acid molecule of claim 1, wherein said nucleic acid comprises between 12 and 100 bases complementary to said RNA.

11. The enzymatic nucleic acid molecule of claim 1, wherein said nucleic acid comprises between 14 and 24 bases complementary to said mRNA.

12. A mammalian cell including an enzymatic nucleic acid molecule of claim 1, wherein said mammalian cell is not a human.

13. The cell of claim 12, wherein said cell is a human cell.

14. An expression vector comprising nucleic acid sequence encoding at least one of the enzymatic nucleic acid molecule of claim 1, in a manner which allows expression of that enzymatic nucleic acid molecule.

15. A mammalian cell including an expression vector of claim 14, wherein said mammalian cell is not a human.

16. The cell of claim 15, wherein said cell is a human cell.

17. A composition comprising the enzymatic nucleic acid molecule of claim 1.

18. The enzymatic nucleic acid molecule of claim 3, wherein said nucleic acid molecule comprises at least five ribose residues, and wherein said nucleic acid comprises phosphorothioate linkages at at least three of the 5' terminal nucleotides, and wherein said nucleic acid comprises a 2'-C-allyl modification at position No. 4 of said nucleic acid, and wherein said nucleic acid comprises at least ten 2'-O-methyl modifications, and wherein said nucleic acid comprises a 3'- end modification.

19. The enzymatic nucleic acid of claim 18, wherein said nucleic acid comprises a 3'--3' linked inverted ribose moiety at said 3' end.

20. The enzymatic nucleic acid molecule of claim 3, wherein said nucleic acid molecule comprises at least five ribose residues, and wherein said nucleic acid molecule comprises phosphorothioate linkages at at least three of the 5' terminal nucleotides, and wherein said nucleic acid comprises a 2'-amino modification at position No. 4 and/or at position No. 7 of said nucleic acid molcule, wherein said nucleic acid molcule comprises at least ten 2'-O-methyl modifications, and wherein said nucleic acid comprises a 3'-end modification.

21. The enzymatic nucleic acid molecule of claim 3, wherein said nucleic acid molecule comprises at least five ribose residues, and wherein said nucleic acid molecule comprises phosphorothioate linkages at at least three of the 5' terminal nucleotides, and wherein said nucleic acid molecule comprises an abasic substitution at position No. 4 and/or at position No. 7 of said nucleic acid molecule, wherein said nucleic acid comprises at least ten 2'-O-methyl modifications, and wherein said nucleic acid molecule comprises a 3'-end modification.

22. The enzymatic nucleic acid molecule of claim 3, wherein said nucleic acid molecule comprises of at least five ribose residues, and wherein said nucleic acid comprises phosphorothioate linkages at at least three of the 5' terminal nucleotides, and wherein said nucleic acid molecule comprises a 6-methyl uridine substitution at position No. 4 and/or at position No. 7 of said nucleic acid molecule, wherein said nucleic acid molecule comprises at least ten 2'-O-methyl modifications, and wherein said nucleic acid molecule comprises a 3' end modification.

23. An enzymatic nucleic acid molecule which specifically cleaves RNA derived from an epidermal growth factor receptor (EGFR) gene encoding an EGFR which does not contain a deletion in its extracellular domain.

24. The enzymatic nucleic acid molecule of claim 23, wherein said nucleic acid molecule is in a hairpin motif.

25. The enzymatic nucleic acid molecule of claim 23, wherein said nucleic acid molecule is in a hammerhead motif.

26. The enzymatic nucleic acid molecule of claim 25, wherein said nucleic acid molecule comprises a stem II region of length greater than or equal to 2 base pairs.

27. The enzymatic nucleic acid molecule of claim 25, wherein the binding arms of said nucleic acid molecule comprises sequences complementary to any of SEQ ID Nos 1-823.

28. The enzymatic nucleic acid molecule of claim 24, wherein the binding arms of said nucleic acid molecule comprises sequences complementary to any of SEQ ID Nos 1759-1870.

29. The enzymatic nucleic acid molecule of claim 24, wherein said nucleic hairpin motif consists essentially of any ribozyme sequence shown as SEQ ID Nos 1647-1758.

30. The enzymatic nucleic acid molecule of claim 25, wherein said nucleic hammerhead motif consists essentially of any ribozyme sequence shown as SEQ ID Nos 824-1646.

31. The enzymatic nucleic acid molecule of claim 23, wherein said nucleic acid molecule is in a hepatitis delta virus, VS nucleic acid, Group I intron, Group II intron, or Rnase P nucleic acid motif.

32. The enzymatic nucleic acid molecule of claim 23, wherein said nucleic acid comprises between 12 and 100 bases complementary to said RNA.

33. The enzymatic nucleic acid molecule of claim 23, wherein said nucleic acid comprises between 14 and 24 bases complementary to said mRNA.

34. A mammalian cell including an enzymatic nucleic acid molecule of claim 23, wherein said mammalian cell is not a human.

35. The cell of claim 34, wherein said cell is a human cell.

36. An expression vector comprising nucleic acid sequence encoding at least one of the enzymatic nucleic acid molecule of claim 23, in a manner which allows expression of that enzymatic nucleic acid molecule.

37. A mammalian cell including an expression vector of claim 36, wherein said mammalian cell is not a human.

38. The cell of claim 37, wherein said cell is a human cell.

39. The enzymatic nucleic acid molecule of claim 25, wherein said nucleic acid comprises at least five ribose residues, and wherein said nucleic acid comprises phosphorothioate linkages at least three of the 5' terminal nucleotides, and wherein said nucleic acid comprises a 2'-C-ally modification at position No. 4 of said nucleic acid, and wherein said nucleic acid comprises at least ten 2'-O-methyl modifications, and wherein said nucleic acid comprises a 3'-end modification.

40. The enzymatic nucleic acid of claim 39, wherein said nucleic acid comprises a 3'-3' linked inverted ribose moiety at said 3' end.

41. The enzymatic nucleic acid molecule of claim 25, wherein said nucleic acid molecule comprises at least five ribose residues, and wherein said nucleic acid molecule comprises phosphorothioate linkages at least three of the 5' terminal nucleotides, and wherein said nucleic acid comprises 2'-amino modification at position No. 4 and/or at position No. 7 of said nucleic acid molecule, wherein said nucleic acid comprises a 2'-O-methyl modifications, and wherein said nucleic acid comprises a 3'-end modification.

42. The enzymatic nucleic acid molecule of claim 25, wherein said nucleic acid molecule comprises at least five ribose residues, and wherein said nucleic acid molecule comprises phosphorothioate linkages at least three of the 5' terminal nucleotides, and wherein said nucleic acid molecule comprises an abasic substitution at position No. 4 and/or at position No. 7 of said nucleic acid molecule, wherein said nucleic acid comprises at least ten 2'-O-methyl modifications, and wherein said nucleic acid molecule comprises a 3'-end modification.

43. The enzymatic nucleic acid molecule of claim 25, wherein said nucleic acid molecule comprises of at least five ribose residues, and wherein said nucleic acid comprises phosphorothioate linkages at least three of the 5' terminal nucleotides, and wherein said nucleic acid molecule comprises a 6-methyl uridine substitution at position No. 4 and/or position No. 7 of said nucleic acid molecule, wherein said nucleic acid molecule comprises at least ten 2'-O-methyl modifications, and wherein said nucleic acid molecule comprises a 3' end modification.

44. A composition comprising the enzymatic nucleic acid molecule of claim 23.

Details for Patent 6,057,156

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 2017-01-31
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Try a Trial 2017-01-31
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b Injection 103132 ⤷  Try a Trial 2017-01-31
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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