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Claims for Patent: 5,276,019

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Claims for Patent: 5,276,019

Title: Inhibitors for replication of retroviruses and for the expression of oncogene products
Abstract:Phosphorothioate oligodeoxyribonucleotide analogs can be used to prevent replication of foreign nucleic acids in the presence of normal living cells, as well as to inhibit the proliferation of neoplastic cells.
Inventor(s): Cohen; Jack S. (Bethesda, MD), Neckers; Len (Bethesda, MD), Stein; Cy (Gaithersburg, MD), Loke; Shee L. (Wheaton, MD), Shinozuka; Kazuo (Kazo, JP)
Assignee: The United States of America as represented by the Department of Health (Washington, DC)
Application Number:07/159,017
Patent Claims: 1. A compound capable of inhibiting the replication or cytopathic effect of a foreign nucleic acid in a host of the formula: ##STR3## wherein: n is in the range of from 2 to 30, inclusive;

X is selected from the group consisting of S and O such that at least one X is S; and

B is selected from the group consisting of adenine, cytosine, guanine, and thymine, such that the compound has a complementary base sequence with a portion of the foreign nucleic acid.

2. The compound of claim 1 wherein n is in the range of from 14 to 30, inclusive.

3. The compound of claim 2 wherein greater than 95% of X are S.

4. The compound of claim 3 wherein X is S.

5. The compound of claim 2 wherein two X are S and the remaining X are O.

6. The compound of claim 5 wherein the two X which are S are at opposite terminal ends of the compound with respect to one another.

7. The compound of claim 2 wherein the number of X which are S is equal to the number of X which are O.

8. The compound of claim 2 wherein the X are grouped in alternating units, said alternating units being, respectively, units in which all X are S and units in which all X are O, and further wherein the number of X in each unit is equal.

9. The compound of claim 8 wherein the number of X in each unit is one.

10. The compound of claim 1 wherein said foreign nucleic acid is a viral nucleic acid.

11. The compound of claim 10 wherein n is in the range of from 14 to 30, inclusive.

12. The compound of claim 11 wherein said viral nucleic acid is a nucleic acid of human immunodeficiency virus.

13. The compound of claim 12 wherein said nucleic acid of human immunodeficiency virus is a gag gene nucleic acid.

14. The compound of claim 12 wherein said nucleic acid of human immunodeficiency virus is a tat-III gene nucleic acid.

15. The compound of claim 12 wherein said nucleic acid of human immunodeficiency virus is an art/trs gene nucleic acid.

16. The compound of claim 11 wherein greater than 95% of X are S.

17. The compound of claim 16 wherein X is S.

18. The compound of claim 16 wherein said viral nucleic acid is a nucleic acid of human immunodeficiency virus.

19. The compound of claim 18 wherein X is S.

20. The compound of claim 18 wherein said nucleic acid of human immunodeficiency virus is a gag gene nucleic acid.

21. The compound of claim 18 wherein said nucleic acid of human immunodeficiency virus is a tat-III gene nucleic acid.

22. The compound of claim 18 wherein said nucleic acid of human immunodeficiency virus is an art/trs gene nucleic acid.

23. A composition for inhibiting the replication or cytopathic effect of a foreign nucleic acid in a host, said composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of the formula: ##STR4## wherein: n is in the range of from 2 to 30, inclusive;

X is selected from the group consisting of S and O such that at least one X is S; and

B is selected from the group consisting of adenine, cytosine, guanine, and thymine, such that the compound has a complementary base sequence with a portion of the foreign nucleic acid.

24. The composition of claim 23 wherein n is in the range of from 14 to 30, inclusive.

25. The composition of claim 24 wherein greater than 95% of X are S.

26. The composition of claim 25 wherein X is S.

27. The composition of claim 23 wherein said foreign nucleic acid is a viral nucleic acid.

28. The composition of claim 27 wherein n is in the range of from 14 to 30, inclusive.

29. The composition of claim 28 wherein said viral nucleic acid is a nucleic acid of human immunodeficiency virus.

30. The composition of claim 29 wherein said nucleic acid of human immunodeficiency virus is a gag gene nucleic acid.

31. The composition of claim 29 wherein said nucleic acid of human immunodeficiency virus is a tat-III gene nucleic acid.

32. The composition of claim 24 wherein said nucleic acid of human immunodeficiency virus is an art/trs gene nucleic acid.

33. The composition of claim 29 wherein greater than 95% of X are S.

34. The composition of claim 33 wherein X is S.

35. A method for inhibiting the replication or cytopathic effect of a foreign nucleic acid in a host comprising the step of administering to the individual an effective amount of a compound of the formula: ##STR5## wherein: n is in the range of from 2 to 30, inclusive;

X is selected from the group consisting of S and O such that at least one X is S; and

B is selected from the group consisting of adenine, cytosine, guanine, and thymine, such that the compound has a complementary base sequence with a portion of the foreign nucleic acid.

36. The method of claim 35 wherein n is in the range of from 14 to 30, inclusive.

37. The method of claim 36 wherein greater than 95% of X are S.

38. The method of claim 37 wherein X is S.

39. The method of claim 35 wherein said foreign nucleic acid is a viral nucleic acid.

40. The method of claim 39 wherein n is in the range of from 14 to 30, inclusive.

41. The method of claim 40 wherein said viral nucleic acid is a nucleic acid of human immunodeficiency virus.

42. The method of claim 41 wherein greater than 95% of X are S.

43. The method of claim 42 wherein X is S.
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