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Details for Patent: 5,286,717

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Details for Patent: 5,286,717

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; She L. (Wheaton, MD), Shinozuka; Kazuo (Kazo, JP)
Assignee: The United States of America as represented by the Department of Health (Washington, DC)
Filing Date:Nov 16, 1992
Application Number:07/976,777
Claims:1. A compound for inhibiting the expression of an oncogene in a host, the compound comprising a mixed linkage oligonucleotide phosphorothioate having a complementary base sequence with a portion of the oncogene.

2. The compound of claim 1 wherein said mixed linkage oligonucleotide phosphorothioate comprises an alternating sequence of nucleoside moieties and linkage moieties such that the linkage moieties are selected from the group consisting of phosphorothioate, methylphosphonate, phosphorotriester, and phosphodiester.

3. The compound of claim 2 having the formula: ##STR5## wherein: n is in the range of from 2 to 30, inclusive;

X is selected from the group consisting of methyl, ethoxy, 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.

4. The compound of claim 3 wherein n is in the range of 14 to 30, inclusive.

5. The compound of claim 3 wherein said oncogene is c-myc.

6. The compound of claim 3 wherein greater than 95 percent of X are S.

7. A composition for inhibiting the expression of an oncogene in a host, the composition comprising a pharmaceutically acceptable carrier and an effective amount of a mixed linkage oligonucleotide phosphorothioate having a complementary base sequence with a portion of the oncogene.

8. The composition of claim 7 wherein said mixed linkage oligonucleotide phosphorothioate comprises an alternating sequence of nucleoside moieties and linkage moieties such that the linkage moieties are selected from the group consisting of phosphorothioate, methylphosphonate, phosphorotriester, and phosphodiester.

9. The composition of claim 8 wherein said mixed linkage oligonucleotide phosphorothioate has the formula: ##STR6## wherein: n is in the range of from 2 to 30, inclusive;

X is selected from the group consisting of methyl, ethoxy, 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 said oncogene.

10. The composition of claim 9 wherein n is in the range of 14 to 30, inclusive.

11. The composition of claim 10 wherein greater than 95 percent of X are S.

12. A method for inhibiting the expression of an oncogene in a host comprising administering to the host an effective amount of a compound comprising a mixed linkage oligonucleotide phosphorothioate having a complementary base sequence with a portion of the oncogene.

13. The method of claim 12 wherein said mixed linkage oligonucleotide phosphorothioate comprises an alternating sequence of nucleoside moieties and linkage moieties such that the linkage moieties are selected from the group consisting of phosphorothioate, methylphosphonate, phosphorotriester, and phosphodiester.

14. The method of claim 13 wherein said mixed linkage oligonucleotide phosphorothioate is defined by the formula: ##STR7## wherein: n is in the range of from 2 to 30, inclusive;

X is selected from the group consisting of methyl, ethoxy, 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 said oncogene.

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

16. The method of claim 15 wherein said step of administering includes administering said compound so that a blood concentration of 0.1 to 100 micromoles/cl is achieved.

17. The method of claim 15 wherein at least 95 percent of said X are S.

18. The method of claim 14 wherein said oncogene is c-myc.

19. The method of claim 18 wherein said step of administering includes administering said compound so that a blood concentration of 0.1 to 100 micromoles/cl is achieved.

20. The method of claim 19 wherein at least 95 percent of said X are S.
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