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Last Updated: March 28, 2024

Claims for Patent: 9,943,539


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Summary for Patent: 9,943,539
Title:2'-methoxy substituted oligomeric compounds and compositions for use in gene modulations
Abstract: Compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes a modified sugar and/or backbone modification. In some embodiments the modification is a 2'-OCH.sub.3 substituent group on a sugar moiety. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleotide of the oligomer has a modified sugar and/or backbone modification.
Inventor(s): Crooke; Stanley T. (Carlsbad, CA)
Assignee: Ionis Pharmaceuticals, Inc. (Carlsbad, CA)
Application Number:15/851,491
Patent Claims: 1. A composition comprising a first oligomer and a second oligomer, wherein: at least a portion of said first oligomer is hybridized with at least a portion of said second oligomer, at least a portion of said first oligomer is complementary to a selected target nucleic acid, each of said first and second oligomers are chimeric oligomers, wherein the second oligomer is a blockmer comprising at least one XXYYXX motif, and wherein each X is an unmodified ribonucleoside and each Y is a nucleoside having a 2'-OCH.sub.3 substituent group.

2. The composition of claim 1 wherein each of said first and second oligomers comprise from about 18 to about 30 linked nucleosides.

3. The composition of claim 1 wherein each of said first and second oligomers comprise from about 21 to about 24 linked nucleosides.

4. The composition of claim 1 wherein each of said first and second oligomers comprise 21 linked nucleosides.

5. The composition of claim 1 wherein each nucleoside of said first and second oligomers is independently selected from an unmodified ribonucleoside, a nucleoside having a 2'-OCH.sub.3 substituent group, and a 2'-deoxythymidine nucleoside.

6. The composition of claim 1 wherein said first oligomer is an antisense oligomer and said second oligomer is a sense oligomer.

7. The composition of claim 1 wherein said first and said second oligomers are a complementary pair of siRNA oligomers.

8. The composition of claim 2 wherein each internucleoside linkage linking the linked nucleosides is, independently, a phosphodiester or phosphorothioate internucleoside linkage.

9. The composition of claim 2 wherein each internucleoside linkage linking the linked nucleosides is a phosphodiester internucleoside linkage.

10. The composition of claim 1 wherein the 5'-terminal nucleoside of said first oligomer has a 5'-phosphate group.

11. The composition of claim 1 wherein at least one of said first or second oligomers has an overhang.

12. The composition of claim 1 wherein each of said first and second oligomers comprises a 3'-overhang consisting of two 2'-deoxythymidine nucleosides.

13. The composition of claim 1 comprising at least two of said XXYYXX motifs.

14. The composition of claim 1, wherein said first oligomer does not comprise an internal DNA segment.

15. The composition of claim 1, wherein said first oligomer is not a deoxy gapmer.

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