Selective reduction of allelic variants
AssigneeIonis Pharmaceuticals, Inc.
InventorsC. Frank Bennett, Susan M. Freier, Sarah Greenlee, Eric E. Swayze
Life of this patent
Estimating the term…
Abstract
Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate diseases, including neurodegenerative diseases, such as Huntington's Disease (HD).
Claims50
A compound comprising a modified oligonucleotide consisting of 20 linked nucleosides and comprising a nucleobase sequence having at least 95% sequence identity to the nucleobase sequence of SEQ ID NO:
- 274, wherein the modified oligonucleotide comprises at least one nucleoside comprising a modified sugar and at least one modified internucleoside linkage, wherein each T in SEQ ID NO:
- 274 is independently a T or a U, and wherein the modified oligonucleotide is a gapmer.
A compound comprising a modified oligonucleotide consisting of 20 linked nucleosides, wherein the modified oligonucleotide is complementary to a differentiating polymorphism site, wherein the modified oligonucleotide comprises at least a 16 contiguous nucleobase portion of the nucleobase sequence of any of SEQ ID NOs:
- 274-276, wherein position 8, 9, or 10 of the modified oligonucleotide, as counted from the 5′ terminus of the modified oligonucleotide, aligns with the differentiating polymorphism site, wherein the modified oligonucleotide comprises at least one nucleoside comprising a modified sugar and at least one modified internucleoside linkage, and wherein each T in SEQ ID NO:
- 274, 275, or 276 is independently a T or a U, and wherein the modified oligonucleotide is a gapmer.
A compound comprising a modified oligonucleotide consisting of 20 linked nucleosides and having a nucleobase sequence comprising a portion that is complementary to at least 16 contiguous nucleobases of nucleobases 167062-167080 or nucleobases 167063-167081 of SEQ ID NO:
- 1, wherein the modified oligonucleotide comprises at least one nucleoside comprising a modified sugar and at least one modified internucleoside linkage, and wherein the modified oligonucleotide is a gapmer.
A compound comprising a modified oligonucleotide consisting of 20 linked nucleosides and comprising the nucleobase sequence of SEQ ID NO:
- 275, wherein the modified oligonucleotide comprises at least one nucleoside comprising a modified sugar and at least one modified internucleoside linkage, wherein each T in SEQ ID NO:
- 275 is independently a T or a U, and wherein the modified oligonucleotide is a gapmer.
A compound comprising a modified oligonucleotide consisting of 20 linked nucleosides and comprising the nucleobase sequence of SEQ ID NO:
- 276, wherein the modified oligonucleotide comprises at least one nucleoside comprising a modified sugar and at least one modified internucleoside linkage, wherein each T in SEQ ID NO:
- 276 is independently a T or a U, and wherein the modified oligonucleotide is a gapmer.
Dependencies are inferred from the claim text.