Selective Reduction of Allelic Variants
AssigneesIonis Pharmaceuticals, Inc., The University of British Columbia
InventorsC. Frank Bennett, Michael Hayden, Susan M. Freier, Sarah Greenlee, Jeffrey Carroll, Simon Warby, 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 huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD).
Claims26
A method for determining whether an agent selectively inhibits expression of a first allelic variant of a gene relative to a second allelic variant of said gene wherein said first allelic variant comprises a first nucleotide at a SNP position and said second allelic variant comprises a second nucleotide at said SNP position, comprising:
- contacting a first cell, tissue or animal with said agent at one or more concentrations, wherein said first cell, tissue or animal is homozygous for said first nucleotide at said SNP position;
- contacting a second cell, tissue or animal with said agent at one or more concentrations, wherein said second cell, tissue or animal is homozygous for said second nucleotide at said SNP position or is heterozygous for said first and said second nucleotides at said SNP position;
- measuring inhibition of expression of said allelic variant in each of said cell, tissue or animal for each of said one or more concentrations of said agent;
- and
- comparing said inhibition of expression in each of said cell, tissue or animal for each of said one or more concentrations of said agent to determine whether said agent selectively inhibits expression of said first allelic variant of said gene relative to said second allelic variant of said gene.
(canceled)
(canceled)
(canceled)
(canceled)
-25. (canceled)
-41. (canceled)
-46. (canceled)
-81. (canceled)
A method of treating Huntington's Disease, comprising selectively reducing expression of a mutant huntingtin allele in an animal in need thereof, comprising administering to the animal a compound, comprising a modified oligonucleotide consisting of 15 to 20 linked nucleosides and fully complementary to the mutant huntingtin allele, wherein position 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the modified oligonucleotide, as counted from the 5′ terminus of the modified oligonucleotide, aligns with any of the SNP sites in the group consisting of rs6446723, rs3856973, rs2285086, rs363092, rs916171, rs6844859, rs7691627, rs4690073, rs2024115,rs1731237, rs362296, rs10015979, rs7659144, rs363096, rs362273, rs16843804, rs362271, rs362275, rs3121419, rs362272, rs3775061, rs34315806, rs363099, rs2298967, rs363088, rs363064, rs363102, rs2798235, rs363080, rs363072, rs363125, rs362303, rs362310, rs10488840, rs362325, rs35892913, rs1936032, rs2276881, rs363070, rs12502045, rs7685686, rs3733217, rs2857936, rs12506200, rs762855, rs4690072, rs363081, rs363075, rs3025849, rs6855981, rs363144, rs3025838, rs2298969, rs362322, rs362306, and rs1006798.
(canceled)
A compound comprising a modified oligonucleotide 15 to 20 linked nucleosides in length, targeted to a huntingtin single nucleotide polymorphism, comprising a 12 nucleobase portion of the nucleobase sequence of any one of SEQ ID NO:
- 6 to 285, wherein position 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the modified oligonucleotide, as counted from the 5′ terminus of the modified oligonucleotide, aligns with the huntingtin single nucleotide polymorphism.
-95. (canceled)
(canceled)
Dependencies are inferred from the claim text.