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US 12,234,447 B2Granted
Modified compounds and uses thereof
AssigneeIonis Pharmaceuticals, Inc.
InventorsPunit P. Seth, Michael Oestergaard, Michael T. Migawa, Xue-Hai Liang, Wen Shen, Stanley T. Crooke, Eric E. Swayze
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Abstract
The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.
Claims21
An oligomeric compound comprising a modified oligonucleotide consisting of 16-20 linked nucleosides, wherein the modified oligonucleotide has a 5′-region, a central region, and a 3′-region, wherein:
- the 5′-region consists of 3-5 linked nucleosides, each comprising modified sugar moiety;
- the 3′ region consists of 3-5 linked nucleosides, each comprising a modified sugar moiety;
- and the central region consists of 8-10 linked nucleosides, wherein the central region has the following formula:
- (Nd)(Nx)(Nd)n
- wherein Nx is a nucleoside comprising a 2′-OMe-β-D-ribofuranosyl sugar moiety and each Nd is a nucleoside comprising a 2′-β-D-deoxyribosyl sugar moiety;
- and n is 6-8.
3 more elements
Dependencies are inferred from the claim text.