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US 2015/0031130 A1Published application
Compounds and methods for enhanced cellular uptake
AssigneeRegulus Therapeutics Inc.
InventorBalkrishen Bhat
Life of this patent
Estimating the term…
Abstract
Described herein are conjugated modified oligonucleotides that are complementary to a target RNA. The conjugate facilitates cellular uptake of the modified oligonucleotide, resulting improved potency.
Claims59
A compound having the structure:
- Ln-linker-X—Nm—X-MO
- wherein each L is, independently, a ligand and n is from 1 to 10;
- each N is, independently, a modified or unmodified nucleoside and m is from 1 to 5;
- each X is, independently, a phosphodiester linkage or a phosphorothioate linkage;
- and MO is a modified oligonucleotide.
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A method of improving the potency of a modified oligonucleotide, comprising
- a. forming a compound having the structure Ln-linker-X—Nm—X-MO, wherein each L is, independently, a ligand and n is from 1 to 10;
- each N is, independently, a modified or unmodified nucleoside and m is from 1 to 5;
- each X is, independently, a phosphodiester linkage or a phosphorothioate linkage;
- and MO is a modified oligonucleotide;
- b. thereby improving the potency of the modified oligonucleotide, relative to the unconjugated modified oligonucleotide.
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A process of making a compound having the structure
- wherein each N is, independently, a modified or unmodified nucleoside and m is from 1 to 5;
- X1 and X2 are each, independently, a phosphodiester linkage or a phosphorothioate linkage;
- and MO is a modified oligonucleotide, the process comprising the steps of:
- providing a solid support containing a conjugate as shown in formula IV;
- deprotecting the DMT group under conditions effective to produce a reactive hydroxyl;
- performing sequential phosphoramidite coupling steps to form Nm;
- performing sequential phosphoramidite coupling steps to form the modified oligonucleotide;
- and
- releasing the conjugated modified oligonucleotide from the solid support.
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Dependencies are inferred from the claim text.