NOVEL NUCLEOTIDES AND OLIGONUCLETIDES AND RNAi AGENTS COMPRISING THE SAME
Patent Information
- Application Number
- ARP20250100601
- Authority / Receiving Office
- AR · AR
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-03-04
- Filing Date
- 2025-03-05
- Publication Date
- 2026-09-02
Claims
The present description relates to novel destabilizing molecules, such as a butadiol portion, modified nucleosides incorporating the butadiol portion, and oligonucleotides and RNAi agents comprising such modified nucleotides that enhance selectivity and / or reduce off-target effects while maintaining or enhancing attenuation of gene expression at the target.
1. An oligonucleotide comprising a compound of the formula: (1), wherein X1 is a 5' portion of the oligonucleotide, X2 and X3 are one or more independently selected nucleotides, X4 is a 3' portion of the oligonucleotide, myn are independently selected from any integer from 0 to 40, and XB is a butadiol-modified nucleotide.
2. An oligonucleotide of claim 1, wherein the compound is of the formula: (2), wherein B is a nucleobase.
23. A compound of the formula: (3), wherein B is a nucleobase and Y is an organic protecting group.
36. A compound of formula: (4), wherein B is a nucleobase, Y is an organic protecting group, and Z is phosphate or is a phosphoramidite represented by a compound of formula (5).
48. An RNAi agent comprising: (a) a coding strand oligonucleotide having a length of 15 to 30 nucleotides, (b) a non-coding strand oligonucleotide comprising the oligonucleotide of any one of claims 1 to 22, wherein the coding strand oligonucleotide and the non-coding strand oligonucleotide form a duplex.
49. An RNAi agent comprising: (a) a coding strand oligonucleotide having a length of 15 to 30 nucleotides, (b) a non-coding strand oligonucleotide comprising the oligonucleotide of claim 21 or claim 22, wherein the coding strand oligonucleotide and the non-coding strand oligonucleotide form a duplex.