Therapeutic oligonucleotides having an inter-nucleoside amide linkage
AssigneeOxford University Innovation Limited
InventorsTom BROWN, Afaf Helmy EL-SAGHEER, Ysobel Ruth BAKER, Pawan KUMAR
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Abstract
The present invention relates to a therapeutic oligonucleotide having a 5′ and a 3′ end and comprising a sequence of nucleosides linked together by inter-nucleoside linkages, wherein: at least one inter-nucleoside linkage is an amide linker moiety; at least one inter-nucleoside linkage is a phosphorothioate linker moiety; and at least one nucleoside present in the oligonucleotide is a locked nucleoside; wherein the at least one locked nucleoside is directly attached to the 3′ end or the 5′ end of the amide linker moeity. The oligonucleotide has preferably structure (IIa) or (llb):
Claims22
An oligonucleotide having a 5′ and a 3′ end and comprising a sequence of nucleosides linked together by inter-nucleoside linkages, wherein:
- at least one inter-nucleoside linkage is an amide linker moiety;
- at least one inter-nucleoside linkage is a phosphorothioate linker moiety;
- and
- at least one nucleoside present in the oligonucleotide is a locked nucleoside;
- wherein the at least one locked nucleoside is directly attached to the 3′ end or the 5′ end of the amide linker moeity;
- or a pharmaceutically acceptable salt or solvate thereof.
An oligonucleotide according to any one of the preceding claims, or a pharmaceutically acceptable salt or solvate thereof, wherein the oligonucleotide comprises a moiety of the structure (IIIa) below:
- C3, C4, Q1, Q2, B, B′, X1, X2, X3, X4, R1, R2, R3, R4 and RN are as defined in any one of the preceding claims;
- wherein B″ is independently a nucleobase;
- and
- R50 is selected from H, C1-4alkoxy, F, OH, OR9, O(CH2)pOR9 or NH2, wherein p is selected from 1, 2 or 3 and R9 is selected from hydrogen or a (1-6C)alkyl.
An oligonucleotide according to any one of the preceding claims, or a pharmaceutically acceptable salt or solvate thereof, for use in therapy.
An oligonucleotide according to any one of the preceding claims, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of a viral infection, cancer, a genetic disorder, a metabolic disease or a bacterial infection.
Dependencies are inferred from the claim text.