US 12,084,656 B2
Products and compositions
Judith Hauptmann, Berlin (DE); Dmitry Samarsky, Berlin (DE); and Christian Frauendorf, Berlin (DE)
Assigned to SILENCE THERAPEUTICS GMBH, Berlin (DE)
Filed by SILENCE THERAPEUTICS GMBH, Berlin (DE)
Filed on Mar. 31, 2021, as Appl. No. 17/219,265.
Application 17/219,265 is a continuation of application No. 16/497,000, granted, now 11,015,198, previously published as PCT/EP2018/058766, filed on Apr. 5, 2018.
Claims priority of application No. 17165129 (EP), filed on Apr. 5, 2017; application No. 1707203 (GB), filed on May 5, 2017; application No. 1708397 (GB), filed on May 25, 2017; and application No. 17201352 (EP), filed on Nov. 13, 2017.
Prior Publication US 2022/0090067 A1, Mar. 24, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/113 (2010.01)
CPC C12N 15/113 (2013.01) [C12N 2310/14 (2013.01); C12N 2310/313 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/351 (2013.01)] 14 Claims
 
1. A nucleic acid for inhibiting expression of a target gene in a cell, comprising at least one duplex region that comprises at least a portion of a first strand and at least a portion of a second strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from said target gene, wherein said first strand includes modified nucleotides at a plurality of positions,
wherein the nucleotides at positions 2 and 14 from the 5′ end of the first strand are modified with a 2′ fluoro modification, and the nucleotides on the second strand which correspond to position 11, or 13, or 11 and 13, or 11-13 of the first strand are modified with a 2′ fluoro modification; wherein the nucleic acid is conjugated with a ligand, wherein the ligand is conjugated to the nucleic acid by a bivalent or trivalent branched linker and wherein the ligand comprises the formula I:
[S-X1-P-X2]3-A-X3-  (I)
wherein:
S represents a saccharide, wherein the saccharide is N-acetyl galactosamine;
X1 represents C3-C6 alkylene or (—CH2—CH2—O)m(—CH2)2— wherein m is 1, 2, or 3;
P is a phosphate or modified phosphate;
X2 is alkylene or an alkylene ether of the formula (—CH2)n—O—CH2— where n=1-6;
A is a branching unit;
X3 represents a bridging unit; and
wherein the nucleic acid is conjugated to X3 via a phosphate or modified phosphate.