Patent ID: 11873488
Assignee: DICERNA PHARMACEUTICALS, INC.
Field: Biotechnology (Chemistry)
Classification: CPC C | IPC C

Claim 0:
1. A double-stranded nucleic acid inhibitor molecule, comprising:
a sense strand comprising 21-66 nucleotides and having a first region (R1) and a second region (R2);
an antisense strand comprising 15-40 nucleotides, wherein the sense strand and antisense strand are separate strands;
a first duplex (D1) formed by the first region of the sense strand and the antisense strand, wherein the first duplex has a length of 15-40 base pairs;
wherein the second region of the sense strand comprises a first subregion (S1), a second subregion (S2) and a tetraloop (L) comprising at least one ligand conjugated nucleotide that joins the first and second subregions, wherein the first and second subregions form a second duplex (D2); and
wherein the second duplex has a length of 1-3 base pairs, wherein the second duplex contains 6 bicyclic nucleotides that form 3 base pairs, 4 bicyclic nucleotides that form 2 base pairs, 2 bicyclic nucleotides that form 1 base pair, 6 nucleotides that form 3 base pairs and include 3 unpaired bicyclic nucleotides, 6 nucleotides that form 3 base pairs and include 2 unpaired bicyclic nucleotides, or 6 nucleotides that form 3 base pairs and include 1 unpaired bicyclic nucleotide, and
wherein every nucleotide on the sense strand and antisense strand is modified at the 2′-carbon of the sugar moiety with a 2′-F or a 2′-OMe, except for the bicyclic nucleotides in the second duplex and the nucleotides in the tetraloop that are conjugated to a sugar ligand moiety.