	US 11,959,081 B2
	Transthyretin (TTR) iRNA compositions and methods of use thereof
Mark K. Schlegel, Boston, MA (US); Adam Castoreno, Framingham, MA (US); and James D. McIninch, Burlington, MA (US)
Assigned to Alnylam Pharmaceuticals, Inc., Cambridge, MA (US)
Filed by Alnylam Pharmaceuticals, Inc., Cambridge, MA (US)
Filed on Sep. 28, 2022, as Appl. No. 17/935,997.
Application 17/935,997 is a continuation of application No. PCT/US2022/039111, filed on Aug. 2, 2022.
Claims priority of provisional application 63/228,830, filed on Aug. 3, 2021.
Prior Publication US 2023/0111813 A1, Apr. 13, 2023
Int. Cl. C07H 21/04 (2006.01); A61K 31/713 (2006.01); C12N 15/113 (2010.01)

CPC C12N 15/113 (2013.01) [A61K 31/713 (2013.01); C12N 2310/315 (2013.01); C12N 2310/322 (2013.01); C12N 2310/351 (2013.01); C12N 2320/30 (2013.01)]

30 Claims

1. A double stranded ribonucleic acid (dsRNA) agent, or salt thereof, for inhibiting expression of transthyretin (TTR) in a cell,

wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region,

wherein the nucleotide sequence of the sense strand differs by no more than 4 bases from the nucleotide sequence 5′-csasagagUfaUfUfCfcauuuuuacu-3′ of SEQ ID NO: 21 and the nucleotide sequence of the antisense strand differs by no more than 4 bases from the nucleotide sequence 5′-asGfsuaaAfaauggaaUfaCfucuugsgsu-3′ of SEQ ID NO: 22,

wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U, respectively; Af, Cf, Gf and Uf are 2′-fluoro A, C, G and U, respectively; s is a phosphorothioate linkage, and wherein at least one strand is conjugated to a ligand.