US 12,460,206 B2
PCSK9 iRNA compositions and methods of use thereof
Anna Borodovsky, Melrose, MA (US); Kallanthottathil G. Rajeev, Wayland, MA (US); Kevin Fitzgerald, Brookline, MA (US); Maria Frank-Kamenetsky, Brookline, MA (US); William Querbes, Boston, MA (US); Martin A. Maier, Belmont, MA (US); Klaus Charisse, Acton, MA (US); Satyanarayana Kuchimanchi, Acton, MA (US); Muthiah Manoharan, Weston, MA (US); and Stuart Milstein, Arlington, MA (US)
Assigned to Alnylam Pharmaceuticals, Inc., Cambridge, MA (US)
Filed by Alnylam Pharmaceuticals, Inc., Cambridge, MA (US)
Filed on Jan. 28, 2022, as Appl. No. 17/586,850.
Application 17/586,850 is a continuation of application No. 16/155,965, filed on Oct. 10, 2018, abandoned.
Application 16/155,965 is a continuation of application No. 14/650,128, granted, now 10,125,369, issued on Nov. 13, 2018, previously published as PCT/US2013/073349, filed on Dec. 5, 2013.
Claims priority of provisional application 61/892,188, filed on Oct. 17, 2013.
Claims priority of provisional application 61/886,916, filed on Oct. 4, 2013.
Claims priority of provisional application 61/793,530, filed on Mar. 15, 2013.
Claims priority of provisional application 61/733,518, filed on Dec. 5, 2012.
Prior Publication US 2023/0002772 A1, Jan. 5, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/11 (2006.01); A61K 31/7115 (2006.01); A61K 31/713 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); A61K 47/54 (2017.01); C12N 15/113 (2010.01)
CPC C12N 15/1137 (2013.01) [A61K 31/713 (2013.01); A61K 47/549 (2017.08); C12Y 304/21 (2013.01); C12N 2310/14 (2013.01); C12N 2310/312 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/343 (2013.01); C12N 2310/351 (2013.01); C12N 2310/3515 (2013.01); C12N 2320/35 (2013.01)] 2 Claims
OG exemplary drawing
 
1. A pharmaceutical composition comprising a double stranded RNAi agent that inhibits the expression of Proprotein convertase subtilisin kexin 9 (PCSK9) in a cell, comprising
an antisense strand consisting of the nucleotide sequence of 5′-asCfsaAfAfAfgCfaAfaAfcAfgGfuCfuagsasa-3′ (SEQ ID NO:1663), and
a sense strand consisting of the nucleotide sequence of 5′-csusagacCfuGfudTuugcuuuugu-3′ (SEQ ID NO:1657) and a ligand,
wherein the ligand is conjugated to the 3′-end of the nucleotide sequence of the sense strand as shown in the following schematic

OG Complex Work Unit Chemistry
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; dT is 2′-deoxythymidine; and X is O,
in a sterile aqueous solution.