	US 12,234,456 B2
	Compositions and methods for modulating APOC3 expression
Bob Dale Brown, Littleton, MA (US); Henryk Dudek, Belmont, MA (US); Utsav Saxena, Watertown, MA (US); and Wen Han, Boston, MA (US)
Assigned to Dicerna Pharmaceuticals, Inc., Lexington, MA (US)
Filed by Dicerna Pharmaceuticals, Inc., Lexington, MA (US)
Filed on Dec. 1, 2022, as Appl. No. 18/060,881.
Claims priority of provisional application 63/264,730, filed on Dec. 1, 2021.
Prior Publication US 2023/0272393 A1, Aug. 31, 2023
Int. Cl. C12N 15/113 (2010.01)

CPC C12N 15/113 (2013.01) [C12N 2310/14 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/351 (2013.01)]

11 Claims

1. An RNAi oligonucleotide for reducing apolipoprotein C-III (APOC3) expression, the oligonucleotide comprising a sense strand and an antisense strand, wherein the sense strand and the antisense strand form a duplex region, wherein

the sense strand is:

[mGs][mU][mA][mG][mG][mU][mU][fG][fC][fU][fU][mA][mA][mA][mA][mG][mG][mG][m A][mA][mG][mC][mA][mG][mC][mC][mG][ademA-GalNAc][ademA-GalNAc][ademA-GalNAc][mG][mG][mC][mU][mG][mC] (SEQ ID NO: 251); and

the antisense strand is:

[MePhosphonate-4O-mUs][fUs][fCs][fC][fC][mU][fU][mU][mU][fA][mA][mG][mC][fA][mA][mC][mC|mU][mA][mCs][mGs][mG] (SEQ ID NO: 252), wherein:

mGs represents 2′-O-methyl guanosine with a phosphorothioate linkage to the neighboring nucleotide;

mU represents 2′-O-methyl uridine with phosphodiester linkages to neighboring nucleotides;

mA represents 2′-O-methyl adenosine with phosphodiester linkages to neighboring nucleotides;

mG represents 2′-O-methyl guanosine with phosphodiester linkages to neighboring nucleotides;

fG represents 2′-fluoro guanosine with phosphodiester linkages to neighboring nucleotides;

fC represents 2′-fluoro cytosine with phosphodiester linkages to neighboring nucleotides;

fU represents 2′-fluoro uridine with phosphodiester linkages to neighboring nucleotides;

mC represents 2′-O-methyl cytosine with phosphodiester linkages to neighboring nucleotides;

ademA-GalNAc represents 2′-aminodiethoxymethanol-Adenine-GalNAc;

MePhosphonate-4O-mUs represents 5′-methoxyphosphonate-4′-oxy uridine with a 3′-phosphorothioate linkage;

fUs represents 2′-fluoro uridine with a phosphorothioate linkage to the neighboring nucleotide;

fCs represents 2′-fluoro cytosine with a phosphorothioate linkage to the neighboring nucleotide;

fA represents 2′-fluoro adenosine with phosphodiester linkages to neighboring nucleotides; and

mCs represents 2′-O-methyl cytosine with a phosphorothioate linkage to the neighboring nucleotide.