US 12,084,662 B2
Compositions and methods for modulating PNPLA3 expression
Utsav Saxena, Watertown, MA (US); Henryk T. Dudek, Belmont, MA (US); Marc Abrams, Natick, MA (US); Anton Turanov, Revere, MA (US); and Bob Dale Brown, Littleton, MA (US)
Assigned to Dicerna Pharmaceuticals, Inc., Lexington, MA (US)
Filed by Dicerna Pharmaceuticals, Inc., Lexington, MA (US)
Filed on Apr. 13, 2022, as Appl. No. 17/719,821.
Claims priority of provisional application 63/174,932, filed on Apr. 14, 2021.
Prior Publication US 2022/0364098 A1, Nov. 17, 2022
Int. Cl. C12N 15/113 (2010.01); A61K 31/7125 (2006.01); C07H 21/02 (2006.01); C12P 19/34 (2006.01)
CPC C12N 15/1137 (2013.01) [A61K 31/7125 (2013.01); C07H 21/02 (2013.01); C12N 2310/315 (2013.01); C12N 2310/32 (2013.01); C12N 2310/321 (2013.01); C12N 2310/3515 (2013.01); C12P 19/34 (2013.01)] 3 Claims
OG exemplary drawing
 
1. An RNAi oligonucleotide for reducing patatin-like phospholipase domain-containing protein 3 (PNPLA3) 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:
[mCs][mU][mA][mA][mC][mU][mA][fA][fA][fA][fU][mA][mA][mU][mG][mU][mU][mU][mA][mA][mG][mC][mA][mG][mC][mC][mG][ademA-GalNAc][ademA-GalNAc][ademA-GalNAc][mG][mG][mC][mU][mG][mC] (SEQ ID NO: 1250), wherein nucleotides at positions 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 31, 32, 33, 34, 35, and 36 are modified with 2′-O-methyl; nucleotides at positions 8, 9, 10, and 11 are modified with 2′-fluoro; the internucleotide linkage between nucleotides at positions 1 and 2 is a phosphorothioate linkage; and
nucleotides at positions 28, 29, and 30 are modified with adem-GalNAc; and
the antisense strand is:
[MePhosphonate-4O-mUs][fUs][fAs][fA][fA][mC][fA][mU][mU][fA][mU][mU][mU][fU][mA][mG][mU][mU][mA][m Gs][mGs][mG] (SEQ ID NO: 1251), wherein nucleotides at positions 1, 6, 8, 9, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, and 22 are modified with 2′-O-methyl; nucleotides at positions 2, 3, 4, 5, 7, 10, and 14 are modified with 2′-fluoro; the internucleotide linkages between nucleotides at positions 1 and 2, positions 2 and 3, positions 3 and 4, positions 20 and 21, and positions 21 and 22 are phosphorothioate linkages; and nucleotide at position 1 is a 4′-phosphate analog comprising 5′-methoxyphosphonate-4′-oxy.