US 12,252,691 B2
Compositions and methods for inhibiting LPA expression
Bob Dale Brown, Littleton, MA (US); Henryk T. Dudek, Belmont, MA (US); Marc Abrams, Natick, MA (US); Wen Han, Boston, MA (US); and Anton Turanov, Revere, MA (US)
Assigned to Dicerna Pharmaceuticals, Inc., Lexington, MA (US)
Filed by Dicerna Pharmaceuticals, Inc., Lexington, MA (US)
Filed on Aug. 16, 2024, as Appl. No. 18/807,591.
Application 18/807,591 is a continuation of application No. 18/040,302, previously published as PCT/US2021/071109, filed on Aug. 5, 2021.
Claims priority of provisional application 63/074,779, filed on Sep. 4, 2020.
Claims priority of provisional application 63/061,676, filed on Aug. 5, 2020.
Prior Publication US 2024/0401053 A1, Dec. 5, 2024
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); C12N 2310/531 (2013.01)] 4 Claims
 
1. An RNAi oligonucleotide for reducing apolipoprotein(a) (LPA) 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 antisense strand is:
5′-[MePhosphonate-40-mUs][fAs][fGs][fA][fU][mG][fA][mC][mC][fA][mA][mG][mC][fU][mU][mG][mG][mC][mA][mAs][mGs][mG]-3′ (SEQ ID NO: 793), and the sense strand is:
5′-[mUs][mU][mG][mC][mC][mA][mA][fG][fC][fU][fU][mG][mG][mU][mC][mA][mU][mC][mU][mA][mG][mC][mA][mG][mC][mC][mG][ademA-GalNAc][ademA-GalNAc][ademA-GalNAc][mG][mG][mC][mU][mG][mC]-3′ (SEQ ID NO: 393), wherein:
mA represents 2′-OMe adenosine;
mC represents 2′-OMe cytosine;
mG represents 2′-OMe guanosine;
mU represents 2′-OMe uridine;
fA represents 2′-F adenosine, fC represents 2′-F cytosine;
fG represents 2′-F guanosine;
fU represents 2′-F uridine;
fAs represents 2′-F adenosine with a 3′-phosphorothioate linkage;
fGs represents 2′-F guanosine with a 3′-phosphorothioate linkage;
mAs represents 2′-OMe adenosine with a 3′-phosphorothioate linkage;
mGs represents 2′-OMe guanosine with a 3′-phosphorothioate linkage;
mUs represents 2′-OMe uridine with a 3′-phosphorothioate linkage;
ademA-GalNAc represents 2′-aminodiethoxymethanol-adenine-GalNAc:

OG Complex Work Unit Chemistry
and MePhosphonate-40-mUs represents

OG Complex Work Unit Chemistry