US 12,435,336 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)
Appl. No. 18/040,302
Filed by Dicerna Pharmaceuticals, Inc., Lexington, MA (US)
PCT Filed Aug. 5, 2021, PCT No. PCT/US2021/071109
§ 371(c)(1), (2) Date Feb. 2, 2023,
PCT Pub. No. WO2022/032288, PCT Pub. Date Feb. 10, 2022.
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 2024/0344063 A1, Oct. 17, 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)] 22 Claims
 
1. A method for treating a subject having a disease, disorder or condition associated with increased LPA expression, the method comprising administering to the subject a therapeutically effective amount of an RNAi oligonucleotide, 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:
(SEQ ID NO: 793)
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′, and
the sense strand is:
(SEQ ID NO: 393)
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′,
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
thereby treating the subject.