IP Library › Granted Patent US 12,252,691
Granted Patent B2
US 12,252,691 · App. 18/807,591 · Granted Mar 18, 2025

Compositions and methods for inhibiting LPA expression

Inventors: Bob Dale Brown (Littleton, MA); Henryk T. Dudek (Belmont, MA); Marc Abrams (Natick, MA); Wen Han (Boston, MA); Anton Turanov (Revere, MA)
Assignee: Dicerna Pharmaceuticals, Inc.
C12N15/113C12N2310/14C12N2310/315C12N2310/321C12N2310/322C12N2310/351C12N2310/531
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Quick Facts
Patent No.
US 12,252,691
App. No.
18/807,591
Granted
Mar 18, 2025
Kind
B2
Abstract

Oligonucleotides are provided herein that inhibit apolipoprotein(a) (LPA) expression. Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders and/or conditions associated with LPA expression.

Claims (22)

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:

and MePhosphonate-40-mUs represents

2. A pharmaceutical composition comprising:

(i) the RNAi oligonucleotide of claim 1 ; and

(ii) a pharmaceutically acceptable carrier, delivery agent or excipient.

3. The pharmaceutical composition of claim 2 , wherein the carrier comprises phosphate buffered saline.

4. The pharmaceutical composition of claim 2 , wherein the carrier comprises water.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 8, 2024
From: BROWN, BOB DALE; DUDEK, HENRYK T.; ABRAMS, MARC; HAN, WEN; TURANOV, ANTON
To: DICERNA PHARMACEUTICALS, INC.
Reel/Frame 068835/0850 →
Continuity (4)
Continuation 18040302
Provisional Application 63074779 · Sep 4, 2020
Provisional Application 63061676 · Aug 5, 2020
Related Publication 20240401053A1 · Dec 5, 2024
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