US 12,655,428 B2Granted

RNAi agents for inhibiting expression of Beta-ENaC, compositions thereof, and methods of use

AssigneeArrowhead Pharmaceuticals, Inc.

InventorsAnthony Nicholas, Casi M. Schienebeck, Erik W. Bush, Tao Pei, Zhao Xu, Zhen Li, Rui Zhu

Life of this patent

Estimating the term…

Loading patent…

Abstract

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a beta-ENaC (SCNN1B) gene. The beta-ENaC RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a beta-ENaC gene. Pharmaceutical compositions that include one or more beta-ENaC RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described beta-ENaC RNAi agents to epithelial cells, such as pulmonary epithelial cells, in vivo, provides for inhibition of beta-ENaC gene expression and a reduction in ENaC activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including chronic obstructive pulmonary disease (COPD).

Claims13

Dependent claims

An RNAi agent for inhibiting expression of a beta-ENaC gene, comprising:

an antisense strand comprising the nucleotide sequence (5′→3′) cPrpusGfsusUfgAfagaugUfaAfcAfgUfuGfsc (SEQ ID NO:
138);
and
a sense strand comprising a nucleotide sequence that is at least partially complementary to the antisense strand;
wherein a represents 2′-O-methyl adenosine, c represents 2′-O-methyl cytidine, g represents 2′-O-methyl guanosine, and u represents 2′-O-methyl uridine;
Af represents 2′-fluoro adenosine, Cf represents 2′-fluoro cytidine, Gf represents 2′-fluoro guanosine, and Uf represents 2′-fluoro uridine;
cPrpu represents a 5′-cyclopropyl phosphonate-2′-O-methyl uridine;
s represents a phosphorothioate linkage;
and wherein all or substantially all of the nucleotides on the sense strand are modified nucleotides.

6 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/731,766Filed 28 Apr 2022 · continuation
Priority: 29 Oct 2019
Published: US 2023/0013022 A119 Jan 2023
Granted: 16 Jun 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C12N 15/113
DNA or RNA fragments; Modified forms thereof ; Non-coding nucleic acids having a biological activity: non-coding nucleic acids modulating the…
C12N 15/1138
Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming…: against…
A61K 31/7105
Compounds having three or more nucleosides or nucleotides: natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine,…
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

Family

Application62/927,637Us provisional application · filed 29 Oct 2019
Application63/024,722Us provisional application · filed 14 May 2020
PCT/US2020/057778Parent of this continuation · filed 28 Oct 2020
US 2023/0013022 A1Pre-grant publication · published 19 Jan 2023
US 12,655,428 B2This patent

From the US filing history. Foreign family members aren’t listed.