Granted Patent B2

US 12,545,911 · App. 18/655,096 · Granted Feb 10, 2026

Inventors: Janne Juha Turunen (The Hague, NL); Petra Geziena De Bruijn (The Hague, NL); Bart Klein (Delft, NL); Roxana Simona Redis (Leiden, NL); Lenka Van Sint Fiet (Wassenaar, NL)

Assignee: ProQR Therapeutics II B.V.

C12N15/111A61K31/7125C12N15/102C12N2310/11C12N2310/321C12N2310/3521C12N2310/3527C12N2320/30

Abstract

Claims (15)

1 . An antisense oligonucleotide (AON) capable of forming a double stranded complex with an alpha-L-iduronidase (IDUA)-encoding target RNA in a cell for the deamination of a target adenosine present in the target RNA by an ADAR enzyme naturally present in the cell, wherein:

a) the AON is complementary to a target RNA region comprising the target adenosine;

b) the nucleotide in the AON that is opposite the target adenosine comprises a deoxyribose with a 2′-H group; and

c) the AON does not comprise a portion that is both: (i) non-complementary to the target RNA region, and (ii) capable of forming an intramolecular stem-loop structure.

2 . The AON of claim 1 , wherein the target adenosine corresponds to the c.1205G>A mutation in the human IDUA gene, which causes Hurler syndrome.

3 . The AON of claim 1 , wherein the nucleotide in the AON that is opposite the target adenosine forms a mismatch with the target adenosine.

4 . The AON of claim 1 , wherein the AON comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 mismatches, wobbles, and/or bulges with the complementary target RNA region.

5 . The AON of claim 1 , wherein the AON comprises a Central Triplet, wherein the middle nucleotide is the nucleotide that is opposite the target adenosine, and wherein the Central Triplet comprises three nucleotides that are RNA-DNA-DNA.

6 . The AON of claim 1 , wherein the AON comprises at least one nucleotide comprising a 2′-O-methyl (2′-OMe) substitution.

7 . The AON of claim 1 , wherein the AON comprises at least one nucleotide comprising a 2′-O-methoxyethyl (2′-MOE) substitution.

8 . The AON of claim 1 , wherein the AON comprises at least one phosphorothioate linkage.

9 . The AON of claim 1 , wherein the AON comprises 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 nucleotides.

10 . The AON of claim 1 , wherein the AON does not comprise a 5′-terminal O6-benzylguanosine.

11 . A pharmaceutical composition comprising the AON of claim 1 and a pharmaceutically acceptable carrier.

12 . A method for treating Hurler syndrome in a human subject in need thereof, comprising administering to the subject the AON of claim 1 .

Assignments (1)

Priority Claims (4)

Continuity (4)

References Cited (393)