Antisense oligonucleotides for the treatment of Stargardt disease

Patent metadata

Field	Value
Publication number	US-12054716-B2
Application number	US-202117552372-A
Country	US
Kind code	B2
Filing date	Dec 16, 2021
Priority date	Dec 13, 2016
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

The present invention relates to the field of medicine. In particular, it relates to novel antisense oligonucleotides that may be used in the treatment, prevention and/or delay of Stargardt disease.

First claim

The invention claimed is:

1. An antisense oligonucleotide for redirecting splicing that is:
complementary or substantially complementary to a polynucleotide with a nucleotide sequence consisting of SEQ ID NO: 81,
and wherein the antisense oligonucleotide comprises a 2′-O alkyl phosphorothioate antisense oligonucleotide, and wherein the antisense oligonucleotide comprises at least one ESE (exon splice enhancer) motif.

2. The antisense oligonucleotide for redirecting splicing according to claim 1 , wherein the part that is complementary or substantially complementary to a polynucleotide with a nucleotide sequence consisting of SEQ ID NO: 81, has a length of from about 8 to about 40 nucleotides.

3. The antisense oligonucleotide for redirecting splicing according to claim 1 that has a length of from about 8 to about 100 nucleotides.

4. The antisense oligonucleotide for redirecting splicing according to claim 1 , wherein said antisense oligonucleotide comprises a sequence selected from the group consisting of SEQ ID NO: 85, 88, and 91.

5. The antisense oligonucleotide for redirecting splicing according to claim 1 , comprising at least one ribonucleotide.

6. A viral vector expressing an antisense oligonucleotide for redirecting splicing according to claim 1 when placed under conditions conducive to expression of the exon skipping antisense oligonucleotide.

7. A pharmaceutical composition comprising an antisense oligonucleotide for redirecting splicing according to claim 1 and a pharmaceutically acceptable excipient.

8. The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is for intravitreal administration and is dosed in an amount ranged from 0.05 mg and 5 mg of total antisense oligonucleotides for redirecting splicing per eye.

9. The pharmaceutical composition according to claim 8 , wherein the pharmaceutical composition is for intravitreal administration and is dosed in an amount ranged from 0.1 and 1 mg of total antisense oligonucleotides for redirecting splicing per eye, such as about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 or 1.0 mg of total antisense oligonucleotides for redirecting splicing per eye.

10. A method for the treatment of an ABCA4-related disease or condition requiring modulating splicing of ABCA4 of an individual in need thereof, said method comprising contacting a cell of said individual with an antisense oligonucleotide comprising a sequence selected from the group consisting of SEQ ID NO: 85, 88 and 91.

11. The method according to claim 10 , wherein the ABCA4-related disease or condition is Stargardt disease.

Assignees

• Stichting Katholieke Univ

Inventors

• Collin Robert Wilhelmus Johanna
• Garanto Iglesias Alejandro
• Cremers Franciscus Peter Maria
• Albert Silvia

Classifications

• C12N2320/33

  Alteration of splicing · CPC title

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• C12N2310/346

  having a combination of backbone and sugar modifications · CPC title

• C12N2310/321

  2'-O-R Modification · CPC title

• C12N2310/315

  Phosphorothioates · CPC title