# US 12,180,471 B2 · Antisense oligonucleotides for the treatment of Stargardt disease

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- Number: US 12,180,471 B2
- Document ID: US12180471B2
- Status: Granted
- Kind: B2
- Application number: 16/604,618
- Filed: 2018-04-13
- Published: 2021-04-22
- Granted: 2024-12-31
- Earliest claimed: 2017-04-13
- Assignees: ProQR Therapeutics II B.V.
- Applicants: ProQR Therapeutics II B.V.
- Inventors: Aliye Seda Yilmaz-Elis; Peter Adamson; Kalyana Chakravarthi Dulla; Iris Antoinette Ernestine Schulkens
- Web page: https://patentgrep.com/patent/US12180471B2

## CPC

- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61P 27/02: Ophthalmic agents
- C12N 2310/11: Antisense
- C12N 2310/315: Phosphorothioates
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/322: 2'-R Modification
- C12N 2320/33: Alteration of splicing
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to the fields of medicine and biotechnology. In particular, it relates to novel antisense oligonucleotides (AONs) that may be used in the treatment, prevention and/or delay of Stargardt disease and/or ABCA4-associated eye disease. More in particular, the invention relates to AONs that are used in inhibiting or blocking exon 39 skipping in the human ABCA4 pre-mRNA.

## Claims

### Claim 1

An antisense oligonucleotide (AON) that is able to inhibit skipping of at least one exon in human ABCA4 pre-mRNA, wherein the exon skipping is due to a c.5461-10T>C mutation in intron 38 of the human ABCA4 gene, wherein said AON comprises or consists of the sequence of any of SEQ ID NO: 12, 31 and 32, wherein said AON has at least one phosphorothioate linkage.

### Claim 2 (depends on 1)

The AON according to claim 1, wherein said AON is an oligoribonucleotide (RNA oligonucleotide) comprising at least one 2′-O alkyl modification.

### Claim 3 (depends on 1)

The AON according to claim 1, wherein said AON is an oligoribonucleotide (RNA oligonucleotide) comprising at least one 2′-methoxyethoxy (2′-MOE) modification.

### Claim 4 (depends on 1)

A pharmaceutical composition comprising the AON according to claim 1, and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is for intravitreal administration.

### Claim 5

A viral vector expressing antisense oligonucleotide (AON) that is able to inhibit skipping of at least one exon in human ABCA4 pre-mRNA, wherein the exon skipping is due to a c.5461-10T>C mutation in intron 38 of the human ABCA4 gene, wherein said AON comprises or consists of the sequence of any of SEQ ID NO: 12, 31 and 32.