# US 2023/0054720 A1 · Antisense Oligonucleotides Targeting ATXN3

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2023/0054720 A1
- Document ID: US20230054720A1
- Status: Published application
- Kind: A1
- Application number: 17/540,495
- Filed: 2021-12-02
- Published: 2023-02-23
- Earliest claimed: 2020-12-03
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Hoffmann-La Roche Inc.
- Inventors: Heidi Rye Hudlebusch; Lykke Pedersen; Erik Funder; Lukasz Kielpinski; Christoffer Sondergaard; Alexander Herbert Stephan; Mads Manso
- Web page: https://patentgrep.com/patent/US20230054720A1

## CPC

- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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)}
- C12N 2310/11: Antisense
- C12N 2310/315: Phosphorothioates
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/3231: having an additional ring, e.g. LNA, ENA
- C12N 2310/3341: 5-Methylcytosine
- C12N 2310/341: Gapmers, i.e. of the type ===---===
- C12N 2310/346: having a combination of backbone and sugar modifications
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to antisense LNA oligonucleotides (oligomers) complementary to ATXN3 pre-mRNA sequences, which are capable of inhibiting the expression of ATXN3 protein. Inhibition of ATXN3 expression is beneficial for the treatment of spinocerebellar ataxia

## Claims

### Claim 1

An antisense oligonucleotide selected from the group consisting of Compound ID Nos. 1122_91, 1122_107, 1122_154, 1122_155, 1122_156, 1122_157, 1122_158, 1122_167, 1122_172,1122_175, 1122_294, 1122_296, 1122_359, 1122_384, 1122_385, 1816_13, 1816_15, 1816_28, 1816_41, 1816_42, 1816_43, 1816_60, 1816_61, 1816_64, 1816_65, 1816_68, and 1816_92, or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

An antisense oligonucleotide according to claim 1 of the following chemical annotation:
a. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[mR]U[sP].[dR](A)[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C)[sP].[LR][5me]C (SEQ ID NO:1122, wherein residue 10 is U) (Compound ID No. 1122_91);
b. [LR]A[sP].[LR]A[sP].[mR]U[sP].[LR][5me]C[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[LR]T[sP].[dR]T[sP].[LR][5me]C[sP].[LR][5me]C (SEQ ID NO:1122, wherein residue 3 is U) (Compound ID No. 1122_107);
c. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5m e]C (SEQ ID NO:1122) (Compound ID No. 1122_154);
d. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5m e]C (SEQ ID NO:1122) (Compound ID No. 1122_155);
e. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5meC][sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[d R]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5me]C (SEQ ID NO:1122) (Compound ID No. 1122_156);
f. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5meC][sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[d R]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5me]C (SEQ ID NO:1122) (Compound ID No. 1122_157);
g. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5m e]C (SEQ ID NO:1122) (Compound ID No. 1122_158);
h. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[MOE]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5m e]C (SEQ ID NO:1122) (Compound ID No. 1122_167);
i. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[mR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5m e]C (SEQ ID NO:1122) (Compound ID No. 1122_172);
j. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[mR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5m e]C (SEQ ID NO:1122) (Compound ID No. 1122_175);
k. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[fR]C[sP].[LR][5me]C (SEQ ID NO:1122) (Compound ID No. 1122_294);
l. [LR]A[sP].[dR]A[sP].[dR]T[sP].[mR]C[sP].[dR]T[sP].[LR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5me]C (SEQ ID NO:1122) (Compound ID No. 1122_296);
m. [LR]A[sP].[LR]A[sP].[LR]T[sP].[LR][5me]C[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[MOPS].[LR]T[sP].[dR]T[sP].[LR][5me]C[sP].[LR][5me]C (SEQ ID NO:1122) (Compound ID No. 1122_359);
n. [LR]A[sP].[LR]A[sP].[LR]T[sP].[LR][5me]C[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[LR]T[MOPS].[dR]T[sP].[LR][5me]C[sP].[LR][5me]C (SEQ ID NO:1122) (Compound ID No. 1122_384);
o. [LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[MOPS].[dR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[dR]C[sP].[dR]T[sP].[LR]T[sP].[LR][5me]C[sP].[LR][5me]C (SEQ ID NO:1122) (Compound ID No. 1122_385);
p. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_13);
q. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_15);
r. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP][fR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_28);
s. [LR]G[sP].[LR]A[sP].[LR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_41);
t. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[MOE]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_42);
u. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[MOE][5me]C[sP].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_43);
v. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[mR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_60);
w. [LR]G[sP].[LR]A[sP].[mR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_61);
x. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[fR]C[sP].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_64);
y. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[mR]C[sP].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_65);
z. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[fR]U[sP].[LR]T (SEQ ID NO:1816, wherein residue 17 is U) (Compound ID No. 1816_68); or
aa. [LR]G[sP].[LR]A[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[sP].[dR]T[sP].[LR]T[sP].[LR]A[sP].[dR]T[sP].[dR]T[sP].[dR]T[sP].[dR]A[sP].[dR]C[sP].[dR]A[sP].[dR]T[sP].[LR][5me]C[MOPS].[LR]T[sP].[LR]T (SEQ ID NO:1816) (Compound ID No. 1816_92);
or a pharmaceutically acceptable salt thereof, wherein
[LR] is a beta-D-oxy-LNA nucleoside,
[LR][5me]C is a beta-D-oxy-LNA 5-methyl cytosine nucleoside,
[dR] is a DNA nucleoside,
[sP] is a phosphorothioate internucleoside linkage (stereo undefined)
[ssP] is a stereodefined Sp phosphorothioate internucleoside linkage
[MOPS] is a 3-methoxypropylphosphonothioate internucleoside linkage
[MOPO] is a 3-methoxypropylphosphonate internucleoside linkage
[mR] is a 2′-O-methyl nucleoside,
[MOE] is a 2′-O-methoxyethyl nucleoside, and
[fR] is a 2′-fluoro nucleoside.

### Claim 3 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12A (Compound ID No. 1122_91); or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12B (Compound ID No. 1122_107); or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12C (Compound ID No. 1122_154); or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12D (Compound ID No. 1122_155); or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12E (Compound ID No. 1122_156); or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12F (Compound ID No. 1122_157); or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12G (Compound ID No. 1122_158); or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12H (Compound ID No. 1122_167); or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12I (Compound ID No. 1122_172); or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12J (Compound ID No. 1122_175); or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12K (Compound ID No. 1122_294); or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12L (Compound ID No. 1122_296); or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12M (Compound ID No. 1122_359); or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12N (Compound ID No. 1122_384); or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12O (Compound ID No. 1122_385); or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12P (Compound ID No. 1816_13); or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12Q (Compound ID No. 1816_15); or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12R (Compound ID No. 1816_28); or a pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12S (Compound ID No. 1816_41); or a pharmaceutically acceptable salt thereof.

### Claim 22 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12T (Compound ID No. 1816_42); or a pharmaceutically acceptable salt thereof.

### Claim 23 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12U (Compound ID No. 1816_43); or a pharmaceutically acceptable salt thereof.

### Claim 24 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12V (Compound ID No. 1816_60); or a pharmaceutically acceptable salt thereof.

### Claim 25 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12W (Compound ID No. 1816_61); or a pharmaceutically acceptable salt thereof.

### Claim 26 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12X (Compound ID No. 1816_64); or a pharmaceutically acceptable salt thereof.

### Claim 27 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12Y (Compound ID No. 1816_65); or a pharmaceutically acceptable salt thereof.

### Claim 28 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12Z (Compound ID No. 1816_68); or a pharmaceutically acceptable salt thereof.

### Claim 29 (depends on 1)

The antisense oligonucleotide according to claim 1, which is the antisense oligonucleotide shown in FIG. 12AA (Compound ID No. 1816_92); or a pharmaceutically acceptable salt thereof.

### Claim 30 (depends on 1)

A conjugate comprising an oligonucleotide according to claim 1, and at least one conjugate moiety covalently attached to said oligonucleotide; or a pharmaceutically acceptable salt thereof.

### Claim 31 (depends on 1)

A pharmaceutical composition comprising an oligonucleotide according to claim 1 or a conjugate thereof and a pharmaceutically acceptable diluent, solvent, carrier, salt and/or adjuvant.

### Claim 32

An in vivo or in vitro method for modulating ATXN3 expression in a target cell which is expressing ATXN3, said method comprising administering an oligonucleotide selected from a group consisting of Compound ID Nos. 1122_91, 1122_107, 1122_154, 1122_155, 1122_156, 1122_157, 1122_158, 1122_167, 1122_172, 1122_175, 1122_294, 1122_296, 1122_359, 1122_384, 1122_385, 1816_13, 1816_15, 1816_28, 1816_41, 1816_42, 1816_43, 1816_60, 1816_61, 1816_64, 1816_65, 1816_68, and 1816_92, a conjugate, a salt, or a pharmaceutical composition thereof in an effective amount to said cell.

### Claim 33

A method for treating or preventing a disease comprising administering a therapeutically or prophylactically effective amount of an oligonucleotide selected from a group consisting of Compound ID Nos. 1122_91, 1122_107, 1122_154, 1122_155, 1122_156, 1122_157, 1122_158, 1122_167, 1122_172, 1122_175, 1122_294, 1122_296, 1122_359, 1122_384, 1122_385, 1816_13, 1816_15, 1816_28, 1816_41, 1816_42, 1816_43, 1816_60, 1816_61, 1816_64, 1816_65 1816_68, and 1816_92, a conjugate, a salt, or a pharmaceutical composition thereof to a subject suffering from or susceptible to the disease.

### Claim 34 (depends on 33)

The method of claim 33, wherein the disease is spinocerebellar ataxia, such as spinocerebellar ataxia 3, such as Machado-Joseph disease

### Claim 35 (depends on 1)

The oligonucleotide, a conjugate, a salt, or a pharmaceutical composition thereof according to claim 1 for use in medicine.

### Claim 36 (depends on 1)

The oligonucleotide, a conjugate, a salt, or a pharmaceutical composition thereof according to claim 1 for use in the treatment or prevention of spinocerebellar ataxia, such as spinocerebellar ataxia 3, such as Machado-Joseph disease, (MJD).

### Claim 37 (depends on 1)

Use of the oligonucleotide, a conjugate, a salt, or a pharmaceutical composition thereof according to claim 1 for the preparation of a medicament for treatment or prevention of spinocerebellar ataxia, such as spinocerebellar ataxia 3, such as Machado-Joseph disease.