# US 11,111,494 B2 · Compositions for modulating Ataxin 2 expression

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- Number: US 11,111,494 B2
- Document ID: US11111494B2
- Status: Granted
- Kind: B2
- Application number: 16/387,308
- Filed: 2019-04-17
- Published: 2020-03-19
- Granted: 2021-09-07
- Earliest claimed: 2014-03-19
- Assignees: Ionis Pharmaceuticals, Inc.
- Applicants: Ionis Pharmaceuticals, Inc.
- Inventors: Susan M. Freier
- Web page: https://patentgrep.com/patent/US11111494B2

## CPC

- 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)}
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- 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 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 2310/345: having at least two different backbone modifications
- C12N 2310/346: having a combination of backbone and sugar modifications
- 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

Disclosed herein are antisense compounds and methods for decreasing Ataxin 2 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Ataxin 2 associated diseases, disorders, and conditions. Such Ataxin 2 associated diseases include spinocerebellar ataxia type 2 (SCA2), amyotropic sclerosis (ALS), and parkinsonism.

## Claims

### Claim 1

An oligomeric compound comprising a modified oligonucleotide consisting of 14 to 30 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide comprises a portion of at least 14 contiguous nucleobases, wherein the portion is complementary to:
an equal length portion of nucleobases 1957-1988 of SEQ ID NO:1
wherein the modified oligonucleotide comprises at least one modification selected from a modified sugar moiety and a modified internucleoside linkage.

### Claim 2

An oligomeric compound comprising a modified oligonucleotide consisting of 14 to 30 linked nucleosides and having a nucleobase sequence comprising at least 14 contiguous nucleobases of the nucleobase sequence of SEQ ID NO: 36 or 37, wherein the modified oligonucleotide comprises at least one modification selected from a modified sugar moiety and a modified internucleoside linkage.

### Claim 3 (depends on 1)

The oligomeric compound of claim 1, wherein the modified oligonucleotide is at least 95% or is 100% complementary to an equal length portion of an Ataxin 2 RNA transcript.

### Claim 4 (depends on 3)

The oligomeric compound of claim 3, wherein the Ataxin 2 RNA transcript has the nucleobase sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

### Claim 5 (depends on 1)

The oligomeric compound of claim 1, wherein the modified oligonucleotide consists of 14 to 20, 15 to 25, 15 to 30, 16 to 30, 17 to 30, 18 to 22, 18 to 30, 19 to 21, 19 to 30, or 20 to 30 linked nucleosides.

### Claim 6 (depends on 1)

The oligomeric compound of claim 1, wherein the modified oligonucleotide consists of 20 linked nucleosides.

### Claim 7 (depends on 1)

The oligomeric compound of claim 1, consisting of a single-stranded modified oligonucleotide.

### Claim 8 (depends on 1)

The oligomeric compound of claim 1, wherein at least one internucleoside linkage of the modified oligonucleotide is a modified internucleoside linkage.

### Claim 9 (depends on 8)

The oligomeric compound of claim 8, wherein at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage.

### Claim 10 (depends on 9)

The oligomeric compound of claim 9, wherein at least one internucleoside linkage is a phosphodiester internucleoside linkage.

### Claim 11 (depends on 9)

The oligomeric compound of claim 9, wherein each modified internucleoside linkage is a phosphorothioate internucleoside linkage.

### Claim 12 (depends on 1)

The oligomeric compound of claim 1, wherein at least one nucleoside of the modified oligonucleotide comprises a modified nucleobase.

### Claim 13 (depends on 12)

The oligomeric compound of claim 12, wherein the modified nucleobase is a 5-methylcytosine.

### Claim 14 (depends on 1)

The oligomeric compound of claim 1, wherein at least one nucleoside of the modified oligonucleotide comprises a modified sugar moiety.

### Claim 15 (depends on 14)

The oligomeric compound of claim 14, wherein the at least one modified sugar moiety is a 2′-substituted sugar moiety.

### Claim 16 (depends on 14)

The oligomeric compound of claim 14, wherein the at least one modified sugar moiety is a bicyclic sugar.

### Claim 17 (depends on 16)

The oligomeric compound of claim 16, wherein the bicyclic sugar comprises a 4′-CH(R)—O-2′ bridge wherein R is, independently, H, C1-C12 alkyl, or a protecting group.

### Claim 18 (depends on 17)

The oligomeric compound of claim 17, wherein R is methyl.

### Claim 19 (depends on 17)

The oligomeric compound of claim 17, wherein R is H.

### Claim 20 (depends on 15)

The oligomeric compound of claim 15, wherein the at least one modified sugar moiety is a 2′-O-methoxyethyl sugar moiety or a 2′-O-methyl sugar moiety.

### Claim 21 (depends on 1)

The oligomeric compound of claim 1, wherein the modified oligonucleotide comprises:
a gap segment consisting of 10 linked deoxyribonucleosides;
a 5′ wing segment consisting of 5 linked nucleosides; and
a 3′ wing segment consisting of 5 linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar moiety.

### Claim 22 (depends on 1)

A pharmaceutical composition comprising the oligomeric compound of claim 1, and a pharmaceutically acceptable carrier or diluent.

### Claim 23 (depends on 1)

The oligomeric compound of claim 1, wherein the modified oligonucleotide is a sodium salt or a potassium salt.

### Claim 24 (depends on 22)

The pharmaceutical composition of claim 22, wherein the pharmaceutically acceptable diluent is phosphate-buffered saline (PBS).

### Claim 25 (depends on 22)

The pharmaceutical composition of claim 22, wherein the modified oligonucleotide of the oligomeric compound is a sodium salt or a potassium salt.

### Claim 26 (depends on 1)

The oligomeric compound of claim 1, wherein at least one nucleoside comprises a modified nucleobase.

### Claim 27 (depends on 25)

The oligomeric compound of claim 25, wherein the modified nucleobase is a 5-methylcytosine.