# US 2013/0281684 A1 · Compositions and their uses directed to huntingtin

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- Number: US 2013/0281684 A1
- Document ID: US20130281684A1
- Status: Published application
- Kind: A1
- Application number: 13/789,368
- Filed: 2013-03-07
- Published: 2013-10-24
- Earliest claimed: 2006-01-26
- Assignees: Isis Pharmaceuticals, Inc.
- Applicants: Isis Pharmaceuticals, Inc.
- Inventors: Susan M. Freier
- Web page: https://patentgrep.com/patent/US20130281684A1

## 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 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- 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 2310/111: spanning the whole gene, or a large part of it
- C12N 2310/31: of the backbone
- C12N 2310/315: Phosphorothioates
- C12N 2310/32: of the sugar
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/322: 2'-R Modification
- C12N 2310/323: modified ring structure
- C12N 2310/3231: having an additional ring, e.g. LNA, ENA
- C12N 2310/33: of the base
- C12N 2310/3341: 5-Methylcytosine
- C12N 2310/335: Modified T or U
- C12N 2310/341: Gapmers, i.e. of the type ===---===
- C12N 2310/346: having a combination of backbone and sugar modifications
- C12N 2320/30: Special therapeutic applications
- 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 compounds, compositions and methods for modulating the expression of huntingtin in a cell, tissue or animal. Further provided are methods of slowing or preventing Huntington's Disease (HD) progression using an antisense compound targeted to huntingtin. Additionally provided are methods of delaying or preventing the onset of Huntington's Disease (HD) in an individual susceptible to Huntington's Disease (HD). Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders.

## Claims

### Claim 1

An antisense oligonucleotide 12 to 35 nucleotides in length comprising at least 12 consecutive nucleotides of a nucleotide sequence selected from the group consisting of SEQ ID NOs 46-357.

### Claim 2 (depends on 1)

The antisense oligonucleotide of claim 1, wherein said antisense oligonucleotide has at least at least 95% complementarity to SEQ ID NO: 4.

### Claim 3 (depends on 1)

The antisense oligonucleotide of claim 1, wherein said antisense oligonucleotide has at least at least 100% complementarity to SEQ ID NO: 4.

### Claim 4 (depends on 1)

The antisense oligonucleotide of claim 1 having at least one modified internucleoside linkage, sugar moiety, or nucleobase.

### Claim 5 (depends on 1)

The antisense oligonucleotide of claim 1 comprising a chimeric oligonucleotide having a gap segment positioned between 5′ and 3′ wing segments.

### Claim 6 (depends on 5)

The antisense oligonucleotide of claim 5, wherein the gap segment of the chimeric oligonucleotide is comprised of 2′-deoxynucleotides and the wing segments are comprised of nucleotides having modified sugar moieties.

### Claim 7 (depends on 6)

The antisense oligonucleotide of claim 6, wherein the modified sugar moiety is 2′-OMe or a bicyclic nucleic acid.

### Claim 8 (depends on 5)

The antisense oligonucleotide of claim 5, wherein the gap segment of the chimeric oligonucleotide consists of ten 2′-deoxynucleotides and each wing segment consists of five 2′-O-methoxyethyl-modified nucleotides.

### Claim 9 (depends on 8)

The antisense oligonucleotide of claim 8, wherein said antisense oligonucleotide is 20 nucleotides in length.

### Claim 10 (depends on 1)

The antisense oligonucleotide of claim 1, wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.

### Claim 11 (depends on 1)

The antisense oligonucleotide of claim 1, wherein the each cytosine is a 5-methylcytosine.

### Claim 12 (depends on 1)

The antisense oligonucleotide of claim 1, wherein said oligonucleotide is 17 to 25 nucleotides in length.

### Claim 13 (depends on 1)

The antisense oligonucleotide of claim 1, wherein said oligonucleotide is 19 to 23 nucleotides in length.

### Claim 14 (depends on 1)

The antisense oligonucleotide of claim 1, wherein said oligonucleotide is 20 nucleotides in length.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising an antisense oligonucleotide of claim 1 and a pharmaceutically acceptable diluent.

### Claim 16 (depends on 1)

The antisense oligonucleotide of claim 1, wherein said nucleotide sequence is selected from the group consisting of SEQ ID NOs: 93, 100, 105, 110, 137, 345, 346, and 353.

### Claim 17 (depends on 16)

The antisense oligonucleotide of claim 16, wherein said antisense oligonucleotide has at least at least 95% complementarity to SEQ ID NO: 4.

### Claim 18 (depends on 16)

The antisense oligonucleotide of claim 16, wherein said antisense oligonucleotide has at least at least 100% complementarity to SEQ ID NO: 4.

### Claim 19 (depends on 16)

The antisense oligonucleotide of claim 16 having at least one modified internucleoside linkage, sugar moiety, or nucleobase.

### Claim 20 (depends on 16)

The antisense oligonucleotide of claim 16 comprising a chimeric oligonucleotide having a gap segment positioned between 5′ and 3′ wing segments.