# US 10,301,649 B2 · Recombinant virus products and methods for inhibition of expression of DUX4

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- Number: US 10,301,649 B2
- Document ID: US10301649B2
- Status: Granted
- Kind: B2
- Application number: 15/295,591
- Filed: 2016-10-17
- Published: 2017-02-02
- Granted: 2019-05-28
- Earliest claimed: 2011-07-25
- Assignees: Nationwide Children's Hospital, Inc.
- Applicants: Nationwide Children's Hospital, Inc.
- Inventors: Scott Quenton Harper; Jian Liu; Sara Coppens; Lindsay Wallace
- Web page: https://patentgrep.com/patent/US10301649B2

## CPC

- C12N 15/86: Viral vectors
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- 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 2310/141: MicroRNAs, miRNAs
- C12N 2320/30: Special therapeutic applications
- C12N 2330/51: Specially adapted vectors
- C12N 2750/00032: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2750/14132: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- 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 RNA interference-based methods for inhibiting the expression of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding microRNAs that knock down the expression of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

## Claims

### Claim 1

A recombinant adeno-associated virus comprising:
a) the DUX4 miRNA-encoding DNA comprising the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or
b) a DNA encoding a DUX4 miRNA comprising an miRNA antisense guide strand, wherein the miRNA antisense guide strand consists of the nucleotide sequence of
SEQ ID NO: 8482,
SEQ ID NO: 8372,
SEQ ID NO: 8371,
SEQ ID NO: 8370,
SEQ ID NO: 8367,
SEQ ID NO: 8366,
SEQ ID NO: 8365,
SEQ ID NO: 8219,
SEQ ID NO: 8218,
SEQ ID NO: 8152,
SEQ ID NO: 8147,
SEQ ID NO: 8145,
SEQ ID NO: 7397,
SEQ ID NO: 7396,
SEQ ID NO: 7395,
SEQ ID NO: 7108,
SEQ ID NO: 7107,
SEQ ID NO: 7106,
SEQ ID NO: 6633,
SEQ ID NO: 6631,
SEQ ID NO: 6622,
SEQ ID NO: 6619,
SEQ ID NO: 6609,
SEQ ID NO: 6608,
SEQ ID NO: 6568,
SEQ ID NO: 6561 or
SEQ ID NO: 6560,
wherein the recombinant adeno-associated virus lacks rep and cap genes.

### Claim 2

A DNA encoding a DUX4 miRNA comprising an miRNA antisense guide strand, wherein the miRNA antisense guide strand consists of the nucleotide sequence of
SEQ ID NO: 8482,
SEQ ID NO: 8372,
SEQ ID NO: 8371,
SEQ ID NO: 8370,
SEQ ID NO: 8367,
SEQ ID NO: 8366,
SEQ ID NO: 8365,
SEQ ID NO: 8219,
SEQ ID NO: 8218,
SEQ ID NO: 8152,
SEQ ID NO: 8147,
SEQ ID NO: 8145,
SEQ ID NO: 7397,
SEQ ID NO: 7396,
SEQ ID NO: 7395,
SEQ ID NO: 7108,
SEQ ID NO: 7107,
SEQ ID NO: 7106,
SEQ ID NO: 6633,
SEQ ID NO: 6631,
SEQ ID NO: 6622,
SEQ ID NO: 6619,
SEQ ID NO: 6609,
SEQ ID NO: 6608,
SEQ ID NO: 6568,
SEQ ID NO: 6561 or
SEQ ID NO: 6560.