# US 11,028,122 B1 · Antisense nucleic acids

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- Number: US 11,028,122 B1
- Document ID: US11028122B1
- Status: Granted
- Kind: B1
- Application number: 17/175,276
- Filed: 2021-02-12
- Published: 2021-07-01
- Granted: 2021-06-08
- Earliest claimed: 2010-09-01
- Assignees: Nippon Shinyaku Co., Ltd.; National Center of Neurology and Psychiatry
- Applicants: Nippon Shinyaku Co., Ltd.; National Center of Neurology and Psychiatry
- Inventors: Naoki Watanabe; Youhei Satou; Shin'ichi Takeda; Tetsuya Nagata
- Web page: https://patentgrep.com/patent/US11028122B1

## CPC

- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- C07H 21/04: with deoxyribosyl as saccharide radical
- C07H 21/00: Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07K 14/4708: {Duchenne dystrophy}
- 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)}
- C12N 2310/11: Antisense
- C12N 2310/3145: with the nitrogen in 3' or 5'-position
- C12N 2310/315: Phosphorothioates
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/3525: MOE, methoxyethoxy
- C12N 2320/33: Alteration of splicing
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention provides an oligomer which efficiently enables to cause skipping of the 53rd exon in the human dystrophin gene. Also provided is a pharmaceutical composition which causes skipping of the 53rd exon in the human dystrophin gene with a high efficiency.

## Claims

### Claim 1

A composition comprising a cationic polymer with a phosphorodiamidate morpholino oligomer (PMO) antisense oligomer that is 100% complementary to a target sequence of 5′-GAACACCUUCAGAACCGGAGGCAAC-3′ (SEQ ID NO: 124),
wherein said PMO antisense oligomer causes skipping of the 53rd exon in a human dystrophin pre-mRNA,
wherein said PMO antisense oligomer hybridizes to said target sequence with Watson-Crick base pairing under physiological conditions,
wherein said PMO antisense oligomer has exactly 25 phosphorodiamidate morpholino monomers, each of which has the formula:
wherein each of R2 and R3 represents a methyl, wherein Base is a nucleobase selected from the group consisting of uracil, cytosine, thymine, adenine, and guanine, and
wherein the 5′ end of said PMO antisense oligomer has a formula selected from the group consisting of:

### Claim 2

A composition that causes skipping of the 53rd exon in a human dystrophin pre-mRNA, comprising a cationic carrier with a 25-mer phosphorodiamidate morpholino oligomer (PMO) antisense oligomer,
wherein said PMO antisense oligomer is 100% complementary to a target sequence of 5′-GAACACCUUCAGAACCGGAGGCAAC-3′ (SEQ ID NO: 124),
wherein each phosphorodiamidate morpholino monomer of said PMO antisense oligomer has the formula:
wherein each of R2 and R3 represents a methyl, wherein Base is a nucleobase selected from the group consisting of uracil, cytosine, thymine, adenine, and guanine, and
wherein said cationic carrier promotes delivery of said composition to a muscle tissue.

### Claim 3 (depends on 2)

The composition of claim 2, wherein said cationic carrier is a cationic polymer.

### Claim 4

A composition comprising:
a) a 25-mer phosphorodiamidate morpholino oligomer (PMO) antisense oligomer that is 100% complementary to a target sequence of 5′-GAACACCUUCAGAACCGGAGGCAAC-3′ (SEQ ID NO: 124), wherein said PMO antisense oligomer causes skipping of the 53rd exon in a human dystrophin pre-mRNA; and
b) a carrier to promote delivery of said PMO antisense oligomer to a muscle tissue.

### Claim 5 (depends on 4)

The composition of claim 4, wherein said carrier is a cationic polymer.