# US 11,078,485 B2 · Compositions comprising alternating 2′-modified nucleosides for use in gene modulation

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- Number: US 11,078,485 B2
- Document ID: US11078485B2
- Status: Granted
- Kind: B2
- Application number: 16/286,075
- Filed: 2019-02-26
- Published: 2020-01-16
- Granted: 2021-08-03
- Earliest claimed: 2002-11-05
- Assignees: Ionis Pharmaceuticals, Inc.
- Applicants: Ionis Pharmaceuticals, Inc.
- Inventors: Charles Allerson; Balkrishen Bhat; Anne B. Eldrup; Muthiah Manoharan; Richard H. Griffey; Brenda F. Baker; Eric E. Swayze
- Web page: https://patentgrep.com/patent/US11078485B2

## 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)}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- 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
- C07H 21/02: with ribosyl as saccharide radical
- C07H 21/04: with deoxyribosyl as saccharide radical
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- C12N 15/1135: {against oncogenes or tumor suppressor genes}
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/315: Phosphorothioates
- C12N 2310/321: 2'-O-R Modification
- C12N 2310/322: 2'-R Modification
- C12N 2310/323: modified ring structure
- C12N 2310/341: Gapmers, i.e. of the type ===---===
- C12N 2310/343: having patterns, e.g. ==--==--==--
- C12N 2310/346: having a combination of backbone and sugar modifications
- C12N 2320/30: Special therapeutic applications
- C12N 2320/51: modulating the chemical stability, e.g. nuclease-resistance
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- 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)

## Abstract

The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.

## Claims

### Claim 1

A composition comprising a first oligomeric compound and a second oligomeric compound, wherein:
said first oligomeric compound is capable of hybridizing with said second oligomeric compound;
said first oligomeric compound is complementary to and capable of hybridizing to a selected nucleic acid target;
each of said first and said second oligomeric compounds independently comprises 20-23 linked nucleosides;
at least one of said first and said second oligomeric compounds comprises a region having the formula X1-Y-X2, wherein Y is a region of from about 5 to about 12 linked nucleosides and each of X1 and X2 is, independently, a plurality of linked nucleosides having the formula FSFS, where one of F and S is a 2′-F modified nucleoside and the other of F and S is a 2′-O-CH3 modified nucleoside; and
each internucleoside linkage of said first and said second oligomeric compound is, independently, a phosphodiester or a phosphorothioate internucleoside linkage.

### Claim 2 (depends on 1)

The composition of claim 1 wherein said first oligomeric compound comprises a 5′-phosphate group.

### Claim 3 (depends on 1)

The composition of claim 1 wherein said second oligomeric compound comprises a 5′-phosphate group.

### Claim 4 (depends on 1)

The composition of claim 1 wherein each of said first and said second oligomeric compounds comprise a 5′-phosphate group.

### Claim 5 (depends on 1)

The composition of claim 1 wherein at least one of said first and said second oligomeric compounds comprises at least one conjugate group.

### Claim 6 (depends on 1)

The composition of claim 1 wherein at least one of said first and said second oligomeric compounds comprises at least one terminal cap moiety attached at the 3′-end, the 5′-end or both the 3′-end and the 5′-end of the oligomeric compound.

### Claim 7 (depends on 1)

A method of inhibiting gene expression comprising contacting one or more cells, a tissue or an animal with a composition of claim 1.