# US 2014/0194614 A1 · Amino-lna, thio-lna and alpha-l-oxy-ln

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- Number: US 2014/0194614 A1
- Document ID: US20140194614A1
- Status: Published application
- Kind: A1
- Application number: 13/841,646
- Filed: 2013-03-15
- Published: 2014-07-10
- Earliest claimed: 2002-11-18
- Assignees: Santaris Pharma A/S
- Applicants: Santaris Pharma A/S
- Inventors: Signe M. Christensen; Nikolaj Dam Mikkelsen; Miriam Frieden; Henrik Frydenlund Hansen; Troels Koch; Daniel Sejer Pedersen; Christoph Rosenbohm; Charlotte Albaek Thrue; Majken Westergaard
- Web page: https://patentgrep.com/patent/US20140194614A1

## 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 31/7088: Compounds having three or more nucleosides or nucleotides
- C07H 19/04: Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H 19/06: Pyrimidine radicals
- C07H 19/16: Purine radicals
- 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 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- C12N 2310/11: Antisense
- C12N 2310/315: Phosphorothioates
- C12N 2310/3231: having an additional ring, e.g. LNA, ENA
- C12N 2310/341: Gapmers, i.e. of the type ===---===
- C12N 2310/344: Position-specific modifications, e.g. on every purine, at the 3'-end
- 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

A novel class of pharmaceuticals which comprises a Locked Nucleic Acid (LNA) which can be used in antisense therapy. These novel oligonucleotides have improved antisense properties. The novel oligonucleotides are composed of at least one LNA selected from beta-D-thio/amino-LNA or alpha-L-oxy/thio/amino-LNA. The oligonucleotides comprising LNA may also include DNA and/or RNA nucleotides.

## Claims

### Claim at position 1

1-43. (canceled)

### Claim 43

A LNA nucleoside having the formula:
wherein X is O; R′ and R″ are independently either H or a terminal group; and (CH2)n is a methylene substituted with methyl, or a pharmaceutically acceptable salt thereof.

### Claim 44

A gapmer oligomer having 10-15 nucleotide units, comprising central region of at least 4, 5, 6, 7 or 8 DNA nucleotides which is flanked both 5′ and 3′ by locked nucleotides having the formula:
wherein X is O; (CH2)n is a methylene substituted with a C1-6 alkyl.

### Claim 45 (depends on 44)

The gapmer oligomer of claim 44 wherein at least one of the locked nucleotides has the formula:
wherein X is O; (CH2)n is a methylene substituted with a methyl group.

### Claim 46 (depends on 45)

The gapmer oligomer of claim 45 wherein all of the locked nucleotides have the formula:
wherein X is O; (CH2)n is a methylene substituted with a methyl group.

### Claim 47 (depends on 44)

The gapmer oligomer of claim 44, wherein the at least one or all the internucleoside linkages are phosphorothioate.

### Claim 48 (depends on 45)

The gapmer oligomer of claim 45, wherein the at least one or all the internucleoside linkages are phosphorothioate.

### Claim 49 (depends on 46)

The gapmer oligomer of claim 46, wherein the at least one or all the internucleoside linkages are phosphorothioate.

### Claim 50 (depends on 47)

The gapmer oligomer of claim 47, wherein the central region is 8-10 nucleotides

### Claim 51 (depends on 48)

The gapmer oligomer of claim 48, wherein the central region is 8-10 nucleotides

### Claim 52 (depends on 49)

The gapmer oligomer of claim 49, wherein the central region is 8-10 nucleotides

### Claim 53 (depends on 50)

The gapmer oligomer of claim 50, wherein the flanks have 1-4 of the locked nucleotides.

### Claim 54 (depends on 51)

The gapmer oligomer of claim 51, wherein the flanks have 1-4 of the locked nucleotides.

### Claim 55 (depends on 52)

The gapmer oligomer of claim 52, wherein the flanks have 1-4 of the locked nucleotides.

### Claim 56 (depends on 50)

The gapmer oligomer of claim 50, wherein the flanks have 2-3 of the locked nucleotides.

### Claim 57 (depends on 51)

The gapmer oligomer of claim 51, wherein the flanks have 2-3 of the locked nucleotides.

### Claim 58 (depends on 52)

The gapmer oligomer of claim 52, wherein the flanks have 2-3 of the locked nucleotides.

### Claim 59 (depends on 56)

The gapmer oligomer according to claim 56, wherein the oligomer has 12-14 nucleotide units.

### Claim 60 (depends on 57)

The gapmer oligomer according to claim 57, wherein the oligomer has 12-14 nucleotide units.

### Claim 61 (depends on 58)

The gapmer oligomer according to claim 58, wherein the oligomer has 12-14 nucleotide units.

### Claim 62

A gapmer oligomer having 12-14 nucleotide units having a central region of at least 8 DNA nucleotides which is flanked both 5′ and 3′ by 1-3 locked nucleotides having the formula:
wherein X is O; (CH2)n is a methylene substituted with methyl group; wherein all the internucleoside linkages are phosphorothioate linkages.

### Claim 63 (depends on 62)

The gapmer oligomer according to claim 62, wherein the central region is of 8 DNA nucleotides.

### Claim 64 (depends on 62)

The gapmer oligomer according to claim 62, wherein the central region is of 9 DNA nucleotides.

### Claim 65 (depends on 62)

The gapmer oligomer according to claim 62, wherein the central region is of 10 DNA nucleotides.

### Claim 66 (depends on 62)

The gapmer oligomer according to claim 62, wherein the 5′ and 3′ flank consists of 1, 2 or 3 of the locked nucleotides.

### Claim 67 (depends on 66)

The gapmer oligomer according to claim 66, wherein the 5′ and 3′ flanks each consist of 2 of the locked nucleotides.

### Claim 68 (depends on 62)

The gapmer according to claim 62, wherein all of the nucleotides other than the central region of at least 8 DNA nucleotides are locked nucleotides having the formula:
wherein X is O; (CH2)n is a methylene substituted with a C1-6 alkyl.

### Claim 69 (depends on 62)

The gapmer according to claim 62 wherein all of the nucleotides other than the central region of at least 8 DNA nucleotides are locked nucleotides having the formula:
wherein X is O; (CH2)n is a methylene substituted with methyl group.