# US 2019/0169610 A1 · Oligomeric compounds comprising bicyclic nucleotides and uses thereof

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- Number: US 2019/0169610 A1
- Document ID: US20190169610A1
- Status: Published application
- Kind: A1
- Application number: 16/000,179
- Filed: 2018-06-05
- Published: 2019-06-06
- Earliest claimed: 2011-02-08
- Assignees: Ionis Pharmaceuticals, Inc.
- Applicants: Ionis Pharmaceuticals, Inc.
- Inventors: Susan M. Freier; Eric E. Swayze
- Web page: https://patentgrep.com/patent/US20190169610A1

## 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)}
- C12N 15/111: {General methods applicable to biologically active non-coding nucleic acids}
- 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 2310/345: having at least two different backbone modifications
- C12N 2310/346: having a combination of backbone and sugar modifications
- C12N 2310/3525: MOE, methoxyethoxy
- C12N 2320/50: Methods for regulating/modulating their activity
- 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 oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

## Claims

### Claim at position 1

-238. (canceled)

### Claim 239

A compound comprising:
a modified oligonucleotide consisting of 10 to 20 linked nucleosides, wherein the modified oligonucleotide comprises:
a 5′-wing consisting of 2 to 5 linked nucleosides;
a 3′-wing consisting of 2 to 5 linked nucleosides; and
a gap between the 5′-wing and the 3′-wing consisting of 6 to 14 linked 2′-deoxynucleosides; and
wherein at least one of the 5′-wing and the 3′-wing comprises at least one bicyclic nucleoside selected from among LNA, α-L-LNA, or ENA; at least one of the 5′-wing and the 3′-wing comprises at least one 2′-substituted nucleoside; and at least one of the 5′-wing and the 3′-wing comprises at least one 2′-deoxynucleoside; and
wherein the nucleobase sequence of the modified oligonucleotide is complementary to the nucleobase sequence of a target nucleic acid.

### Claim 240 (depends on 239)

The compound of claim 239, wherein each of the 5′-wing and the 3′-wing comprises at least one 2′-deoxynucleoside.

### Claim 241 (depends on 239)

The compound of claim 239, wherein the 3′-wing comprises at least one 2′-deoxynucleoside.

### Claim 242 (depends on 239)

The compound of claim 239, wherein the 5′-wing comprises at least one 2′-deoxynucleoside.

### Claim 243 (depends on 239)

The compound of claim 239, wherein the 2′-substituent of the at least one 2′-substituted nucleoside is selected from among OCH3, F, OCH2F, OCHF2, OCF3, OCH2CH3, O(CH2)2F, OCH2CHF2, OCH2CF3, OCH2—CH═CH2, O(CH2)2—OCH3, O(CH2)2—SCH3, O(CH2)2—OCF3, O(CH2)3—N(R4)(R5), O(CH2)2—ON(R4)(R5), O(CH2)2—O(CH2)2—N(R4)(R5), OCH2C(═O)—N(R4)(R5), OCH2C(═O)—N(R6)—(CH2)2—N(R4)(R5) and O(CH2)2—N(R6)—C(═NR7)[N(R4)(R5)] wherein R4, R5, R6 and R7 are each, independently, H or C1-C6 alkyl.

### Claim 244 (depends on 239)

The compound of claim 239, wherein the 2′-substituent of the at least one 2′-substituted nucleoside is selected from among OCH3, F, and O(CH2)2—OCH3.

### Claim 245 (depends on 244)

The compound of claim 244, wherein the 2′-substituent of the at least one 2′-substituted nucleoside is O(CH2)2—OCH3.

### Claim 246 (depends on 244)

The compound of claim 244, wherein the 2′-substituent of the at least one 2′-substituted nucleoside is OCH3.

### Claim 247 (depends on 239)

The compound of claim 239, wherein the 5′-wing does not comprise a bicyclic nucleotide.

### Claim 248 (depends on 239)

The compound of claim 239, wherein the 3′-wing does not comprise a bicyclic nucleotide.

### Claim 249 (depends on 239)

The compound of claim 239, wherein the 5′-wing consists of 2 linked nucleosides.

### Claim 250 (depends on 239)

The compound of claim 239, wherein the 5′-wing consists of 3 linked nucleosides.

### Claim 251 (depends on 239)

The compound of claim 239, wherein the 5′-wing consists of 4 linked nucleosides.

### Claim 252 (depends on 239)

The compound of claim 239, wherein the 5′-wing consists of 5 linked nucleosides.

### Claim 253 (depends on 239)

The compound of claim 239, wherein the gap consists of 9 linked 2′-deoxynucleosides.

### Claim 254 (depends on 239)

The compound of claim 239, wherein the gap consists of 10 linked 2′-deoxynucleosides.

### Claim 255 (depends on 239)

The compound of claim 239, wherein the oligonucleotide consists of 18 linked nucleosides.

### Claim 256 (depends on 239)

The compound of claim 239, wherein the oligonucleotide consists of 20 linked nucleosides.

### Claim 257 (depends on 239)

The compound of claim 239, wherein each internucleoside linkage is a modified internucleoside linkage.

### Claim 258 (depends on 239)

The compound of claim 239, wherein the modified internucleoside linkage is a phosphorothioate linkage.