# US 11,898,145 B2 · Enhanced oligonucleotides for inhibiting RTEL1 expression

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- Number: US 11,898,145 B2
- Document ID: US11898145B2
- Status: Granted
- Kind: B2
- Application number: 17/590,754
- Filed: 2022-02-01
- Published: 2022-08-11
- Granted: 2024-02-13
- Earliest claimed: 2021-02-02
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Hoffmann-La Roche Inc.
- Inventors: Erik Funder; Natascha Hruschka; Susanne Kammler; Erich Koller; Brian Leonard; Souphalone Luangsay; Susanne Mohr; Tobias Nilsson; Søren Ottosen; Lykke Pedersen; Søren V. Rasmussen; Steffen Schmidt; Sabine Sewing; Daniel Turley; Johanna Marie Walther
- Web page: https://patentgrep.com/patent/US11898145B2

## 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 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61P 31/20: for DNA viruses
- C12N 2310/11: Antisense
- C12N 2310/315: Phosphorothioates
- C12N 2310/3231: having an additional ring, e.g. LNA, ENA
- C12N 2310/3341: 5-Methylcytosine
- 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 2310/351: Conjugate
- C12Y 306/01: in phosphorus-containing anhydrides (3.6.1)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Y: ENZYMES

## Abstract

The present disclosure provides antisense oligonucleotides targeting Regulator of telomere elongation helicase 1 (RTEL1). The disclosure also provides, enhanced antisense oligonucleotides targeting RTEL1 for use in treating and/or preventing a hepatitis B virus (HBV) infection. Also disclosed are pharmaceutical compositions and their use.

## Claims

### Claim 1

An antisense oligonucleotide consisting of CTttattataactTgaAtCTC (SEQ ID NO 6), wherein capital letters are beta-D-oxy LNA nucleosides, lowercase letters are DNA nucleosides, all LNA C are 5-methyl cytosine, and all internucleoside linkages are phosphorothioate internucleoside linkages.

### Claim 2 (depends on 1)

The antisense oligonucleotide of claim 1, wherein at least one conjugate moiety is covalently attached to said antisense oligonucleotide.

### Claim 3 (depends on 2)

The antisense oligonucleotide of claim 2, wherein the at least one conjugate moiety binds to the asialoglycoprotein receptor.

### Claim 4 (depends on 2)

The antisense oligonucleotide of claim 2, wherein the conjugate moiety is:

### Claim 5 (depends on 4)

The antisense oligonucleotide of claim 4, wherein the conjugate moiety is the trivalent GalNAc moiety:
or a mixture of both trivalent GalNAc moieties.

### Claim 6 (depends on 2)

The antisense oligonucleotide of claim 2, comprising a linker positioned between the antisense oligonucleotide and the conjugate moiety.

### Claim 7 (depends on 6)

The antisense oligonucleotide of claim 6, wherein the linker comprises 2 to 5 consecutive phosphodiester-linked nucleosides.

### Claim 8

The conjugate that is:

### Claim 9 (depends on 1)

A pharmaceutically acceptable salt of the antisense oligonucleotide of claim 1.

### Claim 10 (depends on 1)

A pharmaceutical composition comprising the antisense oligonucleotide of claim 1 and a pharmaceutically acceptable diluent, solvent, carrier, salt and/or adjuvant.

### Claim 11 (depends on 1)

An in vitro method for modulating RTEL1 expression in a target cell which is expressing RTEL1, said method comprising administering the antisense oligonucleotide of claim 1, in an effective amount to said cell.

### Claim 12 (depends on 1)

A method for treating a hepatitis B virus (HBV) infection in a subject in need thereof, comprising administering a therapeutically effective amount of the antisense oligonucleotide of claim 1 to the subject, wherein said administration results in inhibition of the HBV infection.

### Claim 13 (depends on 2)

A pharmaceutically acceptable salt of the antisense oligonucleotide of claim 2.

### Claim 14 (depends on 2)

A pharmaceutical composition comprising the antisense oligonucleotide of claim 2 and a pharmaceutically acceptable diluent, solvent, carrier, salt and/or adjuvant.

### Claim 15 (depends on 9)

A pharmaceutical composition comprising the pharmaceutically acceptable salt of claim 9 and a pharmaceutically acceptable diluent, solvent, carrier, salt and/or adjuvant.

### Claim 16 (depends on 13)

A pharmaceutical composition comprising the pharmaceutically acceptable salt of the conjugate of claim 13 and a pharmaceutically acceptable diluent, solvent, carrier, salt and/or adjuvant.

### Claim 17 (depends on 12)

The method of claim 12, wherein the hepatitis B virus (HBV) infection is chronic HBV infection.