# US 12,215,321 B2 · Modulators of diacyglycerol acyltransferase 2 (DGAT2)

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,215,321 B2
- Document ID: US12215321B2
- Status: Granted
- Kind: B2
- Application number: 17/677,875
- Filed: 2022-02-22
- Published: 2023-02-16
- Granted: 2025-02-04
- Earliest claimed: 2015-07-10
- Assignees: Ionis Pharmaceuticals, Inc.
- Applicants: Ionis Pharmaceuticals, Inc.
- Inventors: Eric E. Swayze
- Web page: https://patentgrep.com/patent/US12215321B2

## CPC

- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- 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
- C12Y 203/0102: Diacylglycerol O-acyltransferase (2.3.1.20)
- C12N 2310/11: Antisense
- C12N 2310/315: Phosphorothioates
- C12N 2310/3341: 5-Methylcytosine
- C12N 2310/341: Gapmers, i.e. of the type ===---===
- C12N 2310/346: having a combination of backbone and sugar modifications
- C12N 2320/35: based on a specific dosage / administration regimen
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- C12Y: ENZYMES

## Abstract

The present embodiments provide methods, compounds, and compositions useful for inhibiting DGAT2 expression, which may be useful for treating, preventing, or ameliorating a disease associated with DGAT2.

## Claims

### Claim 1

A method of treating, preventing, or ameliorating NAFLD, NASH, lipodystrophy, or partial lipodystrophy in an individual comprising administering to the individual a compound comprising or consisting of a modified oligonucleotide according to the following formula:
or a salt thereof;
wherein administering the compound reduces or inhibits triglyceride synthesis, lipid synthesis and/or insulin resistance in the liver or white adipose tissue of the individual;
thereby treating, preventing, or ameliorating NAFLD, NASH, lipodystrophy, or partial lipodystrophy.

### Claim 2 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable salt is a potassium salt or a sodium salt.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compound is administered as a pharmaceutical composition comprising the compound and a pharmaceutically acceptable diluent.

### Claim 4 (depends on 3)

The method of claim 3, wherein the pharmaceutically acceptable diluent comprises water or saline or phosphate buffered saline (PBS).

### Claim 5 (depends on 1)

The method of claim 1, wherein the individual has, or is at risk of having, NAFLD, NASH, lipodystrophy, or partial lipodystrophy.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound or composition is administered to the individual parenterally.

### Claim 7 (depends on 6)

The method of claim 6, wherein parenterally is subcutaneous administration or intravenous administration.

### Claim 8

A method of treating, preventing, or ameliorating NAFLD, NASH, lipodystrophy, or partial lipodystrophy in an individual comprising administering to the individual a compound comprising or consisting of a modified oligonucleotide according to the following formula:
wherein administering the compound reduces or inhibits triglyceride synthesis, lipid synthesis, and/or insulin resistance, or improves insulin signaling, insulin sensitivity and/or cardiovascular risk profile in the individual;
thereby treating, preventing, or ameliorating NAFLD, NASH, lipodystrophy, or partial lipodystrophy.

### Claim 9 (depends on 8)

The method of claim 8, wherein the compound is administered as a pharmaceutical composition comprising the compound and a pharmaceutically acceptable diluent.

### Claim 10 (depends on 9)

The method of claim 9, wherein the pharmaceutically acceptable diluent comprises water or saline or phosphate buffered saline (PBS).

### Claim 11 (depends on 8)

The method of claim 8, wherein the individual has, or is at risk of having, NAFLD, NASH, lipodystrophy, or partial lipodystrophy.

### Claim 12 (depends on 8)

The method of claim 8, wherein the compound or composition is administered to the individual parenterally.

### Claim 13 (depends on 12)

The method of claim 12, wherein parenterally is subcutaneous administration or intravenous administration.