# US 2024/0189340 A1 · Lipid nanoparticle compositions for delivering circular polynucleotides

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- Number: US 2024/0189340 A1
- Document ID: US20240189340A1
- Status: Published application
- Kind: A1
- Application number: 18/501,950
- Filed: 2023-11-03
- Published: 2024-06-13
- Earliest claimed: 2021-11-08
- Assignees: Orna Therapeutics, Inc.
- Applicants: Orna Therapeutics, Inc.
- Inventors: Allen T. HORHOTA; Junghoon YANG; Kevin J. KAUFFMAN; Thomas BARNES; Robert Alexander WESSELHOEFT; Amy M. BECKER; Gregory MOTZ
- Web page: https://patentgrep.com/patent/US20240189340A1

## CPC

- C07C 229/12: to carbon atoms of acyclic carbon skeletons
- A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543})
- A61K 9/5123: {Organic compounds, e.g. fats, sugars}
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/28: Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
- A61K 47/543: {Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine}
- A61K 48/0033: {the non-active part being non-polymeric}
- C07C 219/06: having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C 229/22: the carbon skeleton being further substituted by oxygen atoms
- C07C 229/24: having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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)

## Abstract

Disclosed herein are novel lipids that can be used in combination with other lipid components, such as helper lipids, structural lipids, and cholesterols, to form lipid nanoparticles for delivery of therapeutic agents, such as nucleic acids (e.g., circular polynucleotides), both in vitro and in vivo.

## Claims

### Claim at position 1

1-107. (canceled)

### Claim 108

An ionizable lipid represented by Formula (13*):
or a pharmaceutically acceptable salt thereof, wherein:
n* is an integer from 1 to 7;
Ra is hydrogen;
Rb is hydrogen or C1-C6 alkyl;
R1 and R2 are each independently —(CH2)qC(O)O(CH2)rCH(R8)(R9),
wherein:
q is an integer from 0 to 12,
r is 0,
R8 is R10, and
R9 and R10 are independently unsubstituted linear C1-C12 alkyl or unsubstituted linear C2-C12 alkenyl.

### Claim 109 (depends on 108)

The ionizable lipid of claim 108, wherein the ionizable lipid is represented by Formula (13a-1), Formula (13a-2), or Formula (13a-3):
wherein n is 1, 2, 3, 4, or 5.

### Claim 110 (depends on 109)

The ionizable lipid of claim 109, wherein n is 2, 3, or 4.

### Claim 111 (depends on 108)

The ionizable lipid of claim 108, wherein q is 3, 4, 5, or 6.

### Claim 112 (depends on 108)

The ionizable lipid of claim 108, wherein Rb is hydrogen.

### Claim 113 (depends on 108)

The ionizable lipid of claim 108, wherein Rb is C1-C6 alkyl.

### Claim 114 (depends on 108)

The ionizable lipid of claim 108, wherein R9 is unsubstituted linear C2-C8 alkyl.

### Claim 115 (depends on 108)

The ionizable lipid of claim 108, wherein R10 is unsubstituted linear C1-C12 alkyl.

### Claim 116 (depends on 108)

The ionizable lipid of claim 108, wherein R9 and R10 are each independently unsubstituted linear C4-C8 alkyl.

### Claim 117 (depends on 108)

The ionizable lipid of claim 108, wherein R9 and R10 are each independently unsubstituted linear C6-C8 alkyl.

### Claim 118 (depends on 108)

The ionizable lipid of claim 108, wherein R1 and R2 are each independently

### Claim 119 (depends on 118)

The ionizable lipid of claim 118, wherein R1 and R2 are the same.

### Claim 120 (depends on 118)

The ionizable lipid of claim 118, wherein R1 and R2 are different.

### Claim 121 (depends on 108)

The ionizable lipid of claim 108, wherein the ionizable lipid is:
or is a pharmaceutically acceptable salt thereof.

### Claim 122 (depends on 108)

The ionizable lipid of claim 108, wherein the ionizable lipid is:
or is a pharmaceutically acceptable salt thereof.

### Claim 123 (depends on 108)

The ionizable lipid of claim 108, wherein the ionizable lipid is:
or is a pharmaceutically acceptable salt thereof.

### Claim 124 (depends on 108)

The ionizable lipid of claim 108, wherein the ionizable lipid is:
or is a pharmaceutically acceptable salt thereof.

### Claim 125

An ionizable lipid represented by Formula (13):
or a pharmaceutically acceptable salt thereof, wherein:
n is 1, 2, 3, or 4;
Ra is hydrogen;
R1 and R2 are each independently —(CH2)qC(O)O(CH2)rCH(R8)(R9),
wherein:
q is 3, 4, 5, or 6,
r is 0,
R8 is R10, and
R9 and R10 are each independently unsubstituted linear C2-C8 alkyl.

### Claim 126 (depends on 125)

The ionizable lipid of claim 125, wherein R1 and R2 are the same.

### Claim 127 (depends on 125)

The ionizable lipid of claim 125, wherein R1 and R2 are different.

### Claim 128 (depends on 125)

The ionizable lipid of claim 125, wherein R1 and R10 are the same.

### Claim 129 (depends on 125)

The ionizable lipid of claim 125, wherein R1 and R10 are different.

### Claim 130 (depends on 125)

The ionizable lipid of claim 125, wherein R1 and R10 are each independently unsubstituted linear C4-C8 alkyl.

### Claim 131 (depends on 125)

A pharmaceutical composition comprising the ionizable lipid of claim 125.

### Claim 132 (depends on 131)

The pharmaceutical composition of claim 131, wherein the pharmaceutical composition further comprises a RNA polynucleotide.

### Claim 133 (depends on 132)

The pharmaceutical composition of claim 132, wherein the RNA polynucleotide is a linear RNA polynucleotide.

### Claim 134 (depends on 132)

The pharmaceutical composition of claim 132, wherein the RNA polynucleotide is a circular RNA polynucleotide.

### Claim 135 (depends on 131)

The pharmaceutical composition of claim 131, wherein the pharmaceutical composition further comprises:
a helper lipid, wherein the helper lipid is DOPE or DSPC,
cholesterol, and
a PEG-lipid, wherein the PEG-lipid is DSPE-PEG(2000) or DMG-PEG(2000).

### Claim 136 (depends on 131)

A method of treating or preventing a disease, disorder, or condition, comprising administering an effective amount of a pharmaceutical composition of claim 131 further comprising a drug.

### Claim 137 (depends on 131)

A method of treating a subject in need thereof comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 131 further comprising a drug.