US 2026/0183418 A1 · IONIZABLE CATIONIC LIPIDS AND LIPID NANOPARTICLES, AND METHODS OF SYNTHESIS AND USE THEREOF

Abstract

The invention provides ionizable cationic lipids and lipid nanoparticles for the delivery of nucleic acids to target cells, such as immune cells and hematopoietic stem cells, and methods of making and using, such lipids and targeted lipid nanoparticles.

Claims38

Dependent claims

A compound of Formula (I):
or a salt thereof, wherein:
Ra1 and Rb1 are each independently C1-12 alkylene;
Xa and Xb are each independently —C(O)O—* or —OC(O)—*, wherein * indicates the point of attachment to Ra1 or Rb1,
Ra2 and Rb2 are each independently a bond or C1-3 alkylene;
Ra3 is
and Rb3 is
wherein Ra3a, Ra3b, Rb3a, and Rb3b are each independently H, C1-12 alkyl optionally substituted with heterocylyl, or —(C1-10 alkylene)-Sn—(C1-10 alkyl), wherein n is each independently 1, 2, or 3;
Rc1 is C1-6 alkylene;
Rc2 is H or C1-6 alkyl;
and
Rc3 is C1-6 alkyl,
wherein:
Rf1 is H, C1-6 alkyl, or
Rf2 is H, C1-6 alkyl, or —C(O)O—C2-6 alkenyl;
Rf3, Rf4, and Rf5 are each independently C1-6 alkylene;
and
Rd1 and Re1 are each independently C1-12 alkylene;
Xd and Xe are each independently —C(O)O—* or —OC(O)—*, wherein * indicates the point of attachment to Rd1 or Rc1;
Rd2 and Re2 are each independently a bond or C1-3 alkylene;
and
Rd3 is
and Rc3 is
wherein Rd3a, Rd3b, Rc3a, and Rc3b are each independently H, C1-12 alkyl optionally substituted with heterocylyl, or —(C1-10 alkylene)-Sn—(C1-10 alkyl), wherein n is each independently 1, 2, or 3;
with the proviso that when Rc1 is —CH2— and Rc2 and Rc3 are each methyl, then none of Ra3a, Ra3b, Rb3a, and Rb3b is H;
when Rc1 is —(CH2)2— and Rc2 and Rc3 are each methyl, then Rb3a is not H and Rb3b is ethyl;
when Rc1 is —(CH2)2— and Rc2, Rc3, or both Rc2 and Rc3 are not methyl, then none of Ra3a, Ra3b, Rb3a, and Rb3b is H;
when Rc1 is —(CH2)3—, Rc2 and Rc3 are each methyl, and one of Ra3a Ra3b, Rb3a, and Rb3b is H, then at least one of Ra3a, Ra3b, Rb3a, and Rb3b that is not H is substituted with a heterocylyl;
and when Rc1 is —(CH2)4—, Rc2 and Rc3 are each methyl, then none of Ra3a, Ra3b, Rb3a, and Rb3b is H.

26 more elements

Facts

Application

19/337,179Filed 23 Sep 2025

Priority

24 Sep 2024

Published

2 Jul 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification17 codes

A61K 9/1272
Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers: comprising non-phosphatidyl surfactants as…
A61K 47/6913
The form being a liposome: the liposome being modified on its surface by an antibody
A61K 9/5123
Excipients; Inactive ingredients: organic compounds, e.g. fats, sugars
A61K 47/541
The modifying agent being an organic compound: organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent

Abstract

Claims38

Dependent claims

A compound of Formula (I):
or a salt thereof, wherein:
Ra1 and Rb1 are each independently C1-12 alkylene;
Xa and Xb are each independently —C(O)O—* or —OC(O)—*, wherein * indicates the point of attachment to Ra1 or Rb1,
Ra2 and Rb2 are each independently a bond or C1-3 alkylene;
Ra3 is
and Rb3 is
wherein Ra3a, Ra3b, Rb3a, and Rb3b are each independently H, C1-12 alkyl optionally substituted with heterocylyl, or —(C1-10 alkylene)-Sn—(C1-10 alkyl), wherein n is each independently 1, 2, or 3;
Rc1 is C1-6 alkylene;
Rc2 is H or C1-6 alkyl;
and
Rc3 is C1-6 alkyl,
wherein:
Rf1 is H, C1-6 alkyl, or
Rf2 is H, C1-6 alkyl, or —C(O)O—C2-6 alkenyl;
Rf3, Rf4, and Rf5 are each independently C1-6 alkylene;
and
Rd1 and Re1 are each independently C1-12 alkylene;
Xd and Xe are each independently —C(O)O—* or —OC(O)—*, wherein * indicates the point of attachment to Rd1 or Rc1;
Rd2 and Re2 are each independently a bond or C1-3 alkylene;
and
Rd3 is
and Rc3 is
wherein Rd3a, Rd3b, Rc3a, and Rc3b are each independently H, C1-12 alkyl optionally substituted with heterocylyl, or —(C1-10 alkylene)-Sn—(C1-10 alkyl), wherein n is each independently 1, 2, or 3;
with the proviso that when Rc1 is —CH2— and Rc2 and Rc3 are each methyl, then none of Ra3a, Ra3b, Rb3a, and Rb3b is H;
when Rc1 is —(CH2)2— and Rc2 and Rc3 are each methyl, then Rb3a is not H and Rb3b is ethyl;
when Rc1 is —(CH2)2— and Rc2, Rc3, or both Rc2 and Rc3 are not methyl, then none of Ra3a, Ra3b, Rb3a, and Rb3b is H;
when Rc1 is —(CH2)3—, Rc2 and Rc3 are each methyl, and one of Ra3a Ra3b, Rb3a, and Rb3b is H, then at least one of Ra3a, Ra3b, Rb3a, and Rb3b that is not H is substituted with a heterocylyl;
and when Rc1 is —(CH2)4—, Rc2 and Rc3 are each methyl, then none of Ra3a, Ra3b, Rb3a, and Rb3b is H.

26 more elements

Ionizable cationic lipids and lipid nanoparticles, and methods of synthesis and use thereof

Life of this patent

Abstract

Claims38

Ionizable cationic lipids and lipid nanoparticles, and methods of synthesis and use thereof

Life of this patent

Abstract

Claims38