Stereochemically enriched compositions for delivery of nucleic acids
View Patent ↗Provided, in part, is a composition comprising one or more chemical entities of formula I, each of which is a compound of formula I: a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, the composition characterized in that greater than a first threshold amount of the total amount of chemical entities of formula I in the composition: are chemical entities of formula I.a, wherein the first threshold amount is 50%; or are chemical entities of formula I.b.1, wherein the first threshold amount is 25%; or are chemical entities of formula I.b.2, wherein the first threshold amount is 25%, wherein the chemical entities of formula I.a, I.b.1, and I.b.2, are described herein, and methods of using such compositions, for example, for the delivery of a polynucleotide in vivo.
1. A composition comprising one or more chemical entities of formula I, each of which is a compound of formula I:
a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, wherein
70% or more of the chemical entities of formula I have the structure set forth by formula I.a.i:
2. The composition of claim 1 , wherein 80% or more of the chemical entities of formula I have the structure set forth by formula I.a.i.
3. The composition of claim 2 , wherein 90% or more of the chemical entities of formula I have the structure set forth by formula I.a.i.
4. A lipid nanoparticle comprising the composition of claim 1 and a polynucleotide.
5. The lipid nanoparticle of claim 4 , wherein 80% or more of the chemical entities of formula I have the structure set forth by formula I.a.i.
6. The lipid nanoparticle of claim 4 , wherein said polynucleotide is mRNA.
7. The lipid nanoparticle of claim 4 , further comprising one or more cationic lipids, non-cationic lipids, cholesterol-based lipids, PEG-modified lipids, and/or polymers.
8. The lipid nanoparticle of claim 4 , wherein 90% or more of the chemical entities of formula I have the structure set forth by formula I.a.i.