Lipids for use in lipid nanoparticle formulations
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11524932-B2
Publication Date
2022-12-13
Expiration Date
Abstract
Compounds are provided having the following structure (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein X, Y, L1, L2, L3, G1, G2 and G3 are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.
Core Innovation
The invention provides a cationic lipid having structure (I) and corresponding pharmaceutically acceptable salt, prodrug, or stereoisomer forms. The disclosed lipids are intended as components of lipid nanoparticles and pharmaceutical compositions for nucleic-acid delivery, and representative pegylated lipid structures are described for use alongside the cationic lipid in lipid nanoparticle compositions.
The lipid nanoparticle compositions include neutral lipids, a steroid, and PEG-lipids together with the cationic lipid having structure (I). The neutral lipid set includes DSPC, DPPC, DMPC, DOPC, POPC, DOPE, and SM, and cholesterol is described as the steroid.
The document further links the disclosed lipid components to nucleic-acid delivery performance using in vivo luciferase mRNA evaluation and presents comparative tables relating compound pKa to in vivo luciferase expression. It also characterizes representative novel cationic lipids as formulations combined with DSPC, cholesterol, and PEG-DMA at fixed molar ratios, with luciferase expression reported in mouse liver after tail-vein injection.
Claims Coverage
The claims coverage centers on one independent compound feature set defined by structure (I) and one lipid nanoparticle feature set including the claimed compound. The claim set identifies three inventive features.
Compound having structure (I) with constrained X/y and substituent patterns
A compound having structure (I) wherein X is N and Y is absent, or X is CR and Y is NR; L1, L2 and L3 are selected from specified carbonyl/heteroatom-containing moiety forms, with G1, G2, G3 linkers defined as C2-C12 alkylene/C2-C12 alkenylene and C1-C8 or C2-C8 heteroalkylene/heteroalkenylene patterns depending on X and Y, R substituents constrained to H or specified alkyl/alkenyl ranges, and x being 0, 1 or 2.
Pharmaceutically acceptable forms and variants
The compound is provided as the compound having structure (I) or a pharmaceutically acceptable salt, prodrug or stereoisomer thereof.
Lipid nanoparticle containing the claimed compound
A lipid nanoparticle including the compound described by structure (I) and/or the compound of the defined structure scope.
The claims focus on the defined cationic lipid structure, its pharmaceutically acceptable forms, and a lipid nanoparticle containing the claimed compound.
Stated Advantages
Improved serum protection
Improved cellular delivery
Increased activity
Increased tolerability
Improved therapeutic index versus prior nucleic-acid LNP formulations
Documented Applications
Use of the defined lipids as components of lipid nanoparticles for delivering nucleic acids, including mRNA, antisense oligonucleotides, miRNA/antagomirs, siRNA, and plasmid DNA.
Use of the lipids in pharmaceutical compositions for therapeutic-agent delivery, including systemic delivery and local delivery.
In vivo luciferase expression in mouse liver measured after tail-vein injection using formulations that include the representative novel cationic lipids mixed with DSPC, cholesterol, and PEG-DMA at fixed molar ratios.
Nucleic-acid delivery.
Interested in licensing this patent?