Lipids for use in lipid nanoparticle formulations
Inventors
Du, Xinyao • Ansell, Steven M. • Tan, Jason Samuel • Blagojevic, Polina • ARNS, Stephen Paul • Gatenyo, Julia
Assignees
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Publication Number
US-12129223-B2
Publication Date
2024-10-29
Expiration Date
Abstract
Compounds are provided having the following structure: or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R3, L1, L2, 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 relates to a compound having the structure (I), or a pharmaceutically acceptable salt or stereoisomer thereof. The structure includes defined linker motifs L1 and L2, with G1, G2, and G3 defined by alkylene or alkenylene patterns with specified carbon-count ranges.
The invention defines multiple variable substituent groups, including Ra, Rb, Rc, Rd, Re, and Rf, R1 and R2, and R3, R4, R5, R6, and R7. R3 is H, OH, CN, carbonyl-containing groups, heteroaryl, or aryl, and R4 and R5 together with the nitrogen or carbon atom to which they are bound form a 5 to 7-membered heterocyclic ring.
The patent presents compositions built around the claimed compound, including a lipid nanoparticle comprising the compound and a therapeutic agent. In further refinements, the therapeutic agent is a nucleic acid selected from antisense RNA and messenger RNA.
Claims Coverage
The claim coverage centers on one independent claim defining a compound of structure (I) with extensive structural constraints, plus lipid nanoparticle embodiments comprising the compound and a therapeutic agent, including nucleic acids. One independent compound feature and one independent lipid nanoparticle feature are present.
Compound defined by structure (I) with specified linker motifs
A compound having structure (I), or a pharmaceutically acceptable salt or stereoisomer thereof, wherein L1 and L2 are defined linker motifs and G1, G2, and G3 are alkylene or alkenylene groups within specified carbon-count ranges.
Substituent constraints for Ra through R7
Ra, Rb, Rc, Rd, Re, and Rf, R1 and R2, and R3, R4, R5, R6, and R7 are constrained to defined classes, including alkyl, alkenyl, hydroxyl, cyano, carbonyl-containing groups, heteroaryl, aryl, and optional heterocycle formation.
Lipid nanoparticles comprising the compound and a therapeutic agent
A lipid nanoparticle comprising the compound of structure (I) and a therapeutic agent, with the nucleic acid selected from antisense RNA and messenger RNA.
Coverage is anchored on the compound of structure (I) with defined linker motifs, chain-forming groups, and constrained substituent sets, and it extends to lipid nanoparticles with nucleic-acid therapeutic agents.
Stated Advantages
Improved serum protection
Improved cellular uptake
Improved in vivo tolerability
Improved therapeutic index
Documented Applications
Use of lipid nanoparticles for delivering therapeutic agents, especially nucleic acids including antisense RNA and messenger RNA.
Compositions and drug administration contexts involving lipid nanoparticles formulated with the compound of structure (I) and therapeutic agents including nucleic acids.
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