Lipid nanoparticle formulations
Inventors
Hope, Michael J. • Mui, Barbara • Lin, Paulo Jia Ching • Barbosa, Christopher J. • Madden, Thomas D. • Ansell, Steven M. • Du, Xinyao
Assignees
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Publication Number
US-12491261-B2
Publication Date
2025-12-09
Expiration Date
Abstract
Improved formulations of lipid nanoparticles are provided. Use of the lipid nanoparticles for delivery of a therapeutic agent and methods for their preparation are also provided.
Core Innovation
The disclosed subject matter provides lipid nanoparticles that include a cationic lipid, a neutral lipid, a steroid, a polymer-conjugated lipid, and a therapeutic agent encapsulated within or associated with the lipid nanoparticle. The cationic lipid is defined by Formula III, Formula IV, Formula V, or related sub-formulas, with representative structures and compounds provided, including variable group classes, linkage options, and substituent definitions.
The structural definitions include L1 and L2 linkage options, G1, G2, and G3 substituent classes, and additional parameters and indices such as x, y, z, n, w, and repeating-unit variables. The polymer-conjugated lipid is defined by Formula VI or Formula VIa in some embodiments, with R12 and R13 as straight or branched saturated or unsaturated alkyl chains containing from 10 to 30 carbon atoms, optionally interrupted by one or more ester bonds, and with w having a mean value ranging from 30 to 60.
The disclosure further characterizes representative lipid nanoparticle formulations by quantitative molar composition ranges and molar ratios, including cationic lipid, neutral lipid, steroid, and polymer-conjugated lipid contents. The therapeutic agent is described as being encapsulated within or associated with the lipid nanoparticle, and in some embodiments is identified as nucleic acid, including antisense and messenger RNA (mRNA).
Claims Coverage
The consolidated claim coverage identifies two independent claim themes: lipid nanoparticle compositions with a defined cationic lipid Formula III motif, and lipid nanoparticle compositions with a defined polymer-conjugated lipid Formula VI motif. Across the provided items, the independent claims center on a lipid nanoparticle comprising a cationic lipid, a neutral lipid, a steroid, a polymer conjugated lipid, and a therapeutic agent encapsulated within or associated with the nanoparticle.
Lipid nanoparticle with Formula III cationic lipid composition
A lipid nanoparticle comprising from 47 to 48 mol percent of a cationic lipid, a neutral lipid, a steroid, a polymer conjugated lipid, and a therapeutic agent, or a pharmaceutically acceptable salt thereof, encapsulated within or associated with the lipid nanoparticle, wherein the cationic lipid has a structure of Formula III or a pharmaceutically acceptable salt or stereoisomer thereof, with defined L1/L2 linkage options and substituent groups including G1, G2, G3, Ra, R1, R2, R3, R4, R5, x, y, z, and n.
Lipid nanoparticle with Formula VI polymer-conjugated lipid
A lipid nanoparticle comprising from 47 to 48 mol percent of a cationic lipid, a neutral lipid, a steroid, a polymer conjugated lipid, and a therapeutic agent, or a pharmaceutically acceptable salt thereof, encapsulated within or associated with the lipid nanoparticle, wherein the polymer-conjugated lipid has Formula VI or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, with R12 and R13 as straight or branched, saturated or unsaturated alkyl chains containing from 10 to 30 carbon atoms, optionally interrupted by one or more ester bonds, and w having a mean value ranging from 30 to 60.
The independent claim scope is unified by the same lipid nanoparticle component set and encapsulated or associated therapeutic agent, while distinguishing the key inventive features by either Formula III cationic lipid structural constraints or Formula VI polymer-conjugated lipid constraints.
Stated Advantages
Improved lipid nanoparticle formulations for intracellular delivery of therapeutic agents.
Combining two cationic lipids increases LNP activity compared with LNPs containing a single cationic lipid with a pKa outside an expected range.
Documented Applications
Intracellular delivery of therapeutic agents, including nucleic acids such as mRNA, antisense, miRNA inhibitors, antagomirs, and siRNA/RNAi.
Luciferase activity in liver and spleen.
Lipid nanoparticle formulations for a therapeutic agent, including nucleic acid, antisense, and messenger RNA (mRNA).
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