Lipid nanoparticle compositions and uses thereof
Inventors
Hennig, Mirko • Alfaifi, Ali Ahmed • Mohapatra, Sakya Sing • Ishimaru, Daniella • Kharitonov, Vladimir Grigor'evich • Baek, Julia Jung-un • Li, Shuang • Lockhart, David J. • Wustman, Brandon A. • Wang, Yufeng • Cefalu, Joseph S.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12133923-B2
Publication Date
2024-11-05
Expiration Date
Abstract
Provided are methods for delivering lipid nanoparticles (LNPs) to a lung cell of a subject suffering from or at risk for primary ciliary dyskinesia (PCD), wherein the method comprises nebulizing a liquid pharmaceutical composition to generate an aerosolized pharmaceutical composition, and administering the aerosolized pharmaceutical composition to the subject.
Core Innovation
The disclosure provides lipid nanoparticle (LNP) formulations and a method for delivering LNPs to the lungs of a subject suffering from or at risk for primary ciliary dyskinesia (PCD) by nebulizing a liquid pharmaceutical composition to generate an aerosolized pharmaceutical composition and administering the aerosolized pharmaceutical composition to the subject. The aerosolized particles are selectively delivered to the tracheobronchial region of the lung of the subject.
The liquid pharmaceutical composition comprises LNPs having mRNA integrity between 75% and 99% and a diameter between 20 nm and 600 nm. The LNPs comprise an ionizable lipid, a phospholipid, a PEG-lipid, and a sterol, and comprise mRNA encoding a dynein axonemal intermediate chain 1 (DNAI1) protein.
The aerosolized pharmaceutical composition comprises aerosol particles having a mass median aerodynamic diameter (MMAD) between 1 μm and 10 μm, a geometric standard deviation (GSD) between 1 and 5, and a fine particle fraction (FPF) percent of at least 50%. The disclosure also includes ionizable cationic lipo-dendrimer structures, dendrimer variants, and pharmaceutically acceptable salts of selected dendrimers, with structural formulae and tabulated example dendrimer structures.
Claims Coverage
One independent claim is identified. The claim coverage centers on four inventive features: nebulized delivery to the tracheobronchial region, constrained LNP mRNA integrity and diameter, defined LNP lipid components with DNAI1-encoding mRNA, and aerosol particle performance constraints.
Nebulized delivery of LNPs to the tracheobronchial region for PCD
A method for delivering lipid nanoparticles (LNPs) to the lungs of a subject suffering from or at risk for primary ciliary dyskinesia (PCD) by nebulizing a liquid pharmaceutical composition to generate an aerosolized pharmaceutical composition and administering the aerosolized pharmaceutical composition so aerosol particles are selectively delivered to the tracheobronchial region of the lung.
LNP composition and mRNA payload constrained by integrity and diameter
The liquid pharmaceutical composition comprises LNPs having mRNA integrity between 75% and 99% and a diameter between 20 nm and 600 nm, and the LNPs comprise an ionizable lipid, a phospholipid, a PEG-lipid, and a sterol.
DNAI1 encoding mRNA in the LNPs
The LNPs comprise mRNA encoding a dynein axonemal intermediate chain 1 (DNAI1) protein.
Aerosol particle performance constraints for selective lung delivery
The aerosolized pharmaceutical composition comprises aerosol particles having a mass median aerodynamic diameter (MMAD) between 1 μm and 10 μm, a geometric standard deviation (GSD) between 1 and 5, and a fine particle fraction (FPF) percent of at least 50%.
The claim coverage is centered on nebulized aerosol delivery of DNAI1-encoding LNPs to the lungs of a PCD subject, with the LNP composition and aerosol particles defined by specific integrity, size, and performance constraints to achieve selective tracheobronchial region delivery.
Stated Advantages
Preferential/selective delivery of aerosolized particles to the tracheobronchial region of the lung.
Preferential delivery promoted by additional SORT lipids.
Documented Applications
Delivery of lipid nanoparticles (LNPs) to the lungs of a subject suffering from or at risk for primary ciliary dyskinesia (PCD) using nebulizing and administration of an aerosolized pharmaceutical composition.
Selective delivery of aerosolized pharmaceutical composition to the tracheobronchial region of the lung.
Preferential delivery (selective organ targeting) promoted by SORT additional lipids.
Interested in licensing this patent?