Lipid nanoparticle compositions and uses thereof
Inventors
Katikaneni, Sahitya • Mahmoudi, Neda • Wang, Peng • Mohapatra, Sakya Sing • Kharitonov, Vladimir Grigor'evich
Assignees
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Publication Number
US-12364773-B2
Publication Date
2025-07-22
Expiration Date
Abstract
Provided are aerosolized pharmaceutical compositions including comprising aerosol particles, the aerosol particles comprising lipid nanoparticles (LNPs). Also provided herein are methods of administering the aerosolized pharmaceutical compositions described herein.
Core Innovation
The invention relates to lipid nanoparticle (LNP) compositions for lung delivery and aerosolization. The LNP composition comprises DODAP, 1,2-dimyristoyl-3-trimethylammonium-propane (14:0 TAP) or 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (14:0 EPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol or sitosterol, and DMG-PEG, and the disclosed formulations include mRNA payloads.
The disclosure also relates to lipid nanoparticle compositions and chemical structures for a PEG-lipid linker/branch terminating group system. It includes structural depictions for multiple SC variants, with labeled arm counts and backbone branching, and describes lipid-forming components with defined alkyl chain lengths and sulfur linkage features.
The document further addresses LNP degradation and de-encapsulation during nebulization and evaluates nebulization impact on mRNA integrity and encapsulation. It also describes aerosol and deposition characterization, and reports claimed cell-targeting preferences in the lung, emphasizing lung cells including secretory/ionocytes and ciliated cells.
Claims Coverage
The independent claims cover one LNP composition defined by a specific set of lipid components and DMG-PEG. Across the provided claim coverage, there are 7 inventive features, with dependent refinements that specify component molar-percentage ranges, mRNA inclusion and lipid:mRNA ratio constraints, specific mRNA payload targets, and DMG-PEG2000.
Specific LNP component combination with DMG-PEG
A lipid nanoparticle (LNP) composition comprising DODAP, 1,2-dimyristoyl-3-trimethylammonium-propane (14:0 TAP) or 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (14:0 EPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol or sitosterol, and a DMG-PEG.
Component-specific molar percentage ranges for full lipid blend
An LNP composition including specified molar-percentage ranges for 4A3-SC7, DODAP, 14:0 TAP, DOPE, cholesterol, and DMG-PEG.
LNP composition including an mRNA component with a lipid:mRNA ratio constraint
An LNP composition including an mRNA component, wherein the lipid:mRNA ratio is less than 40:1.
LNP composition with mRNA at a defined lipid:mRNA ratio
A lipid nanoparticle (LNP) composition that includes mRNA formulated at a lipid:mRNA ratio of 33:1.
mRNA encoding a cystic fibrosis transmembrane conductance regulator (CFTR) protein
A lipid nanoparticle (LNP) composition wherein the contained mRNA encodes a cystic fibrosis transmembrane conductance regulator (CFTR) protein.
mRNA encoding DNAI1
A lipid nanoparticle (LNP) composition wherein the contained mRNA encodes DNAI1.
DMG-PEG2000 in the LNP composition
A lipid nanoparticle (LNP) composition where the DMG-PEG component is DMG-PEG2000.
The claim coverage centers on an LNP formulation defined by DODAP, one of 14:0 TAP or 14:0 EPC, one of DOPE or DSPC, cholesterol or sitosterol, and DMG-PEG, with dependent features further defining molar-percentage ranges, mRNA payload inclusion, lipid:mRNA ratios, encoded protein targets, and the PEG variant DMG-PEG2000.
Stated Advantages
The compositions address LNP degradation and de-encapsulation during nebulization.
Protein expression is assessed after delivery.
Functional readouts include chloride flux and TEER.
Aerosol and deposition characterization is included.
Nebulization impact on mRNA integrity/encapsulation is evaluated.
Documented Applications
Lung delivery.
Aerosolized pharmaceutical compositions.
mRNA payload delivery, including CFTR and DNAI1.
Pulmonary delivery.
Aerosolization and pulmonary administration using a nebulizer.
Delivery of mRNA encoding CFTR.
Delivery of mRNA encoding DNAI1.
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