US20260166071
2026-06-18
Human necessities
A61K31/7105
The patent application focuses on lipid nanoparticle (LNP) compositions encapsulating polynucleotides, such as mRNA, to enhance stability and reduce unwanted reactions. The instability of mRNA poses challenges in maintaining potency during storage and delivery. The application addresses the formation of lipid-mRNA adducts which can diminish the effectiveness of the delivered mRNA. The disclosed methods aim to control these reactions at various stages, including raw materials, formulation processes, and final product management.
A key feature of the composition is its ability to maintain less than 10% of ionizable lipid-polynucleotide adduct impurities relative to the polynucleotide amount, as measured by high-performance liquid chromatography (HPLC). The process involves combining ionizable lipids with polynucleotides and treating them to minimize adduct formation. This treatment can include using reductive treatment agents, reducing agents, chelating agents, or a combination thereof, to prepare the lipid nanoparticle composition.
Adduct impurities refer to covalent modifications of polynucleotides by ionizable lipids, leading to low translation competency. These impurities often result from reactions with secondary amines and reactive aldehyde species derived from decomposed ionizable lipids. The presence of such impurities can hinder mRNA translation, affecting the therapeutic potential of the LNPs. Techniques like HPLC and mass spectrometry are used to detect and quantify these impurities.
The integrity and purity of polynucleotides within the LNPs are assessed through extraction methods followed by HPLC analysis. This involves extracting polynucleotides from the LNPs, evaluating their integrity, and performing HPLC to identify adduct impurities. The HPLC method helps in distinguishing between non-adduct and adduct mRNA, allowing for precise measurement of impurity levels.
The disclosed LNP compositions offer enhanced therapeutic potential by delivering stable, biologically active polynucleotides to target cells. By minimizing adduct formation and maintaining high translation competency, these compositions could significantly improve the efficacy of mRNA-based therapies. The application outlines various strategies to reduce impurities, including pre-treatment with reducing agents and optimizing storage conditions.