Lipids for use in lipid nanoparticle formulations
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11639329-B2
Publication Date
2023-05-02
Expiration Date
Abstract
Compounds are provided having the following structure: [Formula should be inserted here] 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 structure (I), or a pharmaceutically acceptable salt or stereoisomer thereof, with defined substituent elements L1 and L2, linker groups G1, G2 and G3, and variable substituents including R a, R b, R d, R e, R c, R f, R1 and R2, and an N(R4)R5 motif for R3. The substituent definitions specify allowable classes of alkylene, alkenylene, cycloalkylene, and cycloalkenylene groups, and substituted or unsubstituted alkyl and alkenyl groups for each variable position.
The structure (I) further includes R5 as a substituted C1-C12 alkyl in which the substitution uses one or more substituents selected from ORg, NRgC(O)Rh, C(O)Rh, C(O)ORh, OC(O)Rh, and related O- and carbonyl-containing groups, with Rg, Rh and Ri each defined as independent sets of carbon-count-limited alkyl or alkylene options. The integer x is limited to 0, 1 or 2, and the defined substituent choices apply unless otherwise specified.
The described embodiments include lipid nanoparticles formulated with the claimed cationic lipids and compositions including the compound and a nucleic acid. The disclosed context is directed to therapeutic delivery of nucleic acids such as mRNA, siRNA, antisense oligonucleotides, miRNA and miRNA inhibitors, and plasmid DNA, with systemic or local delivery.
Claims Coverage
The provided material includes one independent claim directed to structure (I) with extensive substituent definitions, and additional content that refines the same chemical scaffold and adds composition and formulation embodiments. The inventive features center on defined L1 and L2 linkage forms, G1, G2 and G3 spacer moieties, and the N(R4)R5 architecture with a substituted C1-C12 alkyl R5 and x constrained to 0-2.
Structure (I) compound with defined substituent architecture
A compound having structure (I), or a pharmaceutically acceptable salt or stereoisomer thereof, wherein L1 and L2 are each selected from the enumerated linkage types including O(C(O)R1) and related carbonyl- and heteroatom-containing options; G1, G2 and G3 are each independently selected from the specified alkylene, alkenylene, cycloalkylene, or cycloalkenylene sets; and R a, R b, R d and R e are each independently H, C1-C12 alkyl, or C1-C12 alkenyl, with other variables constrained as defined.
N(R4)R5 motif and substituted C1-C12 alkyl R5 with selected substituents
R3 is N(R4)R5 where R4 is C1-C12 alkyl and R5 is substituted C1-C12 alkyl wherein the substitution is selected from ORg, NRgC(O)Rh, C(O)Rh, C(O)ORh, OC(O)Rh, and ORiOH, with each Rg, Rh and Ri defined as carbon-count-limited alkyl or alkylene options, and with x limited to 0, 1 or 2.
The independent claim scope is centered on compounds defined by structure (I), with strict enumerated and range-constrained substituent definitions for L1 and L2, G1, G2 and G3, R-group classes, and the N(R4)R5 substituent system including a substituted C1-C12 alkyl R5 and x constrained to 0-2.
Stated Advantages
Improved in vivo activity.
Improved tolerability.
Increased therapeutic index.
Protection from serum nuclease degradation and clearance.
Intracellular delivery potential.
Documented Applications
Therapeutic delivery use cases for nucleic acids including mRNA, siRNA, antisense oligonucleotides, miRNA and miRNA inhibitors, and plasmid DNA, using the compound in lipid nanoparticle formulations for systemic or local delivery.
Interested in licensing this patent?