Carbonate containing lipid compounds and compositions for intracellular delivery of therapeutic agents
AssigneeModernaTX, Inc.
InventorsKerry E. BENENATO, Souvik BISWAS, Mark CORNEBISE, Edward HENNESSY, Ellalahewage S. KUMARASINGHE
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Abstract
The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.
Claims20
1-18. (canceled)
A nanoparticle composition comprising about 40 mol % to about 60 mol % ionizable lipid, about 0 mol % to about 20 mol % phospholipid, about 30 mol % to about 50 mol % structural lipid, and about 0 mol % to about 5 mol % PEG lipid
- wherein the ionizable lipid is a compound of Formula (A):
- or its N-oxide, or a salt thereof, wherein
- m is selected from 5, 6, 7, 8, and 9;
- R2 and R3 are each independently selected from the group consisting of H, C1-14 alkyl, and C2-14 alkenyl;
- R4 is selected from —(CH2)nOH, wherein n is selected from 1, 2, 3, 4, and 5, and
- wherein n2 is selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;
- and R10 is —N(R)2, wherein each R is independently selected from the group consisting of C1-6 alkyl, C2-3 alkenyl, and H;
- M and M′ are each independently selected from —OC(O)O— and —C(O)O—;
- wherein at least one of M and M′ is —OC(O)O—;
- R′a is C1-18 alkyl or C2-18 alkenyl;
- and
- R″ is a C3-C13 alkyl, optionally substituted with OH;
- or
- wherein the ionizable lipid is selected from the group consisting of compounds 1-67, and mixtures thereof;
- wherein the phospholipid is selected from the group consisting of:
- 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-diundecanoyl-sn-glycero-phosphocholine (DUPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine (18:0 Diether PC), 1-oleoyl-2-cholesterylhemisuccinoyl-sn-glycero-3-phosphocholine (OChemsPC), 1-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2-dilinolenoyl-sn-glycero-3-phosphocholine, 1,2-diarachidonoyl-sn-glycero-3-phosphocholine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinolenoyl-sn-glycero-3-phosphoethanolamine, 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine, 1,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG), sphingomyelin, and mixtures thereof;
- wherein the structural lipid is selected from the group consisting of cholesterol, fecosterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, and mixtures thereof;
- and
- wherein the PEG lipid is selected from PEG2k-DMG and PEG-1:
- and mixtures thereof.
20-23. (canceled)
Dependencies are inferred from the claim text.