Granted Patent B2

US 12,740,943 · App. 17/761,863 · Granted Sep 22, 2026

Inventors: Kerry E. Benenato (Cambridge, MA); Mark Cornebise (Cambridge, MA); Edward Hennessy (Cambridge, MA); Andrew McKenzie (Cambridge, MA)

Assignee: ModernaTX, Inc.

A61K9/1272A61K31/7105C07C237/10C07C311/05C07D207/456C07D209/14C07D231/56C07D233/88C07D237/22C07D239/22C07D239/38C07D241/20C07D249/14C07D271/08C07D285/10C07D285/18C07D307/68C07D319/12C07F5/027C07F9/36

Abstract

Claims (42)

1 . A is a thiadiazole

to

A is a 1,2,5-thiadiazole.

2 . The compound of claim 1 , having one of the following structures:

3 . The compound of claim 1 , wherein R 4 is

4 . A compound selected from Compounds 1, 2, 82, 84, 85, and 92:

Cpd

Structure

1

2

82

84

85

92

and N-oxides and salts thereof.

5 . An empty lipid nanoparticle (empty LNP) comprising a compound of claim 1 , a phospholipid, a structural lipid, and a PEG lipid.

6 . The empty LNP of claim 5 , comprising about 40 mol % to about 60 mol % said compound, 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 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/or

wherein the PEG lipid is selected from the group consisting of a PEG-modified phosphatidylethanolamine, a PEG-modified phosphatidic acid, a PEG-modified ceramide, a PEG-modified dialkylamine, a PEG-modified diacylglycerol, a PEG-modified dialkylglycerol, and mixtures thereof.

7 . The empty LNP of claim 5 , wherein the PEG lipid is selected from PEG 2k -DMG and PEG-1:

and mixtures thereof.

8 . A loaded lipid nanoparticle (loaded LNP), which comprises the empty LNP of claim 5 and one or more therapeutic and/or prophylactic agents.

9 . The loaded LNP of claim 8 , wherein the one or more therapeutic and/or prophylactic agents is a nucleic acid, wherein the nucleic acid is an RNA, and wherein the RNA is selected from the group consisting of a short interfering RNA (siRNA), an asymmetrical interfering RNA (aiRNA), a RNA interference (RNAi) molecule, a microRNA (miRNA), an antagomir, an antisense RNA, a ribozyme, a Dicer-substrate RNA (dsRNA), a small hairpin RNA (shRNA), a messenger RNA (mRNA), and mixtures thereof.

10 . The loaded LNP of claim 9 , wherein the RNA is an mRNA.

11 . A pharmaceutical composition comprising the loaded LNP of claim 8 and a pharmaceutically acceptable carrier.

12 . A method of delivering a therapeutic and/or prophylactic agent to a cell within a subject, and/or to the organ of a subject, the method comprising administering to the subject the loaded LNP of claim 8 .

13 . A method of producing a polypeptide of interest in a cell within a subject, the method comprising administering to the subject the loaded LNP of claim 10 .

14 . A method of treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the loaded LNP of claim 8 .

Assignments (2)

Continuity (2)

References Cited (400)