Granted Patent B2

US 12,414,918 · App. 17/676,822 · Granted Sep 16, 2025

Inventors: Eun Kyoung Bang (Seoul, KR); Gyo Chang Keum (Seoul, KR); Taek Kang (Seoul, KR); Byung Sun Jeon (Seoul, KR); An Soo Lee (Seoul, KR); Jae Hwan Nam (Bucheon-si, KR); Seo Hyeon Bae (Gimhae-si, KR)

Assignee: SML BIOPHARM CO., LTD.

A61K9/1623B82Y5/00

Abstract

Claims (79)

1. A lipid nanoparticle composition comprising a lipid component,

wherein the lipid nanoparticle composition comprises:

a trehalose derivative compound represented by the following Formula 1; and

a lithocholic acid derivative compound represented by the following Formula 3 as a structural lipid:

wherein R 1 and R 2 are each independently an unsaturated hydrocarbon having 2 to 20 carbon atoms,

wherein at least one of R3 and R4 is a saturated or unsaturated hydrocarbon having 2 to 20 carbon atoms.

2. The lipid nanoparticle composition according to claim 1 , wherein R 1 and R 2 are each independently an alkenyl group having 6 to 20 carbon atoms and including 1 to 3 unsaturated bonds.

3. The lipid nanoparticle composition according to claim 1 , wherein the trehalose derivative compound is a compound represented by the following Formula 2:

4. The lipid nanoparticle composition according to claim 1 , wherein the lipid nanoparticle composition does not comprise a cholesterol lipid as a structural lipid.

5. The lipid nanoparticle composition according to claim 4 , wherein the lithocholic acid derivative compound comprises at least one of the following Formulas 4 to 6:

6. The lipid nanoparticle composition according to claim 4 , wherein the lipid nanoparticle composition further comprises a glycyrrhetinic acid derivative compound represented by the following Formula 7 as a structural lipid:

wherein R 5 and R 6 are each independently a saturated or unsaturated hydrocarbon having 2 to 20 carbon atoms.

7. The lipid nanoparticle composition according to claim 6 , wherein at least one of R 5 and R 6 is a saturated or unsaturated hydrocarbon having 2 to 20 carbon atoms.

8. The lipid nanoparticle composition according to claim 4 , wherein the lipid nanoparticle composition further comprises a diosgenin derivative compound represented by the following Formula 11 as a structural lipid:

wherein R 7 includes —OH, —OMe, —NH 2 , —NHMe, —NME2, —NME3, —SH, -glucose, methyl, or a saturated or unsaturated hydrocarbon having 2 to 20 carbon atoms.

9. The lipid nanoparticle composition according to claim 8 , wherein the diosgenin derivative compound comprises at least one of the following Formulas 12 to 14:

10. The lipid nanoparticle composition according to claim 1 , wherein the lipid nanoparticle composition further comprises an ionic lipid selected from the group consisting of the following compounds:

3-(didodecylamino)-N1,N1,4-tridodecyl-1-piperazineethanamine (KL10),

N1-[2-(didodecylamino)ethyl]-N1,N4,N4-tridodecyl-1,4-piperazinediethanamine (KL22),

14,25-ditridecyl-15,18,21,24-tetraaza-octatriacontane (KL25),

1,2-dilinoleyloxy-N,N-dimethylaminopropane (DLin-DMA),

2,2-dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-K-DMA),

heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate (DLin-MC3-DMA),

2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane (DLin-KC2-DMA),

1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA),

2-({8-[(3β)-cholest-5-en-3-yloxy]octyl}oxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-1-amine (octyl-CLinDMA),

(2R)-2-({8-[(3β)-cholest-5-en-3-yloxy]octyl}oxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-1-amine (octyl-CLinDMA (2R)), and

(2S)-2-({8-[(3β)-cholest-5-en-3-yloxy]octyl}oxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-1-amine (octyl-CLinDMA (2S)).

11. The lipid nanoparticle composition according to claim 1 , wherein the lipid nanoparticle composition further comprises a phospholipid selected from the group consisting of the following compounds:

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 (C 16 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-disthearoyl-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),

dipalmitoylphosphatidylglycerol (DPPG),

palmitoyloleoylphosphatidylethanolamine (POPE),

distearoyl-phosphatidyl-ethanolamine (DSPE),

dipalmitoyl phosphatidyl ethanolamine (DPPE),

dimyristoylphosphoethanolamine (DMPE),

1-stearoyl-2-oleoyl-phosphatidylethanol amine (SOPE),

1-stearoyl-2-oleoyl-phosphatidylcholine (SOPC),

sphingomyelin,

phosphatidylcholine,

phosphatidylethanolamine,

phosphatidylserine,

phosphatidylinositol,

phosphatidic acid,

palmitoyloleoyl phosphatidylcholine,

lysophosphatidylcholine, and

lysophosphatidylethanolamine (LPE).

12. The lipid nanoparticle composition according to claim 1 , further comprising a PEG lipid selected from the group consisting of PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol, PEG-modified dialkylglycerol, and mixtures thereof.

13. The lipid nanoparticle composition according to claim 1 , further comprising an ionic lipid,

wherein a molar ratio of the ionic lipid to the trehalose derivative compound is 1:0.7 to 1:1.3.

14. The lipid nanoparticle composition according to claim 13 , further comprising a lithocholic acid derivative compound of the following Formula 3, a glycyrrhetinic acid derivative compound of the following Formula 7, or a diosgenin derivative compound represented by the following Formula 11 as a structural lipid,

wherein a molar ratio of the ionic lipid to the trehalose derivative compound to the structural lipid is 1:0.70-1.30:1.30-1.8:

wherein R 3 and R 4 are each independently hydrogen or a saturated or unsaturated hydrocarbon having 2 to 20 carbon atoms,

wherein R 5 and R 6 are each independently hydrogen or a saturated or unsaturated hydrocarbon having 2 to 20 carbon atoms,

wherein R 7 includes —OH, —OMe, —NH 2 , —NHMe, —NME2, —NME3, —SH, -glucose, methyl, or a saturated or unsaturated hydrocarbon having 2 to 20 carbon atoms.

15. The lipid nanoparticle composition according to claim 14 , further comprising a phospholipid,

wherein a molar ratio of the ionic lipid to the trehalose derivative compound to the structural lipid to the phospholipid is 1:0.70-1.30:1.30-1.80:0.35-0.45.

16. The lipid nanoparticle composition according to claim 1 , further comprising a therapeutic and/or prophylactic agent.

17. The lipid nanoparticle composition according to claim 16 , wherein the therapeutic and/or prophylactic agent is a vaccine or compound capable of inducing an immune response.

18. The lipid nanoparticle composition according to claim 16 , wherein the therapeutic and/or prophylactic agent is nucleic acid selected from the group consisting of small interfering RNA (siRNA), asymmetric interfering RNA (aiRNA), microRNA (miRNA), dicer-substrate RNA (dsRNA), small hairpin RNA (shRNA), messenger RNA (mRNA), and mixtures thereof.

Assignments (3)

Priority Claims (1)

Continuity (1)

References Cited (21)