Granted Patent B2

US 12,233,160 · App. 18/609,128 · Granted Feb 25, 2025

Inventors: Steven Gregory Reed (Bellevue, WA); Amit Praful Khandhar (Issaquah, WA); Darrick Albert Carter (Seattle, WA)

Assignee: HDT Bio Corp.

A61K9/1075A61K9/19A61K9/5115A61K31/7105A61K31/711A61K47/06A61K47/12A61K47/26B82Y5/00

Abstract

Claims (61)

1. A dried composition of comprising:

a) a lipid carrier, wherein the lipid carrier is a nanoemulsion comprising a hydrophobic core, and one or more lipids, wherein the hydrophobic core comprises one or more inorganic nanoparticles, and wherein the one or more inorganic nanoparticles comprise magnetite (Fe 3 O 4 ), maghemite (y-Fe 2 O 3 ), wüstite (FeO), hematite (alpha (α)-Fe 2 O 3 ), or combinations thereof;

b) optionally one or more nucleic acids; and

c) at least one sugar present in an amount of the composition by weight of 80% to 98%.

2. A dried composition comprising:

a) a lipid carrier, wherein the lipid carrier is a nanoemulsion comprising a hydrophobic core, and one or more lipids;

b) optionally one or more nucleic acids; and

c) at least one sugar present in an amount of the composition by weight of 80% to 98%, wherein the at least one sugar is present in an amount of at least about 50 mg.

3. A dried composition comprising:

a) a lipid carrier, wherein the lipid carrier is a nanoemulsion comprising a hydrophobic core, and one or more lipids, wherein the hydrophobic core further comprises:

squalene at a concentration of up to about 1.88 mg/ml;

sorbitan monostearate at a concentration of up to about 1.86 mg/ml;

polysorbate 80 at a concentration of up to about 1.86 mg/ml; and

optionally, iron oxide at a concentration of up to about 0.01 mg/ml,

b) one or more nucleic acids; and

c) at least one sugar present in an amount of the composition by weight of 80% to 98%, wherein:

the one or more nucleic acids is present in an amount of up to about 200 micrograms (μg), the lipid is a cationic lipid that is present in a concentration of up to about 1.5 mg/ml, and the sugar is sucrose that is present in a concentration of up to about 50 mg/ml.

4. The composition of claim 2 , further comprising citric acid monohydrate present in a concentration of up to about 2.1 mg/ml.

5. The composition of claim 1 , wherein the sugar is present in an amount of the composition by weight of 94% to 96%.

6. The composition of claim 1 , wherein the composition is lyophilized.

7. The composition of claim 1 , wherein the hydrophobic core comprises an oil.

8. The composition of claim 7 , wherein the oil comprises at least one of a-tocopherol, lauroyl polyoxylglyceride, monoacylglycerol, propolis, squalene, mineral oil, grapeseed oil, olive oil, paraffin oil, peanut oil, soybean oil, sunflower oil, soy lecithin, triglyceride, vitamin E, a caprylic/capric triglyceride, a triglyceride ester of saturated coconut/palmkernel oil derived caprylic and capric fatty acids and plant derived glycerol, dihydroisosqualene (DHIS), farnesene and squalane.

9. The composition of claim 1 , wherein the one or more lipids is selected from the group consisting of cationic lipids, anionic lipids, neutral lipids, and any combinations thereof.

10. The composition of claim 1 , wherein the one or more lipids comprises a cationic lipid.

11. The composition of claim 10 , wherein the cationic lipid is selected from the group consisting of 1,2-dioleoyloxy-3-(trimethylammonium)propane (DOTAP); 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC Cholesterol); dimethyldioctadecylammonium (DDA); 1,2-dimyristoyl-3-trimethylammoniumpropane (DMTAP), dipalmitoyl(C16:0)trimethyl ammonium propane (DPTAP); distearoyltrimethylammonium propane (DSTAP); N-[1-(2,3-dioleyloxy)propyl]-N,N,Ntrimethylammonium chloride (DOTMA); N,N-dioleoyl-N,N-dimethylammonium chloride (DODAC); 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC); 1,2-dioleoyl-3-dimethylammonium-propane (DODAP); and 1,2-dilinoleyloxy-3-dimethylaminopropane (DLin-DMA); 1,1′-((2-(4-(2-((2-(bis(2-hydroxydodecyl) amino)ethyl) (2-hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethyl)azanediyl)bis(dodecan-2-ol) (C12-200), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE); N-decyl-N,N-dimethyldecan-1-aminium bromide (DDAB); 2,3-dioleyloxy-N-[2-(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA); ethylphosphatidylcholine (ePC); and any combinations thereof.

12. The composition of claim 1 , wherein the lipid carrier comprises at least one surfactant.

13. The composition of claim 12 , wherein the at least one surfactant is selected from the group consisting of a hydrophobic surfactant, a hydrophilic surfactant, and any combinations thereof.

14. The composition of claim 13 , wherein the hydrophobic surfactant comprises a sorbitan ester selected from the group consisting of sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate, sorbitan monooleate, and sorbitan trioleate; and the hydrophilic surfactant comprises a polysorbate.

15. The composition of claim 1 , wherein the lipid carrier has a z-average hydrodynamic diameter ranging from about 40 nm to about 150 nm, with an average polydispersity index ranging from about 0.1 to about 0.4.

16. The composition of claim 1 , wherein the one or more nucleic acids comprise DNA or RNA.

17. The composition of claim 1 , wherein the one or more nucleic acids are incorporated or complexed with the lipid carrier to form a lipid carrier-nucleic acid complex.

18. The composition of claim 1 , wherein the at least one sugar is selected from the group consisting of sucrose, maltose, trehalose, mannitol, glucose, and any combinations thereof.

19. The composition of claim 3 , further comprising citric acid monohydrate present in a concentration of up to about 2.1 mg/ml.

20. The composition of claim 3 , wherein the sugar is present in an amount of the composition by weight of 94% to 96%.

21. The composition of claim 3 , wherein the composition is lyophilized.

22. The composition of claim 3 , wherein the one or more nucleic acids comprise DNA or RNA.

23. The composition of claim 3 , wherein the one or more nucleic acids are incorporated or complexed with the lipid carrier to form a lipid carrier-nucleic acid complex.

24. The composition of claim 3 , wherein the at least one sugar is selected from the group consisting of sucrose, maltose, trehalose, mannitol, glucose, and any combinations thereof.

25. The composition of claim 2 , wherein the sugar is present in amount of the composition by weight of 94% to 96%.

26. The composition of claim 2 , wherein the composition is lyophilized.

27. The composition of claim 2 , wherein the composition is thermally stable at about-20 degrees Celsius.

28. The composition of claim 2 , wherein the composition is thermally stable at about 2 degrees Celsius to about 8 degrees Celsius.

29. The composition of claim 2 , wherein the composition is thermally stable at about 25 degrees Celsius.

30. The composition of claim 2 , wherein the composition is thermally stable at about 45 degrees Celsius.

31. The composition of claim 2 , wherein the composition is thermally stable for at least 1 week.

32. The composition of claim 2 , wherein the hydrophobic core comprises an oil.

33. The composition of claim 32 , wherein the oil comprises at least one of a-tocopherol, lauroyl polyoxylglyceride, monoacylglycerol, propolis, squalene, mineral oil, grapeseed oil, olive oil, paraffin oil, peanut oil, soybean oil, sunflower oil, soy lecithin, triglyceride, vitamin E, a caprylic/capric triglyceride, a triglyceride ester of saturated coconut/palmkernel oil derived caprylic and capric fatty acids and plant derived glycerol, dihydroisosqualene (DHIS), farnesene and squalane.

34. The composition of claim 2 , wherein the one or more lipids is selected from the group consisting of cationic lipids, anionic lipids, neutral lipids, and any combinations thereof.

35. The composition of claim 34 , wherein the one or more lipids comprises a cationic lipid.

36. The composition of claim 34 , wherein the cationic lipid is selected from the group consisting of 1,2-dioleoyloxy-3-(trimethylammonium) propane (DOTAP); 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC Cholesterol); dimethyldioctadecylammonium (DDA); 1,2-dimyristoyl-3-trimethylammoniumpropane (DMTAP), dipalmitoyl(C16:0)trimethyl ammonium propane (DPTAP); distearoyltrimethylammonium propane (DSTAP); N-[1-(2,3-dioleyloxy)propyl]-N,N,Ntrimethylammonium chloride (DOTMA); N,N-dioleoyl-N,N-dimethylammonium chloride (DODAC); 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC); 1,2-dioleoyl-3-dimethylammonium-propane (DODAP); and 1,2-dilinoleyloxy-3-dimethylaminopropane (DLin-DMA); 1,1′-((2-(4-(2-((2-(bis(2-hydroxydodecyl) amino)ethyl) (2-hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethyl)azanediyl)bis (dodecan-2-ol) (C12-200), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE); N-decyl-N,N-dimethyldecan-1-aminium bromide (DDAB); 2,3-dioleyloxy-N-[2-(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA); ethylphosphatidylcholine (ePC); and any combinations thereof.

37. The composition of claim 2 , wherein the lipid carrier comprises at least one surfactant.

38. The composition of claim 37 , wherein the at least one surfactant is selected from the group consisting of a hydrophobic surfactant, a hydrophilic surfactant, and any combinations thereof.

39. The composition of claim 38 , wherein the hydrophobic surfactant comprises a sorbitan ester selected from the group consisting of sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan tristearate, sorbitan monooleate, and sorbitan trioleate; and the hydrophilic surfactant comprises a polysorbate.

40. The composition of claim 2 , wherein the lipid carrier has a z-average hydrodynamic diameter ranging from about 40 nm to about 150 nm, with an average polydispersity index ranging from about 0.1 to about 0.4.

41. The composition of claim 2 , wherein the one or more nucleic acids comprise DNA or RNA.

42. The composition of claim 41 , wherein the RNA is a self-replicating RNA.

43. The composition of claim 2 , wherein the one or more nucleic acids are incorporated or complexed with the lipid carrier to form a lipid carrier-nucleic acid complex.

44. The composition of claim 43 , wherein the lipid carrier-nucleic acid complex is formed via non-covalent interactions or via reversible covalent interactions.

45. The composition of claim 2 , wherein a molar ratio of the lipid carrier to the one or more nucleic acids, characterized by a nitrogen-to-phosphate (N:P) molar ratio, ranges from about 1:1 to about 150:1.

46. The composition of claim 2 , wherein the at least one sugar is selected from the group consisting of sucrose, maltose, trehalose, mannitol, glucose, and any combinations thereof.

47. The composition of claim 2 , wherein the at least one sugar comprises sucrose.

Assignments (1)

Continuity (4)

References Cited (196)