Targeting of antigen-presenting cells by nanoparticles containing polyoxazoline-lipid conjugates

HK40135106APending Publication Date: 2026-07-17SERINA THERAPEUTICS (AL) INC
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Patent Information

Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
SERINA THERAPEUTICS (AL) INC
Filing Date
2026-05-06
Publication Date
2026-07-17

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Abstract

A method of targeting antigen-presenting cells and delivering an encapsulated payload with lipid nanoparticles including a POZ-lipid conjugate. The encapsulated payload may include, but is not limited to, a nucleic acid payload such as mRNA or modified mRNA. These LNPs are not subject to accelerated blood clearance and they have a low or reduced immunogenicity profile in vivo.
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Description

Abstract: A method for targeting antigen-presenting cells and delivering encapsulated payloads using lipid nanoparticles containing POZ-lipid conjugates. The encapsulated payloads may include, but are not limited to, nucleic acid payloads such as mRNA or modified mRNA. These LNPs do not suffer accelerated blood clearance and have a low or reduced immunogenicity profile in vivo.

Claims

THE CLAIMSWhat is claimed is:

1. A method for preferentially delivering a payload to antigen-presenting cells in a subject comprising: providing a lipid nanoparticle encapsulating the payload, wherein the lipid nanoparticle comprises: a POZ-lipid of Formula I:R-POZ-L-Lipid (I) wherein R comprises an initiating group, POZ comprises poly(ethyloxazoline),L comprises a physiologically degradable linking group, andLipid comprises a non-charged lipid comprising at least one hydrophobic moiety; an ionizable or cationic lipid; a helper lipid; a sterol lipid; and administering an effective amount of the lipid nanoparticle to the subject.

2. The method of claim 1, wherein the antigen-presenting cells comprise splenic macrophage cells, dendritic cells, or combinations thereof.

3. The method of claim 1, wherein POZ comprises [N(COR2)CH2CH2]n, where R2 is ethyl.

4. The method of claim 1, wherein R comprises a hydrogen, a substituted or unsubstituted alkyl, an alkyne-substituted alkyl, a triazole with attached carboxylic acid, or a substituted or unsubstituted aralkyl group.

5. The method of claim 1, wherein L comprises ethers, esters, carboxylate esters, carbonate esters, carbamates, amines, amides, urethanes, disulfides, and combinations thereof.

6. The method of claim 1, wherein Lipid comprises two hydrophobic moi eties.

7. The method of claim 1, wherein Lipid comprises phospholipid, a glycerolipid, a di -alkyl acetamide, or a combination thereof.

8. The method of claim 1, wherein Lipid comprises 1,2-dimyristoyl-sn-glycerol, 1,2- dilauroyl-sn-glycerol, or a combination thereof.

9. The method of claim 1, wherein the payload comprises an oligonucleotide.

10. A method for preferentially delivering a payload to antigen-presenting cells in a subject comprising: providing a lipid nanoparticle encapsulating the payload, wherein the lipid nanoparticle comprises: a POZ-lipid of Formula II:Lipid-Li-(POZ)„a-T (II) whereinLipid comprises a non-charged lipid comprising at least one hydrophobic moiety,Li comprises a physiologically degradable linking group,POZ comprises a polyoxazoline polymer of the structure[N(COR2)CH2CH2], wherein R2is ethyl, n ranges from 1 to 1,000, a is ran, which indicates a random copolymer, or block, which indicates a block copolymer, andT comprises a terminating group;an ionizable or cationic lipid; a helper lipid; a sterol lipid, wherein the payload comprises an oligonucleotide; and administering an effective amount of the lipid nanoparticle to the subject.

11. The method of claim 10, wherein Li comprises ethers, esters, carboxylate esters, carbonate esters, carbamates, amines, amides, urethanes, disulfides, and combinations thereof.

12. The method of claim 10, wherein Li comprises a triazole.

13. The method of claim 10, wherein T comprises Z-B-Q, and wherein Z comprises S, O, or N, B is an optional linking group, and Q is a terminating nucleophile or portion thereof.

14. The method of claim 10, wherein Lipid comprises two hydrophobic moieties.

15. The method of claim 10, wherein Lipid comprises a phospholipid, a glycerolipid, a di-alkyl acetamide, or a combination thereof.

16. The method of claim 10, wherein Lipid comprises 1,2-dimyristoyl-sn-glycerol, 1,2- dilauroyl-sn -glycerol, or a combination thereof.

17. The method of claim 10, wherein the oligonucleotide comprises mRNA, and wherein the antigen-presenting cells comprise splenic macrophage cells, dendritic cells, or combinations thereof.

18. A method for preferentially delivering a payload to antigen-presenting cells in a subject comprising: providing a lipid nanoparticle encapsulating the payload, wherein the lipid nanoparticle comprises: a POZ-lipid of Formula III:R-(POZ)na-Z-L2-Lipid(III) wherein R comprises an initiating group;POZ comprises a polyoxazoline polymer of the structure [N(COR2)CH2CH2], wherein R2 is ethyl; n ranges from 1 to 1,000, a is ran, which indicates a random copolymer, or block, which indicates a block copolymer,Z comprises S, O, or N,L2 comprises a physiologically degradable linking group, andLipid comprises a non-charged lipid comprising at least one hydrophobic group. an ionizable or cationic lipid; a helper lipid; a sterol lipid; and administering an effective amount of the lipid nanoparticle to the subject.

19. The method of claim 18, wherein the payload comprises mRNA.

20. The method of claim 18, wherein the antigen-presenting cells comprise splenic macrophage cells, dendritic cells, or combinations thereof.

21. The method of claim 18, wherein L2 comprises ethers, esters, carboxylate esters, carbonate esters, carbamates, amines, amides, urethanes, disulfides, and combinations thereof.

22. The method of claim 18, wherein Lipid comprises two hydrophobic moieties.

23. The method of claim 18, wherein Lipid comprises a phospholipid, a glycerolipid, a di-alkyl acetamide, or a combination thereof.

24. The method of claim 18, wherein Lipid comprises 1,2-dimyristoyl-sn-glycerol, 1 ,2- dilauroyl-sn-glycerol, or a combination thereof.

25. The method of claim 18, wherein R comprises a hydrogen, or a substituted or unsubstituted alkyl, and wherein n ranges from 15 to 35.

26. A method for preferentially delivering a payload to antigen-presenting cells comprising: providing a lipid nanoparticle encapsulating the payload, wherein the lipid nanoparticle comprises: a POZ-lipid of Formula IV:Lipid(IV) whereinR comprises an initiating group,L3 comprises a physiologically degradable linking group, Lipid comprises a non-charged lipid comprising at least one hydrophobic moiety, n ranges from 1 to 5,R2 is independently selected for each repeating unit from an unsubstituted or substituted alkyl, alkenyl, aralkyl, heterocyclylalkyl, or active functional group, m ranges from 1 to 100. a is ran, which indicates a random copolymer, or block, which indicates a block copolymer, andT comprises a terminating group, an ionizable or cationic lipid; a helper lipid; a sterol lipid; andadministering an effective amount of the lipid nanoparticle to the subject.

27. The compound of claim 26, wherein L3 comprises esters, carboxylate esters, carbonate esters, carbamates, amides, and combinations thereof.

28. The compound of claim 26, wherein L3 comprises a triazole ring.

29. The compound of claim 26, wherein T comprises Z-B-Q, and wherein Z comprises S, O, or N, B is an optional linking group, and Q is a terminating nucleophile or portion thereof.

30. The compound of claim 26, wherein Lipid comprises two hydrophobic moieties.

31. The compound of claim 26, wherein Lipid comprises a phospholipid, a glycerolipid, a di- alkyl acetamide, or a combination thereof.

32. The compound of claim 26, wherein Lipid comprises 1,2-dimyristoyl-sn-glycerol, 1,2- dilauroyl-sn -glycerol, or a combination thereof.

33. The method of claim 26, wherein the payload comprises mRNA, and wherein the antigen- presenting cells comprise splenic macrophage cells, dendritic cells, or combinations thereof.

34. A method of delivering a payload to target tissue of a subject, comprising: providing a lipid nanoparticle encapsulating the payload, wherein the lipid nanoparticle comprises: a POZ-lipid of Formula I:R-POZ-L-Lipid (I) wherein R comprises an initiating group,POZ comprises poly(ethyloxazoline),L comprises a physiologically degradable linking group, andLipid comprises a non-charged lipid comprising at least one hydrophobic moiety; an ionizable or cationic lipid; a helper lipid; a sterol lipid; and administering an effective amount of the lipid nanoparticle to the subject.

35. The method of claim 34, wherein the step of administering comprises intramuscularly injecting the subject.

36. The method of claim 34, wherein the step of administering comprises intramuscularly injecting the subject with a plurality of doses, wherein after a first dose is administered, each subsequent dose is administered after a predetermined amount of time.

37. The method of claim 36, wherein the predetermined amount of time is at least 30 days.

38. The method of claim 34, wherein the target tissue comprises liver, spleen, or a combination thereof.

39. The method of claim 34, wherein POZ comprises [N(COR.2)CH2CH2]n, where R.2 is ethyl.

40. The method of claim 34, wherein R comprises a hydrogen, a substituted or unsubstituted alkyl, an alkyne-substituted alkyl, a triazole with attached carboxylic acid, or a substituted or unsubstituted aralkyl group.

41. The method of claim 34, wherein L comprises ethers, esters, carboxylate esters, carbonate esters, carbamates, amines, amides, urethanes, disulfides, and combinations thereof.

42. The method of claim 34, wherein Lipid comprises phospholipid, a glycerolipid, a di-alkyl acetamide, or a combination thereof.

43. The method of claim 34, wherein Lipid comprises 1,2-dimyristoyl-sn-glycerol, 1,2- dilauroyl-sn-glycerol, or a combination thereof.

44. The method of claim 34, wherein the payload comprises mRNA.

45. A method for delivering a therapeutic level of an immunogenic payload to target tissue of a subject, comprising: administering a plurality of doses of a lipid nanoparticle to the subject, wherein the lipid nanoparticle encapsulates an mRNA encoding an antigen, wherein the lipid nanoparticle comprises an ionizable lipid, a helper lipid, a structural lipid, and a POZ- lipid of Formula I:R-POZ-L-Lipid (I) wherein R comprises an initiating group,POZ comprises poly(ethyloxazoline),L comprises a physiologically degradable linking group, andLipid comprises a non-charged lipid comprising at least one hydrophobic moiety, and wherein the LNP induces an attenuated drug response associated with an LNP.

46. The method of claim 45, wherein the drug response comprises an attenuated induction of IgM, attenuated induction of IgG, an attenuated accelerated blood clearance, or a combination thereof.

47. The method of claim 45, wherein the target tissue comprises liver, spleen, or a combination thereof.

48. The method of claim 45, wherein POZ comprises [N(COR2)CH2CH2]n, where R2 is ethyl.

49. The method of claim 45, wherein R comprises a hydrogen, a substituted or unsubstituted alkyl, an alkyne-substituted alkyl, a triazole with attached carboxylic acid, or a substituted or unsubstituted aralkyl group.

50. The method of claim 45, wherein L comprises ethers, esters, carboxylate esters, carbonate esters, carbamates, amines, amides, urethanes, disulfides, and combinations thereof.