POLY(ALKYLOXAZOLINE)-LIPID CONJUGATES AND LIPID PARTICLES CONTAINING THEM

RU2024125225A3Pending Publication Date: 2026-06-29GENEVANT SCI GMBH

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Patent Information

Authority / Receiving Office: RU · RU
Patent Type: Applications
Current Assignee / Owner: GENEVANT SCI GMBH
Filing Date: 2023-01-30
Publication Date: 2026-06-29

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Claims

1. Poly(alkyloxazoline)-lipid conjugate of Formula I: (I), or a pharmaceutically acceptable salt thereof, where the index n is an integer in the range from 10 to 100; R 1 independently represents C 1-6 alkyl; each R 2 independently selected from the group consisting of hydrogen, C 1-6 alkyl and C 1-6 acyl; and (i) Z is –S(CH2)2C(O)–, and R 3 selected from the group consisting of –NR 3a R 3b , –NR 3a CH2CH(R 3b )2, –CH(R 3b )2i –CH2CH(R 3b )2; or (ii) Z is selected from the group consisting of –Z 1 –OC(O)–, –Z 1 –NHC(O)–, –Z 1 –S(O)2– and –Z 1 –OCH2–, Z 1 selected from the group consisting of a covalent bond, an oligo(ethylene glycol) diradical, and a poly(ethylene glycol) diradical, and R3 selected from the group consisting of –NR 3a R 3b and –CH(R 3b )2; where each R 3a and R 3b independently selected from the group consisting of hydrogen, C 6-22 alkyl, C 6-22 alkenyl and C 6-22 alkynyl, with one or more non-adjacent CH2 groups in R 3a and R 3b optionally and independently replaced by oxygen, provided that at least one R 3a or R 3b selected from the group consisting of C 6-22 alkyl, C 6-22 alkenyl and C 6-22 alkynyl, where one or more non-adjacent CH2 groups in R 3a or R 3b optionally and independently replaced by oxygen.

2. The poly(alkyloxazoline)-lipid conjugate according to claim 1 or a pharmaceutically acceptable salt thereof, where R 1 is ethyl.

3. The poly(alkyloxazoline)-lipid conjugate according to claim 1 or a pharmaceutically acceptable salt thereof, where R 1 is methyl.

4. The poly(alkyloxazoline)-lipid conjugate of claim 1 or a pharmaceutically acceptable salt thereof, wherein each R 1 independently selected from the group consisting of ethyl and methyl.

5. The poly(alkyloxazoline)-lipid conjugate of any one of claims 1-4 or a pharmaceutically acceptable salt thereof, wherein the index n is an integer in the range from about 15 to about 55.

6. The poly(alkyloxazoline)-lipid conjugate of claim 5 or a pharmaceutically acceptable salt thereof, wherein the poly(alkyloxazoline) portion of the conjugate has an average molecular weight in the range of from about 2000 Da to about 5000 Da.

7. A poly(alkyloxazoline)-lipid conjugate according to any one of claims 1-6, having a structure of Formula IIa: (IIa), or a pharmaceutically acceptable salt thereof, where: R 2 selected from the group consisting of hydrogen and methyl; R 3a selected from the group consisting of hydrogen, C 12-18 alkyl and C 12-18 alkenyl; and R 3b selected from the group consisting of C 12-18 alkyl and C 12-18 alkenyl.

8. The poly(alkyloxazoline)-lipid conjugate of claim 7, wherein R 3a and R 3b independently selected from the group consisting of C 12-18 alkyl and C 12-28 alkenyl.

9. A poly(alkyloxazoline)-lipid conjugate according to any one of claims 1-6, having a structure of Formula IIb: (IIb), or a pharmaceutically acceptable salt thereof, where: R 2 selected from the group consisting of hydrogen and methyl; and each R 3c independently selected from the group consisting of C 12-18 alkyl and C 12-28 alkenyl.

10. A poly(alkyloxazoline)-lipid conjugate according to any one of claims 1-6, wherein Z is –Z 1 –OC(O)–, Z 1 is selected from the group consisting of a covalent bond and a poly(ethylene glycol) diradical, and R 3 represents –NR 3a R 3b .

11. A poly(alkyloxazoline)-lipid conjugate according to any one of claims 1-6, wherein Z is –Z 1 –NHC(O)–, Z 1 represents a covalent bond, and R 3 represents –NR 3a R 3b .

12. A poly(alkyloxazoline)-lipid conjugate according to any one of claims 1-6, wherein Z is -Z 1 –OC(O)–, Z 1 represents a covalent bond, and R 3 is –CH(R 3b )2.

13. A poly(alkyloxazoline)-lipid conjugate according to any one of claims 1-6, wherein Z is –Z 1 –S(O)2–, Z 1 represents a covalent bond, and R 3 represents –NR 3a R 3b .

14. A poly(alkyloxazoline)-lipid conjugate according to any one of claims 1-6, wherein Z is –Z 1 –OCH2–, Z 1 represents a covalent bond, and R 3 is –CH(R 3b )2.

15. A poly(alkyloxazoline)-lipid conjugate according to any one of claims 1-6, wherein Z is –Z 1 –NHC(O)–, Z 1 represents a covalent bond, and R 3 represents –CH(R 3b )2.

16. A poly(alkyloxazoline)-lipid conjugate according to any one of claims 10-15, where R 3a and each R 3b independently selected from the group consisting of C 12-18 alkyl and C 12-18 alkenyl.

17. A lipid nanoparticle comprising a poly(alkyloxazoline)-lipid conjugate according to any one of claims 1-16.

18. The lipid nanoparticle of claim 17, further comprising a cationic lipid, a neutral lipid, a sterol, or a combination thereof.

19. A lipid nanoparticle according to claim 17 or 18, further comprising a nucleic acid.

20. A lipid nanoparticle comprising: (a) nucleic acid; (b) a cationic lipid comprising from 30 mol% to 80 mol% of the total lipids present in the lipid nanoparticle; (c) neutral lipid; (d) sterol; and (e) a poly(alkyloxazoline)-lipid conjugate containing from 0.1 mol.% to 10 mol.% of the total amount of lipids present in the lipid nanoparticle.

21. The lipid nanoparticle of claim 20, wherein the cationic lipid comprises from 40 mol.% to 70 mol.% of the total amount of lipids present in the lipid nanoparticle.

22. The lipid nanoparticle of claim 20 or 21, wherein the cationic lipid comprises from 45 mol.% to 65 mol.% of the total amount of lipids present in the lipid nanoparticle.

23. The lipid nanoparticle of any one of claims 20-22, wherein the cationic lipid comprises from 45 mol% to 60 mol% of the total amount of lipids present in the lipid nanoparticle.

24. The lipid nanoparticle of any one of claims 20-23, wherein the cationic lipid comprises from 50 mol% to 60 mol% of the total amount of lipids present in the lipid nanoparticle.

25. The lipid nanoparticle of any one of claims 20-24, wherein the neutral lipid comprises from 3 mol.% to 20 mol.% of the total amount of lipids present in the lipid nanoparticle.

26. The lipid nanoparticle of any one of claims 20-25, wherein the neutral lipid comprises from 5 mol.% to 15 mol.% of the total amount of lipids present in the lipid nanoparticle.

27. The lipid nanoparticle of any one of claims 20-26, wherein the neutral lipid comprises from 8 mol.% to 12 mol.% of the total amount of lipids present in the lipid nanoparticle.

28. The lipid nanoparticle of any one of claims 20-27, wherein the sterol comprises from 10 mol.% to 60 mol.% of the total amount of lipids present in the lipid nanoparticle.

29. The lipid nanoparticle of any one of claims 20-28, wherein the sterol comprises from 20 mol% to 50 mol% of the total amount of lipids present in the lipid nanoparticle.

30. The lipid nanoparticle of any one of claims 20-29, wherein the sterol comprises from 30 mol.% to 40 mol.% of the total amount of lipids present in the lipid nanoparticle.

31. The lipid nanoparticle of any one of claims 20-30, wherein the poly(alkyloxazoline)-lipid conjugate comprises from 0.1 mol% to 5 mol% of the total amount of lipids present in the lipid nanoparticle.

32. The lipid nanoparticle of any one of claims 20-31, wherein the poly(alkyloxazoline)-lipid conjugate comprises from 0.5 mol% to 3 mol% of the total amount of lipids present in the lipid nanoparticle.

33. The lipid nanoparticle of claim 20, wherein the cationic lipid comprises from 50 mol.% to 60 mol.% of the total amount of lipids present in the lipid nanoparticle, the neutral lipid comprises from 8 mol.% to 12 mol.% of the total amount of lipids present in the lipid nanoparticle, the sterol comprises from 30 mol.% to 40 mol.% of the total amount of lipids present in the lipid nanoparticle, and the poly(alkyloxazoline)-lipid conjugate comprises from 0.5 mol.% to 3 mol.% of the total amount of lipids present in the lipid nanoparticle.

34. The lipid nanoparticle of any one of claims 20-33, wherein the neutral lipid comprises a phospholipid.

35. The lipid nanoparticle of any one of claims 20-34, wherein the sterol comprises cholesterol.

36. The lipid nanoparticle of any one of claims 20-35, wherein the poly(alkyloxazoline)-lipid conjugate comprises the poly(alkyloxazoline)-lipid conjugate of any one of claims 1-16.

37. The lipid nanoparticle of any one of claims 19-35, wherein the nucleic acid comprises RNA.

38. The lipid nanoparticle of claim 37, wherein the RNA comprises mRNA.

39. The lipid nanoparticle of any one of claims 19-38, wherein the nucleic acid is completely encapsulated within the lipid nanoparticle.

40. A lipid nanoparticle according to any one of claims 17-39, which has an average diameter in the range of 40 nm to 150 nm.

41. A pharmaceutical composition comprising a lipid nanoparticle according to any one of claims 17-40 and a pharmaceutically acceptable carrier.

42. A pharmaceutical composition according to claim 41, which is intended for intravenous, intramuscular, pulmonary, intracerebral, intrathecal or intranasal administration.

43. A method for introducing a nucleic acid into a cell, comprising: providing contact of the cell with the lipid nanoparticle according to any of claims 17-40 or the pharmaceutical composition according to claims 41 or 42.

44. A method for delivering a nucleic acid to a subject, comprising: administering to a subject a lipid nanoparticle according to any one of claims 17-40 or a pharmaceutical composition according to claims 41 or 42.

45. A method for preventing or treating a disease or disorder in a subject in need thereof, comprising: administering to a subject a lipid nanoparticle according to any one of claims 17-40 or a pharmaceutical composition according to claims 41 or 42.

46. The method of claim 45, wherein the disease or disorder is a viral infection, a liver disease or disorder, a lung disease or disorder, a CNS disease or disorder, or cancer.