Lipid nanoparticle (LNP) delivery systems and formulations

HK40138711APending Publication Date: 2026-10-09PRIME MEDICINE INC
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Patent Information

Application Number
HK62026127025
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-09-29
Filing Date
2026-08-04
Publication Date
2026-10-09
Estimated Expiration
2044-04-18
Patent Text Reader

Abstract

The present disclosure describes compositions, nanoparticles (such as lipid nanoparticles), and / or lipid nanoparticle compositions and methods of their use.
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Description

Abstract This disclosure describes compositions, nanoparticles (e.g., lipid nanoparticles) and / or lipid nanoparticle compositions and methods of using them.

Claims

WHAT IS CLAIMED IS1. A compound of Formula I:Formula I wherein, each X1is independently -(CH2)r- -(CH2CH2O)S- -(OCH2CH2)8- -((CH2)m-C(O)NH)-, or -(C(O)NH-(CH2)m)-, each subscript “m” is independently 1-5; each subscript “o” is independently 1-5; each subscript “r” is independently 1-10; each subscript “s” is independently 1-5; each G1is independently a C1-C6substituted or unsubstituted alkylene; each Rais independently H or a C1-C6substituted or unsubstituted alkyl;L1is -NHC(O)-, -C(O)NH- -NHC(O)O- -OC(O)NH- -NHC(O)NH- -S-S-, orsubscript “p” is independently 1-5;L2is -O-(CH2CH2O)n- -(CH2CH2O)n-O- or -(OCH2CH2O)n- each subscript “n” is independently 1-200; subscript “q1” is independently 0-5; subscript “q2” is independently 0-5;L3is absent, -NHC(O)-, or -C(O)NH-; subscript “q3” is independently 0-5; each R is independently a Ci2-C2o substituted or unsubstituted alkyl; and198SUBSTITUTE SHEET (RULE 26)the indicates an R configuration or an S configuration.

2. The compound of claim 1, wherein the compound of Formula I is a compound of Formula I-a:Formula I-a3. The compound of claim 1, wherein the compound of Formula I is a compound ofFormula I-b:Formula I-b.

4. The compound of claim 1, wherein the compound of Formula I is a compound of Formula I-c:Formula I-c.199SUBSTITUTE SHEET (RULE 26)5. The compound of any one of claims 1-4, wherein L1is -NHC(O).

6. The compound of any one of claims 1-4, wherein L1is -NHC(O)NH-7. The compound of any one of claims 1-4, wherein L1is -S-S-.

8. The compound of any one of claims 1-4, wherein L1is -OC(O)NH-9. The compound of any one of claims 1-8, wherein each X1is -((CH2)m-C(0)NH).

10. The compound of any one of claims 1-8, wherein each X1is -(CFhCEbOX11. The compound of any one of claims 1-8, wherein each X1is -(CH2)r- and each subscript “r” is 5.

12. The compound of any one of claims 1-11, wherein each subscript “o” is 1.

13. The compound of any one of claims 1-12, wherein L2is -O-(CH2CH2O)n-14. The compound of any one of claims 1-12, wherein L2is -(CH2CH2O -.

15. The compound of claim 13 or 14, wherein each subscript “n” is 100 to 200.

16. The compound of any one of claims 1-15, wherein L3is absent.

17. The compound of any one of claims 1-15, wherein L3is present and is -NHC(O)-.

18. The compound of any one of claims 1-17, wherein each R is independently a C14-C18 unsubstituted alkyl.

19. The compound of any one of claims 1-18, wherein the compound of Formula I is any one of a compound of Formula I-c-1 to I-c-4:200SUBSTITUTE SHEET (RULE 26)Formula I-c-3, or201SUBSTITUTE SHEET (RULE 26)Formula I-c-4.

20. A compound selected from the group consisting of Formula I-c-5, I-c-6, 1-c-7, and I- c-8:Formula I-c-6,202SUBSTITUTE SHEET (RULE 26)Formula I-c-8 wherein, each X1is independently -(CH2)r-, -(CH2CH2O)S-, -(OCH2CH2)S-, -((CH2)m- C(O)NH)-, or -(C(O)NH-(CH2)m)-; each subscript “m” is independently 1-5; each subscript “s” is independently 1-5; each subscript “o” is independently 1-5; each subscript “r” is independently 1-10; each subscript “p” is independently 1-5; each subscript “n” is independently 1-200; each subscript “q1” is independently 0-5; each subscript “q2” is independently 0-5; each L3is independently absent, -NHC(O)-, or -C(O)NH-; and each R is independently a Ci2-C2o substituted or unsubstituted alkyl.

21. The compound of claim 20, wherein each X1is -((CH2)m-C(O)NH)-, each subscript “m” is independently 2, and each subscript “o” is independently 1.203SUBSTITUTE SHEET (RULE 26)22. The compound Hf claim 20, wherein each X1is -(CEhCFbOX-, each subscript “s” is independently 2, and each subscript “o” is independently 1.

23. The compound of claim 20, wherein the compound is a compound of Formula I-c-7 and, optionally, each X1is -(CH2)r-, each subscript “r” is independently 5, and each subscript “o” is l.

24. The compound of claim 20, wherein the compound is a compound of Formula I-c-5, L2is -O-(CH2CH2O)n-, and subscript “n” is 100 to 200.

25. The compound of claim 20, wherein the compound is a compound of Formula I-c-6, I-c-7, or I-c-8, each L2is -(OCFhCFhCOn- and each subscript “n” is 100 to 200.

26. The compound of any one of claims 20-25, wherein L3is absent.

27. The compound of claim 26, wherein in Formula I-c-4, subscript “p” is 4, subscript “q1” is 0., and subscript “q2” is 0.

28. The compound of claim 26, wherein in Formulas I-c-6, I-c-7, and I-c-8, each subscript “p” is 2, subscript “q1” is 0, and subscript “q2” is 0.

29. The compound of any one of claims 20-25, wherein L3is present and is -NHC(O)-.

30. The compound of claim 29, wherein in Formula I-a-4, subscript “p” is 4, subscript “q1” is 1 and subscript “q2” is 4.

31. The compound of any one of claims 20-30, wherein each R is independently a C14-C18 unsubstituted alkyl.204SUBSTITUTE SHEET (RULE 26)2. A compound selected from the group consisting of:wherein each subscript “n” is between 10-200.

33. A compound of Formula II:Formula II wherein:A is:each A1, A2, A3, A4, and A5is independentlyeach Y1is independently -NH-, -NHC(O)O-, -OC(O)NH-, -NHC(O)-, or -C(O)NH-; each Y2is independently absent, -(CH2)r , -(CFhCEhCOt-, or -(OCH2CH2)t-; each subscript “t” is independently 1-5; each Y3is independently absent, -NHC(O)-, or -C(O)NH-; each Y4is independently absent or -(CH2)I~; each subscript “r” is independently 1-10; each subscript “d” is independently 0-5; each subscript “c” is independently 0-5; subscript “n” is independently 1-200; subscript “a” is 1-5; subscript “b1” is independently 0-5;M2is absent, -NHC(O)-, or -C(O)NH-; subscript “b2” is independently 0-5;SUBSTITUTE SHEET (RULE 26)subscript “q4” is independently 0-6; each R1is independently a C12-C20substituted or unsubstituted alkyl; and each of thebonds independently indicate an R configuration or an S configuration; with the proviso that at least one of Y2, Y3and Y4is present.

34. The compound of claim 33, wherein the compound of Formula II is a compound of Formula Il-a:Formula Il-a.

35. The compound of claim 33 or 34, wherein the compound of Formula II is a compound of Formula II-a-1, Formula II-a-2, Formula II-a-3, Formula II-a-4, Formula II-a-5, or Formula II-a-6:Formula II-a-3,210SUBSTITUTE SHEET (RULE 26)Formula II-a-6.

36. The compound of any one of claims 33-35, wherein A1, A2, and A3are the same.

37. The compound of any one of claims 33-35, wherein A1and A2are different from A3.

38. The compound of any one of claims 33-35, wherein A1, A2, A4, and A5are the same.

39. The compound of any one of claims 33-35, wherein A1, A2, and A5are the same.

40. The compound of any one of claims 33-39, wherein each of Y1and Y4are present and each of Y2and Y3are absent.

41. The compound of claim 40, wherein each Y1is -C(O)NH- and each Y4is -(QDr-42. The compound of claim 40, wherein each Y1is -OC(O)NH- and each Y4is -(CFh),211SUBSTITUTE SHEET (RULE 26)43. The compound of any one of claims 33-39, wherein each of Y1, Y2, Y3, and Y4are present.

44. The compound of claim 43, wherein each Y1is independently -NHC(O)O-; each Y2is independently -((CH2)r ; each Y3is independently -C(O)NH-; and each Y4is independently -(CH2)r-45. The compound of any one of claims 33-39, wherein each of Y1and Y2are present and each of Y3and Y4are absent.

46. The compound of claim 45, wherein each Y1is independently -OC(O)NH- and each Y2is independently -(CH2CH2O)t-.

47. The compound of any one of claims 33-46, wherein each of A1, A2, A3, A4, and A5is selected from the group consisting of:

48. The compound of any one of claims 33-47, wherein M2is absent.212SUBSTITUTE SHEET (RULE 26)49. The compound of any one of claims 33-47, wherein M2is -NHC(O)-.

50. The compound of any one of claims 33-49, wherein each R1is independently a CH- C 18 unsubstituted alkyl.

51. A compound of Formula III or Formula IV :Formula IV wherein, each A6, A7, and A8is independentlyeach Y1is independently absent, -NHC(O)O-, or -OC(O)NH-; each Y2and Y4is independently -(CHA-; each subscript “r” is independently 1-10; each Y3is independently absent, -NHC(O)-, or -C(O)NH-; each subscript “d” is independently 1-5; each subscript “c” is independently 1-5; subscript “a” is 1-5; subscript “n” is independently 10-100; and each of thebonds independently indicate an R configuration or an 8 configuration; with the proviso that at least one of Y1or Y3is present.213SUBSTITUTE SHEET (RULE 26)52. The compound of claim 51, wherein the compound of Formula III is a compound ofFormula Ill-a or Formula Ill-b:Formula Ill-b.

53. The compound of claim 51, wherein the compound of Formula IV is a compound ofFormula IV-a or Formula IV -b:Formula IV-b.214SUBSTITUTE SHEET (RULE 26)54. The compound of any one of claims 51-53, wherein subscript “a” is 3.

55. The compound of any one of claims 51-53, wherein subscript “a” is 1.

56. The compound of any one of claims 51-55, wherein subscript “n” is independently34-46.

57. The compound of any one of claims 51-55, wherein subscript “n” is independently between 34-36, in a range of 34-36, between 44-46 or in a range of 44-46.

58. The compound of any one of claims 51-57, wherein subscript “c” is 1.

59. The compound of any one of claims 51-58, wherein each of A6, A7, and A8is independently selected from the group consisting of:

60. The compound of any one of claims 51-58, wherein A6and A7are each independently215SUBSTITUTE SHEET (RULE 26)61. The compound of any one of claims 51-58, wherein A6, A7, and A8are each independently216SUBSTITUTE SHEET (RULE 26)62. A compound selected from the group consisting of:SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)226SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)240SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)SUBSTITUTE SHEET (RULE 26)wherein each subscript “n” is between 10-200.

63. A pharmaceutically acceptable salt of a compound of any one of claims 1-62.

64. A lipid nanoparticle (LNP) composition comprising a lipid that comprises a compound of any one of claims 1 -62.

65. A lipid nanoparticle (LNP) composition comprising: a lipid that comprises a compound of any one of claims 1-62; a cationic lipid: a phospholipid; a PEG-containing lipid; and a sterol.

66. The LNP composition of claim 65. further comprising a prime editor comprising a DNA binding domain and a DNA polymerase domain, or one or more polynucleotides encoding the prime editor.

67. The LNP composition of claim 65 or 66. further comprising a prime editing guide RNA (PEgRNA) or a polynucleotide encoding the PEgRNA.

68. The LNP composition of any one of claims 65-67. further comprising a nick guide RNA (ngRNA) or a polynucleotide encoding the ngRNA.

69. The LNP composition of any one of claims 65-68. further comprising a second PEgRNA or a polynucleotide encoding the second PEgRNA.

70. A pharmaceutical composition comprising the LNP composition of any one of claims 65-69.

71. A method for delivering polynucleotides into a target cell comprising: introducing into the target cell at least one lipid nanoparticle comprising a lipid that comprises the compound of any one of claims 1-62 and one or more polynucleotides.

72. A method for delivering a prime editing sy stem into a target cell comprising:introducing into the target cell at least one lipid nanoparticle comprising a lipid that comprises the compound of any one of claims 1-62 and one or more components of a prime editing system.

73. The method of claim 72, wherein the one or more components of a prime editing system comprises a construct encoding prime editor components.

74. The method of claim 72, wherein the one or more components of a prime editing system comprises an mRNA encoding prime editor components.

75. The method of claim 73 or 74, wherein the prime editor components comprise a prime editing guide RNA (PEgRNA), and optionally a nick guide RNA (ngRNA).

76. The method of claim 72 or 74, wherein the prime editor components comprise a PEgRNA pair, wherein the PEgRNA comprises a first PEgRNA and / or a second PEgRNA.

77. The method of claim 72, wherein the one or more components of a prime editing system comprises a construct encoding a prime editor fusion protein or an mRNA encoding a prime editor fusion protein.

78. The method of claim 72, wherein the one or more components of a prime editing system comprises one or more constructs encoding one or more of a prime editor fusion protein, PEgRNA, ngRNA, or a PEgRNA pair.

79. The method of claim 72, wherein the one or more components of a prime editing system comprises a prime editor fusion protein, a PEgRNA, a ngRNA, or a PEgRNA pair.

80. The LNP composition of any one of claims 65-69, wherein the LNP composition is formulated to deliver the at least one polynucleotide or one or more components of the prime editing system to target cells.

81. The method of any one of claims 71-79 or the LNP composition of claim 80, wherein the target cells are or comprise human cells, mammalian cells, liver cells, bone marrow cells, lung cells, eye cells, muscle cells, or cells in the central nervous system.