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EP-4739663-A1 - IONIZABLE LIPIDS

EP4739663A1EP 4739663 A1EP4739663 A1EP 4739663A1EP-4739663-A1

Abstract

The present invention generally relates to the field of ionizable (also termed cationic) lipids, and in particular provides a novel type of such lipids as represented by formula (I). The present invention further provides methods for making such lipids as well as uses thereof, in particular in the preparation of nanoparticle compositions, more in particular nanoparticle compositions comprising active agents. It further provides pharmaceutical formulations comprising nanoparticle compositions based on the ionizable lipids disclosed herein.

Inventors

  • KASMI, Sabah
  • DE COEN, Ruben
  • DE KOKER, STEFAAN
  • DUMBRE, Shrinivas

Assignees

  • eTheRNA immunotherapies NV

Dates

Publication Date
20260513
Application Date
20240705

Claims (15)

  1. CLAIMS 1. An ionizable lipid represented by formula (I) wherein X 1 , and X 2 are each independently selected from -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2 - 12alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene optionally comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from - OH, and -NR a R a ’; each instance of R a and each instance of R a ’ is independently selected from -H, and -C 1-6 alkyl; or each instance of R a and R a ’ taken together with the N atom to which they are attached forms a 5- to 7-membered non-aromatic heterocycle; Y 1 , and Y 2 are each independently selected from -O-, -NR b -, -C(O)-, -OC(O)-, -C(O)O-, - OC(O)O-, -NR b C(O)-, -C(O)NR b -, -NR b C(O)O-, -OC(O)NR b -, -NR b C(S)O-, -NR b C(O)S-, - OC(S)NR b -, -SC(O)NR b -, and -NR b C(O)NR b -; each instance of R b is independently selected from -H, and -C 1-6 alkyl; X 3 , X 4 , X 5 and X 6 are each independently selected from a direct bond, -C 1-12 alkylene-, -C 2 - 1 2 alkenylene, and -C 2-12 alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene optionally further comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, and -NR a R a ’; Q is selected from a direct bond, and Ar 2 ; Ar 1 , and Ar 2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and/or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, -OH, -C 1-6 alkyl, and -O-C 1- 6 alkyl; Z 1 , and Z 2 are each independently selected from -O-, -NR c -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O- , -NR c C(O)-, -C(O)NR c -, -NR c C(O)O-, -OC(O)NR c -, -NR c C(S)O-, -NR c C(O)S-, -OC(S)NR c -, -SC(O)NR c -, and -NR c C(O)NR c -; each instance of R c is independently selected from -H, and -C 1-6 alkyl; R 1 and R 2 are each independently selected from -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl; wherein each of said -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -NR a R a ’, -OC(O)- R 3 , and -C(O)O-R 3 ; each instance of R 3 is independently selected from -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl; wherein each of said -C 2-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, and -NR a R a ’; wherein the total number of C atoms in X 1 , X 3 , X 5 , and R 1 together is at least 8; and wherein the total number of C atoms in X 2 , X 4 , X 6 , and R 2 together is at least 8.
  2. 2. An ionizable lipid as defined in claim 1 and represented by formula (I) wherein X 1 , and X 2 are each independently selected from -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2 - 12alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene optionally comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from - OH, and -NR a R a ’; each instance of R a and each instance of R a ’ is independently selected from -H, and -C 1-6 alkyl; or each instance of R a and R a ’ taken together with the N atom to which they are attached forms a 5- to 7-membered non-aromatic heterocycle; Y 1 , and Y 2 are each independently selected from -OC(O)-, -C(O)O-, -NR b C(O)-, -C(O)NR b , and -NR b C(O)O-; each instance of R b is independently selected from -H, and -C 1-6 alkyl; X 3 , X 4 , X 5 and X 6 are each independently selected from a direct bond, -C 1-12 alkylene-, -C 2 - 12alkenylene, and -C 2-12 alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene optionally further comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, and -NR a R a ’; Q is selected from a direct bond, and Ar 2 ; Ar 1 , and Ar 2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and/or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, -OH, -C 1-6 alkyl, and -O-C1- 6alkyl; Z 1 , and Z 2 are each independently selected from -O-, -NR c -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O- , -NR c C(O)-, -C(O)NR c -, -NR c C(O)O-, -OC(O)NR c -, -NR c C(S)O-, -NR c C(O)S-, -OC(S)NR c -, -SC(O)NR c -, and -NR c C(O)NR c -; each instance of R c is independently selected from -H, and -C 1-6 alkyl; R 1 and R 2 are each independently selected from -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl; wherein each of said -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -NR a R a ’, -OC(O)- R 3 , and -C(O)O-R 3 ; each instance of R 3 is independently selected from -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl; wherein each of said -C 2-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, and -NR a R a ’; wherein the total number of C atoms in X 1 , X 3 , X 5 , and R 1 together is at least 8; and wherein the total number of C atoms in X 2 , X 4 , X 6 , and R 2 together is at least 8.
  3. 3. An ionizable lipid as defined in claim 1 and represented by formula (I) wherein X 1 , and X 2 are each independently -C 1-12 alkylene-; wherein each of said -C 1-12 alkylene- optionally comprises from 1 to 6 heteroatoms selected from N, O and S; each instance of R a and each instance of R a ’ is independently selected from -H, and -C 1-6 alkyl; or each instance of R a and R a ’ taken together with the N atom to which they are attached forms a 5- to 7-membered non-aromatic heterocycle; Y 1 , and Y 2 are each independently selected from -O-, -NR b -, -C(O)-, -OC(O)-, -C(O)O-, - OC(O)O-, -NR b C(O)-, -C(O)NR b -, -NR b C(O)O-, -OC(O)NR b -, -NR b C(S)O-, -NR b C(O)S-, - OC(S)NR b -, -SC(O)NR b -, and -NR b C(O)NR b -; each instance of R b is independently selected from -H, and -C 1-6 alkyl; X 3 , X 4 , X 5 and X 6 are each independently selected from a direct bond, -C 1-12 alkylene-, -C 2 - 12alkenylene, and -C 2-12 alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene optionally further comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, and -NR a R a ’; Q is selected from a direct bond, and Ar 2 ; Ar 1 , and Ar 2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and/or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, -OH, -C 1-6 alkyl, and -O-C1- 6alkyl; Z 1 , and Z 2 are each independently selected from -O-, -NR c -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O- , -NR c C(O)-, -C(O)NR c -, -NR c C(O)O-, -OC(O)NR c -, -NR c C(S)O-, -NR c C(O)S-, -OC(S)NR c -, -SC(O)NR c -, and -NR c C(O)NR c -; each instance of R c is independently selected from -H, and -C 1-6 alkyl; R 1 and R 2 are each independently selected from -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl; wherein each of said -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -NR a R a ’, -OC(O)- R 3 , and -C(O)O-R 3 ; each instance of R 3 is independently selected from -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl; wherein each of said -C 2-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, and -NR a R a ’; wherein the total number of C atoms in X 1 , X 3 , X 5 , and R 1 together is at least 8; and wherein the total number of C atoms in X 2 , X 4 , X 6 , and R 2 together is at least 8.
  4. 4. An ionizable lipid as defined in claim 1 and represented by formula (I) wherein X 1 , and X 2 are each independently selected from -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2 - 12alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene optionally comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from - OH, and -NR a R a ’; each instance of R a and each instance of R a ’ is independently selected from -H, and -C 1-6 alkyl; or each instance of R a and R a ’ taken together with the N atom to which they are attached forms a 5- to 7-membered non-aromatic heterocycle; Y 1 , and Y 2 are each independently selected from -O-, -NR b -, -C(O)-, -OC(O)-, -C(O)O-, - OC(O)O-, -NR b C(O)-, -C(O)NR b -, -NR b C(O)O-, -OC(O)NR b -, -NR b C(S)O-, -NR b C(O)S-, - OC(S)NR b -, -SC(O)NR b -, and -NR b C(O)NR b -; each instance of R b is independently selected from -H, and -C 1-6 alkyl; X 3 , and X 4 are each independently -C 1-6 alkylene-; Q is selected from a direct bond, and Ar 2 ; Ar 1 , and Ar 2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and/or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, -OH, -C 1-6 alkyl, and -O-C1- 6alkyl; X 5 , and X 6 are each independently selected from a direct bond, -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2 - 12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, and -NR a R a ’; Z 1 , and Z 2 are each independently selected from -O-, -NR c -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O- , -NR c C(O)-, -C(O)NR c -, -NR c C(O)O-, -OC(O)NR c -, -NR c C(S)O-, -NR c C(O)S-, -OC(S)NR c -, -SC(O)NR c -, and -NR c C(O)NR c -; each instance of R c is independently selected from -H, and -C 1-6 alkyl; R 1 and R 2 are each independently selected from -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl; wherein each of said -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -NR a R a ’, -OC(O)- R 3 , and -C(O)O-R 3 ; each instance of R 3 is independently selected from -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl; wherein each of said -C 2-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, and -NR a R a ’; wherein the total number of C atoms in X 1 , X 3 , X 5 , and R 1 together is at least 8; and wherein the total number of C atoms in X 2 , X 4 , X 6 , and R 2 together is at least 8.
  5. 5. An ionizable lipid as defined in claim 1 and represented by formula (I) wherein X 1 , and X 2 are each independently selected from -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2 - 12alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene optionally comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from - OH, and -NR a R a ’; each instance of R a and each instance of R a ’ is independently selected from -H, and -C 1-6 alkyl; or each instance of R a and R a ’ taken together with the N atom to which they are attached forms a 5- to 7-membered non-aromatic heterocycle; Y 1 , and Y 2 are each independently selected from -O-, -NR b -, -C(O)-, -OC(O)-, -C(O)O-, - OC(O)O-, -NR b C(O)-, -C(O)NR b -, -NR b C(O)O-, -OC(O)NR b -, -NR b C(S)O-, -NR b C(O)S-, - OC(S)NR b -, -SC(O)NR b -, and -NR b C(O)NR b -; each instance of R b is independently selected from -H, and -C 1-6 alkyl; X 3 , and X 4 are each independently selected from a direct bond, -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2 - 12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, and -NR a R a ’; Q is selected from a direct bond, and Ar 2 ; Ar 1 , and Ar 2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and/or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, -OH, -C 1-6 alkyl, and -O-C1- 6alkyl; X 5 , and X 6 are each a direct bond; Z 1 , and Z 2 are each independently selected from -O-, -NR c -, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O- , -NR c C(O)-, -C(O)NR c -, -NR c C(O)O-, -OC(O)NR c -, -NR c C(S)O-, -NR c C(O)S-, -OC(S)NR c -, -SC(O)NR c -, and -NR c C(O)NR c -; each instance of R c is independently selected from -H, and -C 1-6 alkyl; R 1 and R 2 are each independently selected from -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl; wherein each of said -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -NR a R a ’, -OC(O)- R 3 , and -C(O)O-R 3 ; each instance of R 3 is independently selected from -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl; wherein each of said -C 2-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, and -NR a R a ’; wherein the total number of C atoms in X 1 , X 3 , X 5 , and R 1 together is at least 8; and wherein the total number of C atoms in X 2 , X 4 , X 6 , and R 2 together is at least 8.
  6. 6. An ionizable lipid as defined in claim 1 and represented by formula (I) wherein X 1 , and X 2 are each independently selected from -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2 - 12alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene optionally comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from - OH, and -NR a R a ’; each instance of R a and each instance of R a ’ is independently selected from -H, and -C 1-6 alkyl; or each instance of R a and R a ’ taken together with the N atom to which they are attached forms a 5- to 7-membered non-aromatic heterocycle; Y 1 , and Y 2 are each independently selected from -O-, -NR b -, -C(O)-, -OC(O)-, -C(O)O-, - OC(O)O-, -NR b C(O)-, -C(O)NR b -, -NR b C(O)O-, -OC(O)NR b -, -NR b C(S)O-, -NR b C(O)S-, - OC(S)NR b -, -SC(O)NR b -, and -NR b C(O)NR b -; each instance of R b is independently selected from -H, and -C 1-6 alkyl; X 3 , X 4 , X 5 and X 6 are each independently selected from a direct bond, -C 1-12 alkylene-, -C 2 - 12alkenylene, and -C 2-12 alkynylene; wherein each of said -C 1-12 alkylene-, -C 2-12 alkenylene, and -C 2-12 alkynylene optionally further comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, and -NR a R a ’; Q is selected from a direct bond, and Ar 2 ; Ar 1 , and Ar 2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and/or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, -OH, -C 1-6 alkyl, and -O-C1- 6alkyl; Z 1 , and Z 2 are each independently selected from -O-, and -OC(O)-; each instance of R c is independently selected from -H, and -C 1-6 alkyl; R 1 and R 2 are each independently selected from -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl; wherein each of said -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -NR a R a ’, -OC(O)- R 3 , and -C(O)O-R 3 ; each instance of R 3 is independently selected from -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl; wherein each of said -C 2-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, and -NR a R a ’; wherein the total number of C atoms in X 1 , X 3 , X 5 , and R 1 together is at least 8; and wherein the total number of C atoms in X 2 , X 4 , X 6 , and R 2 together is at least 8.
  7. 7. An ionizable lipid as defined in any one of claims 1 to 7 and represented by formula (Ia) wherein X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , Y 1 , Y 2 , Z 1 , Z 2 , Ar 1 , Ar 2 , R a , R a ’, R b , R c , R 1 , R 2 , and R 3 are as defined in any one of claims 1 to 6; wherein the total number of C atoms in X 1 , X 3 , X 5 , and R 1 together is at least 8; and wherein the total number of C atoms in X 2 , X 4 , X 6 , and R 2 together is at least 8.
  8. 8. An ionizable lipid as defined in any one of claims 1 to 7 and represented by formula (IIa) or (IIb) wherein X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , Y 1 , Y 2 , Z 1 , Z 2 , R a , R a ’, R b , R c , R 1 , R 2 , and R 3 are as defined in any one of claims 1 to 7; wherein the total number of C atoms in X 1 , X 3 , X 5 , and R 1 together is at least 8; and wherein the total number of C atoms in X 2 , X 4 , X 6 , and R 2 together is at least 8.
  9. 9. An ionizable lipid as defined in any one of claims 1 to 8 and represented by formula (IIIa) or (IIIb) wherein X7, and X8 are each independently selected from -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl; wherein each of said -C 6-20 alkyl, -C 6-20 alkenyl and -C 6-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N, and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -NR a R a ’; R5, and R6 are each independently selected from -C 1-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl; wherein each of said -C 2-20 alkyl, -C 2-20 alkenyl and -C 2-20 alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, and -NR a R a ’; X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , Y 1 , Y 2 , Z 1 , Z 2 , Ar 1 , Ar 2 , R a , R a ’, R b , and R c are as defined in any one of claims 1 to 8; wherein the total number of C atoms in X 1 , X 3 , X 5 , X7, and R5 together is at least 8; and wherein the total number of C atoms in X 2 , X 4 , X 6 , X8, and R6 together is at least 8.
  10. 10. An ionizable lipid as defined in claim 1 and being selected from the list comprising:
  11. 11. A nanoparticle or nanoparticle composition comprising an ionizable lipid as defined in any one of claims 1 to 10.
  12. 12. The nanoparticle or nanoparticle composition as defined in claim 11, further comprising a helper lipid, a sterol and/or a stabilizing lipid.
  13. 13. The nanoparticle or nanoparticle composition as defined in any one of claims 11 to 12, further comprising an active agent, in particular a nucleic acid, preferably mRNA.
  14. 14. Use of an ionizable lipid as defined in any one of claims 1 to 10 in the manufacture of a nanoparticle or nanoparticle composition.
  15. 15. A pharmaceutical composition comprising a nanoparticle or nanoparticle composition as defined in any one of claims 11 to 13, and a pharmaceutically acceptable agent.

Description

IONIZABLE LIPIDS FIELD OF THE INVENTION The present invention generally relates to the field of lipids, in particular ionizable (also termed cationic) lipids, and in particular provides a novel type of such lipids as represented by any of the formula disclosed herein. The present invention further provides methods for making such lipids as well as uses thereof, in particular in the preparation of nanoparticle compositions, more in particular nanoparticle compositions comprising active agents. It further provides pharmaceutical formulations comprising nanoparticle compositions based on the ionizable lipids disclosed herein. BACKGROUND TO THE INVENTION Nanoparticles, such as liposomes and lipid nanoparticles are increasingly being used in therapeutic areas for the delivery of active agents, such as small molecules, proteins, nucleic acids, etc. to cells. One of the main requirements for medical use of nanoparticles is that they need to combine efficient and stable encapsulation of the active agents upon storage and in the extracellular environment, with maximum cellular uptake and efficient release of their payload into the cells. Lipid nanoparticles comprising combinations of cationic lipids with other lipid components have been used to facilitate such cellular uptake of active agents. For example, lipid-based nanoparticles are typically composed of a cationic or ionizable lipid that can be protonated at acid pH, a helper lipid (e.g. phospholipid), a stabilizing lipid (e.g. PEGylated lipid) and a sterol, and have been used in the delivery of nucleic acids. Each component of a nanoparticle has specialized functions in stability and activity of the nanoparticles. Therefore, further improvements in cationic or ionizable lipid chemistries are needed to improve efficacy and safety of nanoparticle delivered active agents. Accordingly, the present invention relates to a new class of ionizable lipids as defined by the present set of claims, which have improved characteristics over the currently available classes of ionizable lipids. SUMMARY OF THE INVENTION In a first aspect, the present invention provides a lipid, in particular an ionizable lipid represented by formula (I) wherein X1, and X2 are each independently selected from -C1-12alkylene-, -C2-12alkenylene, and -C2-12 alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from - OH, and -NRaRa’; each instance of Ra and each instance of Ra’ is independently selected from -H, and -C1-6alkyl; or each instance of Ra and Ra’ taken together with the N atom to which they are attached forms a 5- to 7-membered non-aromatic heterocycle; Y1, and Y2 are each independently selected from -O-, -NRb-, -C(O)-, -OC(O)-, -C(O)O-, - OC(O)O-, -NRbC(O)-, -C(O)NRb-, -NRbC(O)O-, -OC(O)NRb-, -NRbC(S)O-, -NRbC(O)S-, - OC(S)NRb-, -SC(O)NRb-, and -NRbC(O)NRb-; each instance of Rb is independently selected from -H, and -C1-6alkyl; X3, X4, X5 and X6 are each independently selected from a direct bond, -C1-12alkylene-, -C2-12 alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, and -NRaRa’; Q is selected from a direct bond, and Ar2; Ar1, and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and/or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, -OH, -C1-6alkyl, and -O-C1- 6alkyl; Z1, and Z2 are each independently selected from -O-, -NRc-, -C(O)-, -OC(O)-, -C(O)O-, -OC(O)O- , -NRcC(O)-, -C(O)NRc-, -NRcC(O)O-, -OC(O)NRc-, -NRcC(S)O-, -NRcC(O)S-, -OC(S)NRc-, -SC(O)NRc-, and -NRcC(O)NRc-; each instance of Rc is independently selected from -H, and -C1-6alkyl; R1 and R2 are each independently selected from -C6-20alkyl, -C6-20alkenyl and -C6-20alkynyl; wherein each of said -C6-20alkyl, -C6-20alkenyl and -C6-20alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -NRaRa’, -OC(O)- R3, and -C(O)O- R3; each instance of R3 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C2-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally further comprises one or more heteroatoms selected from O, N and S and/or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, and -NRaRa’; wherein the total number of C atoms in X1, X3, X5, and R1 together is at least 8; and wherein the total number of C atoms in X