Granted Patent B2

US 12,410,121 · App. 18/612,888 · Granted Sep 9, 2025

Inventors: Julia Gatenyo (Vancouver, CA); Xinyao Du (Richmond, CA)

Assignee: Acuitas Therapeutics, Inc.

C07C219/06A61K9/5123A61K39/12A61K2039/55555

Abstract

Claims (56)

1. A compound having a structure of Formula (I):

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein:

G 1 and G 2 are each independently C 1 -C 6 alkylene;

L 1 and L 2 are each independently —O(C═O)— or —(C═O)O—;

R 1a and R 1b are, at each occurrence, independently H or C 1 -C 12 alkyl;

R 2a and R 2b are, at each occurrence, independently H or C 1 -C 12 alkyl;

R 3a and R 3b are, at each occurrence, independently H or C 1 -C 12 alkyl;

R 4a and R 4b are, at each occurrence, independently H or C 1 -C 12 alkyl;

R 5 and R 6 are each independently H or methyl;

R 7 is —O(C═O)R 10 , —(C═O)OR 10 , —NR 9 (C═O)R 10 or —(C═O)NR 9 R 10 ;

R 8 is OH, —N(R 11 )(C═O)R 12 , —(C═O)NR 11 R 12 , —NR 11 R 12 , —(C═O)OR 12 or —O(C═O)R 12 ;

R 9 is H or C 1 -C 15 alkyl;

R 10 is C 1 -C 15 alkyl;

R 11 is H or C 1 -C 6 alkyl;

R 12 is C 1 -C 6 alkyl;

X is —(C═O)— or a direct bond; and

a, b, c and d are each independently an integer from 1 to 24.

2. A lipid nanoparticle comprising:

i) a compound having a structure Formula (I):

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein:

G 1 and G 2 are each independently C 1 -C 6 alkylene;

L 1 and L 2 are each independently —O(C═O)— or —(C═O)O—;

R 1a and R 1b are, at each occurrence, independently H or C 1 -C 12 alkyl;

R 2a and R 2b are, at each occurrence, independently H or C 1 -C 12 alkyl;

R 3a and R 3b are, at each occurrence, independently H or C 1 -C 12 alkyl;

R 4a and R 4b are, at each occurrence, independently H or C 1 -C 12 alkyl;

R 5 and R 6 are each independently H or methyl;

R 7 is —O(C═O)R 10 , —(C═O)OR 10 , —NR 9 (C═O)R 10 or —(C═O)NR 9 R 10 ;

R 8 is OH, —N(R 11 )(C═O)R 12 , —(C═O)NR 11 R 12 , —NR 11 R 12 , —(C═O)OR 12 or —O(C═O)R 12 ;

R 9 is H or C 1 -C 15 alkyl;

R 10 is C 1 -C 15 alkyl;

R 11 is H or C 1 -C 6 alkyl;

R 12 is C 1 -C 6 alkyl;

X is —(C═O)— or a direct bond; and

a, b, c and d are each independently an integer from 1 to 24; and

ii) a therapeutic agent.

3. A pharmaceutical composition comprising the lipid nanoparticle of claim 2 and a pharmaceutically acceptable diluent or excipient.

4. A method for treating a disease in a patient in need thereof, the method comprising administering the lipid nanoparticle of claim 2 to the patient.

5. A method for vaccinating a patient in need thereof against a viral pathogen, the method comprising administering the lipid nanoparticle of claim 2 to the patient, wherein the therapeutic agent is a viral antigen or an mRNA encoding a viral antigen.

6. A pharmaceutical composition comprising the compound of claim 1 , a therapeutic agent and a pharmaceutically acceptable diluent or excipient.

7. A method for treating a disease in a patient in need thereof, the method comprising administering the pharmaceutical composition of claim 6 to the patient.

8. A method for vaccinating a patient in need thereof against a viral pathogen, the method comprising administering the pharmaceutical composition of claim 2 to the patient, wherein the therapeutic agent is a viral antigen or an mRNA encoding a viral antigen.

9. The compound of claim 1 , having one of the following structures (IA) or (IB):

10. The compound of claim 9 , wherein G 1 is C 2 , C 3 , C 4 , C 5 or C 6 alkylene.

11. The compound of claim 9 , wherein G 2 is C 2 , C 3 or C 4 alkylene.

12. The compound of claim 9 , wherein X is —(C═O)—.

13. The compound of claim 9 , wherein X is a direct bond.

14. The compound of claim 9 , wherein R 7 is —O(C═O)R 10 or —(C═O)OR 10 .

15. The compound of claim 9 , wherein R 7 is —NR 9 (C═O) or —(C═O)NR 9 R 10 .

16. The compound of claim 9 , wherein R 2a , R 2b , R 3a and R 3b are, at each occurrence, H.

17. The compound of claim 9 , wherein

or both, independently has one of the following structures:

18. The compound of claim 9 , wherein a, b, c and d are each independently an integer from 4 to 10.

19. The compound of claim 9 , wherein each of R 5 and R 6 is methyl.

20. The compound of claim 9 , wherein R 8 is OH.

21. The compound of claim 9 , wherein R 8 has the following structure:

Continuity (4)

References Cited (400)

Cited By (3)

US 12,667,627 US 12,678,515 US 12,714,670