Lipids for therapeutic agent delivery formulations

Patent metadata

Field	Value
Publication number	US-9308267-B2
Application number	US-201313913918-A
Country	US
Kind code	B2
Filing date	Jun 10, 2013
Priority date	Jun 8, 2012
Publication date	Apr 12, 2016
Grant date	Apr 12, 2016

Abstract

The description is directed to ionizable lipids useful for enhancing the delivery of therapeutic agents in liposomes.

First claim

What is claimed:

1. An ionizable lipid compound of formula I:

wherein
n and m are independently 1, 2, 3, or 4;
R 1 and R 2 are independently C 10-18 alkyl or C 12-18 alkenyl;
X is —CH 2 — or absent;
L is S—C 1-4 alkylene, —S(O) 2 —C 1-4 alkylene, or

or a pharmaceutically acceptable salt form thereof.

2. The compound of claim 1 , wherein n and m are 1 or 2.

3. The compound of claim 1 , wherein X is absent.

4. The compound of claim 3 , wherein L is

5. The compound of claim 1 , wherein X is —CH 2 .

6. The compound of claim 5 wherein L is —S—C 1-4 alkylene.

7. The compound of claim 6 , wherein L is —S—CH 2 — or —S—CH 2 —CH 2 —.

8. The compound of claim 5 wherein L is —S(O) 2 —C 1-4 alkylene.

9. The compound of claim 8 , wherein L is —S(O) 2 —CH 2 —CH 2 —.

10. The compound of claim 1 , wherein R 1 and R 2 are each C 10-18 alkyl.

11. The compound of claim 1 , wherein R 1 and R 2 are each C 13 alkyl.

12. The compound of claim 1 , wherein R 1 and R 2 are each C 12-18 alkenyl.

13. The compound of claim 1 , wherein R 1 and R 2 are each C 13-17 alkenyl.

14. The compound of claim 1 , wherein R 1 and R 2 are each oleyl or linoleyl.

15. A composition comprising a compound of claim 1 in a lipid nanoparticle comprising a bilayer of lipid molecules.

16. The composition of claim 15 , wherein the compound is 5 to 50 mol % of the lipid molecules.

17. The composition of claim 15 , further comprising a cationic lipid.

18. The composition of claim 17 , wherein the cationic lipid is

19. The composition of claim 17 , wherein the cationic lipid is 5 to 4mol % of the lipid molecules.

20. The composition of claim 17 , wherein the molar ratio of the ionizable lipid and the cationic lipid is about 5:35 to about 35:5.

21. The compound of claim 1 , consisting of a compound with a structure selected from S104, S104-DO, SO2-S104, TU104, TU104-DO, S104-DMO, S104-DLin, TU104-DLin, and T104

Assignees

• Nitto Denko Corp

Inventors

• Payne Joseph E
• Gaudette John A
• Hou Zheng
• Ahmadian Mohammad
• Yu Lei
• Knopov Victor
• Akopian Violetta
• Karmali Priya
• Witte Richard P
• Safarzadeh Neda
• Ying Wenbin
• Zhang Jun

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61P1/18

  for pancreatic disorders, e.g. pancreatic enzymes · CPC title

• C07C235/08

  having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms · CPC title

• C07C271/16

  to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms · CPC title