US 12,121,591 B2
Sulfur-containing ionizable lipids for the delivery of nucleic acids and other therapeutic agents
Deaglan Arnold, London (CA); Nagavenkata Durga Prasad Atmuri, Vancouver (CA); Fariba Saadati, Vancouver (CA); Huy Tran, Vancouver (CA); and Marco A. Ciufolini, Vancouver (CA)
Assigned to NanoVation Therapeutics Inc., Vancouver (CA)
Filed by NanoVation Therapeutics Inc., Vancouver (CA)
Filed on Dec. 21, 2023, as Appl. No. 18/392,458.
Claims priority of provisional application 63/434,506, filed on Dec. 22, 2022.
Prior Publication US 2024/0261430 A1, Aug. 8, 2024
Int. Cl. A61K 47/69 (2017.01); A61K 9/51 (2006.01); A61K 47/20 (2006.01); C07C 323/12 (2006.01); C07C 323/25 (2006.01); C07D 205/04 (2006.01); C07D 317/28 (2006.01)
CPC A61K 47/6929 (2017.08) [A61K 9/5123 (2013.01); A61K 47/20 (2013.01); C07C 323/12 (2013.01); C07C 323/25 (2013.01); C07D 205/04 (2013.01); C07D 317/28 (2013.01); C07B 2200/05 (2013.01)] 10 Claims
 
1. An ionizable, cationic amino lipid or a pharmaceutically acceptable salt thereof comprising:
a protonatable amino head group;
two lipophilic chains, wherein the protonatable amino head group has a central carbon atom to which each of the two lipophilic chains are directly bonded;
at least one of the two lipophilic chains has a structure of Formula A.1:

OG Complex Work Unit Chemistry
wherein the wavy line represents a bond to the central carbon atom;
wherein m and n are independently 2 to 8;
E is an ester group that is (C═O)O or O(C═O);
R1 is a linear, branched, monocyclic or polycyclic, optionally substituted, C3 to C20 alkyl group, comprising 0-2 carbon-carbon double bonds;
R2 is a linear or branched, optionally substituted, C4 to C10 alkyl group, comprising 0-2 carbon-carbon double bonds, or R2 is bound to R3 to form a ring structure as indicated by the dashed curved line;
R3 is H, or a linear or branched, optionally substituted, C4 to C10 alkyl group, comprising 0-2 carbon-carbon double bonds, or R3 is bound to R2 to form a ring structure as indicated by the dashed curved line;
R4 and R5 are, independently, H, or a linear or branched, optionally substituted, C1 to C10 alkyl group, comprising 0-2 carbon-carbon double bonds, or R4 and R5 are bound to each other to form a ring structure;
each lipophilic chain has between 15 and 40 carbon atoms in total; and
wherein (i) a nitrogen atom of the protonatable amino head group of the lipid is positively charged below its pKa; and (ii) the lipid has a Clog P of at least 11.