US 12,491,261 B2
Lipid nanoparticle formulations
Michael J. Hope, Vancouver (CA); Barbara Mui, Vancouver (CA); Paulo Jia Ching Lin, Vancouver (CA); Christopher J. Barbosa, Coquitlam (CA); Thomas D. Madden, Vancouver (CA); Steven M. Ansell, Vancouver (CA); and Xinyao Du, Richmond (CA)
Assigned to Acuitas Therapeutics, Inc., Vancouver (CA)
Filed by Acuitas Therapeutics, Inc., Vancouver (CA)
Filed on Jun. 9, 2023, as Appl. No. 18/332,487.
Application 18/332,487 is a continuation of application No. 16/345,592, granted, now 11,712,481, previously published as PCT/US2017/058619, filed on Oct. 26, 2017.
Application 16/345,592 is a continuation in part of application No. 15/337,434, filed on Oct. 28, 2016, granted, now 10,166,298, issued on Jan. 1, 2019.
Claims priority of provisional application 62/413,319, filed on Oct. 26, 2016.
Prior Publication US 2023/0372537 A1, Nov. 23, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 48/00 (2006.01); A61K 9/127 (2006.01); A61K 47/18 (2017.01); C07C 219/06 (2006.01); C07C 229/12 (2006.01); C07C 229/16 (2006.01); C07C 233/18 (2006.01); C07C 255/24 (2006.01); C12N 9/02 (2006.01)
CPC A61K 48/0033 (2013.01) [A61K 9/127 (2013.01); A61K 47/18 (2013.01); C07C 219/06 (2013.01); C07C 229/12 (2013.01); C07C 229/16 (2013.01); C07C 233/18 (2013.01); C07C 255/24 (2013.01); C12N 9/0069 (2013.01); C12Y 113/12007 (2013.01)] 73 Claims
 
1. A lipid nanoparticle comprising:
i) from 47 to 48 mol percent of a cationic lipid;
ii) a neutral lipid;
iii) a steroid;
iv) a polymer conjugated lipid; and
v) a therapeutic agent, or a pharmaceutically acceptable salt thereof, encapsulated within or associated with the lipid nanoparticle, wherein the cationic lipid has a structure of Formula III:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
one of L1 or L2 is —O(C═O)—, —(C═O)O—, —C(═O)—, —O—, —S(O)x—, —S—S—, —C(═O)S—, SC(═O)—, —NRaC(═O)—, —C(═O) NRa—NRaC(═O) NRa—, —OC(═O) NRa— or —NRaC(═O)O—, and the other of L1 or L2 is —O(C═O)—, —(C═O)O—, —C(═O)—, —O—, —S(O)x—, —S—S—, —C(═O)S—, SC(═O)—, —NRaC(═O)—, —C(═O) NRa, —NRaC(═O) NRa—, —OC(═O) NRa— or —NRaC(═O)O— or a direct bond;
G1 and G2 are each independently unsubstituted C1-C12 alkylene or C1-C12 alkenylene;
G3 is C1-C24 alkylene, C1-C24 alkenylene, C3-C8 cycloalkylene, C3-C8 cycloalkenylene;
Ra is H or C1-C12 alkyl;
R1 and R2 are each independently C6-C24 alkyl or C6-C24 alkenyl;
R3 is H, OR5, CN, —C(═O)OR4, —OC(═O)R4 or —NRaC(═O)R4;
R4 is C1-C12 alkyl;
R5 is H or C1-C6 alkyl; and
x is 0, 1 or 2.