US 11,744,801 B2
Methods of making lipid nanoparticles
Joseph Schariter, Cambridge, MA (US); Kimberly Hassett, Cambridge, MA (US); Mike Smith, Cambridge, MA (US); Orn Almarsson, Cambridge, MA (US); and Luis Brito, Cambridge, MA (US)
Assigned to ModernaTX, Inc., Cambridge, MA (US)
Appl. No. 16/643,037
Filed by ModernaTX, Inc., Cambridge, MA (US)
PCT Filed Aug. 31, 2018, PCT No. PCT/US2018/049251
§ 371(c)(1), (2) Date Feb. 28, 2020,
PCT Pub. No. WO2019/046809, PCT Pub. Date Mar. 7, 2019.
Claims priority of provisional application 62/590,193, filed on Nov. 22, 2017.
Claims priority of provisional application 62/553,085, filed on Aug. 31, 2017.
Claims priority of provisional application 62/553,088, filed on Aug. 31, 2017.
Prior Publication US 2020/0306191 A1, Oct. 1, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/60 (2017.01); B82Y 5/00 (2011.01); A61K 9/127 (2006.01); A61K 9/19 (2006.01)
CPC A61K 9/19 (2013.01) [A61K 47/60 (2017.08); A61K 9/127 (2013.01); A61K 9/1277 (2013.01); B82Y 5/00 (2013.01)] 15 Claims
OG exemplary drawing
 
1. A method of producing a nucleic acid lipid nanoparticle composition, the method comprising:
mixing a lipid solution comprising an ionizable lipid with a solution comprising a nucleic acid thereby forming a precursor nucleic acid lipid nanoparticle, wherein the precursor nucleic acid lipid nanoparticle further comprises a first PEG lipid;
optionally processing the precursor nucleic acid lipid nanoparticle;
adding a second PEG lipid to the precursor nucleic acid lipid nanoparticle thereby forming a modified nucleic acid lipid nanoparticle; and
processing the modified nucleic acid lipid nanoparticle, thereby forming the nucleic acid lipid nanoparticle composition,
wherein:
the first PEG lipid and the second PEG lipid are independently selected from
i) a compound of Formula (PL-II):

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
R3 is —ORO;
RO is hydrogen or unsubstituted alkyl;
r is an integer between 1 and 100;
R5 is optionally substituted C10-40 alkyl, optionally substituted C10-40 alkenyl, or optionally substituted C10-40 alkynyl; and optionally one or more methylene groups of R5 are replaced with optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, optionally substituted heteroarylene, N(RN), O, S, C(O), C(O)N(RN), —NRNC(O), NRNC(O)N(RN), C(O)O, OC(O), OC(O)O, OC(O)N(RN), NRNC(O)O, C(O)S, —SC(O), C(═NRN), C(═NRN)N(RN), NRNC(═NRN), NRNC(═NRN)N(RN), C(S), C(S)N(RN), —NRNC(S), NRNC(S)N(RN), S(O), OS(O), S(O)O, OS(O)O, OS(O)2, S(O)2O, OS(O)2O, —N(RN)S(O), S(O)N(RN), N(RN)S(O)N(RN), OS(O)N(RN), N(RN)S(O)O, S(O)2, N(RN)S(O)2, —S(O)2N(RN), N(RN)S(O)2N(RN), OS(O)2N(RN), or N(RN)S(O)2O; and
each instance of RN is independently hydrogen, optionally substituted alkyl, or a nitrogen protecting group, and
ii) a compound of Formula (PL-III):

OG Complex Work Unit Chemistry
wherein s is an integer between 1 and 100.