US 12,133,923 B2
Lipid nanoparticle compositions and uses thereof
Mirko Hennig, Mountain View, CA (US); Ali Ahmed Alfaifi, Redwood City, CA (US); Sakya Sing Mohapatra, Sunnyvale, CA (US); Daniella Ishimaru, Mountain View, CA (US); Vladimir Grigor'evich Kharitonov, San Diego, CA (US); Julia Jung-un Baek, San Jose, CA (US); Shuang Li, Belmont, CA (US); David J. Lockhart, Redwood City, CA (US); Brandon A. Wustman, San Diego, CA (US); Yufeng Wang, Mountain View, CA (US); and Joseph S. Cefalu, Menlo Park, CA (US)
Assigned to ReCode Therapeutics, Inc., Menlo Park, CA (US)
Filed by ReCode Therapeutics, Inc., Menlo Park, CA (US)
Filed on Jan. 16, 2024, as Appl. No. 18/413,653.
Application 18/413,653 is a continuation of application No. PCT/US2023/082205, filed on Dec. 1, 2023.
Claims priority of provisional application 63/431,166, filed on Dec. 8, 2022.
Claims priority of provisional application 63/485,863, filed on Feb. 17, 2023.
Prior Publication US 2024/0216290 A1, Jul. 4, 2024
Int. Cl. A61K 9/51 (2006.01); A61K 8/86 (2006.01); A61K 9/00 (2006.01); A61K 31/7105 (2006.01); A61K 47/14 (2017.01); A61K 47/18 (2017.01); A61K 47/22 (2006.01); A61K 47/24 (2006.01); A61K 47/28 (2006.01); A61K 48/00 (2006.01); C07C 69/708 (2006.01); C07C 223/02 (2006.01); C07C 321/14 (2006.01); C07D 317/32 (2006.01)
CPC A61K 9/5123 (2013.01) [A61K 9/0078 (2013.01); A61K 48/0033 (2013.01)] 25 Claims
 
1. A method for delivering lipid nanoparticles (LNPs) to the lungs of a subject suffering from or at risk for primary ciliary dyskinesia (PCD), wherein the method comprises nebulizing a liquid pharmaceutical composition to generate an aerosolized pharmaceutical composition, and administering the aerosolized pharmaceutical composition to the subject,
wherein the liquid pharmaceutical composition comprises lipid nanoparticles (LNPs) having:
(a) mRNA integrity of between 75% and 99%, and
(b) a diameter between 20 nm and 600 nm,
wherein the LNPs comprise an ionizable lipid, a phospholipid, a PEG-lipid, and a sterol,
wherein the LNPs comprise mRNA encoding a dynein axonemal intermediate chain 1 (DNAI1) protein,
wherein the aerosolized pharmaceutical composition comprises aerosol particles having:
(a) a mass median aerodynamic diameter (MMAD) between 1 μm and 10 μm,
(b) a geometric standard deviation (GSD) between 1 and 5, and
(c) a fine particle fraction (FPF) percent of at least 50%, and
wherein the aerosolized particles are selectively delivered to the tracheobronchial region of the lung of the subject.