US 12,133,924 B2
Compositions and methods for organ specific delivery of nucleic acids
Qiang Cheng, Dallas, TX (US); Tuo Wei, Dallas, TX (US); and Daniel J. Siegwart, Dallas, TX (US)
Assigned to The Board of Regents of The University of Texas System, Austin, TX (US)
Filed by The Board of Regents of The University of Texas System, Austin, TX (US)
Filed on Dec. 11, 2023, as Appl. No. 18/534,974.
Application 18/534,974 is a continuation of application No. 18/529,992, filed on Dec. 5, 2023.
Application 18/529,992 is a continuation of application No. 18/186,105, filed on Mar. 17, 2023, abandoned.
Application 18/186,105 is a continuation of application No. 17/929,704, filed on Sep. 4, 2022, granted, now 11,648,210, issued on May 16, 2023.
Application 17/929,704 is a continuation of application No. 17/711,911, filed on Apr. 1, 2022, granted, now 11,510,880, issued on Nov. 29, 2022.
Application 17/711,911 is a continuation of application No. 17/572,615, filed on Jan. 10, 2022, granted, now 11,590,085, issued on Feb. 28, 2023.
Application 17/572,615 is a continuation of application No. 17/473,863, filed on Sep. 13, 2021, granted, now 11,304,911, issued on Apr. 19, 2022.
Application 17/473,863 is a continuation of application No. 17/191,895, filed on Mar. 4, 2021, granted, now 11,229,609, issued on Jan. 25, 2022.
Application 17/191,895 is a continuation of application No. PCT/US2019/049565, filed on Sep. 4, 2019.
Claims priority of provisional application 62/726,741, filed on Sep. 4, 2018.
Prior Publication US 2024/0148666 A1, May 9, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07H 21/02 (2006.01); A61K 9/51 (2006.01); A61K 48/00 (2006.01); C12N 9/22 (2006.01); C12N 15/11 (2006.01); C12N 15/113 (2010.01)
CPC A61K 9/5123 (2013.01) [A61K 48/0033 (2013.01); C12N 9/22 (2013.01); C12N 15/11 (2013.01); C12N 15/111 (2013.01); C12N 15/113 (2013.01); C12N 2310/11 (2013.01); C12N 2310/14 (2013.01); C12N 2310/20 (2017.05); C12N 2320/32 (2013.01)] 21 Claims
 
1. A composition comprising a messenger ribonucleic acid (mRNA) with a lipid composition, wherein said mRNA comprises an open reading frame encoding a cystic fibrosis transmembrane regulator (CFTR) protein, wherein said lipid composition comprises:
i. a zwitterionic selective organ targeting (SORT) lipid at a molar percentage from about 5% to about 50%;
ii. an ionizable cationic lipid at a molar percentage of at least about 5%, wherein the ionizable cationic lipid comprises an ammonium group that is positively charged at a pH from about 6 to about 8 and at least two C6-C24 alkyl or alkenyl groups;
iii. a steroid or steroid derivative at a molar percentage from about 15% to about 46%; and
iv. a polymer-conjugated lipid at a molar percentage from about 0.5% to about 10%;
wherein said molar percentage is determined based on the total lipids present in said lipid composition; wherein said composition is formulated for inhalation for delivery to a lung.