US 12,268,754 B2
Composition and methods for treatment of ornithine transcarbamylase deficiency
Kim Askew, Lexington, MA (US); Jou-Ku Chung, Lexington, MA (US); Frank DeRosa, Lexington, MA (US); Michael Heartlein, Lexington, MA (US); Shrirang Karve, Lexington, MA (US); Thomas McCauley, Lexington, MA (US); Lianne Smith, Lexington, MA (US); and Ann J. Barbier, Lexington, MA (US)
Assigned to TRANSLATE BIO, INC., Waltham, MA (US)
Filed by Translate Bio, Inc., Lexington, MA (US)
Filed on Sep. 27, 2021, as Appl. No. 17/448,996.
Application 17/448,996 is a division of application No. 16/228,596, filed on Dec. 20, 2018, granted, now 11,167,043.
Claims priority of provisional application 62/608,547, filed on Dec. 20, 2017.
Prior Publication US 2022/0072152 A1, Mar. 10, 2022
Int. Cl. A61K 48/00 (2006.01); A61K 9/00 (2006.01); A61K 9/127 (2006.01); A61K 9/1272 (2025.01); A61K 38/45 (2006.01); A61K 47/69 (2017.01); A61P 3/00 (2006.01); C12N 15/52 (2006.01); C12N 15/85 (2006.01)
CPC A61K 48/005 (2013.01) [A61K 9/0019 (2013.01); A61K 9/1272 (2013.01); A61K 38/45 (2013.01); A61K 47/6929 (2017.08); A61K 48/0025 (2013.01); A61K 48/0075 (2013.01); A61K 48/0083 (2013.01); A61P 3/00 (2018.01); C12N 15/52 (2013.01); C12N 15/85 (2013.01); C12Y 201/03003 (2013.01)] 18 Claims
 
1. A method of treating ornithine transcarbamylase (OTC) deficiency in a human, comprising administering to a human in need of treatment a pharmaceutical composition comprising an mRNA encoding an ornithine transcarbamylase protein formulated in a lipid nanoparticle,
wherein the mRNA encoding the ornithine transcarbamylase protein is administered at a therapeutic low dose of 0.5 mg/kg or less of mRNA at a dosing interval of once every two weeks or a longer dosing internal for a period sufficient to treat at least one symptom or reduce the level of a biomarker associated with ornithine transcarbamylase deficiency in the human relative to a control.