US 12,453,739 B2
Synergistic enhancement of the delivery of nucleic acids via blended formulations
Frank DeRosa, Lexington, MA (US); Lianne Smith, Lexington, MA (US); Michael Heartlein, Lexington, MA (US); and Braydon Charles Guild, Lexington, MA (US)
Assigned to TRANSLATE BIO, INC., Waltham, MA (US)
Filed by Translate Bio, Inc., Lexington, MA (US)
Filed on Mar. 31, 2020, as Appl. No. 16/836,513.
Application 16/836,513 is a division of application No. 16/157,050, filed on Oct. 10, 2018, granted, now 10,646,504.
Application 16/157,050 is a continuation of application No. 14/775,818, granted, now 10,130,649, issued on Nov. 20, 2018, previously published as PCT/US2014/028498, filed on Mar. 14, 2014.
Claims priority of provisional application 61/789,375, filed on Mar. 15, 2013.
Prior Publication US 2020/0390797 A1, Dec. 17, 2020
Int. Cl. A61K 31/7105 (2006.01); A61K 9/00 (2006.01); A61K 9/1271 (2025.01); A61K 9/1272 (2025.01); A61K 9/14 (2006.01); A61K 48/00 (2006.01)
CPC A61K 31/7105 (2013.01) [A61K 9/1271 (2013.01); A61K 9/1272 (2013.01); A61K 9/145 (2013.01); A61K 9/146 (2013.01); A61K 48/0025 (2013.01); A61K 48/0033 (2013.01); A61K 9/0019 (2013.01); A61K 9/0085 (2013.01)] 20 Claims
OG exemplary drawing
 
1. A pharmaceutical composition for delivery of messenger RNA (mRNA) to a cell, wherein the composition is a single pharmaceutical composition comprising a blend of at least a first lipid nanoparticle and a second separately formed, non-identical lipid nanoparticle,
wherein each lipid nanoparticle comprises one or more PEG-modified lipids,
wherein the first lipid nanoparticle comprises a first cationic lipid and the second lipid nanoparticle comprises a second cationic lipid;
wherein the first cationic lipid and the second cationic lipid are non-identical;
wherein the first lipid nanoparticle encapsulates a first mRNA and the second lipid nanoparticle encapsulates a second mRNA;
wherein the first lipid nanoparticle and the second lipid nanoparticle in the pharmaceutical composition are in a ratio of at least about 2:1 based on the mass of the encapsulated mRNAs; and
wherein expression of a protein or a peptide encoded by the first mRNA or the second mRNA following the delivery of the pharmaceutical composition to the cell exceeds the expression of the protein or the peptide encoded by the first mRNA or the second mRNA administered with the first lipid nanoparticle or the second lipid nanoparticle respectively, but without the other lipid nanoparticle by at least about two-fold, and
wherein the amount of the mRNA required to effectuate a therapeutic effect following the delivery of the pharmaceutical composition to the cell is reduced by at least about two-fold relative to the amount of mRNA required to effectuate a therapeutic effect following the delivery of the first mRNA or the second mRNA administered with the first lipid nanoparticle or the second lipid nanoparticle respectively, but without the other lipid nanoparticle.