US 12,280,117 B2
Lipid nanoparticle formulations for delivery of MRNA
Frank DeRosa, Lexington, MA (US); Michael Heartlein, Lexington, MA (US); and Shrirang Karve, Lexington, MA (US)
Assigned to TRANSLATE BIO, INC., Waltham, MA (US)
Filed by Translate Bio, Inc., Lexington, MA (US)
Filed on Apr. 23, 2021, as Appl. No. 17/239,131.
Application 17/239,131 is a division of application No. 16/599,928, filed on Oct. 11, 2019, granted, now 11,013,812.
Application 16/599,928 is a division of application No. 15/809,605, filed on Nov. 10, 2017, granted, now 10,471,153, issued on Nov. 12, 2019.
Claims priority of provisional application 62/420,421, filed on Nov. 10, 2016.
Claims priority of provisional application 62/420,428, filed on Nov. 10, 2016.
Claims priority of provisional application 62/421,021, filed on Nov. 11, 2016.
Claims priority of provisional application 62/421,007, filed on Nov. 11, 2016.
Claims priority of provisional application 62/464,327, filed on Feb. 27, 2017.
Claims priority of provisional application 62/464,330, filed on Feb. 27, 2017.
Prior Publication US 2021/0353761 A1, Nov. 18, 2021
Int. Cl. A61K 47/54 (2017.01); A61K 9/00 (2006.01); A61K 9/127 (2006.01); A61K 9/1272 (2025.01); A61K 38/17 (2006.01); A61K 47/28 (2006.01); A61K 47/60 (2017.01); A61K 47/69 (2017.01); A61K 48/00 (2006.01); A61P 11/12 (2006.01)
CPC A61K 47/554 (2017.08) [A61K 9/0078 (2013.01); A61K 9/1272 (2013.01); A61K 38/1709 (2013.01); A61K 47/28 (2013.01); A61K 47/543 (2017.08); A61K 47/60 (2017.08); A61K 47/6911 (2017.08); A61K 48/0008 (2013.01); A61K 48/0033 (2013.01); A61K 48/0041 (2013.01); A61K 48/0066 (2013.01); A61K 48/0075 (2013.01); A61P 11/12 (2018.01)] 17 Claims
 
1. A method of delivering messenger RNAs (mRNAs) encoding a protein or a peptide in vivo comprising administering by pulmonary delivery to a subject in need of delivery a composition comprising:
the mRNAs; and
lipid nanoparticles encapsulating the mRNAs, wherein each individual lipid nanoparticle comprises no more than three distinct lipid components, wherein the three lipid components are a non-cationic lipid, a PEG-modified lipid, and a sterol-based cationic lipid, wherein the sterol-based cationic lipid has a structure according to Formula (A),
B-L1-S  (Formula A),
or a protonated form thereof, wherein:
B is a basic functional group selected from
dialkylamino and guanidine;
L1 is an optionally substituted linker group; and
S is a sterol.
 
8. A composition comprising:
messenger RNAs (mRNAs) encoding a protein or a peptide; and
lipid nanoparticles encapsulating the mRNAs, wherein each individual lipid nanoparticle comprises no more than three distinct lipid components, wherein the three lipid components are a non-cationic lipid, a PEG-modified lipid, and a sterol-based cationic lipid, wherein the sterol-based cationic lipid has a structure according to Formula (A),
B-L1-S  (Formula A),
or a protonated form thereof, wherein:
B is a basic functional group selected from
dialkylamino and guanidine;
L1 is an optionally substituted linker group; and
S is a sterol, and
further wherein the lipid nanoparticles have an encapsulation percentage for mRNAs of at least 70%.