US 12,329,811 B2
Seasonal RNA influenza virus vaccines
Raffael Nachbagauer, Cambridge, MA (US); Carole Henry, Cambridge, MA (US); and Patricia Jorquera, Cambridge, MA (US)
Assigned to ModernaTX, Inc., Cambridge, MA (US)
Filed by ModernaTX, Inc., Cambridge, MA (US)
Filed on Jan. 10, 2022, as Appl. No. 17/572,465.
Claims priority of provisional application 63/249,291, filed on Sep. 28, 2021.
Claims priority of provisional application 63/210,409, filed on Jun. 14, 2021.
Claims priority of provisional application 63/174,437, filed on Apr. 13, 2021.
Claims priority of provisional application 63/136,126, filed on Jan. 11, 2021.
Prior Publication US 2023/0000970 A1, Jan. 5, 2023
Int. Cl. A61K 39/145 (2006.01); A61P 31/16 (2006.01); A61K 39/00 (2006.01)
CPC A61K 39/145 (2013.01) [A61P 31/16 (2018.01); A61K 2039/53 (2013.01); A61K 2039/6018 (2013.01)] 24 Claims
 
1. A composition comprising:
(a) a first messenger ribonucleic acid (mRNA) comprising a first open reading frame (ORF) encoding a first hemagglutinin (HA) protein of a first influenza A virus;
(b) a second mRNA comprising a second ORF encoding a second HA protein of a second influenza A virus;
wherein the first and second influenza A viruses are of different subtypes,
(c) a third mRNA comprising a third ORF encoding a third HA protein of a first influenza B virus;
(d) a fourth mRNA comprising a fourth ORF encoding a first neuraminidase (NA) protein of the first influenza A virus;
(e) a fifth mRNA comprising a fifth ORF encoding a second NA protein of the second influenza A virus; and
(f) a sixth mRNA comprising a sixth ORF encoding a third NA protein of the first influenza B virus,
wherein the first mRNA, second mRNA, third mRNA, fourth mRNA, fifth mRNA, and sixth mRNA are in the lipid nanoparticle,
wherein each ORF comprises nucleosides consisting of N1-methylpseudouridine, adenosine, guanosine, and cytidine,
wherein the first mRNA, second mRNA, third mRNA, fourth mRNA, fifth mRNA, and sixth mRNA are at a 1:1:1:1:1:1 mass ratio,
wherein the lipid nanoparticle comprises an ionizable amino lipid, a sterol, a neutral lipid, and a polyethylene glycol (PEG)-modified lipid,
wherein the ionizable amino lipid comprises a compound of Formula (I):

OG Complex Work Unit Chemistry
or a salt thereof, wherein:
R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, and —R″M′R′;
R2 and R3 are independently selected from the group consisting of C1-14 alkyl and C2-14 alkenyl;
R4 is —(CH2)nQ, wherein Q is —OR, and n is selected from 1, 2, 3, 4, and 5;
each R5 is H;
each R6 is H;
M and M′ are independently selected from —C(O)O— and —OC(O)—;
R7 is H;
R is H;
R′ is selected from the group consisting of C1-18 alkyl and C2-18 alkenyl;
R″ is selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.