Granted Patent B2

US 12,453,766 · App. 18/418,127 · Granted Oct 28, 2025

Inventors: Giuseppe Ciaramella (Sudbury, MA); Kapil Bahl (Medford, MA); Amy Espeseth (Chalfont, PA); Andrew J. Bett (Lansdale, PA); Pedro Cejas (Oreland, PA); Lan Zhang (Chalfont, PA); Christine Shaw (Reading, MA)

Assignee: ModernaTX, Inc.

A61K39/12A61K9/0019A61K2039/53A61K2039/55555

Abstract

Claims (40)

1 . A messenger ribonucleic acid (mRNA) comprising an open reading frame (ORF) encoding a prefusion respiratory syncytial virus (RSV) F protein, wherein the ORF encodes an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 5, wherein identity defines the percentage of amino acid residues in the RSV F protein that are identical to residues of SEQ ID NO: 5 after introducing any necessary gaps to align the two full-length sequences.

2 . The mRNA of claim 1 , wherein the mRNA is chemically modified.

3 . The mRNA of claim 2 , wherein the ORF comprises 1-methyl-pseudouridine, adenosine, guanosine, and cytosine.

4 . A vaccine comprising the mRNA of claim 3 formulated in a lipid nanoparticle.

5 . The vaccine of claim 4 , wherein the lipid nanoparticle comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % sterol, and 0.5-15 mol % polyethylene glycol (PEG)-modified lipid.

6 . The vaccine of claim 5 , wherein the ionizable cationic lipid is a compound of Formula (I):

R 1 is selected from the group consisting of C 5-30 alkyl, C 5-20 alkenyl, and —R″M′R′;

R 2 and R 3 are independently selected from the group consisting of C 1-14 alkyl and C 2-14 alkenyl;

R 4 is-(CH 2 ) n Q, wherein Q is —OR, and n is selected from 1, 2, 3, 4, and 5;

each R 5 is H;

each R 6 is H;

M and M′ are independently selected from —C(O)O— and —OC(O)—;

R 7 is H;

R is H;

R′ is selected from the group consisting of C 1-18 alkyl and C 2-18 alkenyl;

R″ is selected from the group consisting of C 3-14 alkyl and C 3-14 alkenyl; and

m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.

7 . The vaccine of claim 6 , wherein:

R 1 is R″M′R′;

R 2 and R 3 are each independently C 1-14 alkyl;

R 4 is (CH 2 ),Q, wherein Q is OH and n is 4;

M and M′ are each independently —OC(O)—;

R 5 , R 6 , and R 7 are each H;

R′ is C 1-12 alkyl substituted with C 6-9 alkyl;

R″ is C 3-14 alkyl; and

m is 6.

8 . The vaccine of claim 6 , wherein:

R 1 is C 5-20 alkenyl;

R 2 and R 3 are each independently C 1-14 alkyl;

R 4 is (CH 2 ) n Q, wherein Q is OH and n is 3;

M is-C(O)O—;

R 5 , R 6 , and R 7 are each H; and

m is 6.

9 . The vaccine of claim 6 , wherein the compound of Formula (I) comprises a compound of Formula (IId),

or a salt thereof, wherein n is 2, 3, or 4.

10 . The vaccine of claim 6 , wherein the compound of Formula (I) is Compound 1:

11 . The vaccine of claim 6 , wherein the neutral lipid is 1,2 distearoyl-sn-glycero-3-phosphocholine (DSPC) and the PEG-modified lipid is 1,2 dimyristoyl-sn-glycerol, methoxypolyethyleneglycol (PEG2000 DMG).

12 . A method comprising administering to a subject the vaccine of claim 11 in a therapeutically effective amount to induce in the subject an RSV F protein neutralizing antibody titer.

13 . A method comprising administering to a subject the vaccine of claim 4 in a therapeutically effective amount to induce in the subject an RSV F protein neutralizing antibody titer.

14 . The method of claim 13 , wherein the mRNA is administered intramuscularly.

Assignments (4)

Continuity (3)

References Cited (400)