Cancer vaccines

Patent metadata

Field	Value
Publication number	US-12582609-B2
Application number	US-201615769710-A
Country	US
Kind code	B2
Filing date	Oct 21, 2016
Priority date	Oct 22, 2015
Publication date	Mar 24, 2026
Grant date	Mar 24, 2026

Abstract

The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

First claim

What is claimed is:

1 . A personalized cancer vaccine for treating a cancer in a subject, comprising:
a messenger ribonucleic acid (mRNA) having an open reading frame (ORF) encoding 5-100 peptide epitopes arranged in a head to tail formation, and a lipid nanoparticle, wherein the lipid nanoparticle comprises 5-25 mol % non-cationic lipid, 25-55 mol % sterol, 0.5-15 mol % polyethylene glycol (PEG)-modified lipid, and 20-60 mol % of a compound of Formula (I):

or a salt thereof, wherein:
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,
wherein:
(i) at least one of the peptide epitopes is a major histocompatibility complex (MHC) class I epitope and at least one of the peptide epitopes is an MHC class II epitope, and
(ii) the mRNA comprises N1-methylpseudouridine.

2 . The personalized cancer vaccine of claim 1 , wherein at least two of the peptide epitopes are linked directly to one another without a linker.

3 . The personalized cancer vaccine of claim 2 , wherein a first peptide epitope is linked at its N-terminus directly to a C-terminus of a second peptide epitope without a linker, and wherein a junction formed by 2-10 amino acids of the N-terminus of the first peptide epitope linked to 2-10 amino acids of the C-terminus of the second peptide epitope does not form an immunogenic peptide.

4 . The personalized cancer vaccine of claim 1 , wherein the compound of Formula (I) comprises a structure of Formula (IA):

or a salt thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; and M 1 is M′.

5 . The personalized cancer vaccine of claim 1 , wherein the compound of Formula (I) comprises a structure of Formula (II):

or a salt thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; and M 1 is M′.

6 . The personalized cancer vaccine of claim 1 , wherein the compound of Formula (I) comprises a structure of Formula (IIa), (IIb), (IIc), or (IIe):

or a salt thereof.

7 . The personalized cancer vaccine of claim 1 , wherein the non-cationic lipid is selected from the group consisting of disteroylphosphatidyl choline (DSPC), 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC), dipalmitoylphosphatidylcholine (DPPC), dioleoyl phosphatidylethanolamine (DOPE) and sphingomyelin (SM).

8 . The personalized cancer vaccine of claim 1 , wherein the PEG-modified lipid is selected from the group consisting of PEG-c-DOMG (R-3-[(ω-methoxy-poly(ethyleneglycol)2000) carbamoyl)]-1,2-dimyristyloxypropyl-3-amine), PEG-DSG (1,2-distearoyl-sn-glycerol, methoxypolyethylene glycol), PEG-DMG (polyethylene glycol-1,2-dimyristoyl-sn-glycerol), PEG-DPG (1,2-dipalmitoyl-sn-glycerol, methoxypolyethylene glycol), and PEG-CDMA (poly(ethyleneglycol)-carbamoyl-1,2-dimyristyloxypropylamine).

9 . The personalized cancer vaccine of claim 1 , wherein the sterol is cholesterol.

10 . The personalized cancer vaccine of claim 1 , wherein the compound of Formula (I) is

11 . The personalized cancer vaccine of claim 1 , wherein the mRNA further comprises a 5′ untranslated region (5′-UTR), a 3′ untranslated region (3′-UTR), a 5′ cap, and a poly-A tail.

12 . The personalized cancer vaccine of claim 1 , wherein the mRNA further comprises at least one chemical modification selected from the group consisting of pseudouridine, N1-ethylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 2-thio-1-methy 1-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methyluridine, 5-methoxyuridine and 2′-O-methyl uridine.

13 . The personalized cancer vaccine of claim 1 , wherein the mRNA is fully modified with N1-methylpseudouridine.

14 . A personalized cancer vaccine for treating a cancer in a subject, comprising:
a messenger ribonucleic acid (mRNA) having an open reading frame (ORF) encoding 5-50 peptide epitopes arranged in a head to tail formation, and a lipid nanoparticle, wherein the lipid nanoparticle comprises 5-25 mol % non-cationic lipid, 25-55 mol % sterol, 0.5-15 mol % PEG-modified lipid, and 20-60 mol % compound of Formula (I):

or a salt thereof, wherein:
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,
wherein:
(i) at least one of the peptide epitopes is an MHC class I epitope and at least one of the peptide epitopes is an MHC class II epitope, and
(ii) the mRNA comprises N1-methylpseudouridine.

15 . The personalized cancer vaccine of claim 14 , wherein at least two of the peptide epitopes are linked directly to one another without a linker.

16 . The personalized cancer vaccine of claim 15 , wherein a first peptide epitope is linked at its N-terminus directly to a C-terminus of a second peptide epitope without a linker, and wherein a junction is formed between 2-10 amino acids of the N-terminus of the first peptide epitope linked to 2-10 amino acids of the C-terminus of the second peptide epitope does not form an immunogenic peptide.

17 . The personalized cancer vaccine of claim 14 , wherein the compound of Formula (I) comprises a structure of Formula (IA):

or a salt thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; m is selected from 5, 6, 7, 8, and 9; and M 1 is M′.

18 . The personalized cancer vaccine of claim 14 , wherein the compound of Formula (I) comprises a structure of Formula (II):

or a salt thereof, wherein 1 is selected from 1, 2, 3, 4, and 5; and M 1 is M′.

Assignees

• Modernatx Inc

Inventors

• Valiante Nicholas
• Zaks Tal
• Huang Eric Yi-Chun

Classifications

• A61K2039/55588

  Adjuvants of undefined constitution · CPC title

• A61K9/10

  Dispersions; Emulsions · CPC title

• A61K39/001114

  CD74, Ii, MHC class II invariant chain or MHC class II gamma chain · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K39/0011 Primary

  Cancer antigens · CPC title