Granted Patent B2

US 12,496,335 · App. 18/338,612 · Granted Dec 16, 2025

Inventors: Benjamin Petsch (Tübingen, DE); Edith Jasny (Stuttgart, DE); Yves Girerd-Chambaz (Messimy, FR)

Assignees: CureVac SE; Sanofi Pasteur

A61K39/12A61K39/385A61K47/6455A61K47/646A61P31/14C07K14/005

Abstract

Claims (28)

1 . An artificial nucleic acid comprising at least one coding region encoding at least one polypeptide comprising Zika virus envelope protein (E), wherein the artificial nucleic acid is a mRNA comprising, in 5′ to 3′ direction, the following elements:

a) a 5′-CAP structure;

b) the at least one coding region comprising a modified nucleic acid sequence encoding the at least one polypeptide comprising Zika virus envelope protein (E), wherein the at least one polypeptide comprises an amino acid sequence at least 95% identical to any one of SEQ ID NOs: 540, 537, 545 or 549, wherein the at least one coding region comprises a nucleic acid sequence identical to the polypeptide coding region of any one of SEQ ID NOs: 3300, 3297, 5505, 5513 or 5517 or a sequence at least 80% identical to the polypeptide coding region of any one of SEQ ID NOs: 3300, 3297, 5505, 5513 or 5517;

c) a heterologous 3′-UTR element comprising a nucleic acid sequence; and

d) a poly (A) sequence comprising 10 to 200 adenosine nucleotides.

2 . The artificial nucleic acid according to claim 1 , wherein (b) the at least one coding region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 537, wherein the at least one coding region comprises a nucleic acid sequence identical to the polypeptide coding region of SEQ ID NO: 3297 or a sequence at least 80% identical to the polypeptide coding region of SEQ ID NO: 3297.

3 . The artificial nucleic acid of claim 1 , further comprising at least one heterologous 5′ untranslated region (UTR) element.

4 . The artificial nucleic acid of claim 3 , wherein the at least one heterologous 5′-UTR element comprises a nucleic acid sequence, which is derived from the 5′-UTR of a TOP gene.

5 . The artificial nucleic acid of claim 1 , wherein the artificial nucleic acid comprises at least one histone stem-loop.

6 . The artificial nucleic acid of claim 1 , wherein the at least one encoded polypeptide comprises at least one signal sequence.

7 . The artificial nucleic acid of claim 1 , wherein the G/C content of the at least one coding region is increased compared to the G/C content of a reference RNA encoding the at least one polypeptide.

8 . The artificial nucleic acid of claim 1 , wherein the at least one heterologous 3′-UTR element comprises a nucleic acid sequence derived from a 3′-UTR of a gene selected from the group consisting of an albumin gene, an α-globin gene, a β-globin gene, a tyrosine hydroxylase gene, a lipoxygenase gene, and a collagen alpha gene.

9 . The artificial nucleic acid of claim 1 , wherein the at least one polypeptide comprises a stem region of the Japanese encephalitis virus E protein.

10 . The artificial nucleic acid of claim 1 , wherein the modified nucleic acid sequence comprises a nucleotide with a base modification selected from pseudouridine or 1-methyl-pseudouridine.

11 . The artificial nucleic acid of claim 10 , wherein the modified nucleic acid sequence comprises a 1-methyl-pseudouridine.

12 . The artificial nucleic acid according to claim 1 , wherein (b) the at least one coding region comprises an amino acid sequence at least 95% identical to SEQ ID NO: 537, wherein the at least one coding region comprises a nucleic acid sequence identical to the polypeptide coding region of SEQ ID NO: 3297 or a sequence at least 85% identical to the polypeptide coding region of SEQ ID NO: 3297.

13 . The artificial nucleic acid according of claim 12 , wherein the at least one polypeptide comprises the amino acid sequence according to SEQ ID NO: 537.

14 . A composition comprising at least one artificial nucleic acid as defined by claim 1 and a pharmaceutically acceptable carrier.

15 . The composition according to claim 14 , wherein the at least one artificial nucleic acid is complexed at least partially with a cationic or polycationic compound and/or a polymeric carrier.

16 . The composition according to claim 15 , wherein the at least one artificial nucleic acid is complexed at least partially with a cationic compound.

17 . The composition according to claim 16 , wherein the cationic compound comprises a cationic lipid.

18 . A kit or kit of parts comprising the artificial nucleic acid according to claim 1 , optionally a liquid vehicle for solubilising, and optionally technical instructions providing information on administration and dosage of the components.

19 . A method of treating a subject with, or protecting a subject from, an infection with Zika virus or a disorder related to an infection with Zika virus comprising administering to said subject the artificial nucleic acid according to claim 1 .

20 . An artificial nucleic acid comprising at least one coding region encoding at least one polypeptide comprising Zika virus envelope protein (E), wherein the artificial nucleic acid is a mRNA comprising, in 5′ to 3′ direction, the following elements:

a) a 5′-CAP structure,

b) the at least one coding region comprising a modified nucleic acid sequence encoding the at least one polypeptide comprising Zika virus envelope protein (E), wherein the at least one polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 537, wherein the at least one coding region comprises a nucleic acid sequence identical to the polypeptide coding region of SEQ ID NO: 3297 or a sequence at least 95% identical to the polypeptide coding region of SEQ ID NO: 3297,

c) a heterologous 3′-UTR element comprising a nucleic acid sequence, and

d) a poly (A) sequence comprising 10 to 200 adenosine nucleotides.

Priority Claims (1)

Continuity (2)

References Cited (165)