Nucleic acid molecules and uses thereof

Patent metadata

Field	Value
Publication number	US-12514918-B2
Application number	US-202519204075-A
Country	US
Kind code	B2
Filing date	May 9, 2025
Priority date	May 4, 2016
Publication date	Jan 6, 2026
Grant date	Jan 6, 2026

Abstract

The present invention is directed to an artificial nucleic acid and to polypeptides suitable for use in treatment or prophylaxis of an infection with Norovirus or a disorder related to such an infection. In particular, the present invention concerns a Norovirus vaccine. The present invention is directed to an artificial nucleic acid, polypeptides, compositions and vaccines comprising the artificial nucleic acid or the polypeptides. The invention further concerns a method of treating or preventing a disorder or a disease, first and second medical uses of the artificial nucleic acid, polypeptides, compositions and vaccines. Further, the invention is directed to a kit, particularly to a kit of parts, comprising the artificial nucleic acid, polypeptides, compositions and vaccines.

First claim

The invention claimed is:

1 . A pharmaceutical composition comprising artificial RNA molecules, said artificial RNA molecules comprising at least three different coding regions each encoding a different Norovirus VP1 polypeptide, at least one of said coding regions having at least 85% identity to the RNA sequence of SEQ ID NO: 9444; 13854; 18264; 22674; 27084; 31494; or 35904 and encoding a polypeptide at least 95% identical to SEQ ID NO: 624,
wherein the artificial RNA molecules each comprise: (i) a 5′ Cap structure; (ii) a poly(A) sequence of 10 to 200 consecutive adenosine nucleotides; and (iii) at least one heterologous 5′ and/or 3′ untranslated region (UTR), wherein the at least three different coding regions encode at least one GII.4 VP1 polypeptide and at least one GI VP1 polypeptide, wherein said artificial RNA molecules are complexed with a cationic or polycationic compound.

2 . The pharmaceutical composition of claim 1 , wherein at least one of the coding regions has at least 90% identity to the RNA sequence of SEQ ID NO: 9444; 13854; 18264; 22674; 27084; 31494; or 35904.

3 . The pharmaceutical composition of claim 2 , wherein the artificial RNA molecules are mRNA molecules.

4 . The pharmaceutical composition of claim 1 , wherein said three different coding regions are each encoded on a separate artificial RNA molecule.

5 . The pharmaceutical composition of claim 4 , wherein said artificial RNA molecules are complexed with lipid nanoparticles (LNPs).

6 . The pharmaceutical composition of claim 5 , wherein the LNPs comprise a cationic lipid, a phospholipid, cholesterol and a PEG-lipid.

7 . The pharmaceutical composition of claim 6 , wherein the LNPs comprise a cationic lipid, DSPC, cholesterol and PEG-lipid.

8 . The pharmaceutical composition of claim 6 , wherein the artificial RNA molecules each comprise a heterologous 5′ and 3′ UTR.

9 . The pharmaceutical composition of claim 8 , wherein the 5′ Cap structure of each of the artificial RNA molecules is a Cap1 structure.

10 . The pharmaceutical composition of claim 8 , wherein the artificial RNA molecules comprise a modified nucleobase moiety.

11 . The pharmaceutical composition of claim 10 , wherein the modified nucleobase moiety is pseudouridine or 1-methyl-pseudouridine.

12 . The pharmaceutical composition of claim 11 , wherein the modified nucleobase moiety is 1-methyl-pseudouridine.

13 . The pharmaceutical composition of claim 12 , wherein at least one of the coding regions has at least 90% identity to the RNA sequence of SEQ ID NO: 22674.

14 . The pharmaceutical composition of claim 13 , wherein at least one of the coding regions encodes a polypeptide at least 98% identical to SEQ ID NO: 624.

15 . The pharmaceutical composition of claim 4 , wherein each of said at least three different coding regions comprises a secretion signal sequence.

16 . The pharmaceutical composition of claim 1 , wherein the at least three different RNA coding regions encode at least two GII VP1 polypeptides and at least one GI VP1 polypeptide.

17 . The pharmaceutical composition of claim 16 , comprising at least four different coding regions each encoding a different Norovirus VP1 polypeptide.

18 . The pharmaceutical composition of claim 17 , comprising at least five different coding regions each encoding a different Norovirus VP1 polypeptide.

19 . A method of stimulating an immune response in a mammalian subject comprising administering to the subject the pharmaceutical composition of claim 1 .

20 . The method of claim 19 , wherein the composition is administered by intramuscular or intradermal injection.

21 . The method of claim 20 , wherein said artificial RNA molecules are complexed with lipid nanoparticles (LNPs).

22 . The method of claim 21 , wherein the composition is administered by intramuscular injection.

23 . The method of claim 21 , wherein the method stimulates functional Norovirus blocking antibodies in the subject as measured by Histo-Blood Group Antigen (HBGA) blocking assay.

24 . The method of claim 21 , wherein the method stimulates a Norovirus specific CD8+ T-cell response in the subject.

25 . A method of stimulating an anti-Norovirus immune response in a mammalian subject comprising administering to the subject a pharmaceutical composition comprising at least three different artificial mRNA molecules, said at least three different artificial mRNA molecules comprising at least three different coding regions each encoding a different Norovirus VP1 polypeptide,
wherein the artificial mRNA molecules each comprise, from 5′ to 3′: (i) a 5′ Cap structure; (ii) a heterologous 5′ untranslated region (UTR); (iii) the coding region encoding the Norovirus VP1 polypeptide; (iv) a heterologous 3′ UTR; and (v) a poly(A) sequence of 10 to 200 consecutive adenosine nucleotides, wherein the at least three different coding regions encode at least one GII.4 VP1 polypeptide and at least one GI VP1 polypeptide, wherein said GII.4 VP1 polypeptide is at least 95% identical to the polypeptide sequence of SEQ ID NO: 624 and wherein said GII.4 VP1 polypeptide is encoded by a RNA sequence at least 85% identical to the RNA sequence of SEQ ID NO: 22674, wherein said artificial mRNA molecules are complexed with a cationic or polycationic compound, wherein the composition is administered by intramuscular or intradermal injection, and wherein the method stimulates production of anti-Norovirus antibodies in the subject to each of the Norovirus VP1 polypeptides encoded by the artificial mRNA molecules.

26 . The method of claim 25 , wherein the composition is administered by intramuscular injection.

27 . The method of claim 25 , wherein the method stimulates functional Norovirus blocking antibodies as measured by Histo-Blood Group Antigen (HBGA) blocking assay.

28 . The method of claim 25 , wherein the method stimulates a Norovirus specific CD8+ T-cell response in the subject.

29 . The method of claim 25 , wherein the artificial RNA molecules are complexed with lipid nanoparticles (LNPs).

30 . The method of claim 29 , wherein the LNPs comprise a cationic lipid, a phospholipid, cholesterol and a PEG-lipid.

31 . A pharmaceutical composition comprising at least three different artificial mRNA molecules, said at least three different artificial mRNA molecules comprising at least three different coding regions each encoding a different Norovirus VP1 polypeptide,
wherein the artificial mRNA molecules each comprise, from 5′ to 3′: (i) a 5′ Cap structure; (ii) a heterologous 5′ untranslated region (UTR); (iii) a coding region encoding a Norovirus VP1 polypeptide; (iv) a heterologous 3′ UTR; and (v) a poly(A) sequence of 10 to 200 consecutive adenosine nucleotides, wherein the at least three different artificial mRNA molecules each encode a different Norovirus VP1 polypeptide, wherein the at least three different artificial mRNA molecules encode at least one GII.4 VP1 polypeptide and at least one GI VP1 polypeptide, wherein said GII.4 VP1 polypeptide is at least 95% identical to the polypeptide sequence of SEQ ID NO: 624 and wherein said GII.4 VP1 polypeptide is encoded by a RNA sequence at least 85% identical to the RNA sequence of SEQ ID NO: 22674, wherein the artificial mRNA molecules optionally comprise a modified nuc

Assignees

• CureVac SE

Inventors

• Rauch Susanne
• Schwendt Kim Ellen
• Petsch Benjamin

Classifications

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• A61K2039/5258

  Virus-like particles · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P31/12

  Antivirals · CPC title

• C12N2770/16034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title