Rabies vaccine

Patent metadata

Field	Value
Publication number	US-12083190-B2
Application number	US-202217746844-A
Country	US
Kind code	B2
Filing date	May 17, 2022
Priority date	Aug 21, 2013
Publication date	Sep 10, 2024
Grant date	Sep 10, 2024

Abstract

The present invention relates to an mRNA sequence, comprising a coding region, encoding at least one antigenic peptide or protein of Rabies virus or a fragment, variant or derivative thereof. Additionally the present invention relates to a composition comprising a plurality of mRNA sequences comprising a coding region, encoding at least one antigenic peptide or protein of Rabies virus or a fragment, variant or derivative thereof.
Furthermore it also discloses the use of the mRNA sequence or the composition comprising a plurality of mRNA sequences for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the prophylaxis or treatment of Rabies virus infections. The present invention further describes a method of treatment or prophylaxis of rabies using the mRNA sequence.

First claim

The invention claimed is:

1. A method of stimulating a protective immune response to rabies virus in a subject comprising administering to the subject a pharmaceutical composition comprising a purified mRNA molecule, said mRNA comprising:
(a) a 5′ Cap;
(b) an open reading frame (ORF) encoding a Rabies virus glycoprotein (RAV-G), wherein the ORF comprises a sequence having at least about 95% identity to the protein coding region of SEQ ID NO: 24; and
(c) a Poly(A) sequence,

wherein the composition is administered by injection.

2. The method of claim 1 , wherein the composition is administered by intramuscular or intradermal injection.

3. The method of claim 2 , wherein the composition is administered by intramuscular injection.

4. The method of claim 1 , wherein the 5′ Cap is a m7GpppN Cap.

5. The method of claim 1 , wherein the mRNA comprises, from 5′ to 3′:
(a) a 5′ Cap;
(b) an open reading frame (ORF) encoding a Rabies virus glycoprotein (RAV-G); and
(c) a 3′ untranslated region (UTR), including the Poly(A) sequence.

6. The method of claim 5 , wherein the Poly(A) sequence comprises 50 to 250 adenosine nucleotides.

7. The method of claim 6 , wherein the mRNA further comprises a 5′ UTR sequence.

8. The method of claim 7 , wherein the 5′UTR is derived from the 5′-UTR of a TOP gene.

9. The method of claim 6 , wherein the 3′ UTR further comprises a histone stem-loop sequence.

10. The method of claim 6 , wherein the ORF has a G/C content that is increased compared with the G/C content an ORF from an original sequence encoding RAV-G.

11. The method of claim 6 , wherein the mRNA is formulated with a cationic or polycationic compound.

12. The method of claim 11 , wherein the a cationic or polycationic compound comprises a cationic lipid.

13. The method of claim 7 , wherein the mRNA comprises at least one base-modified nucleotide.

14. The method of claim 7 , wherein the poly(A) sequence is located at the 3′ terminus of the mRNA.

15. A method of stimulating a protective immune response to rabies virus in a subject comprising administering to the subject a pharmaceutical composition comprising a purified mRNA molecule, said mRNA comprising:
(a) a 5′ Cap;
(b) a 5′ untranslated region (UTR);
(c) an open reading frame (ORF) encoding a Rabies virus glycoprotein (RAV-G), wherein the ORF comprises a sequence having at least about 95% identity to the protein coding region of SEQ ID NO: 24;
(d) a 3′ UTR; and
(e) a Poly(A) sequence,

wherein the composition is administered by intramuscular injection and wherein the mRNA is formulated with cationic lipid.

16. The method of claim 15 , wherein the ORF has a G/C content that is increased compared with the G/C content an ORF from an original sequence encoding RAV-G or an antigenic fragment thereof.

17. The method of claim 15 , wherein the RAV-G is a full length RAV-G.

18. The method of claim 15 , wherein the mRNA comprises at least one base-modified nucleotide.

Assignees

• CureVac SE

Inventors

• Schnee Margit
• Kramps Thomas
• Stitz Lothar
• Petsch Benjamin

Classifications

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C07K14/005

  from viruses · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• A61K48/0075 Primary

  characterised by an aspect of the delivery route, e.g. oral, subcutaneous · CPC title

• A61K39/42

  viral · CPC title