Respiratory syncytial virus (RSV) vaccine

Patent metadata

Field	Value
Publication number	US-11965000-B2
Application number	US-202318463276-A
Country	US
Kind code	B2
Filing date	Sep 7, 2023
Priority date	Aug 21, 2013
Publication date	Apr 23, 2024
Grant date	Apr 23, 2024

Abstract

The present invention relates to an mRNA sequence, comprising a coding region, encoding at least one antigenic peptide or protein of RSV infections Respiratory syncytial virus (RSV) 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 RSV infections Respiratory syncytial virus (RSV) 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 RSV infections Respiratory syncytial virus (RSV) infections. The present invention further describes a method of treatment or prophylaxis of RSV infections using the mRNA sequence.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising a mRNA molecule having a coding sequence encoding a Respiratory Syncytial Virus fusion protein (RSV-F) with a deleted C-terminus (F-del) lacking amino acids 554-574 of native RSV-F, said coding sequence comprising a nucleic acid sequence at least 80% identical to the protein coding portion of the sequence of SEQ ID NO: 33, wherein the mRNA comprises from 5′ to 3′: (i) a 5′-cap structure, (ii) a 5′ untranslated region (UTR); (iii) the coding sequence encoding the F protein; (iv) a 3′ UTR and (v) a poly(A) sequence, wherein the mRNA molecule is formulated with a cationic lipid.

2. The pharmaceutical composition of claim 1 , wherein the 5′ structure is m7GpppN.

3. The pharmaceutical composition of claim 1 , wherein the 5′ cap structure is a Cap1 structure.

4. The pharmaceutical composition of claim 1 , wherein the poly(A) sequence comprises a sequence of 25 to 400 adenosine nucleotides.

5. The pharmaceutical composition of claim 4 , wherein the poly(A) sequence comprises 60 to 250 adenosine nucleotides.

6. The pharmaceutical composition of claim 5 , wherein the poly(A) sequence is at the 3′ end of the mRNA molecule.

7. The pharmaceutical composition of claim 1 , wherein the 3′ UTR comprises a stabilizing sequence from the alpha globin 3′ UTR.

8. The pharmaceutical composition of claim 1 , wherein the composition comprises at least a second, different, mRNA encoding an antigen from a different virus or an antigenic fragment thereof.

9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for intramuscular injection.

10. The pharmaceutical composition of claim 1 , wherein the encoded RSV-F comprises the transmembrane domain of native RSV-F.

11. The pharmaceutical composition of claim 10 , wherein the poly(A) sequence comprises 60 to 250 adenosine nucleotides.

12. The pharmaceutical composition of claim 11 , wherein the 5′ cap structure is a Cap1 structure.

13. A method of stimulating an immune response to Respiratory Syncytial Virus (RSV) in a subject comprising administering to the subject a pharmaceutical composition comprising a mRNA molecule having a coding sequence encoding a RSV fusion protein (RSV-F) with a deleted C-terminus (F-del) lacking amino acids 554-574 of native RSV-F, said coding sequence comprising a nucleic acid sequence at least 80% identical to the protein coding portion of the sequence of SEQ ID NO: 33, wherein the mRNA comprises from 5′ to 3′: (i) a 5′-cap structure, (ii) a 5′ untranslated region (UTR); (iii) the coding sequence encoding the F protein; (iv) a 3′ UTR and (v) a poly(A) sequence of 60 to 250 adenosine nucleotides, wherein the mRNA molecule is formulated with a cationic lipid.

14. The method of claim 13 , wherein the pharmaceutical composition is administered by intramuscular injection.

15. The method of claim 14 , wherein the 5′ cap structure is m7GpppN.

16. The method of claim 14 , wherein the 5′ structure is a Cap1 structure.

17. The method of claim 14 , wherein the poly(A) sequence is at the 3′ end of the mRNA molecule.

18. The method of claim 14 , wherein the 3′ UTR comprises a stabilizing sequence from the alpha globin 3′ UTR.

19. The method of claim 14 , wherein the composition comprises at least a second, different, mRNA encoding an antigen from a different virus or an antigenic fragment thereof.

20. The method of claim 14 , wherein the encoded RSV-F comprises the transmembrane domain of native RSV-F.

21. A method of stimulating an immune response to Respiratory Syncytial Virus (RSV) in a subject comprising administering to the subject a pharmaceutical composition comprising a mRNA molecule having a coding sequence encoding a RSV fusion protein (RSV-F) with a deleted C-terminus (F-del) lacking amino acids 554-574 of native RSV-F, said coding sequence comprising a nucleic acid sequence at least 80% identical to the protein coding portion of the sequence of SEQ ID NO: 33, wherein the mRNA comprises from 5′ to 3′: (i) a 5′ cap structure, (ii) a 5′ untranslated region (UTR); (iii) the coding sequence encoding the F protein; (iv) a 3′ UTR and (v) a poly(A) sequence of 60 to 250 adenosine nucleotides, wherein the mRNA molecule is formulated with a cationic component and wherein the immune response stimulated by the pharmaceutical composition produces an increased amount of RSV neutralizing antibodies compared to a composition comprising a mRNA encoding a full length RSV-F.

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

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

24. The method of claim 22 , wherein the mRNA molecule is formulated with a cationic lipid.

25. The method of claim 22 , wherein the 5′ cap structure is m7GpppN.

26. The method of claim 22 , wherein the 5′ structure is a Cap1 structure.

27. The method of claim 22 , wherein the poly(A) sequence is at the 3′ end of the mRNA molecule.

28. The method of claim 22 , wherein the 3′ UTR comprises a stabilizing sequence from the alpha globin 3′ UTR.

29. The method of claim 22 , wherein the composition comprises at least a second, different, mRNA encoding an antigen from a different virus or an antigenic fragment thereof.

30. The method of claim 22 , wherein the encoded RSV-F comprises the transmembrane domain of native RSV-F.

Assignees

• CureVac SE

Inventors

• Kramps Thomas
• Schnee Margit
• Voss Daniel
• Petsch Benjamin

Classifications

• C07K16/11

  Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV] · CPC title

• C07K14/005 Primary

  from viruses · CPC title

• A61K39/12 Primary

  Viral antigens · CPC title

• A61K39/155

  Paramyxoviridae, e.g. parainfluenza virus · CPC title

• C07K16/1027

  Chemistry & Metallurgy · mapped topic