Respiratory syncytial virus (RSV) vaccine

Patent metadata

Field	Value
Publication number	US-12240873-B2
Application number	US-202418800440-A
Country	US
Kind code	B2
Filing date	Aug 12, 2024
Priority date	Aug 21, 2013
Publication date	Mar 4, 2025
Grant date	Mar 4, 2025

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 purified antigen-providing mRNA molecule with a coding region comprising an antigen coding sequence, said mRNA molecule comprising, from 5′ to 3′:
(a) a 5′ Cap structure;
(b) a 5′ untranslated region (UTR) that is heterologous to the antigen coding region;
(c) the antigen coding sequence encoding a Respiratory Syncytial Virus fusion protein (RSV-F) antigen at least 85% identical to the RSV-F encoded by SEQ ID NO: 33, said RSV-F antigen lacking amino acids 554-574 of native RSV-F protein, wherein said RNA coding sequence is at least 80% identical to the protein coding portion of the sequence of SEQ ID NO: 33,
(d) a 3′ UTR that is heterologous to the antigen coding region; and
(e) a poly (A) sequence of 60 to 250 consecutive adenosine nucleotides.

2. The purified antigen-providing mRNA molecule of claim 1 , wherein at least 70% of the codons in the coding sequence are substituted for codons with increased G/C content relative to a native RSV-F coding sequence.

3. The purified antigen-providing mRNA molecule of claim 2 , wherein at least 90% of the codons in the coding sequence are substituted for codons with increased G/C content relative to a native RSV-F coding sequence.

4. The purified antigen-providing mRNA molecule of claim 1 , wherein the 5′ Cap structure is m7GpppN.

5. The purified antigen-providing mRNA molecule of claim 1 , wherein the 5′ Cap structure is a Cap1 structure.

6. The purified antigen-providing mRNA molecule of claim 1 , wherein the poly (A) sequence is at the 3′ end of the mRNA molecule.

7. The purified antigen-providing mRNA molecule of claim 1 , wherein the encoded RSV-F antigen comprises the transmembrane domain of native RSV-F.

8. The purified antigen-providing mRNA molecule of claim 1 , wherein the encoded RSV-F antigen is at least 95% identical to the RSV-F encoded by SEQ ID NO: 33 over a stretch of 100 amino acids.

9. The purified antigen-providing mRNA molecule of claim 1 , wherein the encoded RSV-F antigen is at least 98% identical to the RSV-F encoded by SEQ ID NO: 33 over a stretch of 100 amino acids.

10. The purified antigen-providing mRNA molecule of claim 9 , wherein the encoded RSV-F antigen comprises the transmembrane domain of native RSV-F.

11. A pharmaceutical composition comprising the purified antigen-providing mRNA molecule of claim 1 and pharmaceutically acceptable carrier.

12. The pharmaceutical composition of claim 11 , wherein the pharmaceutically acceptable carrier comprises a cationic, polycationic or polymeric carrier.

13. The pharmaceutical composition of claim 12 , wherein the pharmaceutically acceptable carrier comprises cationic carrier.

14. The pharmaceutical composition of claim 13 , wherein the pharmaceutically acceptable carrier comprises a cationic lipid.

15. The pharmaceutical composition of claim 12 , wherein the pharmaceutically acceptable carrier comprises a polymeric carrier.

16. The pharmaceutical composition of claim 12 , wherein at least 90% of the codons in the coding sequence are substituted for codons with increased G/C content relative to a native RSV-F coding sequence.

17. The pharmaceutical composition of claim 12 , wherein the encoded RSV-F antigen is at least 98% identical to the RSV-F encoded by SEQ ID NO: 33 over a stretch of 100 amino acids.

18. A method of stimulating an immune response to Respiratory Syncytial Virus (RSV) in a mammalian subject comprising administering to the subject the pharmaceutical composition of claim 12 , wherein the composition is administered by intradermal or intramuscular injection.

19. The method of claim 18 , wherein the pharmaceutical composition is administered by intramuscular injection.

20. The method of claim 18 , wherein the encoded RSV-F antigen is at least 98% identical to the RSV-F encoded by SEQ ID NO: 33 over a stretch of 100 amino acids and wherein at least 90% of the codons in the coding sequence are substituted for codons with increased G/C content relative to a native RSV-F coding sequence.

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

22. The method of claim 18 , wherein stimulating an immune response in the subject comprises stimulating a RSV-specific neutralizing antibody response in the subject.

23. The method of claim 22 , wherein stimulating an immune response in the subject comprises stimulating a RSV-F specific CD8+ T-cell response in the subject.

24. The method of claim 23 , wherein stimulating an immune response in the subject comprises stimulating a T-cell response to the KYKNAVTEL (SEQ ID NO: 38) epitope of RSV-F.

25. The method of claim 22 , wherein the composition is administered in a single dose and wherein upon Respiratory Syncytial Virus (RSV) challenge infection the subject exhibits reduced lung pathology compared to an untreated subject.

26. The method of claim 22 , wherein upon RSV challenge infection the subject exhibits reduced nasal RSV production compared to an untreated subject.

27. A method of stimulating an immune response to Respiratory Syncytial Virus (RSV) in a mammalian subject comprising administering to the subject a pharmaceutical composition comprising a purified antigen-providing mRNA molecule with a coding region comprising an antigen coding sequence, said mRNA molecule comprising, from 5′ to 3′:
(a) a 5′ Cap structure;
(b) a 5′ untranslated region (UTR) that is heterologous to the antigen coding region;
(c) the antigen coding sequence encoding a Respiratory Syncytial Virus fusion protein (RSV-F) antigen at least 85% identical to the RSV-F encoded by SEQ ID NO: 33, said RSV-F antigen lacking amino acids 554-574 of native RSV-F protein, wherein said RNA coding sequence is at least 80% identical to the protein coding portion of the sequence of SEQ ID NO: 33,
(d) a 3′ UTR that is heterologous to the antigen coding region; and
(e) a poly (A) sequence of 60 to 250 consecutive adenosine nucleotides,
wherein said antigen-providing mRNA is a formulated with a cationic carrier,
wherein the composition is administered in a single dose by intramuscular or intradermal injection and wherein upon RSV challenge infection the mammalian subject exhibits reduced disease severity compared to an untreated subject.

28. The method of claim 27 , wherein the encoded RSV-F antigen is at least 98% identical to the RSV-F encoded by SEQ ID NO: 33 over a stretch of 100 amino acids.

29. The method of claim 28 , wherein the encoded RSV-F antigen comprises the transmembrane domain of native RSV-F.

30. The method of claim 28 , wherein the 3′ UTR further comprises a RNA sequence at least 90% identical to SEQ ID NO: 26.

31. The method of claim 29 , wherein the 3′ UTR further comprises a RNA sequence at least 90% identical to SEQ ID NO: 26.

32. The method of claim 31 , wherein the 5′ Cap structure is m7GpppN.

33. The method of claim 31 , wherein the 5′ Cap structure is a Cap1 structure.

34. The method of claim 32 , wherein the composition is administered in a single dose by intramuscular injection.

35. The method of claim 34 , wherein the cationic carrier is a cationic lipid.

36. The method of claim 32 , wherein the mRNA and cationic carrier are present at a nitrogen/ph

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

• A61K2039/6031

  Proteins · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• 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

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title