Coronavirus vaccine

Patent metadata

Field	Value
Publication number	US-11547673-B1
Application number	US-202117233396-A
Country	US
Kind code	B1
Filing date	Apr 16, 2021
Priority date	Apr 22, 2020
Publication date	Jan 10, 2023
Grant date	Jan 10, 2023

Abstract

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

First claim

We claim:

1. A pharmaceutical composition comprising
an RNA comprising the nucleotide sequence of SEQ ID NO: 9 that includes modified uridines.

2. The composition of claim 1 , wherein the RNA comprises a 5′-cap that is or comprises m 2 7,3′-O Gppp(m 1 2′-O )ApG.

3. The composition of claim 1 , wherein the RNA comprises a polyA sequence, wherein the polyA sequence comprises 30 adenine nucleotides followed by 70 adenine nucleotides, wherein the 30 adenine nucleotides and 70 adenine nucleotides are separated by a linker sequence.

4. The composition of claim 1 , wherein the RNA comprises a 5′-UTR that is or comprises a modified human alpha-globin 5′-UTR.

5. The composition of claim 1 , wherein the RNA comprises a 3′-UTR that is or comprises a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA.

6. The composition of claim 1 , wherein the nucleotide sequence includes modified uridines in place of all uridines.

7. The composition of claim 6 , wherein the modified uridines are each N1-methyl-pseudouridine.

8. The composition of claim 1 , wherein the RNA comprises: a 5′ cap, a 5′ UTR, a 3′ UTR, and a polyA sequence.

9. The composition of claim 8 , wherein the 5′ cap is or comprises a cap1 structure.

10. The composition of claim 8 , wherein the polyA sequence comprises at least 100 A nucleotides.

11. The composition of claim 10 , wherein the polyA sequence is an interrupted sequence of A nucleotides.

12. The composition of claim 1 , wherein the RNA is formulated in lipid nanoparticles comprising each of: (i) a cationically ionizable lipid; (ii) a neutral lipid; (iii) a sterol; and (iv) a lipid conjugate.

13. The composition of claim 12 , further comprising at least one salt and/or a cryoprotectant.

14. The composition of claim 13 , wherein the cryoprotectant is or comprises sucrose.

15. The composition of claim 12 , wherein the composition is formulated for intramuscular administration.

16. The composition of claim 12 , wherein the RNA is present in an amount within a range of about 1 μg to about 100 μg per dose in the composition.

17. The composition of claim 12 , wherein the RNA is present in an amount of about 3 μg per dose in the composition.

18. The composition of claim 12 , wherein the RNA is present in an amount of about 10 μg per dose in the composition.

19. The composition of claim 12 , wherein the RNA is present in an amount of about 30 μg per dose in the composition.

20. A pharmaceutical composition comprising:
an RNA comprising a nucleotide sequence that includes modified uridines and encodes a SARS-CoV-2 Spike (S) polypeptide that is at least 95% identical to the polypeptide of SEQ ID NO: 7, and includes proline residues at positions 986 and 987 of SEQ ID NO: 7, wherein the RNA comprises a nucleotide sequence that is at least 95% identical to SEQ ID NO: 20.

21. The composition of claim 20 , wherein the nucleotide sequence encodes a SARS-CoV-2 Spike (S) polypeptide comprising SEQ ID NO: 7.

22. The composition of claim 20 , wherein the nucleotide sequence includes modified uridines in place of all uridines.

23. The composition of claim 22 , wherein the modified uridines are each N1-methyl-pseudouridine.

24. The composition of claim 20 , wherein the RNA comprises a 5′ cap that is or comprises a cap1 structure.

25. The composition of claim 24 , wherein the RNA comprises a 5′-cap that is or comprises m 2 7,3′-O Gppp(m 1 2′-O ) ApG.

26. The composition of claim 20 , wherein the RNA comprises a polyA sequence comprising at least 100 A nucleotides.

27. The composition of claim 26 , wherein the polyA sequence comprises an interrupted sequence of A nucleotides.

28. The composition of claim 27 , wherein the interrupted sequence comprises 30 adenine nucleotides followed by 70 adenine nucleotides, wherein the 30 adenine nucleotides and 70 adenine nucleotides are separated by a linker sequence.

29. The composition of claim 20 , wherein the RNA comprises a 5′-UTR that is or comprises a modified human alpha-globin 5′-UTR.

30. The composition of claim 20 , wherein the RNA comprises a 3′-UTR that is or comprises a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA.

31. The composition of claim 20 , wherein the nucleotide sequence that includes modified uridines and encodes a SARS-CoV-2 Spike (S) polypeptide is codon-optimized for human subjects.

32. The composition of claim 20 , wherein the RNA is formulated in lipid nanoparticles comprising each of: (i) a cationically ionizable lipid; (ii) a neutral lipid; (iii) a sterol; and (iv) a lipid conjugate.

33. The composition of claim 32 , further comprising at least one salt and/or a cryoprotectant.

34. The composition of claim 33 , wherein the cryoprotectant is or comprises sucrose.

35. The composition of claim 32 , wherein the composition is formulated for intramuscular administration.

36. The composition of claim 32 , wherein the RNA is present in an amount within a range of about 1 μg to about 100 μg per dose in the composition.

37. The composition of claim 32 , wherein the RNA is present in an amount of about 3 μg per dose in the composition.

38. The composition of claim 32 , wherein the RNA is present in an amount of about 10 μg per dose in the composition.

39. The composition of claim 32 , wherein the RNA is present in an amount of about 30 μg per dose in the composition.

40. The composition of claim 20 , wherein the RNA comprises the nucleotide sequence of SEQ ID NO: 20.

41. The composition of claim 40 , wherein the nucleotide sequence includes modified uridines in place of all uridines.

42. The composition of claim 41 , wherein the modified uridines are each N1-methyl-pseudouridine.

43. The composition of claim 40 , wherein the RNA comprises a 5′-cap that is or comprises a cap1 structure.

44. The composition of claim 40 , wherein the RNA comprises a 5′-cap that is or comprises m 2 7,3′-O Gppp(m 1 1 2′-O ) ApG.

45. The composition of claim 42 , wherein the RNA comprises a 5′-cap that is or comprises m 2 7,3′-O Gppp(m 1 2′-O ) ApG.

Assignees

• BioNTech SE

Inventors

• Sahin Ugur
• Güler Alptekin
• Kuhn Andreas
• Muik Alexander
• Vogel Annette
• Walzer Kerstin
• Witzel Sonja
• Hein Stephanie
• Türeci Özlem

Classifications

• A61K2039/55555

  Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/7115

  Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine · CPC title

• C12P19/34

  Polynucleotides, e.g. nucleic acids, oligoribonucleotides · CPC title

• A61K31/711

  Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links · CPC title