Coronavirus vaccine

Patent metadata

Field	Value
Publication number	US-12194089-B2
Application number	US-202117276788-A
Country	US
Kind code	B2
Filing date	Feb 3, 2021
Priority date	Feb 4, 2020
Publication date	Jan 14, 2025
Grant date	Jan 14, 2025

Abstract

The present invention is directed to a nucleic acid suitable for use in treatment or prophylaxis of an infection with a coronavirus, preferably with a Coronavirus SARS-COV-2, or a disorder related to such an infection, preferably COVID-19. The present invention is also directed to compositions, polypeptides, and vaccines. The compositions and vaccines preferably comprise at least one of said nucleic acid sequences, preferably nucleic acid sequences in association a lipid nanoparticle (LNP). The invention is also directed to first and second medical uses of the nucleic acid, the composition, the polypeptide, the combination, the vaccine, and the kit, and to methods of treating or preventing a coronavirus infection, preferably a Coronavirus infection.

First claim

The invention claimed is:

1. A composition comprising a mRNA comprising:
(a) at least one coding sequence encoding a SARS-COV-2 spike protein(S) comprising an amino acid sequence at least 90% identical to SEQ ID NO: 10 that is a pre-fusion stabilized spike protein (S_stab) comprising K986P and V987P stabilizing substitutions and further comprising E484K and D614G amino acid substitutions relative to SEQ ID NO: 10;
(b) at least one heterologous untranslated region (UTR); and
(c) at least one pharmaceutically acceptable carrier,
wherein the mRNA is complexed or associated with a lipid nanoparticle (LNP).

2. The composition of claim 1 , wherein the mRNA comprises at least one poly(A) sequence comprising 30 to 200 adenosine nucleotides and a 5′-cap structure.

3. The composition of claim 2 , wherein the at least one coding sequence of the mRNA has a G/C content of at least 50%.

4. The composition of claim 3 , wherein the mRNA comprises an RNA sequence at least 80% identical to SEQ ID NO: 23092.

5. The composition of claim 3 , wherein the at least one heterologous untranslated region is selected from at least one heterologous 5′-UTR and at least one heterologous 3′-UTR.

6. The composition of claim 3 , wherein the spike protein comprises at least three of the following amino acid substitutions relative to SEQ ID NO: 10: L18F, D80A, D215G, delL242, delA243, delL244, R246I, K417N, N501Y, and/or A701V.

7. The composition of claim 6 , wherein the spike protein comprises the following amino acid substitutions relative to SEQ ID NO: 10: L18F, D80A, D215G, delL242, delA243, delL244, R246I, K417N, E484K, N501Y, D614G and A701V.

8. The composition of claim 3 , wherein the composition comprises at least two different mRNA encoding at least two different SARS-COV-2 spike proteins.

9. The composition of claim 8 , wherein the at least two different SARS-COV-2 spike proteins are each at least 95% identical to SEQ ID NO: 10 and comprise the K986P and V987P stabilizing substitutions.

10. The composition of claim 3 , wherein the mRNA comprises a nucleotide analog.

11. The composition of claim 10 , wherein the mRNA comprises a 1-methylpseudouridine substitution.

12. The composition of claim 11 , wherein 100% of the uracil positions in the coding sequence are replaced with 1-methylpseudouridine.

13. The composition of claim 3 , wherein the mRNA is a purified mRNA that has been purified by RP-HPLC and/or TFF.

14. The composition of claim 13 , wherein the mRNA is a purified mRNA that has been purified by RP-HPLC and/or TFF and comprises about 5%, 10%, or 20% less double stranded RNA side products as an RNA that has not been purified with RP-HPLC and/or TFF.

15. A method of stimulating an immune response to a coronavirus spike protein in a subject comprising administering to the subject an effective amount of a composition according to claim 3 .

16. The method of claim 15 , wherein the administering to the subject is by intramuscular injection.

17. A composition comprising a purified RNA comprising:
(i) a 5′ cap structure;
(ii) a 5′ untranslated region (UTR);
(iii) a coding sequence encoding a SARS-COV-2 spike protein(S) comprising an amino acid sequence at least 90% identical to SEQ ID NO: 10 that is a pre-fusion stabilized spike protein (S_stab) comprising K986P and V987P stabilizing substitutions and further comprising E484K and D614G amino acid substitutions relative to SEQ ID NO: 10; and
(iv) a heterologous 3′ UTR comprising at least one poly(A) sequence having 30 to 200 consecutive adenosine nucleotides,
wherein the RNA is complexed or associated with a lipid nanoparticle (LNP) and is formulated in a pharmaceutically acceptable carrier and wherein said purified RNA optionally comprise a 1-methylpseudouridine or a pseudouridine nucleotide substitution at one or more uracil position(s).

18. The composition of claim 17 , wherein the at least one coding sequence of the RNA has a G/C content of at least 50%.

19. The composition of claim 18 , wherein 100% of the uracil positions in the RNA are replaced with 1-methylpseudouridine.

20. The composition of claim 17 , wherein the purified RNA is a replicon RNA.

21. The composition of claim 20 , wherein the replicon RNA encodes replicase elements derived from an alphavirus.

22. The composition of claim 21 , wherein the replicon RNA encodes replicase elements derived from VEE.

23. The composition of claim 21 , wherein the replicon RNA does not comprise a 1-methylpseudouridine or a pseudouridine nucleotide substitution.

24. The composition of claim 19 , wherein the purified RNA is a mRNA.

25. The composition of claim 24 , wherein the coding sequence is at least 95% identical to the RNA sequence of SEQ ID NO: 146.

26. The composition of claim 25 , wherein the coding sequence is at least 97% identical to the RNA sequence of SEQ ID NO: 146.

27. The composition of claim 26 , wherein the coding sequence is at least 98% identical to the RNA sequence of SEQ ID NO: 146.

28. The composition of claim 18 , wherein the RNA has been purified by a method comprising tangential flow filtration (TFF).

29. The composition of claim 18 , wherein the composition further comprises a second purified RNA encoding a second viral antigen.

30. The composition of claim 18 , wherein the 5′ cap structure is a cap1.

31. The composition of claim 18 , wherein the RNA comprises a terminal poly(A) sequence of 30 to 200 consecutive adenosine nucleotides.

32. The composition of claim 18 , wherein the pre-fusion stabilized spike protein comprises K417N, E484K, N501Y, and D614G amino acid substitutions relative to SEQ ID NO: 10.

33. A method of stimulating an immune response to a SARS-COV-2 spike protein in a subject comprising administering to the subject an effective amount of a pharmaceutical composition of claim 18 by intramuscular injection.

34. The method of claim 33 , wherein the subject is a human subject.

35. The method of claim 34 , wherein the composition comprises about 1 μg to about 200 μg of the purified RNA.

36. The method of claim 35 , wherein the composition comprises about 5 μg to about 100 μg of the purified RNA.

37. The method of claim 34 , wherein the pre-fusion stabilized spike protein comprises K417N, E484K, N501Y, and D614G amino acid substitutions relative to SEQ ID NO: 10.

38. The method of claim 36 , wherein the RNA is a mRNA.

39. A container comprising a vaccine dose comprising the pharmaceutical composition of claim 18 , wherein about 5 μg to about 100 μg of the RNA is present in said vaccine dose.

40. The container of claim 39 , wherein the pre-fusion stabilized spike protein comprises K417N, E484K, N501Y, and D614G amino acid substitutions relative to SEQ ID NO: 10.

41. The container of claim 39 , wherein the RNA is a mRNA.

42. The composition of claim 17 , wherein the SARS-COV-2 spike protein(S) comprises an amino acid sequence at least 94% identical to SEQ ID NO: 10.

43. The composition of claim 24 , wherein the SARS-COV-2 spike protein(S) comprises an amino acid sequence at least 94% identical to SEQ ID NO: 10.

44. The me

Assignees

• CureVac SE

Inventors

• Rauch Susanne
• Grosse Hans Wolfgang
• Petsch Benjamin

Classifications

• A61K2039/70

  Multivalent vaccine · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K2039/6018

  Lipids, e.g. in lipopeptides · CPC title