Coronavirus vaccine

Patent metadata

Field	Value
Publication number	US-12186387-B2
Application number	US-202218071499-A
Country	US
Kind code	B2
Filing date	Nov 29, 2022
Priority date	Nov 29, 2021
Publication date	Jan 7, 2025
Grant date	Jan 7, 2025

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

The invention claimed is:

1. A composition or medical preparation comprising an RNA comprising a nucleotide sequence encoding a SARS-COV-2 Spike(S) protein, wherein the SARS-COV-2 S protein comprises:
(a) at least 10 of the following mutations as compared to SEQ ID NO: 1: A67V, Δ69-70, T95I, G142D, Δ143-145, Δ211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, and L981F;
(b) an amino acid sequence that is at least 97% identical to SEQ ID NO: 49, or to an immunogenic fragment thereof;
wherein the RNA optionally comprises a modified uridine in place of one or more uridines.

2. The composition or medical preparation of claim 1 , wherein:
the nucleotide sequence encoding the SARS-COV-2 S protein comprises a nucleotide sequence that is at least 80% identical to SEQ ID NO: 50; and/or
the RNA comprises a nucleotide sequence that is at least 80% identical to SEQ ID NO: 51.

3. The composition or medical preparation of claim 2 , wherein the SARS-COV-2 S protein comprises one or more proline mutations at positions corresponding to one or more of residues 986 and 987 of SEQ ID NO: 1.

4. The composition or medical preparation of claim 2 , wherein the RNA comprises a modified uridine in place of each uridine.

5. The composition or medical preparation of claim 4 , wherein the modified uridine is N1-methyl-pseudouridine (m1ψ).

6. The composition or medical preparation of claim 2 , wherein the RNA comprises one or more of the following:
(a) a 5′-cap that comprises m 2 7,3′-O Gppp(m 1 2′-O )ApG;
(b) a poly(A) sequence comprising at least 100 A nucleotides;
(c) a 5′-UTR that comprises a modified human alpha-globin 5′-UTR; and
(d) a 3′-UTR that 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.

7. The composition or medical preparation of claim 2 , wherein the RNA is formulated in lipid nanoparticles (LNP).

8. The composition or medical preparation of claim 7 , wherein the RNA is present in an amount within a range of about 1 μg to about 100 μg per dose.

9. The composition or medical preparation of claim 8 , wherein the RNA is present in an amount of about 1.5 μg, about 2.5 μg, about 3.0 μg, about 5.0 μg, about 10 μg, about 15 μg, about 30 μg, or about 60 μg per dose.

10. A composition or medical preparation comprising:
(a) a first RNA comprising a nucleotide sequence encoding a SARS-COV-2 Spike(S) protein of a first strain or variant; and
(b) a second RNA comprising a nucleotide sequence encoding a SARS-COV-2 Spike(S) protein of a second variant,
wherein the first strain or variant is different from the second variant, and wherein at least one of the first RNA and the second RNA comprises a nucleotide sequence encoding a SARS-CoV-2 S protein that comprises (i) at least 10 of the following mutations as compared to SEQ ID NO: 1: A67V, Δ69-70, T95I, G142D, Δ143-145, Δ211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, and L981FP and (ii) an amino acid sequence that is at least 97% identical to SEQ ID NO: 49;
wherein each of the first RNA and the second RNA optionally include a modified uridine in place of one or more uridines.

11. A composition or medical preparation comprising a first RNA and a second RNA, wherein:
a) the first RNA comprises (i) a nucleotide sequence encoding a SARS-COV-2 S protein comprising an amino acid sequence that is at least 97% identical to SEQ ID NO: 7, and/or (ii) a nucleotide sequence that is at least 80% identical to SEQ ID NO: 9 or 20; and
b) the second RNA comprises a nucleotide sequence encoding a SARS-COV-2 S protein comprising at least 10 of the following mutations as compared to SEQ ID NO: 1: Δ69/70, G142D, V213G, G339D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, L452R, S477N, T478K, E484A, F486V, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K, wherein (i) the SARS-COV-2 S protein encoded by the nucleotide sequence present in the second RNA comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 69; and/or (ii) the second RNA comprises a nucleotide sequence that is at least 80% identical to SEQ ID NO: 70 or 72;
wherein each of the first RNA and the second RNA optionally include a modified uridine in place of one or more uridines.

12. The composition or medical preparation of claim 2 , wherein the SARS-COV-2 S protein comprises one or more of the following features:
(a) a proline mutation at one or more positions corresponding to residues 817, 892, 899, 942, 986, and 987 of SEQ ID NO: 1;
(b) a mutation that prevents furin cleavage, wherein the mutation is at a location corresponding to residues 682-685 of SEQ ID NO: 1; and
(c) an aspartate to glycine mutation at a position corresponding to residue 614 of SEQ ID NO: 1.

13. The composition or medical preparation of claim 11 , wherein the first RNA and the second RNA each comprise a modified uridine in place of each uridine.

14. The composition or medical preparation of claim 13 , wherein the modified uridine is N1-methyl-pseudouridine (mlv).

15. The composition or medical preparation of claim 11 , wherein the first RNA and the second RNA each comprise one or more of the following features:
(a) a 5′-cap that comprises m 2 7,3′-O Gppp(m 1 2′-O )ApG;
(b) a poly(A) sequence that comprises 30 adenine nucleotides followed by 70 adenine nucleotides, wherein the 30 adenine nucleotides and the 70 adenine nucleotides are separated by a linker sequence;
(c) a 5′-UTR that comprises a modified human alpha-globin 5′-UTR; and
(d) a 3′-UTR that 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.

16. The composition or medical preparation of claim 11 , wherein the first RNA and the second RNA are each formulated as lipid nanoparticles (LNP).

17. The composition or medical preparation of claim 16 , wherein the first RNA and the second RNA are formulated in separate lipid nanoparticles or in the same lipid nanoparticles.

18. The composition or medical preparation of claim 16 , wherein the first RNA and the second RNA are present in a combined amount within a range of about 1 μg to about 100 μg per dose.

19. The composition or medical preparation of claim 16 , wherein:
a) the first RNA and the second RNA are each present in an amount of about 1.5 μg per dose in the composition;
b) the first RNA and the second RNA are each present in an amount of about 5 μg per dose in the composition;
c) the first RNA and the second RNA are each present in an amount of about 15 μg per dose in the composition; or
d) the first RNA and the second RNA are each present in an amount of about 30 μg per dose in the composition.

20. The composition or medical preparation of claim 1 , further comprising an RNA encoding one or more T cell epitopes of SARS-COV-2.

21. The composition or medical preparation of claim 7 , wherein the composition or medical preparation is formulated or is to be formulated for intramuscular administration.

22. A method of eliciting an immune response against SARS-COV-2 in a subject comprising administering the composition or med

Assignees

• BioNTech SE

Inventors

• Muik Alexander
• Poran Asaf
• Swanson Kena Anne
• Yang Qi
• Cai Hui
• Sahin Ugur

Classifications

• C12N2770/20071

  Demonstrated in vivo effect · CPC title

• C12N2770/20043

  viral genome or elements thereof as genetic vector · CPC title

• C12N2770/20034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2770/20022

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C12N2760/16034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title