SARS-CoV-2 vaccine and antibodies
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- RUTGERS THE STATE UNIV
- Filing Date
- 2026-02-18
- Publication Date
- 2026-06-23
Smart Images
Figure 2026102582000001_ABST
Abstract
Claims
1. a. A SARS-CoV-2 peptidegenic protein, wherein the peptidegenic protein has altered conformokinetics compared to a SARS-CoV-2 initiation protein, the SARS-CoV-2 peptidegenic protein is conformomorphic to a SARS-CoV-2 initiation protein, and the SARS-CoV-2 initiation protein is selected from at least one of the proteins listed in Table 2; or b. Spike fragments; or c. A polynucleotide encoding (a) or (b); or d. Any combination of (a), (b), and / or (c) A composition containing the following:
2. The altered three-dimensional structural dynamics a. Investigate the 3-D structure of the SARS-CoV-2 initiation protein, identify the non-surface amino acid residues of the SARS-CoV-2 initiation protein, and generate a SARS-CoV-2 peptidegenic protein by substituting at least one non-surface amino acid residue in the SARS-CoV-2 initiation protein; or b. Investigate a 3D structural model of the SARS-CoV-2 initiation protein, identify the non-surface amino acid residues of the SARS-CoV-2 initiation protein, and generate a SARS-CoV-2 peptidegenic protein by substituting at least one non-surface amino acid residue in the SARS-CoV-2 initiation protein; or c. Identifying non-surface amino acid residues of SARS-CoV-2 initiation proteins by comparing conserved amino acid homology patterns across orthologous proteins to SARS-CoV-2 initiation proteins from different species, and generating SARS-CoV-2 peptidegenic proteins by substituting at least one non-surface amino acid residue in the SARS-CoV-2 initiation protein; or d. Substituting at least one non-surface amino acid residue in the SARS-CoV-2 initiation protein to generate a SARS-CoV-2 peptidegenic protein; or e. Substituting at least one non-surface amino acid residue with a smaller amino acid residue; or f. Substitution of at least one non-surface amino acid residue with alanine or glycine; or g. Removal of at least one disulfide bond in the SARS-CoV-2 initiation protein. The composition according to claim 1, obtained by the means described herein.
3. The composition according to claim 1 or 2, wherein at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids are substituted in the SARS-CoV-2 initiation protein.
4. The structural dynamics of the SARS-CoV-2 initiation protein are a. At least one threonine with valine, alanine, glycine or serine; or b. At least one cysteine with alanine, valine, glycine, serine or threonine; or c. At least one valine is replaced with alanine, glycine, leucine or isoleucine; or d. At least one leucine is replaced with alanine, valine, glycine, or isoleucine; or e. At least one isoleucine with alanine, valine, leucine, or glycine; or f. At least one proline is replaced with methionine, alanine, valine, leucine, isoleucine, or glycine; or g. At least one methionine is replaced with alanine, valine, leucine, isoleucine or glycine; or h. At least one phenylalanine is replaced with tyrosine, methionine, histidine, alanine, valine, leucine, isoleucine or glycine; or i. At least one tyrosine is replaced with phenylalanine, methionine, histidine, alanine, valine, leucine, isoleucine or glycine; or j. At least one tryptophan is replaced with tyrosine, phenylalanine, methionine, histidine, alanine, valine, leucine, isoleucine or glycine; or k. At least one aspartic acid is replaced with glutamic acid, glutamine, asparagine, glycine, serine, threonine, alanine, valine, leucine, or isoleucine; or l. At least one asparagine with glycine, serine, threonine, alanine, valine, leucine, isoleucine, glutamine, glutamic acid or aspartic acid; or m. At least one glutamic acid is replaced with aspartic acid, asparagine, glutamine, glycine, serine, threonine, alanine, valine, leucine, or isoleucine; or n. At least one glutamine is replaced with glutamic acid, aspartic acid, asparagine, glutamine, glycine, serine, threonine, alanine, valine, leucine, or isoleucine; or o. At least one lysine molecule is replaced with arginine, histidine, glycine, serine, threonine, alanine, valine, methionine, leucine, or isoleucine; or p. At least one arginine is replaced with lysine, histidine, glycine, serine, threonine, alanine, valine, methionine, leucine, or isoleucine; or q. At least one histidine is replaced with phenylalanine, tyrosine, lysine, arginine, glycine, serine, threonine, alanine, valine, glutamine, asparagine, leucine, methionine or isoleucine; or r. At least one alanine with glycine or proline; or s. At least one glycine compound with alanine or proline; or t. At least one serine with alanine or glycine; or u. At least one residue is a non-natural amino acid; or v. Any of the above combinations The composition according to any one of claims 1 to 3, which is modified by substitution.
5. The composition according to any one of claims 1 to 4, wherein the SARS-CoV-2 peptidegenic protein is selected from the spike glycoprotein P0DTC2 Spike_SARS2 (SEQ ID NO: 15) or P59594 Spike_CVHSA (SEQ ID NO: 16).
6. The spike protein is located at the following position: (A) Trp353, Tyr365, Phe392, Phe400, Tyr423, Phe497, and / or Phe543 of Sequence ID No. 15; (B) Val308, Ile326, Val350, Ile358, Ala363, Leu387, Val395, Ala397, Val401, Ile402, Ile410, Ile418, Ala419, Leu425, Val433, Ile434, Ala435, Leu492, Val510, Val511, Val512, Leu513, Val524, Val539, Leu552, Ala575, Val576, and / or Leu585 of sequence number 15; (C) Ala363, Ala397, and / or Ala575 of Sequence ID No. 15; (D) Cys336Ala / Cys361Ala and / or Cys379Ala / Cys432Ala of Sequence ID No. 15; (E) Ala419, Ile980, Ala903, Leu916, Ala575, Phe1095, Cys1032, Val576, Tyr365, Ile1115, Ile418, Leu387, Cys649, Leu650, Leu585, Ala1080, Ile410, Tyr423, Ala1087, Tyr695, Ala653, Phe201, Ile1081, Phe497, Ala989, Leu552, Val1104, and / or Cys671 of Sequence ID No. 15; or (F) or equivalent position in sequence numbers 15-16 or 43-110 The composition according to claim 5, which is mutated in any of the following ways.
7. The composition is as follows: a. Amino acids 316-594 of SEQ ID NO: 15 or amino acids 303-580 of SEQ ID NO: 16; b. Amino acids 316-594 of Sequence ID No. 15 with at least one mutation in any one of the following sites: (A) Trp353, Tyr365, Phe392, Phe400, Tyr423, Phe497, and / or Phe543; (B) Ile326, Val350, Ile358, Ala363, Leu387, Val395, Ala397, Val401, Ile402, Ile410, Ile418, Ala419, Leu425, Val433, Ile434, Ala435, Leu492, Val510, V al511, Val512, Leu513, Val524, Val539, Leu552, Ala575, Val576, and / or Leu585; (C) Ala363, Ala397, and / or Ala575; (D) Cys336Ala / Cys361Ala, and / or Cys379Ala / Cys432Ala; (E) Ala419, Ala575, Val576, Tyr365, Ile418, Leu387, Leu585, Ile410, Tyr423, Phe497, and / or Leu552; c. Amino acids 319-591 of Sequence ID No. 15 with at least one mutation in any one of the following sites: (A) Trp353, Tyr365, Phe392, Phe400, Tyr423, Phe497, and / or Phe543; (B) Ile326, Val350, Ile358, Ala363, Leu387, Val395, Ala397, Val401, Ile402, Ile410, Ile418, Ala419, Leu425, Val433, Ile434, Ala435, Leu492, Val510, Val 511, Val512, Leu513, Val524, Val539, Leu552, Ala575, Val576, and / or Leu585; (C) Ala363, Ala397, and / or Ala575; (D) Cys336Ala / Cys361Ala, and / or Cys379Ala / Cys432Ala; and / or (E) Ala419, Ala575, Val576, Tyr365, Ile418, Leu387, Leu585, Ile410, Tyr423, Phe497, and / or Leu552; d. Amino acids 319-541 of Sequence ID No. 15 with at least one mutation in any one of the following sites: (A) Trp353, Tyr365, Phe392, Phe400, Tyr423, and / or Phe497; (B) Ile326, Val350, Ile358, Ala363, Leu387, Val395, Ala397, Val401, Ile402, Ile410, Ile418, Ala419, Leu425, Val433, Ile 434, Ala435, Leu492, Val510, Val511, Val512, Leu513, Val524, and / or Val539; (C) Ala363, and / or Ala397; (D) Cys336Ala / Cys361Ala, and / or Cys379Ala / Cys432Ala; and / or (E) Ala419, Tyr365, Ile418, Leu387, Ile410, Tyr423, and / or Phe497; e. Amino acids 319-541, 319-591, or 316-594 of SEQ ID NO: 15, with at least one mutation in amino acids Y365, I402, and / or V511; f. Amino acids 319-541, 319-591, or 316-594 of SEQ ID NO: 15 with at least one mutation selected from Y365L, I402V, and / or V511A; or g. Equivalent fragments and / or mutations in SEQ ID NOs: 15-16 or 43-110 A composition according to any one of claims 1 to 6, comprising or consisting of any one of the following.
8. The structural dynamics changes of SARS-CoV-2 peptidegenic proteins are a. Change in melting temperature compared to SARS-CoV-2 initiation protein; or b. Changes in the stabilization Gibbs free energy or proteolytic sensitivity assay; or c. The change in Gibbs free energy of stabilization is measured by denaturing agent-regulated equilibrium unfolding, such as urea or guanidinium hydrochloride unfolding. A composition according to any one of claims 1 to 7, measured by [method].
9. Similar three-dimensional structures a. A cross-reactive antibody that binds to both the SARS-CoV-2 peptidegenic protein and the SARS-CoV-2 initiation protein; or b. Cross-reactivity of the cross-reactive antibodies of (a) as measured by immunoprecipitation assay, surface plasmon resonance, isothermal titration calorimetry, oblique incidence reflectance (OI-RD), Western blotting, radioimmunoassay, ELISA (enzyme-linked immunosorbent assay), "sandwich" immunoassay, gel diffusion precipitation reaction, immunodiffusion assay, agglutination assay, complement fixation assay, immunoradioquantification assay, fluorescence immunoassay, and / or protein A immunoassay; or c. The cross-reactive antibody of (a) whose cross-reactivity is measured by a binding assay; or d. 10 －９ A cross-reactive antibody of (a) having a dissociation constant (KD) of M or less; or e. 10 －８ M or less, 10 －７ M or less, or 10 －６ Cross-reactive antibodies of (a) having a dissociation constant (KD) of M or less; A composition according to any one of claims 1 to 8, measured by [method].
10. The composition according to any one of claims 1 to 9, wherein the mutation is selected from at least one of the mutations listed in Table 2.
11. The composition according to any one of claims 1 to 10, wherein the composition is administered directly to an animal.
12. SARS-CoV-2 peptidegenic protein, a. The same SARS-CoV-2 initiation protein; or b. Multiple SARS-CoV-2 initiation proteins; or c. Multiple related SARS-CoV-2 initiation proteins A composition according to any one of claims 1 to 11, derived from [the specified source].
13. A method for administering the composition according to any one of claims 1 to 12.
14. The method according to claim 13, further comprising administering a mixture of polynucleotides encoding a SARS-CoV-2 peptidegenic protein to a target, and introducing the mixture of polynucleotides into an animal such that a SARS-CoV-2 peptidegenic protein is expressed from the polynucleotides.
15. Polynucleotides a. Synthesized in vitro; or b. DNA; or c. In vitro transcribed (IVT) mRNA; or d. IVT mRNA containing a poly(A) tail; or e. IVT mRNA containing a 5' cap The method according to claim 14.
16. Polynucleotides a. Not associated with any targeting component; or b. It associates with a targeting component that can target polynucleotides to cells or organs; or c. The polynucleotide is associated with a targeting component that can target cells or organs, and the targeting component is a vector. The method according to claim 14 or 15.
17. An animal comprising the composition according to any one of claims 1 to 12.
18. The animal according to claim 17, wherein the animal is a mammal, human, mouse, rabbit, llama, or cattle.
19. An animal according to any one of claims 13 to 16 or claim 17 or 18, wherein the animal is injected with the composition.
20. The composition is a. It is injected directly into the muscle of the animal; b. Injected into the animal multiple times. The method according to any one of claims 13 to 16, or the animal according to any one of claims 17 or 18.
21. The method according to any one of claims 13 to 16 or 19 to 20, wherein the method generates an immune response.
22. The method according to claim 21, wherein the immune response includes the production of antibodies.
23. The method according to claim 22, further comprising isolating the antibody.
24. The method according to claim 23, wherein the antibody is a fully human antibody, a chimeric antibody, a humanized antibody, a monoclonal antibody, and / or a polyclonal antibody.
25. An antibody produced by the method according to any one of claims 22 to 24.
26. The method according to claim 25, wherein a polyclonal antibody is further fractionated to obtain a single isolated antibody species.
27. An isolated antibody produced by the method described in claim 26.
28. The antibody according to any one of claims 13 to 16 and 19 to 26, or the antibody according to claim 27, wherein the antibody is affinity mature.
29. Affinity maturation, a. Phage display, yeast display, or ribosome display; or b. Panning technique The method or antibody according to claim 28, which is caused by...
30. An antibody produced by the method described in either claim 28 or 29.
31. A polynucleotide encoding the antibody according to any one of claims 25, 27, or 30.
32. The polynucleotide according to claim 31, further comprising a heterogeneous promoter.
33. The polynucleotide according to claim 31 or 32, further comprising a vector sequence.
34. A host cell comprising a polynucleotide according to any one of claims 1 to 12 or 31 to 33.
35. A mixture of polynucleotides encoding a peptidegenic protein or a mixture of SARS-CoV-2 peptidegenic proteins, wherein the peptidegenic protein is selected from the proteins shown in Table 2.
36. Polynucleotides that encode peptideogenic proteins, a. Encoding a mixture of SARS-CoV-2 peptidegenic proteins derived from the same SARS-CoV-2 initiation protein; or b. Encoding a mixture of SARS-CoV-2 peptidegenic proteins derived from multiple SARS-CoV-2 initiation proteins; or c. Encoding a mixture of SARS-CoV-2 peptidegenic proteins derived from multiple related SARS-CoV-2 initiation proteins; or d. Synthesized in vitro; or e. It is DNA; or f. in vitro transcribed (IVT) mRNA; or g. IVT mRNA containing a poly(A) tail; or h. IVT mRNA containing the 5' cap A mixture of peptidegenic proteins or polynucleotides according to claim 35.