Manipulated GCN4 trimerized motif
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- メボックス リミテッド
- Filing Date
- 2024-05-15
- Publication Date
- 2026-06-09
Smart Images
Figure 2026518692000001_ABST
Abstract
Claims
1. A dehumanized GCN4 trimerized motif.
2. The dehumanized GCN4 trimerized motif according to claim 1, wherein the trimerized motif is a coiled-coil trimerized motif.
3. The dehumanized GCN4 trimerized motif according to claim 1 or 2, comprising or consisting solely of a fragment or variant thereof having at least 70%, 71%, 72%, 73%, 74%, or 75% sequence identity with the amino acid sequence shown in SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, or preferably at least 76%, 77%, 78%, 79%, or 80% sequence identity with the SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO:
3.
4. A dehumanized GCN4 trimerized motif according to any one of claims 1 to 3, comprising or consisting solely of a fragment or variant thereof having substantially the amino acid sequence shown in SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, or having at least 81%, 82%, 83%, 84%, or 85% sequence identity with SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, or preferably at least 86%, 87%, 88%, 89%, or 90% sequence identity with SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO:
3.
5. A dehumanized GCN4 trimerized motif according to any one of claims 1 to 4, comprising or consisting solely of the amino acid sequence substantially shown in SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, or fragments or variants thereof having at least 91%, 92%, 93%, 94%, or 95% sequence identity with SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, or preferably at least 96%, 97%, 98%, or 99% sequence identity therewith.
6. A dehumanized GCN4 trimerized motif according to any one of claims 1 to 5, comprising substantially only the amino acid sequence shown in SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO:
3.
7. A dehumanized GCN4 trimerized motif according to any one of claims 1 to 6, comprising substantially only the amino acid sequence shown in Sequence ID No.
1.
8. The dehumanized GCN4 trimerized motif according to any one of claims 1 to 7, wherein the dehumanized GCN4 trimerized motif has electrostatic interactions between all three helix pairs.
9. The dehumanized GCN4 trimerized motif according to claim 8, wherein the electrostatic interaction between all three helix pairs is an Arg-Glu interaction.
10. The dehumanized GCN4 trimerized motif according to claim 8 or 9, wherein the electrostatic interaction between all three helix pairs includes the interaction between the residue pairs Arg22-Glu101, Arg96-Glu64, and / or Arg52-Glu17.
11. An immunogen comprising a dehumanized GCN4 trimerized motif as described in any one of claims 1 to 10.
12. The immunogen according to claim 11, wherein the immunogen induces an immune response to a viral or bacterial infection.
13. The immunogen according to claim 11 or 12, wherein the immunogen induces an immune response to viruses of the Adenoviridae, Aneroviridae, Arenaviridae, Astroviridae, Bornaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Hepadnaviridae, Hepeviridae, Herpesviridae, Orthomyxoviridae, Papillomaviridae, Paramyxoviridae, Parvoviridae, Picovirinaviridae, Picovirina, Picornaviridae, Pneumoviridae, Polyomaviridae, Poxviridae, Reoviridae, Retroviridae, Laboviridae, Togaviridae, or Deltaviridae families.
14. The immunogen according to any one of claims 11 to 13, wherein the immunogen induces an immune response to a virus selected from the group consisting of measles virus, mumps virus, parainfluenza virus, nipah virus, canine morbillivirus, rinderpest measles virus, and respiratory syncytial virus (RSV).
15. The immunogen according to any one of claims 11 to 14, wherein the immunogen comprises an F protein selected from the group consisting of measles virus F protein, mumps virus F protein, parainfluenza virus F protein, nipah virus F protein, canine morbillivirus F protein, rinderpest measles virus F protein, and respiratory syncytial virus (RSV) F protein.
16. The immunogen according to any one of claims 11 to 15, wherein the immunogen comprises a mumps virus (MuV) fusion ectodomain trimer (F protein), wherein preferably the MuV F ectodomain trimer is fused to the N-terminus of the dehumanized GCN4 trimerized motif.
17. The immunogen according to claim 16, wherein the C-terminal residue of the MuV F ectodomain trimer substantially comprises or consists solely of the amino acid sequence shown in SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7, or fragments or variants thereof.
18. The immunogen according to claim 16 or 17, wherein the MuV F ectodomain trimer comprises or consists solely of the amino acid sequence shown in SEQ ID NO: 8 or SEQ ID NO: 105, or fragments or variants thereof.
19. The immunogen according to any one of claims 16 to 18, wherein the immunogen comprises a MuV HN ectodomain, wherein preferably the MuV HN ectodomain is fused to the C-terminus of the dehumanized GCN4 trimerized motif.
20. The immunogen according to claim 19, wherein the MuV HN ectodomain comprises or consists solely of the amino acid sequence shown in Sequence ID No. 9, or a fragment or variant thereof.
21. The immunogen according to any one of claims 16 to 20, wherein the immunogen comprises a linker region, which preferably is located between the dehumanized GCN4 trimerized motif and the MuV HN ectodomain.
22. The immunogen according to claim 21, wherein the linker region substantially comprises or consists solely of the amino acid sequence shown in SEQ ID NO: 10 or SEQ ID NO: 11, or fragments or variants thereof.
23. The immunogen according to any one of claims 11 to 22, wherein the immunogen comprises or consists solely of the amino acid sequence shown in Sequence ID No. 12, or a fragment or variant thereof.
24. A nucleic acid encoding a dehumanized GCN4 trimerized motif according to any one of claims 1 to 10, or an immunogen according to any one of claims 11 to 23.
25. The nucleic acid according to claim 24, wherein the dehumanized GCN4 trimerized motif is substantially encoded by the nucleotide sequence shown in SEQ ID NO: 103, or a variant or fragment thereof.
26. The nucleic acid according to claim 24, wherein the immunogen is substantially encoded by the nucleotide sequence shown in Sequence ID No. 104, or a variant or fragment thereof.
27. A virus-like particle (VLP) containing an immunogen according to any one of claims 11 to 23.
28. An immunogenic composition comprising an immunogen according to any one of claims 11 to 23 or a VLP according to claim 27, and a pharmaceutically acceptable vehicle.
29. An immunogen according to any one of claims 11 to 23, a virus-like particle according to claim 27, or an immunogenic composition according to claim 28, for therapeutic or preventive use.
30. An immunogen according to any one of claims 11 to 23, a virus-like particle according to claim 27, or an immunogenic composition according to claim 28 for inducing an immune response.
31. The immunogen, virus-like particles, or immunogenic composition for the use described in claim 30, wherein the immunogen, virus-like particles, or immunogenic composition induce an immune response to a viral or bacterial infection, wherein preferably the virus is a virus from the Adenoviridae, Aneroviridae, Arenaviridae, Astroviridae, Bornaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Hepadnaviridae, Hepeviridae, Herpesviridae, Orthomyxoviridae, Papillomaviridae, Paramyxoviridae, Parvoviridae, Picovirinaviridae, Picovirina, Picornaviridae, Pneumoviridae, Polyomaviridae, Poxviridae, Reoviridae, Retroviridae, Labovyridae, Togaviridae, or Deltaviridae.
32. The immunogen, virus-like particles, or immunogenic composition for the use described in claim 30 or 31, wherein the immunogen, virus-like particles, or immunogenic composition induce an immune response to a virus selected from the group consisting of measles virus, mumps virus, parainfluenza virus, nipah virus, canine morbillivirus, rinderpest measles virus, and respiratory syncytial virus (RSV).