RU2013155485A - Антигены f rsv в конформации "перед слиянием" - Google Patents
Антигены f rsv в конформации "перед слиянием" Download PDFInfo
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- 239000000427 antigen Substances 0.000 title 1
- 102000036639 antigens Human genes 0.000 title 1
- 108091007433 antigens Proteins 0.000 title 1
- 241000725643 Respiratory syncytial virus Species 0.000 claims abstract 44
- 230000004927 fusion Effects 0.000 claims abstract 42
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 33
- 229920001184 polypeptide Polymers 0.000 claims abstract 32
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 32
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims abstract 18
- 230000004048 modification Effects 0.000 claims abstract 7
- 238000012986 modification Methods 0.000 claims abstract 7
- 238000012217 deletion Methods 0.000 claims abstract 6
- 230000037430 deletion Effects 0.000 claims abstract 6
- 235000018417 cysteine Nutrition 0.000 claims abstract 4
- 230000013595 glycosylation Effects 0.000 claims abstract 4
- 238000006206 glycosylation reaction Methods 0.000 claims abstract 4
- 230000035772 mutation Effects 0.000 claims abstract 4
- 230000000368 destabilizing effect Effects 0.000 claims abstract 3
- 230000000087 stabilizing effect Effects 0.000 claims abstract 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims abstract 2
- 150000001945 cysteines Chemical class 0.000 claims abstract 2
- 238000003780 insertion Methods 0.000 claims abstract 2
- 230000037431 insertion Effects 0.000 claims abstract 2
- 102000037865 fusion proteins Human genes 0.000 claims 11
- 108020001507 fusion proteins Proteins 0.000 claims 11
- 239000000203 mixture Substances 0.000 claims 8
- 230000002163 immunogen Effects 0.000 claims 7
- 101710160621 Fusion glycoprotein F0 Proteins 0.000 claims 3
- 230000003472 neutralizing effect Effects 0.000 claims 3
- 101100107610 Arabidopsis thaliana ABCF4 gene Proteins 0.000 claims 2
- 101100068078 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) GCN4 gene Proteins 0.000 claims 2
- 241000700605 Viruses Species 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- -1 benzonaphthyridine compound Chemical class 0.000 claims 2
- 230000028993 immune response Effects 0.000 claims 2
- 230000001939 inductive effect Effects 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 239000000178 monomer Substances 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 238000006384 oligomerization reaction Methods 0.000 claims 2
- 238000005829 trimerization reaction Methods 0.000 claims 2
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 claims 1
- 102000030907 Aspartate Carbamoyltransferase Human genes 0.000 claims 1
- 101100022187 Caenorhabditis elegans mab-10 gene Proteins 0.000 claims 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 1
- 108091000126 Dihydroorotase Proteins 0.000 claims 1
- 101710154606 Hemagglutinin Proteins 0.000 claims 1
- 241000351643 Metapneumovirus Species 0.000 claims 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 claims 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 claims 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 claims 1
- 101710176177 Protein A56 Proteins 0.000 claims 1
- 229940096437 Protein S Drugs 0.000 claims 1
- 108010076504 Protein Sorting Signals Proteins 0.000 claims 1
- 241000315672 SARS coronavirus Species 0.000 claims 1
- 101710198474 Spike protein Proteins 0.000 claims 1
- 101800001690 Transmembrane protein gp41 Proteins 0.000 claims 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims 1
- 238000004891 communication Methods 0.000 claims 1
- 125000002228 disulfide group Chemical group 0.000 claims 1
- 239000000839 emulsion Substances 0.000 claims 1
- 239000000185 hemagglutinin Substances 0.000 claims 1
- 230000000091 immunopotentiator Effects 0.000 claims 1
- 206010022000 influenza Diseases 0.000 claims 1
- 101150091368 mab-20 gene Proteins 0.000 claims 1
- 229960001521 motavizumab Drugs 0.000 claims 1
- 229960000402 palivizumab Drugs 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/735—Fusion polypeptide containing domain for protein-protein interaction containing a domain for self-assembly, e.g. a viral coat protein (includes phage display)
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- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18522—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18534—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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Abstract
1. Полипептид F респираторно-синцитиального вируса (RSV) в конформации перед слиянием, содержащий по меньшей мере два встроенных остатка цистеина, где указанные цистеины находятся в непосредственной близости друг с другом и образуют дисульфидную связь, стабилизирующую полипептид F RSV в конформации "перед слиянием".2. Полипептид F RSV в конформации "перед слиянием" по п. 1, где указанные цистеиновые мутации находятся не более чем приблизительно в 10 Å друг от друга.3. Полипептид F RSV в конформации "перед слиянием" по п. 1, где область HRB и область DI и/или DII содержат встроенный остаток цистеина, и между встроенным остатком цистеина в области HRB и встроенным остатком цистеина в области DI или DII образуется дисульфидная связь.4. Полипептид F RSV в конформации "перед слиянием" по п. 1, где область HRA и область DIII содержат встроенный остаток цистеина, и между встроенными остатками цистеина в области HRA и области DIII образуется дисульфидная связь.5. Полипептид F RSV в конформации "перед слиянием" по п. 1, где область HRA содержит по меньшей мере два встроенных остатка цистеина, и между встроенными остатками цистеина в области HRA образуется дисульфидная связь.6. Полипептид F RSV респираторно-синцитиального вируса (RSV) в конформации "перед слиянием", содержащий модификации из конформации "после слияния", выбранные из группы, состоящей из делеции спирали HRA, делеции спирали HRB, встраивания точечных мутаций, добавления участков гликозилирования и их комбинаций, где указанная модификация из конформации "после слияния" дестабилизирует конформацию "после слияния".7. Полипептид F RSV в конформации "перед слиянием" по п. 6, где указанной дестабилизирующей модифика�
Claims (30)
1. Полипептид F респираторно-синцитиального вируса (RSV) в конформации перед слиянием, содержащий по меньшей мере два встроенных остатка цистеина, где указанные цистеины находятся в непосредственной близости друг с другом и образуют дисульфидную связь, стабилизирующую полипептид F RSV в конформации "перед слиянием".
2. Полипептид F RSV в конформации "перед слиянием" по п. 1, где указанные цистеиновые мутации находятся не более чем приблизительно в 10 Å друг от друга.
3. Полипептид F RSV в конформации "перед слиянием" по п. 1, где область HRB и область DI и/или DII содержат встроенный остаток цистеина, и между встроенным остатком цистеина в области HRB и встроенным остатком цистеина в области DI или DII образуется дисульфидная связь.
4. Полипептид F RSV в конформации "перед слиянием" по п. 1, где область HRA и область DIII содержат встроенный остаток цистеина, и между встроенными остатками цистеина в области HRA и области DIII образуется дисульфидная связь.
5. Полипептид F RSV в конформации "перед слиянием" по п. 1, где область HRA содержит по меньшей мере два встроенных остатка цистеина, и между встроенными остатками цистеина в области HRA образуется дисульфидная связь.
6. Полипептид F RSV респираторно-синцитиального вируса (RSV) в конформации "перед слиянием", содержащий модификации из конформации "после слияния", выбранные из группы, состоящей из делеции спирали HRA, делеции спирали HRB, встраивания точечных мутаций, добавления участков гликозилирования и их комбинаций, где указанная модификация из конформации "после слияния" дестабилизирует конформацию "после слияния".
7. Полипептид F RSV в конформации "перед слиянием" по п. 6, где указанной дестабилизирующей модификацией из конформации "после слияния" является делеция спирали HRB.
8. Полипептид F RSV в конформации "перед слиянием" по п. 7, дополнительно содержащий делецию пептида слияния.
9. Полипептид F RSV в конформации "перед слиянием" по п. 6, где указанной дестабилизирующей модификацией из конформации "после слияния" является добавление участка гликозилирования.
10. Полипептид F RSV в конформации "перед слиянием" по п. 9, где указанный участок гликозилирования находится на остатке, выбранном из группы, состоящей из положения 173, положения 175 и положения 184.
11. Полипептид F респираторно-синцитиального вируса (RSV) в конформации "перед слиянием", содержащий три мономера F RSV, где по меньшей мере два мономера содержат встроенный остаток цистеина, и указанные встроенные остатки цистеина находятся в непосредственной близости друг к другу и образуют дисульфидную связь, стабилизирующую полипептид F RSV в конформации "перед слиянием".
12. Полипептид F RSV в конформации "перед слиянием" по п. 1, где полипептид F RSV в конформации "перед слиянием" является растворимым эктодоменом F RSV или гримером растворимого эктодомена F RSV.
13. Химерный белок F в конформации "перед слиянием", содержащий стабилизированный белок F из вируса, иного, чем RSV, содержащий один или несколько нейтрализующих эпитопов F RSV.
14. Химерный белок F в конформации "перед слиянием" по п. 13, где указанный стабилизированный белок F происходит из полипептида F вируса парагриппа или полипептида F метапневмовируса.
15. Химерный белок F в конформации "перед слиянием" по п. 13, где указанный стабилизированный белок F является полипептидом F PIV5 в конформации "перед слиянием" или полипептидом F NDV в конформации "перед слиянием".
16. Химерный белок F в конформации "перед слиянием" по п. 13, где стабилизированный белок F является растворимым эктодоменом.
17. Химерный белок F в конформации "перед слиянием" по п. 13, где указанные нейтрализующие эпитопы F RSV происходят из области HRA F RSV.
18. Химерный белок F в конформации "перед слиянием" по п. 13, где нейтрализующие эпитопы выбраны из группы, состоящей из эпитопов, распознаваемых мотавизумабом, паливизумабом, mAb 11, mAb 151, mAb 1129, mAb 1153, mAb 1200, mAb 1214, mAb 1237, mAb 47F, mAb 7C2, mAb B4, Fab 19, mAb AK13A2, mAb 7.936, mAb 9.936, mAb 19, mAb 20, mAb 10 IF и их комбинациями.
19. Полипептид F RSV в конформации "перед слиянием" по любому из пп. 1-12 или химерный белок F в конформации "перед слиянием" по любому из пп. 13-18, дополнительно содержащий гетерологичный домен олигомеризации, эпитоп или сигнальный пептид.
20. Полипептид F RSV в конформации "перед слиянием" по любому из пп. 1-12 или химерный белок F в конформации "перед слиянием" по любому из пп. 13-18, где указанный гетерологичный домен олигомеризации является доменом тримеризации.
21. Полипептид F RSV в конформации "перед слиянием" по любому из пп. 1-12 или химерный белок F в конформации "перед слиянием" по любому из пп. 13-18, где домен тримеризации происходит из гемагглютинина вируса гриппа, белка шипов вируса SARS, gp41 ВИЧ, NadA, модифицированного GCN4, GCN4 или аспартаткарбамоилтрансферазы.
22. Иммуногенная композиция, содержащая полипептид F RSV в конформации "перед слиянием" по любому из пп. 1-12 или химерный белок F в конформации "перед слиянием" по любому из пп. 13-18.
23. Иммуногенная композиция по п. 22, где указанная композиция дополнительно содержит адъювант.
24. Иммуногенная композиция по п. 23, где адъювант выбран из группы, состоящей из: соли алюминия, эмульсии "сквален-в-воде", соединения бензонафтиридина, фосфолипидного соединения, низкомолекулярного иммунопотенциатора и любых их комбинаций.
25. Выделенная нуклеиновая кислота, кодирующая полипептид F RSV в конформации "перед слиянием" по любому из пп. 1-12 или химерный белок F в конформации "перед слиянием" по любому из пп. 13-18.
26. Выделенная нуклеиновая кислота по п. 25, являющаяся самореплицирующейся молекулой РНК.
27. Иммуногенная композиция, содержащая самореплицирующуюся молекулу РНК по п. 26.
28. Иммуногенная композиция по п. 26, дополнительно содержащая систему доставки РНК.
29. Способ индуцирования у индивидуума иммунного ответа на F RSV, включающий введение индивидууму иммуногенной композиции по любому из пп. 22-24.
30. Способ индуцирования у индивидуума иммунного ответа на F RSV, включающий введение индивидууму иммуногенной композиции по п. 27 или 28.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161486005P | 2011-05-13 | 2011-05-13 | |
| US61/486,005 | 2011-05-13 | ||
| PCT/US2012/037773 WO2012158613A1 (en) | 2011-05-13 | 2012-05-14 | Pre-fusion rsv f antigens |
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| RU2013155485A true RU2013155485A (ru) | 2015-06-20 |
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| RU2013155485/10A RU2013155485A (ru) | 2011-05-13 | 2012-05-14 | Антигены f rsv в конформации "перед слиянием" |
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| US (8) | US20140248314A1 (ru) |
| EP (2) | EP2707385B1 (ru) |
| JP (1) | JP2014519819A (ru) |
| CN (1) | CN103842374A (ru) |
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| BR (1) | BR112013029169B1 (ru) |
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| DK (2) | DK2707385T3 (ru) |
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| FR (1) | FR23C1046I2 (ru) |
| HR (2) | HRP20171703T1 (ru) |
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| RU (1) | RU2013155485A (ru) |
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| SI (2) | SI3275892T1 (ru) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| EP4218799A1 (en) | 2009-07-15 | 2023-08-02 | GlaxoSmithKline Biologicals S.A. | Rsv f protein compositions and methods for making same |
| HUE047796T2 (hu) | 2010-07-06 | 2020-05-28 | Glaxosmithkline Biologicals Sa | RNS bevitele több immunútvonal bekapcsolására |
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- 2012-05-14 CA CA2835644A patent/CA2835644C/en active Active
- 2012-05-14 DK DK17191721.4T patent/DK3275892T3/da active
- 2012-05-14 WO PCT/US2012/037773 patent/WO2012158613A1/en not_active Ceased
- 2012-05-14 PL PL17191721T patent/PL3275892T3/pl unknown
- 2012-05-14 ES ES17191721T patent/ES2782119T3/es active Active
- 2012-05-14 EP EP17191721.4A patent/EP3275892B1/en not_active Revoked
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2017
- 2017-10-20 US US15/789,074 patent/US20180237476A1/en not_active Abandoned
- 2017-11-17 CY CY20171101209T patent/CY1119849T1/el unknown
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2020
- 2020-03-18 HR HRP20200451TT patent/HRP20200451T1/hr unknown
- 2020-03-26 CY CY20201100283T patent/CY1122826T1/el unknown
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2021
- 2021-05-07 US US17/314,649 patent/US20210269489A1/en not_active Abandoned
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2022
- 2022-06-23 US US17/848,247 patent/US20220332767A1/en not_active Abandoned
- 2022-06-23 US US17/848,230 patent/US12139512B2/en active Active
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2023
- 2023-04-27 US US18/308,583 patent/US20230287056A1/en not_active Abandoned
- 2023-11-28 FR FR23C1046C patent/FR23C1046I2/fr active Active
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2024
- 2024-03-05 US US18/596,426 patent/US20240239845A1/en not_active Abandoned
- 2024-09-24 US US18/895,059 patent/US20250042951A1/en active Pending
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