RU2021127872A - Доставка терапевтических полипептидов посредством псевдотипированных онколитических вирусов - Google Patents
Доставка терапевтических полипептидов посредством псевдотипированных онколитических вирусов Download PDFInfo
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- RU2021127872A RU2021127872A RU2021127872A RU2021127872A RU2021127872A RU 2021127872 A RU2021127872 A RU 2021127872A RU 2021127872 A RU2021127872 A RU 2021127872A RU 2021127872 A RU2021127872 A RU 2021127872A RU 2021127872 A RU2021127872 A RU 2021127872A
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Claims (20)
1. Онколитический вирус простого герпеса (ВПГ), содержащий рекомбинантную нуклеиновую кислоту, которая содержит i) первую последовательность нуклеиновой кислоты, кодирующую полипептид, содержащий первый домен, специфичный в отношении антигена, экспрессированного на эффекторной клетке, и второй домен, который связывается с антигеном, экспрессированным на клетке-мишени, причем указанный антиген, экспрессированный на эффекторной клетке, представляет собой FAP, PDL1 или CD47; и ii) вторую последовательность нуклеиновой кислоты, кодирующую полипептид–иммуномодулятор, выбранный из группы, состоящей из цитокина, костимулирующей молекулы, полипептида иммунной контрольной точки, антиангиогенного фактора и матриксной металлопротеиназы (MMP).
2. Онколитический ВПГ по п. 1, где антиген, экспрессированный на клетке-мишени, представляет собой FAP.
3. Онколитический ВПГ по п. 1, где антиген, экспрессированный на клетке-мишени, представляет собой PDL1.
4. Онколитический ВПГ по п. 1, где антиген, экспрессированный на клетке-мишени, представляет собой CD47.
5. Онколитический ВПГ по любому из пп. 1-4, где антиген, экспрессированный на эффекторной клетке, выбирают из CD3, CD16 и NKp46.
6. Онколитический ВПГ по п. 5, где антиген, экспрессированный на эффекторной клетке, представляет собой CD3.
7. Онколитический ВПГ по любому из пп. 1-6, причем первая и вторая последовательности нуклеиновой кислоты экспрессируются с одной последовательности промотора, присутствующей в рекомбинантной нуклеиновой кислоте.
8. Онколитический ВПГ по любому из пп. 1-7, где первая и вторая нуклеиновые кислоты имеют размер 7,2-38 т.о.
9. Онколитический ВПГ по любому из пп. 1-8, где ВПГ представляет собой ВПГ-1.
10. Онколитический ВПГ по любому из пп. 1-9, где полипептид–иммуномодулятор представляет собой цитокин, выбранный из IL-15, IL-12 и CXCL10.
11. Онколитический ВПГ по любому из пп. 1-9, где полипептид-иммуномодулятор включает (i) ингибитор PD–1, PDL–1, CTLA–4, LAG3, TIM3, нейропилин или CCR4; (ii) агонист GITR, OX–40 или CD28; или (iii) комбинацию (i) и (ii).
12. Онколитический ВПГ по любому из пп. 1-11, где один или более гликопротеинов ВПГ модифицируют, чтобы изменить тропизм онколитического ВПГ.
13. Фармацевтическая композиция, содержащая онколитический ВПГ по любому из пп. 1–12.
14. Фармацевтическая композиция по п. 13, дополнительное содержащая фармацевтически приемлемый носитель.
15. Способ лечения рака, включающий введение субъекту терапевтически эффективного количества онколитического ВПГ по любому из пп. 1–12 или его композиции.
16. Способ по п. 15, дополнительно включающий введение субъекту одного или более дополнительных вариантов терапии, включающих лучевую терапию, химиотерапию, иммунотерапию, гормональную терапию или комбинацию указанных вариантов терапии.
17. Способ по п. 15, где субъект получает или будет получать один или более вариантов терапии, включающих хирургическое вмешательство, лучевую терапию, химиотерапию, иммунотерапию, гормональную терапию или комбинацию указанных вариантов терапии.
18. Способ по любому из пп. 15-17, где онколитический ВПГ или композицию на его основе вводят системно.
19. Способ по п. 18, где онколитический ВПГ или композицию на его основе вводят парентерально.
20. Способ по любому из пп. 15-17, где онколитический ВПГ или композицию на его основе вводят в участок–мишень напрямую.
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SG11201811600PA (en) | 2019-01-30 |
RU2019102391A (ru) | 2020-07-30 |
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RU2758007C2 (ru) | 2021-10-25 |
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EP3478321A1 (en) | 2019-05-08 |
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EP3478321A4 (en) | 2020-04-22 |
CN109983121A (zh) | 2019-07-05 |
KR20190035714A (ko) | 2019-04-03 |
JP2019519245A (ja) | 2019-07-11 |
AU2017290828A1 (en) | 2019-01-24 |
WO2018006005A1 (en) | 2018-01-04 |
US20200157221A1 (en) | 2020-05-21 |
US20180057594A1 (en) | 2018-03-01 |
IL263879A (en) | 2019-01-31 |
BR112019000015A2 (pt) | 2019-04-24 |
US11078280B2 (en) | 2021-08-03 |
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