RU2019107976A - Композиция вакцины - Google Patents
Композиция вакцины Download PDFInfo
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- RU2019107976A RU2019107976A RU2019107976A RU2019107976A RU2019107976A RU 2019107976 A RU2019107976 A RU 2019107976A RU 2019107976 A RU2019107976 A RU 2019107976A RU 2019107976 A RU2019107976 A RU 2019107976A RU 2019107976 A RU2019107976 A RU 2019107976A
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- 229960005486 vaccine Drugs 0.000 title 1
- 241000700605 Viruses Species 0.000 claims 32
- 125000003275 alpha amino acid group Chemical group 0.000 claims 25
- 206010028980 Neoplasm Diseases 0.000 claims 19
- 102000004169 proteins and genes Human genes 0.000 claims 19
- 108090000623 proteins and genes Proteins 0.000 claims 19
- 238000000034 method Methods 0.000 claims 15
- 239000000427 antigen Substances 0.000 claims 14
- 230000000890 antigenic effect Effects 0.000 claims 14
- 102000036639 antigens Human genes 0.000 claims 14
- 108091007433 antigens Proteins 0.000 claims 14
- 239000002245 particle Substances 0.000 claims 13
- 239000002773 nucleotide Substances 0.000 claims 12
- 125000003729 nucleotide group Chemical group 0.000 claims 12
- 229940023867 prime-boost vaccine Drugs 0.000 claims 12
- 230000003612 virological effect Effects 0.000 claims 11
- 150000007523 nucleic acids Chemical class 0.000 claims 7
- 201000011510 cancer Diseases 0.000 claims 6
- 108020004707 nucleic acids Proteins 0.000 claims 6
- 102000039446 nucleic acids Human genes 0.000 claims 6
- 241000124008 Mammalia Species 0.000 claims 4
- 241000711970 Vesiculovirus Species 0.000 claims 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 2
- 201000010881 cervical cancer Diseases 0.000 claims 2
- 230000000295 complement effect Effects 0.000 claims 2
- 230000036039 immunity Effects 0.000 claims 2
- 230000001939 inductive effect Effects 0.000 claims 2
- 230000000174 oncolytic effect Effects 0.000 claims 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
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Claims (50)
1. Гетерологичная прайм-буст вакцина для применения в лечении рака у млекопитающего, содержащая
первый вирус, содержащий нуклеиновую кислоту, способную экспрессировать опухолеассоциированный антиген ВПЧ, причем указанный первый вирус способен вызывать иммунитет к указанному опухолеассоциированному антигену ВПЧ;
второй вирус, причем указанный второй вирус представляет собой везикуловирус, при этом второй вирус содержит нуклеиновую кислоту, способную экспрессировать опухолеассоциированный антиген ВПЧ, причем указанный второй вирус способен обеспечивать терапевтический онколитический эффект у указанного млекопитающего;
причем указанный первый вирус иммунологически отличается и физически изолирован от указанного второго вируса; и
при этом либо (i) указанный опухолеассоциированный антиген ВПЧ содержит аминокислотную последовательность, которая по меньшей мере на 80% идентична SEQ ID NO. 7; или (ii) второй вирус представляет собой вирус Maraba MG1.
2. Гетерологичная прайм-буст вакцина по п. 1, характеризующаяся тем, что второй вирус представляет собой Maraba MG1.
3. Гетерологичная прайм-буст вакцина по п. 1 или 2, характеризующаяся тем, что указанный опухолеассоциированный антиген ВПЧ, экспрессируемый указанной нуклеиновой кислотой в указанном первом, указанном втором вирусе, или в обоих вирусах, содержит аминокислотную последовательность, которая по меньшей мере на 80% идентична SEQ ID NO: 7.
4. Гетерологичная прайм-буст вакцина по п. 3, характеризующаяся тем, что указанная аминокислотная последовательность по меньшей мере на 90% идентична SEQ ID NO: 7.
5. Гетерологичная прайм-буст вакцина по п. 3, характеризующаяся тем, что указанная аминокислотная последовательность по меньшей мере на 95% идентична SEQ ID NO: 7.
6. Гетерологичная прайм-буст вакцина по п. 5, характеризующаяся тем, что указанная аминокислотная последовательность содержит SEQ ID NO: 7.
7. Гетерологичная прайм-буст вакцина по п. 6, характеризующаяся тем, что указанная аминокислотная последовательность состоит из SEQ ID NO: 7.
8. Гетерологичная прайм-буст вакцина по п. 6, характеризующаяся тем, что указанная аминокислотная последовательность кодируется нуклеотидной последовательностью SEQ ID NO: 8.
9. Гетерологичная прайм-буст вакцина по п. 8, характеризующаяся тем, что вирус Maraba MG1 содержит обратно-комплементарную и РНК-версию нуклеотидной последовательности SEQ ID NO: 9.
10. Гетерологичная прайм-буст вакцина по любому из пп. 1-9, характеризующаяся тем, что указанный первый вирус включен в состав для внутримышечного введения, и указанный второй вирус включен в состав для внутривенного введения.
11. Гетерологичная прайм-буст вакцина по любому из пп. 1-10, характеризующаяся тем, что указанные первый и второй вирусы экспрессируют один и тот же опухолеассоциированный антиген ВПЧ.
12. Гетерологичная прайм-буст вакцина по любому из пп. 1-11, характеризующаяся тем, что рак представляет собой рак шейки матки.
13. Антигенный белок ВПЧ, содержащий аминокислотную последовательность, которая по меньшей мере на 80% идентична SEQ ID NO: 7.
14. Антигенный белок ВПЧ по п. 13, причем указанный антигенный белок содержит аминокислотную последовательность, которая по меньшей мере на 90% идентична SEQ ID NO: 7.
15. Антигенный белок ВПЧ по п. 13, причем указанный антигенный белок содержит аминокислотную последовательность, которая по меньшей мере на 95% идентична SEQ ID NO: 7.
16. Антигенный белок ВПЧ по п. 13, причем указанный антигенный белок содержит аминокислотную последовательность SEQ ID NO: 7.
17. Антигенный белок ВПЧ по п. 13, причем указанный антигенный белок состоит из аминокислотной последовательности SEQ ID NO: 7.
18. Антигенный белок ВПЧ по п. 16, причем указанный антигенный белок кодируется нуклеотидной последовательностью SEQ ID NO: 8.
19. Выделенная вирусная частица, содержащая последовательность нуклеиновой кислоты, способную кодировать антигенный белок по п. 13.
20. Выделенная вирусная частица по п. 19, причем указанная вирусная частица представляет собой везикуловирус.
21. Выделенная вирусная частица по п. 20, причем указанный выделенный везикуловирус представляет собой частицу Maraba MG1.
22. Выделенная вирусная частица по любому из пп. 19-21, причем указанная нуклеотидная последовательность кодирует белок, содержащий аминокислотную последовательность, которая по меньшей мере на 90% идентична SEQ ID NO:7.
23. Выделенная вирусная частица по любому из пп. 19-21, причем указанная нуклеотидная последовательность кодирует белок, содержащий аминокислотную последовательность, которая по меньшей мере на 95% идентична SEQ ID NO:7.
24. Выделенная вирусная частица по любому из пп. 19-21, причем указанная нуклеотидная последовательность кодирует белок, содержащий аминокислотную последовательность SEQ ID NO: 7.
25. Выделенная вирусная частица по любому из пп. 19-21, причем указанная нуклеотидная последовательность кодирует белок, состоящий из аминокислотной последовательности SEQ ID NO: 7.
26. Выделенная вирусная частица по п. 24, причем указанная аминокислотная последовательность кодируется нуклеотидной последовательностью SEQ ID NO: 8.
27. Выделенная вирусная частица по п. 24, причем вирусная частица Maraba MG1 содержит обратно-комплементарную и РНК-версию нуклеотидной последовательности SEQ ID NO: 9.
28. Выделенная вирусная частица по п. 27, причем обратно-комплементарная и РНК-версия нуклеотидной последовательности SEQ ID NO: 9 способна экспрессировать антиген ВПЧ последовательности SEQ ID NO: 7.
29. Способ лечения млекопитающего с раком, где указанный рак экспрессирует антигенный белок ВПЧ, причем указанный способ включает:
a) введение первого вируса, содержащего нуклеиновую кислоту, способную экспрессировать опухолеассоциированный антиген ВПЧ, причем указанный первый вирус способен вызывать иммунитет к указанному опухолеассоциированному антигену ВПЧ;
b) введение второго вируса, причем указанный второй вирус представляет собой везикуловирус, при этом второй вирус содержит нуклеиновую кислоту, способную экспрессировать опухолеассоциированный антиген ВПЧ, причем указанный второй вирус способен обеспечивать терапевтический онколитический эффект у указанного млекопитающего;
причем указанный первый вирус иммунологически отличается и физически изолирован от указанного второго вируса; и
при этом либо (i) указанный опухолеассоциированный антиген ВПЧ содержит аминокислотную последовательность, которая по меньшей мере на 80% идентична SEQ ID NO. 7; или (ii) второй вирус представляет собой вирус Maraba MG1.
30. Способ по п. 29, в котором указанный второй вирус представляет собой Maraba MG1.
31. Способ по п. 29 или 30, в котором указанный опухолеассоциированный антиген ВПЧ, экспрессируемый указанной нуклеиновой кислотой в указанном первом, указанном втором вирусе, или в обоих вирусах, содержит аминокислотную последовательность, которая по меньшей мере на 80% идентична SEQ ID NO: 7.
32. Способ по п. 31, в котором указанная аминокислотная последовательность по меньшей мере на 90% идентична SEQ ID NO: 7.
33. Способ по п. 32, в котором указанная аминокислотная последовательность по меньшей мере на 95% идентична SEQ ID NO: 7.
34. Способ по п. 33, в котором указанная аминокислотная последовательность содержит SEQ ID NO: 7.
35. Способ по п. 33, в котором указанная аминокислотная последовательность состоит из SEQ ID NO: 7.
36. Способ по п. 34, в котором указанная аминокислотная последовательность кодируется нуклеотидной последовательностью SEQ ID NO: 8.
37. Способ по п. 34, в котором геном Maraba MG1 содержит обратно-комплементарную и РНК-версию нуклеотидной последовательности SEQ ID NO: 9.
38. Способ по любому из пп. 29-37, в котором указанный первый вирус вводят внутримышечно, и второй вирус вводят внутривенно.
39. Способ по любому из пп. 29-38, в котором указанные первый и второй вирусы оба экспрессируют один и тот же опухолеассоциированный антиген ВПЧ.
40. Способ по п. 39, в котором указанный опухолеассоциированный антиген ВПЧ содержит аминокислотную последовательность SEQ ID NO: 7.
41. Способ по любому из пп. 29-40, в котором рак экспрессирует белки E6 или E7 ВПЧ в качестве антигенных белков.
42. Способ по любому из пп. 29-41, в котором рак представляет собой рак шейки матки.
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