RU2017126476A - Новые модуляторы и способы их применения - Google Patents

Новые модуляторы и способы их применения Download PDF

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RU2017126476A
RU2017126476A RU2017126476A RU2017126476A RU2017126476A RU 2017126476 A RU2017126476 A RU 2017126476A RU 2017126476 A RU2017126476 A RU 2017126476A RU 2017126476 A RU2017126476 A RU 2017126476A RU 2017126476 A RU2017126476 A RU 2017126476A
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seq
residues
cancer
kit
variable region
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Орит ФУРД
Скотт Дж. ДИЛЛА
Роберт А. СТАЛЛ
Алекс БЭНКОВИЧ
Александра Лейда Лиана ЛАЗЕТИК
Джеффри БЕРНШТЕЙН
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АббВай Стемсентркс ЭлЭлСи
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Priority claimed from PCT/US2011/050451 external-priority patent/WO2012031280A2/en
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Claims (42)

1. Набор, содержащий один или более контейнеров, содержащих антитело или его антиген-связывающий фрагмент либо конъюгат антитела, содержащий антитело или его антиген-связывающий фрагмент, конъюгированные, связанные или иным образом ассоциированные с цитотоксическим агентом, где антитело или его антиген-связывающий фрагмент связывается с РТК7 (протеинтирозинкиназа 7) человека и содержит:
а) три CDR вариабельной области легкой цепи, представленной в SEQ ID NO: 62, и три CDR вариабельной области тяжелой цепи, представленной в SEQ ID NO: 63; или
б) три CDR вариабельной области легкой цепи, представленной в SEQ ID NO: 64, и три CDR вариабельной области тяжелой цепи, представленной в SEQ ID NO: 65.
2. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 24-34 из SEQ ID NO: 62 для VL CDR1, остатки 50-56 из SEQ ID NO: 62 для VL CDR2, и остатки 89-97 из SEQ ID NO: 62 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 31-35 из SEQ ID NO: 63 для VH CDR1, остатки 50-65 из SEQ ID NO: 63 для VH CDR2, и остатки 95-102 из SEQ ID NO: 63 для VH CDR3; где нумерация CDR является нумерацией по Kabat.
3. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 23-34 из SEQ ID NO: 62 для VL CDR1, остатки 50-56 из SEQ ID NO: 62 для VL CDR2, и остатки 89-97 из SEQ ID NO: 62 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 26-32 из SEQ ID NO: 63 для VH CDR1, остатки 50-58 из SEQ ID NO: 63 для VH CDR2, и остатки 95-102 из SEQ ID NO: 63 для VH CDR3; где нумерация CDR является нумерацией по Chothia.
4. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 30-36 из SEQ ID NO: 62 для VL CDR1, остатки 46-55 из SEQ ID NO: 62 для VL CDR2, и остатки 89-96 из SEQ ID NO: 62 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 30-35 из SEQ ID NO: 63 для VH CDR1, остатки 47-58 из SEQ ID NO: 63 для VH CDR2, и остатки 93-101 из SEQ ID NO: 63 для VH CDR3; где нумерация CDR является нумерацией по MacCallum.
5. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит вариабельную область легкой цепи, имеющую аминокислотную последовательность, которая по меньшей мере на 60% идентична SEQ ID NO: 62, и вариабельную область тяжелой цепи, имеющую аминокислотную последовательность, которая по меньшей мере на 60% идентична SEQ ID NO: 63.
6. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит вариабельную область легкой цепи, представленную в SEQ ID NO: 62, и вариабельную область тяжелой цепи, представленную в SEQ ID NO: 63.
7. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 24-34 из SEQ ID NO: 64 для VL CDR1, остатки 50-56 из SEQ ID NO: 64 для VL CDR2 и остатки 89-97 из SEQ ID NO: 64 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 31-35 из SEQ ID NO: 65 для VH CDR1, остатки 50-65 из SEQ ID NO: 65 для VH CDR2, и остатки 95-102 из SEQ ID NO: 65 для VH CDR3; где нумерация CDR является нумерацией по Kabat.
8. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 23-34 из SEQ ID NO: 64 для VL CDR1, остатки 50-56 из SEQ ID NO: 64 для VL CDR2, и остатки 89-97 из SEQ ID NO: 64 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 26-32 из SEQ ID NO: 65 для VH CDR1, остатки 50-58 из SEQ ID NO: 65 для VH CDR2, и остатки 95-102 из SEQ ID NO: 65 для VH CDR3; где нумерация CDR является нумерацией по Chothia.
9. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит:
а) вариабельную область легкой цепи, содержащую три CDR, представленные как остатки 30-36 из SEQ ID NO: 64 для VL CDR1, остатки 46-55 из SEQ ID NO: 64 для VL CDR2, и остатки 89-96 из SEQ ID NO: 64 для VL CDR3; и
б) вариабельную область тяжелой цепи, содержащую три CDR, представленные как остатки 30-35 из SEQ ID NO: 65 для VH CDR1, остатки 47-58 из SEQ ID NO: 65 для VH CDR2, и остатки 93-101 из SEQ ID NO: 65 для VH CDR3; где нумерация CDR является нумерацией по MacCallum.
10. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит вариабельную область легкой цепи, имеющую аминокислотную последовательность, которая по меньшей мере на 60% идентична SEQ ID NO: 64, и вариабельную область тяжелой цепи, имеющую аминокислотную последовательность, которая по меньшей мере на 60% идентична SEQ ID NO: 65.
11. Набор по п. 1, где антитело или его антиген-связывающий фрагмент содержит вариабельную область легкой цепи, представленную в SEQ ID NO: 64, и вариабельную область тяжелой цепи, представленную в SEQ ID NO: 65.
12. Набор по любому из пп. 1-11, где антитело или его антиген-связывающий фрагмент представляет собой нейтрализирующее антитело, истощающее антитело и/или интернализованное антитело.
13. Набор по любому из пп. 1-11, где антитело или его антиген-связывающий фрагмент представляет собой моноклональное антитело, химерное антитело, CDR-привитое антитело, гуманизированное антитело или его антиген-связывающий фрагмент.
14. Набор по любому из пп. 1-13, содержащий инструкцию по применению набора в обнаружении, диагностике или мониторинге рака.
15. Набор по п. 14, где рак представляет собой рак молочной железы, рак яичников, колоректальный рак, рак поджелудочной железы, рак легкого или рак кожи.
16. Набор по п. 15, где рак представляет собой рак яичников.
17. Набор по п. 15, где рак молочной железы представляет собой трижды отрицательный рак молочной железы.
18. Набор по п. 15, где рак легкого представляет собой немелкоклеточный рак легкого.
19. Набор по любому из пп. 1-13, содержащий инструкцию по применению набора в лечении рака.
20. Набор по п. 19, где рак представляет собой рак молочной железы, рак яичников, колоректальный рак, рак поджелудочной железы, рак легкого или рак кожи.
21. Набор по п. 20, где рак представляет собой рак яичников.
22. Набор по п. 20, где рак молочной железы представляет собой трижды отрицательный рак молочной железы.
23. Набор по п. 20, где рак легкого представляет собой немелкоклеточный рак легкого.
24. Набор по любому из пп. 1-13, содержащий инструкцию по применению набора в снижении частоты появления опухоль-инициирующих клеток у субъекта, имеющего рак.
25. Набор по п. 24, где рак представляет собой рак молочной железы, рак яичников, колоректальный рак, рак поджелудочной железы, рак легкого или рак кожи.
26. Набор по п. 25, где рак представляет собой рак яичников.
27. Набор по п. 25, где рак молочной железы представляет собой трижды отрицательный рак молочной железы.
28. Набор по п. 25, где рак легкого представляет собой немелкоклеточный рак легкого.
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