RU2008101365A - Композиции и способы диагностики и лечения опухоли - Google Patents
Композиции и способы диагностики и лечения опухоли Download PDFInfo
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- RU2008101365A RU2008101365A RU2008101365/13A RU2008101365A RU2008101365A RU 2008101365 A RU2008101365 A RU 2008101365A RU 2008101365/13 A RU2008101365/13 A RU 2008101365/13A RU 2008101365 A RU2008101365 A RU 2008101365A RU 2008101365 A RU2008101365 A RU 2008101365A
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- Y10T428/13—Hollow or container type article [e.g., tube, vase, etc.]
Abstract
1. Выделенное антитело, содержащее по меньшей мере одну HVR-последовательность, выбранную из группы, включающей: ! (а) последовательность HVR-L1, выбранную из одной из последовательностей, представленных в SEQ ID NO:14-34; ! (б) последовательность HVR-L2, выбранную из одной из последовательностей, представленных SEQ ID NO:35-58; ! (в) последовательность HVR-L3, выбранную из одной из последовательностей, представленных в SEQ ID NO:59-73; ! (г) последовательность HVR-H1, выбранную из одной из последовательностей, представленных в SEQ ID NO:74-93; ! (д) последовательность HVR-H2, выбранную из одной из последовательностей, представленных в SEQ ID NO:94-112; и ! (е) последовательность HVR-H3, выбранную из одной из последовательностей, представленных в SEQ ID NO:113-118. ! 2. Выделенное антитело по п.1, дополнительно содержащее последовательность акцепторного человеческого консенсусного каркасного участка HV, выбранную из одной из последовательностей, представленных в SEQ ID NO:184-193. ! 3. Выделенное антитело по п.1, дополнительно содержащее последовательность акцепторного человеческого консенсусного каркасного участка HL, выбранную из одной из последовательностей, представленных в SEQ ID NO:194-197. ! 4. Выделенное антитело по п.1, дополнительно содержащее последовательность акцепторного человеческого консенсусного каркасного участка HV, выбранную из одной из последовательностей, представленных в SEQ ID NO:184-193, и последовательность акцепторного человеческого консенсусного каркасного участка HL, выбранную из одной из последовательностей, представленных в SEQ ID NO:194-197. ! 5. Антитело по п.1, представляющее собой фрагмент антитела. ! 6. Антитело по п.1, представляющее собой химерное или гуманизированное антите�
Claims (36)
1. Выделенное антитело, содержащее по меньшей мере одну HVR-последовательность, выбранную из группы, включающей:
(а) последовательность HVR-L1, выбранную из одной из последовательностей, представленных в SEQ ID NO:14-34;
(б) последовательность HVR-L2, выбранную из одной из последовательностей, представленных SEQ ID NO:35-58;
(в) последовательность HVR-L3, выбранную из одной из последовательностей, представленных в SEQ ID NO:59-73;
(г) последовательность HVR-H1, выбранную из одной из последовательностей, представленных в SEQ ID NO:74-93;
(д) последовательность HVR-H2, выбранную из одной из последовательностей, представленных в SEQ ID NO:94-112; и
(е) последовательность HVR-H3, выбранную из одной из последовательностей, представленных в SEQ ID NO:113-118.
2. Выделенное антитело по п.1, дополнительно содержащее последовательность акцепторного человеческого консенсусного каркасного участка HV, выбранную из одной из последовательностей, представленных в SEQ ID NO:184-193.
3. Выделенное антитело по п.1, дополнительно содержащее последовательность акцепторного человеческого консенсусного каркасного участка HL, выбранную из одной из последовательностей, представленных в SEQ ID NO:194-197.
4. Выделенное антитело по п.1, дополнительно содержащее последовательность акцепторного человеческого консенсусного каркасного участка HV, выбранную из одной из последовательностей, представленных в SEQ ID NO:184-193, и последовательность акцепторного человеческого консенсусного каркасного участка HL, выбранную из одной из последовательностей, представленных в SEQ ID NO:194-197.
5. Антитело по п.1, представляющее собой фрагмент антитела.
6. Антитело по п.1, представляющее собой химерное или гуманизированное антитело.
7. Антитело по п.1, конъюгированное с ингибирующим рост агентом.
8. Антитело по п.1, конъюгированное с цитотоксическим агентом.
9. Антитело по п.8, в котором цитотоксический агент выбран из группы, включающей токсины, антибиотики, радиоактивные изотопы или нуклеолитические ферменты.
10. Антитело по п.8, в котором цитотоксический агент представляет собой токсин.
11. Антитело по п.10, в котором токсин выбран из группы, включающей майтансиноид и калихеамицин.
12. Антитело по п.10, в котором токсин представляет собой майтансиноид.
13. Антитело по п.1, которое продуцируется в бактериях.
14. Антитело по п.1, которое продуцируется в СНО-клетках.
15. Антитело по п.1, которое индуцирует гибель клетки, с которой оно связывается.
16. Антитело по п.15, где клетка представляет собой клетку рака яичника.
17. Антитело по п.1, которое несет обнаруживаемую метку.
18. Выделенное антитело, которое содержит по меньшей мере один из гипервариабельных участков любого антитела, продуцируемого любой из линий клеток гибридомы, представленных в таблице 11.
19. Моноклональное антитело, продуцируемое любой из линий клеток гибридомы, представленных в таблице 11.
20. Клетка гибридомы, которая продуцирует моноклональное антитело, связывающееся в полипептидом ТАТ10772.
21. Способ идентификации первого антитела, которое связывается с антигенным эпитопом ТАТ10772, сшитым со вторым антителом, где второе антитело представляет собой любое из антител по пп.1, 18 или 19, заключающийся в том, что определяют способностью первого антитела блокировать связывание второго антитела с полипептидом ТАТ10772, где способность первого антитела блокировать связывание второго антитела с полипептидом ТАТ10772 составляет по меньшей мере 40%, и при использовании одинаковых концентраций антител свидетельствует о том, что первое антитело обладает способностью связываться с эпитопом, с которым связывается второе антитело.
22. Способ ингибирования роста клетки, которая экспрессирует белок, имеющий аминокислотную последовательность, представленную в SEQ ID NO:2, заключающийся в том, что приводят в контакт клетку с антителом по одному из пп.1, 18 или 19, при этом связывание антитела с белком вызывает ингибирование роста указанной клетки.
23. Способ по п.22, в котором клетка представляет собой клетку рака яичника.
24. Способ терапевтического лечения млекопитающего, которое имеет злокачественную опухоль, содержащую клетки, которые экспрессируют белок, имеющий аминокислотную последовательность, которая представлена в SEQ ID NO:2, заключающийся в том, что вводят млекопитающему в терапевтически эффективном количестве антитело по одному из пп.1, 18 или 19, осуществляя тем самым эффективное лечение млекопитающего.
25. Способ по п.4, в котором злокачественная опухоль представляет собой опухоль яичника.
26. Способ определения присутствия белка ТАТ10772 в образце, в котором предполагается присутствие указанного белка, заключающийся в том, что обрабатывают образец антителом по одному из пп.1, 18 или 19 и определяют связывание антитела с белком в образце, где связывание антитела с белком свидетельствует о присутствии указанного белка в образце.
27. Способ по п.26, в котором образец содержит клетку, которая, как предполагается, экспрессирует указанный белок.
28. Способ по п.27, в котором клетка представляет собой клетку рака яичника.
29. Способ по п.26, в котором антитело несет обнаруживаемую метку.
30. Способ диагностики присутствия опухоли у млекопитающего, заключающийся в том, что определяют уровень экспрессии гена, кодирующего белок, который имеет аминокислотную последовательность, представленную в SEQ ID NO:2, в тест-образце клеток ткани, полученных из организма млекопитающего, и в контрольном образце клеток, полученных из такой же ткани, для которых известно, что они являются здоровыми, где более высокий уровень экспрессии указанного белка в тест-образце по сравнению с контрольным образцом свидетельствует о присутствии опухоли у млекопитающего, из организма которого получен тест-образец.
31. Способ по п.30, в котором стадия определения уровня экспрессии гена, кодирующего указанный белок, заключается в применении олигонуклеотида в гибридизации in situ или РВ-ПЦР-анализе.
32. Способ по п.30, в котором стадия определения уровня экспрессии гена, кодирующего указанный белок, заключается в применении антитела в иммуногистохимическом анализе или анализе методом Вестерн-блоттинга.
33. Способ по п.30, в котором опухоль представляет собой опухоль яичника, молочной железы или поджелудочной железы.
34. Способ диагностического выявления опухоли у млекопитающего, заключающийся в том, что приводят в контакт тест-образец клеток ткани, полученных из организма млекопитающего, с антителом по одному из пп.1, 18 или 19 и выявляют образование комплекса между антителом и белком ТАТ10772 в тест-образце, где образование комплекса свидетельствует о присутствии опухоли в организме млекопитающего.
35. Способ по п.34, в котором тест-образец клеток ткани получают из организма индивидуума, у которого предполагается наличие злокачественной опухоли.
36. Способ по п.35, в котором злокачественная опухоль представляет собой опухоль яичника, молочной железы или поджелудочной железы.
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