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RU2014145633A - Композиции и способы для диагностики и лечения опухолей - Google Patents

Композиции и способы для диагностики и лечения опухолей Download PDF

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RU2014145633A
RU2014145633A RU2014145633A RU2014145633A RU2014145633A RU 2014145633 A RU2014145633 A RU 2014145633A RU 2014145633 A RU2014145633 A RU 2014145633A RU 2014145633 A RU2014145633 A RU 2014145633A RU 2014145633 A RU2014145633 A RU 2014145633A
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antibody
tat194
sequence
seq
cdr
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RU2014145633A
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Сунил Бхакта
Мередит ХАЗЕН
Джо-Энн С. ХОНГО
Джагат Р. ДЖУНУТУЛА
Исидро ХОТЗЕЛ
Юнлэй ШАН
Шан-Фань ЮЙ
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Дженентек, Инк.
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Abstract

1. Выделенное антитело, включающее, по меньшей мере, одну CDR последовательность, выбранную из группы, состоящей из:(a) CDR-L1 последовательности любого из SEQ ID NO:4-10;(b) CDR-L2 последовательности любого из SEQ ID NO:11-16;(c) CDR-L3 последовательности любого из SEQ ID NO: 17-24;(d) CDR-H1 последовательности любого из SEQ ID NO:25-32 или 67;(e) CDR-H2 последовательности любого из SEQ ID NO:33-40 или 68; и(f) CDR-H3 последовательности любого из SEQ ID NO:41-48 или 69-73.2. Выделенное антитело, включающее VH последовательность и VL последовательность, при этом указанная VL последовательность представляет собой любую последовательность из указанных в SEQ ID NO:49-57 или 74.3. Клетка, которая продуцирует антитело по п. 1.4. Выделенная нуклеиновая кислота, которая кодирует антитело по п. 1.5. Способ идентификации первого антитела, которое связывается с ТАТ194 антигенным эпитопом, связанным вторым антителом, при этом указанное второе антитело представляет собой антитело по п. 1, при этом указанный способ включает определение способности указанного первого антитела блокировать связывание указанного второго антитела с ТАТ194 полипептидом, при этом способность указанного первого антитела блокировать связывание указанного второго антитела с указанным ТАТ194 полипептидом, по меньшей мере, на 40% и при равных концентрациях антител указывает на способность указанного первого антитела связываться с эпитопом, связанным указанным вторым антителом.6. Способ ингибирования роста клетки, которая экспрессирует ТАТ194 полипептид, при этом указанный способ включает контактирование указанной клетки с антителом по п. 1, при этом связывание указанного антитела с указанным ТАТ194 полипептидом вызывает ингибирование роста указанной клетки.7. Способ терапевтического лечения млекопитающего, имеющего раковую опухоль, включа

Claims (11)

1. Выделенное антитело, включающее, по меньшей мере, одну CDR последовательность, выбранную из группы, состоящей из:
(a) CDR-L1 последовательности любого из SEQ ID NO:4-10;
(b) CDR-L2 последовательности любого из SEQ ID NO:11-16;
(c) CDR-L3 последовательности любого из SEQ ID NO: 17-24;
(d) CDR-H1 последовательности любого из SEQ ID NO:25-32 или 67;
(e) CDR-H2 последовательности любого из SEQ ID NO:33-40 или 68; и
(f) CDR-H3 последовательности любого из SEQ ID NO:41-48 или 69-73.
2. Выделенное антитело, включающее VH последовательность и VL последовательность, при этом указанная VL последовательность представляет собой любую последовательность из указанных в SEQ ID NO:49-57 или 74.
3. Клетка, которая продуцирует антитело по п. 1.
4. Выделенная нуклеиновая кислота, которая кодирует антитело по п. 1.
5. Способ идентификации первого антитела, которое связывается с ТАТ194 антигенным эпитопом, связанным вторым антителом, при этом указанное второе антитело представляет собой антитело по п. 1, при этом указанный способ включает определение способности указанного первого антитела блокировать связывание указанного второго антитела с ТАТ194 полипептидом, при этом способность указанного первого антитела блокировать связывание указанного второго антитела с указанным ТАТ194 полипептидом, по меньшей мере, на 40% и при равных концентрациях антител указывает на способность указанного первого антитела связываться с эпитопом, связанным указанным вторым антителом.
6. Способ ингибирования роста клетки, которая экспрессирует ТАТ194 полипептид, при этом указанный способ включает контактирование указанной клетки с антителом по п. 1, при этом связывание указанного антитела с указанным ТАТ194 полипептидом вызывает ингибирование роста указанной клетки.
7. Способ терапевтического лечения млекопитающего, имеющего раковую опухоль, включающую клетки, экспрессирующие ТАТ194, при этом указанный способ включает введение указанному млекопитающему терапевтически эффективного количества
антитела по п. 1 с обеспечением, таким образом, эффективного лечения указанного млекопитающего.
8. Способ определения присутствия ТАТ194 белка в образце, в котором предполагают наличие указанного белка, при этом указанный способ включает обработку указанного образца антителом по п. 1 и определение связывания указанного антитела с указанным белком в указанном образце, при этом связывание антитела с указанным белком указывает на присутствие указанного белка в указанном образце.
9. Способ диагностики присутствия опухоли у млекопитающего, при этом указанный способ включает определение уровня экспрессии гена, кодирующего ТАТ194 полипептид, в тестируемом образце клеток ткани, полученных от указанного млекопитающего и в контрольном образце известных нормальных клеток из той же ткани, при этом повышенный уровень экспрессии указанного ТАТ194 полипептида в тестируемом образце по сравнению с контрольным образцом свидетельствует о присутствии опухоли у млекопитающего, от которого был получен тестируемый образец.
10. Способ диагностики присутствия опухоли у млекопитающего, при этом указанный способ включает контактирование тестируемого образца клеток ткани, полученных от указанного млекопитающего, с антителом по п. 1 и детектирование образования комплекса между указанным антителом и ТАТ194 белком в тестируемом образце, при этом образование комплекса свидетельствует о присутствии опухоли у указанного млекопитающего.
11. Способ доставки цитотоксического или диагностического агента в клетку, которая экспрессирует ТАТ194 полипептид, при этом указанный способ включает обеспечение цитотоксического агента или диагностического агента, конъюгированного с антителом, которое связывается с указанным ТАТ194 полипептидом с образованием конъюгата антитело-агент, и обработку указанной клетки конъюгатом антитело-агент.
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