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RU2016119423A - МЫШИ, ЭКСПРЕССИРУЮЩИЕ ЛЕГКУЮ ЦЕПЬ С ВАРИАБЕЛЬНОЙ ОБЛАСТЬЮ λ ЧЕЛОВЕКА И КОНСТАНТНОЙ ОБЛАСТЬЮ МЫШИ - Google Patents

МЫШИ, ЭКСПРЕССИРУЮЩИЕ ЛЕГКУЮ ЦЕПЬ С ВАРИАБЕЛЬНОЙ ОБЛАСТЬЮ λ ЧЕЛОВЕКА И КОНСТАНТНОЙ ОБЛАСТЬЮ МЫШИ Download PDF

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RU2016119423A
RU2016119423A RU2016119423A RU2016119423A RU2016119423A RU 2016119423 A RU2016119423 A RU 2016119423A RU 2016119423 A RU2016119423 A RU 2016119423A RU 2016119423 A RU2016119423 A RU 2016119423A RU 2016119423 A RU2016119423 A RU 2016119423A
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hvλ3
light chain
human
hvλ2
allele
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RU2016119423A
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RU2016119423A3 (ru
RU2724736C2 (ru
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Линн МАКДОНАЛЬД
Шон СТИВЕНС
Джаган ГУРЕР
Эндрю Дж. МЕРФИ
Каролина А. ХОСИАВА
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Ридженерон Фармасьютикалз, Инк.
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Claims (29)

1. Способ получения последовательности нуклеиновой кислоты вариабельной области λ легкой цепи, включающий:
(a) получение клетки из мыши, содержащей эндогенный аллель λ (лямбда) легкой цепи, содержащий неперегруппированный генный сегмент Vλ легкой цепи иммуноглобулина человека и непегруппированный генный сегмент Jλ иммуноглобулина человека, функционально связанные с λ константным геном (Сλ), причем мышь содержит делецию в первом генном кластере Vλ-Jλ-Cλ эндогенного аллеля λ легкой цепи мыши и замену, полную или частичную, генных сегментов Vλ-Jλ второго генного кластера Vλ-Jλ-Cλ аллеля генными сегментами Vλ и Jλ человека; и
(b) клонирование из указанной клетки последовательности нуклеиновой кислоты вариабельной области λ легкой цепи, происходящей из генного сегмента Vλ и генного сегмента Jλ.
2. Способ по п. 1, в котором эндогенный аллель λ (лямбда) легкой цепи содержит:
(a) по меньшей мере 12 неперегруппированных генных сегментов Vλ человека; или
(b) 13-28 неперегруппированных генных сегментов Vλ человека.
3. Способ по п. 2, в котором генные сегменты Vλ человека включают:
(a) hVλ3-1, hVλ4-3, hVλ2-8, hVλ3-9, hVλ3-10, hVλ2-11 и hVλ3-12; или
(b) hVλ2-14, hVλ3-16, hVλ2-18, hVλ3-19, hVλ3-21, hVλ3-22, hVλ2-23, hVλ3-25 и hVλ3-27.
4. Способ по п. 1, в котором мышь содержит совокупность генных сегментов Vλ человека.
5. Способ по п. 4, в котором эндогенный аллель λ (лямбда) легкой цепи содержит:
(a) по меньшей мере 12 неперегруппированных генных сегментов Vλ человека; или
(b) 13-28 неперегруппированных генных сегментов Vλ человека.
6. Способ по п. 5, в котором генные сегменты Vλ человека включают:
(a) hVλ3-1, hVλ4-3, hVλ2-8, hVλ3-9, hVλ3-10, hVλ2-11 и hVλ3-12; или
(b) hVλ2-14, hVλ3-16, hVλ2-18, hVλ3-19, hVλ3-21, hVλ3-22, hVλ2-23, hVλ3-25 и hVλ3-27.
7. Способ по п. 1, в котором эндогенный аллель λ (лямбда) легкой цепи содержит один неперегруппированный генный сегмент Jλ человека, который представляет собой hJλ1.
8. Способ по п. 1, в котором эндогенный аллель λ (лямбда) легкой цепи содержит четыре неперегруппированных генных сегмента Jλ человека.
9. Способ по п. 8, в котором четыре неперегруппированных генных сегмента Jλ человека представляют собой Jλ1, Jλ2, Jλ3 и Jλ7.
10. Способ по п. 1, в котором эндогенный аллель λ (лямбда) легкой цепи лишен энлогенного генного сегмента Vλ.
11. Способ по любому из пп. 1, 2, 4, 5, 7 и 10, в котором эндогенный аллель κ (каппа) легкой цепи делетирован.
12. Способ по п. 11, в котором клетка представляет собой гибридому.
13. Способ по п. 11, в котором клетка представляет собой В-клетку.
14. Способ по п. 1, в котором эндогенный аллель λ (лямбда) легкой цепи мыши содержит:
(а) непрерывную последовательность локуса λ легкой цепи человека, которая простирается от Vλ3-12 до Vλ3-1;
(b) непрерывную последовательность локуса λ легкой цепи человека, которая простирается от Vλ3-27 до Vλ3-1; или
(c) непрерывную последовательность локуса λ легкой цепи человека, которая простирается от Vλ3-2 9 до Vλ3-1 и непрерывную последовательность локуса λ легкой цепи человека, которая простирается от Vλ5-52 до Vλ1-40.
15. Способ по любому из пп. 1-10 и 14, в котором клетка представляет собой гибридому.
16. Способ по любому из пп. 1-10 и 14, в котором клетка представляет собой В-клетку.
RU2016119423A 2010-06-22 2011-06-22 МЫШИ, ЭКСПРЕССИРУЮЩИЕ ЛЕГКУЮ ЦЕПЬ С ВАРИАБЕЛЬНОЙ ОБЛАСТЬЮ λ ЧЕЛОВЕКА И КОНСТАНТНОЙ ОБЛАСТЬЮ МЫШИ RU2724736C2 (ru)

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US61/357,317 2010-06-22
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