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RU2010130851A - ВАРИАНТЫ Fc С ИЗМЕНЕННЫМ СВЯЗЫВАНИЕМ C FcRn - Google Patents

ВАРИАНТЫ Fc С ИЗМЕНЕННЫМ СВЯЗЫВАНИЕМ C FcRn Download PDF

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RU2010130851A
RU2010130851A RU2010130851/10A RU2010130851A RU2010130851A RU 2010130851 A RU2010130851 A RU 2010130851A RU 2010130851/10 A RU2010130851/10 A RU 2010130851/10A RU 2010130851 A RU2010130851 A RU 2010130851A RU 2010130851 A RU2010130851 A RU 2010130851A
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antibody
immunoadhesin
modification
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Аарон ЧЕМБЕРЛЕН (US)
Аарон ЧЕМБЕРЛЕН
Бассил ДАХЬЯТ (US)
Бассил ДАХЬЯТ
Джон Рудолф ДЕЗЬЯРЛЕЙС (US)
Джон Рудолф ДЕЗЬЯРЛЕЙС
Шер Бахадур КАРКИ (US)
Шер Бахадур КАРКИ
Грегори Алан ЛАЗАР (US)
Грегори Алан ЛАЗАР
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Ксенкор, Инк. (Us)
Ксенкор, Инк.
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Abstract

1. Вариантная область Fc, содержащая по меньшей мере одну модификацию по сравнению с областью Fc человека дикого типа, причем указанная модификация выбрана из группы, включающей 252Y/428L, 252Y/434S и 428L/434S, где нумерация приведена согласно индексу EU. ! 2. Вариантная область Fc по п.1, в котором указанная модификация представляет собой 428L/434S. ! 3. Вариантная область Fc по п.1, в котором указанная модификация представляет собой 252Y/428L. ! 4. Вариантная область Fc по п.1, в котором указанная модификация представляет собой 252Y/434S. ! 5. Вариантная область Fc по п.1, при этом указанный вариант содержит антитело или иммуноадгезин, и при этом указанная область Fc выбрана из группы, включающей IgG1, lgG2, lgG3 и lgG4. ! 6. Вариантная область Fc по п.5, которая содержит область Fc IgG1. ! 7. Вариантная область Fc по п.5, которая содержит область Fc IgG2. ! 8. Вариантная область Fc по п.5, которая обладает более длительным временем полужизни в сыворотке у млекопитающего по сравнению с указанным антителом или иммуноадгезином, содержащим указанную область Fc дикого типа. ! 9. Вариантная область Fc по п.8, причем указанное млекопитающее представляет собой мышь, экспрессирующую FcRn человека, или низший примат. ! 10. Вариантная область Fc по п.8, причем указанное млекопитающее представляет собой человека. ! 11. Вариантная область Fc по п.5, причем указанное антитело или иммуноадгезин обладает специфичностью в отношении антигена, выбранного из группы, включающей: фактор роста эндотелия сосудов (VEGF), фактор некроза опухолей α (TNF-α), CD25, рецептор эпидермального фактора роста (EGFR) и IgE. ! 12. Вариантное антитело или вариантный иммуноадгезин, содержащий вариант области Fc lgG2, причем указанное вариантное а�

Claims (17)

1. Вариантная область Fc, содержащая по меньшей мере одну модификацию по сравнению с областью Fc человека дикого типа, причем указанная модификация выбрана из группы, включающей 252Y/428L, 252Y/434S и 428L/434S, где нумерация приведена согласно индексу EU.
2. Вариантная область Fc по п.1, в котором указанная модификация представляет собой 428L/434S.
3. Вариантная область Fc по п.1, в котором указанная модификация представляет собой 252Y/428L.
4. Вариантная область Fc по п.1, в котором указанная модификация представляет собой 252Y/434S.
5. Вариантная область Fc по п.1, при этом указанный вариант содержит антитело или иммуноадгезин, и при этом указанная область Fc выбрана из группы, включающей IgG1, lgG2, lgG3 и lgG4.
6. Вариантная область Fc по п.5, которая содержит область Fc IgG1.
7. Вариантная область Fc по п.5, которая содержит область Fc IgG2.
8. Вариантная область Fc по п.5, которая обладает более длительным временем полужизни в сыворотке у млекопитающего по сравнению с указанным антителом или иммуноадгезином, содержащим указанную область Fc дикого типа.
9. Вариантная область Fc по п.8, причем указанное млекопитающее представляет собой мышь, экспрессирующую FcRn человека, или низший примат.
10. Вариантная область Fc по п.8, причем указанное млекопитающее представляет собой человека.
11. Вариантная область Fc по п.5, причем указанное антитело или иммуноадгезин обладает специфичностью в отношении антигена, выбранного из группы, включающей: фактор роста эндотелия сосудов (VEGF), фактор некроза опухолей α (TNF-α), CD25, рецептор эпидермального фактора роста (EGFR) и IgE.
12. Вариантное антитело или вариантный иммуноадгезин, содержащий вариант области Fc lgG2, причем указанное вариантное антитело или иммуноадгезин содержит от одной до пяти модификаций по сравнению с областью Fc lgG2 дикого типа, при этом по меньшей мере одна из указанных модификаций расположена в положении 434, где нумерация приведена согласно индексу EU, и при этом указанное вариантное антитело или вариантный иммуноадгезин обладает более продолжительным временем полужизни в сыворотке у млекопитающего по сравнению с указанным антителом или иммуноадгезином, содержащим указанную область Fc lgG2 дикого типа.
13. Вариантное антитело или вариантный иммуноадгезин по п.12, который содержит по меньшей мере одну модификацию в положении 434S и одну модификацию в положении, выбранном из группы, включающей: 252 и 428.
14. Вариантное антитело или вариантный иммуноадгезин по п.12, причем указанное млекопитающее представляет собой мышь, экспрессирующую FcRn человека, или низший примат.
15. Вариантное антитело или вариантный иммуноадгезин по п.12, причем указанное млекопитающее представляет собой человека.
16. Вариантная область Fc, содержащая по меньшей мере две модификации по сравнению с областью Fc человека дикого типа, причем по меньшей мере одна модификация представляет собой 428L и по меньшей мере одна модификация расположена в положении 252 или 434, где нумерация приведена согласно индексу EU.
17. Вариантная область Fc по п.16, в котором указанная область Fc содержит антитело или иммуноадгезин, и указанное антитело или иммуноадгезин содержит область Fc IgG1 или lgG2, и указанный вариант обладает более продолжительным временем полужизни в сыворотке у млекопитающего по сравнению с указанным антителом или иммуноадгезином, содержащим указанную область Fc человека дикого типа, и указанное млекопитающее представляет собой мышь, экспрессирующую FcRn человека, низший примат или людей.
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CN112955240B (zh) * 2018-10-25 2022-09-16 豪夫迈·罗氏有限公司 抗体FcRn结合的修饰

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