RU2010135624A - Стабилизированные антитела против ангиопоэтина-2 и их применение - Google Patents

Стабилизированные антитела против ангиопоэтина-2 и их применение Download PDF

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RU2010135624A
RU2010135624A RU2010135624/10A RU2010135624A RU2010135624A RU 2010135624 A RU2010135624 A RU 2010135624A RU 2010135624/10 A RU2010135624/10 A RU 2010135624/10A RU 2010135624 A RU2010135624 A RU 2010135624A RU 2010135624 A RU2010135624 A RU 2010135624A
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seq
antibody
cancer
variable region
chain variable
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Ваэ БЕДИАН (US)
Ваэ БЕДИАН
Вилльям ДАЛЛЬ'АКВА (US)
Вилльям ДАЛЛЬ'АКВА
Херрен ВУ (US)
Херрен ВУ
Майкл БОУЭН (US)
Майкл БОУЭН
Джеффри БРАУН (US)
Джеффри БРАУН
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Крис СТАННАРД
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Медиммун Лимитед (Gb)
Медиммун Лимитед
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Abstract

1. Выделенное антитело, которое связывается с ангиопоэтином-2 (Ang-2), причем антитело включает вариабельную область легкой цепи: ! a) SEQ ID No:3 (MEDI1); ! b) SEQ ID No:4 (MEDI2); ! c) SEQ ID No:5 (MEDI3); ! d) SEQ ID No:6 (MEDI4); или !e) SEQ ID No:8 (MEDI6). ! 2. Антитело по п.1, причем антитело включает вариабельную область легкой цепи SEQ ID No:3 (MEDI1). ! 3. Антитело по п.1, причем антитело продуцируется с высокой эффективностью в клетках-хозяевах млекопитающих, которая равна или в 2 раза или более превышает эффективность продуцирования антитела против Ang-2, содержащего SEQ ID No:1 и SEQ ID No:2 (3.19.3). ! 4. Антитело по п.1, причем антитело проявляет скорость агрегации, которая по меньшей мере на 10% ниже скорости агрегации антитела против Ang-2, содержащего SEQ ID No:1 и SEQ ID No:2 (3.19.3), которую определяли в аналогичных условиях. ! 5. Антитело по п.1, причем антитело дополнительно включает вариабельную область тяжелой цепи SEQ ID No:7 (MEDI5). ! 6. Антитело по п.1, причем антитело включает вариабельную область легкой цепи SEQ ID No:3 (MEDI1) и вариабельную область тяжелой цепи SEQ ID No:7 (MEDI5). ! 7. Антитело по п.6, причем антитело проявляет температуру плавления, которая является более высокой, чем температура плавления антитела против Ang-2, содержащего SEQ ID No:1 и SEQ ID No:2 (3.19.3). ! 8. Выделенная нуклеиновая кислота, кодирующая по меньшей мере одно выделенное антитело, которое связывается с ангиопоэтином-2 (Ang-2), включающее вариабельные области легкой и тяжелой цепи SEQ ID No:3 (MEDI1) и SEQ ID No:7 (MEDI5). ! 9. Композиция, содержащая: ! a) выделенное антитело, которое связывается с Ang-2, причем антитело включает вариабельную область легкой цепи SEQ ID No:3 (MEDI1) и вариабельную область тяжелой цепи SEQ ID No: 7 (MEDI5); и ! b) эксципиент, ! для применения в ингибировании ангиоге�

Claims (15)

1. Выделенное антитело, которое связывается с ангиопоэтином-2 (Ang-2), причем антитело включает вариабельную область легкой цепи:
a) SEQ ID No:3 (MEDI1);
b) SEQ ID No:4 (MEDI2);
c) SEQ ID No:5 (MEDI3);
d) SEQ ID No:6 (MEDI4); или
e) SEQ ID No:8 (MEDI6).
2. Антитело по п.1, причем антитело включает вариабельную область легкой цепи SEQ ID No:3 (MEDI1).
3. Антитело по п.1, причем антитело продуцируется с высокой эффективностью в клетках-хозяевах млекопитающих, которая равна или в 2 раза или более превышает эффективность продуцирования антитела против Ang-2, содержащего SEQ ID No:1 и SEQ ID No:2 (3.19.3).
4. Антитело по п.1, причем антитело проявляет скорость агрегации, которая по меньшей мере на 10% ниже скорости агрегации антитела против Ang-2, содержащего SEQ ID No:1 и SEQ ID No:2 (3.19.3), которую определяли в аналогичных условиях.
5. Антитело по п.1, причем антитело дополнительно включает вариабельную область тяжелой цепи SEQ ID No:7 (MEDI5).
6. Антитело по п.1, причем антитело включает вариабельную область легкой цепи SEQ ID No:3 (MEDI1) и вариабельную область тяжелой цепи SEQ ID No:7 (MEDI5).
7. Антитело по п.6, причем антитело проявляет температуру плавления, которая является более высокой, чем температура плавления антитела против Ang-2, содержащего SEQ ID No:1 и SEQ ID No:2 (3.19.3).
8. Выделенная нуклеиновая кислота, кодирующая по меньшей мере одно выделенное антитело, которое связывается с ангиопоэтином-2 (Ang-2), включающее вариабельные области легкой и тяжелой цепи SEQ ID No:3 (MEDI1) и SEQ ID No:7 (MEDI5).
9. Композиция, содержащая:
a) выделенное антитело, которое связывается с Ang-2, причем антитело включает вариабельную область легкой цепи SEQ ID No:3 (MEDI1) и вариабельную область тяжелой цепи SEQ ID No: 7 (MEDI5); и
b) эксципиент,
для применения в ингибировании ангиогенеза раковой опухоли у животного, нуждающегося в этом.
10. Композиция по п.9, причем композиция дополнительно содержит один или несколько других противоопухолевых терапевтических агентов.
11. Композиция по п.9, где рак выбран из группы, состоящей из меланомы, рака ободочной кишки, колоректального рака, рака легких, мелкоклеточного рака легких, немелкоклеточного рака легких, рака молочной железы, рака прямой кишки, рака желудка, глиомы, рака предстательной железы, рака яичника, рака яичек, рака щитовидной железы, рака почек, рака печени, гепатоклеточного рака, рака поджелудочной железы, рака мозга, рака шеи, глиобластомы, эндометриального рака и рака центральной нервной системы.
12. Композиция, содержащая:
a) выделенное антитело, которое связывается с Ang-2; и
b) эксципиент,
для применения в профилактике, лечении или контроле ангиогенеза, ассоциированного с заболеванием, у животного, нуждающегося в этом.
13. Композиция по п.12, где ангиогенез, ассоциированный с заболеванием, ассоциирован с серонегативным артритом, сероположительным артритом, артритом, ассоциированным с другими артропатиями, остеоартритом или SLE; и необязательно,
где сероположительный артрит представляет собой ревматоидный артрит.
14. Композиция по п.12, дополнительно содержащая один или несколько противовоспалительных терапевтических агентов; и необязательно,
где противовоспалительный терапевтический агент представляет собой антагонист TNF-α.
15. Композиция по п.12, где антитело включает вариабельную область легкой цепи SEQ ID No:3 (MEDI1) и вариабельную область тяжелой цепи SEQ ID No:7 (MEDI5).
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