RU2014132888A - Стабильные и растворимые антитела, ингибирующие vegf - Google Patents
Стабильные и растворимые антитела, ингибирующие vegf Download PDFInfo
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- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 title claims abstract 10
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- 230000002401 inhibitory effect Effects 0.000 title 1
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Abstract
1. Рекомбинантное антитело, содержащее вариабельную область тяжелой цепи (VH), где VH содержит СDRH1, СDRH2 и СDRH3 последовательности SEQ ID NO:8, SEQ ID NO:20 и SEQ ID NO:32 соответственно и вариабельную область легкой цепи (VL), где VL содержит СDRL1, СDRL2 и СDRL3 последовательности SEQ ID NO:43, SEQ ID NO:55 и SEQ ID NO:66 соответственно.2. Рекомбинантное антитело по п. 1, где вариабельная область тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:164 и вариабельная область легкой цепи содержит аминокислотную последовательность SEQ ID NO:87.3. Антиген-связывающий фрагмент рекомбинантного антитела по п. 1 или 2, где фрагмент представляет собой scFv или Fab, F(ab')или Fab'.4. Антиген-связывающий фрагмент по п. 3, где фрагмент представляет собой scFv и где вариабельная область тяжелой цепи и вариабельная область легкой цепи связаны последовательностью SEQ ID NO:181.5. Фармацевтическая композиция, содержащая рекомбинантное антитело по п. 1 или 2.6. Фармацевтическая композиция, содержащая антиген-связывающий фрагмент по п. 3.7. Фармацевтическая композиция, содержащая антиген-связывающий фрагмент по п. 4.8. Способ лечения VEGF-опосредованного заболевания у человека, включающий введение индивидууму терапевтически эффективного количества антитела по п. 1 или 2, обеспечивая таким образом, лечение VEGF-опосредованного заболевания.9. Способ по п. 8, где VEGF-опосредованное заболевание выбрано из группы, состоящей из возрастной дегенерации желтого пятна, неоваскулярной глаукомы, диабетической ретинопатии, ретинопатии недоношенных, ретролентальной фиброплазии, карцином молочной железы, карцином легких, желудочных карцином, эзофагеальных карцином, колоректальных карцином, карцином печени, ка�
Claims (13)
1. Рекомбинантное антитело, содержащее вариабельную область тяжелой цепи (VH), где VH содержит СDRH1, СDRH2 и СDRH3 последовательности SEQ ID NO:8, SEQ ID NO:20 и SEQ ID NO:32 соответственно и вариабельную область легкой цепи (VL), где VL содержит СDRL1, СDRL2 и СDRL3 последовательности SEQ ID NO:43, SEQ ID NO:55 и SEQ ID NO:66 соответственно.
2. Рекомбинантное антитело по п. 1, где вариабельная область тяжелой цепи содержит аминокислотную последовательность SEQ ID NO:164 и вариабельная область легкой цепи содержит аминокислотную последовательность SEQ ID NO:87.
3. Антиген-связывающий фрагмент рекомбинантного антитела по п. 1 или 2, где фрагмент представляет собой scFv или Fab, F(ab')2 или Fab'.
4. Антиген-связывающий фрагмент по п. 3, где фрагмент представляет собой scFv и где вариабельная область тяжелой цепи и вариабельная область легкой цепи связаны последовательностью SEQ ID NO:181.
5. Фармацевтическая композиция, содержащая рекомбинантное антитело по п. 1 или 2.
6. Фармацевтическая композиция, содержащая антиген-связывающий фрагмент по п. 3.
7. Фармацевтическая композиция, содержащая антиген-связывающий фрагмент по п. 4.
8. Способ лечения VEGF-опосредованного заболевания у человека, включающий введение индивидууму терапевтически эффективного количества антитела по п. 1 или 2, обеспечивая таким образом, лечение VEGF-опосредованного заболевания.
9. Способ по п. 8, где VEGF-опосредованное заболевание выбрано из группы, состоящей из возрастной дегенерации желтого пятна, неоваскулярной глаукомы, диабетической ретинопатии, ретинопатии недоношенных, ретролентальной фиброплазии, карцином молочной железы, карцином легких, желудочных карцином, эзофагеальных карцином, колоректальных карцином, карцином печени, карцином яичника, ком, арренобластом, карцином шейки матки, эндометриальной карциномы, эндометриальной гиперплазии, эндометриоза, фибросарком, хориокарциномы, рака головы и шеи, назофарингеальной карциномы, карцином гортани, гепатобластомы, саркомы Капоши, меланомы, кожных карцином, гемангиомы, кавернозной гемангиомы, гемангиобластомы, карцином поджелудочной железы, ретинобластомы, астроцитомы, глиобластомы, Шванномы, олигодендроглиомы, медуллобластомы, нейробластом, рабдомиосаркомы, остеогенной саркомы, лейомиосарком, карцином мочеполовых путей, карцином щитовидной железы, опухоли Вильмса, почечно-клеточной карциномы, рака предстательной железы, аномальной пролиферации сосудов, ассоциированной с факоматозом, эдемы (например, ассоциированной с опухолями головного мозга), синдрома Мейжа, ревматоидного артрита, псориаза и атеросклероза.
10. Способ лечения VEGF-опосредованного заболевания у человека, включающий введение индивидууму терапевтически эффективного количества антиген-связывающего фрагмента по п. 3, обеспечивая, таким образом, лечение VEGF-опосредованного заболевания.
11. Способ по п. 10, где VEGF-опосредованное заболевание
выбрано из группы, состоящей из возрастной дегенерации желтого пятна, неоваскулярной глаукомы, диабетической ретинопатии, ретинопатии недоношенных, ретролентальной фиброплазии, карцином молочной железы, карцином легких, желудочных карцином, эзофагеальных карцином, колоректальных карцином, карцином печени, карцином яичника, ком, арренобластом, карцином шейки матки, эндометриальной карциномы, эндометриальной гиперплазии, эндометриоза, фибросарком, хориокарциномы, рака головы и шеи, назофарингеальной карциномы, карцином гортани, гепатобластомы, саркомы Капоши, меланомы, кожных карцином, гемангиомы, кавернозной гемангиомы, гемангиобластомы, карцином поджелудочной железы, ретинобластомы, астроцитомы, глиобластомы, Шванномы, олигодендроглиомы, медуллобластомы, нейробластом, рабдомиосаркомы, остеогенной саркомы, лейомиосарком, карцином мочеполовых путей, карцином щитовидной железы, опухоли Вильмса, почечно-клеточной карциномы, рака предстательной железы, аномальной пролиферации сосудов, ассоциированной с факоматозом, эдемы (например, ассоциированной с опухолями головного мозга), синдрома Мейжа, ревматоидного артрита, псориаза и атеросклероза.
12. Биспецифическая молекула, содержащая антитело по п. 1 или 2 или антиген-связывающий фрагмент по п. 3 или 4.
13. Биспецифическая молекула по п. 12, которая является мультиспецифичной.
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