RU2017137740A - Анти-vegf/dll4-иммуноглобулины с двойными вариабельными доменами и их применения - Google Patents
Анти-vegf/dll4-иммуноглобулины с двойными вариабельными доменами и их применения Download PDFInfo
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- RU2017137740A RU2017137740A RU2017137740A RU2017137740A RU2017137740A RU 2017137740 A RU2017137740 A RU 2017137740A RU 2017137740 A RU2017137740 A RU 2017137740A RU 2017137740 A RU2017137740 A RU 2017137740A RU 2017137740 A RU2017137740 A RU 2017137740A
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- 229940072221 immunoglobulins Drugs 0.000 title 1
- 102000014914 Carrier Proteins Human genes 0.000 claims 14
- 108091008324 binding proteins Proteins 0.000 claims 14
- 229920001184 polypeptide Polymers 0.000 claims 9
- 102000004196 processed proteins & peptides Human genes 0.000 claims 9
- 108090000765 processed proteins & peptides Proteins 0.000 claims 9
- 102100033553 Delta-like protein 4 Human genes 0.000 claims 3
- 101000872077 Homo sapiens Delta-like protein 4 Proteins 0.000 claims 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims 3
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Claims (38)
1. Связывающий белок, содержащий полипептидную цепь, при этом полипептидная цепь содержит VD1-(X1)n-VD2-C-(X2)n, где
VD1 означает первый вариабельный домен тяжелой цепи;
VD2 означает второй вариабельный домен тяжелой цепи;
C означает константный домен тяжелой цепи;
X1 означает линкер, при условии, что он не является CH1;
X2 означает Fc-область;
n равен 0 или 1; и
при этом связывающий белок связывает DLL4 и VEGF, при этом VD1 и VD2 независимо содержат три CDR из последовательности SEQ ID NO:39, 41, 43, 45, 47, 49, 51 или 53, и при этом по меньшей мере один VD1 и/или VD2 содержит три CDR из последовательности SEQ ID NO:39.
2. Связывающий белок по п.1, в котором VD1 и VD2 независимо содержат последовательности SEQ ID NO:39, 41, 43, 45, 47, 49, 51 или 53, и при этом по меньшей мере один из VD1 и/или VD2 содержит последовательность SEQ ID NO:39.
3. Связывающий белок, содержащий полипептидную цепь, при этом полипептидная цепь содержит VD1-(X1)n-VD2-C-(X2)n, где
VD1 означает первый вариабельный домен легкой цепи;
VD2 означает второй вариабельный домен легкой цепи;
C означает константный домен легкой цепи;
X1 означает линкер, при условии, что он не является CH1 или CL;
X2 не содержит Fc-области;
n равен 0 или 1; и
при этом связывающий белок связывает DLL4 и VEGF, при этом VD1 и VD2 независимо содержат три CDR из последовательности SEQ ID NO:40, 42, 44, 46, 48, 50, 52 или 54, и при этом по меньшей мере один из VD1 и/или VD2 содержит три CDR из последовательности SEQ ID NO:40.
4. Связывающий белок по п.3, в котором VD1 и VD2 независимо содержат последовательности SEQ ID NO:40, 42, 44, 46, 48, 50, 52 или 54, и при этом по меньшей мере один из VD1 и/или VD2 содержит последовательность SEQ ID NO:40.
5. Связывающий белок по п.1 или 3, в котором (X1)n в тяжелой и/или легкой цепи означает (X1)0, и/или (X2)n в тяжелой и/или легкой цепи означает (X2)0.
6. Связывающий белок, содержащий первую и вторую полипептидные цепи, при этом первая полипептидная цепь содержит первый VD1-(X1)n-VD2-C-(X2)n, где
VD1 означает первый вариабельный домен тяжелой цепи;
VD2 означает второй вариабельный домен тяжелой цепи;
C означает константный домен тяжелой цепи;
X1 означает линкер, при условии, что он не является CH2;
X2 означает Fc-область;
n равен 0 или 1; и
при этом вторая полипептидная цепь содержит второй VD1-(X1)n-VD2-C-(X2)n, где
VD1 означает первый вариабельный домен легкой цепи;
VD2 означает второй вариабельный домен легкой цепи;
C означает константный домен легкой цепи;
X1 означает линкер, при условии, что он не является CH1 или CL;
X2 не содержит Fc-область;
n равен 0 или 1; и
при этом связывающий белок связывает DLL4 и VEGF, при этом вариабельные домены тяжелой цепи VD1 и VD2 независимо содержат три CDR из последовательности SEQ ID NO:39, 41, 43, 45, 47, 49, 51 или 53, при этом по меньшей мере один из вариабельных доменов тяжелой цепи VD1 и/или VD2 содержит три CDR из последовательности SEQ ID NO:39; и при этом вариабельные домены легкой цепи VD1 и VD2 независимо содержат три CDR из последовательности SEQ ID NO:40, 42, 44, 46, 48, 50, 52 или 54, при этом по меньшей мере один из вариабельных доменов легкой цепи VD1 и/или VD2 содержит три CDR из последовательности SEQ ID NO:40.
7. Связывающий белок по п.6, в котором вариабельные домены тяжелой цепи VD1 и VD2 независимо содержат последовательности SEQ ID NO:39, 41, 43, 45, 47, 49, 51 или 53, при этом по меньшей мере один из вариабельных доменов тяжелой цепи VD1 и/или VD2 содержит последовательность SEQ ID NO:39; и при этом вариабельные домены легкой цепи VD1 и VD2 независимо содержат последовательности SEQ ID NO:40, 42, 44, 46, 48, 50, 52 или 54, при этом по меньшей мере один из вариабельных доменов легкой цепи VD1 и/или VD2 содержит последовательность SEQ ID NO:40.
8. Связывающий белок по п.1, 3 или 6, в котором X1 содержит любую из последовательностей SEQ ID NO:1-38 или основанную на G/S последовательность.
9. Связывающий белок по п.6, в котором связывающий белок содержит две первых полипептидных цепи и две вторых полипептидных цепи.
10. Связывающий белок по п.1, 3 или 6, в котором Fc-область представляет собой Fc-область с вариантом последовательности.
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