RU2014149553A - Биспецифические анти-vegf/анти-ang-2 антитела - Google Patents
Биспецифические анти-vegf/анти-ang-2 антитела Download PDFInfo
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- 239000000427 antigen Substances 0.000 claims abstract 16
- 102000036639 antigens Human genes 0.000 claims abstract 16
- 108091007433 antigens Proteins 0.000 claims abstract 16
- 108010048036 Angiopoietin-2 Proteins 0.000 claims abstract 6
- 102100034608 Angiopoietin-2 Human genes 0.000 claims abstract 6
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract 6
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 6
- 101000924533 Homo sapiens Angiopoietin-2 Proteins 0.000 claims abstract 4
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 claims abstract 4
- 206010028980 Neoplasm Diseases 0.000 claims abstract 4
- 201000011510 cancer Diseases 0.000 claims abstract 4
- 102000058223 human VEGFA Human genes 0.000 claims abstract 4
- 208000019553 vascular disease Diseases 0.000 claims abstract 4
- 102000009088 Angiopoietin-1 Human genes 0.000 claims abstract 2
- 108010048154 Angiopoietin-1 Proteins 0.000 claims abstract 2
- 101000924552 Homo sapiens Angiopoietin-1 Proteins 0.000 claims abstract 2
- 102000044072 human ANGPT1 Human genes 0.000 claims abstract 2
- 102000047825 human ANGPT2 Human genes 0.000 claims abstract 2
- 150000007523 nucleic acids Chemical class 0.000 claims 4
- 102000039446 nucleic acids Human genes 0.000 claims 4
- 108020004707 nucleic acids Proteins 0.000 claims 4
- 238000000034 method Methods 0.000 claims 2
- 238000004113 cell culture Methods 0.000 claims 1
- 239000013604 expression vector Substances 0.000 claims 1
- 230000006798 recombination Effects 0.000 claims 1
- 238000005215 recombination Methods 0.000 claims 1
- 239000006228 supernatant Substances 0.000 claims 1
- 239000013598 vector Substances 0.000 claims 1
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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Abstract
1. Биспецифическое антитело, специфически связывающееся с фактором роста сосудистого эндотелия человека - VEGF и ангиопоэтином-2 человека - ANG-2, включающее первый сайт связывания антигена, который специфически связывается с VEGF человека, и второй сайт связывания антигена, который специфически связывается с ANG-2 человека,гдеi) каждый из указанных сайтов связывания антигена представляет пару вариабельного домена тяжелой цепи антитела и вариабельного домена легкой цепи антитела;ii) указанный первый сайт связывания антигена, специфически связывающийся с VEGF,включает в вариабельном домене тяжелой цепи область CDR3 SEQ ID NO: 9, область CDR2 SEQ ID NO: 10 и область CDR1 SEQ ID NO: 11 и в вариабельном домене легкой цепи область CDR3 SEQ ID NO: 12, область CDR2 SEQ ID NO: 13 и область CDR1 SEQ ID NO: 14;иiii) указанный второй сайт связывания антигена, специфически связывающийся с ANG-2, включает в вариабельном домене тяжелой цепи область CDR3 SEQ ID NO: 78, область CDR2 SEQ ID NO: 79 и область CDR1 SEQ ID NO: 80, и в вариабельном домене легкой цепи область CDR3 SEQ ID NO: 81, область CDR2 SEQ ID NO: 82, область CDR1 SEQ ID NO: 83.2. Биспецифическое антитело п. 1, отличающееся тем, что соотношение величин связывающегося сродства KD (сайта связывания антигена, специфичного в отношении VEGF)/KD (сайта связывания антигена, специфичного в отношении ANG-2) составляет 1,0-10,0.3. Биспецифическое антитело по п. 1 или 2, отличающееся тем, что второй сайт связывания антигена, который специфически связывается с ANG-2 человека, не связывается специфически с ангиопоэтином 1 человека (ANG-1).4. Фармацевтическая композиция, включающая антитело по одному из пп. 1-3.5. Фармацевтическая композиция по п. 4 для лечения рака.6. Фармацевтическая композиция по п. 4 для лечения сосудистых заболеваний.7. Биспецифическое антитело по п. 1 или 2 для лечения рака.8. Биспецифическое антитело по п. 1 или 2 для лечения сосудистых заболев
Claims (13)
1. Биспецифическое антитело, специфически связывающееся с фактором роста сосудистого эндотелия человека - VEGF и ангиопоэтином-2 человека - ANG-2, включающее первый сайт связывания антигена, который специфически связывается с VEGF человека, и второй сайт связывания антигена, который специфически связывается с ANG-2 человека,
где
i) каждый из указанных сайтов связывания антигена представляет пару вариабельного домена тяжелой цепи антитела и вариабельного домена легкой цепи антитела;
ii) указанный первый сайт связывания антигена, специфически связывающийся с VEGF,
включает в вариабельном домене тяжелой цепи область CDR3 SEQ ID NO: 9, область CDR2 SEQ ID NO: 10 и область CDR1 SEQ ID NO: 11 и в вариабельном домене легкой цепи область CDR3 SEQ ID NO: 12, область CDR2 SEQ ID NO: 13 и область CDR1 SEQ ID NO: 14;
и
iii) указанный второй сайт связывания антигена, специфически связывающийся с ANG-2, включает в вариабельном домене тяжелой цепи область CDR3 SEQ ID NO: 78, область CDR2 SEQ ID NO: 79 и область CDR1 SEQ ID NO: 80, и в вариабельном домене легкой цепи область CDR3 SEQ ID NO: 81, область CDR2 SEQ ID NO: 82, область CDR1 SEQ ID NO: 83.
2. Биспецифическое антитело п. 1, отличающееся тем, что соотношение величин связывающегося сродства KD (сайта связывания антигена, специфичного в отношении VEGF)/KD (сайта связывания антигена, специфичного в отношении ANG-2) составляет 1,0-10,0.
3. Биспецифическое антитело по п. 1 или 2, отличающееся тем, что второй сайт связывания антигена, который специфически связывается с ANG-2 человека, не связывается специфически с ангиопоэтином 1 человека (ANG-1).
4. Фармацевтическая композиция, включающая антитело по одному из пп. 1-3.
5. Фармацевтическая композиция по п. 4 для лечения рака.
6. Фармацевтическая композиция по п. 4 для лечения сосудистых заболеваний.
7. Биспецифическое антитело по п. 1 или 2 для лечения рака.
8. Биспецифическое антитело по п. 1 или 2 для лечения сосудистых заболеваний.
9. Нуклеиновая кислота, кодирующая биспецифическое антитело по одному из пп. 1-4.
10. Векторы экспрессии, содержащие нуклеиновую кислоту по п. 9, способные экспрессировать указанную нуклеиновую кислоту в прокариотических или эукариотических клетках-хозяевах.
11. Прокариотическая или эукариотическая клетка-хозяин, включающая вектор по п. 10.
12. Способ получения биспецифического антитела по одному из пп. 1-3, отличающийся экспрессией нуклеиновой кислоты по п. 9 в прокариотических или эукариотических клетках-хозяевах и выделением указанного биспецифического антитела из указанных клеток или супернатанта культуры клеток.
13. Антитело, полученное методом рекомбинации по п. 12.
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EP08017607.6 | 2008-10-08 | ||
EP08017607 | 2008-10-08 | ||
EP08021834 | 2008-12-16 | ||
EP08021834.0 | 2008-12-16 |
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RU2011117410/10A Division RU2542382C2 (ru) | 2008-10-08 | 2009-10-07 | Биспецифические анти-vegf/анти-ang-2 антитела |
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RU2014149553A true RU2014149553A (ru) | 2016-06-27 |
RU2640253C2 RU2640253C2 (ru) | 2017-12-27 |
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RU2014149553A RU2640253C2 (ru) | 2008-10-08 | 2014-12-09 | Биспецифические анти-vegf/анти-ang-2 антитела |
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EP (3) | EP2781526A1 (ru) |
JP (2) | JP5368570B2 (ru) |
KR (2) | KR20130118994A (ru) |
CN (2) | CN102753577B (ru) |
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WO2002051438A2 (en) | 2000-12-22 | 2002-07-04 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Use of repulsive guidance molecule (rgm) and its modulators |
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