RU2486204C2 - Антитела против сd26 и способы их применения - Google Patents
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Abstract
Настоящее изобретение относится к иммунологии и биотехнологии. Предложено антитело, которое специфически связывается с CD26 человека. Описаны варианты соответствующей кодирующей НК, вектор экспрессии и варианты клетки-хозяина для получения антитела. Раскрыты способы ингибирования (пролиферации клеток, роста опухоли) и способ лечения состояния, обусловленного экспрессией CD26, а также фармацевтическая композиция, использующие антитело по п.1. Описаны способы ингибирования (роста опухоли, пролиферации метастазирования), использующие фармацевтическую композицию. Раскрыта E.coli для продуцирования антитела, депонированная под номером доступа в АТСС РТА-7695. Использование изобретения может найти применение в лечении расстройств иммунной системы, связанных с экспрессией CD26, в том числе рака. 13 н. и 16 з.п. ф-лы, 42 ил., 14 табл., 14 пр.
Description
Claims (29)
1. Антитело или его функциональный фрагмент, содержащее
(a) вариабельный участок тяжелой цепи, содержащий аминокислотную последовательность SEQ ID NO:22, и
(b) вариабельный участок легкой цепи, содержащий аминокислотную последовательность SEQ ID NO:18;
и где антитело или его фрагмент связывает CD26 человека.
(a) вариабельный участок тяжелой цепи, содержащий аминокислотную последовательность SEQ ID NO:22, и
(b) вариабельный участок легкой цепи, содержащий аминокислотную последовательность SEQ ID NO:18;
и где антитело или его фрагмент связывает CD26 человека.
2. Антитело по п.1, которое связывается с пептидами YSLRWISDHEYLY (SEQ ID NO:45; пептид 6), TWSPVGHKLAYVW (SEQ ID NO:47; пептид 55), RISLQWLRRIQNY (SEQ ID NO:49; пептид 132), YVKQWRHSYTASY (SEQ ID NO:50; пептид 37) и EEEVFSAYSALWW (SEQ ID NO:51; пептид 79).
3. Антитело по п.1, которое представляет собой моноклональное антитело.
4. Антитело по п.1, которое представляет собой гуманизированное антитело.
5. Антитело по п.1, где его функциональный фрагмент выбран из группы, состоящей из Fab, Fab', Fab'-SH, Fv, scFv и F(ab')2.
6. Антитело по п.1, которое не является моноклональным антителом мыши.
7. Антитело по п.1, которое является выделенным.
8. Антитело по п.1, которое связывается с CD26 человека с КD приблизительно 6 нМ или менее.
9. Полинуклеотид, кодирующий антитело по п.1.
10. Вектор экспрессии, содержащий полинуклеотид по п.9.
11. Клетка-хозяин, использующаяся для получения антитела по пп.1-8, содержащая полинуклеотид по п.9.
12. Полинуклеотид, кодирующий антитело по п.1, содержащий последовательность нуклеиновой кислоты, состоящей из SEQ ID NO:4.
13. Полинуклеотид, кодирующий антитело по п.1, содержащий последовательность нуклеиновой кислоты, состоящей из SEQ ID NO:8.
14. Клетка-хозяин, использующаяся для получения антитела по пп.1-8, содержащая полинуклеотид по п.12.
15. Фармацевтическая композиция для лечения состояния, обусловленного экспрессией CD26, у субъекта, содержащая эффективное количество антитела по п.1 и фармацевтически приемлемый наполнитель.
16. Способ ингибирования пролиферации клетки, экспрессирующей CD26, включающий контактирование клетки с антителом по п.1.
17. Способ лечения состояния, обусловленного экспрессией CD26, у субъекта, включающий введение субъекту эффективного количества композиции, содержащей антитело по п.1.
18. Способ по п.17, где состояние представляет собой аутоиммунное заболевание.
19. Способ по п.17, где состояние представляет собой реакцию "трансплантат против хозяина".
20. Способ по п.17, где состояние представляет собой злокачественную опухоль.
21. Способ по п.20, где злокачественная опухоль представляет собой гематологическую злокачественную опухоль.
22. Способ по п.20, где субъект имеет экспрессирующую CD26 опухоль или имел экспрессирующую CD26 опухоль, которую удалили.
23. Способ по п.20, где злокачественная опухоль представляет собой лимфому, рак почки, рак предстательной железы или рак легкого.
24. Способ ингибирования роста опухоли у субъекта, который обладает экспрессирующей CD26 опухолью или который обладал экспрессирующей CD26 опухолью, которую удалили, включающий введение субъекту фармацевтической композиции по п.15.
25. Способ ингибирования метастазирования экспрессирующих CD26 клеток злокачественной опухоли у субъекта, включающий введение субъекту фармацевтической композиции по п.15.
26. Способ по п.17, где субъект является человеком.
27. Способ по п.20, дополнительно включающий стадию лечения субъекта посредством химиотерапии, лучевой терапии, хирургического вмешательства, гормональной терапии или дополнительной иммунотерапии.
28. E.coli для продуцирования антитела, которое связывает CD26 человека, где E.coli депонирована под номером доступа в АТСС РТА-7695.
29. Антитело по п.1, содержащее:
(а) тяжелую цепь, состоящую из последовательности:
EVQLVESGAGVKQPGGTLRLTCTASGFSLTTYGVHWRQAPGKGLEWV GVIWGDGRTDYDAAFMS
RVTISKDTSKSTVYLQMNSLRAEDTAVYYCMRNRHDWFDYWGQGTTV TVSSASTKGPSVFPLAP
SSKSTSGGTAA.LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSWTVPSSSLG
TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPE
VTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLT VLHQDWLNGKEYKCK
VSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQ
PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPGK (SEQ ID NO:219) и
(b) легкую цепь, состоящую из последовательности:
DILLTQSPSSLSATPGERATITCRASQGIRNNLNWYQQKPGQAPRLLIYYS
SNLQSGVPSRFSG SGSGTDFTLTISRLQPEDVAAYYCQQSKLPFTFGSGTKVEIKRTVAAPSV
FIFPPSDEQLKSGT
ASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST LTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:220).
(а) тяжелую цепь, состоящую из последовательности:
EVQLVESGAGVKQPGGTLRLTCTASGFSLTTYGVHWRQAPGKGLEWV GVIWGDGRTDYDAAFMS
RVTISKDTSKSTVYLQMNSLRAEDTAVYYCMRNRHDWFDYWGQGTTV TVSSASTKGPSVFPLAP
SSKSTSGGTAA.LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSWTVPSSSLG
TQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPE
VTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLT VLHQDWLNGKEYKCK
VSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQ
PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN HYTQKSLSLSPGK (SEQ ID NO:219) и
(b) легкую цепь, состоящую из последовательности:
DILLTQSPSSLSATPGERATITCRASQGIRNNLNWYQQKPGQAPRLLIYYS
SNLQSGVPSRFSG SGSGTDFTLTISRLQPEDVAAYYCQQSKLPFTFGSGTKVEIKRTVAAPSV
FIFPPSDEQLKSGT
ASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST LTLSKADYEKHKVYA CEVTHQGLSSPVTKSFNRGEC (SEQ ID NO:220).
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Application Number | Priority Date | Filing Date | Title |
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US70180205P | 2005-07-22 | 2005-07-22 | |
US60/701,802 | 2005-07-22 | ||
PCT/US2006/028702 WO2007014169A2 (en) | 2005-07-22 | 2006-07-24 | Anti-cd26 antibodies and methods of use thereof |
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RU2008106760A RU2008106760A (ru) | 2009-08-27 |
RU2486204C2 true RU2486204C2 (ru) | 2013-06-27 |
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US (2) | US7462698B2 (ru) |
EP (1) | EP1907425B1 (ru) |
JP (1) | JP4997239B2 (ru) |
KR (1) | KR20080039929A (ru) |
CN (1) | CN101282994B (ru) |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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RU2742953C2 (ru) * | 2015-09-11 | 2021-02-12 | И'с АК Ко., Лтд. | Композиция для лечения рака, объединяющая анти-cd26 антитело и другое противораковое средство |
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WO2007014169A2 (en) | 2005-07-22 | 2007-02-01 | Y's Therapeutics Co, Ltd. | Anti-cd26 antibodies and methods of use thereof |
US20100135993A1 (en) * | 2007-03-14 | 2010-06-03 | The University Of Tokyo | Method of treating malignant mesothelioma |
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EP1907425B1 (en) | 2014-01-08 |
WO2007014169A3 (en) | 2007-05-10 |
CN101282994A (zh) | 2008-10-08 |
AU2006272713A1 (en) | 2007-02-01 |
CN101282994B (zh) | 2013-09-18 |
KR20080039929A (ko) | 2008-05-07 |
EP1907425A2 (en) | 2008-04-09 |
RU2008106760A (ru) | 2009-08-27 |
JP4997239B2 (ja) | 2012-08-08 |
JP2009502139A (ja) | 2009-01-29 |
BRPI0613770A2 (pt) | 2009-05-19 |
CA2615615A1 (en) | 2007-02-01 |
US20070105771A1 (en) | 2007-05-10 |
IL188748A0 (en) | 2008-08-07 |
US7462698B2 (en) | 2008-12-09 |
WO2007014169A2 (en) | 2007-02-01 |
US20090136523A1 (en) | 2009-05-28 |
US8030469B2 (en) | 2011-10-04 |
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