RU2019103083A - МУТАЦИИ ErbB3 ПРИ РАКЕ - Google Patents
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Claims (37)
1. Вещество для выявления ErbB3-обусловленного рака желудочно-кишечного тракта для применения в образце ткани желудочно-кишечного тракта, полученном у пациента, содержащее полинуклеотидный агент, способный специфически связываться с ErbB3 мутационным кодоном в нуклеотидной последовательности ErbB3, где мутационный кодон кодирует i) аминокислотную заместительную мутацию в SEQ ID NO: 2 в положении, выбранном из группы из 809, 232, 262, 325, 60, 111, 135, 295, 406, 453 и 1164, или ii) стоп-кодон в SEQ ID NO: 2 в положении 193, и где полинуклеотидный агент содержит полинуклеотид, комплементарный формуле
где
X отсутствует, если а равно 0, или X представляет собой последовательность нуклеиновой кислоты, содержащую 1-250 нуклеотидов последовательности нуклеиновой кислоты ErbB3, если а равно 1-250;
Y является ErbB3 мутационным кодоном; и
Z отсутствует, если а равно 0, или Z представляет собой последовательность нуклеиновой кислоты, содержащую 1-250 нуклеотидов последовательности нуклеиновой кислоты ErbB3, если b равно 1-250; и
и где суммарная длина полинуклеотида с формулой Xa-Y-Zb составляет по крайней мере семь нуклеотидов в длину и меньше 250 нуклеотидов в длину.
2. Вещество для выявления рака по п. 1, отличающееся тем, что нуклеотидная последовательность ErbB3 содержит SEQ ID NO: 230 или 1.
3. Вещество для выявления рака по любому из пп. 1-2, где агент для обнаружения конъюгирован с детектируемой меткой.
4. Вещество для выявления рака по п. 3, где детектируемая метка выбрана из группы, состоящей из радиоизотопа, флуоресцентной метки, биолюминесцентной метки и ферментной метки.
5. Вещество для выявления рака по любому из пп. 1-4, где мутация выбрана из Q809R, A232V, Р262Н, P262S, G325R, M60K, Y111C, R135L, V295A, M406K, М406Т, R453H и T1164A и стоп-кодона в положении 193.
6. Способ определения наличия ErbB3-обусловленного рака желудочно-кишечного тракта у пациента, включающий выявление в биологическом образце, полученном из желудочно-кишечного тракта пациента, заместительной мутации в нуклеотидной последовательности, кодирующей ErbB3, где заместительная мутация приводит к i) аминокислотной замене в SEQ ID NO: 2 в положении, выбранном из группы из 104, 809, 232, 262, 284, 325, 60, 111, 135, 295, 406, 453 и 1164, или ii) стоп-кодону в SEQ ID NO: 2 в положении 193, и где указанная заместительная мутация указывает на наличие у пациента ErbB3-обусловленного рака желудочно-кишечного тракта.
7. Способ по п. 6, где мутация выбрана из V104M, V104L, Q809R, A232V, Р262Н, P262S, G284R, G325R, M60K, Y111C, R135L, V295A, M406K, М406Т, R453H и Т1164А, или стоп-кодона в положении 193.
8. Способ по п. 6 или 7, дополнительно включающий введение терапевтического средства пациенту, идентифицированного как имеющей ErbB3-обусловленный рак желудочно-кишечного тракта.
9. Способ по п. 8, отличающийся тем, что терапевтическое средство является ингибитором ErbB.
10. Способ по п. 9, отличающийся тем, что ингибитор ErbB выбран из группы, состоящей из антагониста EGFR, антагониста ErbB2, антагониста ErbB3, антагониста ErbB4 и антагониста EGFR/ErbB3.
11. Способ по п. 10, отличающийся тем, что ингибитор является низкомолекулярным ингибитором.
12. Способ по п. 10, отличающийся тем, что антагонист является антагонистическим антителом.
13. Способ по п. 12, отличающийся тем, что антитело выбрано из группы, состоящей из моноклонального антитела, биспецифического антитела, химерного антитела, антитела человека, гуманизированного антитела и фрагмента антитела.
14. Вещество для выявления рака по п. 1 или способ по п. 6, отличающиеся тем, что рак желудочно-кишечного тракта является раком желудка или раком толстой кишки.
15. Способ по п. 6, дополнительно включающий получение образца от пациента.
16. Способ по п. 6, отличающийся тем, что выявление включает амплификацию или секвенирование мутации и выявление мутации или ее последовательности.
17. Способ по п. 16, отличающийся тем, что амплификация включает смешивание амплификационного праймера или пары амплификационных праймеров с нуклеотидной матрицей, выделенной из образца.
18. Способ по п. 17, отличающийся тем, что праймер или пара праймеров является комплементарной либо частично комплементарной участку близлежащему к или содержащему указанную мутацию и способен инициировать полимеризацию нуклеиновой кислоты полимеразой на нуклеотидной матрице.
19. Способ по п. 17, дополнительно включающий удлинение праймера или пары праймеров в реакции полимеризации ДНК, включающей полимеразу и нуклеотидную матрицу, с образованием ампликона.
20. Способ по п. 16, отличающийся тем, что заместительную мутацию выявляют способом, который включает один или более из следующих этапов: секвенирование мутации в геномной ДНК, выделенной из биологического образца, гибридизацию мутации или ее ампликона с матрицей, обработку мутации или ее ампликона рестрикционным ферментом или ПЦР амплификацию мутации в режиме настоящего времени.
21. Способ по п. 16, включающий частичное либо полное секвенирование мутации в нуклеиновой кислоте, выделенной из биологического образца.
22. Способ по п. 16, отличающийся тем, что амплификация включает проведение полимеразной цепной реакции (ПЦР), ПЦР с обратной транскриптазой (ПЦР-ОТ) или лигазной цепной реакции (ЛЦР) с участием нуклеиновой кислоты, выделенной из биологического образца в качестве матрицы в ПЦР, ПЦР-ОТ или ЛЦР.
23. Применение ингибитора ErbB в способе лечения ErbB3-обусловленного рака желудочно-кишечного тракта у нуждающегося в этом пациента, включающем:
a) выявление в биологическом образце, полученном из желудочно-кишечного тракта пациента, заместительной мутации в нуклеотидной последовательности, кодирующей ErbB3, где заместительная мутация приводит к i) аминокислотной замене в SEQ ID NO: 2 в положении, выбранном из группы, состоящей из 104, 809, 232, 262, 284, 325, 60, 111, 135, 295, 406, 453 и 1164, или ii) стоп-кодону в SEQ ID NO: 2 в положении 193, и где указанная заместительная мутация указывает на наличие у пациента ErbB3-обусловленного рака желудочно-кишечного тракта; и
b) введение указанному пациенту ингибитора ErbB.
24. Применение по п. 23, где мутация выбрана из V104M, V104L, Q809R, A232V, Р262Н, P262S, G284R, G325R, M60K, Y111C, R135L, V295A, M406K, М406Т, R453H и T1164A, или стоп-кодона в положении 193.
25. Применение по п. 23 или 24, отличающийся тем, что ингибитор ErbB выбран из группы, состоящей из антагониста EGFR, антагониста ErbB2, антагониста ErbB3, антагониста ErbB4 и антагониста EGFR/ErbB3.
26. Применение по п. 25, отличающийся тем, что ингибитор является низкомолекулярным ингибитором.
27. Применение по п. 25, отличающийся тем, что антагонист является антагонистическим антителом.
28. Применение по п. 27, отличающийся тем, что антитело выбрано из группы, состоящей из моноклонального антитела, биспецифического антитела, химерного антитела, антитела человека, гуманизированного антитела и фрагмента антитела.
29. Применение по п. 23, отличающийся тем, что рак желудочно-кишечного тракта является раком желудка или раком толстой кишки.
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US10221230B2 (en) * | 2013-02-25 | 2019-03-05 | Ohio State Innovation Foundation | HER-1, HER-3 and IGF-1R compositions and uses thereof |
CA2959775A1 (en) | 2014-09-08 | 2016-03-17 | Yeda Research And Development Co. Ltd. | Compositions and methods for treating cancer resistant to a tyrosine kinase inhibitor (tki) |
WO2016038609A1 (en) | 2014-09-08 | 2016-03-17 | Yeda Research And Development Co. Ltd. | Anti-her3 antibodies and uses of same |
KR102469700B1 (ko) * | 2016-09-15 | 2022-11-23 | 우니베르지테트 스튜트가르트 | Her3에 대한 항원 결합 단백질 |
JPWO2020059772A1 (ja) * | 2018-09-20 | 2021-08-30 | 第一三共株式会社 | 抗her3抗体−薬物コンジュゲート投与によるher3変異がんの治療 |
CN111187835B (zh) * | 2019-02-02 | 2023-03-31 | 中国科学院上海营养与健康研究所 | 胰腺癌的靶点erbb2及其在诊断和治疗中的应用 |
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-
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- 2012-11-29 MX MX2014006529A patent/MX2014006529A/es unknown
- 2012-11-29 CN CN201710084997.7A patent/CN106987620A/zh active Pending
- 2012-11-29 KR KR1020147017927A patent/KR20140098834A/ko not_active Application Discontinuation
- 2012-11-29 CN CN201280067318.0A patent/CN104271761B/zh not_active Expired - Fee Related
- 2012-11-29 RU RU2014126098A patent/RU2014126098A/ru not_active Application Discontinuation
- 2012-11-29 US US13/694,413 patent/US20130195870A1/en not_active Abandoned
- 2012-11-29 AU AU2012346540A patent/AU2012346540C1/en not_active Ceased
- 2012-11-29 BR BR112014012979-7A patent/BR112014012979A2/pt not_active IP Right Cessation
- 2012-11-29 JP JP2014544721A patent/JP2015500638A/ja active Pending
- 2012-11-29 SG SG11201402510TA patent/SG11201402510TA/en unknown
- 2012-11-29 RU RU2019103083A patent/RU2019103083A/ru not_active Application Discontinuation
- 2012-11-29 CA CA2857114A patent/CA2857114A1/en not_active Abandoned
- 2012-11-29 EP EP12801651.6A patent/EP2785864A2/en not_active Withdrawn
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AU2012346540A1 (en) | 2014-07-03 |
WO2013081645A3 (en) | 2013-07-25 |
KR20140098834A (ko) | 2014-08-08 |
CN104271761B (zh) | 2017-03-15 |
JP2015500638A (ja) | 2015-01-08 |
CN104271761A (zh) | 2015-01-07 |
SG11201402510TA (en) | 2014-06-27 |
CN106987620A (zh) | 2017-07-28 |
MX2014006529A (es) | 2014-11-25 |
RU2014126098A (ru) | 2016-01-27 |
HK1201301A1 (en) | 2015-08-28 |
IL232713A0 (en) | 2014-07-31 |
BR112014012979A2 (pt) | 2020-10-20 |
EP2785864A2 (en) | 2014-10-08 |
JP2018085998A (ja) | 2018-06-07 |
US20130195870A1 (en) | 2013-08-01 |
AU2012346540C1 (en) | 2019-07-04 |
WO2013081645A2 (en) | 2013-06-06 |
NZ625380A (en) | 2016-10-28 |
CA2857114A1 (en) | 2013-06-06 |
AU2012346540B2 (en) | 2018-09-13 |
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