RU2015125638A - Идентификация пациентов, нуждающихся в совместной терапии с использованием ингибитора pd-l1 - Google Patents
Идентификация пациентов, нуждающихся в совместной терапии с использованием ингибитора pd-l1 Download PDFInfo
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- 238000002560 therapeutic procedure Methods 0.000 title claims 6
- 239000012271 PD-L1 inhibitor Substances 0.000 title claims 5
- 229940121656 pd-l1 inhibitor Drugs 0.000 title claims 5
- 238000000034 method Methods 0.000 claims 14
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims 9
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims 9
- 206010028980 Neoplasm Diseases 0.000 claims 8
- 201000011510 cancer Diseases 0.000 claims 8
- 102000015694 estrogen receptors Human genes 0.000 claims 8
- 108010038795 estrogen receptors Proteins 0.000 claims 8
- 239000003112 inhibitor Substances 0.000 claims 7
- 239000002246 antineoplastic agent Substances 0.000 claims 6
- 229940127089 cytotoxic agent Drugs 0.000 claims 6
- 239000003446 ligand Substances 0.000 claims 5
- 238000003776 cleavage reaction Methods 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- 229920001184 polypeptide Polymers 0.000 claims 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- 230000007017 scission Effects 0.000 claims 4
- 230000019491 signal transduction Effects 0.000 claims 4
- 150000004579 taxol derivatives Chemical class 0.000 claims 4
- 102000008070 Interferon-gamma Human genes 0.000 claims 3
- 108010074328 Interferon-gamma Proteins 0.000 claims 3
- 238000003782 apoptosis assay Methods 0.000 claims 3
- 229960003130 interferon gamma Drugs 0.000 claims 3
- 230000005522 programmed cell death Effects 0.000 claims 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 229930012538 Paclitaxel Natural products 0.000 claims 2
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims 2
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims 2
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 claims 2
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 2
- 206010017758 gastric cancer Diseases 0.000 claims 2
- 229940022353 herceptin Drugs 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- 230000001394 metastastic effect Effects 0.000 claims 2
- 206010061289 metastatic neoplasm Diseases 0.000 claims 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 2
- 229960001592 paclitaxel Drugs 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 229910052698 phosphorus Inorganic materials 0.000 claims 2
- 102000005962 receptors Human genes 0.000 claims 2
- 108020003175 receptors Proteins 0.000 claims 2
- 230000008054 signal transmission Effects 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- 125000002456 taxol group Chemical group 0.000 claims 2
- 229960000575 trastuzumab Drugs 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
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Claims (64)
1. Способ определения потребности ракового пациента в совместной терапии с использованием ингибитора PD-L1,
(I) в котором для пациента показана терапия, включающая модулятор пути передачи сигналов HER2/neu (ErbB2) и химиотерапевтическое средство, или (II) в котором пациент подвергается терапии, включающей модулятор пути передачи сигналов HER2/neu (ErbB2) и химиотерапевтическое средство, включающий стадии, на которых
а) измеряют in vitro в образце из организма указанного пациента уровень экспрессии рецептора эстрогена (ER) и лиганда программированной клеточной гибели-1 (PD-L1),
б) классифицируют пациента как нуждающегося в совместной терапии с использованием ингибитора PD-L1, если измеренный на стадии (а) уровень экспрессии ER является низким или она отсутствует и уровень экспрессии лиганда программированной клеточной гибели-1 (PD-L1) является повышенным по сравнению с контролем.
2. Способ по п. 1, дополнительно включающий измерение in vitro в образце из организма указанного пациента уровня экспрессии интерферона-гамма (IFNγ) и классификации пациента как нуждающегося в совместной терапии с использованием ингибитора PD-L1, если измеренный уровень экспрессии интерферон-гамма (IFNγ) является пониженным по сравнению с контролем.
3. Способ по п. 1, где уровень экспрессии ER представляет собой ER(-).
4. Способ по п. 1, где указанный модулятор пути передачи сигналов HER2/neu (ErbB2) представляет собой ингибитор отщепления HER.
5. Способ по п. 4, в которой ингибитор отщепления HER представляет собой антитело к HER.
6. Способ по п. 5 где указанное антитело к HER связывается с HER-рецептором, выбранным из группы, состоящей из EGFR, HER2 и HER3.
7. Способ по п. 6, где указанное антитело к HER2 представляет собой герцептин/трастузумаб.
8. Способ по п. 1, где указанное химиотерапевтическое средство представляет собой таксол или производное таксола, где указанное производное таксола предпочтительно представляет собой додетаксел.
9. Способ по п. 1, где указанный ингибитор лиганда программированной клеточной гибели-1 (PD-L1) представляет собой антитело, которое специфически связывается с PD-L1 (антитело к PD-L1).
10. Способ по п. 9, где указанное антитело содержит полипептид вариабельной области тяжелой цепи, содержащий последовательность HVR-H1, HVR-H2 и HVR-H3, в которой:
(а) последовательность HVR-H1 представляет собой
GFTFSX1SWIH (SEQ ID NO: 1);
(б) последовательность HVR-H2 представляет собой
AWIX2PYGGSX3YYADSVKG (SEQ ID NO: 2);
(в) последовательность HVR-H3 представляет собой
RHWPGGFDY (SEQ ID NO: 3);
кроме того, в которой: X1 обозначает D или G; Х2 обозначает S или L; Х3 обозначает Т или S.
11. Способ по п. 10, где указанный полипептид тяжелой цепи находится в комбинации с вариабельной областью легкой цепи, содержащей HVR-L1, HVR-L2 и HVR-L3, где:
(а) последовательность HVR-L1 представляет собой
RASQX4X5X6TX7X8A (SEQ ID NO: 8);
(б) последовательность HVR-L2 представляет собой
SASX9LX10S (SEQ ID NO: 9);
(в) последовательность HVR-L3 представляет собой
QQX11X12X13X14PX15T (SEQ ID NO: 10);
где, кроме того: Х4 обозначает D или V; Х5 обозначает V или I; Х6 обозначает S или N; Х7 обозначает А или F; Х8 обозначает V или L; Х9 обозначает F или Т; Х10 обозначает Y или А; X11 обозначает Y, G, F или S; Х12 обозначает L, Y, F или W; X13 обозначает Y, N, А, Т, G, F или I; Х14 обозначает Н, V, Р, Т или I; X15 обозначает A, W, R, Р или Т.
12. Способ по п. 10, где указанное антитело содержит последовательность вариабельной области тяжелой и легкой цепи, где:
(а) тяжелая цепь содержит HVR-H1, HVR-H2 и HVR-H3, которые обладают по меньшей мере 85%-ной идентичностью по всей длине последовательности с GFTFSDSWIH (SEQ ID NO: 15), AWISPYGGSTYYADSVKG (SEQ ID NO: 16) и RHWPGGFDY (SEQ ID NO: 3) соответственно, и
(б) легкая цепь содержит HVR-L1, HVR-L2 и HVR-L3, которые обладают по меньшей мере 85%-ной идентичностью по всей длине последовательности с RASQDVSTAVA (SEQ ID NO: 17), SASFLYS (SEQ ID NO: 18) и QQYLYHPAT (SEQ ID NO: 19) соответственно.
13. Способ по п. 1, где указанный рак представляет собой солидный рак, предпочтительно рак молочной железы или рак желудка.
14. Способ по п. 1 где указанный модулятор пути передачи сигналов HER2/neu (ErbB2), указанное химиотерапевтическое средство и указанный ингибитор лиганда программированной клеточной гибели-1 (PD-L1) применяют в неоадъювантном режиме, или адъювантном режиме, или в метастатическом режиме.
15. Применение фармацевтической композиции, содержащей модулятор пути передачи сигналов HER2/neu (ErbB2) и ингибитор лиганда программированной клеточной гибели-1 (PD-L1) для лечения рака, если установлено, что указанный рак характеризуется низким уровнем экспрессии ER или ее отсутствием и характеризуется повышенным уровнем экспрессии лиганда программированной клеточной гибели-1 (PD-L1) по сравнению с контролем.
16. Применение по п. 15, где фармацевтическая композиция содержит дополнительно химиотерапевтическое средство.
17. Применение по п. 15, где указанный рак обладает пониженным уровнем экспрессии интерферона-гамма (IFNγ) по сравнению с контролем.
18. Применение по п. 15, где уровень экспрессии ER представляет собой ER(-).
19. Применение по п. 15, где указанный модулятор пути передачи сигналов HER2/neu (ErbB2) представляет собой ингибитор отщепления HER.
20. Применение по п. 19, где указанный ингибитор отщепления HER представляет собой антитело к HER.
21. Применение по п. 20, где указанное антитело к HER связывается с HER-рецептором, выбранным из группы, состоящей из EGFR, HER2 и HER3.
22. Применение по п. 21, где указанное антитело к HER2 представляет собой герцептин/трастузумаб.
23. Применение по п. 16, где указанное химиотеревтическое средство представляет собой таксол или производное таксола, где указанное производное таксола предпочтительно представляет собой додетаксел.
24. Применение по п. 15, где указанный ингибитор лиганда программированной клеточной гибели-1 (PD-L1) представляет собой антитело, которое специфически связывается с PD-L1 (антитело к PD-L1).
25. Применение по п. 24, где указанное антитело содержит полипептид вариабельной области тяжелой цепи, содержащий последовательность HVR-H1, HVR-Н2 и HVR-H3, в которой:
(а) последовательность HVR-H1 представляет собой
GFTFSX1SWIH (SEQ ID NO: 1);
(б) последовательность HVR-H2 представляет собой
AWIX2PYGGSX3YYADSVKG (SEQ ID NO: 2);
(в) последовательность HVR-H3 представляет собой
RHWPGGFDY (SEQ ID NO: 3);
кроме того, в которой: X1 обозначает D или G; Х2 обозначает S или L; Х3 обозначает Т или S.
26. Применение по п. 25, где указанный полипептид тяжелой цепи находится в комбинации с вариабельной областью легкой цепи, содержащей HVR-L1, HVR-L2 и HVR-L3, где:
(а) последовательность HVR-L1 представляет собой
RASQX4X5X6TX7X8A (SEQ ID NO: 8);
(б) последовательность HVR-L2 представляет собой
SASX9LX10S (SEQ ID NO: 9);
(в) последовательность HVR-L3 представляет собой
QQX11X12X13X14PX15T (SEQ ID NO: 10);
где, кроме того: Х4 обозначает D или V; Х5 обозначает V или I; Х6 обозначает S или N; Х7 обозначает А или F; Х8 обозначает V или L; Х9 обозначает F или Т; X10 обозначает Y или А; X11 обозначает Y, G, F или S; X12 обозначает L, Y, F или W; X13 обозначает Y, N, А, Т, G, F или I; Х14 обозначает Н, V, Р, Т или I; X15 обозначает A, W, R, Р или Т.
27. Применение по п. 25, где указанное антитело содержит последовательность вариабельной области тяжелой цепи и легкой цепи, где:
тяжелая цепь содержит HVR-H1, HVR-H2 и HVR-H3, которые обладают по меньшей мере 85%-ной идентичностью по всей длине последовательности с GFTFSDSWIH (SEQ ID NO: 15), AWISPYGGSTYYADSVKG (SEQ ID NO: 16) и RHWPGGFDY (SEQ ID NO: 3) соответственно, и
(б) легкая цепь содержит HVR-L1, HVR-L2 и HVR-L3, которые обладают по меньшей мере 85%-ной идентичностью по всей длине последовательности с RASQDVSTAVA (SEQ ID NO: 17), SASFLYS (SEQ ID NO: 18) и QQYLYHPAT (SEQ ID NO: 19) соответственно.
28. Применение по п. 15, где указанный рак представляет собой солидный рак, предпочтительно рак молочной железы или рак желудка.
29. Применение по п. 15, где указанный модулятор пути передачи сигналов HER2/neu (ErbB2), указанное химиотерапевтическое средство и указанный ингибитор лиганда программированной клеточной гибели-1 (PD-L1) применяют в неоадъювантном режиме, или адъювантном режиме, или в метастатическом режиме.
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- 2013-11-29 KR KR1020157014102A patent/KR102291355B1/ko active IP Right Grant
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- 2013-11-29 BR BR112015012644A patent/BR112015012644A2/pt not_active Application Discontinuation
- 2013-11-29 EP EP13814848.1A patent/EP2926142B2/en active Active
- 2013-11-29 JP JP2015544488A patent/JP6998646B2/ja active Active
- 2013-11-29 MX MX2015006756A patent/MX363188B/es unknown
- 2013-11-29 CN CN201380062234.2A patent/CN104813168B/zh active Active
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- 2013-11-29 RU RU2015125638A patent/RU2692773C2/ru active
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2015
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EP2926142B2 (en) | 2022-07-06 |
CA2889298C (en) | 2024-01-02 |
US20160333414A1 (en) | 2016-11-17 |
US20180274038A1 (en) | 2018-09-27 |
BR112015012644A2 (pt) | 2017-12-19 |
US20220170115A1 (en) | 2022-06-02 |
JP7181854B2 (ja) | 2022-12-01 |
US20200199690A1 (en) | 2020-06-25 |
EP3511718A1 (en) | 2019-07-17 |
EP2926142A1 (en) | 2015-10-07 |
JP6998646B2 (ja) | 2022-02-04 |
JP2016508028A (ja) | 2016-03-17 |
CN104813168A (zh) | 2015-07-29 |
MX2015006756A (es) | 2015-08-05 |
KR102291355B1 (ko) | 2021-08-19 |
CN104813168B (zh) | 2017-10-20 |
RU2692773C2 (ru) | 2019-06-27 |
US20220282337A1 (en) | 2022-09-08 |
MX363188B (es) | 2019-03-13 |
KR20150091058A (ko) | 2015-08-07 |
WO2014083178A1 (en) | 2014-06-05 |
HK1208911A1 (en) | 2016-03-18 |
EP2926142B1 (en) | 2018-11-07 |
US20220090212A1 (en) | 2022-03-24 |
JP2020099324A (ja) | 2020-07-02 |
CA2889298A1 (en) | 2014-06-05 |
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