RU2016122041A - Новые анти-клаудин антитела и способы их применения - Google Patents
Новые анти-клаудин антитела и способы их применения Download PDFInfo
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- 206010028980 Neoplasm Diseases 0.000 claims 10
- 201000011510 cancer Diseases 0.000 claims 10
- 238000000034 method Methods 0.000 claims 10
- 102100038449 Claudin-6 Human genes 0.000 claims 6
- 101000882898 Homo sapiens Claudin-6 Proteins 0.000 claims 6
- 210000000130 stem cell Anatomy 0.000 claims 6
- 102100026097 Claudin-9 Human genes 0.000 claims 4
- 101000912661 Homo sapiens Claudin-9 Proteins 0.000 claims 4
- 108090000623 proteins and genes Proteins 0.000 claims 4
- 102000004169 proteins and genes Human genes 0.000 claims 4
- 210000004027 cell Anatomy 0.000 claims 3
- 102000039446 nucleic acids Human genes 0.000 claims 3
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 150000007523 nucleic acids Chemical class 0.000 claims 3
- 210000004881 tumor cell Anatomy 0.000 claims 3
- 206010033128 Ovarian cancer Diseases 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims 2
- 239000012634 fragment Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 101710112752 Cytotoxin Proteins 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 239000002619 cytotoxin Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940127121 immunoconjugate Drugs 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 201000005249 lung adenocarcinoma Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
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- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6857—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from lung cancer cell
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- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6869—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3023—Lung
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
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Claims (42)
1. Антитело, которое связывается с раковыми стволовыми клетками, экспрессирующими, по меньшей мере, один белок из семейства CLDN.
2. Антитело по п.1, где антитело специфично связывается с CLDN6.
3. Антитело по п.1, где антитело специфично связывается с CLDN6 и CLDN9.
4. Антитело по п.3, где антитело специфично связывается с CLDN6 и CLDN9 с практически одинаковой кажущейся аффинностью связывания.
5. Антитело по п.1, где антитело специфично связывается с CLDN6 и CLDN9 с практически одинаковой кажущейся аффинностью связывания.
6. Антитело по пп. 1-5, которое представляет собой интернализирующееся антитело.
7. Антитело, которое связывается, по меньшей мере, с одним членом семейства CLDN и конкурирует за связывание с антителом, содержащим:
вариабельную область легкой цепи (VL) с последовательностью SEQ ID NO: 21 и вариабельную область тяжелой цепи (VH) с последовательностью SEQ ID NO: 23; или
VL с последовательностью SEQ ID NO: 25 и VH с последовательностью SEQ ID NO: 27; или
VL с последовательностью SEQ ID NO: 29 и VH с последовательностью SEQ ID NO: 31; или
VL с последовательностью SEQ ID NO: 33 и VH с последовательностью SEQ ID NO: 35; или
VL с последовательностью SEQ ID NO: 37 и VH с последовательностью SEQ ID NO: 39; или
VL с последовательностью SEQ ID NO: 41 и VH с последовательностью SEQ ID NO: 43; или
VL с последовательностью SEQ ID NO: 45 и VH с последовательностью SEQ ID NO: 47; или
VL с последовательностью SEQ ID NO: 49 и VH с последовательностью SEQ ID NO: 51; или
VL с последовательностью SEQ ID NO: 53 и VH с последовательностью SEQ ID NO: 55; или
VL с последовательностью SEQ ID NO: 57 и VH с последовательностью SEQ ID NO: 59.
8. Антитело по п.7, где антитело специфично связывается с CLDN6.
9. Антитело по п.7, где антитело специфично связывается с CLDN6 и CLDN9.
10. Антитело по п.7, где антитело представляет собой гибридное, CDR-привитое, гуманизированное или рекомбинантное антитело или его фрагмент.
11. Антитело по п.7, где антитело представляет собой интернализирующееся антитело.
12. Гуманизированное антитело, которое связывается, по меньшей мере, с одним белком из семейства CLDN и конкурирует за связывание с антителом, содержащим три CDRs вариабельной области легкой цепи (CDRL) с последовательностью, представленной в SEQ ID NO: 61; и три CDRs вариабельной области тяжелой цепи (CDRH) с последовательностью, представленной в SEQ ID NO: 63; или три CDRL с последовательностью, представленной в SEQ ID NO: 65, и три CDRH с последовательностью, представленной в SEQ ID NO: 67; или три CDRL с последовательностью, представленной в SEQ ID NO: 69, т три CDRH с последовательностью, представленной в SEQ ID NO: 71; три CDRL с последовательностью, представленной в SEQ ID NO: 73, и три CDRH с последовательностью, представленной в SEQ ID NO: 75.
13. Гуманизированное антитело по п.12, содержащее VH и VL, где VL имеет три CDRLs, включающие в себя CDRL1 с последовательностью SEQ ID NO: 151, CDRL2 с последовательностью SEQ ID NO: 152 и CDRL3 с последовательностью SEQ ID NO: 153; или VL имеет три CDRLs, включающие в себя CDRL1 с последовательностью SEQ ID NO: 157, CDRL2 с последовательностью SEQ ID NO: 158 и CDRL3 с последовательностью SEQ ID NO: 159; или VL имеет три CDRLs, включающие в себя CDRL1 с последовательностью SEQ ID NO: 163, CDRL2 с последовательностью SEQ ID NO: 164 и CDRL3 с последовательностью SEQ ID NO: 165; или VL имеет три CDRLs, включающие в себя CDRL1 с последовательностью SEQ ID NO: 169, CDRL2 с последовательностью SEQ ID NO: 170 и CDRL3 с последовательностью SEQ ID NO: 171.
14. Гуманизированное антитело по п.12, содержащее VL и VH, где VH имеет три CDRs (CDRH), включающие в себя CDRH1 с последовательностью SEQ ID NO: 154, CDRH2 с последовательностью SEQ ID NO: 155 и CDRH3 с последовательностью SEQ ID NO: 156; или VH имеет три CDRHs, включающие в себя CDRH1 с последовательностью SEQ ID NO: 160, CDRH2 с последовательностью SEQ ID NO: 161 и CDRH3 с последовательностью SEQ ID NO: 162; или VH имеет три CDRHs, включающие в себя CDRH1 с последовательностью SEQ ID NO: 166, CDRH2 с последовательностью SEQ ID NO: 167 и CDRH3 с последовательностью SEQ ID NO: 168; или VH имеет три CDRHs, включающие в себя CDRH1 с последовательностью SEQ ID NO: 172, CDRH2 с последовательностью SEQ ID NO: 173 и CDRH3 с последовательностью SEQ ID NO: 174.
15. Гуманизированное антитело по п.12, содержащее VL и VH, где VL имеет три CDRLs, включающие в себя CDRL1 с последовательностью SEQ ID NO: 151, CDRL2 с последовательностью SEQ ID NO: 152 и CDRL3 с последовательностью SEQ ID NO: 153, и VH имеет три CDRHs, включающие в себя CDRH1 с последовательностью SEQ ID NO: 154, CDRH2 с последовательностью SEQ ID NO: 155 и CDRH3 с последовательностью SEQ ID NO: 156; или антитело, содержащее VL и VH, где VL имеет три CDRLs, включающие в себя CDRL1 с последовательностью SEQ ID NO: 157, CDRL2 с последовательностью SEQ ID NO: 158 и CDRL3 с последовательностью SEQ ID NO: 159, и VH имеет три CDRHs, включающие в себя CDRH1 с последовательностью SEQ ID NO: 160, CDRH2 с последовательностью SEQ ID NO: 161 и CDRH3 с последовательностью SEQ ID NO: 162; или антитело, содержащее VL и VH, где VL имеет три CDRLs, включающие в себя CDRL1 с последовательностью SEQ ID NO: 163, CDRL2 с последовательностью SEQ ID NO: 164 и CDRL3 с последовательностью SEQ ID NO: 165, и VH имеет три CDRHs, включающие в себя CDRH1 с последовательностью SEQ ID NO: 166, CDRH2 с последовательностью SEQ ID NO: 167 и CDRH3 с последовательностью SEQ ID NO: 168; или антитело, содержащее VL и VH, где VL имеет три CDRLs, включающие в себя CDRL1 с последовательностью SEQ ID NO: 169, CDRL2 с последовательностью SEQ ID NO: 170 и CDRL3 с последовательностью SEQ ID NO: 171, и VH имеет три CDRHs, включающие в себя CDRH1 с последовательностью SEQ ID NO: 172, CDRH2 с последовательностью SEQ ID NO: 173 и CDRH3 с последовательностью SEQ ID NO: 174.
16. Гуманизированное антитело, которое связывается, по меньшей мере, с одним белком из семейства CLDN, содержащее полноразмерную легкую цепь, представленную в SEQ ID NO: 114, и полноразмерную тяжелую цепь, представленную в SEQ ID NO: 115; или полноразмерную легкую цепь, представленную в SEQ ID NO: 116, и полноразмерную тяжелую цепь, представленную в SEQ ID NO: 117; или полноразмерную легкую цепь, представленную в SEQ ID NO: 118, и полноразмерную тяжелую цепь, представленную в SEQ ID NO: 119; или полноразмерную легкую цепь, представленную в SEQ ID NO: 120, и полноразмерную тяжелую цепь, представленную в SEQ ID NO: 121.
17. Антитело по любому из пп. 1-16, где антитело конъюгировано с полезной нагрузкой.
18. Нуклеиновая кислота, кодирующая антитело по любому из пп. 1-16.
19. Нуклеиновая кислота по п.17, которая содержится в векторе.
20. Нуклеиновая кислота по п.18, которая экспрессируется в клетке-хозяине.
21. Конъюгат антитела с лекарственным средством (КАЛС), содержащий гибридное, CDR-привитое, гуманизированное или рекомбинантное человеческое антитело или его фрагмент, которое связывается с раковыми стволовыми клетками, экспрессирующими, по меньшей мере, один белок из семейства CLDN, где это антитело конъюгировано с цитотоксическим агентом.
22. КАЛС, имеющий формулу Ab-[L-D]n, где Ab представляет собой антитело по пп. 1-16; L представляет собой необязательный линкер; D представляет собой лекарственное средство; и n представляет собой целое число от примерно 1 до примерно 20.
23. Фармацевтическая композиция, содержащая КАЛС по п.22.
24. Способ лечения рака, включающий в себя введение нуждающемуся в этом субъекту фармацевтической композиции по п.23.
25. Способ по п.24, где рак выбран из рака яичника, рака легкого, рака молочной железы и рака поджелудочной железы.
26. Способ по п.25, где рак представляет собой аденокарциному легкого.
27. Способ по п.26, где рак представляет собой рака яичника.
28. Способ по п.24, дополнительно включающий в себя введение субъекту, по меньшей мере, одного дополнительного терапевтического вещества.
29. Способ уменьшения количества раковых стволовых клеток в популяции опухолевых клеток, где этот способ включает в себя приведение популяции опухолевых клеток, содержащей раковые стволовые клетки и опухолевые клетки, отличные от раковых стволовых клеток, в контакт с анти-CLDN КАЛС, в результате чего происходит уменьшение частоты раковых стволовых клеток.
30. Способ по п.29, где приведение в контакт осуществляется in vivo.
31. Способ по п.29, где приведение в контакт осуществляется in vitro.
32. Способ доставки цитотоксина в клетку, включающий в себя приведение этой клетки в контакт с КАЛС по п.22.
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-
2014
- 2014-11-05 JP JP2016552471A patent/JP6515111B2/ja not_active Expired - Fee Related
- 2014-11-05 BR BR112016010169A patent/BR112016010169A2/pt not_active Application Discontinuation
- 2014-11-05 WO PCT/US2014/064165 patent/WO2015069794A2/en not_active Ceased
- 2014-11-05 PE PE2016000592A patent/PE20160870A1/es unknown
- 2014-11-05 RU RU2016122041A patent/RU2016122041A/ru not_active Application Discontinuation
- 2014-11-05 CN CN201480068471.4A patent/CN105813650A/zh active Pending
- 2014-11-05 EP EP14860725.2A patent/EP3065776A4/en not_active Withdrawn
- 2014-11-05 KR KR1020167015010A patent/KR20160070191A/ko not_active Withdrawn
- 2014-11-05 CA CA2928671A patent/CA2928671A1/en not_active Abandoned
- 2014-11-05 US US15/034,992 patent/US10053511B2/en active Active
- 2014-11-05 AU AU2014346792A patent/AU2014346792A1/en not_active Abandoned
- 2014-11-05 MX MX2016005763A patent/MX2016005763A/es unknown
- 2014-11-05 SG SG11201603397QA patent/SG11201603397QA/en unknown
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2015
- 2015-11-05 AR ARP150103600A patent/AR102554A1/es unknown
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2016
- 2016-04-20 IL IL245237A patent/IL245237A0/en unknown
- 2016-04-27 PH PH12016500781A patent/PH12016500781A1/en unknown
- 2016-05-06 CL CL2016001102A patent/CL2016001102A1/es unknown
- 2016-05-16 ZA ZA201603308A patent/ZA201603308B/en unknown
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2018
- 2018-08-20 US US16/105,651 patent/US20190077876A1/en not_active Abandoned
Also Published As
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| RU2016122041A3 (ru) | 2018-03-27 |
| EP3065776A4 (en) | 2017-04-19 |
| AR102554A1 (es) | 2017-03-08 |
| IL245237A0 (en) | 2016-06-30 |
| WO2015069794A2 (en) | 2015-05-14 |
| CA2928671A1 (en) | 2015-05-14 |
| WO2015069794A3 (en) | 2015-06-18 |
| JP2016536020A (ja) | 2016-11-24 |
| US20190077876A1 (en) | 2019-03-14 |
| MX2016005763A (es) | 2016-08-19 |
| SG11201603397QA (en) | 2016-05-30 |
| ZA201603308B (en) | 2019-11-27 |
| CN105813650A (zh) | 2016-07-27 |
| US10053511B2 (en) | 2018-08-21 |
| AU2014346792A1 (en) | 2016-06-02 |
| EP3065776A2 (en) | 2016-09-14 |
| US20160289332A1 (en) | 2016-10-06 |
| BR112016010169A2 (pt) | 2017-12-05 |
| PE20160870A1 (es) | 2016-09-09 |
| WO2015069794A9 (en) | 2015-07-30 |
| PH12016500781A1 (en) | 2016-06-13 |
| KR20160070191A (ko) | 2016-06-17 |
| CL2016001102A1 (es) | 2017-02-10 |
| JP6515111B2 (ja) | 2019-05-22 |
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| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
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