RU2018123717A - Комбинированные лечения, их применения и способы - Google Patents
Комбинированные лечения, их применения и способы Download PDFInfo
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- RU2018123717A RU2018123717A RU2018123717A RU2018123717A RU2018123717A RU 2018123717 A RU2018123717 A RU 2018123717A RU 2018123717 A RU2018123717 A RU 2018123717A RU 2018123717 A RU2018123717 A RU 2018123717A RU 2018123717 A RU2018123717 A RU 2018123717A
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- 238000000034 method Methods 0.000 title claims 6
- 238000011282 treatment Methods 0.000 title claims 3
- 102000025171 antigen binding proteins Human genes 0.000 claims 13
- 108091000831 antigen binding proteins Proteins 0.000 claims 13
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims 9
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims 9
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims 9
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 201000011510 cancer Diseases 0.000 claims 5
- 230000002519 immonomodulatory effect Effects 0.000 claims 4
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims 3
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims 3
- 229940127089 cytotoxic agent Drugs 0.000 claims 3
- 239000002254 cytotoxic agent Substances 0.000 claims 3
- 231100000599 cytotoxic agent Toxicity 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 2
- 229940127121 immunoconjugate Drugs 0.000 claims 2
- MFRNYXJJRJQHNW-DEMKXPNLSA-N (2s)-2-[[(2r,3r)-3-methoxy-3-[(2s)-1-[(3r,4s,5s)-3-methoxy-5-methyl-4-[methyl-[(2s)-3-methyl-2-[[(2s)-3-methyl-2-(methylamino)butanoyl]amino]butanoyl]amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]amino]-3-phenylpropanoic acid Chemical compound CN[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 MFRNYXJJRJQHNW-DEMKXPNLSA-N 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical group CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229960003301 nivolumab Drugs 0.000 claims 1
- 229960002621 pembrolizumab Drugs 0.000 claims 1
- 102220199908 rs150665982 Human genes 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 239000004474 valine Substances 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- 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
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68031—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being an auristatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- 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
- 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
- A61K47/6849—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 receptor, a cell surface antigen or a cell surface determinant
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—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
- A61K47/50—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
- 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
- A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- 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
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39516—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum from serum, plasma
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- General Chemical & Material Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Claims (30)
1. Комбинация, содержащая терапевтически эффективное количество антигенсвязывающего белка, который связывает ВСМА, и терапевтически эффективное количество по меньшей мере одного антигенсвязывающего белка, который связывает иммуномодулирующую мишень.
2. Комбинация по п.1, где иммуномодулирующая мишень представляет собой PD1 или OX40.
3. Комбинация по любому из предшествующих пунктов, где антигенсвязывающий белок, который связывает BCMA, конъюгирован с цитотоксическим агентом в виде иммуноконъюгата, и цитотоксический агент представляет собой МMAE или MMAF.
4. Комбинация по п.3, где цитотоксический агент конъюгирован с антигенсвязывающим белком, который связывает ВСМА, через линкер, и линкер представляет собой цитруллин-валин или малеимидокапроил.
5. Комбинация по любому из предшествующих пунктов, где антигенсвязывающий белок, который связывает BCMA, содержит CDRH3 из варианта N99D SEQ. ID. NO: 200.
6. Комбинация по пп. 1-4, где антигенсвязывающий белок, который связывает ВСМА, содержит CDRH3 из SEQ. ID. No: 3 или ее вариант.
7. Комбинация по п.1, где антигенсвязывающий белок, который связывает BCMA, содержит CDRH1 из SEQ. ID. NO: 1, CDRH2 из SEQ. ID. NO: 2, CDRH3 из SEQ. ID. NO: 200, CDRL1 из SEQ. ID. NO: 4, CDRL2 из SEQ. ID. NO: 5, CDRL3 из SEQ. ID. NO: 6 или их варианты.
8. Комбинация по любому из предшествующих пунктов, где антигенсвязывающий белок, который связывает BCMA, содержит вариабельную область тяжелой цепи из SEQ. ID. NO: 23 и вариабельную область легкой цепи из SEQ. ID. NO: 31.
9. Комбинация по п.2, где антигенсвязывающий белок, который связывает PD-1, представляет собой пембролизумаб или ниволумаб.
10. Комбинация по п.2, где антигенсвязывающий белок, который связывает OX40, содержит CDRH1 из SEQ. ID. NO: 219, CDRH2 из SEQ. ID. NO: 220, CDRH3 из SEQ. ID. NO: 221, CDRL1 из SEQ. ID. NO: 222, CDRL2 из SEQ. ID. NO: 223, CDRL3 из SEQ. ID. NO: 224, или их варианты.
11. Комбинация по п.2, где антигенсвязывающий белок, который связывает OX40, содержит вариабельную область тяжелой цепи из SEQ. ID. NO: 229 и вариабельную область легкой цепи из SEQ. ID. NO: 230.
12. Комбинация, содержащая:
i) антигенсвязывающий белок, который связывает BCMA, в котором антигенсвязывающий белок, который связывает BCMA, представляет собой иммуноконъюгат, содержащий антитело против BCMA, содержащее CDRH1 из SEQ. ID. NO: 1, CDRH2 из SEQ. ID. NO: 2, CDRH3 из SEQ. ID. NO: 200, CDRL1 из SEQ. ID. NO: 4, CDRL2 из SEQ. ID. NO: 5, CDRL3 из SEQ. ID. NO: 6, или их варианты, конъюгированное с MMAF; и
ii) пембролизумаб или ниволумаб.
13. Комбинация, содержащая:
i) антигенсвязывающий белок, который связывает BCMA, в котором антигенсвязывающий белок, который связывает BCMA, представляет собой иммуноконъюгат, содержащий антитело против BCMA, содержащее CDRH1 из SEQ. ID. NO: 1, CDRH2 из SEQ. ID. NO: 2, CDRH3 из SEQ. ID. NO: 200, CDRL1 из SEQ. ID. NO: 4, CDRL2 из SEQ. ID. NO: 5, CDRL3 из SEQ. ID. NO: 6, или их варианты, конъюгированное с MMAF; и
ii) антигенсвязывающий белок, который связывает OX40, содержащий CDRH1 из SEQ. ID. NO: 219, CDRH2 из SEQ. ID. NO: 220, CDRH3 из SEQ. ID. NO: 221, CDRL1 из SEQ. ID. NO: 222, CDRL2 из SEQ. ID. NO: 223, CDRL3 из SEQ. ID. NO: 224, или их варианты.
14. Фармацевтическая композиция, содержащая комбинацию по любому из пп. 1-13.
15. Способ лечения рака у млекопитающего, нуждающегося в этом, включающий введение терапевтически эффективного количества комбинации, содержащей терапевтически эффективное количество антигенсвязывающего белка, который связывает ВСМА, и терапевтически эффективное количество по меньшей мере одного антигенсвязывающего белка, который связывает иммуномодулирующую мишень.
16. Способ по п.15, где иммуномодулирующая мишень представляет собой PD1 или OX40.
17. Способ по п.15, где млекопитающее представляет собой человека.
18. Способ по п.15, где рак представляет собой множественную миелому или неходжкинскую лимфому.
19. Способ лечения рака у человека, нуждающегося в этом, включающий введение терапевтический эффективного количества комбинации, содержащей:
i) терапевтический эффективное количество антигенсвязывающего белка, который связывает BCMA, где антигенсвязывающий белок, который связывает BCMA, представляет собой иммуноконъюгат, содержащий антитело против BCMA, содержащее CDRH1 из SEQ. ID. NO: 1, CDRH2 из SEQ. ID. NO: 2, CDRH3 из SEQ. ID. NO: 200, CDRL1 из SEQ. ID. NO: 4, CDRL2 из SEQ. ID. NO: 5, CDRL3 из SEQ. ID. NO: 6, или их варианты, конъюгированное с MMAF; и
ii) терапевтически эффективное количество пембролизумаба или ниволумаба.
20. Способ лечения рака у человека, нуждающегося в этом, включающий введение терапевтически эффективного количества комбинации, содержащей:
i) терапевтически эффективное количество антигенсвязывающего белка, который связывает BCMA, где антигенсвязывающий белок, который связывает BCMA, представляет собой иммуноконъюгат, содержащий антитело против BCMA, содержащее CDRH1 из SEQ. ID. NO: 1, CDRH2 из SEQ. ID. NO: 2, CDRH3 из SEQ. ID. NO: 200, CDRL1 из SEQ. ID. NO: 4, CDRL2 из SEQ. ID. NO: 5, CDRL3 из SEQ. ID. NO: 6, или их варианты, конъюгированное с MMAF; и
ii) терапевтически эффективное количество антигенсвязывающего белка, который связывает OX40, содержащего CDRH1 из SEQ. ID. NO: 219, CDRH2 из SEQ. ID. NO: 220, CDRH3 из SEQ. ID. NO: 221, CDRL1 из SEQ. ID. NO: 222, CDRL2 из SEQ. ID. NO: 223, CDRL3 из SEQ. ID. NO: 224, или их варианты.
21. Комбинация по любому из пп. 1-13 для применения при лечении рака.
22. Применение комбинации по любому из пп. 1-13 для изготовления лекарственного средства для лечения рака.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US201562261481P | 2015-12-01 | 2015-12-01 | |
US62/261,481 | 2015-12-01 | ||
PCT/IB2016/057275 WO2017093942A1 (en) | 2015-12-01 | 2016-12-01 | Combination treatments and uses and methods thereof |
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RU2018123717A true RU2018123717A (ru) | 2020-01-14 |
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RU2018123717A RU2018123717A (ru) | 2015-12-01 | 2016-12-01 | Комбинированные лечения, их применения и способы |
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Country | Link |
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US (1) | US20190256608A1 (ru) |
EP (2) | EP4015537A1 (ru) |
JP (3) | JP2019505476A (ru) |
KR (1) | KR20180083936A (ru) |
CN (1) | CN108884161A (ru) |
AU (1) | AU2016362774A1 (ru) |
BR (1) | BR112018011228A2 (ru) |
CA (1) | CA3006934A1 (ru) |
ES (1) | ES2913208T3 (ru) |
IL (1) | IL259570A (ru) |
RU (1) | RU2018123717A (ru) |
WO (1) | WO2017093942A1 (ru) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
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US10478494B2 (en) | 2015-04-03 | 2019-11-19 | Astex Therapeutics Ltd | FGFR/PD-1 combination therapy for the treatment of cancer |
SG11201806261XA (en) | 2016-02-17 | 2018-09-27 | Seattle Genetics Inc | Bcma antibodies and use of same to treat cancer and immunological disorders |
US20200023072A1 (en) * | 2016-10-11 | 2020-01-23 | Medimmune Limited | Antibody-drug conjugates with immune-mediated therapy agents |
CN111094353A (zh) * | 2017-09-14 | 2020-05-01 | 葛兰素史密斯克莱知识产权发展有限公司 | 用于癌症的组合治疗 |
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WO2017093942A1 (en) | 2017-06-08 |
JP7305822B2 (ja) | 2023-07-10 |
JP2019505476A (ja) | 2019-02-28 |
EP4015537A1 (en) | 2022-06-22 |
CA3006934A1 (en) | 2017-06-08 |
IL259570A (en) | 2018-07-31 |
JP2022068232A (ja) | 2022-05-09 |
EP3383907B1 (en) | 2022-02-23 |
CN108884161A (zh) | 2018-11-23 |
EP3383907A1 (en) | 2018-10-10 |
US20190256608A1 (en) | 2019-08-22 |
JP7350118B2 (ja) | 2023-10-02 |
ES2913208T3 (es) | 2022-06-01 |
BR112018011228A2 (pt) | 2019-01-15 |
JP2022088466A (ja) | 2022-06-14 |
AU2016362774A1 (en) | 2018-05-31 |
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