RU2016111137A - Сконструированные конъюгаты против dll3 и способы применения - Google Patents

Сконструированные конъюгаты против dll3 и способы применения

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Publication number
RU2016111137A
RU2016111137A RU2016111137A RU2016111137A RU2016111137A RU 2016111137 A RU2016111137 A RU 2016111137A RU 2016111137 A RU2016111137 A RU 2016111137A RU 2016111137 A RU2016111137 A RU 2016111137A RU 2016111137 A RU2016111137 A RU 2016111137A
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antibody
conjugate
dll3
comprises
drug
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RU2016111137A
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RU2016111137A3 (ru )
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Уильям Роберт АРАТУН
Ишаи ПАДАВЕР
Луис Антонио КАНО
Викрам Натварсинджи СИСОДИЯ
Картик Нараян МАНИ
Дэвид ЛИУ
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ЭББВИ СТЕМСЕНТРКС ЭлЭлСи
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • C07K16/3023Lung
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/54Medicinal 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 organic compound
    • A61K47/55Medicinal 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 organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6849Medicinal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6851Medicinal 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/68Medicinal 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
    • A61K47/6835Medicinal 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
    • A61K47/6851Medicinal 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
    • A61K47/6857Medicinal 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/53Hinge
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Claims (28)

1. Конъюгат антитела с лекарственным средством с формулой:
Ab-[L-D]n или его фармацевтически приемлемая соль, где
a) Ab включает антитело к DLL3 с одним или более неспаренными цистеинами;
b) L содержит необязательный линкер;
c) D содержит ПБД; и
d) n представляет собой целое число приблизительно от 1 до приблизительно 8.
2. Конъюгат антитела с лекарственным средством по п. 1, где антитело к DLL3 содержит моноклональное антитело.
3. Конъюгат антитела с лекарственным средством по пп. 1 или 2, где антитело к DLL3 содержит интернализированное антитело.
4. Конъюгат антитела с лекарственным средством по любому из пп. 1-3, где антитело к DLL3 содержит гуманизированное антитело или антитело с привитой CDR.
5. Конъюгат антитела с лекарственным средством по любому из пп. 1-4, где антитело к DLL3 содержит два неспаренных цистеина.
6. Конъюгат антитела с лекарственным средством по любому из пп. 1-5, где антитело к DLL3 содержит легкую цепь каппа.
7. Конъюгат антитела с лекарственным средством по п. 6, где антитело к DLL3 содержит легкую цепь, где C214 включает неспаренный цистеин.
8. Конъюгат антитела с лекарственным средством по любому из пп. 1-7, где антитело к DLL3 содержит тяжелую цепь IgG1.
9. Конъюгат антитела с лекарственным средством по п. 8, где антитело к DLL3 содержит тяжелую цепь, где C220 включает неспаренный цистеин.
10. Конъюгат антитела с лекарственным средством по любому из пп. 1-9, где антитело к DLL3 выбрано из группы, состоящей из hSC16.13, hSC16.15, hSC16.25, hSC16.34 и hSC16.56, или антитела, которое конкурирует за связывание с DLL3 человека с любым одним из hSC16.13, hSC16.15, hSC16.25, hSC16.34 и hSC16.56.
11. Конъюгат антитела с лекарственным средством по любому из пп. 1-10, где ПБД содержит ПБД, выбранный из группы, состоящей из ПБД1, ПБД2, ПБД3, ПБД4 и ПБД5.
12. Конъюгат антитела с лекарственным средством по любому из пп. 1-11, где конъюгат антитела с лекарственным средством содержит расщепляемый линкер.
13. Конъюгат антитела с лекарственным средством по п. 12, где расщепляемый линкер содержит дипептид.
14. Фармацевтическая композиция, включающая конъюгат антитела с лекарственным средством по любому из пп. 1-13 и фармацевтически приемлемый носитель.
15. Способ лечения рака у субъекта, включающий введение указанному субъекту фармацевтической композиции по п. 14.
16. Способ по п. 15, где рак включает мелкоклеточный рак легких.
17. Способ получения конъюгата антитела с лекарственным средством по любому из пп. 1-13, включающий стадии:
a) создания антитела к DLL3, содержащего неспаренный цистеин;
b) селективного восстановления антитела к DLL3; и
c) конъюгации селективно восстановленного антитела к DLL3 с ПБД.
18. Способ по п. 17, где стадия селективного восстановления антитела к DLL3 включает стадию контакта антитела со стабилизатором.
19. Способ по любому из пп. 17 - 19, дополнительно включающий стадию очистки конъюгата антитела с лекарственным средством с использованием препаративной хроматографии.
20. Конъюгат антитела с лекарственным средством, содержащий АЛС, выбранный из группы, состоящей из АЛС1, АЛС2, АЛС3, АЛС4 и АЛС5, где Ab содержит сконструированное антитело к DLL3.
RU2016111137A 2013-08-28 2014-08-28 RU2016111137A3 (ru)

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US201361871173 true 2013-08-28 2013-08-28
US61/871,173 2013-08-28
PCT/US2014/053304 WO2015031693A1 (en) 2013-08-28 2014-08-28 Engineered anti-dll3 conjugates and methods of use

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US (1) US20160175460A1 (ru)
EP (1) EP3038659A4 (ru)
KR (1) KR20160047567A (ru)
CN (1) CN105873612A (ru)
CA (1) CA2922544A1 (ru)
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WO2014031174A1 (en) 2012-08-24 2014-02-27 The Regents Of The University Of California Antibodies and vaccines for use in treating ror1 cancers and inhibiting metastasis
CA2922547A1 (en) 2013-08-28 2015-03-05 Stemcentrx, Inc. Site-specific antibody conjugation methods and compositions
CN105792836A (zh) 2013-08-28 2016-07-20 施特姆森特克斯股份有限公司 新型sez6调节剂以及应用方法
CN107530443A (zh) * 2015-03-04 2018-01-02 艾伯维施特姆森特克斯有限责任公司 工程化的位点特异性抗体和使用方法
GB201506394D0 (en) * 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
GB201506393D0 (en) * 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
GB201506402D0 (en) * 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
GB201506407D0 (en) * 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
GB201506405D0 (en) * 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
GB201506399D0 (en) * 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
GB201506389D0 (en) * 2015-04-15 2015-05-27 Berkel Patricius H C Van And Howard Philip W Site-specific antibody-drug conjugates
GB201506388D0 (en) * 2015-04-15 2015-05-27 Berkel Patricius H C Van And Cancer Res Technology Ltd And Howard Philip W Site-specific antibody-drug conjugates
CN108025085A (zh) * 2015-06-23 2018-05-11 拜耳制药股份公司 Ksp抑制剂与抗b7h3抗体的抗体药物缀合物(adc)
GB201602363D0 (en) * 2016-02-10 2016-03-23 Adc Therapeutics Sa And Medimmune Ltd Pyrrolobenzodiazepine conjugates

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EP1817341A2 (en) * 2004-11-29 2007-08-15 Seattle Genetics, Inc. Engineered antibodies and immunoconjugates
RU2008129028A (ru) * 2005-12-16 2010-01-27 Дженентек, Инк. (Us) Способ диагностики, прогнозировния и лечения глиомы
US20130058947A1 (en) * 2011-09-02 2013-03-07 Stem Centrx, Inc Novel Modulators and Methods of Use
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CN103998450B (zh) * 2011-10-14 2017-03-08 麦迪穆有限责任公司 吡咯并苯并二氮杂卓
GB201302447D0 (en) * 2013-02-12 2013-03-27 Oxford Biotherapeutics Ltd Therapeutic and diagnostic target

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WO2015031693A1 (en) 2015-03-05 application
CN105873612A (zh) 2016-08-17 application
CA2922544A1 (en) 2015-03-05 application
RU2016111137A3 (ru) 2018-07-12 application
KR20160047567A (ko) 2016-05-02 application
EP3038659A4 (en) 2017-07-26 application
US20160175460A1 (en) 2016-06-23 application
EP3038659A1 (en) 2016-07-06 application

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