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

Сконструированные конъюгаты против dll3 и способы применения Download PDF

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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
paragraphs
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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    • 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
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    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
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    • 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
    • A61K47/68035—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a pyrrolobenzodiazepine
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    • 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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    • 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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    • C07—ORGANIC CHEMISTRY
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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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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 Сконструированные конъюгаты против dll3 и способы применения RU2016111137A (ru)

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PCT/US2014/053304 WO2015031693A1 (en) 2013-08-28 2014-08-28 Engineered anti-dll3 conjugates and methods of use

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KR (1) KR20160047567A (ru)
CN (1) CN105873612A (ru)
AU (1) AU2014312210A1 (ru)
BR (1) BR112016004073A8 (ru)
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ES2812849T3 (es) 2012-02-24 2021-03-18 Abbvie Stemcentrx Llc Anticuerpos anti-DLL3 y procedimientos de utilización de los mismos
PL3489261T3 (pl) 2012-08-24 2021-08-16 The Regents Of The University Of California Przeciwciała i szczepionki do stosowania w leczeniu nowotworów z ekspresją ROR1 i w hamowaniu przerzutu
WO2014130879A2 (en) 2013-02-22 2014-08-28 Stem Centrx, Inc. Novel antibody conjugates and uses thereof
EP3338793A1 (en) 2013-08-28 2018-06-27 AbbVie Stemcentrx LLC Novel sez6 modulators and methods of use
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