RU2019113758A - Конъюгат "цистеин-модифицированное антитело-лекарственное средство" и способ его получения - Google Patents

Конъюгат "цистеин-модифицированное антитело-лекарственное средство" и способ его получения Download PDF

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RU2019113758A
RU2019113758A RU2019113758A RU2019113758A RU2019113758A RU 2019113758 A RU2019113758 A RU 2019113758A RU 2019113758 A RU2019113758 A RU 2019113758A RU 2019113758 A RU2019113758 A RU 2019113758A RU 2019113758 A RU2019113758 A RU 2019113758A
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cysteine
antibody
cytotoxin
light chain
conjugate
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RU2019113758A
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RU2762594C2 (ru
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И Чжу
Иси ВАН
Ши ЧЖО
Цзе ЛИ
Лань ЧЭНЬ
Вэйли ВАНЬ
Юнго ЮЙ
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Сычуань Байли Фарм Ко., Лтд.
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    • 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
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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
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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    • C07—ORGANIC CHEMISTRY
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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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
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Claims (14)

1. Конъюгат «цистеин-модифицированное антитело-цитотоксин», содержащий антитело и цитотоксин, где антитело содержит встроенный цистеин в участке встраивания цистеина, где участок встраивания цистеина включает положение 205 константной области легкой цепи каппа/λ по системе нумерации по Kabat, положение 206 константной области легкой цепи по системе нумерации по Kabat или положение 439 константной области тяжелой цепи IgG по системе нумерации по Kabat.
2. Конъюгат «цистеин-модифицированное антитело-цитотоксин» по п.1, где участок встраивания цистеина содержит аминокислотную последовательность, выбранную из LC-205ins: GLSSPCVTKSF, LC-206ins: GLSSPVCTKSF, и HC-439ins: TQKSLSCLSPGK, и где "C" является встроенным цистеином в положении 205 константной области легкой цепи, положении 206 константной области легкой цепи или положении 439 константной области тяжелой цепи.
3. Конъюгат «цистеин-модифицированное антитело-цитотоксин» по п.1, где встроенный цистеин содержит свободную тиоловую группу, где цитотоксин конъюгируют со свободной тиоловой группой посредством линкера, где антитело содержит легкую цепь, имеющую аминокислотную последовательность, выбранную из GLSSPCVTKSF и GLSSPVCTKSF, где антитело содержит тяжелую цепь, имеющую аминокислотную последовательность TQKSLSCLSPGK, и где C является встроенным цистеином в положении 205 легкой цепи, положении 206 легкой цепи или положении 439 тяжелой цепи антитела.
4. Конъюгат «цистеин-модифицированное антитело-цитотоксин» по п.1, где антитело содержит легкую цепь, где легкая цепь имеет изотип каппа (κ) или лямбда (λ).
5. Конъюгат «цистеин-модифицированное антитело-цитотоксин» по п.1, где антитело содержит тяжелую цепь, где тяжелая цепь имеет изотип IgG1, IgG2, IgG3 или IgG4.
6. Конъюгат «цистеин-модифицированное антитело-цитотоксин» по п.1, где встроенный цистеин содержит тиоловую группу (-SH).
7. Конъюгат «цистеин-модифицированное антитело-цитотоксин» по п.6, где тиоловая группа сконфигурирована для химической конъюгации.
8. Конъюгат «цистеин-модифицированное антитело-цитотоксин» по п. 1, где цитотоксин выбран из MMAE, MMAF, PBD, SN-38, Dox или их производного.
9. Способ получения конъюгата «цистеин-модифицированное антитело-цитотоксин» по п.1, включающий
восстановление антитела с помощью восстановителя для получения восстановленного антитела, где антитело содержит встроенный цистеин, содержащий тиоловую группу, экранированную защитной группой, и где восстановленное антитело содержит встроенный цистеин, из которого защитная группа удалена для получения свободной тиоловой группы,
удаление защитной группы и восстановителя посредством катионообменной хроматографии или ультрафильтрации,
окисление восстановленного антитела для получения окисленного антитела, содержащего межцепочечную дисульфидную связь,
конъюгацию линкера-цитотоксина со свободной тиоловой группой на встроенном цистеине для получения конъюгата «цистеин-модифицированное антитело-цитотоксин», и
удаление неконъюгированного линкера-цитотоксина посредством катионообменной хроматографии или ультрафильтрации.
RU2019113758A 2016-10-08 2017-09-30 Конъюгат "цистеин-модифицированное антитело-лекарственное средство" и способ его получения RU2762594C2 (ru)

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CN110872339A (zh) * 2018-08-30 2020-03-10 中国人民解放军军事科学院军事医学研究院 含有芳硝基的连接子、含连接子的抗体偶联药物及连接子的用途
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EP1791565B1 (en) * 2004-09-23 2016-04-20 Genentech, Inc. Cysteine engineered antibodies and conjugates
CA2683568A1 (en) * 2007-05-08 2008-11-20 Genentech, Inc. Cysteine engineered anti-muc16 antibodies and antibody drug conjugates
TW200918089A (en) * 2007-07-16 2009-05-01 Genentech Inc Humanized anti-CD79b antibodies and immunoconjugates and methods of use
AU2008312457B2 (en) * 2007-10-19 2014-04-17 Genentech, Inc. Cysteine engineered anti-TENB2 antibodies and antibody drug conjugates
SI2657253T1 (sl) * 2008-01-31 2017-10-30 Genentech, Inc. Protitelesa proti CD79b in imunokonjugati in postopki za uporabo
EP2507381A4 (en) * 2009-12-04 2016-07-20 Hoffmann La Roche PLURISPECIFIC ANTIBODIES, ANTIBODY ANALOGUES, COMPOSITIONS AND METHODS
CN105143271A (zh) * 2013-02-08 2015-12-09 Irm责任有限公司 用于修饰抗体以制备免疫缀合物的特定位点
WO2015157595A1 (en) * 2014-04-11 2015-10-15 Medimmune, Llc Conjugated compounds comprising cysteine-engineered antibodies
WO2016131769A2 (en) * 2015-02-16 2016-08-25 Lonza Ltd Antibodies
CN106467575B (zh) * 2015-08-18 2020-07-31 四川百利药业有限责任公司 半胱氨酸改造的抗体-毒素偶联物
US20170216452A1 (en) * 2015-11-30 2017-08-03 Pfizer Inc. Antibodies and antibody fragments for site-specific conjugation
CN106866822A (zh) * 2016-12-25 2017-06-20 四川百利药业有限责任公司 半胱氨酸改造的抗体‑毒素偶联物

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