RU2013151455A - Антитела и другие молекулы, которые связывают в7-н1 и pd-1 - Google Patents

Антитела и другие молекулы, которые связывают в7-н1 и pd-1 Download PDF

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RU2013151455A
RU2013151455A RU2013151455/10A RU2013151455A RU2013151455A RU 2013151455 A RU2013151455 A RU 2013151455A RU 2013151455/10 A RU2013151455/10 A RU 2013151455/10A RU 2013151455 A RU2013151455 A RU 2013151455A RU 2013151455 A RU2013151455 A RU 2013151455A
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antibody
var
molecule
heavy chain
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Соломон Лангерманн
Линда Лью
Шэнон МАРШАЛЛ
Шэн ЯО
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Эмплиммьюн, Инк.
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    • 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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    • 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
    • C07K16/2827—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 B7 molecules, e.g. CD80, CD86
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    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins

Abstract

1. Молекула, содержащая антигенсвязывающий фрагмент антитела, которая иммуноспецифически связывается с В7-Н1 или PD-1.2. Молекула по п.1, где указанный иммуноспецифически связанный В7-Н1 или PD-1 экспрессируется на поверхности живой клетки в эндогенной концентрации или концентрации, полученной в результате трансфекции.3. Молекула по любому из пп.1-2, где указанный В7-Н1 представляет собой В7-Н1 человека и указанный PD-1 представляет собой PD-1 человека.4. Молекула по любому из пп.1-2, где указанный антигенсвязывающий фрагмент связывается с В7-Н1, и где указанная живая клетка представляет собой опухолевую клетку, инфицированную патогеном клетку или антигенпрезентирующую клетку.5. Молекула по любому из пп.1-2, где указанный антигенсвязывающий фрагмент связывается с PD-1, и где указанная живая клетка представляет собой Т-клетку.6. Молекула по п.1, где указанная молекула представляет собой моноклональное антитело, антитело человека, химерное антитело или гуманизированное антитело.7. Молекула по п.6, где указанная молекула является биспецифическим, триспецифическим или мультиспецифическим антителом.8. Молекула по п.1 или 6, где молекула связывается с В7-Н1, и где их указанный антигенсвязывающий фрагмент содержит шесть CDR, где указанные CDR содержат по меньшей мере одну консенсусную CDR из CDR антител 1Е12, 1F4, 2G11, ЗВ6 и 3D10 против В7-Н1 со всеми оставшимися CDR, выбранными из:(A) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 1Е12 против В7-Н1;(B) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 1F4 против В7-Н1;(C) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 2G11 против В7-Н1;(D) трех CDR легкой цепи и трех CDR тяжелой цепи антитела ЗВ6 против В7-Н1; или(Е) трех CDR ле

Claims (20)

1. Молекула, содержащая антигенсвязывающий фрагмент антитела, которая иммуноспецифически связывается с В7-Н1 или PD-1.
2. Молекула по п.1, где указанный иммуноспецифически связанный В7-Н1 или PD-1 экспрессируется на поверхности живой клетки в эндогенной концентрации или концентрации, полученной в результате трансфекции.
3. Молекула по любому из пп.1-2, где указанный В7-Н1 представляет собой В7-Н1 человека и указанный PD-1 представляет собой PD-1 человека.
4. Молекула по любому из пп.1-2, где указанный антигенсвязывающий фрагмент связывается с В7-Н1, и где указанная живая клетка представляет собой опухолевую клетку, инфицированную патогеном клетку или антигенпрезентирующую клетку.
5. Молекула по любому из пп.1-2, где указанный антигенсвязывающий фрагмент связывается с PD-1, и где указанная живая клетка представляет собой Т-клетку.
6. Молекула по п.1, где указанная молекула представляет собой моноклональное антитело, антитело человека, химерное антитело или гуманизированное антитело.
7. Молекула по п.6, где указанная молекула является биспецифическим, триспецифическим или мультиспецифическим антителом.
8. Молекула по п.1 или 6, где молекула связывается с В7-Н1, и где их указанный антигенсвязывающий фрагмент содержит шесть CDR, где указанные CDR содержат по меньшей мере одну консенсусную CDR из CDR антител 1Е12, 1F4, 2G11, ЗВ6 и 3D10 против В7-Н1 со всеми оставшимися CDR, выбранными из:
(A) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 1Е12 против В7-Н1;
(B) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 1F4 против В7-Н1;
(C) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 2G11 против В7-Н1;
(D) трех CDR легкой цепи и трех CDR тяжелой цепи антитела ЗВ6 против В7-Н1; или
(Е) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 3D10 против В7-Н1.
9. Молекула по п.8, где указанные шесть CDR представляют собой:
(A) три CDR легкой цепи и три CDR тяжелой цепи антитела 1Е12 против В7-Н1;
(B) три CDR легкой цепи и три CDR тяжелой цепи антитела 1F4 против В7-Н1;
(C) три CDR легкой цепи и три CDR тяжелой цепи антитела 2G11 против В7-Н1;
(D) три CDR легкой цепи и три CDR тяжелой цепи антитела ЗВ6 против В7-Н1; или
(Е) три CDR легкой цепи и три CDR тяжелой цепи антитела 3D10 против В7-Н1.
10. Молекула по п.6, где указанная молекула связывается с В7-Н1 и содержит вариабельный домен антитела h3D10 Var I, h3D10 Var 2, h3D10 Var 3, h3D10 Var 4, h3D10 Var 5, h3D10 Var 6, h3D10 Var 7, h3D10 Var 8, h3D10 Var 9, h3D10 Var 10, h3D10 Var 11, h3D10 Var 12, h3D10 Var 13 или h3D10 Var 14.
11. Молекула по любому из пп.1 или 6, где молекула связывается с PD-1, и где указанный антигенсвязывающий фрагмент содержит шесть CDR, где указанные CDR содержат по меньшей мере одну консенсусную CDR из CDR антител 1Е3, 1Е8 и 1Н3 против PD-1 со всеми оставшимися CDR, выбранными из:
(A) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 1ЕЗ против PD-1;
(B) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 1Е8 против PD-1; или
(C) трех CDR легкой цепи и трех CDR тяжелой цепи антитела 1Н3 против PD-1.
12. Молекула по п.11, где указанные шесть CDR представляют собой:
(A) три CDR легкой цепи и три CDR тяжелой цепи антитела 1Е3 против PD-1;
(B) три CDR легкой цепи и три CDR тяжелой цепи антитела 1Е8 против PD-1; или
(C) три CDR легкой цепи и три CDR тяжелой цепи антитела 1Н3 против PD-1.
13. Молекула по п.6, где указанная молекула связывается с PD-1 и содержит вариабельный домен антитела h1H3 Var I, h1H3 Var 2, h1H3 Var 3, h1H3 Var 4, h1H3 Var 5, h1H3 Var 6, h1H3 Var 7, h1H3 Var 8, h1H3 Var 9, h1H3 Var 10, h1H3 Var 11, h1H3 Var 12, h1H3 Var 13 или h1H3 Var 14.
14. Молекула по любому из пп.1 или 6, где указанная молекула помечены поддающейся определению меткой или содержат конъюгированные токсин, лекарственное средство, рецептор, фермент, лиганд рецептора.
15. Молекула по любому из пп.1 или 6, где указанная молекула:
(A) модулирует передачу сигнала, опосредуемую В7-Н1 или PD-1;
(B) ослабляет способность В7-Н1 связываться с рецептором В7-Н1 или ослабляет способность PD-1 связываться с лигандом PD-1;
(C) является агонистом В7-Н1 или PD-1 в отношении опосредуемой ими передачи сигнала;
(D) опосредует пролиферацию Т-клеток; или
(Е) повышает продукцию IFN-γ.
16. Фармацевтическая композиция, содержащая терапевтически эффективное количество молекулы по п.15 и физиологически приемлемый носитель или эксципиент.
17. Применение фармацевтической композиции по п.16 для лечения злокачественного новообразования, аутоиммунного заболевания, инфекционного заболевания или заболевания, влияющего на количество Т-клеток или на их здоровое состояние.
18. Применение по п.17, где указанное лечение является профилактическим и предлагается перед возникновением любого симптома указанного злокачественного новообразования, указанного аутоиммунного заболевания, указанного инфекционного заболевания или указанного заболевания, влияющего на количество Т-клеток или на их здоровое состояние.
19. Применение молекулы по любому из пп.1-14 для диагностики злокачественного новообразования, аутоиммунного заболевания, инфекционного заболевания или заболевания, влияющего на количество Т-клеток или на их здоровое состояние, у индивидуума с помощью анализа клеток указанного индивидуума на их способность связываться с В7-Н1 или PD-1.
20. Применение по любому из пп.17-19, где:
(A) указанное инфекционное заболевание представляет собой хроническое вирусное заболевание; или
(B) указанное аутоиммунное заболевание представляет собой заболевание трансплантат против хозяина.
RU2013151455A 2011-04-20 2012-04-19 Антитела и другие молекулы, которые связывают в7-н1 и pd-1 RU2625034C2 (ru)

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Cited By (3)

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CN103608040A (zh) 2014-02-26
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US9205148B2 (en) 2015-12-08
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