RU2014136702A - Одноцепочечные антитела и другие гетеромультимеры - Google Patents

Одноцепочечные антитела и другие гетеромультимеры Download PDF

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RU2014136702A
RU2014136702A RU2014136702A RU2014136702A RU2014136702A RU 2014136702 A RU2014136702 A RU 2014136702A RU 2014136702 A RU2014136702 A RU 2014136702A RU 2014136702 A RU2014136702 A RU 2014136702A RU 2014136702 A RU2014136702 A RU 2014136702A
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Бернд ВРАНИК
Дэн Л. ИТОН
Эрин Х. КРИСТЕНСЕН
Цзяньшэн ВУ
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Дженентек, Инк.
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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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    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • 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
    • 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
    • C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • 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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • 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
    • C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components

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Abstract

1. Одноцепочечное антитело, содержащее один полипептид, содержащий следующие компоненты:(a) первый домен VH (VH) и второй домен VH (VH),(b) линкер HD; и(c) один или несколько константных доменов тяжелой цепи,где указанные один или несколько константных доменов тяжелой цепи выбраны из первого домена CH2 (CH2), первого домена CH3 (CH3), второго домена CH2 (CH2) и второго домена СН3 (CH3); игде указанные компоненты расположены относительно друг друга в направлении от N-конца к С-концу следующим образом: VH-необязательный CH2-необязательный CH3-HD линкер-VH-необязательный CH2-необязательный CH3.2. Одноцепочечное антитело, содержащее один полипептид, содержащий следующие домены, расположенные относительно друг друга в направлении от N-конца к С-концу: VL-CL-CLH линкер-VH-CH1-шарнир-CH2-CH3-HD линкер-VL-CL-CLH линкер-VH-CH1-шарнир-CH2-CH3.3. Полинуклеотид, кодирующий одноцепочечное антитело по п. 1.4. Вектор, содержащий полинуклеотид по п. 3.5. Клетка-хозяин, содержащая вектор по п. 4.6. Способ получения одноцепочечного антитела по п. 1, где указанный способ включает культивирование клетки-хозяина, которая содержит вектор по п. 4, в культуральной среде.7. Антитело, содержащее следующие компоненты:(a) первый и второй идентичные полипептиды, каждый из которых содержит домен VL и домен CL; и(b) третий полипептид, содержащий:(i) первый домен VH (VH), и второй домен VH (VH),(ii) HD линкер,(iii) первый шарнирный домен (шарнир) или второй шарнирный домен (шарнир), или оба шарнирных домена; и(iv) один или несколько константных доменов тяжелой цепи,где указанные один или несколько константных доменов тяжелой цепи выбраны из первого домена CH1 (CH1), первого домена CH2 (CH2), первого домена CH3 (CH3), второго домена CH1 (CH1), второго домена СН2 (CH2), второго домена CH3 (CH3); игде указанные компоненты указанного третьего полипептида расположены относительно друг друг

Claims (24)

1. Одноцепочечное антитело, содержащее один полипептид, содержащий следующие компоненты:
(a) первый домен VH (VH1) и второй домен VH (VH2),
(b) линкер HD; и
(c) один или несколько константных доменов тяжелой цепи,
где указанные один или несколько константных доменов тяжелой цепи выбраны из первого домена CH2 (CH21), первого домена CH3 (CH31), второго домена CH2 (CH22) и второго домена СН3 (CH32); и
где указанные компоненты расположены относительно друг друга в направлении от N-конца к С-концу следующим образом: VH1-необязательный CH21-необязательный CH31-HD линкер-VH2-необязательный CH22-необязательный CH32.
2. Одноцепочечное антитело, содержащее один полипептид, содержащий следующие домены, расположенные относительно друг друга в направлении от N-конца к С-концу: VL1-CL1-CLH линкер1-VH1-CH11-шарнир1-CH21-CH31-HD линкер-VL2-CL2-CLH линкер2-VH2-CH12-шарнир2-CH22-CH32.
3. Полинуклеотид, кодирующий одноцепочечное антитело по п. 1.
4. Вектор, содержащий полинуклеотид по п. 3.
5. Клетка-хозяин, содержащая вектор по п. 4.
6. Способ получения одноцепочечного антитела по п. 1, где указанный способ включает культивирование клетки-хозяина, которая содержит вектор по п. 4, в культуральной среде.
7. Антитело, содержащее следующие компоненты:
(a) первый и второй идентичные полипептиды, каждый из которых содержит домен VL и домен CL; и
(b) третий полипептид, содержащий:
(i) первый домен VH (VH1), и второй домен VH (VH2),
(ii) HD линкер,
(iii) первый шарнирный домен (шарнир1) или второй шарнирный домен (шарнир2), или оба шарнирных домена; и
(iv) один или несколько константных доменов тяжелой цепи,
где указанные один или несколько константных доменов тяжелой цепи выбраны из первого домена CH1 (CH11), первого домена CH2 (CH21), первого домена CH3 (CH31), второго домена CH1 (CH12), второго домена СН2 (CH22), второго домена CH3 (CH32); и
где указанные компоненты указанного третьего полипептида расположены относительно друг друга в направлении от N-конца к С-концу следующим образом: VH1-необязательный CH11-необязательный шарнир1-необязательный CH21-необязательный CH31-HD линкер-VH2-необязательный CH12-необязательный шарнир2-необязательный CH22-необязательный CH32.
8. Антитело, содержащее следующие компоненты:
(a) первый полипептид, содержащий первый домен VL (VL1) и первый домен CL (CL1); и
(b) второй полипептид, содержащий:
(i) первый домен VH (VH1) и второй домен VH (VH2),
(ii) HD линкер,
(iii) второй домен VL (VL2) и второй домен CL (CL2),
(iv) CLH линкер,
(v) первый шарнирный домен (шарнир1) или второй шарнирный домен (шарнир2), или оба шарнирных домена; и
(vi) один или несколько константных доменов тяжелой цепи,
где указанные один или несколько константных доменов тяжелой цепи выбраны из первого домена CH1 (CH11), первого домена CH2 (CH21), первого домена CH3 (CH31), второго домена CH1 (CH12), второго домена СН2 (CH22), второго домена CH3 (CH32); и
где указанные компоненты указанного второго полипептида расположены относительно друг друга в направлении от N-конца к С-концу следующим образом: VH1-необязательный CH11-необязательный шарнир1-необязательный CH21-необязательный CH31-HD линкер-VL2-CL2-CLH линкер-VH2-необязательный CH12-необязательный шарнир2-необязательный CH22-необязательный CH32.
9. Антитело, содержащее следующие компоненты:
(a) первый полипептид, содержащий:
(i) первый домен VL (VL1) и второй домен CL (CL1),
(ii) CLH линкер,
(iii) первый домен VH (VH1) и второй домен VH (VH2),
(iv) HD линкер,
(v) первый шарнирный домен (шарнир1) или второй шарнирный домен (шарнир2), или оба шарнирных домена; и
(vi) один или несколько константных доменов тяжелой цепи, и
(b) второй полипептид, содержащий второй домен VL (VL2) и второй домен CL (CL2);
где указанные один или несколько константных доменов тяжелой цепи указанного первого полипептида выбраны из первого домена CH1 (CH11), первого домена CH2 (CH21), первого домена CH3 (CH31), второго домена CH1 (CH12), второго домена СН2 (CH22), второго домена CH3 (CH32); и
где указанные компоненты указанного первого полипептида расположены относительно друг друга в направлении от N-конца к С-концу следующим образом: VL1-CL1-CLH линкер-VH1-необязательный CH11-необязательный шарнир1-необязательный CH21-необязательный CH31-HD линкер-VH2-необязательный CH12-необязательный шарнир2-необязательный CH22-необязательный CH32.
10. Полинуклеотид, кодирующий антитело по любому из пп. 7-9.
11. Вектор, содержащий полинуклеотид по п. 10.
12. Клетка-хозяин, содержащая вектор по п. 11.
13. Способ получения антитела по любому из пп. 7-9, где указанный способ включает культивирование клетки-хозяина, которая содержит вектор по п. 11, в культуральной среде.
14. Гетеромультимер, содержащий следующие компоненты:
(a) адгезин,
(b) первый домен CH2 (CH21) или первый домен CH3 (CH31), или оба домена,
(c) HD линкер,
(d) домен VH; и
(e) один или несколько константных доменов тяжелой цепи, выбранных из домена CH1, второго домена CH2 (CH22), или второго домена CH3 (CH32),
где указанные компоненты указанного гетеромультимера расположены относительно друг друга в направлении от N-конца к С-концу следующим образом: адгезин-необязательный CH21-необязательный СН31-HD линкер-VH-необязательный CH1-необязательный CH22-необязательный CH32.
15. Полинуклеотид, кодирующий гетеромультимер по п. 14.
16. Вектор, содержащий полинуклеотид по п. 15.
17. Клетка-хозяин, содержащая вектор по п. 16.
18. Способ получения гетеромультимера по п. 14, где указанный способ включает культивирование клетки-хозяина, которая содержит вектор по п. 16, в культуральной среде.
19. Одноцепочечное антитело, содержащее один полипептид, содержащий следующие домены, расположенные относительно друг друга в направлении от N-конца к С-концу следующим образом: VL1-CL1-CLH линкер1-VH1-CH11-шарнир1-CH21-CH31-HD линкер-VL2-CL2-CLH линкер2-VH2-CH12-шарнир2-CH22-CH32, где каждый из CLH линкера1, CLH линкера2 и HD линкера содержит аминокислотную последовательность, расщепляемую эндопептидазой фурином.
20. Полинуклеотид, кодирующий одноцепочечное антитело по п. 19.
21. Вектор, содержащий полинуклеотид по п. 20.
22. Клетка-хозяин, содержащая вектор по п. 21.
23. Способ получения одноцепочечного антитела по п. 19, где указанный способ включает культивирование клетки-хозяина, которая содержит вектор по п. 21, в культуральной среде.
24. Способ по п. 23, где указанный способ дополнительно включает выделение указанного одноцепочечного антитела из указанной клетки-хозяина или из указанной культуральной среды.
RU2014136702A 2012-02-10 2013-02-08 Одноцепочечные антитела и другие гетеромультимеры RU2644341C2 (ru)

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US20150133638A1 (en) 2015-05-14
RU2644341C2 (ru) 2018-02-08
CA2861124A1 (en) 2013-08-15
HK1203079A1 (en) 2015-10-16
JP2015508077A (ja) 2015-03-16
BR112014019579A8 (pt) 2017-07-11
US9688758B2 (en) 2017-06-27
WO2013119966A2 (en) 2013-08-15
BR112014019579A2 (pt) 2019-10-15
CN104105711B (zh) 2018-11-30
KR20140127854A (ko) 2014-11-04
JP2018070634A (ja) 2018-05-10
MX2014009565A (es) 2014-11-10
EP2812357A2 (en) 2014-12-17
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