RU2010133892A - Гуманизированные моноклональные антитела против человеческого nkg2a - Google Patents
Гуманизированные моноклональные антитела против человеческого nkg2a Download PDFInfo
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- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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Abstract
1. Выделенное человеческое или гуманизированное антитело против NKG2A, которое ! (а) связывается с внеклеточной частью человеческого рецептора CD94/NKG2A, который экспрессируется на поверхности CD94/NKG2A-положительного лимфоцита, ! (б) снижает ингибиторную активность человеческого рецептора CD94/NKG2A и ! (в) не конкурирует с HLA-E за связывание с человеческим CD94/NKG2A рецептором. ! 2. Антитело по п.1, которое связывается с CD94/NKG2A с KD по меньшей мере в 100-раз ниже, чем для человеческого рецептора CD94/NKG2C. ! 3. Антитело по п.1, которое конкурирует с антителом Z199 за связывание с человеческим рецептором CD94/NKG2A. ! 4. Антитело по п.1, которое связывается с тем же эпитопом, что и антитело Z199. ! 5. Антитело по п.1, которое связывается с сегментом NKG2A (SEQ ID NO:11), содержащим аминокислотные остатки P94-N107, М189-Е197, или и те, и другие. ! 6. Антитело по п.1, которое связывается с эпитопом, содержащим аминокислотные остатки, выбранные из Р94, S95, Т96, L97, I98, Q99, R100, Н101, L106, М189, или Е197 NKG2A (SEQ ID NO:11), или любую их комбинацию. ! 7. Антитело по п.1, которое является гуманизированным антителом Z199. ! 8. Антитело по п.7, содержащее аминокислотные остатки Y31, L49 и Р94 вариабельного домена легкой цепи (VL) антитела Z199 (SEQ ID NO:2), и аминокислотные остатки Y57, Y102 и Р103 вариабельного домена тяжелой цепи (VH) антитела Z199 (SEQ ID NO:4). ! 9. Антитело по п.7, содержащее по меньшей мере одну обратную мутацию в последовательности каркасного участка VL или VH доменов. ! 10. Антитело по п.7, содержащее аминокислотный остаток Р45 VL домена Z199. ! 11. Антитело по п.7, содержащее аминокислотные остатки 24-33, 49-55 и 88-96 VL домена Z199 и аминокислотные остатки 31-35, 50-60, 62, 64, 66 и 99-108 VH домена Z199. ! 12. Антитело по п.7, содержащее серии (S), вставленный между амин
Claims (17)
1. Выделенное человеческое или гуманизированное антитело против NKG2A, которое
(а) связывается с внеклеточной частью человеческого рецептора CD94/NKG2A, который экспрессируется на поверхности CD94/NKG2A-положительного лимфоцита,
(б) снижает ингибиторную активность человеческого рецептора CD94/NKG2A и
(в) не конкурирует с HLA-E за связывание с человеческим CD94/NKG2A рецептором.
2. Антитело по п.1, которое связывается с CD94/NKG2A с KD по меньшей мере в 100-раз ниже, чем для человеческого рецептора CD94/NKG2C.
3. Антитело по п.1, которое конкурирует с антителом Z199 за связывание с человеческим рецептором CD94/NKG2A.
4. Антитело по п.1, которое связывается с тем же эпитопом, что и антитело Z199.
5. Антитело по п.1, которое связывается с сегментом NKG2A (SEQ ID NO:11), содержащим аминокислотные остатки P94-N107, М189-Е197, или и те, и другие.
6. Антитело по п.1, которое связывается с эпитопом, содержащим аминокислотные остатки, выбранные из Р94, S95, Т96, L97, I98, Q99, R100, Н101, L106, М189, или Е197 NKG2A (SEQ ID NO:11), или любую их комбинацию.
7. Антитело по п.1, которое является гуманизированным антителом Z199.
8. Антитело по п.7, содержащее аминокислотные остатки Y31, L49 и Р94 вариабельного домена легкой цепи (VL) антитела Z199 (SEQ ID NO:2), и аминокислотные остатки Y57, Y102 и Р103 вариабельного домена тяжелой цепи (VH) антитела Z199 (SEQ ID NO:4).
9. Антитело по п.7, содержащее по меньшей мере одну обратную мутацию в последовательности каркасного участка VL или VH доменов.
10. Антитело по п.7, содержащее аминокислотный остаток Р45 VL домена Z199.
11. Антитело по п.7, содержащее аминокислотные остатки 24-33, 49-55 и 88-96 VL домена Z199 и аминокислотные остатки 31-35, 50-60, 62, 64, 66 и 99-108 VH домена Z199.
12. Антитело по п.7, содержащее серии (S), вставленный между аминокислотными остатками 30 и 31 VL домена Z199.
13. Выделенное антитело, связывающееся с человеческим рецептором CD94/NKG2A и содержащее
(а) CDR-L1, содержащий SEQ ID NO:5;
(б) CDR-L2, содержащий SEQ ID NO:6;
(в) CDR-L3, содержащий SEQ ID NO:7;
(г) CDR-H1, содержащий SEQ ID NO:8;
(д) CDR-H2, содержащий SEQ ID NO:9;
(е) CDR-H3, содержащий SEQ ID NO:10;
(ж) человеческие каркасные участки VL и VH; и
(з) аминокислоту пролин (Р) в положении 46 по нумеарции Кабата (Kabat) в VL домене.
14. Антитело по п.13, содержащее константный домен человеческого lgG4, возможно, содержащий мутацию S241P.
15. Композиция, содержащая антитело по любому из предшествующих пунктов и фармацевтически приемлемый носитель, дилюент или наполнитель.
16. Антитело по любому из пп.1-14 для применения в лечении злокачественных неоплазий, вирусных инфекций, воспалительных нарушений и/или аутоиммунных заболеваний.
17. Способ получения антитела по любому из пп.1-14, включающий культивирование клеток-хозяев, трансформированных одним или более векторами, содержащими фрагмент нуклеиновой кислоты, кодирующей антитело, при условиях, которые способствуют экспрессии фрагмента (фрагментов) нуклеиновой кислоты и, возможно, выделение полученных антител.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08150601.6 | 2008-01-24 | ||
| EP08150601 | 2008-01-24 |
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| Publication Number | Publication Date |
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| RU2010133892A true RU2010133892A (ru) | 2012-02-27 |
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| RU2010133892/10A RU2010133892A (ru) | 2008-01-24 | 2009-01-23 | Гуманизированные моноклональные антитела против человеческого nkg2a |
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|---|---|
| US (2) | US8796427B2 (ru) |
| EP (2) | EP2247619A1 (ru) |
| JP (1) | JP5774312B2 (ru) |
| KR (1) | KR20100110864A (ru) |
| CN (1) | CN101952317B (ru) |
| AU (1) | AU2009207644A1 (ru) |
| BR (1) | BRPI0908508A2 (ru) |
| CA (1) | CA2712220A1 (ru) |
| IL (1) | IL206639A0 (ru) |
| MX (1) | MX2010007935A (ru) |
| RU (1) | RU2010133892A (ru) |
| WO (1) | WO2009092805A1 (ru) |
| ZA (1) | ZA201004752B (ru) |
Families Citing this family (67)
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| RU2499001C2 (ru) | 2006-06-30 | 2013-11-20 | Ново Нордиск А/С | Антитела к nkg2a и их применения |
| US8796427B2 (en) | 2008-01-24 | 2014-08-05 | Novo Nordisk A/S | Humanized anti-human NKG2A monoclonal antibody |
| CN107693791B (zh) | 2010-02-26 | 2022-06-07 | 诺沃—诺迪斯克有限公司 | 包含稳定抗体的组合物 |
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| IL206639A0 (en) | 2010-12-30 |
| US8796427B2 (en) | 2014-08-05 |
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| KR20100110864A (ko) | 2010-10-13 |
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| AU2009207644A1 (en) | 2009-07-30 |
| MX2010007935A (es) | 2010-08-23 |
| US20140341896A1 (en) | 2014-11-20 |
| BRPI0908508A2 (pt) | 2016-03-22 |
| US20110052606A1 (en) | 2011-03-03 |
| ZA201004752B (en) | 2011-04-28 |
| US9422368B2 (en) | 2016-08-23 |
| CN101952317B (zh) | 2015-07-22 |
| EP2628753A1 (en) | 2013-08-21 |
| EP2247619A1 (en) | 2010-11-10 |
| JP5774312B2 (ja) | 2015-09-09 |
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