RU2012142231A - Антитела против csf-1r человека и их применение - Google Patents

Антитела против csf-1r человека и их применение Download PDF

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RU2012142231A
RU2012142231A RU2012142231/10A RU2012142231A RU2012142231A RU 2012142231 A RU2012142231 A RU 2012142231A RU 2012142231/10 A RU2012142231/10 A RU 2012142231/10A RU 2012142231 A RU2012142231 A RU 2012142231A RU 2012142231 A RU2012142231 A RU 2012142231A
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antibody
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ФЕРТИГ Георг
ФИДЛЕР Александер
КАЛУЦА Клаус
ТОМАС Марлене
РИС Карола
ЗЕЕБЕР Штефан
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Ф.Хоффманн-Ля Рош Аг
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Abstract

1. Антитело, связывающееся с CSF-1R человека, отличающееся связыванием с тем же эпитопом, что и антитело, депонированное в коллекции под номером DSM ACC2922.2. Антитело по п.1, отличающееся тем, что включает в качестве области CDR3 вариабельного домена тяжелой цепи области CDR3 последовательности SEQ ID NO:1, SEQ ID NO:9 или SEQ ID NO:17.3. Антитело по п.2, отличающееся тем, чтоа) вариабельный домен тяжелой цепи включает область CDR3 последовательности SEQ ID NO:1, область CDR2 последовательности SEQ ID NO:2 и область CDR1 последовательности SEQ ID NO:3, и вариабельный домен легкой цепи включает область CDR3 последовательности SEQ ID NO:4, область CDR2 последовательности SEQ ID NO:5 и область CDR1 последовательности SEQ ID NO:6; илиб) вариабельный домен тяжелой цепи включает область CDR3 последовательности SEQ ID NO:9, область CDR2 последовательности SEQ ID NO:10 и область CDR1 последовательности SEQ ID NO:11, и вариабельный домен легкой цепи включает область CDR3 последовательности SEQ ID NO:12, область CDR2 последовательности SEQ ID NO:13 и область CDR1 последовательности SEQ ID NO:14; илив) вариабельный домен тяжелой цепи включает область CDR3 последовательности SEQ ID NO:17, область CDR2 последовательности SEQ ID NO:18 и область CDR1 последовательности SEQ ID NO:19, и вариабельный домен легкой цепи включает область CDR3 последовательности SEQ ID NO:20, область CDR2 последовательности SEQ ID NO:21 и область CDR1 последовательности SEQ ID NO:22; илиг) вариант антител по пунктам а), б) или в) имеет пересаженную область CDR, является гуманизированным или у него ослаблен Т-клеточный эпитоп.4. Антитело по п.3, отличающееся тем, что включаета) аминокислотную последовательность вариабельного домена тяжелой цепи, которая имеет последовательность SEQ ID NO:7, и аминокислотную пос�

Claims (16)

1. Антитело, связывающееся с CSF-1R человека, отличающееся связыванием с тем же эпитопом, что и антитело, депонированное в коллекции под номером DSM ACC2922.
2. Антитело по п.1, отличающееся тем, что включает в качестве области CDR3 вариабельного домена тяжелой цепи области CDR3 последовательности SEQ ID NO:1, SEQ ID NO:9 или SEQ ID NO:17.
3. Антитело по п.2, отличающееся тем, что
а) вариабельный домен тяжелой цепи включает область CDR3 последовательности SEQ ID NO:1, область CDR2 последовательности SEQ ID NO:2 и область CDR1 последовательности SEQ ID NO:3, и вариабельный домен легкой цепи включает область CDR3 последовательности SEQ ID NO:4, область CDR2 последовательности SEQ ID NO:5 и область CDR1 последовательности SEQ ID NO:6; или
б) вариабельный домен тяжелой цепи включает область CDR3 последовательности SEQ ID NO:9, область CDR2 последовательности SEQ ID NO:10 и область CDR1 последовательности SEQ ID NO:11, и вариабельный домен легкой цепи включает область CDR3 последовательности SEQ ID NO:12, область CDR2 последовательности SEQ ID NO:13 и область CDR1 последовательности SEQ ID NO:14; или
в) вариабельный домен тяжелой цепи включает область CDR3 последовательности SEQ ID NO:17, область CDR2 последовательности SEQ ID NO:18 и область CDR1 последовательности SEQ ID NO:19, и вариабельный домен легкой цепи включает область CDR3 последовательности SEQ ID NO:20, область CDR2 последовательности SEQ ID NO:21 и область CDR1 последовательности SEQ ID NO:22; или
г) вариант антител по пунктам а), б) или в) имеет пересаженную область CDR, является гуманизированным или у него ослаблен Т-клеточный эпитоп.
4. Антитело по п.3, отличающееся тем, что включает
а) аминокислотную последовательность вариабельного домена тяжелой цепи, которая имеет последовательность SEQ ID NO:7, и аминокислотную последовательность вариабельного домена легкой цепи, которая имеет последовательность SEQ ID NO:8; или
б) аминокислотную последовательность вариабельного домена тяжелой цепи, которая имеет последовательность SEQ ID NO:15, и аминокислотную последовательность вариабельного домена легкой цепи, которая имеет последовательность SEQ ID NO:16; или
в) аминокислотную последовательность вариабельного домена тяжелой цепи, которая имеет последовательность SEQ ID NO:23, и аминокислотную последовательность вариабельного домена легкой цепи, которая имеет последовательность SEQ ID NO:24; или
г) вариант антител по пунктам а), б) или в), который имеет пересаженную область CDR, является гуманизированным или у него ослаблен Т-клеточный эпитоп.
5. Антитело по пп.1-4, отличающееся тем, что указанное антитело относится к подклассу IgG4 человека или подклассу IgG1 человека.
6. Фармацевтическая композиция, отличающаяся включением антитела или фрагмента антитела по пп.1-5.
7. Антитело по пп.1-5 для лечения рака.
8. Антитело по пп.1-5 для лечения разрежения костей.
9. Антитело по пп.1-5 для предупреждения или лечения метастазов.
10. Антитело по пп.1-5 для лечения воспалительных заболеваний.
11. Нуклеиновая кислота, кодирующая тяжелую цепь антитела, связывающегося с CSF-1R, отличающаяся тем, что указанное антитело включает вариабельный домен по п.2, 3 или 4.
12. Векторы экспрессии, отличающиеся тем, что включают нуклеиновую кислоту по п.11 для экспрессии антитела, связывающегося с CSF-1R, в прокариотических или эукариотических клетках-хозяевах.
13. Прокариотические или эукариотические клетки-хозяева, включающие вектор по п.12.
14. Способ получения рекомбинантного антитела по пп.1-5, отличающийся экспрессией нуклеиновой кислотой по п.11 в прокариотических или эукариотических клетках-хозяевах и выделением указанного антитела из указанных клеток или супернатанта культур клеток.
15. Антитело, связывающееся с CSF-1R человека, отличающееся тем, что
а) вариабельный домен тяжелой цепи включает область CDR3 последовательности SEQ ID NO:1, область CDR2 последовательности SEQ ID NO:2 и область CDR1 последовательности SEQ ID NO:3, и вариабельный домен легкой цепи включает область CDR3 последовательности SEQ ID NO:4, область CDR2 последовательности SEQ ID NO:5 и область CDR1 последовательности SEQ ID NO:6; или
б) вариабельный домен тяжелой цепи включает область CDR3 последовательности SEQ ID NO:9, область CDR2 последовательности SEQ ID NO:10 и область CDR1 последовательности SEQ ID NO:11, и вариабельный домен легкой цепи включает область CDR3 последовательности SEQ ID NO:12, область CDR2 последовательности SEQ ID NO:13 и область CDR1 последовательности SEQ ID NO:14; или
в) вариабельный домен тяжелой цепи включает область CDR3, которая имеет последовательность последовательности SEQ ID NO:17, область CDR2 последовательности SEQ ID NO:18 и область CDR1 последовательности SEQ ID NO:19, и вариабельный домен легкой цепи включает область CDR3 последовательности SEQ ID NO:20, область CDR2 последовательности SEQ ID NO:21 и область CDR1 последовательности SEQ ID NO:22; или
г) вариант антител по пунктам а), б) или в) имеет пересаженную область CDR, является гуманизированным или у него ослаблен Т-клеточный эпитоп.
16. Антитело по п.15, отличающееся тем, что включает
а) аминокислотную последовательность вариабельного домена тяжелой цепи, которая имеет последовательность SEQ ID NO:7, и аминокислотную последовательность вариабельного домена легкой цепи, которая имеет последовательность SEQ ID NO:8; или
б) аминокислотную последовательность вариабельного домена тяжелой цепи, которая имеет последовательность SEQ ID NO:15, и аминокислотную последовательность вариабельного домена легкой цепи, которая имеет последовательность SEQ ID NO:16; или
в) аминокислотную последовательность вариабельного домена тяжелой цепи, которая имеет последовательность SEQ ID NO:23, и аминокислотную последовательность вариабельного домена легкой цепи, которая имеет последовательность SEQ ID NO:24; или
г) вариант антител по пунктам а), б) или в), который имеет пересаженную область CDR, является гуманизированным или у него ослаблен Т-клеточный эпитоп.
RU2012142231A 2010-03-05 2011-03-03 Антитела против csf-1r человека и их применение RU2617971C2 (ru)

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US10030073B2 (en) 2018-07-24
US20170114139A1 (en) 2017-04-27
US20150080556A1 (en) 2015-03-19
RU2617971C2 (ru) 2017-04-28
KR20120138801A (ko) 2012-12-26
CA2789076A1 (en) 2011-09-09
US20120329997A1 (en) 2012-12-27
US20170015752A1 (en) 2017-01-19
HK1176948A1 (zh) 2013-08-09
JP6005825B2 (ja) 2016-10-12
US20150175696A1 (en) 2015-06-25
BR112012020372A2 (pt) 2017-01-10
JP2013521765A (ja) 2013-06-13
US9169323B2 (en) 2015-10-27
WO2011107553A1 (en) 2011-09-09

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