ПОНС Джом (US),ЧЭБОТ Джеффри Рэймонд (US),ЧАПАРРО РИДЖЕРС Хавьер (US),ГОМЕС Брюс Чарльз (US),ЛЯН Хон (US),МАЯВАЛА Капил (US),МЕТТЕТАЛЬ Второй Джером Томас (US),РАДЖПАЛ Арвинд (US),ШЕЛТОН Дэвид Льюис (
申请号：
RU2012137490/15
公开号：
RU2012137490A
申请日:
2011.03.09
申请国别(地区):
RU
年份:
2014
代理人:
摘要：
1. An antibody with pH-dependent binding that specifically binds an antigen with a higher affinity at pH 7.4 than at pH 6.0, where the ratio of equilibrium dissociation constants (K) and / or the ratio of dissociation rate constants (k) at pH 6.0 / pH 7.4 and at 25 ° C is more than 2, 3, 4, 8, 10, 16 or more, or is in the range between 2, 3, 4, 8, 10, 16 or more, and where the antibody has a reduced clearance from plasma in vivo when interacting with the specified antigen compared to an antibody that does not exhibit pH-dependent binding, which has a similar affinity against the antigen at pH 7.4, but it has to be compared ratio Ki / or kpri pH 6.0 / pH 7.4 less than 2.2. An antibody with a pH-dependent binding that specifically binds an antigen with a higher affinity at pH 7.4 than at pH 6.0, where the Ki / ratio or k ratio at pH 6.0 / pH 7.4 and at 25 ° C is more than 2, 3, 4, 8, 10, 16 or more, or is in the range between 2, 3, 4, 8, 10, 16 or more, and where the antigen is both membrane-bound and soluble in vivo, and where the antibody mediates increased localization in the cell membrane receptor compared to an antibody that has a similar affinity for this antigen at pH 7.4, but has a comparative my ratio Ki / or kpri pH 6.0 / pH 7.4 less than 2.3. The antibody according to claim 1 or 2, where the antigen is not an interleukin-6.4 receptor. The antibody of claim 2, wherein the antigen is a soluble receptor that is a non-signaling trap receptor. The antibody of claim 2, wherein said pH-dependent antibody is a drug-antibody conjugate that mediates an antibody-dependent cell-mediated cyto1. Антитело с рН-зависимым связыванием, которое специфически связывает антиген с более высокой аффинностью при рН 7,4, чем при рН 6,0, где отношение равновесных констант диссоциации (K) и/или отношение констант скорости диссоциации (k) при рН 6,0/рН 7,4 и при 25°С составляет более чем 2, 3, 4, 8, 10, 16 или более, или находится в интервале между 2, 3, 4, 8, 10, 16 или более, и где а
