HUMAN ANTI-IL-6 ANTIBODIES WITH A LONG-TERM REDUCED PERIOD OF IN VIVO AND THEIR APPLICATION FOR TREATMENT OF ONCOLOGICAL, AUTOIMMUNE DISEASES AND INFLAMMATORY DISEASES
БОУЭН Майкл (US),ВУ Херрен (US),ДАЛЛЬ'АКВА Вильям (US),КИНЕР Питер (US),ДЖАЛЛАЛ Бахия (US),КОЙЛ Антони (US),ДАЛЛЬАКВА Вильям (US)
申请号：
RU2011135422/10
公开号：
RU2011135422A
申请日:
2010.01.29
申请国别(地区):
RU
年份:
2013
代理人:
摘要：
1. An isolated antibody that specifically binds to IL-6, characterized in that it contains a variable domain and a human IgG constant domain having one or more amino acid substitutions relative to the wild-type human IgG constant domain, the antibody having a prolonged half-life compared to the period elimination half-life of an antibody containing the indicated variable domain and human IgG wild-type constant domain. 2. The antibody according to claim 1, characterized in that at least one amino acid substitution is selected from the group consisting of: M252Y, M252F, M252W, M252T, S254T, T256S, T256R, T256Q, T256E, T256D, T256T, L309P, Q311S, H433R, H433K, H433S, H433I, H433P, H433Q, N434H, N434F, N434Y and N436H； or combinations thereof, where amino acid residues are numbered according to the EU index, as in Kabat. 3. The antibody according to claim 2, characterized in that at least one amino acid substitution is selected from the group consisting of: M252Y, S254T, T256E, H433K, N434F and N436H； or combinations thereof, where amino acid residues are numbered according to the EU index, as in Kabat. 4. The antibody according to claim 1, characterized in that the modified IgG constant domain contains M252Y, S254T and T256E amino acid substitutions, where the amino acid residues are numbered in accordance with the EU index, as in Kabat. 5. The antibody according to claim 1, characterized in that the IgG is IgG1.6. The antibody according to claim 1, characterized in that the variable domain contains: a) VH CDR1 having an amino acid sequence identical to or containing 1, 2 or 3 substitutions of amino acid residues relative to SEQ ID NO: 1； b) VH CDR2 having an amino acid sequence, identical or containing 1, 2 or 3 substitutions of amino acid residues relative to SEQ ID NO: 2； c) VH CDR3, having1. Выделенное антитело, которое специфично связывается с IL-6, отличающееся тем, что содержит вариабельный домен и человеческий IgG константный домен, имеющий одно или более амино
