GERDES Kristian (CH),ГЕРДЕС Кристиан (CH),KLAJN Kristian (CH),КЛАЙН Кристиан (CH),NIKOLINI Valeriya G. (CH),НИКОЛИНИ Валерия Г. (CH),UMANA Pablo (CH),УМАНА Пабло (CH),GERDES Kristian,ГЕРДЕС Кристиан,KLAJN Kristian,КЛАЙН Кристиан,NIKOLINI Valeriya G.,НИКОЛИНИ Валерия Г.,UMANA Pablo,УМАНА Пабло
申请号:
RU2015107889
公开号:
RU0002650788C2
申请日:
2013.08.05
申请国别(地区):
RU
年份:
2018
代理人:
摘要:
FIELD: biochemistry.SUBSTANCE: described is a combination of an immunoconjugate which comprises (i) a first antibody targeted at a fibroblast activating protein (FAP) and comprising a heavy chain variable region of SEQ ID NO: 12 and a light chain variable region of SEQ ID NO: 11, a heavy chain variable region of SEQ ID NO: 17 and a light chain variable region of SEQ ID NO: 16, a heavy chain variable region of SEQ ID NO: 47 and a light chain variable region of SEQ ID NO: 46, a heavy chain variable region of SEQ ID NO: 63 and a light chain variable region of SEQ ID NO: 62 or a heavy chain variable region of SEQ ID NO: 67 and a light chain variable region of SEQ ID NO: 66 or targeted at the carcinoembryonic antigen (CEA) and comprising a heavy chain variable region of SEQ ID NO: 114 and a light chain variable region of SEQ ID NO: 115, wherein the first antibody is a full-length IgG-class antibody and includes amino acid substitutions of L234A, L235A and P329G (EU numbering represented by Cabot) in the heavy chains of immunoglobulin, and (ii) a mutant human IL-2 molecule comprising amino acid substitutions of F42A, Y45A and L72G, and a second antibody selected from the group (i) an IgG class antibody targeted at the epidermal growth factor receptor (EGFR) containing a heavy chain variable domain SEQ ID NO: 102 and a light chain variable domain of SEQ ID NO: 103, wherein the antibody is engineered to have an increased ratio of non-fucose oligosaccharides to the Fc region as compared to an non-engineered antibody, (ii) an IgG class antibody to HER3 comprising a heavy chain variable domain of SEQ ID NO: 142 and the light chain variable domain of SEQ ID NO: 146, wherein the antibody is engineered to have an increased ratio of non-fucose oligosaccharides to the Fc region as compared to an non-engineered antibody, and (iii) cetuximab, for use in the treatment of cancer in an individual in need thereof. Also described are a pharmaceutical composition for the treatment of cance