COMPOSITION COMPRISING TWO ANTIBODIES ENGINEERED TO HAVE REDUCED AND INCREASED EFFECTOR FUNCTION Russian patent published in 2018 - IPC C07K16/32 C07K16/40 A61P35/00 C07K16/30 C07K16/28 

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 cancer, comprising the described combination, and methods of using the disclosed combination, such as methods of treating cancer and stimulating effector cell function in an individual.

EFFECT: invention allows the median survival and / or overall survival to be extended compared to individual components or combinations with Proleukin.

13 cl, 8 dwg, 6 tbl, 7 ex