| abstract |
FIELD: biotechnology. n SUBSTANCE: invention relates to biotechnology. Isolated multispecific heteromultimeric construct for inducing the killing of a B cell is described, comprising: first polypeptide construct comprising a CD3 binding polypeptide construct, that binds to the human CD3 complex on at least one CD3 expressing cell, wherein the first polypeptide construct is an scFv region; a second polypeptide construct comprising an antigen-binding polypeptide construct, which binds to the target human CD19 antigen on at least one B cell, the second polypeptide construct being a Fab region or scFv region; and the heterodimeric human IgG1 Fc region containing the variant of the immunoglobulin CH3 domain containing the first CH3 sequence and the second CH3 sequence, First CH3 sequence contains the amino acid substitutions in L351, F405 and Y407, and the second CH3 sequence contains amino acid substitutions in T366, K392 and T394, while the amino acid substitutions for L in L351 are Y, F or W, for F in F405 are A or G and for Y in Y407 are V, M, L or I, and the amino acid substitutions for T in T366 are L, I, M or V, for K in K392 are M, I, L or V and for T in T394 are W, Y or F, wherein both the first polypeptide construct and the second polypeptide construct are linked to the N-terminus of the human IgG1 heterodimeric Fc region. Pharmaceutical composition for inducing killing of a B cell comprising said multispecific heteromultimeric construct is also provided. Method of treating a cancerous disease is also provided, including non-treatable at least one selected from a CD19-lytic antibody, CD20-lytic antibody and blinatumomab, a method for treating an autoimmune condition in a mammal in need thereof, method of treating an inflammatory condition in a mammal in need thereof comprising administering to said mammal a composition comprising an effective amount of said pharmaceutical composition, optionally in combination with other pharmaceutically active molecules. n EFFECT: also, a kit for inducing killing of a B-cell containing said multispecific heteromultimeric construct and instructions for its use is also described. n 29 cl, 37 dwg, 34 ex, 13 tbl |