Patent ID: 6551592
Filing Date: 2003-04-22
Classification: A61K,A61P,C07K

Abstract:
A method of treatment of a human or animal subject suffering from a tumor disease consisting of administering to said subject an effective amount of an intact heterologous bispecific antibody having isotype combinations selected from the group consisting of:rat-IgG2b/mouse-IgG2a, rat-IgG2b/mouse-IgG2b, rat-IgG2b/mouse-IgG3, rat-IgG2b/human-IgG1, rat-IgG2b/human-IgG2, rat-IgG2b/human-IgG3(oriental allotype G3m(st)=binding to protein A), rat-IgG2b/human-IgG4, rat-IgG2b/rat-IgG2c, mouse-IgG2a/human-IgG3(caucasian allotypes G3m(b+g)=no binding to protein A), mouse-IgG2a/mouse-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG3 Caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), mouse-IgG2a/rat-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), mouse-IgG2a/human-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), mouse-(VH-CH1,VL-CL)-human-IgG1/rat-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), mouse-(VH-CH1,VL-CL)-human-IgG4/rat-(VH-CH1,VL-CL)-human-IgG4-(hinge)-human-IgG4(N-terminal region of CH2)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A (C-terminal region of CH2:>aa position 251)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A (CH3), rat-IgG2b/mouse-(VH-CH1,VL-CL)-human-IgG1-(hinge-CH2-CH3), rat-IgG2b/mouse-(VH-CH1,VL-CL)-human-IgG3-(hinge-CH2-CH3, oriental allotype), rat-IgG2b/mouse-(VH-CH1,VL-CL)-human-IgG4-(hinge-CH2-CH3)human-IgG1/human-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), human-IgG1/rat-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG4(N-terminal region of CH2)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A (C-terminal region of CH2:>aa position 251)-human-IgG3 Caucasian allotypes G3m(b+g)=no binding to protein A (CH3), human-IgG1/mouse-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG4(N-terminal region of CH2)-human-IgG3 Caucasian allotypes G3m(b+g)=no binding to protein A (C-terminal region of CH2:>aa position 251)-human-IgG3 Caucasian allotypes G3m(b+g)=no binding to protein A (CH3), human-IgG1/rat-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG2(N-terminal region of CH2)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A (C-terminal region of CH2:>aa position 251)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A (CH3), human-IgG1/mouse-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG2(N-terminal region of CH2)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A (C-terminal region of CH2:>aa position 251)-human-IgG3 Caucasian allotypes G3m(b+g)=no binding to protein A (CH3), human-IgG1/rat-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), human-IgG1/mouse-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), human-IgG2/human-(VH-CH1,VL-CL)-human-IgG2-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), human-IgG4/human-(VH-CH1,VL-CL)-human-IgG4-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), human-IgG4/human-(VH-CH1,VL-CL)-human-IgG4-(hinge)-human-IgG4(N-terminal region of CH2)-human-IgG3 Caucasian allotypes G3m(b+g)=no binding to protein A (C-terminal region of CH2:>aa position 251)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A (CH3), mouse-IgG2b/rat-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), mouse-IgG2b/human-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3), and mouse-IgG2b/mouse-(VH-CH1,VL-CL)-human-IgG1-(hinge)-human-IgG3 caucasian allotypes G3m(b+g)=no binding to protein A-(CH2-CH3); wherein said antibody provides the following properties and effects: (a) binding to a T cell and activating said T cell; (b) binding to tumor-associated antigens on a tumor cell; (c) binding, through its Fc portion to the Fc receptor of Fc receptor-positive cells; (d) activation of said Fc receptor-positive cell by said binding of said antibodies to the Fc receptor-positive cell and, thereby initiating or increasing the expression of cytokines and/or co-stimulatory molecules; (e) inducing a physiological activation of the T cell by a member selected from the group consisting of co-stimulatory molecules and cytokines, this activation being indicated by up-regulation of activation markers, killing of the tumor cell, T cell proliferation or a combination thereof, inducing anti-tumor immunity.