Multispecific antibodies

The present invention relates to multispecific antibodies, their manufacture and use. In a specific embodiment the invention is a multispecific antibody of human IgG1, human IgG2, human IgG3 or human IgG4 subclass, comprising: a first light chain and a first heavy chain of a first antibody which specifically binds to a first antigen; and a second light chain and a second heavy chain of a second antibody which specifically binds to a second antigen, and wherein the variable domains VL and VH in the second light chain and second heavy chain of the second antibody are replaced by each other; and wherein in the constant domain CL of the first light chain under the amino acid at position 124 is substituted independently by lysine (K), or arginine (R), and wherein in the constant domain CH1 of the first heavy chain under the amino acid at position 147 or the amino acid at position 213 is substituted independently by glutamic acid (E) or aspartic acid (D). These substitutions promote the formation of the multispecific antibody product by domain replacement/exchange in one binding arm (CrossMab VH-VL).