A method of preparing a bispecific antibody that specifically binds VEGF and DLL4, wherein the bispecific antibody comprises a first and a second immunoglobulin CH3 domain-containing polypeptide, the method comprising substituting at least one amino acid within the CH3 domain of the first immunoglobulin polypeptide and substituting at least one amino acid within the CH3 domain of the second immunoglobulin polypeptide to promote formation of a bispecific antibody, wherein the bispecific antibody is selected from the group consisting of: (a) a human IgG1, wherein the amino acids at positions in the first immunoglobulin polypeptide corresponding to positions 253 and 292 of SEQ ID NO:32 are replaced with glutamate or aspartate, and wherein the amino acids at positions in the second immunoglobulin polypeptide corresponding to positions 240 and 282 of SEQ ID NO:32 are replaced with lysine; (b) a human IgG2, wherein the amino acids at positions in the first immunoglobulin polypeptide corresponding to positions 249 and 288 of SEQ ID NO:33 are replaced with glutamate or aspartate, and wherein the amino acids at positions in the second immunoglobulin polypeptide corresponding to positions 236 and 278 of SEQ ID NO:33 are replaced with lysine; (c) a human IgG3, wherein the amino acids at positions in the first immunoglobulin polypeptide corresponding to positions 300 and 339 of SEQ ID NO:34 are replaced with glutamate or aspartate, and wherein the amino acids at positions in the second immunoglobulin polypeptide corresponding to positions 287 and 329 of SEQ ID NO:34 are replaced with lysine; and (d) a human IgG4, wherein the amino acids at positions in the first immunoglobulin polypeptide corresponding to positions 250 and 289 of SEQ ID NO:35 are replaced with glutamate or aspartate, and wherein the amino acids at positions in the second immunoglobulin polypeptide corresponding to positions 237 and 279 of SEQ ID NO:35 are replaced with lysine, wherein the first CH3-domain containing polypeptide comprises a first immunoglobulin heavy chain polypeptide that specifically binds to a first immunoglobulin light chain polypeptide, and the second CH3-domain containing polypeptide comprises a second immunoglobulin heavy chain polypeptide that specifically binds to a second immunoglobulin light chain polypeptide; and wherein the first immunoglobulin light chain polypeptide and the second immunoglobulin light chain polypeptide are identical in amino acid sequence. (a) a human IgG1, wherein the amino acids at positions in the first immunoglobulin polypeptide corresponding to positions 253 and 292 of SEQ ID NO:32 are replaced with glutamate or aspartate, and wherein the amino acids at positions in the second immunoglobulin polypeptide corresponding to positions 240 and 282 of SEQ ID NO:32 are replaced with lysine; (b) a human IgG2, wherein the amino acids at positions in the first immunoglobulin polypeptide corresponding to positions 249 and 288 of SEQ ID NO:33 are replaced with glutamate or aspartate, and wherein the amino acids at positions in the second immunoglobulin polypeptide corresponding to positions 236 and 278 of SEQ ID NO:33 are replaced with lysine; (c) a human IgG3, wherein the amino acids at positions in the first immunoglobulin polypeptide corresponding to positions 300 and 339 of SEQ ID NO:34 are replaced with glutamate or aspartate, and wherein the amino acids at positions in the second immunoglobulin polypeptide corresponding to positions 287 and 329 of SEQ ID NO:34 are replaced with lysine; and (d) a human IgG4, wherein the amino acids at positions in the first immunoglobulin polypeptide corresponding to positions 250 and 289 of SEQ ID NO:35 are replaced with glutamate or aspartate, and wherein the amino acids at positions in the second immunoglobulin polypeptide corresponding to positions 237 and 279 of SEQ ID NO:35 are replaced with lysine,