A method for producing an isolated bispecific antibody comprising: a) obtaining a nucleic acid sequence encoding a first immunoglobulin heavy chain comprising a first variable region that binds a first epitope, wherein the first immunoglobulin heavy chain comprises an IgG1 isotype constant domain comprising the amino acid sequence of SEQ ID NO: 1, an IgG2 isotype constant domain comprising the amino acid sequence of SEQ ID NO: 2, an IgG3 isotype constant domain comprising the amino acid sequence of SEQ ID NO: 3, or an IgG4 isotype constant domain comprising the amino acid sequence of SEQ ID NO: 4; b) obtaining a second nucleic acid sequence encoding a second immunoglobulin heavy chain comprising a second variable region that binds a second epitope, wherein the second immunoglobulin heavy chain comprises an IgG1, IgG2, IgG3 or IgG4 isotype constant domain that comprises a modification in its CH1 domain that eradicates or reduces binding to an affinity reagent targeting the human IgG1, IgG2, IgG3 and IgG4 CH1 domain, wherein the IgG1 isotype constant domain comprises the amino acid sequence of SEQ ID NO: 15, the IgG2 isotype constant domain comprises the amino acid sequence of SEQ ID NO: 16, the IgG3 isotype constant domain comprises the amino acid sequence of SEQ ID NO: 17, or the IgG4 isotype constant domain comprises the amino acid sequence of SEQ ID NO: 18; c) obtaining a third nucleic acid sequence encoding an immunoglobulin light chain that pairs with the first and the second immunoglobulin heavy chain; d) introducing the first, second, and third nucleic acid sequences into a mammalian cell in vitro; e) allowing the cell to express a bispecific antibody; and f) isolating the bispecific antibody based on the ability of the bispecific antibody to bind the affinity reagent targeting the human IgG1, IgG2, IgG3 and IgG4 CH1 domain. a) obtaining a nucleic acid sequence encoding a first immunoglobulin heavy chain comprising a first variable region that binds a first epitope, wherein the first immunoglobulin heavy chain comprises an IgG1 isotype constant domain comprising the amino acid sequence of SEQ ID NO: 1, an IgG2 isotype constant domain comprising the amino acid sequence of SEQ ID NO: 2, an IgG3 isotype constant domain comprising the amino acid sequence of SEQ ID NO: 3, or an IgG4 isotype constant domain comprising the amino acid sequence of SEQ ID NO: 4; b) obtaining a second nucleic acid sequence encoding a second immunoglobulin heavy chain comprising a second variable region that binds a second epitope, wherein the second immunoglobulin heavy chain comprises an IgG1, IgG2, IgG3 or IgG4 isotype constant domain that comprises a modification in its CH1 domain that eradicates or reduces binding to an affinity reagent targeting the human IgG1, IgG2, IgG3 and IgG4 CH1 domain, wherein the IgG1 isotype constant domain comprises the amino acid sequence of SEQ ID NO: 15, the IgG2 isotype constant domain comprises the amino acid sequence of SEQ ID NO: 16, the IgG3 isotype constant domain comprises the amino acid sequence of SEQ ID NO: 17, or the IgG4 isotype constant domain comprises the amino acid sequence of SEQ ID NO: 18; c) obtaining a third nucleic acid sequence encoding an immunoglobulin light chain that pairs with the first and the second immunoglobulin heavy chain; d) introducing the first, second, and third nucleic acid sequences into a mammalian cell in vitro; e) allowing the cell to express a bispecific antibody; and f) isolating the bispecific antibody based on the ability of the bispecific antibody to bind the affinity reagent targeting the human IgG1, IgG2, IgG3 and IgG4 CH1 domain.