The C1.18.4 antibody (IgG2a, kappa) in nature is suitable for use as an isotype-matched control antibody to estimate the degree of non-specific binding by an antigen-specific antibody. The recombinant C1.18.4 IgG2a kappa isotype control and mutants (natural and engineered mIgG2a isotype controls) are useful for in vitro and in vivo studies from ELISA, Western blot (WB), to cell-based assay to animal model study. Mouse IgG2a antibodies are similar to human IgG1 antibodies in many aspects, thus researchers like to use the isotype of mouse IgG2a in mouse studies. Most of the therapeutic antibody drugs carry the natural human IgG1 constant regions. More and more engineered mutants in the human IgG1 Fc fragment have been tested during therapeutic antibody drug development. The corresponding mutations have been introduced to mouse IgG2a to study enhancement and abrogation effects of Fc binding. We generated recombinant C1.18.4 mIgG2a isotype control mutants, the same mutations as those in the therapeutic antibodies and candidates because such mouse IgG2a isotype control mutants are needed when clients test their engineered antibody candidates. For example, P329G substitution combined with L234A L235A (mIgG2a LALAPG, Fc silenced) was shown to decrease effector functions by disrupting the Fc/Fcγ receptor interface.