Bispecific antibodies combine the specificity of two antibodies into one molecule. During the past two decades, advancement in protein engineering enabled the development of more than 100 bispecific formats, three of which are approved by the FDA for clinical use. In parallel to protein engineering methods, advancement in conjugation chemistries have spurred the use of chemical engineering approaches to generate bispecific antibodies. Herein, we review selected chemical strategies employed to generate bispecific antibodies that cannot be made using protein engineering methods.
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