abstract |
Disclosed herein are conditionally active multivalent target-binding proteins which comprise two binding moieties, two linkers, two target antigen binding domains, and a constant domain. Each binding moiety comprises non-CDR loops for masking the binding of a target antigen binding domain to its target and CDRs for binding a further target. The multivalent target-binding proteins are activated upon cleavage of the cleavable linkers. Also disclosed are pro immune modulating molecules comprising dual binding moieties comprising non-CDR loops and cleavable linkers, that prohibit the binding of a target binding domain to their targets (e.g., binding of an antibody to an immune modulatory target is masked by the dual binding moieties). The dual binding moieties further have specificity for a bulk serum protein or a dual binding moiety target (e.g., a tumor antigen, an immune modulatory protein). Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of using such formulations are further provided. |