Methods of making multispecific antigen-binding molecules

Abstract

The present invention provides multispecific antigen-binding molecules and methods of making or selecting same. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone. In other embodiments of the invention, the target molecule is a tumor associated antigen, and the simultaneous binding of the tumor associated antigen and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention causes or facilitates the targeted killing of tumor cells.

1 - 35 . (canceled) 
     
     
         36 . A library comprising a plurality of production cells, each transformed with a polynucleotide encoding an antibody light chain, a polynucleotide encoding a tag-specific binding protein heavy chain, and a different polynucleotide encoding a destroyer-specific binding protein heavy chain. 
     
     
         37 . The library of  claim 36 , wherein the destroyer-specific binding protein binds CD63. 
     
     
         38 . The library of  claim 36 , wherein the destroyer-specific binding protein binds APLP2. 
     
     
         39 . The library of  claim 36 , wherein the destroyer-specific binding protein binds ASGR1.