Multi-specific binding molecules targeting aberrant cells

Abstract

Described are proteinaceous molecules comprising at least two, preferably three to six, binding domains that bind specifically to at least two different binding sites on aberrant cells. These multi-domain and multi-specific binding molecules are preferably used in selectively modulating biological processes. The provided binding molecules are of particular use in pharmaceutical compositions for the treatment of diseases related to cellular aberrancies, such as cancers and autoimmune diseases.

What is claimed is: 
     
         1 . A proteinaceous molecule comprising at least two different specific binding domains for different binding sites separated by at least one linker wherein the proteinaceous molecule comprises a single polypeptide chain. 
     
     
         2 . The proteinaceous molecule of  claim 1 , comprising at least three specific binding domains for different binding sites separated from each other by at least one linker. 
     
     
         3 . The proteinaceous molecule of  claim 1 , wherein at least one such binding domain is a Vh domain. 
     
     
         4 . The proteinaceous molecule of  claim 1 , wherein at least one such binding domain is a ligand for a receptor, or a receptor binding fragment and/or derivative of such a ligand. 
     
     
         5 . The proteinaceous molecule of  claim 1 , further comprising an effector moiety. 
     
     
         6 . The proteinaceous molecule of  claim 1 , comprising at least two Vh domains. 
     
     
         7 . The proteinaceous molecule of  claim 1 , comprising at least two Vh domains specific for different binding sites and an Fc monomer. 
     
     
         8 . A dimeric proteinaceous molecule comprising:
 two proteinaceous molecules of  claim 7  dimerized through two Fc monomers.   
     
     
         9 . A hetero-dimeric molecule comprising:
 two different proteinaceous molecules of  claim 7 .   
     
     
         10 . A pharmaceutical formulation comprising:
 the proteinaceous molecule of  claim 1 , and   suitable excipient(s).   
     
     
         11 . A nucleic acid molecule encoding the proteinaceous molecule of  claim 1 . 
     
     
         12 . A vector comprising the nucleic acid molecule of  claim 11 . 
     
     
         13 . A cell comprising the nucleic acid molecule of  claim 11 . 
     
     
         14 . A method for producing a proteinaceous molecule, the method comprising:
 culturing the cell of  claim 13 ,   allowing for expression of the proteinaceous molecule, and   separating the proteinaceous molecule from the culture.   
     
     
         15 . A proteinaceous molecule according to  FIG. 1  or  FIG. 2 . 
     
     
         16 . A proteinaceous molecule comprising:
 at least two different specific binding domains for different binding sites separated by at least one linker,   wherein at least one such binding domain is a Vh domain,   wherein at least one such binding domain is a ligand for a receptor, and   wherein the proteinaceous molecule comprises a single polypeptide chain.   
     
     
         17 . The proteinaceous molecule of  claim 16 , further comprising an effector moiety. 
     
     
         18 . The proteinaceous molecule of  claim 17 , comprising at least two Vh domains. 
     
     
         19 . The proteinaceous molecule of  claim 18 , wherein the at least two Vh domains are specific for different binding sites and an Fc monomer.