Improved dual specificity polypeptide molecule

Abstract

The present invention relates to a bispecific polypeptide molecule comprising a first polypeptide chain and a second polypeptide chain providing a binding region derived from a T cell receptor (TCR) being specific for a major histocompatibility complex (MHC)-associated peptide epitope, and a binding region derived from an antibody capable of recruiting human immune effector cells by specifically binding to a surface antigen of said cells, as well as methods of making the bispecific polypeptide molecule, and uses thereof.

What is claimed is: 
     
         1 . A polypeptide comprising a heavy chain variable domain (VH) and a light chain variable domain (VL) of hBMA031 antibody comprising the amino acid sequences of the heavy chain variable domain (VH) and the light chain variable domain (VL) of the hBMA031 antibody as comprised in SEQ ID NOs: 22 and 23, respectively. 
     
     
         2 . A heavy chain variable domain (VH) and a light chain variable domain (VL) comprising the amino acid sequences of the heavy chain variable domain (VH) and the light chain variable domain (VL) of hBMA031 antibody as comprised in SEQ ID NOs: 22 and 23, respectively. 
     
     
         3 . The polypeptide of  claim 1 , wherein the polypeptide:
 specifically binds to a TCR-CD3 complex of human T cells; and   is capable of recruiting human immune effector cells by specifically binding to a surface antigen of said effector cell.   
     
     
         4 . The polypeptide of  claim 1 , wherein the VH domain and the VL domain each comprise no more than one, two, three, four, or five amino acid substitutions, deletions, or insertions. 
     
     
         5 . The polypeptide of  claim 3 , wherein the polypeptide specifically binds to the TCR-CD3 complex with a binding affinity (KD) of 1 µM or less. 
     
     
         6 . A nucleic acid encoding the polypeptide of  claim 1 . 
     
     
         7 . An expression vector comprising the nucleic acid of  claim 6 . 
     
     
         8 . A host cell expressing the vector of  claim 7 . 
     
     
         9 . A pharmaceutical composition comprising the polypeptide of  claim 1  and one or more pharmaceutically acceptable carriers or excipients. 
     
     
         10 . A method of producing a polypeptide, comprising culturing the host cell of  claim 8  in a medium and harvesting the polypeptide from the host cell and/or from the medium. 
     
     
         11 . The VH domain and the VL domain of  claim 2 , wherein the VH domain and the VL domain:
 specifically bind to a TCR-CD3 complex of human T cells; and   are capable of recruiting human immune effector cells by specifically binding to a surface antigen of said effector cell.   
     
     
         12 . The VH domain and the VL domain of  claim 2 , wherein the VH domain and the VL domain each comprise no more than one, two, three, four or five amino acid substitutions, deletions, or insertions. 
     
     
         13 . The VH domain and the VL domain of  claim 11 , wherein the VH domain and the VL domain specifically bind to the TCR-CD3 complex with a binding affinity (KD) of 1 µM or less. 
     
     
         14 . A nucleic acid encoding the VH domain and the VL domain of  claim 2 . 
     
     
         15 . An expression vector comprising the nucleic acid of  claim 14 . 
     
     
         16 . A host cell expressing the vector of  claim 15 . 
     
     
         17 . A pharmaceutical composition comprising the VH domain and the VL domain of  claim 2  and one or more pharmaceutically acceptable carriers or excipients. 
     
     
         18 . A method of producing a VH domain and a VL domain, comprising culturing the host cell of  claim 16  in a medium and harvesting the VH domain and the VL domain from the host cell and/or from the medium. 
     
     
         19 . A dual specificity polypeptide molecule comprising a first polypeptide chain comprising SEQ ID NO: 22 and a second polypeptide comprising SEQ ID NO: 23. 
     
     
         20 . A nucleic acid encoding the dual specificity polypeptide molecule of  claim 19 .