Novel antigen associated with the neovasculature of tumour metastases

Abstract

The invention relates to a binding member that binds the Extra Domain-A (ED-A) isoform of fibronectin for the treatment of tumour metastases.

We claim: 
     
         1 . A method of delivering a molecule to the neovasculature of tumour metastases in a human or animal, comprising administering to the human or animal an antibody which binds the ED-A isoform of fibronectin, wherein the antibody is conjugated to the molecule. 
     
     
         2 . The method of  claim 1 , wherein the human or animal has been determined to be suffering from a tumour metastases. 
     
     
         3 . The method of  claim 1 , wherein the antibody binds the ED-A of fibronectin. 
     
     
         4 . The method of  claim 1 , wherein the molecule is a detectable label, a radioisotope, and/or has biocidal or cytotoxic activity. 
     
     
         5 . The method of  claim 1 , wherein the antibody comprises a VH domain and a VL domain, wherein the VH domain comprises a framework and a set of complementarity determining regions HCDR1, HCDR2 and HCDR3, wherein:
 HCDR1 has amino acid sequence SEQ ID NO: 83,   HCDR2 has amino acid sequence SEQ ID NO: 4, and   HCDR3 has amino acid sequence SEQ ID NO: 5;   
       and wherein the VL domain comprises a framework and a set of complementarity determining regions LCDR1, LCDR2 and LCDR3, wherein:
 LCDR1 has amino acid sequence SEQ ID NO: 86, 
 LCDR2 has amino acid sequence SEQ ID NO: 7, and 
 LCDR3 has amino acid sequence SEQ ID NO: 8. 
 
     
     
         6 . The method of  claim 5 , wherein the VH domain framework is a human germline framework. 
     
     
         7 . The method of  claim 6 , wherein the antibody comprises the VH domain of SEQ ID NO: 81; or the VH domain of SEQ ID NO: 81, except that the amino acid at position 5 of the VH domain is a leucine residue (L) rather than a valine residue (V). 
     
     
         8 . The method of  claim 5 , wherein the VL domain framework is a human germline framework. 
     
     
         9 . The method of  claim 7 , wherein the antibody comprises the VL domain of SEQ ID NO: 82; or the VL domain of SEQ ID NO: 82, except that the amino acid at position 18 of the VL domain is an arginine residue (R) rather than a lysine residue (K). 
     
     
         10 . The method of  claim 1 , wherein the antibody comprises a single chain Fv, or is a diabody.