Blood-brain barrier targeting antibodies

Abstract

This invention provides antibodies that bind brain endothelial cell receptors resulting in endocytosis/transcytosis of the receptor and bound ligands. In some embodiments, the ligand comprises the antibody in combination with a pharmaceutically active compound and the antibody directs delivery of the compound across the blood brain barrier (BBB). The invention also provides methods of identifying endothelial cell specific antibodies by panning the library against cultured cell monolayers. The invention further allows for identifying endothelial cell receptors that bind the antibody thereby providing target receptors against which to isolate further cognate ligands and their associated transport systems and by which to identify transcytosis transporters targeted by the antibodies.

1 . A method of delivering a pharmaceutically active compound to a subject's brain, comprising administering to a subject a pharmaceutically active compound in combination with an antibody or antibody fragment that is specific to neural cell adhesion molecule (NCAM), whereby the NCAM directs delivery of the pharmaceutically active compound across the blood brain barrier to the subject's brain. 
     
     
         2 . The method according to  claim 1 , wherein the antibody is a single chain fragment variable (scFv) antibody. 
     
     
         3 . The method according to  claim 1 , wherein the antibody or antibody fragment comprises the amino acid sequence set forth in SEQ ID NO:14. 
     
     
         4 . A composition comprising an isolated antibody or antibody fragment that is specific to neural cell adhesion molecule (NCAM) in combination with a pharmaceutically active compound. 
     
     
         5 . The composition according to  claim 4 , wherein the antibody is a single chain fragment variable (scFv) antibody. 
     
     
         6 . The composition according to  claim 4 , wherein the antibody or antibody fragment comprises the amino acid sequence set forth in SEQ ID NO:14. 
     
     
         7 . An isolated polypeptide comprising an antibody fragment comprising the amino acid sequence set forth in SEQ ID NO:14.