Antibodies recognizing tau

Abstract

The invention provides antibodies that specifically bind tau. The antibodies inhibit or delay tau-associated pathologies and associated symptomatic deterioration.

1 - 151 . (canceled) 
     
     
         152 . A method of making a monoclonal antibody, comprising:
 (a) immunizing a mouse with human tau or a fragment comprising residues 113-136 of SEQ ID NO:1,   (b) epitope mapping the resultant antibodies, and   (c) selecting an antibody that binds to a first peptide consisting of amino acids 113-127 of SEQ ID NO:1 and to a second peptide consisting of amino acids 122-136 of SEQ ID NO:1, wherein binding to the second peptide is less than binding to the first peptide.   
     
     
         153 . The method of  claim 152 , wherein the antibody binds a peptide consisting of amino acids 118-133 of SEQ ID NO:1 or a peptide consisting of amino acids 119-128 of SEQ ID NO:1. 
     
     
         154 . The method of  claim 152 , wherein the mouse is immunized with 383 amino acid human tau (4RON). 
     
     
         155 . The method of  claim 152 , wherein the fragment consists of residues 113-136 of SEQ ID NO:1, optionally linked to a carrier. 
     
     
         156 . A method of identifying an antibody that binds to an epitope within residues 113-136 of SEQ ID NO:1: comprising
 providing a display library of antibodies; and   screening the display library to identify an antibody binding within residues 113-136 of SEQ ID NO:1.   
     
     
         157 . The method of  claim 156 , wherein the display library displays antibodies as Fv fragments. 
     
     
         158 . The method of  claim 156 , wherein the display library is produced by immunizing a rodent with human tau or a fragment thereof and cloning nucleic acids encoding heavy and light chains of antibodies into a display vector. 
     
     
         159 . The method of  claim 156 , wherein the screening is performed by determining binding of library members to a fragment of human tau consisting of residues 113-136 of SEQ ID NO:1. 
     
     
         160 . The method of  claim 156 , wherein the screening is performed by determining binding of library members to human tau in the presence of a reference antibody, which binds to an epitope within residues 113-136 of SEQ ID NO:1. 
     
     
         161 . The method of  claim 160 , wherein the reference antibody is characterized by a mature heavy chain variable region of SEQ ID NO: 7 and a mature light chain variable region of SEQ ID NO:11. 
     
     
         162 . A method of identifying an antibody that competes for binding with a reference antibody for binding to human tau, comprising
 contacting human tau with the antibody in the presence and absence of the reference antibody and determining binding of the antibody to human tau, wherein decreased binding in the presence of the reference antibody indicates the antibody competes with the reference antibody for binding to human tau, wherein the reference antibody is characterized by a mature heavy chain variable region of SEQ ID NO: 7 and a mature light chain variable region of SEQ ID NO:11.   
     
     
         163 . The method of  claim 162 , further comprising further comprising mapping the epitope bound by the antibody on human tau by determining binding to mutants of human tau. 
     
     
         164 . The method of  claim 162 , further comprising mapping the epitope bound by the antibody on human tau by X-ray crystallography.