Anti-PHF-Tau Antibodies and Uses Thereof

Abstract

Monoclonal anti-PHF-tau antibodies and antigen-binding fragments thereof are described. Also described are nucleic acids encoding the antibodies, compositions comprising the antibodies, methods of producing the antibodies, and use of the antibodies for treating or preventing conditions such as tauopathies.

1 .- 22 . (canceled) 
     
     
         23 . An isolated antibody or antigen binding fragment thereof which binds to PHF tau comprising: a) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1, b) a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2, c) a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3, d) a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:13, e) a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:14, and f) a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:15. 
     
     
         24 . The isolated antibody or antigen binding fragment thereof of  claim 23  comprising: a) the heavy chain variable region CDR1 having the amino acid sequence of SEQ ID NO:1, b) the heavy chain variable region CDR2 having the amino acid sequence of SEQ ID NO:2, c) the heavy chain variable region CDR3 having the amino acid sequence of SEQ ID NO:3, d) the light chain variable region CDR1 having the amino acid sequence of SEQ ID NO:13, e) the light chain variable region CDR2 having the amino acid sequence of SEQ ID NO:14, and f) the light chain variable region CDR3 having the amino acid sequence of SEQ ID NO:15. 
     
     
         25 . The isolated monoclonal antibody or antigen-binding fragment of  claim 24  comprising a human heavy chain IgG1 constant region and a human light chain kappa constant region. 
     
     
         26 . An isolated nucleic acid encoding the monoclonal antibody or antigen-binding fragment of  claim 24 . 
     
     
         27 . A vector comprising the isolated nucleic acid of  claim 26 . 
     
     
         28 . A host cell comprising the nucleic acid of  claim 27 . 
     
     
         29 . A pharmaceutical composition comprising the isolated monoclonal antibody or antigen-binding fragment of  claim 24  and a pharmaceutically acceptable carrier. 
     
     
         30 . A method of reducing pathological tau aggregation or spreading of tauopathy in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 29 . 
     
     
         31 . A method of slowing progression of a tauopathy in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of  claim 29 . 
     
     
         32 . The method of  claim 31  wherein the tauopathy is selected from the group consisting of Alzheimer's disease, frontotemporal dementia, and progressive supranuclear palsy. 
     
     
         33 . The method of  claim 32  wherein the tauopathy is Alzheimer's disease. 
     
     
         34 . The method of  claim 33  wherein the Alzheimer's disease is familial Alzheimer's disease. 
     
     
         35 . The method of  claim 33  wherein the Alzheimer's disease sporadic Alzheimer's disease. 
     
     
         36 . The method of  claim 32  wherein the tauopathy is frontotemporal dementia. 
     
     
         37 . The method of  claim 36  wherein the frontotemporal dementia is frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). 
     
     
         38 . The method of  claim 32  wherein the tauopathy is progressive supranuclear palsy. 
     
     
         39 . A method of producing the monoclonal antibody or antigen-binding fragment of  claim 24  comprising culturing a cell comprising a nucleic acid encoding the antibody or antigen-binding fragment under conditions to produce the antibody or antigen-binding fragment, and recovering the antibody or antigen-binding fragment from the cell or cell culture. 
     
     
         40 . A method of detecting the presence of PHF-tau in a biological sample from a subject, comprising contacting the biological sample with the antibody or antigen-binding fragment of  claim 24  and detecting binding of the antibody or antigen-binding fragment to PHF-tau in the sample from the subject. 
     
     
         41 . The method of  claim 40  wherein the biological sample is a blood, serum, plasma, interstitial fluid, or cerebral spinal fluid sample.