Methods of Treating a Tauopathy

Abstract

The present disclosure provides methods of treating a tauopathy, involving administering an anti-Tau antibody. The present disclosure also provides anti-Tau antibodies, and formulations comprising same, for use in the methods.

1 .- 62 . (canceled) 
     
     
         63 . A method of monitoring progression of a tauopathy in an individual, the method comprising:
 a) determining a first level of a Tau polypeptide in a biological sample obtained from the individual at a first time point;   b) determining a second level of a Tau polypeptide in a biological sample obtained from the individual at a second time point; and   c) comparing the second level of Tau with the first level of Tau, wherein said determining comprises:
 i) contacting the biological sample with an antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41; and 
 ii) quantitating binding of the antibody to Tau polypeptide present in the sample. 
   
     
     
         64 . The method of  claim 63 , wherein the biological sample is cerebrospinal fluid, blood, plasma, serum, urine, or saliva. 
     
     
         65 . The method of  claim 63 , wherein the quantitated Tau polypeptide is total Tau polypeptide. 
     
     
         66 . The method of  claim 63 , wherein the quantitated Tau polypeptide is an N-terminal fragment of a full-length Tau polypeptide. 
     
     
         67 . The method of  claim 63 , wherein the first time point is a time point before initiation of a treatment regimen, and wherein the second time point is a time point after initiation of a treatment regimen. 
     
     
         68 . A method of detecting a Tau polypeptide in a living individual in vivo, the method comprising:
 a) administering to the individual an antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41; and   b) detecting binding of the antibody to tau polypeptide in a brain tissue in the individual using an imaging method.   
     
     
         69 . The method of  claim 68 , wherein the antibody comprises a contrast agent suitable for use in the imaging method. 
     
     
         70 . The method of  claim 68 , wherein the imaging method is magnetic resonance imaging or positron emission tomography. 
     
     
         71 . An in vitro method of detecting a Tau polypeptide in a biological sample obtained from an individual, the method comprising:
 a) contacting the biological sample with an antibody competes for binding to an epitope within the N-terminal region of Tau with an antibody that comprises:   i) light chain complementarity-determining regions (CDRs) of an antibody depicted in  FIG. 1B ; and heavy chain CDRs of an antibody depicted in  FIG. 1A ; or   ii) light chain CDRs of an antibody depicted in  FIG. 2B ; and heavy chain CDRs of an antibody depicted in  FIG. 2A ; and   b) detecting binding of the antibody to Tau polypeptide present in the sample.   
     
     
         72 . The method of  claim 71 , wherein the biological sample is blood, serum, plasma, urine, saliva, or cerebrospinal fluid. 
     
     
         73 . The method of  claim 71 , wherein the individual is suspected of having a tauopathy, has been diagnosed as having a tauopathy, or has a genetic predisposition to developing a tauopathy. 
     
     
         74 . The method of  claim 71 , wherein the method is quantitative. 
     
     
         75 . The method of  claim 71 , wherein the Tau polypeptide detected is total Tau polypeptide. 
     
     
         76 . The method of  claim 71 , wherein the Tau polypeptide detected is an N-terminal fragment of a full-length Tau polypeptide. 
     
     
         77 . A method of reducing the level of Aβ 40  and/or Aβ 42  in a neuronal cell and/or extracellular fluid in an individual, the method comprising administering to the individual:
 a) an effective amount of an antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41; or 
 b) a pharmaceutical composition comprising the antibody. 
 
     
     
         78 . (canceled) 
     
     
         79 . (canceled) 
     
     
         80 . A method of determining the amount of extracellular Tau (eTau) unbound to an anti-eTau antibody in a sample of cerebrospinal fluid (CSF) or interstitial fluid (ISF) obtained from a subject undergoing therapy with the anti-eTau antibody, the method comprising:
 a) contacting an immobilized antibody with a sample of CSF or ISF obtained from the subject,   wherein the immobilized antibody comprises a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41, said contacting being under conditions suitable for binding of the unbound eTau to the immobilized antibody; and   b) determining the amount of eTau bound to the immobilized antibody, wherein the amount of eTau bound to the immobilized antibody is an indication of the amount of eTau unbound to the anti-Tau antibody in the sample.   
     
     
         81 . The method of  claim 80 , wherein the amount of eTau bound to the immobilized antibody is determined using a detectably labeled third antibody that does not compete with the immobilized antibody for binding to the eTau. 
     
     
         82 . The method of  claim 80 , wherein the sample is cerebrospinal fluid. 
     
     
         83 .- 84 . (canceled) 
     
     
         85 . The method of  claim 80 , comprising determining the level of total tau in the sample. 
     
     
         86 . The method of  claim 80 , comprising comparing the level of unbound Tau in the sample to the level of total tau in a CSF or ISF sample obtained from the individual before treatment with the anti-eTau antibody. 
     
     
         87 . (canceled) 
     
     
         88 . The method of  claim 86 , comprising adjusting the treatment regimen based on the compared level. 
     
     
         89 .- 93 . (canceled) 
     
     
         94 . A nucleic acid or nucleic acids encoding an antibody comprising a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:37 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:41. 
     
     
         95 . An expression vector or expression vectors comprising the nucleic acid or nucleic acids of  claim 94 . 
     
     
         96 . A host cell comprising the expression vector or expression vectors of  claim 95 . 
     
     
         97 . The host cell of  claim 96 , wherein the host cell is a HeLa cell, a CHO cell, a 293 cell, a Vero cell, a NIH3T3 cell, a CS cell, a HEK cell, or a BHK cell.