Anti-tau antibodies and uses thereof

Abstract

Provided herein are antibodies that specifically bind Tau and methods of using the same.

What is claimed: 
     
         1 . A labeled antibody or antigen-binding fragment comprising a monoclonal antibody, or an antigen-binding fragment thereof, that specifically binds a human Tau, wherein the antibody comprises:
 a heavy chain variable domain (HCVD) comprising SEQ ID NO: 268 and a light chain variable domain (LCVD) comprising SEQ ID NO: 465;   a HCVD comprising SEQ ID NO: 268 and a LCVD comprising SEQ ID NO: 581;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 402 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 572;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 572; or   a HCVD comprising SEQ ID NO: 196 and a LCVD comprising SEQ ID NO: 411.   
     
     
         2 . The labeled antibody or antigen-binding fragment of  claim 1  comprising a fluorescent label, chromophoric label, electron-dense label, chemiluminescent label, radioactive labels, enzyme, or detectable ligand. 
     
     
         3 . A nucleic acid molecule encoding a monoclonal antibody, or an antigen-binding fragment thereof, that specifically binds a human Tau, wherein the antibody comprises:
 a heavy chain variable domain (HCVD) comprising SEQ ID NO: 268 and a light chain variable domain (LCVD) comprising SEQ ID NO: 465;   a HCVD comprising SEQ ID NO: 268 and a LCVD comprising SEQ ID NO: 581;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 402 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 572;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 572; or   a HCVD comprising SEQ ID NO: 196 and a LCVD comprising SEQ ID NO: 411.   
     
     
         4 . A vector comprising the nucleic acid molecule of  claim 3 . 
     
     
         5 . A cell that expresses the nucleic acid molecule of  claim 3 . 
     
     
         6 . A method of producing an anti-Tau antibody or antigen-binding fragment comprising culturing a cell according to  claim 5  under conditions suitable for producing the antibody or antigen-binding fragment. 
     
     
         7 . The method according to  claim 6  further comprising recovering the antibody or antigen-binding fragment. 
     
     
         8 . A method for decreasing sarkosyl-insoluble Tau levels in a subject in need thereof, the method comprising administering to the subject a monoclonal antibody, or an antigen-binding fragment thereof, that specifically binds a human Tau, wherein the antibody comprises:
 a heavy chain variable domain (HCVD) comprising SEQ ID NO: 268 and a light chain variable domain (LCVD) comprising SEQ ID NO: 465;   a HCVD comprising SEQ ID NO: 268 and a LCVD comprising SEQ ID NO: 581;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 402 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 572;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 572; or   a HCVD comprising SEQ ID NO: 196 and a LCVD comprising SEQ ID NO: 411.   
     
     
         9 . A method for inhibiting Tau aggregation in a subject in need thereof, the method comprising administering to the subject a monoclonal antibody, or an antigen-binding fragment thereof, that specifically binds a human Tau, wherein the antibody comprises:
 a heavy chain variable domain (HCVD) comprising SEQ ID NO: 268 and a light chain variable domain (LCVD) comprising SEQ ID NO: 465;   a HCVD comprising SEQ ID NO: 268 and a LCVD comprising SEQ ID NO: 581;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 402 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 572;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 572; or   a HCVD comprising SEQ ID NO: 196 and a LCVD comprising SEQ ID NO: 411.   
     
     
         10 . A method of treating a Tauopathy in a subject in need thereof, the method comprising: administering to the subject a monoclonal antibody, or an antigen-binding fragment thereof, that specifically binds a human Tau, wherein the antibody comprises:
 a heavy chain variable domain (HCVD) comprising SEQ ID NO: 268 and a light chain variable domain (LCVD) comprising SEQ ID NO: 465;   a HCVD comprising SEQ ID NO: 268 and a LCVD comprising SEQ ID NO: 581;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 402 and a LCVD comprising SEQ ID NO: 545;   a HCVD comprising SEQ ID NO: 384 and a LCVD comprising SEQ ID NO: 572;   a HCVD comprising SEQ ID NO: 393 and a LCVD comprising SEQ ID NO: 572; or   a HCVD comprising SEQ ID NO: 196 and a LCVD comprising SEQ ID NO: 411, under conditions effective to treat the Tauopathy in the subject.   
     
     
         11 . The method according to  claim 10 , wherein the Tauopathy is Alzheimer's disease, frontotemporal dementia, or progressive supranuclear palsy. 
     
     
         12 . The method according to  claim 11 , wherein the frontotemporal dementia is Pick's disease.