Anti-tauc3 antibodies and uses thereof

A method of treating a neurodegenerative disorder in a subject comprising administering a therapeutically effective amount of an anti-TauC3 antibody to the subject, wherein the anti-TauC3 antibody comprises (a) a variable heavy chain (VH) polypeptide possessing at least 70% sequence identity to SEQ ID NO:

• 13, and a variable light chain (VL) polypeptide possessing at least 70% sequence identity to SEQ ID NO:
• 14, SEQ ID NO:
• 15, SEQ ID NO:
• 16, SEQ ID NO:
• 17, or SEQ ID NO:
• 18;
• and has a binding affinity (KD) for TauC3 from 1×1010 to 1×10−12 M;
• and a binding affinity (KD) for a full length tau of from 1×10−4 to 1×10−8 M.

An antigen-binding fragment of an antibody comprising (a) a heavy chain variable region comprising CDR1 homologous to SEQ ID NO:

• 7, CDR2 homologous to SEQ ID NO:
• 8, and CDR3 homologous to SEQ ID NO:
• 9;
• and (b) a light chain variable region comprising CDR1 homologous to SEQ ID NO:
• 10, CDR2 homologous to SEQ ID NO:
• 11, and CDR3 homologous to SEQ ID NO:
• 12;
• and having a binding affinity (KD) for TauC3 of from 1×10-10 and 1×10-12 and an off-rate (Kd) of 1×10-3 s-1 or less (e.g., from 1×10-4 to 1×10-3 s-1), and a binding affinity (KD) for SEQ ID NO:1 of from 1×10-4 to 1×10-8 M, or no detectable binding with SEQ ID NO:1.

An isolated anti-tauC3 antibody, which has a binding affinity (KD) for TauC3 from 1×10−10 to 1×10−12 M, and a binding affinity (KD) for a full length tau of from 1×10−4 to 1×10−8M, wherein the antibody comprises (a) a variable heavy chain (VH) polypeptide comprising CDR1 represented by SEQ ID NO:

• 7, CDR2 represented by SEQ ID NO:
• 8, and CDR3 represented by SEQ ID NO:
• 9;
• and (b) a variable light chain (VL) polypeptide comprising CDR1 represented by SEQ ID NO:
• 10, CDR2 represented by SEQ ID NO:
• 11, and CDR3 represented by SEQ ID NO:
• 12;
• and is a humanized antibody or a chimeric antibody.