US 2022/0177558 A1 · TREATMENT OF TAUPATHY DISORDERS BY TARGETING NEW TAU SPECIES

Abstract

The invention relates to a method of treatment of Tauopathy disorder using antibody that specifically binds news Tau species, especially Tau species starting from the methionine residue at position (11), said methionine being N-alpha acetylated (AcMet11-Tau). The invention also relates to an antibody that specifically binds this new tau species. Inventors have discovered that AcMet11-Tau is a pathological Tau species that is involved in Tau pathology development. Inventors have demonstrated the causal link between AcMet11-Tau species and Tau pathology by showing that brain expression of AcMet11-Tau species potentiate Tau pathology development in Thy-Tau Transgenic mice and is involved in pathological process, at least by accelerating Tau pathology. Inventors have also used passive immunization approach based on a specific monoclonal antibody (2H2D11) in order to demonstrate that the reduction/neutralization of this Tau species in the Thy-Tau22 transgenic model of Tau pathology lead to protective effect towards Tau pathology and associated memory deficits. Furthermore, the inventors subcloned 2C12 hybridoma and selected the 2C1C8, a further antibody against N-alpha-acetyl-Met11-Tau (AcMet11-Tau). They demonstrate that the 2C1C8 antibody displayed also specificity towards N-alpha-terminally acetylated methionine11 of Tau protein and labels neurons displaying neurofibrillary degeneration in the hippocampus of Thy-Tau22 transgenic mice.

Claims15

Dependent claims

A method of treating a Tauopathy disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-Tau antibody, wherein said anti-Tau antibody binds to an epitope comprising the following amino acid sequence:

(N-α-acetyl)MEDHAGTYGLG (SEQ ID NO:8).

An anti-Tau antibody wherein said antibody comprises:

(a) a heavy chain wherein the variable domain comprises:
a H-CDR1 having 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% of identity with the sequence set forth as SEQ ID NO:
11, and
a H-CDR2 having 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% of identity with the sequence set forth as SEQ ID NO:
12, and
a H-CDR3 having 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% of identity with the sequence set forth as SEQ ID NO:
13;
(b) a light chain wherein the variable domain comprises:
a L-CDR1 having 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% of identity with the sequence set forth as SEQ ID NO:
14, and
a L-CDR2 having 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% of identity with the sequence set forth as SEQ ID NO:
15, and
a L-CDR3 having 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% of identity with the sequence set forth as SEQ ID NO:
16
wherein the anti-Tau antibody binds to AcMet11-Tau polypeptide with substantially the same affinity as an antibody having a variable light chain domain (VL) and/or a variable heavy chain domain (VH) of the antibody 2H2D11.

12 more elements

Dependencies are inferred from the claim text.

Treatment of taupathy disorders by targeting new tau species

Life of this patent

Treatment of taupathy disorders by targeting new tau species

Life of this patent

Abstract

Claims15