Anti-tau antibodies and methods of use
Inventors
Adolfsson, Oskar • Ayalon, Gai • Hotzel, Isidro • Di Cara, Danielle Marie
Assignees
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Publication Number
US-12486319-B2
Publication Date
2025-12-02
Expiration Date
Abstract
The invention provides anti-Tau antibodies and methods of using the same.
Core Innovation
The invention provides an isolated antibody that binds human Tau. The antibody comprises HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3, where each region is defined by a specific amino acid sequence corresponding to SEQ ID NOs: 192, 193, 194, 195, 196, and 197. In this way, the antibody is structurally specified by complementarity-determining region sequences that determine binding to human Tau.
The document characterizes antibody variants by binding kinetics and affinity across Tau forms and presentation formats. It reports kinetic affinity data against human Tau, including Tau monomer and formats such as IgG1, IgG4, and IgG4-S228P.YTE, and it includes cross-species binding to cynomolgus Tau. Epitope mapping is described as indicating binding within Tau amino acids 2-24.
The document also addresses antibody variant selection in terms of thermal-stress stability, normalized Rmax, and a Stability Index, together with reduced susceptibility to deamidation associated with the light-chain N28 G29 N30 motif. In addition, it reports in vivo pharmacokinetics/pharmacodynamics in mice and cynomolgus monkeys for Tau-binding antibody variants bearing Fc YTE modifications, including Cmax, AUCinf, clearance, and plasma total Tau measurements.
Claims Coverage
The claims coverage centers on an isolated antibody binding human Tau with six specified HVR sequences. The independent claim is refined by dependent claims that further constrain VH/VL sequence identity, isotype, and point mutations, and extend to an immunoconjugate with a second therapeutic agent.
Tau-binding isolated antibody with specified HVR sequences
An isolated antibody that binds human Tau, wherein the antibody comprises HVR-H1 with the amino acid sequence of SEQ ID NO: 192, HVR-H2 with the amino acid sequence of SEQ ID NO: 193, HVR-H3 with the amino acid sequence of SEQ ID NO: 194, HVR-L1 with the amino acid sequence of SEQ ID NO: 195, HVR-L2 with the amino acid sequence of SEQ ID NO: 196, and HVR-L3 with the amino acid sequence of SEQ ID NO: 197.
VH/VL at least 95% identical to specified sequences
The isolated antibody comprises heavy chain variable region (VH) and/or light chain variable region (VL) sequences that are at least 95% identical to SEQ ID NOs: 190 and 191.
IgG1 or IgG4 antibody isotype
The isolated antibody is an IgG1 or an IgG4 antibody.
Point mutations M252Y, S254T, and T256E
The isolated antibody comprises M252Y, S254T, and T256E mutations.
Immunoconjugate with a second therapeutic agent
An immunoconjugate comprises the antibody of claim 1 and a second therapeutic agent.
Across the claim set, the core is an isolated human Tau-binding antibody defined by specified HVR-H1/H2/H3 and HVR-L1/L2/L3 sequences. Dependent features further restrict VH/VL sequence identity, specify IgG1 or IgG4 isotypes, add point mutations including M252Y, S254T, and T256E, and extend the coverage to an immunoconjugate containing a second therapeutic agent.
Stated Advantages
Binds monomeric Tau with reported kinetic affinity data across Tau forms and presentation formats.
Provides an isolated antibody with defined HVR complementarity-determining region sequences for binding human Tau.
Includes variants described with thermal-stress stability characterization and reduced susceptibility to deamidation.
Documented Applications
Therapeutic and diagnostic uses for Tau protein associated diseases (tauopathies), including Alzheimer’s disease and progressive supranuclear palsy, are described.
Methods to detect Tau aggregates are described.
Labeled antibodies are described as a format.
Pharmaceutical compositions comprising the antibodies are described.
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