Tau binding compounds
Inventors
Carter, Todd • Hou, Jinzhao • KURELLA, Vinodhbabu • Capili, Allan D. • Liu, Wencheng • Chung, Hiu Yan • Holth, Jerrah • Kavanagh, Dillon • Paranjpe, Maneesha Anand
Assignees
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Publication Number
US-12709641-B2
Publication Date
2026-08-18
Expiration Date
Abstract
The present disclosure provides anti-tau antibodies and vectorization thereof (e.g., into AAV particles). Also provided are methods of using anti-tau antibodies and/or AAV particles for prevention, treatment, and/or diagnosis of neurological indications.
Core Innovation
The invention provides tau-binding antibodies defined by specified combinations of heavy- and light-chain complementarity determining regions, alongside encoding nucleic acids and recombinant expression embodiments. These antibodies bind human tau, including enriched paired helical filament tau, pathological tau epitopes, and human tau residues 409-436, generally displaying weak or no binding to wild-type tau. Additionally, selected sequence-defined antibodies inhibit tau aggregation.
The disclosure describes adeno-associated viral genomes and viral particles carrying anti-tau antibody payloads with configurable expression-control elements for targeted delivery. Documented utilities encompass immunohistochemical detection, selective staining of Alzheimer's disease brain tissue, and reduced pathogenic tau AT8 immunoreactivity in a seeding model. These embodiments support the diagnosis, prevention, and treatment of tauopathies and other central nervous system neurological disorders.
Claims Coverage
The claims identify three independent claims covering sequence-defined tau-binding antibodies and encoding nucleic acids across three inventive features.
Tau-binding antibody with specified CDR combinations
Independent claim 1 covers an antibody that binds tau comprising heavy- and light-chain variable regions with specified combinations of complementarity determining regions.
Tau-binding antibody with alternative specified CDR combinations
Independent claim 23 covers an antibody that binds tau comprising heavy- and light-chain variable regions with alternative specified combinations of complementarity determining regions.
Nucleic acid encoding a tau-binding antibody
Independent claim 35 covers a nucleic acid encoding a tau-binding antibody comprising specified combinations of heavy- and light-chain complementarity determining regions.
The independent claims cover sequence-defined tau-binding antibodies and nucleic acids encoding them, while dependent claims further address antibody formats, sequence characteristics, binding properties, host cells, production methods, and pharmaceutical compositions.
Stated Advantages
The described antibodies generally show weak or no binding to wild-type tau while binding enriched paired helical filament tau.
Selected antibodies reduce or inhibit tau aggregation.
Several antibodies stain Alzheimer's disease brain tissue with little or no staining in non-Alzheimer's disease tissue.
Documented Applications
Diagnostic use, including immunohistochemical detection of tau in brain tissue.
Prevention or therapeutic treatment of tauopathies and other neurological disorders, including central nervous system conditions.
Antibody delivery utilizing adeno-associated viral genomes and viral particles directed to central nervous system or muscle tissues.
Recombinant expression and production of tau-binding antibodies using host cells and encoding nucleic acids.
Pharmaceutical compositions comprising a specified tau-binding antibody and a pharmaceutically acceptable excipient.
Characterization of antibody binding to enriched paired helical filament tau and assessment of tau-aggregation inhibition.
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