Antibodies to phosphorylated tau aggregates
Inventors
Winderickx, Joris • Vanmechelen, Eugeen • Van Leuven, Fred
Assignees
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Publication Number
US-9447179-B2
Publication Date
2016-09-20
Expiration Date
Abstract
This invention concerns affinity tools for oligomeric forms of tau protein. It relates to the field of neurodegeneration, more particularly to the field of tau-related diseases and tauopathy. The invention provides novel tau antibodies and antibody fragments, nucleic acids encoding such antibodies and antibody fragments, cell lines producing such antibodies and antibody fragments, antibody compositions, and kits for the detection of aggregated tau and for the diagnosis of diseases involving aggregated tau. The invention further provides methods for the detection of aggregated tau, for the diagnosis of diseases involving aggregated tau, and for the identification of compositions interfering with the formation and/or stability of tau aggregates.
Core Innovation
The invention relates to an isolated tau antibody, antibody-like scaffold or antibody fragment that specifically comprises variable regions defined by amino acid sequences in the CDR1, CDR2 and CDR3 regions. The light chain variable region includes CDR1, CDR2 and CDR3 amino acid sequences as set out in SEQ ID NO: 22, SEQ ID NO: 23 and SEQ ID NO: 24, and the heavy chain variable region includes CDR1, CDR2 and CDR3 amino acid sequences as set out in SEQ ID NO: 19, SEQ ID NO: 20 and SEQ ID NO: 21.
The invention relates to affinity-tool antibodies and antibody fragments that preferentially bind oligomeric and high-molecular-weight phosphorylated tau aggregates. It is directed to immunological materials for detecting aggregated tau and for use in diagnosis of tauopathies, and the document positions the affinity tools to recognize phosphorylated tau aggregates with preferential binding.
The document further describes anti-tau monoclonal antibodies, including ADx210, ADx211 and ADx215, and includes deposited hybridoma cell lines producing antibodies with preferential binding to phosphorylated tau aggregates. It also includes peptide epitopes corresponding to the ADx215-recognized tau epitope, including SEQ ID NO: 27 and SEQ ID NO: 29, as controls, internal standards, calibrators and kit components for tau diagnostics.
Claims Coverage
The provided claim coverage identifies two sequence-defined tau-binding antibody subject matters: one independent claim defined by exact CDR amino acid sequences for both the light chain and heavy chain variable regions, and one claim category directed to affinity-tool antibodies or antibody-like scaffolds or fragments that preferentially bind phosphorylated tau aggregates. Together, the claims focus on sequence-specific and binding-specific inventive features.
Cdr-defined isolated tau antibody variable regions
An isolated tau antibody, antibody-like scaffold or antibody fragment comprising a light chain variable region with CDR1, CDR2 and CDR3 amino acid sequences as set out in SEQ ID NO: 22, SEQ ID NO: 23 and SEQ ID NO: 24, and a heavy chain variable region with CDR1, CDR2 and CDR3 amino acid sequences as set out in SEQ ID NO: 19, SEQ ID NO: 20 and SEQ ID NO: 21.
Preferential binding to phosphorylated tau aggregates
Affinity-tool antibodies and antibody fragments that preferentially bind oligomeric and high-molecular-weight phosphorylated tau aggregates.
Overall, the claim coverage is directed to sequence-defined isolated tau antibodies, antibody-like scaffolds or fragments, and to affinity-tool antibodies or antibody fragments characterized by preferential binding to phosphorylated tau aggregates.
Stated Advantages
Supports detecting aggregated tau.
Enables monitoring minimal (residual) disease after tau-vaccine treatment by detecting immunological complexes.
Supports predicting patient responsiveness to tau-vaccine treatment by comparing immunological complex levels before and after therapy.
Supports diagnostic and predictive testing for tau-associated disease.
Preferential binding to oligomeric and high-molecular-weight phosphorylated tau aggregates.
Provides peptide epitopes and kit components for use in tau diagnostic assays.
Supports diagnosis of tauopathies using detection formats described in the document.
Documented Applications
Diagnostic and predictive testing for tau-associated disease using aggregated-tau detection with anti-tau monoclonal antibodies ADx210 and ADx215.
Detecting aggregated tau using antigen-antibody complex readouts, including ELISA and bead-based Luminex xMAP detection formats.
Monitoring minimal (residual) disease after tau-vaccine treatment by detecting immunological complexes.
Predicting patient responsiveness to tau-vaccine treatment by comparing immunological complex levels before and after therapy.
Diagnosis of tauopathies, including tauopathy contexts such as Alzheimer’s disease.
Use of ADx215 epitope peptides as assay controls, internal standards, calibrators, and kit components in diagnostic assays and kit formats.
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