Anti-Tau antibodies and methods of use
Inventors
Adolfsson, Oskar • Wildsmith, Kristin Ruth • Van Der Brug, Marcel • Muhs, Andreas
Assignees
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Publication Number
US-10836817-B2
Publication Date
2020-11-17
Expiration Date
Abstract
The invention provides anti-Tau antibodies and methods of using the same.
Core Innovation
The invention relates to anti-Tau antibodies that bind human Tau and are defined at the sequence level by heavy- and light-chain hypervariable region options, including HVR-H1/H2/H3 and HVR-L1/L2/L3 amino-acid sequences using multiple alternative SEQ ID NOs. The antibodies include humanized options and variants defined with acceptor human framework selection and VH/VL sequence identity thresholds, including substitutions and indels outside HVRs.
The disclosure describes humanized anti-Tau antibodies produced by grafting CDRs onto human consensus VH and Vk frameworks, with examples including 37D3-H9, 125B11-H3, 94B2-C1, and related humanized variants. Functional characterization includes affinity and kinetic screening by SPR against human Tau monomer and epitope mapping using Tau fragments, with binding identified within Tau amino acids approximately 2–24 and including binding to phosphorylated Tau.
The anti-Tau antibodies are described across multiple formats and effector contexts, including monoclonal, chimeric, humanized, human antibodies and antibody fragments such as Fv, Fab, Fab′, scFv, and diabody. The disclosure also describes Fc and glycosylation-related considerations, IgG4 formats, FcRn-binding and half-life-related substitutions, thermal stress stability assessment, LC-MS/MS deamidation analyses, and in vivo PK/PD evaluations in mice and cynomolgus monkeys.
Claims Coverage
The independent claim set provided includes one antibody product claim and four independent diagnostic, prognostic, and monitoring method claims. Collectively, the inventive features are the specific sets of HVR-H1/HVR-H2/HVR-H3 and HVR-L1/HVR-L2/HVR-L3 sequences that define anti-Tau antibodies, and the use of those defined antibodies in patient selection, treatment monitoring, and progression monitoring.
Isolated anti-Tau antibody defined by multiple HVR sequence sets
An isolated antibody that binds to human Tau, wherein the antibody comprises specified HVR-H1/HVR-H2/HVR-H3 and HVR-L1/HVR-L2/HVR-L3 amino-acid sequence sets using multiple alternative SEQ ID NO combinations.
Selecting a patient for anti-Tau therapy using detection of Tau with defined HVR sequence sets
A method of selecting a patient for treatment with a therapeutic anti-Tau antibody by detecting Tau in a sample from the subject with a detection anti-Tau antibody comprising specified HVR-H1/HVR-H2/HVR-H3 and HVR-L1/HVR-L2/HVR-L3 amino-acid sequence sets.
Monitoring treatment using detection of Tau with defined HVR sequence sets
A method of monitoring treatment with a therapeutic anti-Tau antibody by detecting Tau in a sample from a subject undergoing treatment with a detection anti-Tau antibody comprising specified HVR-H1/HVR-H2/HVR-H3 and HVR-L1/HVR-L2/HVR-L3 amino-acid sequence sets.
Monitoring progression of cognitive impairment using detection of Tau with defined HVR sequence sets
A method of monitoring the progression of cognitive impairment in a subject with a tauopathy by detecting Tau in a sample from the subject with a detection anti-Tau antibody comprising specified HVR-H1/HVR-H2/HVR-H3 and HVR-L1/HVR-L2/HVR-L3 amino-acid sequence sets.
Across the independent claims provided, the principal inventive content is the definition of anti-Tau antibodies by particular heavy- and light-chain HVR sequence sets. Independent methods then use Tau detection with those defined antibodies for patient selection, monitoring treatment, and monitoring progression of cognitive impairment in a subject with a tauopathy.
Stated Advantages
Enables binding to human Tau using sequence-defined heavy- and light-chain hypervariable region options.
Provides antibodies with defined epitope scope, including binding to the same epitope as enumerated antibodies and defined Tau fragment binding regions.
Supports multiple antibody formats and effector-context coverage, including Fc and glycosylation-related considerations.
Provides detection of Tau forms in samples and supports monitoring disease/progression and treatment selection.
Documented Applications
Detection of Tau forms using the anti-Tau antibodies.
Patient selection based on detection using anti-Tau antibodies with defined HVR sequences or SEQ ID sets.
Monitoring disease progression, including cognitive impairment and tauopathy, using detection anti-Tau antibodies.
Monitoring treatment using detection anti-Tau antibodies for treatment selection and/or monitoring treatment response.
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