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Publication Number
US-9927443-B2
Publication Date
2018-03-27
Expiration Date
Abstract
Methods to estimate safety and/or efficacy of therapeutic drugs, which include portable devices for anti-drug antibody (ADA) testing and databases containing anonymized data from humans and/or animal models, and related analyses, are provided. These methods and compositions can be used in various applications, including but not restricted to the following: uniform testing of patients for ADA; selection of therapeutic drug for patient treatment; evaluation of the need to change therapeutic drug or to apply tolerance regimens; selection of patients for clinical trials; comparison of therapeutic drugs marketed for a given disease and also gene therapy; scientific guidance for discovering and/or developing therapeutic drugs; postmarketing surveillance of therapeutic drugs.
Core Innovation
The invention relates to a method for assessing risks associated with human immune responses against therapeutic drugs by using a portable device capable of testing for human anti-drug antibodies (ADAs). The portable device includes labeled entities immobilized on the device, where the labeled entities bind to a constant region of human ADAs, and where labeled entities bound to ADAs complex flow towards one or more capture reagent immobilized on the device, wherein the capture reagent comprises the therapeutic drugs or regions of the therapeutic drugs immobilized on the device.
The method includes detecting a visible signal resulting from binding of ADAs to one or more therapeutic drugs or regions of the therapeutic drugs immobilized on the device, and correlating the detected signal with the presence or absence of ADAs in a human subject.
The invention also describes use of an anonymized, data-driven database accessible from the portable device, enabling correlation of ADA test results with contextual risk and immune response factors drawn from other subjects. The database includes data such as associations involving MHC class II/HLA types, epitope mapping, genetic and immune tolerance-related associations, ADA incidence, and additional factors such as chemistry, manufacturing and control (CMC) factors, including protein aggregation, subvisible particles, glycosylation, and deamidation, together with guidance for downstream therapeutic decision support.
The system supports multiple therapeutic-drug and clinical-use cases including patient stratification, therapeutic drug selection and switching, tolerance-regimen guidance, clinical trial patient selection, drug comparison including biosimilars/biobetters and gene therapy, scientific guidance for drug discovery, and postmarketing surveillance, with illustrative examples including IFN-beta and insulin.
Claims Coverage
The independent claim covers an ADA risk-assessment workflow using a portable point-of-care device with immobilized labeled entities, a capture reagent comprising therapeutic drugs or drug regions, visible-signal detection, and correlation of the signal with the presence or absence of ADAs. The dependent claims refine coverage by adding database access via a device code and by expanding which database content and downstream uses are addressed.
Portable device ADA risk assessment with immobilized labeled entities and capture reagent
Contacting a biological sample from a human subject with a portable device capable of testing for human anti-drug antibodies (ADAs) against one or more therapeutic drugs, wherein labeled entities are immobilized on the portable device, wherein said labeled entities on said device bind to a constant region of the human ADAs, wherein the labeled entities bound to ADAs complex flow towards one or more capture reagent immobilized on the device, and wherein the capture reagent comprises said therapeutic drugs or regions of said therapeutic drugs.
Visible signal detection from ADA binding and correlation to presence or absence
Detecting a visible signal resulting from binding of ADAs to one or more therapeutic drugs or regions of said therapeutic drugs immobilized on the device, and correlating signal with presence or absence of ADAs.
Device code to access an anonymized ADA database from other subjects
Using a code on the portable device to access a database containing ADA data obtained from other human subjects using the same portable device.
Genetic analyses and immune tolerance associations in the ADA database
Using a database that provides genetic analyses from human patients and their associations with human ADA responses or immune tolerance, where the ADA data used for testing these associations is obtained using the portable device.
Therapeutic drug content in the database for ADA-related analysis
The database includes information for specified therapeutic drugs including insulin, interferon-beta, therapeutic antibody, enzyme replacement therapy, and protein or peptide drugs, optionally conjugated with a chemical entity or moiety.
Database guidance to rank and select therapeutic drugs
Using a database that provides guidance to rank and select therapeutic drugs.
Comparing incidence of ADAs for a therapeutic protein drug versus gene therapy antibodies
Comparing therapeutic drugs and gene therapy in a given therapeutic area by comparing the incidence of human ADAs against a therapeutic protein drug versus the incidence of human antibodies against the same protein following gene therapy that corrects a genetic defect in a human patient.
Overall claim coverage combines portable, immobilized-entity ADA testing with visible-signal detection and signal-to-ADA presence correlation, with optional portable-device-accessible database features that incorporate anonymized ADA data from other subjects, including genetic and immune tolerance associations and expanded drug-specific and guidance-oriented database content, and database-enabled downstream uses such as drug ranking/selection and comparison involving gene therapy incidence of ADAs versus antibodies.
Stated Advantages
Enables assessing risks associated with human immune responses against therapeutic drugs by correlating detected visible signals with the presence or absence of ADAs.
Supports patient stratification and therapeutic drug selection and switching based on portable ADA testing and database correlation.
Provides tolerance-regimen guidance and clinical trial patient selection using portable ADA testing with database context.
Enables drug comparison across therapeutic areas, including biosimilars/biobetters and gene therapy comparisons involving incidence of human ADAs versus antibodies.
Provides scientific guidance for drug discovery and supports postmarketing surveillance using portable ADA testing and database information.
Documented Applications
Patient stratification based on portable point-of-care ADA testing and anonymized database correlation.
Therapeutic drug selection and switching based on portable ADA testing and database correlation.
Tolerance-regimen guidance based on portable ADA testing and database correlation.
Clinical trial patient selection using portable ADA testing and database information.
Drug comparison for biosimilars/biobetters and for gene therapy, including comparison of incidence of ADAs versus antibodies in gene therapy scenarios.
Scientific guidance for drug discovery using portable ADA testing and database content.
Postmarketing surveillance using portable ADA testing and database information.
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