Risk Assessment for Therapeutic Drugs

• US 20160320405A1
• Filed: 04/05/2016
• Published: 11/03/2016
• Est. Priority Date: 04/10/2015
• Status: Active Grant

• Current Assignee: Conquerab Inc.
• Original Assignee: Conquerab Inc.
• Inventors: Barbosa, Maria D. F. S.
• Granted Patent: US 9,927,443 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/54391 based on vertical flow
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: G05B 15/00 Systems controlled by a computer G05B13/00, G05B19/00 take precedence; automatic controllers with particular characteristics G05B11/00
• CPC Class Codes: G06F 7/06 Arrangements for sorting, selecting, merging, or comparing data on individual record carriers
• CPC Class Codes: G16H 10/20 for electronic clinical trials or questionnaires
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

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 human 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.

Claims

1. Methods and compositions for assessing risks associated with immune responses against therapeutic drugs (or lack thereof), comprising clinical (and/or nonclinical) data and analyses logistically organized in databases.

4. In another embodiment, the databases of claim 1 contain genetic data, comprising but not restricted to human leucocyte antigen (HLA) types, genetic mutations, and analyses of associations (or lack thereof) with ADA responses or immune tolerance.

5. In another embodiment, the databases of claims 1 and 4 comprise data from animal models and/or from humans, and,

Wherein the humans have an autoimmune disease and/or

Wherein the humans are diabetes patients and/or

Wherein the humans are multiple sclerosis patients and/or

Wherein the humans are rheumatoid arthritis patients and/or

Wherein the humans are cancer patients and/or

Wherein the humans have a rare disease and/or

Wherein the humans have cardiovascular disease and/or

Wherein the humans have other diseases and/or

Wherein the humans are healthy individuals.

6. In another embodiment the databases of claims 1, 4 and 5 contain information regarding therapeutic drugs, including but not restricted to gene therapy, and,

Wherein the therapeutic drug is insulin, native or modified and/or

Wherein the therapeutic drug is an interferon-β

, native or modified, or other therapy for an autoimmune disease and/or

Wherein the therapeutic drug is a therapeutic antibody, including but not restricted to anti-cancer drugs and/or

Wherein the therapeutic drug is an enzyme replacement therapy and/or

Wherein the therapeutic drug is an anti-inflammation therapy and/or

Wherein the therapeutic drug is a vaccine and/or

Wherein the therapeutic drug is for other applications

7. In another embodiment, the databases of claims 1, 4, 5 and 6 can be combined to various degrees and can have differential levels of access and security

8. In another embodiment, the databases of claims 1, 4, 5, 6 and 7 comprise information that can be used for individual applications or for combined purposes, and,

Wherein the databases are used to assess the likelihood of host anti-drug antibody responses;

and/or to assess likelihood of host neutralizing antibody responses; and

/or to predict drug efficacy and/or safety; and

/or to guide therapy selection; and

/or to assess likelihood of adverse reactions upon administration of a therapeutic drug to a patient or animal model; and

/or to estimate an effective therapeutic drug dose; and

/or to obtain scientific guidance for engineering of biotherapeutics with improved properties, including but not restricted to reduced immunogenicity; and

/or to obtain scientific guidance for drug discovery and/or development; and

/or for postmarketing surveillance of therapeutic drugs.

9. In another embodiment, the databases of claims 1, 4, 4, 6, 7, and 8 contain ADA data obtained with various assays other than the data obtained with the portable device of claims 2 and 3.

17. In another embodiment, the databases of claims 1, 4, 5, 6, 7, and 8, either alone or in combinations with ADA testing devices of claims 2, 3, 9, 10, 11, 12, 13, 14, 15 and 16 can be used to compare therapeutic drugs and gene therapy within a given therapeutic area.

18. In another embodiment, the databases of claims 1, 4, 5, 6, 7, 8 and 9, either alone or in combinations with ADA testing devices of claims 2, 3, 10, 11, 12, 13, 14, 15 and 16 can be used to evaluate therapeutic drugs prior to, during or after analysis of patient megadata (big data), and,

Wherein the effect of anti-drug antibodies and their possible associations with the etiology of diseases can be tested and/or

Wherein the influence of genetic components can be investigated and/or

Wherein conclusions can be used to guide discovery and/or development of novel therapeutic entities.

2. A portable device for testing anti-drug antibodies (ADAs) in tissues and body fluids, including but not restricted to blood, serum and plasma. That device can be constructed using the entire therapeutic drug, and/or using specific regions of the therapeutic drug or degradation products, including but not restricted to peptides and/or polyethylene glycol.

3. In another embodiment the device of claim 2 has a code or other means of allowing access to a database.

10. In another embodiment, the portable devices of claims 2 and 3 can enable point of care testing, and/or patient self-testing.

11. In another embodiment, the portable devices of claims 2 and 3 can be used as a companion diagnostic test for therapeutic drugs.

12. In another embodiment, the portable devices of claims 2 and 3 are based on lateral-flow technology or vertical flow technology, and,

Wherein the device detects IgG, or IgM, or both IgG and IGM, or IgE, or several immunoglobulin isotypes, individually or in combinations.

13. In another embodiment, the portable devices of claims 2 and 3 use test strips or other matrix for localized reactions, and,

Wherein the device detects IgG, or IgM, or both IgG and IGM, or IgE, or several immunoglobulin isotypes, individually or in combinations.

14. In another embodiment, the devices of claims 2, 3, 10, 11, and 12 allow antibody epitope mapping.

15. In another embodiment, the devices of claims 2, 3, 10, 11, 12 and 13 are used to test for anti-drug antibodies prior to or during clinical (or preclinical) studies, and,

Wherein the device is used to test pre-existing ADAs and their indication of risk of adverse reactions resulting from treatment with a therapeutic drug or drug combination, or following gene therapy and/or

Wherein the device is used to gather data used to test associations between genetic components and ADA responses and/or

Wherein the device is used to test pre-existing antibodies and their indication of risk of developing neutralizing antibodies against therapeutic drugs or following gene therapy.

16. In another embodiment, the devices of claims 2 and 3 are used to monitor ADA after gene therapy.