DISPOSABLE DEVICE FOR RAPID POINT-OF-CARE DETECTION AND COMPARISON OF ANTIBODY RESPONSES AGAINST THERAPEUTIC PROTEINS IN RHEUMATOID ARTHRITIS PATIENTS

用于快速护理点检测和比较类风湿性关节炎患者治疗性蛋白抗体反应的一次性装置

• 批准号: 10545283
• 负责人: Maria D. F. S. Barbosa
• 金额: $ 25.9万
• 依托单位: CONQUERAB, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10545283
• 关键词: Acids; Adverse event; Antibodies; Antibody Response; Big Data; Binding; Biological Assay; Blinded; Blood; Blood specimen; Buffers; Cellular Phone; Chimeric Proteins; Clinical; Clinical Research; Collaborations; Complex; Custom; Data; Databases; Detection; Development; Device Designs; Devices; Dissociation; Dose; Drops; Enzyme-Linked Immunosorbent Assay; Fingers; Florida; Goals; Grant; Health care facility; Hour; Human; Immunoassay; Immunoglobulin G; Infusion procedures; Legal patent; Monoclonal Antibodies; Morphology; Patients; Pharmaceutical Preparations; Phase; Plasma; Preparation; Protein Engineering; Proteins; Quality Control; Rapid diagnostics; Rapid screening; Reagent; Reflux; Reproducibility; Rheumatoid Arthritis; Risk Assessment; Safety; Sales; Sampling; Serum; Signal Transduction; Source; Specificity; Speed; Step training; System; T-Lymphocyte Epitopes; Technology; Testing; Therapeutic; Therapeutic Monoclonal Antibodies; Time; Training; Universities; Work; adalimumab; alternative treatment; anti-IgG; antibody detection; antibody test; base; cross reactivity; design; genetic association; human monoclonal antibodies; immunogenicity; in vitro testing; in-vitro diagnostics; infliximab; innovation; interest; multiplex diagnostics; point of care; point-of-care detection; point-of-care diagnostics; pre-clinical; precision medicine; rheumatologist; sample collection; screening; test strip; therapeutic protein

PROJECT SUMMARY/ABSTRACT The goal of this project is to develop a multiplexed rapid point-of-care diagnostic (“disposable device”) to detect antibodies (“Abs”) against therapeutic monoclonal antibodies (“mAbs”) approved for the treatment of Rheumatoid Arthritis (RA). Patients often develop anti-mAb Abs, which may abrogate the therapeutic mAb efficacy and/or cause adverse events. We have devised a unique use of chimeric proteins as capture reagents in multiplexed disposable devices, which eliminate nonspecific signal during anti-mAb Ab screening, and allows direct comparison of their immunogenicity and risk assessment. The scientific approach is described in granted U.S. patents assigned to ConquerAb Inc. The disposable device allows Ab isotype detection in less than 15 minutes from one drop of blood, and can be used before the next drug infusion (trough mAb concentration) for detection of free anti-mAb Abs, suggesting selection of dose or an alternative treatment. In addition, this disposable device will harmonize Ab detection, allowing integration of patient data generated at different point-of-care facilities (big data). Existing assays for anti-mAb detection, such as enzyme-linked immunosorbent assay (ELISA) require preparation of serum or plasma, sample handling, multiple steps, trained operators, may take days to provide results, and are more prone to errors. In addition, some of those assays may use an acid dissociation step, which unfortunately may denature Abs. Another problem is that the time of sample collection can vary, resulting in samples that have different concentrations of mAbs in complex with anti-mAb Abs, leading to inconsistent results that cannot be validly integrated. For this Phase 1 we propose development of a multiplexed diagnostic for detection of anti-mAb Abs with a proprietary technology. The test strip will also be incorporated into a patented self-contained disposable device, and tested in a clinical study with anonymized RA patients. This is an innovative strategy that can have a major impact in detecting, comparing and mitigating unwanted immunogenicity of protein-based therapies, and also in the utilization of big data for precision medicine.

项目概要/摘要 该项目的目标是开发一种多重快速护理点诊断（“一次性设备”），以 检测针对已批准用于治疗的治疗性单克隆抗体（“mAb”）的抗体（“Abs”） 类风湿性关节炎 (RA) 患者经常会产生抗单克隆抗体，这可能会导致治疗性单克隆抗体失效。 我们设计了嵌合蛋白作为捕获试剂的独特用途。 在多重一次性设备中，消除抗 mAb 抗体筛选过程中的非特异性信号，以及 允许直接比较它们的免疫原性和风险评估，其科学方法描述于。 授予 ConquerAb Inc. 的美国专利。该一次性设备可在更短的时间内检测 Ab 同型 一滴血不到 15 分钟，可在下次药物输注前使用（通过 mAb 浓度）用于检测游离抗单克隆抗体，建议选择剂量或替代治疗。 此外，这种一次性设备将协调抗体检测，允许整合在 不同的护理点设施（大数据）。 免疫吸附测定 (ELISA) 需要制备血清或血浆、样品处理、多个步骤、 训练有素，可能需要几天的时间才能提供结果，并且更容易出现错误。 测定可能会使用酸解离步骤，不幸的是，这可能会使抗体变性。 样品采集时间可能会有所不同，导致样品在复合物中具有不同浓度的 mAb 与抗 mAb 抗体一起使用，导致结果不一致，无法有效整合到第一阶段。 建议开发一种多重诊断方法，利用专有技术检测抗单克隆抗体。 该测试条还将被纳入获得专利的独立一次性设备中，并在临床中进行测试 对匿名 RA 患者进行的研究是一项创新策略，可以对检测、 比较和减轻基于蛋白质的疗法的不需要的免疫原性，以及利用 精准医疗大数据。