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

项目总结/摘要 该项目的目标是开发一种多路复用快速床旁诊断（“一次性设备”）， 检测针对被批准用于治疗以下疾病的治疗性单克隆抗体（“mAb”）的抗体（“Ab”） 风湿性关节炎（RA）。患者通常会产生抗mAb Ab，这可能会废除治疗性mAb 有效性和/或引起不良事件。我们设计了一种独特的使用嵌合蛋白作为捕获试剂 在多路复用一次性装置中，其在抗mAb抗体筛选期间消除非特异性信号，以及 允许直接比较它们的免疫原性和风险评估。科学方法描述于 授予ConquerAb Inc.的美国专利一次性装置允许在更短的时间内进行Ab同种型检测。 从一滴血开始超过15分钟，并且可以在下一次药物输注之前使用（通过mAb 浓度）用于检测游离抗mAb Ab，提示选择剂量或替代治疗。在 此外，这种一次性设备将协调Ab检测，允许整合在 不同的护理点设施（大数据）。用于抗mAb检测的现有测定法，例如酶联免疫吸附测定法（ELISA）。 免疫吸附测定（ELISA）需要制备血清或血浆、样品处理、多个步骤 受过训练的操作员可能需要几天才能提供结果，并且更容易出错。此外，其中一些 测定可以使用酸解离步骤，不幸的是，这可能使Ab变性。另一个问题是 样品采集时间可能不同，导致样品中的mAb浓度不同， 与抗mAb Ab，导致不能有效整合的不一致结果。在第一阶段，我们 建议采用专有技术开发用于检测抗mAb Ab的多重诊断。 该试纸还将被纳入一个专利的自含式一次性设备，并在临床试验中进行测试。 匿名RA患者的研究。这是一种创新的战略，可以在检测， 比较和减轻基于蛋白质的疗法的不需要的免疫原性，以及 精准医疗的大数据

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.