Homogeneous assay for monoclonal antibody detection in serum

描述（由申请人提供）：本申请的长期目标是开发一种设备，用于提供患者血清中抗体药物状态的快速床旁分析。抗体广泛用于各种应用中，作为治疗剂和生物测定中的试剂。检测和定量抗体的能力是其许多应用中的关键方面。在需要确定诊断和/或预后因素的医学应用中，检测生物样品中的抗体和其他蛋白质治疗剂是至关重要的。然而，确定特定抗体的药代动力学可能是有问题的，特别是当针对高背景进行检测时，如在生物样品中。有两个关键应用。(1)抗体药物的给药时间表和给药途径在开发时具有许多不确定性，并且通常通过临床前和临床研究进行改进，其中迫切需要简单和可靠的药代动力学测定。给定抗体靶标的特定生物学也可导致常规剂量递增范例的额外并发症。(2)如果可以基于每次注射后在患者血清中检测到的抗体水平来调整每个患者的剂量，则抗体癌症药物将更经济和更安全，因为在传统的剂量方案中没有捕获患者代谢和肿瘤负荷的巨大可变性。已经开发了一种增强的检测系统，其可以快速确定血液样品中存在的抗体药物的浓度。本研究将专注于该技术的开发，以进一步提高检测的可靠性和灵敏度。Alemtuzumab（抗CD52）将用作试验优化的开发模型。它目前常用于慢性淋巴细胞白血病（CLL）患者。研究将包括三个阶段。1)一级均相抗体检测方法的建立。2)一种新的高灵敏度检测增强技术的发展。3)测定试剂盒的确定和实施，以允许护理点检测和分析。

DESCRIPTION (provided by applicant): The long term goal of this application is to develop a device to provide rapid point of care analysis of the state of antibodies drugs within patient serum. Antibodies are widely used in a variety of applications, as therapeutic agents and reagents in biological assays. The ability to detect and quantify antibodies is a key aspect in many of their applications. Detection of antibodies and other protein therapeutics in a biological sample is critical in medical applications requiring determination of diagnostic and/or prognostic factors. However, determining the pharmacokinetics of a particular antibody can be problematic, especially when the detection is performed against a high background, as in a biological sample. There are two key applications. (1) Dosing schedules and routes of administration for antibody drugs are developed with many uncertainties and are often refined through pre-clinical and clinical studies where the need for simple and reliable pharmacokinetic assays is acute. The specific biology of a given antibody target can also lead to additional complications from the conventional dose escalation paradigm. (2) Antibody cancer drugs would be more economical and safer if the dose for each patient could be adjusted based on the antibody levels detected in the serum of the patient after each injection since the great variability in patient metabolism and tumor load is not captured in traditional dosage schemes. An enhanced detection system has been developed that can rapidly determine the concentration of antibody drugs present from blood samples. This research will focus on the development of this technology to further improve the assay in terms of reliability and sensitivity. Alemtuzumab (anti-CD52) will be used as a development model for assay refinement. It is currently used commonly in patients with chronic lymphocytic leukemia (CLL). The research will consist of three phases. 1) Development of a first order homogeneous assay for measurement of antibody. 2) Development of a novel enhancement technique for high sensitivity detection. 3) Determination and implementation of an assay kit to allow for point of care detection and analysis.