Development of Plant Derived Antibodies for Drugs Abuse

描述（由申请人提供）： 该联合I期/II期STTR项目的目标是检验抗药单克隆抗体是与苯环利定（PCP）滥用相关的医疗问题的安全有效疗法的假设。目前没有治疗急性或慢性五氯苯酚滥用引起的医疗问题的特效药。因此，迫切需要可以预防或最大限度地减少PCP影响的长效药物，以及对患者日常依从性的需求。我们假设，基于抗体的药物（在本STTR的I期开发和生产），其极其有利的药代动力学特性和独特的作用机制，可能会提供新的希望，作为一种创新和新颖的药物治疗PCP滥用。该项目设计的药物是一种植物产生的嵌合单克隆抗体，它是由抗PCP小鼠单克隆抗体的抗原结合可变区和人IgG 2抗体的恒定区改造而成。这种名为ch-mAb 6 B5的新药将结合小鼠抗PCP单克隆抗体的有效性和人类单克隆抗体的安全性。该STTR的I期应用集中于使用烟草植物在重组的、基于植物的表达和制造系统中表达该抗体。该系统已经成功地将产品交付给临床进行人体测试，并且已经存在强大的商业化制造系统。通过在表达和制造中使用这种新的范例，该STTR的目标是为药物滥用治疗提供安全、有效和具有成本效益的疗法。需要这种组合的表达、制造和临床努力来确认这种方法的实用性。由于药物滥用的增加，对保健的长期影响可能非常大，并将成为公共负担。在这一领域很少有治疗方法，这些类型的行业/学术联盟是必要的，以使这些治疗方法向前发展。 这个第二阶段STTR项目的目标是测试的假设，即抗药物单克隆抗体是一种安全有效的治疗与苯环己哌啶（PCP）滥用相关的医疗问题。目前没有治疗急性或慢性五氯苯酚滥用引起的医疗问题的特效药。因此，迫切需要可以预防或最大限度地减少PCP影响的长效药物，以及对患者日常依从性的需求。我们假设，基于抗体的药物（在本STTR的I期开发和生产），其极其有利的药代动力学特性和独特的作用机制，可能会提供新的希望，作为一种创新和新颖的药物治疗PCP滥用。该项目设计的药物是一种植物产生的嵌合单克隆抗体，它是由抗PCP小鼠单克隆抗体的抗原结合可变区和人IgG 2抗体的恒定区改造而成。这种名为ch-mAb 6 B5的新药将结合小鼠抗PCP单克隆抗体的有效性和人类单克隆抗体的安全性。在第二阶段STTR项目期间，ch-mAb 6 B5将在人体临床试验中进行测试，以确定它在治疗PCP滥用方面是否安全有效。在这些研究中，将使用志愿者PCP滥用者中的安全性和药代动力学测量来确定ch-mAb 6 B5的安全性特征、给药策略和生物剂量。然后将在一组因PCP滥用而接受门诊认知行为治疗的类似患者中确定chmAb 6 B5的疗效和作用持续时间。从这些I期和II期临床试验中获得的客观知识将用于确定药物的安全性和临床情况（例如，慢性PCP滥用），其中药物可能是有效和有益的。

DESCRIPTION (provided by applicant): The goal of this combination Phase I / Phase II STTR project is to test the hypothesis that anti-drug monoclonal antibodies are a safe and effective therapy for the medical problems associated with phencyclidine (PCP) abuse. There are currently no specific medications for treating the medical problems caused by acute or chronic PCP abuse. Thus, long-lasting medications that could prevent or minimize PCP effects, and the need for day-to-day patient compliance are sorely needed. We hypothesize that antibody-based medications (developed and produced in Phase I of this STTR), with their extremely favorable pharmacokinetic properties and unique mechanisms of action might provide new hope as an innovative and novel medication for treating PCP abuse. The medication designed for this project is a chimeric monoclonal antibody produced in plants, which was engineered from the antigen binding variable regions of an anti-PCP mouse monoclonal antibody and the constant regions of a human IgG2 antibody. This new medication, called ch-mAb6B5, will have a combination of the proven effectiveness of the mouse anti-PCP monoclonal antibody combined with the safety of a human monoclonal antibody. The Phase I application of this STTR focuses on the expression of this antibody in a recombinant, plant based expression and manufacturing system using tobacco plants. This system has already successfully delivered products to the clinic for human testing and a strong commercialized manufacturing system already exists. By using this new paradigm in expression and manufacturing, the goal of this STTR is to provide safe, efficacious and cost effective therapies for drug abuse treatment. This combined expression, manufacturing and clinical effort is needed to confirm the utility of this approach. The potential for long term impact on health care due to increase in drug abuse could be very large and will be a public burden. Very few therapies are available in this area and these types of industry/academic consortia are necessary to bring these treatments forward. The goal of this Phase II STTR project is to test the hypothesis that anti-drug monoclonal antibodies are a safe and effective therapy for the medical problems associated with phencyclidine (PCP) abuse. There are currently no specific medications for treating the medical problems caused by acute or chronic PCP abuse. Thus, long-lasting medications that could prevent or minimize PCP effects, and the need for day-to-day patient compliance are sorely needed. We hypothesize that antibody-based medications (developed and produced in Phase I of this STTR), with their extremely favorable pharmacokinetic properties and unique mechanisms of action might provide new hope as an innovative and novel medication for treating PCP abuse. The medication designed for this project is a chimeric monoclonal antibody produced in plants, which was engineered from the antigen binding variable regions of an anti-PCP mouse monoclonal antibody and the constant regions of a human IgG2 antibody. This new medication, called ch-mAb6B5, will have a combination of the proven effectiveness of the mouse anti-PCP monoclonal antibody combined with the safety of a human monoclonal antibody. During this Phase II STTR project, ch-mAb6B5 will be tested in human clinical trials to determine if it is safe and effective in the treatment of PCP abuse. In these studies, safety and pharmacokinetic measurements in volunteer human PCP abusers will be used to determine the safety profile, dosing strategy, and biological dose of ch-mAb6B5. The efficacy and duration of action of chmAb6B5 will then be determined in a similar group of patients undergoing outpatient cognitive-behavioral therapy for their PCP abuse. The objective knowledge gained from these Phase I and II clinical trials will be used to determine safety of the medications and the clinical scenarios (e.g., chronic PCP abuse) in which the medications could be efficacious and beneficial.