Anthrax Immune Globulin to Prevent & Treat Anthrax: Advanced Product Development

描述（由申请方提供）：虽然抗菌剂对炭疽感染的早期阶段有效，但延迟开始抗菌剂治疗或感染抗生素耐药菌株可产生危及生命的毒血症，抗菌剂对此无效。在这种情况下，需要中和毒素，因为抗菌剂杀死营养细胞，对毒素没有影响。B的多克隆抗体。炭疽外毒素有可能立即中和毒素，提供一种拯救生命的医疗对策，并填补了一个重要的未得到满足的需求。已在动物研究中证明了已获许可的疫苗BioThrax（r）或其主要蛋白质成分保护性抗原（PA）的抗体预防和治疗吸入性炭疽的有效性。此外，人免疫球蛋白在治疗感染性疾病，特别是细菌毒血症方面具有长期的安全性和成功历史。本文提出的是静脉注射用炭疽免疫球蛋白（AIGIV）的高级开发。AIGIV来源于BioThrax免疫供体的源血浆，并使用FDA批准的免疫球蛋白纯化工艺生产。与其他高风险的未经证实的技术相比，使用经证实的技术和许可的生产工艺为开发有效的可许可抗毒素提供了低风险方法。EIS通过其姊妹公司BioPort获得了唯一获得FDA批准的炭疽疫苗，因此处于独特的地位，能够生产长期生产AIGIV所需的BioThrax源血浆。AIGIV高级开发计划允许在2006年12月之前发布cGMP AIGIV批次，这可以使AIGIV剂量在授予后18个月内可用于紧急使用授权。该产品适用于治疗由对抗生素敏感或耐药的B引起的吸入性炭疽。炭疽病在18-65岁的人。对于有接触或已经接触过耐药或敏感的B的风险的个人，将寻求预防吸入性炭疽的额外适应症。炭疽病（接触前和接触后预防）。AIGIV高级开发的具体目的是：1）使用cGMP AIGIV在兔和恒河猴模型中进行药代动力学和耐受性研究以及关键动物规则有效性研究，以及2）开发和验证抗PA IgG和TNA测定，以支持生产和测量动物血清中的AIGIV活性。AIGIV的初始cGMP批次将用于动物规则研究，以确定针对雾化B提供预防和治疗保护的剂量。炭疽孢子攻击。

DESCRIPTION (provided by applicant): While antimicrobials are effective against the early stages of anthrax infection, delayed initiation of antimicrobial therapy or infection with an antibiotic resistant strain can produce a life-threatening toxemic state for which antimicrobials are not effective. In such cases, neutralization of the toxin is required because antimicrobials kill vegetative cells and have no effect on the toxin. Polyclonal antibodies to the B. anthracis exotoxin have the potential to immediately neutralize the toxin, providing a life-saving medical countermeasure and filling an important unmet need. The effectiveness of antibodies to the licensed vaccine BioThrax(r) or its major protein component, protective antigen (PA), to prevent and treat inhalational anthrax has been demonstrated in animal studies. In addition, human immune globulins have a long history of safety and success in treating infectious disease, and in particular, bacterial toxemia. Proposed herein is the advanced development of anthrax immune globulin for intravenous use (AIGIV). AIGIV is derived from Source Plasma from BioThrax-immunized donors and is produced using an FDA-approved immune globulin purification process. The use of a proven technology and a licensed manufacturing process provides a low- risk approach for the development of an effective, licensable antitoxin compared to other high-risk unproven technologies. EIS, through its sister company BioPort, has access to the only FDA-approved anthrax vaccine, and thus is in the unique position to generate the quantities of BioThrax Source Plasma necessary to produce AIGIV on a long-term basis. The AIGIV advanced development plan allows for release of a cGMP AIGIV lot by December 2006, which could make AIGIV doses available for use under Emergency Use Authorization within 18 months of award. The product would be indicated for treatment of inhalational anthrax due to antibiotic-susceptible or antibiotic-resistant B. anthracis in persons 18-65 years of age. An additional indication will be sought for the prophylaxis of inhalational anthrax for individuals at risk for having contact with, or who have contacted, either antibiotic-resistant or antibiotic-susceptible B. anthracis (pre-exposure and post-exposure prophylaxis). The Specific Aims for advanced development of AIGIV are to: 1) Conduct pharmacokinetic and tolerability studies, and pivotal Animal Rule efficacy studies in the rabbit and rhesus macaque models using cGMP AIGIV, and 2) Develop and validate anti-PA IgG and TNA assays to support manufacturing and for the measurement of AIGIV activity in animal sera. The initial cGMP lot of AIGIV will be used for Animal Rule studies to define the dose which provides prophylactic and therapeutic protection against aerosolized B. anthracis spore challenge.