MR191_ An Immunoprotectant for Marburg Virus

MR191_马尔堡病毒免疫保护剂

• 批准号: 9478966
• 负责人: Ronald T Aimes
• 金额: $ 100万
• 依托单位: MAPP BIOPHARMACEUTICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9478966
• 关键词: Acute; Address; Aerosols; Africa; Animal Model; Animals; Anthrax disease; Antibodies; Antibody Therapy; Binding; Biological Products; Bioreactors; Bioterrorism; Categories; Cell Line; Cells; Centers for Disease Control and Prevention (U.S.); Chemicals; Chinese Hamster Ovary Cell; Clinical Research; Collaborations; Dangerousness; Data; Development; Disease; Disease Outbreaks; Dose; Ebola virus; Emerging Communicable Diseases; Event; Family; Filovirus; Frankfurt-Marburg Syndrome Virus; Grant; Health Personnel; Iatrogenesis; In Vitro; Industry Standard; Infection; Infection prevention; Infectious Agent; Inhalation; Investigational New Drug Application; Laboratories; Lethal Dose 50; Medical; Modeling; Monoclonal Antibodies; Passive Immunization; Passive Transfer of Immunity; Pharmaceutical Preparations; Phase; Positioning Attribute; Production; Prophylactic treatment; Research; Safety; Security; Small Business Innovation Research Grant; Survivors; Technology; Testing; Texas; Therapeutic; Therapeutic Intervention; Tissues; Toxic effect; Toxicology; Treatment Efficacy; United States; United States Food and Drug Administration; Universities; Vaccines; Viral Hemorrhagic Fevers; Virus; Virus Diseases; base; cell bank; cross reactivity; drug candidate; experimental study; first-in-human; human monoclonal antibodies; in vivo evaluation; lead candidate; man; member; mortality; nonhuman primate; prevent; programs; response; therapeutic candidate; weapons

PROJECT SUMMARY Mapp Biopharmaceutical, Inc. (Mapp) is developing antibody-based therapeutics to treat a number of infectious agents, including some of the most dangerous known to man: the filoviruses. Marburg virus is a filovirus endemic to Africa and causes an often lethal hemorrhagic fever. Presently there are no approved vaccines or therapeutics to treat Marburg virus infections and this remains a major unmet medical need. Along with its collaborators, Mapp has screened over 100 antibodies from a number of different species that bind to or neutralize Marburg virus in vitro. Several of these have been shown to block the infection of cells and a few have shown potency when tested in animal models of Marburg. Recently, several fully-human monoclonal antibodies have been identified and recovered from a Marburg virus infection survivor. MR191, the lead candidate and the focus of this proposal, has been shown to completely protect non-human primates when challenged with a lethal dose of Marburg virus or the related Ravn virus. Mapp proposes to develop MR191 as a therapeutic candidate to treat Marburg and Ravn virus infections. A Chinese Hamster Ovary (CHO) cell line to produce MR191 will be created, characterized, and cell banks will be generated. This cell line will support production of MR191 at a research scale that will be tested in a non-human primate model of Marburg virus infection to determine the therapeutic window (i.e., how late after infection can MR191 be administered and still result in 100% efficacy) as well as dose determination studies (i.e., what is the lowest dose that gives 100% efficacy). Additionally, the toxicity of MR191 will be evaluated in non-human primates and the data will enable the submission of a New Investigational Drug Application (IND) to the U.S. Food and Drug Administration. Upon completion of the scope of this project, Mapp will be positioned to produce MR191 in compliance with current Good Manufacturing Practices (cGMPs) in advance of submitting the IND. This will enable the conduct of the first-in-human studies for this important filovirus MCM.

项目概要 Mapp Biopharmaceutical, Inc. (Mapp) 正在开发基于抗体的疗法来治疗多种感染性疾病 病原体，包括一些人类已知的最危险的病毒：丝状病毒。马尔堡病毒是一种丝状病毒 非洲流行并引起致命的出血热。目前还没有批准的疫苗或 治疗马尔堡病毒感染的疗法，这仍然是一个未满足的重大医疗需求。 Mapp 与其合作者一起筛选了来自许多不同物种的 100 多种抗体，这些抗体结合 体外中和马尔堡病毒。其中一些已被证明可以阻止细胞的感染和 在马尔堡病毒动物模型中进行测试时，很少有药物显示出效力。最近，几个全人单克隆 已从马尔堡病毒感染幸存者身上鉴定并回收了抗体。 MR191，领先 候选者和该提案的重点，已被证明可以完全保护非人类灵长类动物 受到致命剂量的马尔堡病毒或相关拉文病毒的攻击。 Mapp 提议开发 MR191 作为治疗马尔堡病毒和 Ravn 病毒感染的候选药物。一个 将创建、鉴定产生 MR191 的中国仓鼠卵巢 (CHO) 细胞系，并建立细胞库 生成的。该细胞系将支持 MR191 的研究规模生产，并将在非人类身上进行测试 马尔堡病毒感染的灵长类动物模型以确定治疗窗口（即感染后多晚可以 MR191 的施用仍然具有 100% 的功效）以及剂量确定研究（即，什么是 达到 100% 疗效的最低剂量）。此外，MR191的毒性将在非人类身上进行评估 灵长类动物和数据将有助于向美国提交新的研究药物申请（IND） 食品和药物管理局。 该项目范围完成后，Mapp 将按照以下标准生产 MR191： 在提交 IND 之前遵守当前的良好生产规范 (cGMP)。这将使行为 这种重要的丝状病毒 MCM 的首次人体研究。