Core B: Industrialization Core

核心B：工业化核心

• 批准号: 10088388
• 负责人: Kartik Chandran
• 金额: $ 10.18万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-14 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10088388
• 关键词: Address; Advanced Development; Antibodies; Antibody Therapy; Categories; Category A pathogen; Cells; Communicable Diseases; Crimean-Congo Hemorrhagic Fever Virus; Custom; DNA; Data Set; Development; Disease; Ebola; Ebola virus; Ensure; Formulation; Genes; Goals; Government; Hantavirus; Health; Hendra Virus; Human; Immune response; Industrialization; Industry; Infection; Inflammatory; Investigational New Drug Application; Laboratory Procedures; Lassa virus; Lebanon; Marburgvirus; Methods; Monitor; Monoclonal Antibodies; Muscle Cells; National Security; Nipah Virus; Oncology; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Point Mutation; Process; Public Health; Recombinants; Research Project Grants; Resources; Risk; Safety; Survivors; Technology; Testing; Therapeutic; Therapeutic Monoclonal Antibodies; Toxicology; United States Food and Drug Administration; Vaccines; Viral; Virulent; Virus; animal efficacy; base; cell bank; clinical development; cross reactivity; efficacy study; expectation; experience; glycosylation; high risk; human tissue; lead candidate; manufacturability; member; monoclonal antibody production; neglect; pathogen; priority pathogen; product development; prophylactic; screening; Address; Advanced Development; Antibodies; Antibody Therapy; Categories; Category A pathogen; Cells; Communicable Diseases; Crimean-Congo Hemorrhagic Fever Virus; Custom; DNA; Data Set; Development; Disease; Ebola; Ebola virus; Ensure; Formulation; Genes; Goals; Government; Hantavirus; Health; Hendra Virus; Human; Immune response; Industrialization; Industry; Infection; Inflammatory; Investigational New Drug Application; Laboratory Procedures; Lassa virus; Lebanon; Marburgvirus; Methods; Monitor; Monoclonal Antibodies; Muscle Cells; National Security; Nipah Virus; Oncology; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Point Mutation; Process; Public Health; Recombinants; Research Project Grants; Resources; Risk; Safety; Survivors; Technology; Testing; Therapeutic; Therapeutic Monoclonal Antibodies; Toxicology; United States Food and Drug Administration; Vaccines; Viral; Virulent; Virus; animal efficacy; base; cell bank; clinical development; cross reactivity; efficacy study; expectation; experience; glycosylation; high risk; human tissue; lead candidate; manufacturability; member; monoclonal antibody production; neglect; pathogen; priority pathogen; product development; prophylactic; screening

ABSTRACT: CORE B Monoclonal antibodies (mAbs) are one of the most successful classes of drugs with the proven ability to address a variety of human health needs ranging from oncology, inflammatory diseases, and infectious diseases. Recent studies have demonstrated efficacy of mAbs against the most virulent infections including Nipah, Hendra, Ebola, Marburg and Lassa. Antibodies isolated from human survivors, the focus of the Prometheus CETR, have the advantage of having been a component of a successful host response to a pathogen. Further, these mAbs were positively selected for by the human immune response to the target pathogen. Therefore, these survivor mAbs will have an increased chance of being safe and efficacious compared to mAbs generated from other platforms. MAbs also offer a stunning degree of customization based on the importance of mechanisms of action. Different classes, sub-types, point mutations and N-glycosylation states can dramatically impact the potency of a prophylactic or therapeutic mAb candidate. The manufacturing platforms, formulation methods, and safety profiles of mAbs are well-established. Thus, mAbs offer a low-risk technology platform for prophylactics and therapeutics for the Category A threats (i.e. agents that pose the highest risk to national security and public health) to be addressed by the Prometheus CETR. Core B, in conjunction with Research Project III, will also evaluate the use of DNA-encoded mAbs (DMAbs), a potentially transformative technology that turns the patient’s own muscle cells into mAb producers. The Industrialization Core (Core B) is focused on ensuring the down-selection process of the CETR results in: 1. Manufacturable mAbs; 2. A product that satisfies the Target Product Profile (TPP); 3. Data sets and materials (e.g. cell banks) that are appropriate and supportive of regulatory filings with the Food and Drug Administration (FDA) to transition the products into advanced development. The Industrialization Core has two Aims: 1) Provide product development experience to Research Projects and the Cores to assure studies are compatible with industry and regulatory expectations, and 2) Transition products to advanced development.

摘要：核心b 单克隆抗体（mAb）是最成功的类药物之一，具有证明的能力 满足各种人类健康需求，从肿瘤学，炎症性疾病和感染性不等 疾病。最近的研究表明，mAb对最有毒的感染的效率 包括Nipah，Hendra，Ebola，Marburg和Lassa。从人类生存中分离出的抗体， Prometheus cetr的重点，具有成为成功宿主的组成部分的优势 对病原体的反应。此外，这些mAb被人类免疫积极选择 对目标病原体的反应。因此，这些表面mabs将有更多的机会 与其他平台产生的mAB相比，安全有效。 mabs也提供 基于行动机制的重要性的惊人定制程度。不同的类， 亚类型，点突变和N-糖基化态可以极大地影响A的效力 预防性或治疗性mAb候选者。制造平台，制定方法和 mab的安全性概况已建立。那就是，mabs为低风险的技术平台 对A类威胁的预防和治疗 国家安全和公共卫生）将由Prometheus Cetr解决。核心，结合 通过研究项目III，还将评估DNA编码mABS（DMAB）的使用，这是一种潜在的 将患者自己的肌肉细胞变成mAb生产者的变革性技术。 工业化核心（核心B）的重点是确保CERTER的下调过程 结果：1。可制造的mab； 2。满足目标产品概况（TPP）的产品； 3。数据 适当且支持监管文件的套装和材料（例如细胞库） 食品和药物管理局（FDA）将产品转换为先进的开发。这 工业化核心有两个目标：1）为研究项目提供产品开发经验 并且要确保研究的核心与行业和监管期望兼容，以及2） 过渡产品向高级开发。