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

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）是最成功的一类药物，已证明具有以下能力： 满足各种人类健康需求，从肿瘤学，炎症性疾病， 疾病最近的研究表明，单克隆抗体对最致命的感染有效 包括尼帕、亨德拉、埃博拉、马尔堡和拉萨。从人类幸存者身上分离出的抗体， Prometheus CETR的焦点，具有成为成功主机组件的优势 对病原体的反应此外，这些mAb被人免疫系统阳性选择。 对目标病原体的反应。因此，这些存活mAb将有增加的机会， 与从其他平台产生的mAb相比是安全和有效的。MAb还提供 基于作用机制的重要性的惊人的定制程度。不同的阶级， 亚型、点突变和N-糖基化状态可显著影响免疫调节剂的效力。 预防性或治疗性mAb候选物。生产平台、配制方法和 单克隆抗体的安全性特征已得到充分证实。因此，单克隆抗体提供了一个低风险的技术平台， A类威胁的药物和治疗药物（即对 国家安全和公共卫生）将由Prometheus CETR解决。核心B，结合 与研究项目III，还将评估使用DNA编码的单克隆抗体（DMAbs），一个潜在的 这是一项革命性的技术，可以将患者自己的肌肉细胞转化为mAb生产者。 工业化核心（核心B）的重点是确保CETR的向下选择过程 结果表明：1.可制造的mAb; 2.符合目标产品概况（TPP）的产品; 3.数据 适用于并支持向监管机构提交的器械和材料（如细胞库） 美国食品和药物管理局（FDA）将产品过渡到高级开发阶段。的 产业化核心有两个目的：1）为研究项目提供产品开发经验 和核心，以确保研究符合行业和监管预期，以及2） 将产品过渡到高级开发阶段。