Industrialization of Antibody-based Contraceptive MPTs

抗体避孕MPT产业化

基本信息

批准号：
9624284
负责人：
Kevin John Whaley
金额：
$ 133.85万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-14 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9624284
关键词：
Address Animals Antibodies Automobile Driving Bacteria Cells Clinical Clinical Research Communities Complex Contraceptive Agents Contraceptive methods Development Emerging Technologies Evaluation Film Future Generations Glycoproteins HIV Human Human Volunteers Immunoglobulin Fragments Immunoglobulins Industrialization Insecta Laboratories Leukocytes Methods Monoclonal Antibodies Mucous body substance Nicotiana Oryctolagus cuniculus Pharmaceutical Preparations Pharmacology Study Pharmacology and Toxicology Phase Plants Prevention Process Rattus Research Research Project Grants Safety Sexual Transmission Simplexvirus Specificity Speed Sperm Agglutination System Technology Therapeutic Time Transgenic Organisms Trichoderma Vagina Vaginal Ring Woman Yeasts base capsule cost fungus human monoclonal antibodies male novel pathogen pre-clinical research preclinical study programs reproductive tract research and development sperm cell vector

项目摘要

PROJECT ONE: ABSTRACT The purpose of the Industrialization Project is to manufacture an antibody-based product for use in women to achieve contraception. The Human Contraceptive Antibody (HCA) will be formulated in a vaginal film for on- demand protection, and in an intravaginal ring (IVR) for long-term protection. The addition of antibody-based contraception will be the commercial driver for a more comprehensive future version of MB66 (anti-HIV/HSV), an antibody-based multipurpose prevention technology (MPT) that is currently in a Phase 1 safety trial. Because of their potency, specificity, and safety profile, human monoclonal antibodies (mAbs) are leading candidates for the generation of highly specific, but mechanistically diverse, contraceptive MPTs. The industrialization process of HCA (a Contraception Development Research Project) is turning a laboratory process into a consistent and well-characterized process that can mass-produce a quality product. The challenges involved in successful industrialization are complex, though highly underestimated in the scientific community. Fortunately, manufacturing platforms for monoclonal antibodies have made significant technical and therapeutic advances over the last several decades. Although each platform may offer some manufacturing advantages, only Nicotiana and Trichoderma are likely to be able to address the unmet needs of large, cost-sensitive markets like antibody-based contraceptives. The near-term driving factors for the Industrialization Project are speed, quality and research costs favoring transient expression of fully assembled antibodies in the plant Nicotiana, while the long-term drivers for large, cost-sensitive markets are rapid cycle time (days to weeks), low commercial manufacturing cost (<$10/g of DS), and large commercial scale (>10 metric tons of DS) favoring antibody expression in the fungus Trichoderma. The Specific Aims of Project One are: 1. To manufacture GMP HCA drug substance (DS) in Nicotiana, and an HCA-film (drug product, DP) for preclinical and clinical studies. 2. To conduct IND-enabling preclinical studies of HCA film. 3. To develop sustained release capsules of HCA that can be incorporated in to intravaginal rings. 4. To industrialize low cost and large-scale Trichoderma manufacturing for an antibody-based Contraceptive MPT.

项目一：摘要工业化项目的目的是生产一种基于抗体的产品，用于女性实现避孕。人类避孕抗体（HCA）将在阴道膜中配制，用于需求保护，并在阴道内环（IVR）中进行长期保护。基于抗体的添加避孕将成为更全面的未来版本MB66（抗HIV/HSV）的商业驱动力，基于抗体的多用途预防技术（MPT）目前正在1阶段安全试验中。由于其效力，特异性和安全性，人类单克隆抗体（mAb）处于领先地位生成高度特定但机械多样性避孕的MPT的候选人。 HCA（避孕开发研究项目）的工业化过程正在转向实验室处理一个一致且良好的过程，可以大量生产优质的产品。这成功的工业化涉及的挑战很复杂，尽管在科学中被高估了社区。幸运的是，单克隆抗体的制造平台已成为重要的技术在过去的几十年中的治疗进展。尽管每个平台可能会提供一些制造优势，只有Nicotiana和Trichoderma可能能够满足未满足的需求大型，成本敏感的市场，例如基于抗体的避孕药。近期驱动因素工业化项目是速度，质量和研究成本，有利于瞬时组装的瞬时表达植物烟草中的抗体，而大型，成本敏感市场的长期驱动因素是快速周期时间（天到几周），低商业制造成本（<$ 10/g ds）和大型商业规模（> 10 ds的公制ds）有利于真菌trichoderma中的抗体表达。项目第一的具体目的是： 1。在烟草中生产GMP HCA药物（DS）和HCA-FILM（药物， DP）用于临床前和临床研究。 2。进行HCA膜的临床前研究。 3。为了开发可将HCA的持续释放胶囊掺入到阴道内环中。 4。为基于抗体的低成本和大规模的毛d虫制造工业化避孕MPT。