Industrialization of Antibody-based Contraceptive MPTs

项目一：摘要 工业化项目的目的是制造一种基于抗体的产品，用于妇女 实现避孕。人类避孕抗体(HCA)将被制成阴道膜，用于-- 要求保护，并在阴道内环(IVR)进行长期保护。以抗体为基础的添加 避孕将是MB66(抗艾滋病毒/单纯疱疹病毒)更全面的未来版本的商业驱动力， 一种基于抗体的多用途预防技术(MPT)，目前处于第一阶段安全试验。 由于其效力、特异性和安全性，人类单抗(MAbs)处于领先地位。 产生高度具体但机械上多样化的避孕MPT的候选者。 避孕开发研究项目HCA的产业化进程正在变成一个实验室 将这一过程转化为一致的、具有良好特性的过程，从而能够批量生产高质量的产品。这个 成功的工业化所涉及的挑战是复杂的，尽管在科学界被高度低估 社区。幸运的是，制造单抗的平台已经取得了重大的技术进步 以及过去几十年的治疗进展。尽管每个平台可能会提供一些 制造优势，只有烟草和木霉可能能够解决未得到满足的需求 以抗体为基础的避孕药等对成本敏感的大型市场。近期推动经济增长的因素 产业化项目的速度、质量和研究成本有利于全装配的瞬时表达 植物中的抗体尼古丁，而长期推动大型、对成本敏感的市场的是快速周期 时间(几天到几周)、低商业制造成本(10美元/克DS)和大型商业规模(&gt；10 公吨的DS)有利于在真菌木霉中表达抗体。 项目一的具体目标是： 1.在烟草中制造GMP HCA药材(DS)和HCA膜(药品， Dp)，用于临床前和临床研究。 2.开展Hca膜的IND临床前研究。 3.研制可植入阴道环内的羟基喜树碱缓释胶囊。 4.木霉抗体基低成本规模化生产 避孕药MPT。

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.