Industrialization of Antibody-based Contraceptive MPTs

项目一：摘要 工业化项目的目的是生产一种用于妇女的抗体产品， 实现避孕。人类避孕抗体（HCA）将配制在阴道膜中， 需要保护，并在阴道环（IVR）的长期保护。添加基于抗体的 避孕将是MB 66（抗HIV/HSV）更全面的未来版本的商业驱动力， 这是一种基于抗体的多用途预防技术（MPT），目前正在进行1期安全性试验。 由于其效力、特异性和安全性，人单克隆抗体（mAb）在免疫治疗中处于领先地位。 产生高度特异性但机制多样的避孕MPT的候选者。 HCA（避孕发展研究项目）的产业化进程正在将一个实验室 将工艺转化为一个一致的、具有良好特征的工艺，可以大规模生产优质产品。的 成功的工业化所面临的挑战是复杂的，尽管科学界对这些挑战的估计被高度低估。 社区幸运的是，单克隆抗体的制造平台已经取得了重大的技术进步。 和治疗上的进步。虽然每个平台都可能提供一些 由于烟草的生产优势，只有烟草和木霉可能能够满足未满足的需求 对成本敏感的大型市场，如抗体避孕药。短期驱动因素 产业化项目的速度，质量和研究成本有利于完全组装的瞬态表达 烟草中的抗体，而大型，成本敏感型市场的长期驱动因素是快速循环 时间（数天至数周）、低商业生产成本（<$10/g DS）和大商业规模（>10 公吨DS），有利于真菌木霉中的抗体表达。 项目一的具体目标是： 1.在Nicotiana中生产GMP HCA原料药（DS）和HCA薄膜（制剂， DP）用于临床前和临床研究。 2.开展HCA薄膜的IND临床前研究。 3.目的：研制可用于阴道环内的HCA缓释胶囊。 4.为了实现低成本和大规模的木霉生产的工业化， 避孕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.