Antibody-based Contraceptive MPTs: Preclinical and Clinical Research

CRC概述：摘要 我们建议建立一个避孕研究中心(CRC)，以开发一种基于 一种有效的抗精子单抗(MAb)的局部应用。我们计划制造第一个 由HCA人单抗组成的新一代HCA避孕产品，按GMP标准在 创新的高性价比单抗平台(尼古丁)，并配制成一种薄膜，与 阴道粘膜提供短期(按需)避孕。Hca膜将在体外进行疗效测试。 和安全性，将进行IND使能研究，并在向FDA提交IND申请后，HCA膜 将在两个第一阶段临床试验中进行安全性和有效性测试。一个原型的HCA-阴道内环(IVR)将 还应以提供长期(30天)避孕保护为目标进行开发。HCA-IVR将 在体外和非人灵长类动物(NHP)模型中进行PK/PD抗体的初步评估 分配和安全。该计划还将生产和测试具有潜在增强作用的HCA多价变体 用于第二代HCA避孕产品的精子捕获能力。在未来，HCA可以 在电影或IVR中单独用于避孕，或与单抗或其他杀微生物剂联合使用 针对STI病原体，提高多用途疫苗的可接受性、有效性和市场性 预防技术(MPT)产品。

CRC OVERVIEW: ABSTRACT We propose to establish a Contraceptive Research Center (CRC) to develop a new contraception method based on the topical use of a potent antisperm monoclonal antibody (mAb). We propose to manufacture a first generation HCA contraceptive product comprised of HCA human mAb, produced to GMP standards in an innovative cost-effective mAb platform (Nicotiana), and formulated into a film that dissolves on contact with the vaginal mucosa to deliver short-term (on-demand) contraception. The HCA film will be tested in vitro for efficacy and safety, IND-enabling studies will be performed, and after filing an IND application with the FDA the HCA film will be tested for safety and efficacy in two Phase 1 clinical trials. A prototype HCA-intravaginal ring (IVR) will also be developed with the goal to provide long-term (>30 day) contraceptive protection. The HCA-IVR will undergo testing in vitro and in a nonhuman primate (NHP) model for preliminary assessment of PK/PD, antibody distribution and safety. The program will also produce and test HCA multivalent variants with potential enhanced sperm trapping capabilities for use in second generation HCA contraception products. In the future HCA could be used alone in films or IVRs for contraception, or in combination with mAbs or other microbicidal compounds directed against STI pathogens, to enhance the acceptability, efficacy and marketability of Multipurpose Prevention Technology (MPT) products.