Recombinant Antibodies as Intra-Vaginal Spermicides

重组抗体作为阴道内杀精剂

• 批准号: 6404870
• 负责人: Michael A. Coppola
• 金额: $ 29.15万
• 依托单位: CONTRAVAC, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-29 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6404870
• 关键词: contraceptives; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; fertility immunology; human tissue; immunologic substance development /preparation; male; molecular cloning; monoclonal antibody; recombinant proteins; spermicide; transfection

DESCRIPTION (provided by applicant): World population is predicted to reach 10 billion people by the year 2050, increasing more than 75 percent over the current population. Development of new contraceptive options is necessary to provide accessible birth control to all individuals regardless of sociological, financial, or educational limitations. Current literature implicates marketed spermicidal formulations in cervical and vaginal irritation leading to lesions and acquisition of sexually transmitted diseases. Reassessment of these spermicides by the FDA may result in increased costs or their removal from the market. New, inexpensive spermicides with improved safety and effectiveness must be developed. The long-term goal of this research proposal is the development of a marketable topical intra-vaginal contraceptive product based on an anti-sperm monoclonal antibody, S19. This mAb inhibits human sperm function and gamete interactions in vitro. During Phase I of the project, a recombinant single chain fragment variable region (scFv) miniantibody derived from S19 was engineered and shown to have the same anti-sperm reactivity as the native mAb. This scFv is termed RASA, for Recombinant Anti-Sperm Antibody. In the proposed Phase II study, we will first humanize RASA, and re-assess the immunoactivity of the new scFv. Second, we will develop an efficient, cost-effective platform for production and purification of large amounts of RASA in a bacterial or yeast expression system. Third, we will formulate the immunoactive humanized recombinant scFv with candidate intra-vaginal delivery vehicles including Novasomes, a trilamellar liposome-based vehicle, and test the activity of these RASA preparations to determine optimal formulation conditions and dosing. Finally, the stability and safety of the optimized formulation will be assessed. PROPOSED COMMERCIAL APPLICATION: Topical intra-vaginal contraceptive.

描述（申请人提供）：预计世界人口将达到10 到2050年，十亿人口增长了75％以上 当前人口。开发新的避孕措施是必要的 不论社会学， 财务或教育限制。当前的文献含义被销售 宫颈和阴道刺激中的精子制剂导致病变 并获得性传播疾病。重新评估这些 FDA的杀精子可能导致成本增加或从 市场。新的，廉价的杀精子剂具有提高的安全性和有效性 必须开发。该研究建议的长期目标是 开发基于销售的局部避孕产品 在抗植物单克隆抗体上，S19。此mAb抑制人类精子 在体外功能和配子相互作用。在项目的第一阶段， 重组单链片段变量区域（SCFV）微缩合衍生 从S19进行了设计，并证明具有与 本地mab。该SCFV称为RASA，用于重组抗植物抗体。在 拟议的II期研究，我们将首先使RASA人性化，并重新评估 新SCFV的免疫活性。其次，我们将发展一个有效的效率 用于生产和净化大量的成本效益平台 细菌或酵母表达系统中的RASA。第三，我们将制定 候选体内递送的免疫活性人性化重组SCFV 包括Novasomes，三层脂质体的车辆在内的车辆和测试 这些RASA准备的活性以确定最佳配方 条件和给药。最后，优化的稳定性和安全性 将评估配方。 拟议的商业应用： 局部性体内避孕药。