Development of ColdSol TMfor Rhinovirus Infections

针对鼻病毒感染的 ColdSol TM 的开发

• 批准号: 6549536
• 负责人: Fang Fang
• 金额: $ 59.31万
• 依托单位: PERLAN THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6549536
• 关键词: Escherichia coli; biotherapeutic agent; cell adhesion molecules; common cold; disease /disorder prevention /control; dosage forms; drug screening /evaluation; immunologic substance development /preparation; immunopharmacology; monoclonal antibody; peptide library; protein engineering; protein purification; respiratory epithelium; respiratory virus; rhinovirus

DESCRIPTION (provided by applicant): The common cold is the most prevalent disease affecting humans, and 70% of cases are caused by rhinoviruses (HRV). The majority of HRV serotypes bind ICAM-1 on nasal epithelial cells as the initial step in the infectious cycle: therefore preventing HRV from binding to ICAM-1 should prevent HRV attachment and thereby either prevent or shorten the duration and decrease symptoms of existing colds. A human clinical trial using intranasal administration of an anti-ICAM whole antibody delayed the onset of colds by up to 2 days and decreased symptoms 50% but failed to prevent initial infection, It is now known that the antibody CAM-1 dissociation rate is similar to that of the HRV virion itself indicating that the antibody has no innate advantage in functional affinity over the virus in occupying available receptors. We have generated a tetravalent humanized antibody against ICAM-1 for the prevention and treatment of human rhinovirus (HRV) infections. This protein shows significant functional improvement over the monodonal antibody and it can be produced in bacteria at much lower cost. The goals of the proposed phase II study is to fully characterize the biological, physical and chemical properties of the tetravalent anti-ICAM antibody, optimize the production process, establish quality control assays and to optimize the nasal spray formulation. Result from these studies will support filing of IND to obtain approval from FDA for clinical trials.

描述（由申请人提供）：普通感冒是影响人类最普遍的疾病，70% 的病例是由鼻病毒 (HRV) 引起的。大多数 HRV 血清型与鼻上皮细胞上的 ICAM-1 结合，作为感染周期的第一步：因此，阻止 HRV 与 ICAM-1 结合应该阻止 HRV 附着，从而预防或缩短持续时间并减轻现有感冒的症状。一项使用鼻内施用抗 ICAM 完整抗体的人体临床试验可将感冒发作延迟长达 2 天，症状减轻 50%，但未能预防初次感染。现在已知抗体 CAM-1 解离率与 HRV 病毒体本身的解离率相似，表明该抗体在占据可用受体方面与病毒相比，在功能亲和力方面没有先天优势。我们已经产生了一种针对 ICAM-1 的四价人源化抗体，用于预防和治疗人鼻病毒 (HRV) 感染。这种蛋白质比单克隆抗体显示出显着的功能改进，并且可以以低得多的成本在细菌中生产。拟议的 II 期研究的目标是全面表征四价抗 ICAM 抗体的生物、物理和化学特性，优化生产工艺，建立质量控制测定并优化鼻喷雾剂配方。这些研究的结果将支持提交 IND 申请，以获得 FDA 临床试验的批准。