Development of ColdSol TMfor Rhinovirus Infections

描述（由申请人提供）：普通感冒是影响人类的最普遍的疾病，70%的病例是由鼻病毒（HRV）引起的。大多数HRV血清型结合鼻上皮细胞上的ICAM-1作为感染周期的初始步骤：因此，防止HRV结合ICAM-1应防止HRV附着，从而预防或缩短现有感冒的持续时间并减少症状。使用鼻内施用抗ICAM全抗体的人临床试验将感冒的发作延迟了多达2天，并且使症状减少了50%，但未能预防初始感染。现在已知抗体CAM-1解离速率与HRV病毒体本身的解离速率相似，这表明抗体在占据可用受体方面与病毒相比在功能亲和力上没有先天优势。我们已经产生了一个四价人源化抗体ICAM-1的预防和治疗人鼻病毒（HRV）感染。这种蛋白质显示出比单克隆抗体显著的功能改善，并且它可以以低得多的成本在细菌中产生。拟定的II期研究的目的是充分表征四价抗ICAM抗体的生物学、物理和化学性质，优化生产工艺，建立质量控制测定并优化鼻喷雾剂制剂。这些研究的结果将支持IND申请，以获得FDA的临床试验批准。

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.