Development of ColdSol TMfor Rhinovirus Infections

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血清型将ICAM-1与鼻上皮细胞结合作为感染周期的第一步：因此，阻止HRV与ICAM-1结合应防止HRV附着，从而预防或缩短现有感冒的持续时间并减轻症状。一项人体临床试验使用鼻内给药抗icam全抗体可将感冒的发病时间推迟2天，并将症状减轻50%，但未能预防初次感染。现在已知抗体CAM-1的解离率与HRV病毒粒子本身的解离率相似，表明该抗体在占据可用受体方面没有先天优势。我们制备了一种抗ICAM-1的四价人源抗体，用于预防和治疗人鼻病毒（HRV）感染。这种蛋白在功能上比单抗有显著的改善，并且可以在细菌中以更低的成本生产。拟建的II期研究的目标是全面表征四价抗icam抗体的生物、物理和化学性质，优化生产工艺，建立质量控制方法，优化鼻喷剂配方。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.