Methods of generating conditionally active biologic proteins, in particular therapeutic or diagnostic proteins, which are more active at an aberrant condition than at a normal physiological condition. The methods include discovery methods using libraries of proteins and assays employing physiological concentrations of components of bodily fluids. The conditionally active biologic proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety. Criteria for selecting starting proteins for the discovery methods, as well as formats of the proteins are also disclosed.
产生条件活性
生物蛋白质,特别是治疗或诊断蛋白质的方法,这些蛋白质在异常状态下比正常生理状态下更有活性。这些方法包括使用蛋白质库的发现方法和使用生理浓度的体液成分的检测方法。有条件活性的
生物蛋白质可以进一步进化、与其他分子连接、掩蔽、通过附加可裂解分子降低活性。此外,还公开了为发现方法选择起始蛋白质的标准以及蛋白质的格式。