NHLBI MAINTENANCE OF CANINE MODELS OF HUMAN BLEEDING DISORDERS- TASK AREA B CORE SCIENTIFIC PROJECT TO DEVELOP A BISPECIFIC MONOCLONAL ANTIBODY

本TO的目的是开发一种双特异性单克隆抗体，其将结合犬凝血FIX和FX，用于预防A型血友病犬（含和不含犬FVIII抑制性抗体）的出血。该双特异性单克隆抗体将通过修饰目前在犬血浆中不起作用的人产品（emicizumab或HemLibra™）来制备。 来自FDA的任务订单提案代表了开发一种双特异性单克隆抗体的临床重要工作，该抗体将结合犬凝血FIX和FX，用于预防A型血友病犬（含和不含犬FVIII抑制性抗体）的出血。该抗体的开发将通过大大增加具有抑制剂的血友病A犬的存活率来实现抑制剂形成、预防和消融的研究。它还将提供一个急需的动物模型系统，用于研究人类使用emicizumab时发生的不完全理解的血栓形成并发症，并解决自FDA批准药物以来出现的一系列临床问题。该提案包括里程碑和带有明确成功标准的时间轴。现场环境优越，团队经验丰富。提供了明确的时间表、里程碑和既定程序。

The goal of this TO is to develop a bispecific monoclonal antibody that will bind canine coagulation FIX and FX for preventing bleeding in hemophilia A dogs with and without inhibitory antibodies to canine FVIII. This bispecific monoclonal antibody will be made by modifying the human product (emicizumab or HemLibra™) that currently does not work in canine plasma. The task order proposal from the UNC represents clinically significant work to develop a bispecific monoclonal antibody that will bind canine coagulation FIX and FX for preventing bleeding in hemophilia A dogs with and without inhibitory antibodies to canine FVIII. The development of this antibody will enable studies of inhibitor formation, prevention and ablation by greatly increasing the survival rate of hemophilia A dogs with inhibitors. It will also provide a critically needed animal model system for investigating incompletely understood thrombotic complications that have occurred with emicizumab use in humans and for addressing a series of clinical questions that have arisen since the FDA granted drug approval. The proposal includes milestones and a timeline with defined success criteria. The UNC site has an excellent environment and the team is experienced. Clear timelines, milestones and established procedures are provided.