Long Acting Thrombopoietin For Treating Thrombocytopenia

描述（由申请人提供）：血小板生成素（TPO）是一种刺激巨核细胞（血小板前体）增殖和分化的细胞因子。重组人血小板生成素是一种很有前途的治疗方法，可刺激骨髓抑制化疗引起的血小板减少症患者的血小板生成。我们提出产生修饰的TPO蛋白，其在体内刺激血小板形成方面等于或上级于天然TPO，但其需要较低频率的给药，大约每周一次至每三周一次。最佳地，化合物可以每个化疗周期施用一次。在第一阶段，我们将确定在TPO的网站，可以修改而不影响蛋白质的体外生物活性。在II期，我们将生产足够量的修饰TPO蛋白，用于血小板减少症动物模型的试验。新型TPO蛋白质的改进特性将减少每位患者所需的TPO量，提高患者依从性和生活质量，并为患者和医疗保健提供者节省大量成本。这些蛋白质将在治疗由骨髓抑制化疗和药物并发症引起的血小板减少症中发现效用。从这些研究中获得的信息将有助于创造用于治疗癌症、传染病和造血系统疾病的结构相关细胞因子和生长因子的长效版本。 拟议的商业应用： 正在开发的长效TPO蛋白可能用于恢复化疗引起的血小板减少症患者的血小板生成。美国血小板刺激剂市场估计超过3亿美元。这些经过修饰的TPO蛋白将需要比现有产品更少的剂量，为患者和医疗保健提供者节省大量成本。其他预期获益包括提高药物疗效、降低毒性和改善患者生活质量。

DESCRIPTION (provided by applicant): Thrombopoietin (TPO) is a cytokine that stimulates the proliferation and differentiation of megakaryocytes, the precursors to blood platelets. Recombinant human TPO is a promising treatment for stimulating platelet production in patients with thrombocytopenia resulting from myelosuppressive chemotherapy. We propose to create modified TPO proteins that are equal or superior to natural TPO at stimulating platelet formation in vivo, but which require less frequent dosing, on the order of once per week to once every third week. Optimally, the compound could be administered once per chemotherapy cycle. During Phase I we will identify sites in TPO that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will manufacture sufficient quantities of the modified TPO proteins for testing in animal models of thrombocytopenia. The improved characteristics of the novel TPO proteins will reduce the amount of TPO required per patient, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. These proteins will find utility in treating thrombocytopenia resulting from myelosuppressive chemotherapy and drug complications. Information gained from these studies will aid in creating long-acting versions of structurally related cytokines and growth factors for use in treating cancer, infectious disease and hematopoietic disorders. PROPOSED COMMERCIAL APPLICATIONS: The long-acting TPO proteins under development potentially can be used to restore platelet production in patients with thrombocytopenia resulting from chemotherapy. The U.S. market for platelet-stimulating agents is estimated to be in excess of $300 million. These modified TPO proteins will require much less frequent dosing than existing products, providing significant cost savings to patients and healthcare providers. Additional expected benefits include improved drug efficacy, reduced toxicity and improved patient quality of life.