LONG-ACTING IL-11 FOR TREATING THROMBOCYTOPENIA

白细胞介素11(IL-11)是一种刺激巨核细胞增殖和分化的细胞因子，巨核细胞是血小板的前体。重组人IL-11用于刺激骨髓抑制化疗引起的血小板减少患者的血小板生成。IL-11在体内的半衰期很短，必须每天注射。我们建议创造修饰的IL-11蛋白，在刺激体内血小板形成方面与天然IL-11相等或更好，但需要更少的频率，大约每周一次或每隔一周一次。在第一阶段，我们将确定IL-11中可以在不显著影响蛋白质体外生物活性的情况下进行修饰的位置。在第二阶段，我们将生产足够数量的修饰IL-11蛋白，用于在血小板减少症的动物模型中进行测试。新型IL-11蛋白的改进特性将减少每个患者所需的IL-11数量，提高患者的依从性和生活质量，并为患者和医疗保健提供者节省大量成本。从这些研究中获得的信息将有助于创造结构上相关的细胞因子和生长因子的长效版本，用于治疗癌症、传染病和造血系统疾病。拟议的商业应用：重组人IL-11用于恢复化疗引起的血小板减少患者的血小板生成。据估计，美国的血小板刺激剂市场规模超过3亿美元。正在开发的改进的IL-11蛋白质将比现有产品需要更少的频率剂量，为患者和医疗保健提供者提供显著的成本节约。其他潜在的好处包括改善药物疗效和改善患者的生活质量。

Interleukin-11 (IL-11) is a cytokine that stimulates proliferation and differentiation of megakaryocytes, which are precursors to platelets. Recombinant human IL-11 is used to stimulate platelet production in patients with thrombocytopenia resulting from myelosuppressive chemotherapy. IL-11 has a short in vivo half-life and must be administered by daily injections. We propose to create modified IL-11 proteins that are equal or superior to natural IL- 11 at stimulating platelet formation in vivo, but which require less frequent dosing, on the order of once per week or once every other week. During Phase I we will identify sites in IL-11 that can be modified without significantly affecting the protein's in vitro bioactivity. During Phase II, we will manufacture sufficient quantities of the modified IL-11 proteins for testing in animal models of thrombocytopenia. The improved characteristics of the novel IL-11 proteins will reduce the amount of IL-11 required per patient, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. 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 hematopoeitic disorders. PROPOSED COMMERCIAL APPLICATIONS: Recombinant human IL-11 is 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. The modified IL-11 proteins under development will require much less frequent dosing than existing products, providing significant cost savings to patients and healthcare providers. Additional potential benefits include improved drug efficacy and improved patient quality of life.