Long-Acting IL-11 for Treating Thrombocytopenia

描述（由申请人提供）：白细胞介素11 （IL-11）是一种刺激血小板增殖、成熟和功能激活的细胞因子。重组人IL- 11被批准并上市，用于治疗某些接受骨髓抑制性癌症化疗的血小板减少症患者，其市场估计为5亿美元。IL-11体内半衰期短，必须每天皮下注射才能达到最佳疗效。研究人员建议创造一种改良的IL-11蛋白，这种蛋白在刺激体内血小板形成方面与天然IL-11相同，甚至更好，但需要更少的剂量，大约每周一次到每三周一次。在第一阶段，研究人员确定了IL- 11中可以在不影响蛋白质体外生物活性的情况下进行修饰的位点。在II期，将生产足够数量的修饰IL-11蛋白，用于在正常啮齿动物和化学诱导的血小板减少啮齿动物模型中测试药代动力学和疗效。在临床环境中，新型IL-11蛋白的改进特性将减少每位患者所需的IL-11量，提高患者的依从性，并为患者和医疗保健提供者节省可观的成本。其他潜在的好处包括改善药物疗效，易于使用和改善患者的生活质量。从这些研究中获得的信息将有助于创造长效的结构相关细胞因子和生长因子，用于治疗癌症、传染病和造血疾病

DESCRIPTION (provided by applicant): Interleukin 11 (IL-11) is a cytokine that stimulates proliferation, maturation and functional activation of platelets. Recombinant human IL- 11 is approved and marketed as a treatment for thrombocytopenia in certain patients undergoing myelosuppressive cancer chemotherapy, the market for which is estimated to be $500 million. IL-11 has a short in vivo half-life and must be administered daily by subcutaneous injection to achieve optimal efficacy. The investigators 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 to once every third week. During Phase I the investigators identified sites in IL- 11 that can be modified without affecting the protein's in vitro bioactivity. During Phase II, sufficient quantities of the modified IL-11 proteins will be manufactured for testing of pharmacokinetics and efficacy in normal rodents and in rodent models of chemically induced thrombocytopenia. In the clinical setting, the improved properties of the novel IL-11 proteins will reduce the amount of IL-11 required per patient, improve patient compliance, and result in considerable cost savings to patients and healthcare providers. Additional potential benefits include improved drug efficacy, ease of use and improved patient quality of life. 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