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、成熟和功能活化的细胞因子。重组人IL-11已被批准并上市，用于治疗某些接受骨髓抑制性癌症化疗的患者的血小板减少症，其市场估计为5亿美元。IL-11具有短的体内半衰期，并且必须每天通过皮下注射施用以实现最佳功效。研究人员提出创建修饰的IL-11蛋白，其在体内刺激血小板形成方面等同于或上级于天然IL-11，但其需要较低频率的给药，大约每周一次至每三周一次。在第一阶段，研究人员确定了IL-11的位点，这些位点可以被修饰而不影响蛋白质的体外生物活性。在II期期间，将生产足量的修饰IL-11蛋白，用于在正常啮齿动物和化学诱导血小板减少症啮齿动物模型中检测药代动力学和疗效。在临床环境中，新型IL-11蛋白质的改善的性质将减少每位患者所需的IL-11的量，改善患者依从性，并为患者和医疗保健提供者节省大量成本。其他潜在益处包括提高药物疗效、易用性和改善患者生活质量。从这些研究中获得的信息将有助于创造结构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

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