Long-Acting IFN-gamma for Treating Immunodeficiencies

描述（申请人提供）：干扰素-γ是一种T细胞衍生的细胞因子，对许多细胞类型具有抗病毒和免疫调节作用。重组人干扰素-γ被批准用于治疗慢性肉芽肿性疾病和严重的恶性骨硬化症。目前正在研究的其他适应症包括特发性肺纤维化、肝纤维化、丙型肝炎和卵巢癌。 干扰素-γ在皮下施用后具有短的半衰期（25 - 35分钟），这需要频繁施用并降低潜在功效。我们建议创建聚合物修饰的干扰素-γ-蛋白，其可以比现有的干扰素-γ产品更少地施用，但具有更大的效力。在第一阶段，我们将确定在干扰素-γ，可以被修改，而不影响蛋白质的体外生物活性的网站。在第二阶段，我们将开发生产工艺，以生产足够数量的经修饰的干扰素-γ蛋白，用于动物疾病模型的测试。新的干扰素-γ蛋白质的改善的特性应减少每个患者所需的干扰素-γ的量，增强功效，降低毒性，改善患者依从性和生活质量，并为患者和医疗保健提供者节省相当大的成本。干扰素-γ是结构相关的生长因子和细胞因子大家族的成员。从这些研究中获得的信息将有助于创造该基因家族其他成员的长效版本，用于治疗癌症，传染病和造血系统疾病

DESCRIPTION (provided by applicant): Interferon-gamma is a T cell-derived cytokine that exhibits anti-viral and immunomodulatory effects on many cell types. Recombinant human interferon-gamma is approved for the treatment of chronic granulomatous disease and severe malignant osteopetrosis. Other indications currently being investigated inhuman clinical trials include idiopathic pulmonary fibrosis, liver fibrosis, hepatitis C and ovarian cancer. Interferon-gamma has a short half-life after subcutaneous administration (25-35 min) that necessitates frequent administration and reduces potential efficacy. We propose to create polymer modified interferon-gamma-proteins that can be administered less frequently, but with greater potency, than existing interferon-gamma products. During Phase I we will identify sites in interferon-gamma that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will develop manufacturing processes to produce sufficient quantities of the modified interferon-gamma proteins for testing in animal disease models. The improved characteristics of the novel interferon-gamma proteins should reduce the amount of interferon gamma required per patient, enhance efficacy, reduce toxicity, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. Interferon-gamma is a member of a large family of structurally related growth factors and cytokines. Information gained from these studies will aid in creating long-acting versions of other members of this gene family for use in treating cancer, infectious disease and hematopoietic disorders