NOVEL L-NUCLEOSIDE COMBINATION ANTI-HBV THERAPY

描述（改编自申请人的摘要）：这是一个新的，快速的轨道 该申请解释了对用于治疗糖尿病的额外治疗剂的需求。 治疗慢性B型肝炎病毒（HBV）感染。发现新的非 具有强效抗HBV活性的细胞毒性L-核苷，当用于 组合，协同地起作用。据报道，这些L-核苷 抑制病毒DNA聚合酶和复制而不影响 细胞聚合酶或线粒体功能，并已显示 显著降低慢性土拨鼠肝炎模型中的病毒载量。 SBIR第1和第2阶段的资金将用于选择和开发 具有最大潜力的L-核苷的组合， 商业化第一阶段将确定药理学、毒理学和 两种和三种L核苷组合在土拨鼠中的抗病毒效力 慢性肝炎模型。 拟定商业应用： 慢性治疗B型肝炎病毒感染。 延迟进展为肝硬化， 肝细胞癌 可能消除B型肝炎病毒。

DESCRIPTION (Adapted from Applicant's Abstract): This is a new, fast track application that explains the need for additional therapeutics for the treatment of chronic hepatitis B virus (HBV) infection. Discovery of novel non cytotoxic L-nucleosides with potent anti-HBV activity that, when used in combination, act synergistically is described. These L-nucleosides are reported to inhibit the viral DNA polymerase and replication without effect upon cellular polymerases or mitocohndrial function and have been shown to significantly reduce viral load in the chronic woodchuck hepatitis model. Funding from SBIR phase 1 and 2 will be used to select and develop the combination of the L-nucleosides with the greatest potential for commercialization. Phase 1 will determine pharmacology, toxicology and antiviral potency of two and three L nucleoside combinations in the woodchuck chronic hepatitis model. PROPOSED COMMERCIAL APPLICATION: Chronic treatment of Hepatitis B virus infection. Delay in progression to cirrhosis and hepatocellular carcinoma. Possible elimination of Hepatitis B virus.