Low Antigenicity Factor VIII

描述（申请人的描述逐字）：我们的目标是获得 注册低抗原性重组fVIII产品用于治疗 具有抗人FVIII中和抗体的患者。这样的抑制剂 患者包括那些患有血友病A的人，当 用替代人FVIII治疗的患者，以及患有“获得性 产生针对内源性FVIII自身抗体的”血友病“患者。的 对威尔产生抑制剂是一种严重的，可能危及生命的 条件目前的治疗方案仅限于所谓的“旁路” 试剂”和血浆衍生的猪FVIII（Hyate：C）。代理商是 非生理性的，偶尔会引起凝血级联反应。 这可能导致严重的并发症，如弥漫性血管内 血栓形成或心肌梗塞。Hyate：C的使用目前受到以下限制 由血浆来源引起的监管、治疗者和患者问题 产品和副作用归因于产品的相对杂质。 申请人独家获得重组猪FVIII。申请人已经 获得了大量的体外和体内数据，支持 用于开发为低抗原性fVIII产品的重组猪Will。 申请人的SBIR项目的第二阶段应包括： 产品的临床前开发，向FDA提交IND，以及 产品在血友病A患者中的初步安全性和有效性研究。在 临床前阶段，产品的安全性和免疫原性将 在小鼠和食蟹猴中进行了研究。将获得药代动力学数据 一个高度预测性的血友病A狗模型。在ND被提交后， 将在临床试验中研究产品的安全性和药代动力学 其中大约12名抑制剂患者将接受该产品。 拟定商业应用： 大约26%的血友病A患者产生抗体。 很大一部分 不能成功地用人FVIII治疗。 一种重组低抗原性凝血因子VIII， 该产品将在FVIII抑制剂患者市场上竞争良好，并成为一线治疗药物 “获得性血友病。"

DESCRIPTION (Applicant's Description Verbatim): Our goal is to obtain registration of a low antigenicity recombinant fVIII product for the treatment of patients with neutralizing antibodies against human fVIII. Such inhibitor patients include those with hemophilia A who develop alloantibodies when treated with replacement human fVIII, as well as patients with "acquired hemophilia" who develop autoantibodies against endogenous fVIII. The development of an inhibitor to Will is a serious, potentially life threatening condition. Current treatment options are limited to so-called "bypassing" agents" and plasma derived porcine fVIII (Hyate:C). Bypassing agents are nonphysiologic and occasionally cause overdrive of the coagulation cascade. This may result in severe complications, such as disseminated intravascular thrombosis or myocardial infarction. Use of Hyate:C is currently limited by regulatory, treater and patient concerns arising from the plasma source of the product and side effects attributable to the relative impurity of the product. Applicant has exclusive access to recombinant porcine fVIII. Applicant has obtained substantial in vitro and in vivo data that supports the suitability of recombinant porcine Will for development as a low antigenicity fVIII product. Phase II of applicant's SBIR project shall include: completion of the preclinical development of the product, submission of an IND to the FDA, and initial safety and efficacy studies of the product in hemophilia A patients. In the preclinical stage, the safety and immunogenicity of the product will be studied in mice and cynomolgus monkeys. Pharmacokinetic data will be obtained in a highly predictive dog model of hemophilia A. After an ND is filed, the safety and pharmacokinetics of the product will be studied in a clinical trial in which approximately twelve inhibitor patients shall receive the product. PROPOSED COMMERCIAL APPLICATION: Approximately 26% of all hemophilia A patients develop antibodies. A significant portion cannot successfully be treated with human fVIII. A recombinant, low antigenicity fVIII product would compete well in the fVIII inhibitor patient market and be a first line therapy for "acquired hemophilia."