Low Antigenicity Factor VIII

描述(申请者逐字描述)：我们的目标是获得 用于治疗的低抗原性重组FVIII产物的注册 抗人FVIII中和抗体阳性的患者。这种抑制剂 患者包括血友病A患者，他们在以下情况下会产生同种抗体 接受人类FVIII替代物治疗，以及“获得性”患者 血友病患者会产生针对内源性FVIII的自身抗体。 对意志的抑制是一种严重的、潜在的生命威胁 条件。目前的治疗方法仅限于所谓的“搭桥术”。 试剂“和血浆来源的猪FVIII(Hyate：C)。旁路试剂是 非生理性的，偶尔会引起凝血级联的过度驱动。 这可能会导致严重的并发症，如播散性血管内出血。 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、治疗者和患者的担忧 产品和副作用可归因于产品的相对杂质。 申请人有权独家获得重组猪FVIII。申请者有 获得了大量的体外和体内数据，支持了 重组猪将作为一种低抗原性的FVIII产品开发。 申请人的SBIR项目第二阶段应包括：完成 该产品的临床前开发，向FDA提交IND，以及 该产品在血友病A患者中的初步安全性和有效性研究。在……里面 临床前阶段，该产品的安全性和免疫原性将是 在老鼠和食蟹猴身上进行了研究。将获得药代动力学数据 在一个高度预测血友病A的狗模型中，在ND被提交后， 该产品的安全性和药代动力学将在临床试验中进行研究 其中大约12名抑制剂患者将接受该产品。 建议的商业应用： 大约26%的血友病A患者会产生抗体。很大一部分 不能用人类FVIII成功治疗。重组、低抗原性的FVIII 该产品将在FVIII抑制剂患者市场上具有很强的竞争力，并成为一线治疗药物 是“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."