CC49/RIGS, a diagnostic radiopharmaceutical monoclonal antibody, for enhanced liv

描述(由申请人提供)：在基于选定的替代商业焦点的过渡时期不活跃之后，并在与美国食品和药物管理局协商后，NeoProbe Corporation正在迅速重新启动努力，开发和商业化125碘标记的HuCC49�CH2抗肿瘤相关糖蛋白72(TAG-72)单抗结构，用于辅助癌症外科医生为患者手术切除从结肠癌或直肠腺癌扩散或转移的肝肿瘤。TAG-72是一种腺癌特异性产物，既在肿瘤中心有显著的生产，又有很强的肿瘤边缘清晰度。HuCC49�CH2与TAG-72结合具有很高的亲和力和特异性。当125I-HuCC49�CH2与TAG-72结合时，它会发出放射性信号，外科医生使用的手持伽马探测探头可以检测到该信号。这个信号在手术过程中实时定义，通知外科医生外科医生试图切除的癌症的位置和程度。这将在两个方面帮助外科医生，这将为患者提供好处 并提高他们的护理质量。首先，它将帮助外科医生将整个肿瘤从 避免在手术切除的边缘留下少量的癌症。其次，它将允许外科医生识别小的、难以识别的或隐蔽的肿瘤，这些肿瘤可能已经扩散到肝脏之外，特别是扩散到附近或肝周淋巴结，引流肿瘤区域。为了完成用于所述预期用途的125I-HuCC49NeoProbe CH2的开发和商业化，�必须完成临床前测试桥接研究包和两项人体临床试验。涉及化学、制造和控制(CMC)验证研究的产品研究已经启动并接近完成。FDA确实需要一套临床前动物研究的过渡包。这些临床前动物研究的目的是为了证明目前生产的125I-HuCC49�CH2的生产批次与以前使用的诊断药物批次相当。在CMC和临床前研究完成后，NeoProbe将执行美国食品和药物管理局要求的标准化临床试验，检查产品安全性，并将培训外科医生如何使用125I-HuCC49�CH2用于放射免疫引导手术(RIGS)和协调手术程序。这项标准化试验将为该产品的关键第三阶段临床试验奠定基础，展示125I-HuCC49�CH2/RISS系统的安全性和有效性，并将支持向美国食品和药物管理局提出的保密申请，寻求许可将该产品推向市场，用于治疗结肠癌和直肠腺癌的肝转移。NeoProbe正在为所需的部分临床前动物研究工作和标准化临床试验寻求SBIR快速通道拨款支持。

DESCRIPTION (provided by applicant): After an interim period of inactivity based on a select alternative commercial focus, and after consultation with the FDA, Neoprobe Corporation is rapidly reinitiating efforts to develop and commercialize 125Iodine-labeled HuCC49�CH2 anti-Tumor Associated Glycoprotein-72 (TAG-72) monoclonal antibody construct as an aid to cancer surgeons who are operating on patients to remove liver tumors that have spread or metastasized from adenocarcinomas of the colon or rectum. TAG-72 is an adenocarcinoma specific product with both notable production in the tumor center and strong tumor margin definition. HuCC49�CH2 binds to TAG-72 with very high affinity and specificity. When 125I-HuCC49�CH2 binds to TAG-72, it emits a radioactive signal that can be detected a handheld gamma detection probe utilized by the surgeon. This signal, defined in real time during the surgery, informs the surgeon as to the location and extent of the cancer that the surgeon is trying to remove. This will assist the surgeon in two ways that will provide benefit to the patient and improve their quality of care. First, it will help the surgeon remove the entire tumor from the liver and avoid leaving small amounts of cancer at the margins of the surgical resection. Second, it will permit surgeons identify small, difficult to identify or occult tumors that may hav spread beyond the liver, especially to nearby or perihepatic lymph nodes that drain the tumor area. To complete the development and commercialization of 125I-HuCC49�CH2 for the intended use described, Neoprobe must complete a preclinical testing bridging study packet and two human clinical trials. The product studies involving validation of chemistry, manufacturing, and controls (CMC) studies have already been initiated and are near completion. The FDA does require a bridging packet of preclinical animal studies. The purpose of these preclinical animal studies is to show that the current production lots of 125I-HuCC49�CH2 are equivalent to the lots of diagnostic drug used previously. After the CMC and preclinical studies are completed, Neoprobe will perform an FDA requested standardization clinical trial that will examine product safety and will train surgeons on the use of 125I-HuCC49�CH2 for the intended use in radioimmunoguided surgery (RIGS) and harmonize surgical procedures. This standardization trial will set the stage for a pivotal Phase 3 clinical trial of the product demonstrating the safey and efficacy of the 125I-HuCC49�CH2/RIGS system and will support an NDA application to the FDA seeking permission to market the product for use in liver metastases of adenocarcinomas of the colon and rectum. Neoprobe is seeking SBIR Fast Track grant support for part of the required preclinical animal study effort and for the standardization clinical trial.