OTHER FUNCTIONS SBIR PHASE II TOPIC 275, GENERIC ERBITUX FOR TREATMENT OF EGFR+

作为我们与NCI的I期SBIR合同的延续，该II期申请旨在进一步开发生物仿制药爱必妥抗体（命名为ch 225），用于EGFR+、KRAS突变阴性的结直肠癌和头颈癌的免疫治疗。2011年，美国有141，210例结肠癌和直肠癌新发病例，49，380例死亡，占结直肠癌患者治疗费用的122亿美元。除了结直肠癌是美国男性和女性中第三大常见癌症和第三大癌症相关死亡原因之外，头部和癌症还占了45，000例符合Erbitux治疗条件的额外病例。根据这些统计数据，爱必妥是肿瘤学中的一种重要治疗方式，如果目前的临床试验证明其在非小细胞肺癌中的有效性是成功的，其商业价值将在不久的将来大大增加。在该合同的第一阶段，使用基因工程方法在实验室中开发了具有与爱必妥相似特性的ch 225。广泛的表征研究使用质谱、BiaCore分析、糖基化谱分析和EGFR阳性和阴性细胞系的结合特征证明其与市售爱必妥的相似性。基于这些结果，该II期合同申请将通过专注于细胞中的功能研究（包括信号转导途径的鉴定、其对肿瘤细胞的作用模式及其体内作用（包括PK/PD分析）和对EGFR+肿瘤模型的疗效），进一步将ch 225开发至临床。

As a continuation of our Phase I SBIR contract with the NCI, this Phase II application is directed towards the further development of a biosimilar Erbitux antibody, designated ch225, for the immunotherapy of EGFR+, KRAS mutation negative colorectal and head and neck cancers. In 2011, there were 141,210 new cases of colon and rectal cancers and 49,380 deaths in the United States accounting for the 12.2 billion dollars spent on colorectal cancer treatment of patients. In addition to colorectal cancer which is the third most common cancer and the third leading cause of cancer-related mortality in both men and women in the United States, head and cancer accounts for 45,000 additional cases that are eligible for Erbitux treatment. Based upon these statistics, Erbitux is an important treatment modality in oncology and if current clinical trials to demonstrate its effectiveness in non-small cell lung cancer are successful, its commercial value will greatly increase in the near future. In Phase I of this contract, ch225 with similar characteristics to Erbitux was developed in the laboratory using genetic engineering methods. Extensive characterization studies demonstrated its close identity to commercial Erbitux using mass spectroscopy, BiaCore analysis, glycosylation profiling, and binding characteristics on EGFR positive and negative cell lines. Based upon these results, this Phase II contract application will further the development of ch225 to the clinic by focusing on functional studies in cells including the identification of signal transduction pathways, its mode of action on tumor cells, and the its action in vivo including PK/PD analyses, and efficacy againt EGFR+ tumor models.