Novel Platform Technology for Developing Therapeutic Human mAbs

描述（由申请人提供）：尽管在治疗和早期检测方面取得了重大进展，但癌症仍然是对社会的重大疾病威胁。治疗性单克隆抗体是一种有效的新疗法，最近被开发为针对许多类型癌症的靶向疗法。在美国，超过17种单克隆抗体已被批准用于治疗多种疾病。其优点是特异性高、副作用可预测、通过临床试验更快速、成本更低。然而，重大的障碍仍然存在，包括抗体开发的低效率，杂交瘤细胞系的不稳定性，患者对外来蛋白质或碳水化合物序列的不良免疫反应，以及商业上，由于需要获得开发有效抗体治疗所需的多种技术而产生的版税堆积问题。目前还没有技术平台可以通过直接转化人免疫细胞来开发产生人单克隆抗体的细胞系。这样的抗体可以测试特定的治疗特性和细胞系，直接扩展到更大的抗体制造，而不需要使用额外的平台技术。本文描述的方法允许更快地发现高价值的治疗产品，这将使治疗性人类单克隆抗体个性化和革命性，因为基因组学和蛋白质组学的新时代继续为发现可药物靶点提供巨大的机会。该I期计划的目标是利用ABL-MYC逆转录病毒转化技术开发全人源单克隆抗体。自1999年以来，NeoClone已经利用这种方法商业化开发用于研究和诊断用途的小鼠抗体。如果这项提议成功，我们的小鼠抗体技术的优势将保持不变：快速，高效，低成本的高亲和力单克隆抗体的开发。治疗方法的其他优势将是完全人抗体序列，稳定的细胞系，准确的翻译后修饰，不需要进一步成熟来提高亲和力。此外，这项技术有可能使用患者自身的细胞来开发抗体。一种更快速、更有效的治疗性抗体技术将是对抗癌症和其他致命疾病方法库的一个受欢迎的补充。治疗性单克隆抗体正在成为治疗癌症最有效的靶向药物方法之一。NeoClone公司拟将其成功的单克隆抗体技术应用于人类治疗性单克隆抗体的快速开发。这种方法的潜在优势是更快速和有效的药物开发，更少的潜在有害副作用。

DESCRIPTION (provided by applicant): Despite significant advances in treatment and early detection, cancer remains a significant disease threat to society. Therapeutic monoclonal antibodies are effective new treatments that have recently been developed as targeted therapies against many types of cancer. Over 17 monoclonal antibodies have been approved in the US for treating a variety of diseases. The advantages are high specificity, predictable side effects, and more rapid and less expensive advancement through clinical trials. Significant hurdles remain, however, including the low efficiency of antibody development, instability of hybridoma cell lines, adverse patient immune responses to foreign protein or carbohydrate sequences, and commercially, royalty stacking issues from the need to access the multiple technologies required to develop an efficacious antibody therapeutic. There is currently no technology platform that allows one to develop human monoclonal antibody producing cell lines by direct transformation of human immune cells. Such antibodies can be tested for specific therapeutic characteristics and the cell lines directly scaled for larger antibody manufacturing without the use of additional platform technologies. The approach described herein is one that allows for more rapid discovery of high value therapeutic products, that will both personalize and revolutionize the therapeutic human monoclonal antibody as the new era of genomics and proteomics continues to provide enormous opportunity for the discovery of druggable targets. The objective of this Phase I proposal is utilize the ABL-MYC retroviral transformation technology for the development of fully human monoclonal antibodies. NeoClone has utilized this approach commercially since 1999 to develop murine antibodies for research and diagnostic use. If successful in this proposal, the advantages of our murine antibody technology would hold true: rapid, efficient, cost effective development of high affinity monoclonal antibodies. Additional advantages for therapeutics would be fully human antibody sequence, stable cell lines, accurate post-translational modifications and no need for further maturation to improve affinity. Additionally, this technology would have the potential to use the patient's own cells for antibody development. A more rapid and efficacious therapeutic antibody technology would be a welcome addition to the arsenal of approaches to combat cancer and other deadly diseases. Therapeutic monoclonal antibodies are emerging as one of the most effective targeted drug approaches for cancer. NeoClone is proposing to adapt it's successful monoclonal antibody technology to enable rapid development of fully human therapeutic monoclonal antibodies. The potential advantages of this approach are more rapid and efficient drug development with less potential for deleterious side effects.