Shatz Whitney, Ng Domingos, Dutina George, Wong Athena W, Dunshee Diana Ronai, Sonoda Junichiro, Shen Amy, Scheer Justin M
a Department of Protein Chemistry , Genentech Inc. , South San Francisco , CA , USA.
b Department of Early Stage Cell Culture , Genentech Inc. , South San Francisco , CA , USA.
MAbs. 2016 Nov/Dec;8(8):1487-1497. doi: 10.1080/19420862.2016.1234569.
Bispecific antibodies have shown promise in the clinic as medicines with novel mechanisms of action. Lack of efficient production of bispecific IgGs, however, has limited their rapid advancement. Here, we describe a single-reactor process using mammalian cell co-culture production to efficiently produce a bispecific IgG with 4 distinct polypeptide chains without the need for parallel processing of each half-antibody or additional framework mutations. This method resembles a conventional process, and the quality and yield of the monoclonal antibodies are equal to those produced using parallel processing methods. We demonstrate the application of the approach to diverse bispecific antibodies, and its suitability for production of a tissue specific molecule targeting fibroblast growth factor receptor 1 and klotho β that is being developed for type 2 diabetes and other obesity-linked disorders.
双特异性抗体作为具有新型作用机制的药物已在临床上展现出前景。然而，双特异性IgG缺乏高效生产方法限制了它们的快速发展。在此，我们描述了一种利用哺乳动物细胞共培养生产的单反应器工艺，可高效生产具有4条不同多肽链的双特异性IgG，无需对每个半抗体进行平行处理或额外的框架突变。该方法类似于传统工艺，单克隆抗体的质量和产量与使用平行处理方法生产的相当。我们展示了该方法在多种双特异性抗体中的应用，以及其适用于生产一种针对成纤维细胞生长因子受体1和klothoβ的组织特异性分子，该分子正被开发用于治疗2型糖尿病和其他与肥胖相关的疾病。
