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Generation of Therapeutic Multispecific Antibodies Using a Modular Domain Antibody Approach

机译:使用模块化结构域抗体方法产生治疗性多特异性抗体

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Multi-specific antibody therapy is a rapidly growing pharmaceutical area, with a market expected to reach US$ 1-2 billion in the next five years. However, development of multi-specific antibodies in the IgG format is challenging, with extensive engineering necessary to generate multi-specificity and is usually limited to bi-specificity, the molecules can be aggregation prone and difficult to produce and purify. A modular architecture for antibodies, in which new specificities can be added simply by inserting new modules, would therefore be extremely beneficial to generate multi-specific therapeutic antibodies. We have developed and stabilized a small and modular domain antibody format ("Mody", patent filed) based on the variable heavy (VH) domain of Herceptin IgG antibody. It packs identical binding capabilities as a full-length IgG in a molecule 10 times smaller. The Mody format is easy to assemble into multi-specific molecules by linking Modies generated against different targets at the DNA level to generate a bispecific molecule, or linked to a Fc fragment for extended half-life in blood. In this poster, we present the current status of the technology.
机译:多特异性抗体治疗是一个快速成长的制药领域,与市场预计将达到US $ 1-2十亿在未来五年。然而,在IgG形式的多特异性抗体的发展是具有挑战性的,与需要产生多特异性和通常限于双特异性广泛的工程,该分子可以是易聚集并且难以生产和纯化。一种模块化体系结构的抗体,其中,新的特异性可通过插入新的模块简单地相加,因此将是非常有益的,以产生多特异性的治疗性抗体。我们已经开发和稳定一个小的模块化结构域抗体形式(“么”,专利申请)基于赫赛汀IgG抗体的可变重(VH)结构域。它包在一个分子相同的结合能力作为全长IgG小10倍。么格式是容易通过链接在DNA水平上针对不同的靶标产生Modies以生成双特异性分子组装成多特异性分子,或连接到用于血液半衰期延长一个Fc片段。在这张海报中,我们提出了当前的技术状态。

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