Jones Tim D, Carter Paul J, Plückthun Andreas, Vásquez Max, Holgate Robert G E, Hötzel Isidro, Popplewell Andrew G, Parren Paul W H I, Enzelberger Markus, Rademaker Hendrik J, Clark Michael R, Lowe David C, Dahiyat Bassil I, Smith Victoria, Lambert John M, Wu Herren, Reilly Mary, Haurum John S, Dübel Stefan, Huston James S, Schirrmann Thomas, Janssen Richard A J, Steegmaier Martin, Gross Jane A, Bradbury Andrew R M, Burton Dennis R, Dimitrov Dimiter S, Chester Kerry A, Glennie Martin J, Davies Julian, Walker Adam, Martin Steve, McCafferty John, Baker Matthew P
a Antitope Ltd. (part of Abzena Plc.), Babraham Research Campus , Cambridge CB22 3AT , UK.
b Genentech Inc., 1 DNA Way , South San Francisco , CA 94080 , USA.
MAbs. 2016;8(1):1-9. doi: 10.1080/19420862.2015.1114320.
An important step in drug development is the assignment of an International Nonproprietary Name (INN) by the World Health Organization (WHO) that provides healthcare professionals with a unique and universally available designated name to identify each pharmaceutical substance. Monoclonal antibody INNs comprise a -mab suffix preceded by a substem indicating the antibody type, e.g., chimeric (-xi-), humanized (-zu-), or human (-u-). The WHO publishes INN definitions that specify how new monoclonal antibody therapeutics are categorized and adapts the definitions to new technologies. However, rapid progress in antibody technologies has blurred the boundaries between existing antibody categories and created a burgeoning array of new antibody formats. Thus, revising the INN system for antibodies is akin to aiming for a rapidly moving target. The WHO recently revised INN definitions for antibodies now to be based on amino acid sequence identity. These new definitions, however, are critically flawed as they are ambiguous and go against decades of scientific literature. A key concern is the imposition of an arbitrary threshold for identity against human germline antibody variable region sequences. This leads to inconsistent classification of somatically mutated human antibodies, humanized antibodies as well as antibodies derived from semi-synthetic/synthetic libraries and transgenic animals. Such sequence-based classification implies clear functional distinction between categories (e.g., immunogenicity). However, there is no scientific evidence to support this. Dialog between the WHO INN Expert Group and key stakeholders is needed to develop a new INN system for antibodies and to avoid confusion and miscommunication between researchers and clinicians prescribing antibodies.
药物研发中的一个重要步骤是由世界卫生组织（WHO）指定国际非专利名称（INN），为医疗保健专业人员提供一个独特且全球通用的指定名称，以识别每种药物物质。单克隆抗体的INN由一个“-mab”后缀和一个表示抗体类型的词干组成，例如，嵌合型（-xi-）、人源化型（-zu-）或人源型（-u-）。WHO发布的INN定义规定了新的单克隆抗体治疗药物的分类方式，并根据新技术对定义进行调整。然而，抗体技术的快速发展模糊了现有抗体类别之间的界限，并催生了大量新的抗体形式。因此，修订抗体的INN系统就如同瞄准一个快速移动的目标。WHO最近修订了抗体的INN定义，现在基于氨基酸序列同一性。然而，这些新定义存在严重缺陷，因为它们含糊不清，且与数十年的科学文献相悖。一个关键问题是对与人类种系抗体可变区序列的同一性设定了一个任意阈值。这导致对体细胞突变的人源抗体、人源化抗体以及源自半合成/合成文库和转基因动物的抗体分类不一致。这种基于序列的分类意味着不同类别之间存在明确的功能差异（例如免疫原性）。然而，没有科学证据支持这一点。需要WHO INN专家组与关键利益相关者进行对话，以开发一个新的抗体INN系统，避免研究人员和开具抗体处方的临床医生之间产生混淆和沟通不畅。
