Year: 2015
Type: editorial
Abstract: 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.
Source: mAbs
Authors: Tim D. Jones, Paul J. Carter, Andreas Plückthun, Max Vásquez, Robert G.E. Holgate, Isidro Hötzel, Andrew G. Popplewell, Paul W.H.I. Parren, Markus Enzelberger, Hendrik J. Rademaker, Michael R. Clark, David C. Lowe, Bassil I. Dahiyat, Victoria Smith, John M. Lambert, Herren Wu, Mary Reilly, John S. Haurum, Stefan Dübel, James S. Huston, Thomas Schirrmann, Richard A.J. Janssen, Martin Steegmaier, Jane A. Gross, Andrew R.M. Bradbury, Dennis R. Burton, Dimiter S. Dimitrov, Kerry A. Chester, Martin J. Glennie, Julian Davies, Adam Walker, Steve Martin, John McCafferty, Matthew P. Baker
Institutions: Abzena (United Kingdom), Genentech, University of Zurich, Adimab (United States), UCB Pharma (United Kingdom), Leiden University Medical Center, Genmab (Netherlands), MorphoSys (Germany), Xencor (United States), Gilead Sciences (United States), ImmunoGen (United States), Opsona Therapeutics (Ireland), F-star (United Kingdom), Technische Universität Braunschweig, Galapagos (Netherlands), Roche Pharma AG (Germany), Emergent BioSolutions (United States), Los Alamos National Laboratory, Scripps Research Institute, Frederick National Laboratory for Cancer Research, National Cancer Institute, Center for Cancer Research, University College London, Southampton General Hospital, University of Southampton, Addenbrooke's Hospital, GlaxoSmithKline Research & Development Limited (United Kingdom)
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,575
OpenAlex ID: W2198982668