title: The INNs and outs of antibody nonproprietary names.
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.
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authors.forename: Tim D
authors.initials: TD
authors.lastname: Jones
authors.affiliation: b Genentech Inc., 1 DNA Way , South San Francisco , CA 94080 , USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Carter
authors.affiliation: c Department of Biochemistry , University of Zurich , Zurich CH-8057 , Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Plückthun
authors.affiliation: d Adimab LLC., 7 Lucent Drive , Lebanon , NH 03766 , USA.
authors.forename: Max
authors.initials: M
authors.lastname: Vásquez
authors.affiliation: a Antitope Ltd. (part of Abzena Plc.), Babraham Research Campus , Cambridge CB22 3AT , UK.
authors.forename: Robert G E
authors.initials: RG
authors.lastname: Holgate
authors.affiliation: b Genentech Inc., 1 DNA Way , South San Francisco , CA 94080 , USA.
authors.forename: Isidro
authors.initials: I
authors.lastname: Hötzel
authors.affiliation: e UCB Pharma., 208 Bath Road , Slough SL1 3WE , UK.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Popplewell
authors.affiliation: f Genmab, PO Box 85199, 3508 AD , Utrecht , The Netherlands.|g Leiden University Medical Center, Department of Immunohematology and Blood Transfusion , Leiden University Medical Center , Albinusdreef 2, 2333 ZA Leiden , The Netherlands.
authors.forename: Paul W H I
authors.initials: PW
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authors.initials: HJ
authors.lastname: Rademaker
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authors.affiliation: j MedImmune Ltd., Milstein Building, Granta Park , Cambridge CB21 6GH , UK.
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authors.affiliation: n MedImmune., One MedImmune Way , Gaithersburg , MD 20878 , USA.
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authors.lastname: Haurum
authors.affiliation: q Technische Universität Braunschweig., Institute of Biochemistry, Biotechnology and Bioinformatics Spielmannstr. 7 , 38106 Braunschweig , Germany.
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authors.initials: RA
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authors.forename: Andrew R M
authors.initials: AR
authors.lastname: Bradbury
authors.affiliation: x The Scripps Research Institute., 10550 North Torrey Pines Road , La Jolla , CA 92037 , USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: y Protein Interactions Section., Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick , MD 21702 , USA.
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
authors.affiliation: z UCL Cancer Institute., 72 Huntley Street , London WC1E 6BT , UK.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Chester
authors.affiliation: aa Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton General Hospital , Southampton , Hampshire SO16 6YD , UK.
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authors.lastname: Glennie
authors.affiliation: ab Lilly Biotechnology Center San Diego , CA 92121 , USA.
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authors.affiliation: ac GSK., Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Hills Road , Cambridge , CB2 2GG , UK.
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authors.lastname: Walker
authors.affiliation: ad GSK, Medicines Research Centre, Gunnels Wood Road , Stevenage , Herts , SG1 2NY , UK.
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authors.affiliation: ae Iontas Ltd., Babraham Research Campus , Cambridge CB22 3AT , UK.
authors.forename: John
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authors.affiliation: a Antitope Ltd. (part of Abzena Plc.), Babraham Research Campus , Cambridge CB22 3AT , UK.
authors.forename: Matthew P
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authors.lastname: Baker
mesh_terms: D000818:Animals; D000906:Antibodies; D006801:Humans; D009626:Terminology as Topic
chemical_list: D000906:Antibodies
keywords: Complementarity Determining Region (CDR); International Immunogenetics Information System (IMGT); International Nonproprietary Name (INN); World Health Organization (WHO); antibody; chimeric; definition; framework; humanized; monoclonal