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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.

SUBMITTER: Jones TD

PROVIDER: S-EPMC4966553 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The INNs and outs of antibody nonproprietary names.

Jones Tim D TD Carter Paul J PJ Plückthun Andreas A Vásquez Max M Holgate Robert G E RG Hötzel Isidro I Popplewell Andrew G AG Parren Paul W H I PW Enzelberger Markus M Rademaker Hendrik J HJ Clark Michael R MR Lowe David C DC Dahiyat Bassil I BI Smith Victoria V Lambert John M JM Wu Herren H Reilly Mary M Haurum John S JS Dübel Stefan S Huston James S JS Schirrmann Thomas T Janssen Richard A J RA Steegmaier Martin M Gross Jane A JA Bradbury Andrew R M AR Burton Dennis R DR Dimitrov Dimiter S DS Chester Kerry A KA Glennie Martin J MJ Davies Julian J Walker Adam A Martin Steve S McCafferty John J Baker Matthew P MP

mAbs 20160101 1

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 monoclona ...[more]

PMID: 26716992

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Project description:BackgroundConfusion between look-alike and sound-alike (LASA) medication names (such as mercaptamine and mercaptopurine) accounts for up to one in four medication errors, threatening patient safety. Error reduction strategies include computerized physician order entry interventions, and 'Tall Man' lettering. The purpose of this study is to explore the medication name designation process, to elucidate properties that may prime the risk of confusion.Methods and findingsWe analysed the formal and semantic properties of 7,987 International Non-proprietary Names (INNs), in relation to naming guidelines of the World Health Organization (WHO) INN programme, and have identified potential for errors. We explored: their linguistic properties, the underlying taxonomy of stems to indicate pharmacological interrelationships, and similarities between INNs. We used Microsoft Excel for analysis, including calculation of Levenshtein edit distance (LED). Compliance with WHO naming guidelines was inconsistent. Since the 1970s there has been a trend towards compliance in formal properties, such as word length, but longer names published in the 1950s and 1960s are still in use. The stems used to show pharmacological interrelationships are not spelled consistently and the guidelines do not impose an unequivocal order on them, making the meanings of INNs difficult to understand. Pairs of INNs sharing a stem (appropriately or not) often have high levels of similarity (<5 LED), and thus have greater potential for confusion.ConclusionsWe have revealed a tension between WHO guidelines stipulating use of stems to denote meaning, and the aim of reducing similarities in nomenclature. To mitigate this tension and reduce the risk of confusion, the stem system should be made clear and well ordered, so as to avoid compounding the risk of confusion at the clinical level. The interplay between the different WHO INN naming principles should be further examined, to better understand their implications for the problem of LASA errors.

Project description:For more than 250 years, the taxonomic enterprise has remained almost unchanged. Certainly, the tools of the trade have improved: months-long journeys aboard sailing ships have been reduced to hours aboard jet airplanes; advanced technology allows humans to access environments that were once utterly inaccessible; GPS has replaced crude maps; digital hi-resolution imagery provides far more accurate renderings of organisms that even the best commissioned artists of a century ago; and primitive candle-lit microscopes have been replaced by an array of technologies ranging from scanning electron microscopy to DNA sequencing. But the basic paradigm remains the same. Perhaps the most revolutionary change of all - which we are still in the midst of, and which has not yet been fully realized - is the means by which taxonomists manage and communicate the information of their trade. The rapid evolution in recent decades of computer database management software, and of information dissemination via the Internet, have both dramatically improved the potential for streamlining the entire taxonomic process. Unfortunately, the potential still largely exceeds the reality. The vast majority of taxonomic information is either not yet digitized, or digitized in a form that does not allow direct and easy access. Moreover, the information that is easily accessed in digital form is not yet seamlessly interconnected. In an effort to bring reality closer to potential, a loose affiliation of major taxonomic resources, including GBIF, the Encyclopedia of Life, NBII, Catalog of Life, ITIS, IPNI, ICZN, Index Fungorum, and many others have been crafting a "Global Names Architecture" (GNA). The intention of the GNA is not to replace any of the existing taxonomic data initiatives, but rather to serve as a dynamic index to interconnect them in a way that streamlines the entire taxonomic enterprise: from gathering specimens in the field, to publication of new taxa and related data.

Project description:Podocyte effacement and loss characterizes glomerulopathies such as diabetic nephropathy, lupus, and glomerular toxicity. Human primary podocyte-like epithelial cells cultured from urine (ECU) were characterized as a window to understand podocyte regeneration in these glomerulopathies. Cytokines TNF, and VEGF stimulated regrowth, whereas FGF-1 and IL1 inhibited growth, consistent with other podocyte or parietal epithelial cell models. Review of published micrographs indicated that podocyte foot processes in rodent kidneys interdigitated exclusively with foot processes from other cells, suggesting podocytes practice self-avoidance. In culture, ECU avoided close interactions with other cells arising from the same clone, until enough cells grew for the culture to become confluent. In contrast, ECU derived from multiple clones associated actively to form contiguous monolayers. Gene expression profiling of eight clonal ECU colonies using RNA sequencing revealed that each colony expressed a highly variable profile of the 53 Protocadherin genes. Variable combinations of the 53 Protocadherin PCDHA-, PCDHB-, and PCDHG- gene products are known to act homophilically to direct self-avoidance interactions in human neurons, so PCDH- genes are postulated to govern self-avoidance similarly in podocytes. Such protocadherin profiles could be considered cell names. Transcriptional profiles of ECUs suggest they may represent intermediate stages of Parietal Epithelial Cells (PECs) differentiating into podocytes. They further suggest that each podocyte practices self-avoidance, interdigitating selectively with other cells in the glomerulus. To enable further investigation of multi-clonal podocyte interactions, five podocyte clones were immortalized using temperature-sensitive SV40 Large T antigen. These results suggest that non-self interdigitation of new podocytes with remnant podocytes may facilitate replacement of dying podocytes and re-establishment of a functional filtration barrier.

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The INNs and outs of antibody nonproprietary names.

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The INNs and outs of antibody nonproprietary names.

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