Nomenclature of monoclonal antibodies

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List of stems for
monoclonal antibody nomenclature (revision 2022)[1][2][3][4]
Prefix Target substem Stem
meaning meaning
variable -ami- serum amyloid protein
(SAP)/amyloidosis (pre-substem) 		-bart artificial antibody
-ba- bacterial -ment fragment (derived from a
variable domain
)
-ci- cardiovascular -mig multi-immunoglobulin (e.g. BsMAb)
-de- metabolic or endocrine pathways -tug unmodified
immunoglobulin
-eni-
enzyme inhibition
-fung- fungal
-gro- skeletal muscle mass related growth factors
and receptors (pre-substem)
-ki- cytokine and cytokine receptor
-ler- allergen
-ne- neural
-os- bone
-pru-
immunosuppressive
-sto-
immunostimulatory
-ta-
tumor
-toxa- toxin
-vet- veterinary use (sub-stem)
-vi- viral

The nomenclature of monoclonal antibodies is a naming scheme for assigning generic, or nonproprietary, names to

bacterium or a virus. Monoclonal antibodies are those that were produced in identical cells, often artificially, and so share the same target object. They have a wide range of applications including medical uses.[5]

This naming scheme is used for both the

International Nonproprietary Names (INN)[6] and the United States Adopted Names (USAN)[7] for pharmaceuticals. In general, word stems are used to identify classes of drugs, in most cases placed word-finally. All monoclonal antibody names assigned until 2021 end with the stem -mab; newer names have different stems. Unlike most other pharmaceuticals, monoclonal antibody nomenclature uses different preceding word parts (morphemes) depending on structure and function. These are officially called substems and sometimes erroneously infixes, even by the USAN Council itself.[7]

The scheme has been revised several times: in 2009, in 2017, in 2021, and in 2022.[1][2][8][4]

Components

Fc region
is the cluster at the bottom.

Stem

Until 2021, the stem -mab was used for all monoclonal antibodies as well as for their fragments, as long as at least one

antigen-binding fragments[10] and single-chain variable fragments,[11]
among other artificial proteins.

The new scheme, published in November 2021, divides antibodies into four groups: Group 1 uses the stem -tug for full-length unmodified immunoglobulins, those that might occur as such in the immune system. Group 2 has the stem -bart for full-length antibodies artificial, which contain one or more engineered regions (at least one

Fc region.[1][2]

Other antibody parts (such as Fc regions) and antibody mimetics use different naming schemes.

Substem for source

humanized (bottom left), chimeric/humanized (bottom middle), and human (bottom right) monoclonal antibodies.
Human parts are shown in brown, non-human parts in blue. The variable domains are the boxes on top of each antibody; the CDRs
within these domains are represented as triple loops.

For antibodies named until early 2017, the substem preceding the stem denotes the animal from which the antibody was obtained.

Mus musculus, the house mouse) or other non-human organisms. Neither INN nor USAN has ever been requested for antibodies from rats (theoretically -a-), hamsters (-e-) and primates (-i-).[9]

These non-human antibodies are recognized as foreign by the human immune system and may be rapidly

gomiliximab. Purely human antibodies used -u-.[3]

Rat/mouse hybrid antibodies can be engineered with binding sites for two different antigens. These drugs, termed trifunctional antibodies, had the substem -axo-.[14]

Newer antibody names omit this part of the name.[8]

Substem for target

The substem preceding the source of the antibody refers to the medicine's target. Examples of targets are

diagnostic
agents are not distinguished by this nomenclature.

In the naming scheme as originally developed, these substems mostly consist of a consonant, a vowel, then another consonant. The final letter may be dropped if the resulting name would be difficult to pronounce otherwise. Examples include -ci(r)- for the circulatory system, -li(m)- for the

musculoskeletal system ever received an INN. Combination of target and source substems resulted in endings like -limumab (immune system, human) or -ciximab (circulatory system, chimeric, consonant r dropped).[7]

New and shorter target substems were adopted in 2009. They mostly consist of a consonant, plus a vowel which is omitted if the source substem begins with a vowel. For example, human antibodies targeting the immune system receive names ending in -lumab instead of the old -limumab. Some endings like -ciximab remained unchanged.[3] The old system employed seven different substems for tumor targets, depending on the type of tumor. Because many antibodies are investigated for several tumor types, the new convention only has -t(u)-.[7]

With the source substem being discontinued in 2017, the need for dropping the target substem's final vowel disappeared.[8]

Prefix

The prefix carries no special meaning. It should be unique for each medicine and contribute to a well-sounding name.[3] This means that antibodies with the same source and target substems are only distinguished by their prefix. Even antibodies targeting exactly the same structure are differently prefixed, such as the adalimumab and golimumab, both of which are TNF inhibitors but differ in their chemical structure.[15][16]

Additional words

A second word following the name of the antibody indicates that another substance is attached,[3] which is done for several reasons.

Overview

List of stems for monoclonal antibody nomenclature[3][7][21][22][23][24]
Prefix Target substem Source substem (until 2017) Stem
~1993 2009–2017 2017–2021 from 2021 meaning meaning old from 2021 meaning
variable — -ami- -ami- -ami- serum amyloid protein
(SAP)/amyloidosis (pre-substem) 		-a- rat -mab -bart artificial antibody
-anibi- — — — angiogenesis (inhibitor) -e- hamster -ment fragment (derived from a
variable domain
)
-ba(c)- -b(a)- -ba- -ba- bacterial -i- primate -mig multi-immunoglobulin (e.g. BsMAb)
-ci(r)- -c(i)- -ci- -ci- cardiovascular -o- mouse -tug unmodified
immunoglobulin
-d(e)- -d(e)-[a] -de-[a] -de- endocrine -u- human
— — -eni-[b] -eni-
enzyme inhibition
 -xi-
chimeric
(human/foreign)
-fung- -f(u)- -fung- -fung- fungal -zu- humanized
-gr(o)- -gros- -gros- -gro-[c] skeletal muscle mass related growth factors
and receptors (pre-substem) 		-xizu- chimeric/humanized hybrid
-ki(n)- -k(i)- -ki- -ki- formerly: interleukin; from 2020: cytokine and cytokine receptor -axo- rat/mouse hybrid
(see trifunctional antibody)
-les- — — — inflammatory lesions[25]
-li(m)- -l(i)- -li- -ler- immunomodulating allergen -vet- veterinary use (pre-substem)[d]
-pru-
immunosuppressive
-sto-
immunostimulatory
-mul- — — — musculoskeletal system[26]
-ne(u)(r)- -n(e)- -ne- -ne- neural (nervous system)
-os- -s(o)- -os- -os- bone
-co(l)- -t(u)- -ta- -ta- colonic tumor
tumor
-go(t)- testicular tumor
-go(v)- ovarian tumor
-ma(r)- mammary tumor
-me(l)- melanoma
-pr(o)- prostate tumor
-tu(m)- miscellaneous tumor
-toxa- -tox(a)- -toxa- -toxa- toxin
— — -vet- -vet- veterinary use (pre-stem)[d]
-vi(r)- -v(i)- -vi- -vi- viral
  1. ^ a b not mentioned in documents of the 2010s
  2. ^ introduced between 2017 and 2021
  3. ^ changed in 2019 from -gros- to -gro- to avoid naming conflicts with -os-
  4. ^ a b can be inserted between target substem and stem, as in lo-ki-vet-mab (This part of the name was originally listed under the source substems and moved to the target substems when the former were dropped in 2017.[8])

History

Emil von Behring, one of the discoverers of antibodies

tetanus toxins were neutralized in the bloodstream of animals by substances they called antitoxins, which were specific for the respective toxin.[27] Behring received the first Nobel Prize in Physiology or Medicine for their find in 1901.[28] A year after the discovery, Paul Ehrlich used the term antibodies (German Antikörper) for these antitoxins.[29]

The principle of monoclonal antibody production, called

Georges Köhler and César Milstein,[30] who were awarded the 1984 Medicine Nobel Prize for their discovery together with Niels Kaj Jerne.[31] Muromonab-CD3 was the first monoclonal antibody to be approved for clinical use in humans, in 1986.[32]

The World Health Organization (WHO) introduced the system of International Nonproprietary Names in 1950, with the first INN list being published three years later. The stem -mab for monoclonal antibodies was proposed around 1990, and the current system with target and source substems was developed between 1991 and 1993. Due to the collaboration between the WHO and the United States Adopted Names Council, antibody USANs have the same structure and are largely identical to INNs. Until 2009, more than 170 monoclonal antibodies received names following this nomenclature.[9][33]

In October 2008, the WHO convoked a working group to revise the nomenclature of monoclonal antibodies, to meet challenges discussed in April the same year. This led to the adoption of the new target substems in November 2009.[9] In spring 2010, the first new antibody names were adopted.[34]

In April 2017, at the WHO's 64th Consultation on International Nonproprietary Names for Pharmaceutical Substances, it was decided to drop the source substem and from that meeting onwards, it is no longer used in new antibody names.[35] The revised nomenclature was published in May 2017.[23] The difficulty in capturing the complexity and subtleties of the many methods by which antibody drugs can be produced is one of the reasons that the INN dropped the source substem, as is the need for creating more clearly distinguishable names.[36][23]

The 2021 revision, published in November 2021, replaced the hitherto universal stem -mab with four distinct stems depending on the basic structure. Also, the target substem -li- for

immunostimulatory antibodies (-sto-) and those targeting allergens (-ler-).[1][4]

Examples

1980s

  • The monoclonal antibody muromonab-CD3, approved for clinical use in 1986, was named before these conventions took effect, and consequently its name does not follow them. Instead, it is a contraction from "murine monoclonal antibody targeting CD3".[32]

Convention until 2009

  • Adalimumab is a drug targeting
    TNF alpha. Its name can be broken down into ada-lim-u-mab. Therefore, the drug is a human monoclonal antibody targeting the immune system. If adalimumab had been named between 2009 and 2017, it would have been adalumab (ada-li-u-mab). After 2017, it would be adalimab (ada-li-mab).[15]
  • Abciximab is a commonly used medication to prevent platelets from clumping together. Broken down into ab-ci-xi-mab, its name shows the drug to be a chimeric monoclonal antibody used on the cardiovascular system. This and the following two names would look the same if the 2009 convention were applied.[37]
  • The name of the breast cancer medication trastuzumab can be analyzed as tras-tu-zu-mab. Therefore, the drug is a humanized monoclonal antibody used against a tumor.[38]
  • Alacizumab pegol is a PEGylated humanized antibody targeting the circulatory system.[18]
  • Technetium (99mTc) pintumomab[39] and technetium (99mTc) nofetumomab merpentan are radiolabeled antibodies, merpentan being a chelator that links the antibody nofetumomab to the radioisotope technetium-99m.[40]
  • Rozrolimupab is a polyclonal antibody. Broken down into rozro-lim-u-pab, its name shows the drug to be a human polyclonal antibody (-pab) acting on the immune system.[41]

Convention from 2009 to 2017

  • antineoplastic. Its name is composed of the components olara-t-u-mab. This shows that the drug is a human monoclonal antibody acting against tumors.[34]
  • The name of benralizumab, a drug designed for the treatment of asthma, has the components benra-li-zu-mab, marking it as a humanized antibody acting on the immune system.[42]

Convention from 2017 to 2021

  • Belantamab mafodotin (belan-ta-mab) is also an antineoplastic. It is conjugated to a cytotoxic agent that is chemically related to monomethyl auristatin E.[43]

See also

References

  1. ^ a b c d World Health Organization (November 2021), New INN monoclonal antibody (mAb) nomenclature scheme: Geneva, November 2021 (PDF), retrieved 2021-11-09.
  2. ^ a b c World Health Organization (2021-10-31), New INN monoclonal antibody (mAb) nomenclature scheme: International Nonproprietary Names scheme for monoclonal antibody (mAb), retrieved 2021-11-09.
  3. ^ a b c d e f g "General policies for monoclonal antibodies" (PDF). World Health Organization. 2009-12-18. Retrieved 2010-06-08.
  4. ^ a b c "New INN monoclonal antibody (mAb) nomenclature scheme (May 2022)". WHO. 2 May 2022. Retrieved 9 May 2022.
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  6. ^ "Guidelines on the Use of International Nonproprietary Names (INNs) for Pharmaceutical Substances" (PDF). 1997. pp. 27–28. Retrieved 2007-08-15.
  7. ^ a b c d e f "AMA (USAN) Monoclonal antibodies". United States Adopted Names. 2007-08-07. Archived from the original on October 18, 2011. Retrieved 2007-08-15.
  8. ^ a b c d World Health Organization (2017-05-26), Revised monoclonal antibody (mAb) nomenclature scheme: Geneva, 26 May 2017 (PDF), retrieved 2021-11-09.
  9. ^ a b c d "International Nonproprietary Names" (PDF). WHO Drug Information. 23 (3). World Health Organization: 195–199. 2009. Retrieved 2010-12-08.
  10. ^ "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. 18 (1). World Health Organization: 61. 2004. Archived from the original (PDF) on September 19, 2007. Retrieved 2010-06-08.
  11. ^ "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. 15 (2). World Health Organization: 121. 2001. Retrieved 2010-06-08.
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  16. ^ "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. 18 (2). World Health Organization: 167. 2004. Archived from the original (PDF) on November 4, 2005. Retrieved 2011-02-13.
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  18. ^ a b "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. 22 (3). World Health Organization: 221. 2008. Retrieved 2010-06-08.
  19. ^ "Drug Dictionary: Glembatumumab vedotin". National Cancer Institute. 2011-02-02.
  20. ^ a b "ATC/DDD Classification (final)". WHO Drug Information. 15 (2). World Health Organization. 2001. Archived from the original on July 22, 2011. Retrieved 2011-02-13.
  21. ^ "The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances" (PDF). World Health Organization. 2009. pp. 107–109, 168–169. Retrieved 2010-02-22.
  22. ^ "Monoclonal Antibodies". American Medical Association. 4 May 2016. Retrieved 7 August 2020.
  23. ^ a b c "Revised monoclonal antibody (mAb) nomenclature scheme" (PDF). Geneva: World Health Organization (WHO). 26 May 2017.
  24. ^ International Nonproprietary Names (INN) for biological and biotechnological substances (a review) (PDF) (Report). 2019. WHO/EMP/RHT/TSN/2019.1.
  25. ISBN 978-3-527-32937-3
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  26. ^ Entry on Stamulumab. at: Römpp Online. Georg Thieme Verlag, retrieved 2021-11-17.
  27. PMID 20318414
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  28. ^ "The Nobel Prize in Physiology or Medicine 1901". Nobel Foundation. Retrieved 2011-02-19.
  29. S2CID 222200504
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  31. ^ "The Nobel Prize in Physiology or Medicine 1984". Nobel Foundation. Retrieved 2011-02-14.
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  33. ^ "International Nonproprietary Names". Drugs.com. Retrieved 2010-12-08.
  34. ^ a b "Statement on a Nonproprietary name adopted by the USAN Council: Olaratumab" (PDF). American Medical Association. 2010-03-08. Retrieved 2010-06-08. {{cite journal}}: Cite journal requires |journal= (help)
  35. ^ "64th Consultation on International Nonproprietary Names for Pharmaceutical Substances, Geneva, 4-7 April 2017 Executive Summary" (PDF). World Health Organization. 2017-07-31. Retrieved 2017-08-22.
  36. PMID 28621572
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  37. ^ "Abciximab". Drugs.com. Retrieved 2010-03-13.
  38. ^ "Trastuzumab". Drugs.com. Retrieved 2010-06-08.
  39. ^ "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. 16 (3). World Health Organization: 264. 2002. Archived from the original (PDF) on 2010-01-21. Retrieved 2010-06-08.
  40. ^ "International Nonproprietary Names (INN) for Pharmaceutical Substances: Names for radicals & groups comprehensive list" (PDF). World Health Organization. 2002: 22. Archived from the original (PDF) on July 3, 2011. Retrieved 2010-12-24. {{cite journal}}: Cite journal requires |journal= (help)
  41. ^ USAN Council. "Statement On A Nonproprietary Name Adopted By The Usan Council - Rozrolimupab" (PDF). American Medical Association. Retrieved 2020-12-06.
  42. ^ "Statement on a Nonproprietary name adopted by the USAN Council: Benralizumab" (PDF). American Medical Association. 2010-03-08. Retrieved 2010-06-08. {{cite journal}}: Cite journal requires |journal= (help)
  43. hdl:10665/330907
    . License: CC BY-NC-SA 3.0 IGO.
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