International Nonproprietary Names (INN) for biological and biotechnological substances (a review)

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INN Working Document 05.179
Update 2012
International Nonproprietary Names (INN)
for biological and biotechnological substances
(a review)
INN Working Document 05.179
Distr.: GENERAL
ENGLISH ONLY
2012
International Nonproprietary Names (INN)
for biological and biotechnological substances
(a review)
Programme on International Nonproprietary Names (INN)
Quality Assurance and Safety: Medicines
Essential Medicines and Health Products (EMP)
International Nonproprietary Names (INN)
for biological and biotechnological substances
(a review)
© World Health Organization 2012
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CONTENTS
0.
INTRODUCTION ..................................................................................................... iv
1.
PHARMACOLOGICAL CLASSIFICATION OF BIOLOGICAL AND
BIOTECHNOLOGICAL SUBSTANCES ................................................................. 1
2.
CURRENT STATUS OF EXISTING STEMS OR SYSTEMS FOR BIOLOGICAL
AND BIOTECHNOLOGICAL SUBSTANCES ...................................................... 4
3.
2.1.
Groups with respective stems ............................................................................. 4
2.2.
Groups with respective pre-stems ....................................................................... 5
2.3.
Groups with INN schemes .................................................................................. 5
2.4.
Groups without respective stems / pre-stems and without INN schemes ........... 5
GENERAL POLICIES FOR BIOLOGICAL AND BIOTECHNOLOGICAL
SUBSTANCES .......................................................................................................... 6
3.1.
General policies for blood products .................................................................... 6
3.2.
General policies for fusion proteins .................................................................... 6
3.3.
General policies for gene therapy products ........................................................ 6
3.4.
General policies for glycosylated compounds .................................................... 7
3.5.
General policies for immunoglobulins fractionated from plasma ...................... 8
3.6.
General policies for monoclonal antibodies ....................................................... 8
3.7.
General policies for non-glycosylated compounds ........................................... 11
3.8.
General policies for skin substitutes ................................................................. 11
3.9.
General policies for transgenic products........................................................... 11
i
4.
3.10.
General policies for vaccines ............................................................................ 11
3.11.
General policies for cell therapy products ........................................................ 12
SUMMARY OF INN ASSIGNED TO BIOLOGICAL AND
BIOTECHNOLOGICAL SUBSTANCES ............................................................... 13
4.1.
Antimicrobial, bactericidal permeability increasing polypeptides ................... 13
4.2.
Antisense oligonucleotides ............................................................................... 13
4.3.
Antithrombins ................................................................................................... 13
4.4.
Blood coagulation cascade inhibitors ............................................................... 14
4.5.
Blood coagulation factors ................................................................................. 14
4.6.
Colony stimulating factors ................................................................................ 15
4.7.
Enzymes ............................................................................................................ 16
4.8.
Erythropoietin type blood factors ..................................................................... 19
4.9.
Gene therapy products ...................................................................................... 19
4.10.
Growth factors .................................................................................................. 20
4.11.
Growth hormone (GH) derivatives ................................................................... 21
4.12.
Growth hormone antagonists ............................................................................ 22
4.13.
Heparin derivatives including low molecular mass heparins ........................... 22
4.14.
Hirudin derivatives............................................................................................ 22
4.15.
Pituitary hormone-release inhibiting peptides .................................................. 22
4.16.
Insulins .............................................................................................................. 23
4.17.
Interferons ......................................................................................................... 24
4.18.
Interleukin receptor antagonists ........................................................................ 24
4.19.
Interleukin type substances ............................................................................... 25
ii
5.
4.20.
Monoclonal antibodies ...................................................................................... 26
4.21.
Oxytocin derivatives ......................................................................................... 29
4.22.
Peptides and glycopeptides (for special groups of peptides see -actide, -pressin,
-relin, -tocin) ..................................................................................................... 29
4.23.
Peptide vaccines / recombinant vaccines .......................................................... 31
4.24.
Pituitary / placental glycoprotein hormones ..................................................... 32
4.25.
Pituitary hormone-release stimulating peptides ................................................ 33
4.26.
Receptor molecules, native or modified ........................................................... 33
4.27.
Synthetic polypeptides with a corticotropin-like action ................................... 34
4.28.
Thrombomodulins ............................................................................................. 34
4.29.
Toxins ............................................................................................................... 35
4.30.
Vasoconstrictors, vasopressin derivatives ........................................................ 35
4.31.
Various .............................................................................................................. 35
CURRENT CHALLENGES .................................................................................... 41
REFERENCES ................................................................................................................. 42
ANNEX 1.......................................................................................................................... 44
The list of INN for composite proteins published ........................................................ 44
ANNEX 2.......................................................................................................................... 53
Transliteration of Greek letters in English, French and Spanish .................................. 53
ANNEX 3.......................................................................................................................... 54
The previous naming scheme for monoclonal antibodies............................................. 54
iii
0. INTRODUCTION
More than 50 years ago, WHO established the International Nonproprietary Name (INN)
Expert Group / WHO Expert Committee on Specifications for Pharmaceutical
Preparations, to assign nonproprietary names to medicinal substances, so that each
substance would be recognized globally by a unique name. These INNs do not give
proprietary rights, unlike a trade mark, and can be used freely as they are public property.
INNs have been assigned to biological products since the early days of the INN
Programme. As well as many names for individual substances, animal insulin
preparations were given an INN in Recommended list 3 in 1959. In the period up to 1980,
names were assigned to antibiotics, synthetic peptides, hormones and other proteins. In
names of compounds related by structure and / or function, specific letter groups, called
stems, are included to aid recognition by health professionals. The -actide for synthetic
polypeptides with a corticotrophin-like action is an example.
In 1982, the name insulin human was proposed for the recombinant protein identical to
natural human insulin, and since then names have been assigned to a growing number of
recombinant products. Within the INN Programme, names have not been assigned to
natural human blood products or vaccines. For those groups of biological products, the
WHO Expert Committee on Biological Standardization (ECBS) has been adopting the
scientific names of the biological products within the definitions of respective
requirements.
Since the time when insulin human became the first recommended INN (rINN) for a
recombinant product, the range of biological / biotechnological products has increased in
size and complexity. For example, new stems have been introduced for tissue
plasminogen activators (-plase) among other groups. Analogues of recombinant
glycosylated proteins produced in different cell systems have been classified using Greek
letters as indicators in the sequence of product introduction: erythropoietin (epoetin alfa,
beta and so on) and glycoprotein hormones (follitropin) are examples. In the 1990s, a
systematic scheme for naming monoclonal antibodies was implemented, based on the
stem -mab, which indicates the origin (mouse, human, etc) of the antibody and its
intended use: tumour, immunomodulator and so on.
As a result of the scientific and technical developments currently taking place, new
products of biotechnology and other biological products are being introduced and more
products can be expected for the treatment or prevention of disease. Examples of such
new products include recombinant blood products, transgenic products (human proteins
expressed in animals or plants), products for gene therapy and novel vaccines.
iv
As this area is becoming more and more complex and challenging, the INN Expert Group
has requested the WHO-INN Secretariat to prepare a working document intended to
summarize and review the past and present INN situation in this field.
This document, first published on the website of the INN Programme in 2006, therefore
presents an inventory of the policy decisions taken by the INN Expert Group during all
these years of change, and of the names assigned to biological and biotechnological
substances. Considering the potential for further developments in the field of biologicals,
this review is intended to be a living document which will be regularly updated to include
new policies, and future INNs assigned.
Comments and suggestions from all interested parties are most welcome and will be
presented to the INN Expert Group for their consideration and for possible incorporation
in future updates of this review.
You are reading the current updated version, also available as pdf-copy at:
http://www.who.int/medicines/services/inn/publication/en/index.html.
v
1. PHARMACOLOGICAL CLASSIFICATION OF
BIOLOGICAL AND BIOTECHNOLOGICAL
SUBSTANCES (1)
Alimentary tract and metabolism
insulins (see item 4.16).
Anti-infectives
antimicrobial, bactericidal permeability increasing polypeptides (see
item 4.1).
Antineoplastics
peptide vaccines / recombinant vaccines (see item 4.23)
toxins (see item 4.29).
Blood and agents acting on the haemopoietic system
antithrombins (see item 4.3)
blood coagulation cascade inhibitors (see item 4.4)
blood coagulation factors (see item 4.5)
erythropoietin type blood factors (see item 4.8)
heparin derivatives including low molecular mass heparins (see item 4.13)
hirudin derivatives (see item 4.14)
thrombomodulins (see item 4.28).
1
Immunomodulators and immunostimulants
colony stimulating factors (see item 4.6)
interferons (see item 4.17)
interleukin receptor antagonists (see item 4.18)
interleukin type substances (see item 4.19)
monoclonal antibodies (see item 4.20)
receptor molecules, native or modified (see item 4.26).
Hormones, hormone antagonists, hormone-release stimulating peptides
or hormone-release inhibiting peptides (excluding insulins)
growth hormone (GH) derivatives (see item 4.11)
growth hormone antagonists (see item 4.12)
oxytocin derivatives (see item 4.21)
pituitary / placental glycoprotein hormones (see item 4.24)
pituitary hormone-release stimulating peptides (see item 4.25)
synthetic polypeptides with a corticotropin-like action (see item 4.27)
vasoconstrictors, vasopressin derivatives (see item 4.30).
Various
antisense oligonucleotides (see item 4.2)
enzymes (see item 4.7)
gene therapy products (see item 4.9)
growth factors (see item 4.10)
2
peptides and glycopeptides (for special groups of peptides see -actide (see
item 4.27), -pressin (see item 4.30), -relin (see item 4.25), -tocin (see
item 4.21)) (see item 4.22).
3
2. CURRENT STATUS OF EXISTING STEMS OR
SYSTEMS FOR BIOLOGICAL AND
BIOTECHNOLOGICAL SUBSTANCES(1) (2) (3) (4) (5) (6) (7)
2.1.
Groups with respective stems
Name of the group
Stem
antisense oligonucleotides
-rsen
blood coagulation cascade inhibitors
-cogin
blood coagulation factors
-cog
colony stimulating factors
-stim
Enzymes
-ase
erythropoietin type blood factors
-poetin
growth factors
-ermin
growth hormone derivatives
som-
heparin derivatives including low molecular mass heparins
-parin
hirudin derivatives
-irudin
pituitary hormone-release inhibiting peptides
-relix
interleukin receptor antagonists
-kinra
interleukin type substances
-kin
monoclonal antibodies
-mab
oxytocin derivatives
-tocin
peptides and glycopeptides (for special groups of peptides -tide
see -actide, -pressin, -relin, -tocin)
pituitary hormone-release stimulating peptides
-relin
receptor molecules, native or modified (a preceding infix -cept
should designate the target)
synthetic polypeptides with a corticotropin-like action
-actide
vasoconstrictors, vasopressin derivatives
-pressin
4
2.2.
Groups with respective pre-stems
Name of the group
Pre-stem
aptamers, classical and mirror ones
-apt-
antimicrobial, bactericidal permeability increasing polypeptides
-ganan
Neurotrophins
-neurin
2.3.
Groups with INN schemes
Name of the group
Antithrombins
gene therapy products
Insulins
Interferons
pituitary / placental glycoprotein hormones
2.4.
Groups without respective stems / pre-stems and without
INN schemes
Name of the group
growth hormone antagonists
Thrombomodulins
Toxins
5
3. GENERAL POLICIES FOR BIOLOGICAL AND
BIOTECHNOLOGICAL SUBSTANCES
3.1.
3.2.
3.3.
General policies for blood products (4)
•
INNs have not been assigned to natural human blood products.
•
Many natural blood products have well-established names, so the
recombinant version should have a distinctive name reflecting as
much as possible the established name used in the field.
•
It is essential to add "activated" to the name of the blood product
when this is presented for therapeutic use in its activated form.
General policies for fusion proteins1 (4)
•
INNs have been assigned to some fusion proteins. If a stem
exists for one or the other part of the fusion protein, this stem
should be brought into the name. This allows the constant part of
a fusion protein to be recognized in the name.
•
At present it is considered unnecessary to indicate that the
product is a fusion product within the name, but this position
may need to be reviewed in the future.
General policies for gene therapy products (2)
In 2005, the two-word nomenclature scheme for gene therapy products was
formally adopted by the members of the INN Expert Group designated to
deal with the selection of nonproprietary names. The 2012 updated scheme
is shown in Table 1.
1
The list of INN for composite proteins published is given in Annex 1, including some fusion proteins.
6
Table 1 Two-word scheme for gene therapy products (updated in 2012)
prefix
word 1
(gene
component)
random to
contribute to
euphonious
and
distinctive
name
e.g. al-; bet-;
val-
word 2
(vector
component)
random to
contribute to
euphonious
and
distinctive
name
infix
to identify the gene using, when available,
existing infixes for biological products or
using similar infix as for the protein for which
the gene codes.
suffix
-(a vowel)gene
e.g. -(o)gene
e.g.-cima-: cytosine deaminase
-ermin-: growth factor
-kin-: interleukin
-lim-: immunomodulator
-lip-: human lipoprotein lipase
-mul-: multiple gene
-stim-: colony stimulating factor
-tima-: thymidine kinase
-tusu-: tumour suppression
e.g. -adeno-: adenovirus
-cana-: canarypox virus
-foli-: fowlpox virus
-herpa-: herpes virus
-lenti-: lentivirus
-morbilli-: paramyxoviridae morbillivirus
-parvo-: adeno-associated virus
(parvoviridae dependovirus)
-retro-: other retrovirus
-vaci-: vaccinia virus
-vec (nonreplicating viral
vector)
-repvec
(replicating
viral vector)
-plasmid
(plasmid vector)
In the case of non-plasmid naked DNA products, there is no need for a second word
in the name.
3.4.
General policies for glycosylated compounds (8)
For glycoproteins / glycopeptides
7
3.5.
•
For groups identified with a stem, e.g. for erythropoetins: -poetin,
differences in the amino acid chain are indicated by using a
random prefix and differences in the glycosylation pattern are
indicated by another designator expressed by a Greek letter2 spelt
in full and added as a second word to the name (e.g. epoetin alfa
(66), darbepoetin alfa (85) see item 4.8).
•
For blood coagulation factors obtained by recombinant
biotechnology, the differences in the glycosylation pattern are
indicated by a Greek letter spelt in full and added as a second
word to the name (e.g. eptacog alfa (activated) (77), octocog alfa
(73)); when the amino acid sequence differs from the natural
product this is indicated by using a random prefix (e.g.
beroctocog alfa (98)); see item 4.5.
•
Similarly, for enzymes identified with a stem -ase obtained by
recombinant biotechnology and differing in the amino acid chain,
these differences are indicated by using a random prefix and
differences in the glycosylation pattern are indicated by a Greek
letter spelt in full and added as a second word to the name (e.g.
alglucosidase alfa (91), bucelipase alfa (95)); see item 4.7.
•
The Greek letters should be used in the Greek alphabetical order
(see Annex 2).
General policies for immunoglobulins fractionated from
plasma (9) (10)
Not to select an INN for immunoglobulins fractionated from plasma is the
current policy.
The "systematic" or descriptive name is essential since the prescriber must
know all the information conveyed by it and there is no benefit in assigning
an INN from which it will not be readily apparent.
3.6.
General policies for monoclonal antibodies (1) (3) (11)3
•
INN for monoclonal antibodies (mAbs) are composed of a prefix,
a substem A, a substem B and a suffix.
2
The transliteration of Greek letters in English, French and Spanish is given in Annex 2.
It contains the revised naming scheme for monoclonal antibodies; the previous naming scheme for
monoclonal antibodies is given in Annex 3.
3
8
•
The common stem for mAbs is -mab, placed as a suffix.
•
The stem -mab is to be used for all products containing an
immunoglobulin variable domain which binds to a defined target.
•
Substem B indicates the species on which the immunoglobulin
sequence of the mAb is based (shown in Table 2).
Table 2 Substem B for the species
a
axo (pre-sub-stem)
Rat
rat-mouse
e
Hamster
i
Primate
o
Mouse
u
Human
xi
chimeric
-xizuzu
chimeric-humanized
Humanized
The distinction between chimeric and humanized antibodies is as follows:
Chimeric: A chimeric antibody is one of which both chain types are chimeric as a
result of antibody engineering. A chimeric chain is a chain that contains a foreign
variable domain (V-D-J-REGION) (originating from one species other than
human, or synthetic) linked to a constant region (C-REGION) of human origin.
Humanized: A humanized antibody is one of which both chain types are
humanized as a result of antibody engineering. A humanized chain is a chain in
which the complementarity determining regions (CDR) of the variable domains
are foreign (originating from one species other than human, or synthetic) whereas
the remaining chain is of human origin. By extension an antibody is described as
humanized if more recent protocoles were used for the humanization.
The –xizu- infix is used for an antibody having both chimeric and humanized
chains.
The -axo- infix is used for an antibody having both rat and mouse chains.
9
•
Substem A indicates the target (molecule, cell, organ) class
(shown in Table 3).
Table 3 Substem A for target class
-b(a)-
Bacterial
-c(i)-
cardiovascular
-f(u)-
Fungal
-k(i)-
interleukin
-l(i)-
immunomodulating
-n(e)- (under
discussion
Neural
-s(o)-
Bone
-tox(a)-
Toxin
-t(u)-
Tumour
-v(i)-
Viral
In principle, a single letter, e.g. -b- for bacterial is used as substem A.
Whenever substem B starts with a consonant (e.g. x or z), to avoid
problems in pronunciation, an additional vowel indicated in the table,
e.g. -ba- is inserted.
Prefix
The prefix should be random i.e.. the only requirement is to contribute to a
euphonious and distinctive name.
Second word
If the monoclonal antibody is conjugated to another protein or to a chemical (e.g.
chelator), identification of this conjugate is accomplished by use of a separate,
second word or acceptable chemical designation. For instance, for mAbs
conjugated to a toxin, the suffix -tox is used in the second word.
If the monoclonal antibody is radiolabelled, the radioisotope is listed first in the
INN, e.g. technetium (99mTc) nofetumomab merpentan (81).
The prefix peg- can be used for pegylated mAbs, but this should be avoided if it
leads to over-long INN. In most cases, it is best to adopt two-word INN for
10
pegylated mAbs, with the first word describing the mAb and the second being
pegol or a related designation.
3.7.
General policies for non-glycosylated compounds (8)
For proteins / peptides:
3.8.
•
Identification of the group with a stem, e.g. for hirudin
analogues:-irudin, and indication of differences in the amino acid
chain by using a random prefix (e.g. bivalirudin (72)).
•
Identification of the group with a word, e.g. insulin, and
indication of differences in the composition of the amino acid
chain as a second element of the name (e.g. insulin argine (58)).
General policies for skin substitutes (4)
The products within this system are made of cells within a matrix, and skin
substitutes can be considered to be engineered tissue and thus fall outside
the scope of the INN system.
3.9.
3.10.
General policies for transgenic products (4)
•
If an INN already exists, the same name should be used for the
transgenic product, qualified in some way to identify that this
product is transgenic.
•
A similar system to that used for glycosylated recombinant
products is suggested to differentiate new or additional sources
of the same substance, and the source of the substance should be
included in the definition of the INN.
General policies for vaccines (4) (5) (6) (7)
•
At present, vaccines are not included within the INN system, but
names are assigned through recommendations of the Expert
Committee on Biological Standardization and through the
pharmacopoeial monograph.
11
3.11.
•
During the INN Consultation in 1993, it was agreed that the
prerequisite for an INN application for a recombinant vaccine4
would be fulfilled if the manufacturer was able to provide all
information outlined in the guidelines entitled Definition of INNs
for Substances Prepared by Biotechnology (WHO /
(12)
Pharm S / Nom 1348 ).
•
During the INN Consultation in 1998, following discussion on
recombinant viruses, the experts agreed not to attempt to name
live viruses.
•
Another approach in vaccine technology seems to be the
development of peptide vaccines5 (epitopes involved in immune
response formation): since these peptides are chemically welldefined, their naming will be less problematic.
General policies for cell therapy products
During the 55th INN Consultation in 2012, the INN Expert Group decided in
principle to name some cell therapy products. A possible INN naming
scheme for cell therapy products is currently under development.
4
5
The definition of recombinant vaccines is given in item 4.23.
The definition of peptide vaccines is given in item 4.23.
12
4. SUMMARY OF INN ASSIGNED TO BIOLOGICAL AND
BIOTECHNOLOGICAL SUBSTANCES(1) (3) (7) (8) (13) (14) (15) (16)
(17) (18) (19) (20) (21)
4.1.
Antimicrobial, bactericidal permeability increasing
polypeptides
The pre-stem for antimicrobial, bactericidal permeability increasing
polypeptides is -ganan.
iseganan (85)6, omiganan (89), pexiganan (78).
4.2.
Antisense oligonucleotides
The common stem for antisense oligonucleotides is -rsen.
afovirsen (97), aganirsen (103), alicaforsen (97), anivamersen (105),
aprinocarsen (97), beclanorsen (101), cenersen (97), custirsen (99),
drisapersen (106), eteplirsen (103), fomivirsen (97), gataparsen (103),
mipomersen (100), miravirsen (101), oblimersen (97), radavirsen (106),
trabedersen (98), trecovirsen (97).
4.3.
Antithrombins
antithrombin III (60), antithrombin alfa (93) (Rec. Glycoprotein (432aa)
from transgenic goats), antithrombin gamma (107).
6
The numbers in parentheses indicate the Proposed list number.
13
4.4.
Blood coagulation cascade inhibitors
The common stem for blood coagulation cascade inhibitors is -cogin.
drotrecogin alfa (activated) (86), pegnivacogin (106), taneptacogin alfa
(90), tifacogin (78).
4.5.
Blood coagulation factors
The common stem for blood coagulation factors is -cog.
The sub-stems -eptacog, -octocog, –nonacog/–trenonacog and -tridecacog
have been selected up to date for recombinant blood coagulation factors.
A prefix will be necessary if the amino acid sequence does not match
that of the naturally occurring material.
In accordance with the general policy, alfa, beta, etc, will be added for
the glycoproteins (see item 3.4 - general policies for glycosylated
compounds).
When the additional statement "activated" is needed, e.g. for the blood
coagulation factor VIIa, it should be spelt out in full and added in
parentheses after the name.
blood coagulation factor VII: -eptacog
eptacog alfa (activated) (77), eptacog alfa pegol (activated) (101),
vatreptacog alfa (activated) (98)
blood factor VIII: -octocog
beroctocog alfa (98), moroctocog alfa (72), octocog alfa (73), simoctocog
alfa (104), turoctocog alfa (104)
blood factor IX: -nonacog (with Ala at the position 148 (Ala-alloform))
nonacog alfa (77), nonacog beta pegol (104)
-trenonacog (with Thr at the position 148 (Thr-alloform))
14
trenonacog alfa (107)
blood coagulation factor XIII: -tridecacog
catridecacog (99)
recombinant von Willebrand factor (vWF): -vonicog
vonicog alfa (102).
4.6.
Colony stimulating factors
The common stem for colony stimulating factors is -stim.
ancestim (79) (cell growth factor), garnocestim (86) (immunomodulator),
pegacaristim (80) (megakaryocyte growth factor), romiplostim (97)
(thrombopoietin receptor (MPL) agonist)
combination of two different types of colony stimulating factors: -distim
leridistim (80), milodistim (75)
granulocyte colony stimulating factor (G-CSF) type substances: -grastim
balugrastim (107), empegfilgrastim (107), filgrastim (64), lenograstim (64),
lipegfilgrastim (107), nartograstim (66), pegfilgrastim (86),
pegnartograstim (80)
granulocyte macrophage colony stimulating factor (GM-CSF) types
substances: -gramostim
ecogramostim (62), molgramostim (64), regramostim (65), sargramostim
(66)
macrophage stimulating factors (M-CSF) type substances: -mostim
cilmostim (71), lanimostim (91), mirimostim (65)
interleukin-3 analogues and derivatives: -plestim
15
daniplestim (76), muplestim (74).
4.7.
Enzymes
The common stem for enzymes, in general, is -ase.
Sub-stems are referring to the activity of the substances.
proteinase:
with -ase suffix:
brinase (22), calaspargase pegol (105), kallidinogenase (22), ocrase (28),
pegaspargase (64), promelase (47), rasburicase (82), serrapeptase (31),
sfericase (40), streptokinase (6), urokinase (48), urokinase alfa (77)
without -ase suffix:
batroxobin (29), bromelains (18), chymopapain (26), chymotrypsin (10),
defibrotide (44), fibrinolysin (human) (10), sutilains (18)
Lipase: -lipase
bucelipase alfa (95), burlulipase (107), rizolipase (22), sebelipase alfa (107)
enzymes with superoxide dismutase activity: -dismase
•
ledismase (70), sudismase (58)
•
isomerase (belongs to this group but in which the preferred stem
has not been used)
orgotein (31), pegorgotein (72)
plasminogen activator combined with another enzyme: -diplase
amediplase (79)
tissue-type-plasminogen activators: -teplase
alteplase (73), desmoteplase (80), duteplase (62), lanoteplase (76),
monteplase (72), nateplase (73), pamiteplase (78), reteplase (69), silteplase
(65), tenecteplase (79)
16
anistreplase (59) (belongs to this group but in which the preferred stem has
not been used)
urokinase-type-plasminogen activators: -uplase
nasaruplase (76), nasaruplase beta (86), saruplase (76)
others:
agalsidase alfa (84): human alpha-galactosidase isoenzyme A, isolated
from human cell line, clone RAG 001, glycoform α
agalsidase beta (84): α-galactosidase (human clone λAG18 isoenzyme A
subunit protein moiety reduced), glycoform β
alfimeprase (85): [3-L-serine]fibrolase-(3-203)-peptide (fibrolase :
fibrinolytic enzyme isolated from Agkistrodon contrix contrix venom)
alglucerase (68): glucosylceramidase (human placenta isoenzyme protein
moiety reduced)
alglucosidase alfa (91): human lysosomal prepro-α-glucosidase-(57-952)peptide 199-arginine-223-histidine variant
asfotase alfa (104): tissue-nonspecific alkaline phosphatase- IgG1 fusion
protein;human tissue-nonspecific isozyme alkaline phosphatase (APTNAP, EC=3.1.3.1) fusion protein with leucyl-lysyl-human
immunoglobulin G1 Fc region {(6-15)-H-CH2-CH3 of IGHG1*03} fusion
protein with aspartyl-isoleucyl-deca(aspartic acid), dimer (493-493':496496')-bisdisulfide
condoliase (106): endolyase, chondroitin ABC (C-ABC).
glycosaminoglycan lyase chondroitin ABC endolyase 1 (chondroitinase
ABC) Proteus vulgaris
crisantaspase (107): L-asparaginase (EC 3.5.1.1, L-asparagine
amidohydrolase) Erwinia chrysanthemi tetramer α4
dornase alfa (70): deoxyribonuclease (human clone 18-1 protein moiety)
epafipase (85): 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine deacetylase(6-400)-peptide(human)
eufauserase (84): broad spectrum serine-protease enzyme, extracted from
the Antartic krill (Euphausia superba)
17
galsulfase (92): N-acetylgalactosamine 4-sulfatase (human CSL4S-342
cell)
glucarpidase (92): recombinant glutamate carboxypeptidase
(carboxypeptidase G2)
hyalosidase (50): hyaluronoglucosaminidase or E.C. 3.2.1.35
hyaluronidase (1): enzymes of various origins which depolymerize
hyaluronic acid
idursulfase (90): α-L-iduronate sulfate sulfatase
idursulfase beta (106): iduronate 2-sulfatase (α-L-iduronate sulfate
sulfatase), human proenzyme produced in CHO cells (glycoform beta)
imiglucerase (72): 495-L-histidineglucosylceramidase (human placenta
isoenzyme protein moiety)
laronidase (86): 8- L-histidine-α-L-iduronidase (human)
pegademase (63): adenosine deaminase, reaction product with succinic
anhydride, esters with polyethylene glycol monomethyl ether
The source of the product should be indicated
pegloticase (98): tetramer α4 of des-(1-5)-[6-threonine,45-threonine, 290lysine, 300-serine]uricase (EC 1.7.3.3, urate oxidase) from Sus scrofa
(porcine), non acetylated, of which some of the lysine 6-amine residues are
engaged in a carbamate linkage with a monomethylic ether of
polyoxyethylene (macrogol)
pegadricase (105): pegylated Urate Oxidase from Candida utilis,
[198-threonine(S>T)]uricase (EC 1.7.3.3, urate oxidase) Pichia jadinii
(Yeast) (Candida utilis) tetramer, 6-amino group of an average of 3 lysine
residues, mostly in position 16, 19, and 85 of each monomer, are amidified
with α-(3-carboxypropanoyl)-ω-methoxypoly(oxyethylene)
penicillinase (10): an enzyme obtained by fermentation from cultures of
B.Cereus
ranpirnase (81): ribonuclease (Rana pipiens)
senrebotase (107): L-methionylglycyl-L-seryl-des-(445-glycine,446-Ltyrosine)-[2-L-glutamic acid,432,442,444,447-tetra-L-aspartic
acid]botulinum neurotoxin A precursor 27-L-alanine variant light chain
18
(433-41')-disulfide with [14-L-arginine,15-L-lysine]human nociceptin
fusion protein with L-alanyl-L-leucyl-L-alanyltris(tetraglycyl-L-seryl)[3-L-valine,4-L-leucine,5-L-glutamine-418-L-leucine,419-L-aspartic
acid]botulinum neurotoxin A heavy chain-(1-419)-peptide
streptodornase (6): enzyme obtained from cultures of various strains of
Streptococcus hemolyticus and capable of hydrolysing
desoxyribonucleoproteins
taliglucerase alfa (101): L-glutamyl-L-phenylalanyl-[495(497)-Lhistidine(R>H)]human glucosylceramidase (beta-glucocerebrosidase)
peptide with L-aspartyl-L-leucyl-L-leucyl-L-valyl-L-aspartyl-L-threonyl-Lmethionine,glycosylated peptide 1-506
tilactase (50): β-D-galactosidase or EC 3.2123
velaglucerase alfa (98): human glucosylceramidase (EC 3.2.1.45 or betaglucocerebrosidase), glycoform α.
4.8.
Erythropoietin type blood factors
The common stem for erythropoietin type blood factors is -poetin.
In the case of erythropoietins, it was decided to select epoetin together
with a Greek letter to differentiate between compounds of the same
amino acid sequence as human erythropoietin which vary in the
glycosylation pattern (see item 3.4 - general policies for glycosylated
compounds).
Substances with different amino acid sequences will be named using the
-poetin stem and a random prefix.
darbepoetin alfa (85), epoetin alfa (66), epoetin beta (62), epoetin gamma
(67), epoetin delta (85), epoetin epsilon (72), epoetin zeta (95), epoetin theta
(95), epoetin kappa (97), epoetin omega (73).
4.9.
Gene therapy products
alferminogene tadenovec (95), alipogene tiparvovec (99), amolimogene
bepiplasmid (98), beperminogene perplasmid (95), contusugene ladenovec
(97), golnerminogene pradenovec (101), riferminogene pecaplasmid (100),
19
rilimogene galvacirepvec (107), rilimogene glafolivec (107), sitimagene
ceradenovec (97), taberminogene vadenovec (100), talimogene
laherparepvec (104), tipapkinogene sovacivec (102), velimogene aliplasmid
(97), vocimagene amiretrorepvec (107).
4.10.
Growth factors
The common stem for growth factors is -ermin.
Sub-stems allow distinction between the various types of growth factors.
INNs for tumour necrosis factors (TNF) are also classified under the
stem -ermin.
vascular endothelial growth factors: -bermin
telbermin (85)
epidermal growth factors: -dermin
murodermin (63), nepidermin (97)
fibroblast growth factors: -fermin
ersofermin (66), palifermin (88), repifermin (82), sprifermin (105),
trafermin (74), velafermin (94)
leukaemia-inhibiting factors: -filermin
emfilermin (82)
tumour necrosis factors: -nermin
ardenermin (88), dulanermin (99), plusonermin (73), sonermin (68),
tasonermin (78)
platelet-derived growth factors: -plermin
becaplermin (74)
20
insulin-like growth factors: -sermin
mecasermin (66), mecasermin rinfabate (92)
transforming growth factors: -termin
cetermin (74), liatermin (81)
bone morphogenetic proteins: -otermin
avotermin (77), dibotermin alfa (89), eptotermin alfa (92),
radotermin (92)
others:
dapiclermin (93) (modified ciliary neurotrophic factor (CNTF)).
4.11.
Growth hormone (GH) derivatives
The common stem for growth hormone derivatives is som-.
human growth hormone derivatives:
somatrem (54), somatropin (74), somatropin pegol (103)
For substances other than human, suffixes are added to indicate the
species specificity of the structure.
bovine-type substances: -bove
somagrebove (63), somavubove (63), sometribove (74), somidobove (58)
porcine-type substances: -por
somalapor (62), somenopor (62), somfasepor (66), sometripor (75)
salmon-type substances: -salm
somatosalm (69)
21
others (growth hormone related peptides):
somatorelin (57) (pituitary hormone-release stimulating peptides, see
item 4.25), somatostatin (46) (growth hormone release inhibitor).
4.12.
Growth hormone antagonists
pegvisomant (82).
4.13.
Heparin derivatives including low molecular mass heparins
The common stem for heparin derivatives including low molecular mass
heparins is -parin.
ardeparin sodium (68), adomiparin sodium (104), bemiparin sodium (75),
certoparin sodium (70), dalteparin sodium (77), deligoparin sodium (89),
enoxaparin sodium (77), heparin sodium (54), livaraparin calcium (86),
minolteparin sodium (74), nadroparin calcium (78), parnaparin sodium (77),
reviparin sodium (78), semuloparin sodium (99), sevuparin sodium (106),
tafoxiparin sodium (102), tinzaparin sodium (77).
4.14.
Hirudin derivatives
The common stem for hirudin derivatives is -irudin.
bivalirudin (72), desirudin (76), lepirudin (76), pegmusirudin (77).
4.15.
Pituitary hormone-release inhibiting peptides
The common stem for pituitary hormone-release inhibiting peptides is
-relix.
22
abarelix (78), cetrorelix (66), degarelix (86), detirelix (56), ganirelix (65),
iturelix (79), ozarelix (94), prazarelix (81), ramorelix (69), teverelix (78).
4.16.
Insulins
Up to now, the insulin derivatives have been named using the two-word
approach. The compounds named represent a structure with an
additional amino acid, such as insulin argine (58), or represent
modifications of the amino acid sequence, i.e. insulin aspart (76).
biphasic insulin injection (16), compound insulin zinc suspension (06),
dalanated insulin (104), globin zinc insulin injection (06), insulin argine
(58), insulin aspart (76), insulin defalan (37), insulin degludec (101), insulin
detemir (80), insulin glargine (76), insulin glulisine (84), insulin human (48),
insulin lispro (72), insulin peglispro (107), insulin tregopil (103), insulin
zinc suspension (amorphous) (04), insulin zinc suspension (crystalline) (04),
isophane insulin (04), neutral insulin injection (15), protamine zinc insulin
injection (06)
argine: B30-yl-L-arginyl-L-arginine
aspart: [B28-L-aspartic acid]
dalanated: des-B30-alanine
defalan: des-B1-phenylalanine
degludec: N6, B29-[N-(15-carboxypentadecanoyl)-L-γ-glutamyl]-des-30B-Lthreonine
detemir: N6,B29-tetradecanoyl-des-B30-L-threonine
glargine: [A21-glycine], B30-yl-L-arginyl-L-arginine
glulisine: [B3-lysine, B29-glutamic acid]
lispro: [B28-L-lysine, B29-L-proline]
tregopil: N6, B29-(4,7,10,13-tetraoxatetradecanoyl).
23
4.17.
Interferons
Interferon was published as an INN in 1962 with a general definition
based on the origin and activity, e.g. "a protein formed by the
interaction of animal cells with viruses capable of conferring on animal
cells resistance to virus infection".
The name was revised in the 1980s when human interferon and its
variations alfa, beta and gamma were produced by recombinant
biotechnology. The INN Expert Group would have preferred to replace
the old INN interferon by alfaferon, betaferon and gammaferon;
however, this approach could not be adopted as these names had
already been registered as trade marks. The system adopted was thus to
take interferon alfa, interferon beta and interferon gamma, and to
provide, when necessary, for further distinction by additional numbers,
or in the case of mixtures, by additional codes. Additional Arabic
numbers can be used to distinguish subspecies which differ significantly
in primary amino acid sequence, but are still considered to belong to
one of the primary groups e.g. Interferon alfa-1, interferon alfa- 2.
Small (lower case) letters are used to subdivide such groups further on
the basis of less significant differences like one, two or three amino acid
differences or post translational modifications, including glycosylation
e.g. Interferon alfa-2a, Interferon alfa-2b, Interferon beta-1a,
Interferon beta-1b.
albinterferon alfa-2b (99), cepeginterferon alfa-2b (105), interferon alfa
(73), interferon alfacon-1 (77), interferon beta (73), interferon gamma (73),
peginterferon alfa-2a (84), peginterferon alfa-2b (84), peginterferon
lambda-1a (105).
4.18.
Interleukin receptor antagonists
The common stem for interleukin receptor antagonists is -kinra.
interleukin-1 (IL-1) receptor antagonists: -nakinra
anakinra (72)
interleukin-4 (IL-4) receptor antagonists: -trakinra
pitrakinra (87).
24
4.19.
Interleukin type substances
The common stem for interleukin type substances is -kin.
In accordance with general policy for naming glycosylated proteins (see
item 3.4), it was agreed to publish the INNs for glycosylated interleukins
with alfa, beta.
interleukin-1 (IL-1) analogues and derivatives: -nakin
interleukin-1α analogues and derivatives: -onakin
pifonakin (77)
interleukin-1β analogues and derivatives: -benakin
mobenakin (72)
interleukin-2 (IL-2) analogues and derivatives: -leukin
adargileukin alfa (89), aldesleukin (63), celmoleukin (65), denileukin
diftitox (78), pegaldesleukin (74), teceleukin (67), tucotuzumab celmoleukin
(95)
interleukin-3 (IL-3) analogues and derivatives: -plestim (belongs to this
group but in which the preferred stem has not been used)
daniplestim (76), muplestim (74)
interleukin-4 (IL-4) analogues and derivatives: -trakin
binetrakin (82)
interleukin-6 (IL-6) analogues and derivatives: -exakin
atexakin alfa (72)
interleukin-8 (IL-8) analogues and derivatives: -octakin
emoctakin (74)
interleukin-10 (IL-10) analogues and derivatives: -decakin
ilodecakin (81)
25
interleukin-11 (IL-11) analogues and derivatives: -elvekin
oprelvekin (76)
interleukin-12 (IL-12) analogues and derivatives: -dodekin
edodekin alfa (79)
interleukin-13 (IL-13) analogues and derivatives: -tredekin
cintredekin besudotox (92)
a recombinant human interleukin-18 (IL-18) with 157 amino acids:
iboctadekin (92)
a recombinant human interleukin-21: -enicokin
denenicokin (99)
neurotrophins (interleukin-78, brain derived neurotropic factor): -neurin
(pre-stem)
abrineurin (84).
4.20.
Monoclonal antibodies
The common stem for monoclonal antibodies is -mab.
INNs for monoclonal antibodies alphabetically by origin:
-axomab (pre-sub-stem, rat-murine hybrid)
catumaxomab (93), ertumaxomab (93)
-omab (mouse origin)
abagovomab (95), afelimomab (80), altumomab (80), anatumomab
mafenatox (86), arcitumomab (74), bectumomab (81), besilesomab (92),
biciromab (66), blinatumomab (100), capromab (80), detumomab (80),
dorlimomab aritox (66), edobacomab (80), edrecolomab (74), elsilimomab
(89), enlimomab (80), enlimomab pegol (77), epitumomab (97), epitumomab
cituxetan (89), faralimomab (81), gavilimomab (84), ibritumomab tiuxetan
26
(86), igovomab (86), imciromab (66), inolimomab (80), lemalesomab (86),
maslimomab (66), minretumomab (80), mitumomab (82), moxetumomab
pasudotox (102), nacolomab tafenatox (80), naptumomab estafenatox (96),
nerelimomab (81), odulimomab (81), oregovomab (86), racotumomab (100),
satumomab (81), solitomab (106), sulesomab (86), taplitumomab paptox
(84), technetium (99mTc) fanolesomab (86), technetium (99mTc) nofetumomab
merpentan (81), technetium (99mTc) pintumomab (86), telimomab aritox (66),
tenatumomab (99), tositumomab (80), vepalimomab (80), zolimomab aritox
(80)
-umab (human origin)
actoxumab (107), adalimumab (85), adecatumumab (90), alirocumab (107),
atinumab (104), atorolimumab (80), belimumab (89), bertilimumab (88),
bezlotoxumab (107), briakinumab (101), brodalumab (105), canakinumab
(97), carlumab (104), cixutumumab (100), conatumumab (99),
daratumumab (101), denosumab (94), drozitumab (103), duligotumab (107),
efungumab (95), enoticumab (107), exbivirumab (91), fasinumab (107),
fezakinumab (101), figitumumab (100), flanvotumab (106), foralumab (103),
foravirumab (100), fresolimumab (101), fulranumab (104), ganitumab (103),
gantenerumab (97), glembatumumab (102), golimumab (91), icrucumab
(104), inclacumab (106), intetumumab (101), ipilimumab (94), iratumumab
(94), lerdelimumab (86), lexatumumab (95), libivirumab (91), lirilumab
(107), lucatumumab (98), mapatumumab (93), mavrilimumab (102),
metelimumab (88), morolimumab (79), namilumab (104), narnatumab (105),
nebacumab (66), necitumumab (100), nivolumab (107), ofatumumab (93),
olaratumab (103), orticumab (107), oxelumab (105), panitumumab (96),
panobacumab (100), patritumab (106), placulumab (107), pritumumab (89),
radretumab (104), rafivirumab (100), ramucirumab (100), raxibacumab
(92), regavirumab (80), rilotumumab (101), robatumumab (100), roledumab
(103), sarilumab (106), secukinumab (102), sevirumab (66), sifalimumab
(104), sirukumab (105), stamulumab (95), tabalumab (105), teprotumumab
(101), tralokinumab (102), tremelimumab (97), tuvirumab (66), urelumab
(104), ustekinumab (99), vesencumab (104), votumumab (80), zalutumumab
(93), zanolimumab (92), ziralimumab (84)
-ximab (chimeric origin)
abciximab (80), amatuximab (104), basiliximab (81), bavituximab (95),
brentuximab vedotin (103), cetuximab (82), clenoliximab (77), ecromeximab
(87), ensituximab (103), futuximab (107), galiximab (89), girentuximab
(101), indatuximab ravtansine (105), infliximab (77), iodine (124I)
girentuximab (101), keliximab (81), lumiliximab (90), pagibaximab (93),
priliximab (80), rituximab (77), siltuximab (100), teneliximab (87),
ublituximab (104), vapaliximab (87), volociximab (93), zatuximab (107)
27
-xizumab (chimeric-humanized origin)
otelixizumab (99)
-zumab (humanized origin)
alacizumab pegol (98), alemtuzumab (83), anrukinzumab (98), apolizumab
(87), aselizumab (88), bapineuzumab (93), benralizumab (102),
bevacizumab (86), bivatuzumab (86), blosozumab (105), cantuzumab
mertansine (105), cantuzumab ravtansine (105), caplacizumab (106),
cedelizumab (81), certolizumab pegol (97), citatuzumab bogatox (99),
clazakizumab (107), yttrium (90Y) clivatuzumab tetraxetan (102),
crenezumab (105), dacetuzumab (98), daclizumab (78), dalotuzumab (107),
demcizumab (107), eculizumab (87), efalizumab (85), elotuzumab (100),
enavatuzumab (104), enokizumab (104), epratuzumab (82), erlizumab (84),
etaracizumab (99), etrolizumab (104), farletuzumab (100), felvizumab (77),
fontolizumab (87), gemtuzumab (83), gevokizumab (104), ficlatuzumab
(105), ibalizumab (97), imgatuzumab (107), inotuzumab ozogamicin (92),
itolizumab (103), ixekizumab (105), labetuzumab (85), lampalizumab (107),
lebrikizumab (101), ligelizumab (107), lintuzumab (86), lorvotuzumab
mertansine (103), matuzumab (88), mepolizumab (81), milatuzumab (98),
mogamulizumab (104), motavizumab (95), natalizumab (79), nimotuzumab
(94), obinutuzumab (101), ocaratuzumab (107), ocrelizumab (95),
olokizumab (103), omalizumab (84), onartuzumab (104), oportuzumab
monatox (100), ozoralizumab (105), palivizumab (79), parsatuzumab (107),
pascolizumab (87), pateclizumab (105), perakizumab (107), pertuzumab
(89), pexelizumab (86), ponezumab (104), quilizumab (106), ranibizumab
(90), reslizumab (85), romosozumab (106), rontalizumab (101), rovelizumab
(81), ruplizumab (83), samalizumab (105), sibrotuzumab (86), simtuzumab
(107), siplizumab (87), solanezumab (107), sontuzumab (94), suvizumab
(102), tadocizumab (94), talizumab (89), tanezumab (99), tefibazumab (92),
teplizumab (97), tigatuzumab (98), tocilizumab (90), toralizumab (87),
trastuzumab (78), trastuzumab emtansine (103), tregalizumab (104),
tucotuzumab celmoleukin (95), urtoxazumab (90), vatelizumab (105),
vedolizumab (100), veltuzumab (98), visilizumab (84), vorsetuzumab (107),
vorsetuzumab mafodotin (107), yttrium 90Y tacatuzumab tetraxetan (93)
Others: muromonab-CD3 (59) (the first monoclonal antibody to which an
INN was assigned belongs to this group but it was named before the stem
was established).
28
4.21.
Oxytocin derivatives
The common stem for oxytocin derivatives is -tocin.
argiprestocin (13), aspartocin (11), carbetocin (45), cargutocin (35),
demoxytocin (22), nacartocin (51), oxytocin (13).
4.22.
Peptides and glycopeptides
for special groups of peptides see -actide (see item 4.27), -pressin (see
item 4.30), -relin (see item 4.25), -tocin (see item 4.21)
The common stem for peptides and glycopeptides is -tide.
analgesic: leconotide (86), ziconotide (78)
angiogenesis inhibitor: cilengitide (81)
angiotensin converting-enzyme inhibitor: teprotide (36)
antianaemic: peginesatide (103)
anti-inflammatory: icrocaptide (89)
antiarrythmic: danegaptide (101), rotigaptide (94)
antidepressant: nemifitide (87)
antidiabetic: amlintide (76), davalintide (101), exenatide (89), lixisenatide
(99), pramlintide (74), seglitide (57)
antidiarrhoeal: lagatide (75)
antithrombotic: eptifibatide (78) (-fiba- is a pre-substem for platelet
aggregation inhibitor (GPIIb/IIIa receptor antagonist))
antiviral: enfuvirtide (85), tifuvirtide (91)
atrial natriuretic factor type substance: anaritide (57), cenderitide (105),
neseritide (80), ularitide (69)
autoimmune disorders: dirucotide (100)
cardiac stimulant: carperitide (65)
29
cicatrisation promoter: ensereptide (107)
diagnostic: betiatide (58), bibapcitide (78), ceruletide (34), depreotide (80),
fluciclatide (18F) (103), maraciclatide (103), mertiatide (60),
pendetide (70), technetium (99mTc) apcitide (86), technetium
(99mTc) etarfolatide (107), teriparatide (50)
expectorant (in cystic fibrosis): lancovutide (99)
gastro-intestinal bleeding / antineoplastic: edotreotide (84), ilatreotide (68),
lanreotide (64), octreotide (52),
pentetreotide (66), vapreotide
(62)
gastro-intestinal functions normalizing agent: linaclotide (97), plecanatide
(104)
glucagon-like peptide (GLP) analogues: -glutide
albiglutide (97), dulaglutide (103), elsiglutide (104), liraglutide (87),
semaglutide (101), taspoglutide (99), teduglutide (90)
growth stimulant-veterinary: nosiheptide (35)
gut motility increasing: ociltide (52)
hormone analogue: semparatide (80)
immunological agents - antineoplastics: almurtide (74), delmitide (92),
edratide (89), goralatide (72),
mifamurtide (95), murabutide (49),
pentigetide (60), pimelautide (53),
prezatide copper acetate (67),
rolipoltide (94), romurtide (61),
tabilautide (60), temurtide (60),
tigapotide (95)
immunological agents for active immunization: -motide (see item 4.23)
amilomotide (105), asudemotide (107), disomotide (94), elpamotide (103),
latromotide (107), ovemotide (94), pradimotide (107), tertomotide (98),
tiplimotide (82), trempamotide (107)
inhibition of growth hormone release: pasireotide (90)
30
kallicrein inhibitor: ecallantide (93)
melanocortin receptor agonist: afamelanotide (99), bremelanotide (95)
neuromodulator / neuroprotective agent: davunetide (100), ebiratide (56),
obinepitide
(96),
vanutide
cridificar (100)
peptic ulcer: sulglicotide (29), triletide (50)
pulmonary surfactant: lusupultide (80), sinapultide (78)
sedative: emideltide (70)
thrombin receptor as an agonist, promoter of bone and skin wound healing:
rusalatide (96)
transforming growth factor beta-1 inhibitor: disitertide (99)
treatment of Parkinson's disease: doreptide (59), pareptide (38)
zonulin antagonist (in celiac disease): larazotide (99)
other: defibrotide (44) (nucleotide).
4.23.
Peptide vaccines / recombinant vaccines
Definition of peptide vaccines: vaccine in which antigens are produced
from synthetic peptides and transported through the bloodstream by an
adjuvant, in order to stimulate an immune response.
Definition of recombinant vaccines: vaccine produced from a cloned gene.
Description of recombinant vaccines: there are certain antigens on viruses
and bacteria which are better at stimulating an antibody response by the
animal than others. The genes for these antigens can be isolated, and made
to produce large quantities of the antigens they code for. A recombinant
vaccine contains these antigens, not the whole organism. Compare with
"modified live vaccine" and "killed vaccine".
The following substances are peptide vaccines (see item 4.22): -motide
31
amilomotide (105), asudemotide (107), disomotide (94), elpamotide (103),
latromotide (107), ovemotide (94), pradimotide (107), tertomotide (98),
tiplimotide (82).
The following substance is the recombinant vaccine:
verpasep caltespen (95) (heat-shock protein HSP 65 (Mycobacterium bovis
strain BCG) fusion protein with transcription factor E7 (human papilloma
virus 16)).
The suffix -tespen is the indicator of heat shock protein.
4.24.
Pituitary / placental glycoprotein hormones
The names selected by the International Union of Pure and Applied
Chemistry–International Union of Biochemistry (IUPAC-IUB) have, to
date, been chosen for compounds with an amino acid sequence identical
to that of the naturally occurring human hormones. Addition of a
Greek letter as the second part of the name will allow differentiation of
different glycosylation patterns for compounds produced by
biotechnology (see item 3.4 - general policies for glycosylated
compounds).
follicle stimulating hormones: ending in (-)follitropin
corifollitropin alfa (80), follitropin alfa (71), follitropin beta (75), follitropin
gamma (106), urofollitropin (57), varfollitropin alfa (101)
gonadotropin: ending in -gonadotropin
choriogonadotropin alfa (76), chorionic gonadotrophin (01): chorionic
gonadotropins, obtained from human serum and urine during pregnancy and
has both lutropin and follitropin activity
serum gonadotrophin (01): used for the follicle stimulating hormone (FSH,
follitropin) from serum of pregnant mares
luteinizing hormones: ending in (-)lutropin
lutropin alfa (71).
32
4.25.
Pituitary hormone-release stimulating peptides
The common stem for pituitary hormone-release stimulating peptides is
-relin.
LHRH-release-stimulating peptides:
avorelin (74), buserelin (36), deslorelin (61), fertirelin (42), gonadorelin
(32), goserelin (55), histrelin (53), leuprorelin (47), lutrelin (51), nafarelin
(50), peforelin (93), triptorelin (58), zoptarelin doxorubicin (107)
growth hormone release-stimulating peptides: -morelin
anamorelin (97), capromorelin (83), dumorelin (59), examorelin (72),
ipamorelin (78), lenomorelin (106), macimorelin (100), pralmorelin (77),
rismorelin (74), sermorelin (56), somatorelin (57), tabimorelin (86),
tesamorelin (96), ulimorelin (103)
thyrotropin releasing hormone analogues: -tirelin
azetirelin (60), montirelin (58), orotirelin (58), posatirelin (60), protirelin
(31), taltirelin (75)
thyrotropin alfa (78) (thyrotropin releasing hormone (TRH) analog, belongs
to this group but in which the preferred stem has not been used)
other: corticorelin (66) (diagnostic agent).
4.26.
Receptor molecules, native or modified
The stem for receptor molecules, native or modified is -cept.
A preceding infix should designate the target.
B-cell activating factor receptors: -babriobacept (98)
vascular endothelial growth factor receptors: -beraflibercept (96), conbercept (105)
complement receptors: -comirococept (91)
33
subgroup of interferon receptors: -farbifarcept (86)
lymphocyte function-associated antigen 3 receptors: -lefaalefacept (84)
interleukin-1 receptors: -narilonacept (95)
tumour necrosis factor receptors: -nercept.
baminercept (99), etanercept (81), lenercept (72), onercept (86),
pegsunercept (95)
cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) receptors: -taabatacept (91), belatacept (93)
transmembrane activator and calcium modulator and cyclophilin ligand
interactor: -taciatacicept (95)
transforming growth factor receptors: -terdalantercept (105), sotatercept (104)
antiviral receptors: -viralvircept sudotox (69).
4.27.
Synthetic polypeptides with a corticotropin-like action
The common stem for synthetic polypeptides with a corticotropin-like
action is -actide.
alsactide (45), codactide (24), giractide (29), norleusactide (18), seractide
(31), tetracosactide (18), tosactide (24), tricosactide (44), tridecactide (97).
4.28.
Thrombomodulins
sothrombomodulin alfa (101), thrombomodulin alfa (94).
34
4.29.
Toxins
toxin ML-1 (mistletoe lectin I) (Viscum album): aviscumine (86).
4.30.
Vasoconstrictors, vasopressin derivatives
The common stem for vasoconstrictors, vasopressin derivatives is
-pressin.
argipressin (13), desmopressin (33), felypressin (13), lypressin (13),
ornipressin (22), selepressin (105), terlipressin (46), vasopressin injection
(16).
4.31.
Various
•
alisporivir (100): [8-(N-methyl-D-alanine),9-(N-ethyl-L-valine)]cyclosporine
•
agatolimod (98): DNA, d(P-thio)(T-C-G-T-C-G-T-T-T-T-G-T-C-G-T-T-T-T-GT-C-G-T-T)
•
angiotensin II (65): 5-L-isoleucineangiotensin II (the source of the material should
be indicated)
•
angiotensinamide (12): N-{1-{N-{N-{N-[N-(N2asparaginylarginyl)valyl]tyrosyl}valyl}histidyl}prolyl}-3-phenylalanine
• bamosiran (106): siRNA inhibitor of β2-adrenergic receptor production
•
bevasiranib (99): siRNA inhibitor of Vascular Endothelial Growth Factor (VEGF)
production
•
blisibimod (107): B-cell activating factor (BAFF)-binding peptide
fragment/human IgG1 Fc fusion protein
35
•
calcitonin (80): a polypeptide hormone that lowers the calcium concentration in
blood (the species specificity should be indicated in brackets behind the name)
•
conestat alfa (107): human plasma protease C1 inhibitor (C1 esterase inhibitor)
(N,O-glycosylated recombinant protein expressed in the mammary gland of
transgenic rabbits), glycoform α
•
delcasertib (105): human immunodeficiency virus 1 protein Tat-(46-57)-peptide
(1→1')-disulfide with L-cysteinyl-[mouse protein kinase C delta type-(8-17)peptide]
•
epelestat (92): human recombinant neutrophil elastase inhibitor, bovine pancreatic
trypsin inhibitor (BPTI) homologue
•
edifoligide (89): oligonucleotide
•
egaptivon pegol (104): a pegylated aptamer which binds von Willebrand factor;
5'-O-{[6-(carboxyamino)hexyl]hydroxyphosphoryl}-2'-O-methylguanylyl(3'→5')-2'-O-methylcytidylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-Omethyluridylyl-(3'→5')-2'-deoxyguanylyl-(3'→5')-2'-deoxycytidylyl-(3'→5')-2'deoxyadenylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-O-methyluridylyl(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-O-methylcytidylyl-(3'→5')-2'-Omethylcytidylyl-(3'→5')-2'-O-methyluridylyl-(3'→5')-2'-O-methyluridylyl(3'→5')-2'-O-methylcytidylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-Omethylguanylyl-(3'→5')-2'-O-methylcytidylyl-(3'→5')-2'-deoxycytidylyl-(3'→5')2'-O-methyl-P-thioguanylyl-(3'→5')-thymidylyl-(3'→5')-2'-O-methylguanylyl(3'→5')-2'-deoxycytidylyl-(3'→5')-2'-deoxyguanylyl-(3'→5')-2'-deoxyguanylyl(3'→5')-thymidylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-O-methylcytidylyl(3'→5')-2'-deoxycytidylyl-(3'→5')-2'-O-methyluridylyl-(3'→5')-2'deoxycytidylyl-(3'→5')-2'-deoxycytidylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')2'-O-methyluridylyl-(3'→5')-2'-deoxycytidylyl-(3'→5')-2'-O-methyladenylyl(3'→5')-2'-O-methylcytidylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-Omethylcytidylyl-(3'→3')-thymidine, carbamate ester with monomethyl ether of
polyethylene gycol (20 kDa)
•
hemoglobin glutamer (80): the species specificity should be indicated in brackets
behind the name, "(bovine)"; the average mass of the polymer is given as e.g.
haemoglobin glutamer-250 for 250kD
•
hemoglobin crosfumaril (76): hemoglobin A0 (human α2β2 tetrameric subunit), αchain 99,99'-diamide with fumaric acid
36
•
hemoglobin raffimer (89)
•
imetelstat (101): oligonucleotide telomerase inhibitor;
3'-amino-3'-deoxy-P-thiothymidylyl-(3'→5')-3'-amino-2',3'-dideoxy-Pthioadenylyl-(3'→5')-3'-amino-2',3'-dideoxy-P-thioguanylyl-(3'→5')-3'-amino2',3'-dideoxy-P-thioguanylyl-(3'→5')-3'-amino-2',3'-dideoxy-P-thioguanylyl(3'→5')-3'-amino-3'-deoxy-P-thiothymidylyl-(3'→5')-3'-amino-3'-deoxy-Pthiothymidylyl-(3'→5')-3'-amino-2',3'-dideoxy-P-thioadenylyl-(3'→5')-3'-amino2',3'-dideoxy-P-thioguanylyl-(3'→5')-3'-amino-2',3'-dideoxy-P-thioadenylyl(3'→5')-3'-amino-2',3'-dideoxy-P-thiocytidylyl-(3'→5')-3'-amino-2',3'-dideoxy-Pthioadenylyl-(3'→5')-3'-amino-2',3'-dideoxyadenosine 5'-{O-[2-hydroxy3-(hexadecanoylamino)propyl] hydrogen phosphorothioate}
•
iodinated (125I) human serum albumin (24): human serum albumin iodinated with
radioactive iodine (125I)
•
iodinated (131I) human serum albumin (24): human serum albumin iodinated with
radioactive iodine (131I)
•
iroplact (74): N-L-methionyl blood platelet factor 4 (human subunit)
•
ismomultin alfa (91): 47-261-Glycoprotein gp 39 (human clone CDM8-gp39
reduced)
•
litenimod (96): (3'-5')d(P-thio)(T-A-A-A-C-G-T-T-A-T-A-A-C-G-T-T-A-T-G-AC-G-T-C-A-T)
•
macrosalb (131I) (33): macroaggregated iodinated (131I) human albumin
•
macrosalb (99mTc)(33): technetium (99mTc) labelled macroaggregated human
serum albumin
•
metenkefalin (97): L-tyrosylglycylglycyl-L-phenylalanyl-L-methionine
β-endorphin human-(1-5)-peptide
•
metreleptin (82): N-methionylleptin (human)
37
•
mirostipen (85): [23-methionine] human myeloid progenitor inhibitory factor 1(23-99)-peptide
•
nagrestipen (76): 26-L-alaninelymphokine MIP 1α (human clone pAT464
macrophage inflammatory)
•
ocriplasmin (101): truncated human plasmin:
human plasmin heavy chain A-(543-561)-peptide (548-666;558-566)-bisdisulfide
with human plasmin light chain B
•
opebacan (83): 132-L-alanine-1-193-bactericidal / permeability-increasing protein
(human)
•
orgotein (31): a group of soluble metalloproteins isolated from liver, red blood
cells, and other mammalian tissues
•
ovandrotone albumin (52): 3-[(3,17-dioxoandrost-4-en-7α-yl)thio]propionic acid,
serum albumin conjugate
•
parathyroid hormone (90): non glycosylated human parathyroid hormone, the
origin should be indicated between brackets after the INN, for example (r. E. coli)
for recombinant produced by Escherichia coli
•
pegaptanib (88): 5'-ester of (2'-deoxy-2'-fluoro)C-Gm-Gm-A-A-(2'-deoxy-2'fluoro)U-(2'-deoxy-2'-fluoro)C-Am-Gm-(2'-deoxy-2'-fluoro)U-Gm-Am-Am-(2'deoxy-2'-fluoro)U-Gm-(2'-deoxy-2'-fluoro)C-(2'-deoxy-2'-fluoro)U-(2'-deoxy-2'fluoro)U-Am-(2'-deoxy-2'-fluoro)U-Am-(2'-deoxy-2'-fluoro)C-Am-(2'-deoxy-2'fluoro)U-(2'-deoxy-2'-fluoro)C-(2'-deoxy-2'-fluoro)C-Gm-(3'→3')-dT with α,α'[[(1S)-1-[[5-(phosphonooxy)pentyl]carbamoyl]pentane-1,5diyl]bis(iminocarbonyl)]bis[ω-methoxypoly(oxyethane-1,2-diyl)]
•
pegdinetanib (103): 94 residues protein derived from human fibronectin 10th type
III domain, pegylated:
glycyl[1438-L-arginine(D>R),1439-L-histidine(A>H),1441-Lhistidine(A>H),1442-L-phenylalanine(V>F),1443-L-proline(T>P),1444-Lthreonine(V>T),1467-L-leucine(G>L),1468-L-glutamine(S>Q),1469-Lproline(K>P),1470-L-proline(S>P),1492-L-aspartic acid(G>D),1493glycine(R>G),1494-L-arginine(G>R),1495-L-asparagine(D>N),1496glycine(S>G),1497-L-arginine(P>R),1498-L-leucine(A>L),1499-Lleucine(S>L),1501-L-isoleucine(K>I),1515-S-[(3RS)-1-(1-{[α-
38
methylpoly(oxyethylene)]carbamoyl}-3-[({[αmethylpoly(oxyethylene)]carbamoyl}oxy)methyl]-8,13-dioxo1,4-dioxa-9,12-diazapentadecan-15-yl)-2,5-dioxopyrrolidin-3-yl]L-cysteine(S>C)]human fibronectin-(1424-1516)-peptide
•
rintatolimod (102): poly[5']-inosinylyl-(3'→) duplex with poly[dodecakis[3']cytidylyl-(5'→)3')-uridylyl-(5'→)
•
secretin (01): hormone of the duodenal mucosa which activates the pancreatic
secretion and lowers the blood-sugar level
•
secretin human (106): human peptide hormone secretin
•
serelaxin (105): human relaxin 2 (relaxin H2)
•
talactoferrin alfa (93): recombinant human lactoferrin
•
tadekinig alfa (90): interleukin-18 binding protein (human gene IL 18BP isoform
a precursor)
•
thrombin alfa (97): human thrombin (recombinant, glycoform α)
•
tiprelestat (103): human elafin (elastase-specific inhibitor, skin-derived
antileukoproteinase, peptidase inhibitor 3)
•
torapsel (91): 42-89-glycoprotein (human clone PMT21:PL85 P-selectin
glycoprotein ligand 1) fusion protein with immunoglobulin (human constant
region)
•
trebananib (106): immunoglobulin G1 Fc fragment fused with two synthetic
polypeptides that bind the Homo sapiens ANGPT2 (angiopoietin 2);
methionyl (1) -gamma1 heavy chain fragment (2-228) [Homo sapiens IGHG1*01
hinge (EPKSC 1-5>del) (2-11), CH2 (12-121), CH3 (122-228)] fused, at the Cterminal end, with a synthetic polypeptide that comprises two 14-mer amino acid
repeats that bind angiopoietin 2 (229-287) [linker (229-235) -14-mer (236-249) –
linker (250-271) -14-mer (272-285) -leucyl-glutamate]; (7-7':10-10')-bisdisulfide
dimer
•
tremacamra (78): 1-453-glycoprotein ICAM-I (human reduced)
39
•
troplasminogen alfa (99): thrombin-activable plasminogen;
endo-[(558a(559)-558h(365))-human coagulation factor XI-(363-370)-peptide]des-(559-562)-[606(610)-lysine,623(627)-lysine]human plasminogen, glycoform
α
•
votucalis (96): methionyl[145-leucine]FS-HBP2 (Rhipicephalus appendiculatus
(Brown ear tick) Female-Specific Histamine-Binding Protein 2).
40
5. CURRENT CHALLENGES
The challenges currently faced include the following:
•
The INN Expert Group, when selecting names for recombinant proteins, has
to deal not with substances with well-defined structures but with products of
highly complex composition or even with mixtures of such products.
•
It is not only modified proteins that might differ from their naturally occurring
counterparts, products derived by expression of the natural gene in foreign
host cells may also differ structurally, biologically or immunologically from
the natural protein.
•
Glycoproteins particularly may occur in forms that differ in the structure of
one or more of their carbohydrate units, a phenomenon known as
microheterogeneity and resulting in a heterogeneous population of molecules.
Such differences may affect both the size and the charge of individual
glycoproteins.
•
A variety of novel biotechnology-derived products are under development, all
of which will require specific policies on how to deal with such products.
•
Clearly, the INN nomenclature of biological medicinal products is an area of
increasing complexity.
41
REFERENCES
1.
The use of stems in the selection of International Nonproprietary Names (INN) for
pharmaceutical substances, 2011, WHO/EMP/QSM/2011.3 *
2.
International nomenclature and gene therapy products (WHO Drug Information,
Vol.19, N°2, 2005, p.103) *
3.
Pre-stems, INN Working Document 12.317 rev.P, 23/10/2012 *
4.
Consultation on International Nonproprietary Names (INN) and biological products, INN
Working Document 00.118 (2002)
5.
INNs for biotechnological products: collaboration with other parties, WHO/Pharm S/Nom
1763 (1999)
6.
INNs for recombinant vaccines and viruses, WHO/Pharm S/Nom 1719 (1998)
7.
INNs for biosynthetic vaccines, WHO/Pharm S/Nom 1419 (1994)
8.
INN nomenclature for peptides, glycopeptides, proteins and glycoproteins, WHO/Pharm
S/Nom 1428 (1994)
9.
INNs for immunoglobulins, WHO/Pharm S/Nom 1517 (1995)
10.
INNs for immunoglobulins, WHO/Pharm S/Nom 101 (1967)
11.
General policies for monoclonal antibodies, INN Working Document 09.251, 24/06/2009 *
12.
Definition of INNs for substances prepared by biotechnology, WHO/Pharm S/Nom 1348
(1992)
13.
International Nonproprietary Names (INN) for pharmaceutical substances, Lists
1-107 of proposed INN and Lists 1-68 of Recommended INN, Cumulative List N°14, 2012
14.
Guidelines on the use of International Nonproprietary Names (INNs) for pharmaceutical
substances, WHO/Pharm S/Nom 1570 (1997)
42
15.
INNs of the -tropin (trophin) series: pituitary hormones, WHO/Pharm S/Nom 1406 (19931995)
16.
INNs for blood factors, WHO/Pharm S/Nom 1362 (1994)
17.
INNs for growth factor, WHO/Pharm S/Nom 1318 (1991)
18.
INNs for heparin derivatives, WHO/Pharm S/Nom 1031 (1985-1991)
19.
Nomenclature of insulin injections, WHO/Pharm S/Nom 1127 (1986)
20.
Generic names for genetically-engineered insulins, WHO/Pharm S/Nom 737 (1980-1983)
21.
International nonproprietary names (INN) for pharmaceitucal substances: names for radicals,
groups & others (Comprehensive list), WHO/EMP/QSM/2012.2 *
* These documents are available on the INN Programme Website at:
http://www.who.int/medicines/services/inn/en/.
43
ANNEX 1
7
The list of INN for composite proteins published
classified by groups
-anib (angiogenesis inhibitors)
trebananib (106)
immunoglobulin G1 Fc fragment fused with two synthetic polypeptides that bind
the Homo sapiens ANGPT2 (angiopoietin 2);
methionyl (1) -gamma1 heavy chain fragment (2-228) [Homo sapiens IGHG1*01
hinge (EPKSC 1-5>del) (2-11), CH2 (12-121), CH3 (122-228)] fused, at the Cterminal end, with a synthetic polypeptide that comprises two 14-mer amino acid
repeats that bind angiopoietin 2 (229-287) [linker (229-235) -14-mer (236-249) –
linker (250-271) -14-mer (272-285) -leucyl-glutamate]; (7-7':10-10')-bisdisulfide
dimer
-ase
asfotase alfa (104)
tissue-nonspecific alkaline phosphatase- IgG1 fusion protein;human tissuenonspecific isozyme alkaline phosphatase (AP-TNAP, EC=3.1.3.1) fusion protein
with leucyl-lysyl-human immunoglobulin G1 Fc region {(6-15)-H-CH2-CH3 of
IGHG1*03} fusion protein with aspartyl-isoleucyl-deca(aspartic acid), dimer
(493-493':496-496')-bisdisulfide
senrebotase (107)
L-methionylglycyl-L-seryl-des-(445-glycine,446-L-tyrosine)-[2-L-glutamic
acid,432,442,444,447-tetra-L-aspartic acid]botulinum neurotoxin A precursor 27L-alanine variant light chain (433-41')-disulfide with [14-L-arginine,15-Llysine]human nociceptin fusion protein with L-alanyl-L-leucyl-Lalanyltris(tetraglycyl-L-seryl)-[3-L-valine,4-L-leucine,5-L-glutamine-418-Lleucine,419-L-aspartic acid]botulinum neurotoxin A heavy chain-(1-419)-peptide
7
It should be noted that this list may not be comprehensive and the descriptions under the names are the
ones published.
44
-cept
abatacept (91)
1-25-oncostatin M (human precursor) fusion protein with CTLA-4 (antigen)
(human) fusion protein with immunoglobulin G1 (human heavy chain fragment),
bimolecular (146→146')-disulfide
aflibercept (96)
des-432-lysine-[human vascular endothelial growth factor receptor
1-(103-204)-peptide (containing Ig like C2 type 2 domain) fusion protein with
human vascular endothelial growth factor receptor 2-(206-308)-peptide
(containing Ig like C2 type 3 domain fragment) fusion protein with human
immunoglobulin G1-(227 C-terminal residues)-peptide (Fc fragment)], (211211':214-214')-bisdisulfide dimer
atacicept (95)
[86-serine,101-glutamic acid,196-serine,197-serine,222-aspartic acid,224leucine][human tumor necrosis factor receptor superfamily member 13B-(30110)-peptide (TACI fragment containing TNFR-Cys 1 and TNFR-Cys 2) fusion
protein with human immunogobulin G1-(232 C-terminal residues)-peptide
(γ1-chain Fc fragment), (92-92':95-95')-bisdisulfide dimer
baminercept (99)
human tumor necrosis factor receptor superfamily member 3 (lymphotoxin-β
receptor, TNF C receptor)-(2-195)-peptide (fragment of extracellular domain)
fusion protein with human immunoglobulin heavy constant γ1 chain Fc fragment
[227 residues, hinge (195-205) des-(1-4),C5>V, CH2 (206-315), CH3 (316-421)
des-K107]
conbercept (105)
fusion protein for immune applications (FPIA) comprising Homo sapiens FLT1
(fms-related tyrosine kinase 1, vascular endothelial growth factor receptor 1,
VEGFR1, vascular permeability factor receptor, tyrosine-protein kinase FRT)
fragment, fused with Homo sapiens KDR (kinase insert domain receptor, vascular
endothelial growth factor receptor 2, VEGFR2, protein-tyrosine kinase receptor
FLK1, CD309) fragment, fused with Homo sapiens immunoglobulin G1 Fc
fragment;
45
FLT1, 132-232 precursor fragment (1-101) -KDR, 227-421 precursor fragment
(102-296) -glycyl-prolyl-glycyl (297-299) -gamma1 chain H-CH2-CH3 fragment
(300-526) [Homo sapiens IGHG1*03 hinge 6-15 P13>L (307) (300-309), CH2
(310-419), CH3-CH-S (420-526)]; (305-305':308-308')-bisdisulfide dimer
dalantercept (105)
fusion protein for immune applications (FPIA) comprising Homo sapiens
ACVRL1 (activin A receptor type II-like 1, activin receptor-like kinase 1, ALK1,
ALK-1, serine/threonine-protein kinase receptor R3, SKR3, transforming growth
factor-beta superfamily receptor type I, TGF-B superfamily receptor type I, TSR-I,
HHT2, ORW2) fragment, fused with Homo sapiens immunoglobulin G1 Fc
fragment;
ACVR2L1, 22-120 precursor fragment (1-99) -threonyl-triglycyl (100-103) gamma1 chain H-CH2-CH3 fragment (104-328) [Homo sapiens IGHG1*03 hinge
8-15 (104-111), CH2 L1.3>A (115), G1>A (118), A115>V (211) (112-221), CH3
S85.3>P (284) (222-328)]; (107-107':110-110')-bisdisulfide dimer
rilonacept (95)
[653-glycine][human interleukin-1 receptor accessory protein-(1-339)-peptide
(extracellular domain fragment) fusion protein with human type 1 interleukin-1
receptor-(5-316)-peptide (extracellular domain fragment) fusion protein with
human immunoglobulin G1-(229 C-terminal residues)-peptide (Fc fragment)],
(659-659':662-662')-bisdisulfide dimer
sotatercept (104)
fusion protein for immune applications (FPIA) comprising ACVR2A (activin
receptor type 2A, activin receptor type IIA) fragment fused with immunoglobulin
G1 Fc fragment, and binding activin, a member of the TGF beta family;
ACVR2A, 21-135 precursor fragment (1-115) -threonyl-triglycyl linker (116-119)
-gamma1 chain H-CH2-CH3 fragment (120-344) [Homo sapiens IGHG1*03
hinge (120-127), CH2, A115>V (128-237), CH3 (238-344)]; (123-123':126-126')bisdisulfide dimer
-cept & -tox
alvircept sudotox 8(69)
8
The names and the descriptions of toxins are published in Annex 4-1 of "International Nonproprietary
Names (INN) for pharmaceutical substances. Names for radicals, groups & others: comprehensive list
(WHO/EMP/QSM/2012.2)".
46
N2-L-methionyl-1-178-antigen CD4 (human clone pT4B protein moiety
reduced)(178→248')-protein with 248- L-histidine-249- L-methionine-250- Lalanine-251- L-glutamic acid-248-613-exotoxin A(Pseudomonas aeruginosa
reduced)
interferon
albinterferon alfa-2b (97)
human serum albumin (585 residues) fusion protein with human interferon α-2b
(165 residues)
-kin & -tox
cintredekin besudotox (92)
toxin hIL13-PE38QQR (plasmid phuIL13-Tx)
denileukin diftitox (78)
N-L-methionyl-387-L-histidine-388-L-alanine-1-388-toxin (Corynebacterium
diphtheriae strain C7) (388→2')-protein with 2-133-interleukin 2 (human clone
pTlL2-21a)
-mab & dotin
vorsetuzumab mafodotin (107)
immunoglobulin G1-kappa auristatin F conjugate, anti-[Homo
sapiens CD70 (tumor necrosis factor superfamily member 7,
TNFSF7, CD27LG, CD27L)], humanized monoclonal antibody
conjugated to auristatin F;
gamma1 heavy chain (1-448) [humanized VH (Homo sapiens
IGHV1-2*02 (86.70%) -(IGHD)-IGHJ6*01) [8.8.11] (1-118) -Homo
sapiens IGHG1*01 (119-448)], (221-218')-disulfide (if not
conjugated) with kappa light chain (1'-218') [humanized V-KAPPA
(Homo sapiens IGKV4-1*01 (79.20%) -IGKJ1*01) [10.3.9] (1'-111') Homo sapiens IGKC*01 (112'-218')]; (227-227":230-230")bisdisulfide dimer; conjugated, on an average of 3 to 5 cysteinyl, to
47
monomethylauristatin F (MMAF), via a non-cleavable
maleimidocaproyl (mc) linker
mafodotin
N-{(2R,3R)-3-[(2S)-1-[(3R,4S,5S)-4-({N-[6-(2,5-dioxo-2,5-dihydro1H-pyrrol-1-yl)hexanoyl]-N-methyl-L-valyl-L-valyl}methylamino)3-methoxy-5-methylheptanoyl]pyrrolidin-2-yl]-3-methoxy2-methylpropanoyl}-L-phenylalanine
-mab & -kin
tucotuzumab celmoleukin (95)
immunoglobulin G1, anti-(tumor associated calcium signal transducer 1 (KS 1/4
antigen)) (human-mouse monoclonal huKS-IL2 heavy chain) fusion protein with
interleukin 2 (human), disulfide with human-mouse monoclonal huKS-IL2 light
chain, dimer
-mab & -tox
anatumomab mafenatox (86)
immunoglobulin G 1, anti-(human tumor-associated glycoprotein 72) (humanmouse clone pMB125 Fab fragment γ1-chain) fusion protein with enterotoxin A
(227-alanine) (Staphylococcus aureus) complex with mouse clone pMB125 κchain)
citatuzumab bogatox (99)
immunoglobulin Fab fusion protein, anti-[Homo sapiens tumor-associated
calcium signal transducer 1 (TACSTD1, gastrointestinal tumor-associated protein
2, GA733-2, epithelial glycoprotein 2, EGP-2, epithelial cell adhesion molecule
Ep-CAM, KSA, KS1/4 antigen, M4S, tumor antigen 17-1A, CD326)], humanized
Fab fused with Bougainvillea spectabilis Willd rRNA N-glycosidase [type I
ribosome inactivating protein (RIP), bouganin], VB6-845; gamma1 heavy chain
fragment (1-225) [hexahistidyl (1-6) -humanized VH from 4D5MOC-B (Homo
sapiens FR/Mus musculus CDR, Homo sapiens IGHJ4*01, V124>L) [8.8.9] (7122) -Homo sapiens IGHG1*01 CH1-hinge fragment EPKSC (123-225)], (225219')-disulfide with kappa fusion chain (1'-481') [humanized V-KAPPA from
clone 4D5MOC-B (Homo sapiens FR/Mus musculus CDR, Homo sapiens
48
IGKJ1*01, I126>L) [11.3.9] (1'-112') -Homo sapiens IGKC*01 (113'-219') -12mer furin linker (proteolytic cleavage spacer from Pseudomonas exotoxin A)
(220'-231') -Bougainvillea spectabilis Willd bouganin fragment (27-276 from
precursor, V354'>A, D358'>A, Y364'>N, I383'>A) (232'-481')]
dorlimomab aritox (66)
ricin A chain-antibody ST 1 F(ab')2 fragment immunotoxin
moxetumomab pasudotox (102)
immunoglobulin Fv fragment fused to Pseudomonas toxin, anti-[Homo sapiens
CD22 (sialic acid-binding Ig-like lectin 2, Siglec-2, SIGLEC2, Leu-14, Blymphocyte cell adhesion molecule, BL-CAM)], Mus musculus monoclonal
antibody disulfide stabilized Fv fragment with the variable heavy VH domain
fused with the truncated form PE38 of Pseudomonas aeruginosa exotoxin A (VHPE38), disulfide linked with the variable kappa domain (V-KAPPA)];
VH-PE38 (1-476) comprising the VH domain (1-123) [methionyl -Mus musculus
VH [(IGHV5-12-1*01 -(IGHD)-IGHJ3*01) [8.8.16] (2-123)] fused with a 7-mer
linker (124-130) and with the Pseudomonas aeruginosa exotoxin A (ETA) PE38
fragment (131-476) [277-638 precursor fragment with del 389-405>N (131-476),
containing domain II (131-243) with furin proteolytic cleavage site (152-164),
domain Ib (244-267), domain III (268-476)], (45-101')-disulfide with V-KAPPA
(1'-108') [methionyl -Mus musculus V-KAPPA [(IGHKV10-96*01 -IGKJ1*01)
[6.3.9] (2'-108')]
nacolomab tafenatox (80)
immunoglobulin G1, anti-(human colorectal tumor antigen C242) Fab fragment
(mouse monoclonal r-C242Fab-SEA clone pkP941 γ1-chain) fusion protein with
enterotoxin A (Staphylococcus aureus), disulfide with mouse monoclonal rC242Fab-SEA clone pkP941 κ-chain
naptumomab estafenatox (96)
immunoglobulin fragment, anti-[trophoblast glycoprotein (TPBG, 5T4)]
monoclonal 5T4 gamma1 heavy chain fragment fusion protein [Mus musculus VH
(5T4V14: H41>P, S44>G, I69>T, V113>G)-IGHG1_CH1)] - [Glycyl-GlycylProlyl] - superantigen SEA/E-120 (synthetic), non-disulfide linked with
monoclonal 5T4 kappa light chain [Mus musculus V-KAPPA (5T4V18: F10>S,
T45>K, I63>S, F73>L, T77>S, L78>V, L83>A)-IGKC]
49
oportuzumab monatox (100)
immunoglobulin scFv fusion protein, anti-[Homo sapiens tumor-associated
calcium signal transducer 1 (TACSTD1, gastrointestinal tumor-associated protein
2, GA733-2, epithelial glycoprotein 2, EGP- 2, epithelial cell adhesion molecule
Ep-CAM, KSA, KS1/4 antigen, M4S1, tumor antigen 17-1A, CD326)] humanized
monoclonal antibody scFv fused with Pseudomonas aeruginosa exotoxin A;
hexahistidyl -humanized scFv [V-KAPPA (Homo sapiens IGKV1- 39*01 (78%)IGKJ1*01, I126>L) [11.3.9] (7-118) -26-mer linker -VH (Homo sapiens IGHV74-1*02 -(IGHD)-IGHJ4*01, V124>L) [8.8.9] (145-260)] -20-mer linker Pseudomonas aeruginosa exotoxin A (ETA) [277-633 precursor fragment,
containing domain II (281-393) with furin proteolytic cleavage site (302-313),
domain Ib (394-433), domain III (434-637)] (281-637) -hexahistidyl-lysylaspartyl-glutamylleucyl
taplitumomab paptox (84)
immunoglobulin G1, anti-(human antigen CD19) (mouse monoclonal B43 γ1-
chain), disulfide with mouse monoclonal B43 κ-chain, dimer, disulfide with
protein PAP (pokeweed antiviral)
telimomab aritox (66)
ricin A chain-antibody T 101 Fab fragment immunotoxin
zolimomab aritox (80)
immunoglobulin G1, anti-(human CD5 (antigen) heavy chain) (mouse
monoclonal H65-RTA γ1-chain), disulfide with mouse monoclonal H65-RTA
light chain, dimer, disulfide with ricin (castor bean A-chain)
-stim (colony stimulating factors)
balugrastim (107)
human serum albumin (585 residues) fusion protein with des-(1-alanine,37valine,38-serine,39-glutamic acid)-human granulocyte colony-stimulating factor
(pluripoietin)
50
romiplostim (97)
L-methionyl[human
immunogloblin heavy constant gamma 1-(227 C-terminal
residues)-peptide (Fc fragment)] fusion protein with 41 amino acids peptide, (77':10,10')-bisdisulfide dimer
-tide
albiglutide (97)
([8-glycine]human glucagon-like peptide 1-(7-36)-peptidyl)([8-glycine]human
glucagon-like peptide 1-(7-36)-peptidyl)(human serum albumin (585 residues))
cenderitide (105)
natriuretic peptide receptor type B (NPR-B) agonist;
human C-type natriuretic peptide-(32-53)-peptide (CNP-22) fusion protein with
eastern green mamba (Dendroaspis angusticeps) natriuretic peptide-(24-38)peptide
dulaglutide (103)
glucagon-like peptide-1-immunoglobulin G4 fusion protein, [2-glycyl,16-Lglutamyl,30-glycyl][human glucagon-like peptide 1-(7-37)-peptide] {(8-A>G,22G>E,36-R>G)-GLP-1(7-37)} fusion protein with tris(tetraglycyl-L-seryl)-Lalanine (linker) fusion protein with des-276-lysine-[57-L-proline,63-L-alanine,64L-alanine]human immunoglobulin G4 Fc region {(10-S>P)-H-(4-F>A,5-L>A)CH2-(107-K>-)-CH3 of IGHG4*01}, dimer (55-55':58-58')-bisdisulfide
elsiglutide (104)
[2-glycine(A>G),3-glutamic acid(D>E),8-serine(D>S),10-leucine(M>L),11serine(N>S),16-alanine(N>A),24-alanine(N>A),28-alanine(Q>A)]human
glucagon-like peptide 2 (GLP-2) fusion protein with hexalysinamide
vanutide cridificar (100)
inactivated diphtheria toxin (carrier) covalently linked to human beta-amyloid
protein 42 short fragments: pentadecakis[N6-Lys-(sulfanylacetyl)]-[52-glutamic
51
acid(G>E)]diphtheria toxin Corynebacterium diphtheriae thioether with human
beta-amyloid protein 42-(1-7)-peptidylcysteine
Others
torapsel (91)
42-89-glycoprotein (human clone PMT21:PL85 P-selectin glycoprotein ligand
fusion protein with immunoglobulin (human constant region)
transferrin aldifitox (95)
a conjugate of the precursor of human serotransferrin (siderophillin) with a
primary amine group used to form an amidine with (4-iminobutane-1,4diyl)sulfanediyl[(3RS)-2,5-dioxopyrrolidine-1,3-diyl]-1,3-phenylenecarbonyl and
forming an N-benzoyl derivative of a primary amine group of diphtheria [550-Lphenylalanine]toxin from Corynebacterium diphtheriae-(26-560)-peptide
verpasep caltespen (95)
60 kDa chaperonin 2 (heat shock protein 65 from Mycobacterium bovis
strain BCG) fusion protein with L-histidylprotein E7 from human papillomavirus
type 16.
zoptarelin doxorubicin (107)
[6-D-lysine]human gonadoliberin-1 (LHRH) and doxorubicin covalently linked
together with glutaric acid:
5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-N6-[5-(2-{(2S,4S)-4-[(3amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-2,5,12-trihydroxy-7-methoxy6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-2-yl}-2-oxoethoxy)-5-oxopentanoyl]D-lysine-L-leucyl-L-arginyl-L-prolylglycinamide
52
ANNEX 2
Transliteration of Greek letters in English, French and Spanish
Upper case
A
Lower case
α
B
Γ
∆
Ε
Ζ
Η
Θ
Ι
Κ
Λ
Μ
Ν
Ξ
Ο
Π
Ρ
Σ
Τ
Υ
Φ
Χ
Ψ
Ω
β
γ
δ
ε
ζ
η
θ
ι
κ
λ
µ
ν
ξ
ο
π
ρ
σ
τ
υ
ϕ
χ
ψ
ω
English
alfa
(and not alpha)
beta
gamma
delta
epsilon
zeta
eta
theta
iota
kappa
lambda
mu
nu
xi
omicron
pi
rho
sigma
tau
upsilon
phi
chi
psi
omega
French
alfa
(and not alpha)
bêta
gamma
delta
epsilon
zêta
êta
thêta
iota
kappa
lambda
mu
nu
xi
omicron
pi
rhô
sigma
tau
upsilon
phi
khi
psi
oméga
Spanish
alfa
beta
gamma
delta
épsilon
dseta
eta
zeta
iota
kappa
lambda
mi
ni
xi
ómicron
pi
ro
sigma
tau
ípsilon
fi
ji
psi
omega
*
*
* letters to be avoided
53
ANNEX 3
The previous naming scheme for monoclonal antibodies
General policies for monoclonal antibodies
•
The common stem for monoclonal antibodies is -mab.
•
Sub-stems for source of product:
a
axo (presub-stem)
rat
rat-murine
hybrid
e
hamster
i
primate
o
mouse
u
human
xi
chimeric
zu
humanized
The distinction between chimeric and humanized antibodies is as follows:
A chimeric antibody is one that contains contiguous foreign-derived amino acids
comprising the entire variable region of both heavy and light chains linked to
heavy and light constant regions of human origin.
A humanized antibody has segments of foreign-derived amino acids interspersed
among variable region segments of human-derived amino acid residues and the
humanized heavy-variable and light-variable regions are linked to heavy and light
constant regions of human origin.
54
•
Sub-stems for disease or target class:
-ba(c)-
bacterial
-ci(r)-
cardiovascular
-fung-
fungal
-ki(n)- (presub-stem)
interleukin
-le(s)-
inflammatory lesions
-li(m)-
immunomodulator
-os-
bone
-vi(r)-
viral
-co(l)-
colon
-go(t)-
testis
-go(v)-
ovary
-ma(r)-
mammary
-me(l)-
melanoma
-pr(o)-
prostate
-tu(m)-
miscellaneous
tumours:
Whenever there is a problem in pronunciation, the final letter of the sub-stems for
diseases or targets may be deleted, e.g. -vi(r)-, -ba(c)-, -li(m)-, -co(l)-, etc.
Prefix
Should be random e.g. the only requirement is to contribute to a euphonious and
distinctive name.
55
Second word
If the product is radiolabelled or conjugated to another chemical, such as toxin,
identification of this conjugate is accomplished by use of a separate, second word
or acceptable chemical designation.
If the monoclonal antibody is used as a carrier for a radioisotope, the latter will be
listed first in the INN, e.g. technetium (99mTc) pintumomab (86).
-toxa- infix
For monoclonals conjugated to a toxin, the infix -toxa- can be inserted either into
the first (main) name or included in the second word.
56

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