In October, 2008, the International Nonproprietary Name (INN) Working Group Meeting on Nomenclature for Monoclonal Antibodies (mAb), met to review and streamline the monoclonal antibody nomenclature scheme. Based on the group's recommendations and on further discussions, the INN Experts published changes to the monoclonal antibody nomenclature scheme. In 2011, the INN Experts published an updated biologics review with revisions to the monoclonal antibody nomenclature scheme language.
The USAN Council (USANC) has modified its own scheme to facilitate international harmonization. This document outlines the updated monoclonal antibody nomenclature scheme and supercedes previous schemes. It also explains policies regarding post-translational modifications and the use of two-word names.
The USANC has no plans to retroactively change names already coined. They believe that retroactively changing the names of the monoclonal antibodies would confuse physicians, other health care professionals and patients.
Manufacturers should be aware that nomenclature practices are continually evolving. Consequently, further updates and changes may occur any time that the USANC believes such changes are necessary. Changes to the monoclonal antibody nomenclature scheme, however, should be carefully considered and implemented only when necessary.
Elements of a name
The suffix "-mab" is used for monoclonal antibodies, antibody fragments and radiolabeled antibodies. For polyclonal mixtures of antibodies, "-pab" is used. The -pab suffix applies to polyclonal pools of recombinant monoclonal antibodies, as opposed to polyclonal antibody preparations isolated from blood. It differentiates polyclonal antibodies from individual monoclonal antibodies named with -mab.
Sequence of stems and infixes
The order for combining the key elements of a monoclonal antibody name is as follows: 1) prefix, 2) infix representing the target or disease, 3) infix indicating the source, and 4) the stem used as a suffix.
Prefix + Target/disease class infix + Source infix + Stem
To create a unique name, a distinct, compatible syllable or syllables should be selected as the starting prefix.
Suggested prefixes should comply with the USAN Program's rules for coining names. In addition, we ask that manufacturers be mindful of the potential for conflicts with the names of other monoclonal antibodies, because about 200 monoclonal antibodies have already been named. Although it is desirable for names to be as short as possible, a prefix that is two or more syllables long may be necessary to distinguish the name from those previously assigned.
Target/disease class infix
The general disease state subclass must be incorporated into the name. This is accomplished with the target/disease class infix. The USANC has approved specific syllables to denote diseases or targets. Additional subclasses may be added as necessary.
The choice of infix is determined by the available information regarding initial clinical indications and antibody action. If necessary, the USANC may request more details and evidence regarding antibody action and indications.
The target/disease infix has been truncated to a single letter when the source infix begins with a vowel. Using a single letter can create problems with pronunciation, such as with humanized and chimeric antibodies, therefore a second letter, a vowel, is added. The infixes that refer to the disease or target class are shown in the table.
Target/Disease Class Infixes for Monoclonal Antibodies (infix, definition and example suffixes as used):
definition: skeletal muscle mass related growth factors and receptors as target
definition: neurons as targets
definition: viruses, antiviral indications
The tumor-specific infixes have been discontinued because most monoclonal antibodies with oncology indications are investigated for more than one type of tumor. Thus, the following infixes are no longer used: -col- (colon cancer), -mel- (melanoma), -got- (testes), -gov- (ovarian), and -po- (prostate).
Identification of the "source" of the antibody is an important safety consideration because some products may cause source-specific antibodies to develop in patients. Because an antibody may be based on the sequence of one species but manufactured in cell lines derived from another, "source" is defined as referring to the species on which the immunoglobulin sequence of the mAb is based. This definition harmonizes with that used by the INN Program.
A series of infixes which immediately precede -mab or -pab indicate the source. A limited subset of infixes used most often accounts for nearly all the monoclonal antibody names.
Source Infixes Used Frequently
definition: fully human
Source Infixes Used Seldom or Never
definition: rat/mouse chimer
definition: combination of humanized and chimeric chains
USAN Modified Designations for Monoclonal Antibodies
In several instances, the name of a monoclonal antibody incorporates additional clarifying words.
If the antibody is conjugated to a payload, such as radiolabel or toxin, this conjugate is identified by using a separate, second word or other acceptable chemical designation. For monoclonals conjugated to a toxin, the "-tox" stem must be included as part of the name selected for the toxin (e.g., zolimomab aritox, in which aritox identifies ricin A-chain). In other cases (e.g., brentuximab vedotin) the payload may receive a name based on a stem or a chemical name.
For radiolabeled products, the word order is 1) name of the isotope, 2) element symbol, 3) isotope number, and 4) name of the monoclonal antibody, as follows:
-technetium Tc 99m biciromab
-indium In 111 altumomab pentetate
The peg- prefix may be used for pegylated mAbs, but it should be avoided if it leads to an overly long name. Usually a two-word name is preferable with the first word referring to the monoclonal antibody and "pegol" as the second word.
When firms apply to name an antibody conjugated to a payload, they should file separate USAN applications for the antibody and the payload, as well as the application for the conjugate. This allows the USANC to assign separate USAN designations to each component. The USAN Modified application may be used for the additional names.
Required application information
For the USANC to select a nonproprietary name for a monoclonal antibody or fragment, the nomenclature application must provide the following relevant information:
1) The immunoglobulin class and subclass and the type of associated light chain.
2) Identity of the fragment of the immunoglobulin used (if applicable).
3) Species source from which the coding region for the immunoglobulin orginated, and specific, complete origin or all parts of chimeric, humanized or semisynthetic immunoglobulins.
4) The antigen specificity of the immunoglobulin, including its source.
5) The clone designation (specify if vector or vector-cell combination).
6) For conjugated monoclonal antibodies, the identity of any linkers, chelators, toxins, and/or isotopes present.
7) Identity of other modifications to the antibody, e.g., reduction of disulfide bonds, glycosylation or deglycosylation, amino acid modification, or substitution. If these modifications are present, their location(s) should be noted on the sequence or in the accompanying information.
8) The complete amino acid sequence, in an editable MS Word format.