Im IMGT/mAb-DB: the IMGT® database for Muno ene therapeutic monoclonal antibodies G Information Tics system® C. Poiron, Y. Wu, C. Ginestoux, F. Ehrenmann, P. Duroux and M-P Lefranc IMGT®, the international ImMunoGeneTics information system®, Laboratoire d’ImmunoGénétique Moléculaire LIGM, Université Montpellier 2, Institut de Génétique Humaine IGH, CNRS UPR 1142, 141 rue de la Cardonille, F-34396 Montpellier cedex 05, France http://www.imgt.org [email protected]

IMGT/mAb-DB is the monoclonal antibodies database of IMGT®, the international ImMunoGeneTics information The IMGT/mAb-DB Query page allows requests on several elds. These are organized in 5 sections: system® (http://www.imgt.org) that is the global reference in immunogenetics and immunoinformatics. 1 1 IMGT/mAb DB ID IMGT/mAb-DB provides a unique expertised resource on 2 immunoglobulins (IG) or monoclonal antibodies (mAb) with 2 INN and other names clinical indications, and on fusion proteins for immune applications (FPIA). IMGT/mAb-DB is a relational 3 3 characteristics and structure database using the open source MySQL (http://www.mysql.com) management system database. 4 speci city (target name Since 2008, amino acid sequences of mAb (suffix -mab) 4 and target species) and of FPIA (suffix -cept) from the World Health 5 clinical indication, Organization(WHO)/International Nonproprietary Name (INN) 5 development status and Programme have been entered in IMGT®. clinical domain. Lefranc, M.-P. mAbs, 3:1-2 (2011)

A query on a name allows to retrieve the International For each entry, IMGT/mAb-DB provides the origin species IMGT/mAb-DB also provides information on company, clinical Nonproprietary Name (INN) and INN lists numbers as provided (human, rat, murine, humanized or chimeric), the isotype and indication (more than 200 in the database), developement by the World Health Organization (WHO)/INN Programme, the format, links to IMGT/2Dstructure-DB (amino acid sequences status, organization that approved the drug such as Food and Common name from literature, the Proprietary name if the and IMGT Colliers de Perles), links to IMGT/3Dstructure-DB Drugs Administration (FDA) or European Medicines Agency antibodyIMGT/mAb-DB: or fusion protein Relation for immune with other application IMGT/databases (FPIA) is a (3D structures), speci city (target), origin clone species and (EMA), application (diagnostic or therapeutic) and clinical registered trademark (symbol®). origin clone name. domain.

IMGT/mAb-DB: Relations with other IMGT® databases Link to IMGT/2Dstructure-DB

Genetic approach Genomic approach IMGT/LIGM-DB Structural approach Sequences nucleotide/ Genes amino acid sequence 3D Structures Monoclonal Antibodies IMGT/

2Dstructure-DB INN sequences genes/ 3D Structures/

genes/ nucleotide sequences amino acid sequence proteins IMGT/ mAb-DB 3D Structures IMGT/GENE-DB genes/ IMGT/ 3D Structures 3Dstructure-DB

In November 2010, IMGT/mAb-DB contains 343 entries (175 -mab, 15 -cept), 213 have an INN and, among them, 81 have sequences in IMGT/2Dstructure-DB and 14 have 3D structures in IMGT/3Dstructure-DB. By providing links to IMGT/2Dstructure-DB and IMGT/3Dstructure-DB for entries available in these databases, IMGT/mAb-DB facilitates comparative studies of antibodies and FPIA, and of their constitutive chains, even if 3D structures are not yet available. Ehrenmann, F. et al. Nucleic Acids Res., 38, D301 - D307 (2010)

mAbs and FPIA approved for therapeutic and diagnostic use (in 2010) Conjugated or radiolabelled mAbs in IMGT/mAb-DB

adalimumab panitumumab golimumab canakinumab ustekinumab 5 Human (2002) (2006) (2009) (2009) (2009) Monoclonal antibodies can be used: mAbs HUMIRA® / VECTIBIX™ SIMPONI™ ILARIS® STELARA™ TRUDEXA® conjugated with another molecule radiolabelled with an isotope

muromonab-CD3 edrecolomab ibritumomab tiuxetan tositumomab capromab 5 Murine Calicheamicin, a cytotoxic antitumor antibiotic Indium-111: (1992) (1995) (2002) (2003) (1996) * mAbs ORTHOCLONE OKT3® PANOREX® ZEVALIN® BEXXAR® PROSTASCINT® Ex: gentuzumab ozogamicin , MYLOTARG ® Half-Life 2.80 days, used in Scientists believe Alexander the Great was killed by calicheamicin, nuclear medicine to observe abciximab rituximab basiliximab infliximab cetuximab a dangerous compound produced by a bacteria ( Micromonospora 5 Chimeric (1994) (1997) (1998) (1998) (2004) tumors and LCD mAbs REOPRO® MABTHERA® / SIMULECT® REMICADE® ERBITUX® echinospora) found in water. (Squires N. , Telegraph, 03 August 2010) RITUXAN® manufacturing, Exotoxin A from Pseudomonas Aeruginosa Ex: capromab, PROSTASCINT® daclizumab palivizumab trastuzumab alemtuzumab omalizumab ranibizumab eculizumab natalizumab bevacizumab certolizumab pegol nimotuzumab Ex: oportuzumab monatox, PROXINIUM™ VICINIUM™ 11 Humanized (1997) (1998) (1998) (2001) (2003) (2006) (2007) (2008) (2008) (2008) (2008) Iodine-131: mAbs ZENAPAX® SYNAGIS® HERCEPTIN® CAMPATH® / XOLAIR® LUCENTIS® SOLIRIS™ TYSABRI® AVASTIN® CIMZIA® THERACIM® MABCAMPATH® Monomethyl auristatin E (MMAE), a synthetic antineoplastic agent Half-Life 8 days, used in Ex: glembatumumab vedotin nuclear medicine to observe etanercept alefacept abatacept rilonacept a thyroid gland and 4 FPIA (1998) (2003) (2005) (2008) ENBREL® AMEVIVE® ORENCIA® ARCALYST™ radiotherapy on cancers Bouganin, from Bougainvillea spectabilis Willd toxin such as lymphoma, Ex: citatuzumab bogatox In September 2010, IMGT/mAb-DB contains 30 monoclonal antibodies and FPIA on the Ex: tositumomab, BEXXAR® market: 29 of them (25 mAb and 4 FPIA) are for therapeutic use and 1 (shown with *) is for diagnostic use. In November 2010, IMGT/mAb-DB contains: 17 INN radiolabelled and 11 INN conjugated.

IMGT® founder and director: Marie-Paule Lefranc ([email protected]) Bioinformatics manager: Véronique Giudicelli ([email protected]) AGENCE NATIONALE DE LA Computer manager: Patrice Duroux ([email protected]) RECHERCHE Webmaster: Chantal Ginestoux ([email protected]) © Copyright 1995-2010 IMGT®, the international ImMunoGeneTics information system® ©2010 C. Poiron and M.-P. Lefranc