International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 75

WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 93 International Nonproprietary Names for Pharmaceutical Substances (INN) RECOMMENDED International Nonproprietary Names: List 75 Notice is hereby given that, in accordance with paragraph 7 of the Procedure for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances [Off. Rec. Wld Health Org., 1955, 60, 3 (Resolution EB15.R7); 1969, 173, 10 (Resolution EB43.R9); Resolution EB115.R4 (EB115/2005/REC/1)], the following names are selected as Recommended International Nonproprietary Names. The inclusion of a name in the lists of Recommended International Nonproprietary Names does not imply any recommendation of the use of the substance in medicine or pharmacy. Lists of Proposed (1–113) and Recommended (1–74) International Nonproprietary Names can be found in Cumulative List No. 16, 2015 (available in CD-ROM only). Dénominations communes internationales des Substances pharmaceutiques (DCI) Dénominations communes internationales RECOMMANDÉES: Liste 75 Il est notifié que, conformément aux dispositions du paragraphe 7 de la Procédure à suivre en vue du choix de Dénominations communes internationales recommandées pour les Substances pharmaceutiques [Actes off. Org. mond. Santé, 1955, 60, 3 (résolution EB15.R7); 1969, 173, 10 (résolution EB43.R9); résolution EB115.R4 (EB115/2005/REC/1)] les dénominations ci-dessous sont choisies par l’Organisation mondiale de la Santé en tant que dénominations communes internationales recommandées. L’inclusion d’une dénomination dans les listes de DCI recommandées n’implique aucune recommandation en vue de l’utilisation de la substance correspondante en médecine ou en pharmacie. On trouvera d’autres listes de Dénominations communes internationales proposées (1–113) et recommandées (1–74) dans la Liste récapitulative No. 16, 2015 (disponible sur CD-ROM seulement). Denominaciones Comunes Internacionales para las Sustancias Farmacéuticas (DCI) Denominaciones Comunes Internacionales RECOMENDADAS: Lista 75 De conformidad con lo que dispone el párrafo 7 del Procedimiento de Selección de Denominaciones Comunes Internacionales Recomendadas para las Sustancias Farmacéuticas [Act. Of. Mund. Salud, 1955, 60, 3 (Resolución EB15.R7); 1969, 173, 10 (Resolución EB43.R9); Résolution EB115.R4 (EB115/2005/REC/1) EB115.R4 (EB115/2005/REC/1)], se comunica por el presente anuncio que las denominaciones que a continuación se expresan han sido seleccionadas como Denominaciones Comunes Internacionales Recomendadas. La inclusión de una denominación en las listas de las Denominaciones Comunes Recomendadas no supone recomendación alguna en favor del empleo de la sustancia respectiva en medicina o en farmacia. Las listas de Denominaciones Comunes Internacionales Propuestas (1–113) y Recomendadas (1–74) se encuentran reunidas en Cumulative List No. 16, 2015 (disponible sólo en CD-ROM). Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 94 Latin, English, French, Spanish: Recommended INN DCI Recommandée DCI Recomendada Chemical name or description; Molecular formula; Graphic formula Nom chimique ou description; Formule brute; Formule développée Nombre químico o descripción; Fórmula molecular; Fórmula desarrollada acalabrutinibum acalabrutinib 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin- 2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin- 2-yl)benzamide acalabrutinib 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin- 2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin- 2-yl)benzamide acalabrutinib 4-{8-amino-3-[(2S)-1-(but-2-inoil)pirrolidin- 2-il]imidazo[1,5-a]pirazin-1-il}-N-(piridin- 2-il)benzamida C26H23N7O2 N N N NH2 N H O N N O H3C H afasevikumabum # afasevikumab immunoglobulin G1-kappa, anti-[Homo sapiens IL17A (interleukin 17A, IL-17A) and Homo sapiens IL17F (interleukin 17F, IL-17F)], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-453) [Homo sapiens VH (IGHV3- 9*01 (96.00%) -(IGHD)-IGHJ2*01) [8.8.16] (1-123) - IGHG1*03, G1m3 (CH1 (124-221), hinge (222-236), CH2 (237-346), CH3 (347-451), CHS (452-453)) (124-453)], (226-215')-disulfide with kappa light chain (1'-215') [Homo sapiens V-KAPPA (IGKV3-11*01 (98.90%) -IGKJ4*01) [6.3.10] (1'-108') -IGKC*01, Km3 (109'-215')]; dimer (232- 232'':235-235'')-bisdisulfide afasévikumab immunoglobuline G1-kappa, anti-[Homo sapiens IL17A (interleukine 17A, IL-17A) et Homo sapiens IL17F (interleukine 17F, IL-17F)], Homo sapiens anticorps monoclonal; WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 95 chaîne lourde gamma1 (1-453) [Homo sapiens VH (IGHV3-9*01 (96.00%) -(IGHD)-IGHJ2*01) [8.8.16] (1-123) -IGHG1*03, G1m3 (CH1 (124-221), charnière (222-236), CH2 (237-346), CH3 (347-451), CHS (452-453)) (124- 453)], (226-215')-disulfure avec la chaîne légère kappa (1'- 215') [Homo sapiens V-KAPPA (IGKV3-11*01 (98.90%) - IGKJ4*01) [6.3.10] (1'-108') -IGKC*01, Km3 (109'-215')]; dimère (232-232'':235-235'')-bisdisulfure afasevikumab inmunoglobulina G1-kappa, anti-[Homo sapiens IL17A (interleukina 17A, IL-17A) y Homo sapiens IL17F (interleukina 17F, IL-17F)], anticuerpo monoclonal de Homo sapiens; cadena pesada gamma1 (1-453) [Homo sapiens VH (IGHV3-9*01 (96.00%) -(IGHD)-IGHJ2*01) [8.8.16] (1-123) -IGHG1*03, G1m3 (CH1 (124-221), bisagra (222-236), CH2 (237-346), CH3 (347-451), CHS (452-453)) (124- 453)], (226-215')-disulfuro con la cadena ligera kappa (1'- 215') [Homo sapiens V-KAPPA (IGKV3-11*01 (98.90%) - IGKJ4*01) [6.3.10] (1'-108') -IGKC*01, Km3 (109'-215')]; dímero (232-232'':235-235'')-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaEVQLVESGGG LVQPGRSLRL SCAASGFTFD DYAMHWVRQA PGKGLEWVSG 50 INWSSGGIGY ADSVKGRFTI SRDNAKNSLY LQMNSLRAED TALYYCARDI 100 GGFGEFYWNF GLWGRGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC 150 LVKDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG 200 TQTYICNVNH KPSNTKVDKR VEPKSCDKTH TCPPCPAPEL LGGPSVFLFP 250 PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE 300 QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR 350 EPQVYTLPPS REEMTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT 400 PPVLDSDGSF FLYSKLTVDK SRWQQGNVFS CSVMHEALHN HYTQKSLSLS 450 PGK 453 Light chain / Chaîne légère / Cadena ligera EIVLTQSPAT LSLSPGERAT LSCRASQSVR SYLAWYQQKP GQAPRLLIYD 50 ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQQ RSNWPPATFG 100 GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150 VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200 GLSSPVTKSF NRGEC 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 150-206 267-327 373-431 22''-96'' 150''-206'' 267''-327'' 373''-431'' Intra-L (C23-C104) 23'-88' 135'-195' 23'''-88''' 135'''-195''' Inter-H-L (h 5-CL 126) 226-215' 226''-215''' Inter-H-H (h 11, h 14) 232-232'' 235-235'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilaciónH VH N57: 52, 52'' (2% of the glycans) H CH2 N84.4: 303, 303'' (98% of the glycans) Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados aglatimagenum besadenovecum # aglatimagene besadenovec adenovirus (serotype 5) non replicant with a deletion in the E1/E2 region containing the herpes virus thymidine kinase gene (Herpes simplex virus HSV-tk) under the control of a Rous sarcoma virus (RSV) long terminal repeat promoter aglatimagène bésadénovec adénovirus (sérotype 5) non répliquant, délété de la région E1/E2, contenant le gène de la thymidine kinase du virus de l'herpès (virus Herpes simplex HSV-tk) sous le contrôle de la séquence LTR (terminale longue répétée) du virus du sarcome de Rous (RSV) Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 96 aglatimagén besadenovec adenovirus (serotipo 5), no replicante, con una deleción en la región E1/E2, que contiene el gen de la timidina kinasa del virus del herpes (Herpes simplex virus HSV-tk) bajo el control de la secuencia LTR (secuencia larga terminal repetida) del virus del sarcoma de Rous (RSV) alofanibum alofanib 3-{[4-methyl-2-nitro-5-(pyridin- 3-yl)phenyl]sulfamoyl}benzoic acid alofanib acide 3-{[4-méthyl-2-nitro-5-(pyridin- 3-yl)phenyl]sulfamoyl}benzoïque alofanib ácido 3-{[4-metil-2-nitro-5-(piridin- 3-il)fenil]sulfamoil}benzoico C19H15N3O6S CO2HS H N NO2H3C N O O altiratinibum altiratinib N-{4-[(2-cyclopropanecarboxamidopyridin-4-yl)oxy]- 2,5-difluorophenyl}-N'-(4-fluorophenyl)cyclopropane- 1,1-dicarboxamide altiratinib N-{4-[(2-cyclopropanecarboxamidopyridin-4-yl)oxy]- 2,5-difluorophényl}-N'-(4-fluorophényl)cyclopropane- 1,1-dicarboxamide altiratinib N-{4-[(2-ciclopropanocarboxamidopiridin-4-il)oxi]- 2,5-difluorofenil}-N'-(4-fluorofenil)ciclopropano- 1,1-dicarboxamida C26H21F3N4O4 O N H N H F O O F N H N O F amcasertibum amcasertib N-[2-(diethylamino)ethyl]-2,4-dimethyl-5-{[2-oxo- 5-(2-phenyl-1,3-thiazol-4-yl)-1,2-dihydro-3H-indol- 3-ylidene]methyl}-1H-pyrrole-3-carboxamide amcasertib N-[2-(diéthylamino)éthyl]-2,4-diméthyl-5-{[2-oxo- 5-(2-phényl-1,3-thiazol-4-yl)-1,2-dihydro-3H-indol- 3-ylidène]méthyl}-1H-pyrrole-3-carboxamide WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 97 amcasertib N-[2-(dietilamino)etil]-2,4-dimetil-5-{[5-(2-fenil-1,3-tiazol- 4-il)- 2-oxo-1,2-dihidro-3H-indol-3-ilideno]metil}-1H-pirrol- 3-carboxamida C31H33N5O2S H N O N S H N NH NCH3 H3C O CH3 CH3 apalutamidum apalutamide 4-{7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo- 6-thioxo-5,7-diazaspiro[3.4]octan-5-yl}-2-fluoro- N-methylbenzamide apalutamide 4-{7-[6-cyano-5-(trifluorométhyl)pyridin-3-yl]-8-oxo- 6-thioxo-5,7-diazaspiro[3.4]octan-5-yl}-2-fluoro- N-méthylbenzamide apalutamida 4-{7-[6-ciano-5-(trifluorometil)piridin-3-il]-8-oxo- 6-tioxo-5,7-diazaspiro[3.4]octan-5-il}-2-fluoro- N-metilbenzamida C21H15F4N5O2S NN N N H O F S O CF3 CNH3C ascrinvacumabum # ascrinvacumab immunoglobulin G2-kappa, anti-[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)], Homo sapiens monoclonal antibody; gamma2 heavy chain (1-444) [Homo sapiens VH (IGHV4- 31*02 (98.00%) -(IGHD) -IGHJ4*01) [10.7.10] (1-118) - IGHG2*01, G2m.. (CH1 (119-216), hinge (217-228), CH2 (229-337), CH3 (338-442), CHS (443-444)) (119-444)], (132-215')-disulfide with kappa light chain (1'-215') [Homo sapiens V-KAPPA (IGKV3-20*01 (99.00%) -IGKJ5*01) [7.3.9] (1'-108') -IGKC*01, Km3 (109'-215')]; dimer (220- 220'':221-221'':224-224'':227-227'')-tetrakisdisulfide Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 98 ascrinvacumab immunoglobuline G2-kappa, anti-[Homo sapiens ACVRL1 (réceptor de type II-like 1 de l’activine A, kinase 1 réceptor- like de l’activine, ALK1, ALK-1, récepteur R3 sérine/thréonine-protéine kinase, SKR3, récepteur de type I de la superfamille du facteur de croissance transformant bêta, récepteur de type I de la superfamille TGF-B, TSR-I, HHT2, ORW2)], Homo sapiens anticorps monoclonal; chaîne lourde gamma2 (1-444) [Homo sapiens VH (IGHV4-31*02 (98.00%) -(IGHD) -IGHJ4*01) [10.7.10] (1- 118) -IGHG2*01, G2m.. (CH1 (119-216), charnière (217- 228), CH2 (229-337), CH3 (338-442), CHS (443-444)) (119-444)], (132-215')-disulfure avec la chaîne légère kappa (1'-215') [Homo sapiens V-KAPPA (IGKV3-20*01 (99.00%) -IGKJ5*01) [7.3.9] (1'-108') -IGKC*01, Km3 (109'- 215')]; dimère (220-220'':221-221'':224-224'':227-227'')- tétrakisdisulfure ascrinvacumab inmunoglobulina G2-kappa, anti-[Homo sapiens ACVRL1 (receptor de tipo II-like 1 de la activina A, kinasa 1 receptor-like de la activina, ALK1, ALK-1, receptor R3 serina/treonina-proteína kinasa, SKR3, receptor de tipo I de la superfamilia del factor de crecimiento transformador beta, receptor de type I de la superfamilia TGF-B, TSR-I, HHT2, ORW2)], Homo sapiens anticuerpo monoclonal; cadena pesada gamma2 (1-444) [Homo sapiens VH (IGHV4-31*02 (98.00%) -(IGHD) -IGHJ4*01) [10.7.10] (1- 118) -IGHG2*01, G2m.. (CH1 (119-216), bisagra (217- 228), CH2 (229-337), CH3 (338-442), CHS (443-444)) (119-444)], (132-215')-disulfuro con la cadena ligera kappa (1'-215') [Homo sapiens V-KAPPA (IGKV3-20*01 (99.00%) -IGKJ5*01) [7.3.9] (1'-108') -IGKC*01, Km3 (109'-215')]; dimero (220-220'':221-221'':224-224'':227-227'')- tetrakisdisulfuro WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 99 avacincaptadum pegolum avacincaptad pegol 5'-O-({[6-(1-{(2RS)-2,3-bis[ω-methoxypoly(oxyethane-1,2- diyl)]propoxy}formamido)hexyl]oxy}hydroxyphosphoryl)-2'- deoxy-2'-fluoro-cytidylyl-(3'→5')-2'-O-methylguanylyl- (3'→5')-2'-deoxy-2'-fluorocytidylyl-(3'→5')-2'-deoxy-2'- fluorocytidylyl-(3'→5')-guanylyl-(3'→5')-2'-deoxy-2'- fluorocytidylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-O- methylguanylyl-(3'→5')-2'-deoxy-2'-fluorouridylyl-(3'→5')-2'- deoxy-2'-fluorocytidylyl-(3'→5')-2'-deoxy-2'-fluorouridylyl- (3'→5')-2'-deoxy-2'-fluorocytidylyl-(3'→5')-2'-O- methyladenylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'-O- methylguanylyl-(3'→5')-2'-deoxy-2'-fluorocytidylyl-(3'→5')- guanylyl-(3'→5')-2'-deoxy-2'-fluorocytidylyl-(3'→5')-2'- deoxy-2'-fluorouridylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')- 2'-O-methyladenylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')- 2'-deoxy-2'-fluorouridylyl-(3'→5')-2'-deoxy-2'-fluorocytidylyl- (3'→5')-2'-deoxy-2'-fluorouridylyl-(3'→5')-2'-O- methylguanylyl-(3'→5')-2'-O-methyladenylyl-(3'→5')-2'-O- methylguanylyl-(3'→5')-2'-deoxy-2'-fluorouridylyl-(3'→5')-2'- deoxy-2'-fluorouridylyl-(3'→5')-2'-deoxy-2'-fluorouridylyl- (3'→5')-adenylyl-(3'→5')-2'-deoxy-2'-fluorocytidylyl-(3'→5')- 2'-deoxy-2'-fluorocytidylyl-(3'→5')-2'-deoxy-2'-fluorouridylyl- (3'→5')-2'-O-methylguanylyl-(3'→5')-2'-deoxy-2'- fluorocytidylyl-(3'→5')-2'-O-methylguanylyl-(3'→3')- thymidine avacincaptad pégol 5'-O-({[6-(1-{(2RS)-2,3-bis[ω-méthoxypoly(oxyéthane-1,2- diyl)]propoxy}formamido)hexyl]oxy}hydroxyphosphoryl)-2'- déoxy-2'-fluoro-cytidylyl-(3'→5')-2'-O-méthylguanylyl- (3'→5')-2'-déoxy-2'-fluorocytidylyl-(3'→5')-2'-déoxy-2'- fluorocytidylyl-(3'→5')-guanylyl-(3'→5')-2'-déoxy-2'- fluorocytidylyl-(3'→5')-2'-O-méthylguanylyl-(3'→5')-2'-O- méthylguanylyl-(3'→5')-2'-déoxy-2'-fluorouridylyl-(3'→5')-2'- déoxy-2'-fluorocytidylyl-(3'→5')-2'-déoxy-2'-fluorouridylyl- (3'→5')-2'-déoxy-2'-fluorocytidylyl-(3'→5')-2'-O- méthyladénylyl-(3'→5')-2'-O-méthylguanylyl-(3'→5')-2'-O- méthylguanylyl-(3'→5')-2'-déoxy-2'-fluorocytidylyl-(3'→5')- guanylyl-(3'→5')-2'-déoxy-2'-fluorocytidylyl-(3'→5')-2'- déoxy-2'-fluorouridylyl-(3'→5')-2'-O-méthylguanylyl-(3'→5')- 2'-O-méthyladénylyl-(3'→5')-2'-O-méthylguanylyl-(3'→5')- 2'-déoxy-2'-fluorouridylyl-(3'→5')-2'-déoxy-2'-fluorocytidylyl- (3'→5')-2'-déoxy-2'-fluorouridylyl-(3'→5')-2'-O- méthylguanylyl-(3'→5')-2'-O-méthyladénylyl-(3'→5')-2'-O- méthylguanylyl-(3'→5')-2'-déoxy-2'-fluorouridylyl-(3'→5')-2'- déoxy-2'-fluorouridylyl-(3'→5')-2'-déoxy-2'-fluorouridylyl- (3'→5')-adénylyl-(3'→5')-2'-déoxy-2'-fluorocytidylyl-(3'→5')- 2'-déoxy-2'-fluorocytidylyl-(3'→5')-2'-déoxy-2'-fluorouridylyl- (3'→5')-2'-O-méthylguanylyl-(3'→5')-2'-déoxy-2'- fluorocytidylyl-(3'→5')-2'-O-méthylguanylyl-(3'→3')- thymidine Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 100 avacincaptad pegol 5'-O-({[6-(1-{(2RS)-2,3-bis[ω-metoxipoli(oxietano-1,2- diil)]propoxi}formamido)hexil]oxi}hidroxifosforil)-2'-desoxi- 2'-fluoro-citidilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'-desoxi- 2'-fluorocitidilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')- guanilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')-2'-O- metilguanilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'-desoxi-2'- fluorouridilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')-2'- desoxi-2'-fluorouridilil-(3'→5')-2'-desoxi-2'-fluorocitidilil- (3'→5')-2'-O-metiladenilil-(3'→5')-2'-O-metilguanilil-(3'→5')- 2'-O-metilguanilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')- guanilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')-2'-desoxi- 2'-fluorouridilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'-O- metiladenilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'-desoxi-2'- fluorouridilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')-2'- desoxi-2'-fluorouridilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'- O-metiladenilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'-desoxi- 2'-fluorouridilil-(3'→5')-2'-desoxi-2'-fluorouridilil-(3'→5')-2'- desoxi-2'-fluorouridilil-(3'→5')-adenilil-(3'→5')-2'-desoxi-2'- fluorocitidilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')-2'- desoxi-2'-fluorouridilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'- desoxi-2'-fluorocitidilil-(3'→5')-2'-O-metilguanilil-(3'→3')- timidina C395H492F21N142O262P39 (C2H4O)2n H3CO O n O H3CO n O O H N = R O PO OH (3'-5') R-dflC-mG-dflC-dflC-G-dflC-mG-mG-dflU-dflC-dflU-dflC- mA-mG-mG-dflC-G-dflC-dflU-mG-mA-mG-dflU-dflC-dflU-mG- mA-mG-dflU-dflU-dflU-A-dflC-dflC-dflU-mG-dflC-mG3'-3'dT Legend dfl = 2'-deoxy-2'-fluoro m = 2'-O-methyl avelumabum # avelumab immunoglobulin G1-lambda1, anti-[Homo sapiens CD274 (programmed death ligand 1, PDL1, PD-L1, B7 homolog 1, B7H1)], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-450) [Homo sapiens VH (IGHV3- 23*01 (90.80%) -(IGHD)-IGHJ4*01) [8.8.13] (1-120) - IGHG1*01, Gm17,1 (CH1 (121-218), hinge (219-233), CH2 (234-343), CH3 (344-448), CHS (449-450) (121-450)], (223-215')-disulfide with lambda1 light chain (1'-216') [Homo sapiens V-LAMBDA (IGLV2-14*01 (99.00%) - IGLJ1*01) [9.3.10] (1'-110') -IGLC1*02 (111'-216')]; dimer (229-229'':232-232'')-bisdisulfide avélumab immunoglobuline G1-lambda1, anti-[Homo sapiens CD274 (ligand 1 de mort programmée, PDL1, PD-L1, homologue 1 de B7, B7H1)], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-450) [Homo sapiens VH (IGHV3-23*01 (90.80%) -(IGHD)-IGHJ4*01) [8.8.13] (1- 120) -IGHG1*01, Gm17,1 (CH1 (121-218), charnière (219- 233), CH2 (234-343), CH3 (344-448), CHS (449-450) (121-450)], (223-215')-disulfure avec la chaîne légère lambda1 (1'-216') [Homo sapiens V-LAMBDA (IGLV2- 14*01 (99.00%) -IGLJ1*01) [9.3.10] (1'-110') -IGLC1*02 (111'-216')]; dimère (229-229'':232-232'')-bisdisulfure WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 101 avelumab inmunoglobulina G1-lambda1, anti-[Homo sapiens CD274 (ligando 1 de muerte programada, PDL1, PD-L1, homólogo 1 de B7, B7H1)], anticuerpo monoclonal de Homo sapiens; cadena pesada gamma1 (1-450) [Homo sapiens VH (IGHV3-23*01 (90.80%) -(IGHD)-IGHJ4*01) [8.8.13] (1- 120) -IGHG1*01, Gm17,1 (CH1 (121-218), bisagra (219- 233), CH2 (234-343), CH3 (344-448), CHS (449-450) (121-450)], (223-215')-disulfuro con la cadena ligera lambda1 (1'-216') [Homo sapiens V-LAMBDA (IGLV2-14*01 (99.00%) -IGLJ1*01) [9.3.10] (1'-110') -IGLC1*02 (111'-216')]; dímero (229-229'':232- 232'')-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaEVQLLESGGG LVQPGGSLRL SCAASGFTFS SYIMMWVRQA PGKGLEWVSS 50 IYPSGGITFY ADTVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARIK 100 LGTVTTVDYW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK 150 DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT 200 YICNVNHKPS NTKVDKKVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP 250 KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 300 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ 350 VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV 400 LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK 450 Light chain / Chaîne légère / Cadena ligera QSALTQPASV SGSPGQSITI SCTGTSSDVG GYNYVSWYQQ HPGKAPKLMI 50 YDVSNRPSGV SNRFSGSKSG NTASLTISGL QAEDEADYYC SSYTSSSTRV 100 FGTGTKVTVL GQPKANPTVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV 150 AWKADGSPVK AGVETTKPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT 200 HEGSTVEKTV APTECS 216 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 147-203 264-324 370-428 22''-96'' 147''-203'' 264''-324'' 370''-428'' Intra-L (C23-C104) 22'-90' 138'-197' 22'''-90''' 138'''-197''' Inter-H-L (h 5-CL 126) 223-215' 223''-215''' Inter-H-H (h 11, h 14) 229-229'' 232-232'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 300, 300'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados Other post-translational modifications / Autres modifications post-traductionnelles / Otras modificaciones post-traduccionales H CHS K2 C-terminal lysine clipping: 450, 450' belizatinibum belizatinib 4-fluoro-N-(6-{[4-(2-hydroxypropan-2-yl)piperidin- 1-yl]methyl}-1-{cis-4-[(propan-2-yl)carbamoyl]cyclohexyl}- 1H-benzimidazol-2-yl)benzamide bélizatinib 4-fluoro-N-(6-{[4-(2-hydroxypropan-2-yl)pipéridin- 1-yl]méthyl}-1-{cis-4-[(propan-2-yl)carbamoyl]cyclohexyl}- 1H-benzimidazol-2-yl)benzamide belizatinib 4-fluoro-N-(6-{[4-(2-hidroxipropan-2-il)piperidin- 1-il]metil}-1-{cis-4-[(propan-2-il)carbamoil]ciclohexil}- 1H-benzoimidazol-2-il)benzamida Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 102 C33H44FN5O3 N H3C HO CH3 N H N N O F NH O CH3 H3C bexagliflozinum bexagliflozin (1S)-1,5-anhydro-1-C-[4-chloro-3-({4-[2- (cyclopropyloxy)ethoxy]phenyl}methyl)phenyl]- D-glucitol bexagliflozine (1S)-1,5-anhydro-1-C-[4-chloro-3-({4-[2- (cyclopropyloxy)éthoxy]phényl}méthyl)phényl]- D-glucitol bexagliflozina (1S)-1,5-anhidro-1-C-[3-({4-[2- (ciclopropiloxi)etoxi]fenil}metil)-4-clorofenil]-D-glucitol C24H29ClO7 O OH OH HO HO O Cl O bictegravirum bictegravir (2R,5S,13aR)-8-hydroxy-7,9-dioxo-N-[(2,4,6- trifluorophenyl)methyl]-2,3,4,5,7,9,13,13a-octahydro- 2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine- 10-carboxamide bictégravir (2R,5S,13aR)-8-hydroxy-7,9-dioxo-N-[(2,4,6- trifluorophényl)méthyl]-2,3,4,5,7,9,13,13a-octahydro- 2,5-méthanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazépine- 10-carboxamide WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 103 bictegravir (2R,5S,13aR)-8-hidroxi-7,9-dioxo-N-[(2,4,6- trifluorofenil)metil]-2,3,4,5,7,9,13,13a-octahidro- 2,5-metanopirido[1',2':4,5]pirazino[2,1-b][1,3]oxazepina- 10-carboxamida C21H18F3N3O5 O N N H O OH O H N F F O F H H bleselumabum # bleselumab immunoglobulin G4-kappa, anti-[Homo sapiens CD40 (tumor necrosis factor receptor superfamily member 5, TNFRSF5)], human monoclonal antibody; gamma4 heavy chain (1-448) [Homo sapiens VH (IGHV4- 39*01 (92.90%) -(IGHD)-IGHJ5*01) [10.7.13] (1-121) - IGHG4*01 (CH1 (122-219), hinge S10>P (229) (220-231), CH2 (232-341), CH3 (342-446), CHS (447-448)) (122- 448)], (135-213')-disulfide with kappa light chain (1’-213’) [Homo sapiens (V-KAPPA (IGKV1-13*02 (98.90%) - IGKJ1*01) [6.3.8] (1'-106') -IGKC*01, Km3 (107'-213')]; dimer (227-227":230-230")-bisdisulfide blésélumab immunoglobuline G4-kappa, anti-[Homo sapiens CD40 (membre 5 de la superfamille des récepteurs du TNF, TNFRSF5)], anticorps monoclonal humain; chaîne lourde gamma4 (1-448) [Homo sapiens VH (IGHV4-39*01 (92.90%) -(IGHD)-IGHJ5*01) [10.7.13] (1- 121) -IGHG4*01 (CH1 (122-219), charnière S10>P (229) (220-231), CH2 (232-341), CH3 (342-446), CHS (447- 448)) (122-448)], (135-213')-disulfure avec la chaîne légère kappa (1’-213’) [Homo sapiens (V-KAPPA (IGKV1-13*02 (98.90%) -IGKJ1*01) [6.3.8] (1'-106') -IGKC*01, Km3 (107'- 213')]; dimère (227-227":230-230")-bisdisulfure bleselumab inmunoglobulina G4-kappa, anti-[Homo sapiens CD40 (miembro 5 de la superfamilia de receptores del TNF, TNFRSF5)], anticuerpo monoclonal humano; cadena pesada gamma4 (1-448) [Homo sapiens VH (IGHV4-39*01 (92.90%) -(IGHD)-IGHJ5*01) [10.7.13] (1- 121) -IGHG4*01 (CH1 (122-219), bisagra S10>P (229) (220-231), CH2 (232-341), CH3 (342-446), CHS (447- 448)) (122-448)], (135-213')-disulfuro con la cadena ligera kappa (1’-213’) [Homo sapiens (V-KAPPA (IGKV1-13*02 (98.90%) -IGKJ1*01) [6.3.8] (1'-106') -IGKC*01, Km3 (107'- 213')]; dímero (227-227":230-230")-bisdisulfuro Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 104 Heavy chain / Chaîne lourde / Cadena pesadaQLQLQESGPG LLKPSETLSL TCTVSGGSIS SPGYYGGWIR QPPGKGLEWI 50 GSIYKSGSTY HNPSLKSRVT ISVDTSKNQF SLKLSSVTAA DTAVYYCTRP 100 VVRYFGWFDP WGQGTLVTVS SASTKGPSVF PLAPCSRSTS ESTAALGCLV 150 KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTK 200 TYTCNVDHKP SNTKVDKRVE SKYGPPCPPC PAPEFEGGPS VFLFPPKPKD 250 TLMISRTPEV TCVVVDVSQE DPEVQFNWYV DGVEVHNAKT KPREEQFNST 300 YRVVSVLTVL HQDWLNGKEY KCKVSNKGLP SSIEKTISKA KGQPREPQVY 350 TLPPSQEEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD 400 SDGSFFLYSR LTVDKSRWQE GNVFSCSVMH EALHNHYTQK SLSLSLGK 448 Light chain / Chaîne légère / Cadena ligera AIQLTQSPSS LSASVGDRVT ITCRASQGIS SALAWYQQKP GKAPKLLIYD 50 ASNLESGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ FNSYPTFGQG 100 TKVEIKRTVA APSVFIFPPS DEQLKSGTAS VVCLLNNFYP REAKVQWKVD 150 NALQSGNSQE SVTEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL 200 SSPVTKSFNR GEC 213 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-97 148-204 262-322 368-426 22''-97'' 148''-204'' 262''-322'' 368''-426'' Intra-L (C23-C104) 23'-88' 133'-193' 23'''-88''' 133'''-193''' Inter-H-L (CH1 10-CL 126) 135-213' 135''-213''' Inter-H-H (h 8, h 11) 227-227'' 230-230'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 298, 298'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados brigatinibum brigatinib 2-[(5-chloro-2-{2-methoxy-4-[4-(4-methylpiperazin- 1-yl)piperidin-1-yl]anilino}pyrimidin- 4-yl)amino]phenyl}dimethyl-λ5-phosphanone brigatinib 2-[(5-chloro-2-{2-méthoxy-4-[4-(4-méthylpipérazin- 1-yl)pipéridin-1-yl]anilino}pyrimidin- 4-yl)amino]phényl}diméthyl-λ5-phosphanone brigatinib 2-[(5-cloro-2-{2-metoxi-4-[4-(4-metilpiperazin- 1-il)piperidin-1-il]anilino}pirimidin- 4-il)amino]fenil}dimetil-λ5-fosfanona C29H39ClN7O2P NH P N N Cl CH3 CH3 O H N N N N H3C O CH3 capsaicinum capsaicin (6E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]- 8-methylnon-6-enamide capsaïcine (6E)-N-[(4-hydroxy-3-méthoxyphényl)méthyl]- 8-méthylnon-6-énamide capsaicina (6E)-N-[(4-hidroxi-3-metoxifenil)metil]-8-metilnon- 6-enamida WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 105 C18H27NO3 N H O OCH3 OH H3C CH3 cenerimodum cenerimod (2S)-3-{4-[5-(2-cyclopentyl-6-methoxypyridin-4-yl)- 1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenoxy}propane- 1,2-diol cénérimod (2S)-3-{4-[5-(2-cyclopentyl-6-méthoxypyridin-4-yl)- 1,2,4-oxadiazol-3-yl]-2-éthyl-6-méthylphénoxy}propane- 1,2-diol cenerimod (2S)-3-{4-[5-(2-ciclopentil-6-metoxipiridin-4-il)- 1,2,4-oxadiazol-3-il]-2-etil-6-metilfenoxi}propano-1,2-diol C25H31N3O5 NO N N O OH H OH CH3 CH3 OCH3 cenobamatum cenobamate (1R)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl carbamate cénobamate carbamate de (1R)-1-(2-chlorophényl)- 2-(2H-tétrazol-2-yl)éthyle cenobamato carbamato de (1R)-1-(2-clorofenil)-2-(2H-tetrazol- 2-il)etilo C10H10ClN5O2 N N NN Cl OH NH2 O Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 106 cergutuzumabum amunaleukinum # cergutuzumab amunaleukin immunoglobulin G1-kappa fused to IL2 (interleukin 2), anti- [Homo sapiens CEACAM5 (carcinoembryonic antigen- related cell adhesion molecule 5, CEA, CD66e)], humanized monoclonal antibody fused to IL2; gamma1 heavy chain (1-451) [humanized VH (Homo sapiens IGHV1-18*01 (82.70%) -(IGHD)-IGHJ6*01) [8.8.14] (1-121) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (122-219), hinge (220-234), CH2 L1.3>A (238), L1.2>A (239), P114>G (333) (235-344), CH3 Y5>C (353), T22>S (370), L24>A (372), Y86>V (411) (345-449), CHS (450- 451)) (122-451)], (224-215')-disulfide with kappa light chain (1’-215’) [humanized V-KAPPA (Homo sapiens IGKV1- 16*01 (82.10%) -IGKJ2*01) [6.3.10] (1'-108') -Homo sapiens IGKC*01, Km3 (109'-215')]; gamma1 heavy chain fused to IL2 (1''-598'') [humanized VH (Homo sapiens IGHV1-18*01 (82.70%) -(IGHD)-IGHJ6*01) [8.8.14] (1''- 121'') -Homo sapiens IGHG1*01, G1m17,1 (CH1 (122''- 219''), hinge (220''-234''), CH2 L1.3>A (238''), L1.2>A (239''), P114>G (333'') (235''-344''), CH3 S10>C (358''), T22>W (370''), (345''-449''), CHS K2>del (450'')) (122''- 450'') -15-mer (tris(tetraglycyl-seryl)) linker (451''-465'') - Homo sapiens IL2 (Pr21-153) T23>A (468''), F62>A (507''), Y65>A (510''), L92>G (547''), C145>A (590'') (466''-598'')], (224''-215''')-disulfide with kappa light chain (1'''-215''') [humanized V-KAPPA (Homo sapiens IGKV1-16*01 (82.10%) -IGKJ2*01) [6.3.10] (1'''-108''') -Homo sapiens IGKC*01, Km3 (109'''-215''')]; dimer (230-230":233-233")- bisdisulfide cergutuzumab amunaleukine immunoglobuline G1-kappa fusionnée à l’IL2 (interleukine 2), anti-[Homo sapiens CEACAM5 (molécule d’adhésion cellulaire 5 apparentée à l’antigène carcinoembryonaire, CEA, CD66e)], anticorps monoclonal humanisé fusionné à l’IL2; chaîne lourde gamma1 (1-451) [VH humanisé (Homo sapiens IGHV1-18*01 (82.70%) -(IGHD)-IGHJ6*01) [8.8.14] (1-121) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (122-219), charnière (220-234), CH2 L1.3>A (238), L1.2>A (239), P114>G (333) (235-344), CH3 Y5>C (353), T22>S (370), L24>A (372), Y86>V (411) (345-449), CHS (450- 451)) (122-451)], (224-215')-disulfure avec la chaîne légère kappa (1’-215’) [V-KAPPA humanisé (Homo sapiens IGKV1-16*01 (82.10%) -IGKJ2*01) [6.3.10] (1'-108') - Homo sapiens IGKC*01, Km3 (109'-215')]; chaîne lourde gamma1 fusionnée à l’IL2 (1''-598'') [VH humanisé (Homo sapiens IGHV1-18*01 (82.70%) -(IGHD)-IGHJ6*01) [8.8.14] (1''-121'') -Homo sapiens IGHG1*01, G1m17,1 (CH1 (122''-219''), charnière (220''-234''), CH2 L1.3>A (238''), L1.2>A (239''), P114>G (333'') (235''-344''), CH3 S10>C (358''), T22>W (370''), (345''-449''), CHS K2>del (450'')) (122''-450'') -15-mer (tris(tétraglycyl-séryl)) linker (451''-465'') -Homo sapiens IL2 (Pr21-153) T23>A (468''), F62>A (507''), Y65>A (510''), L92>G (547''), C145>A (590'') (466''-598'')], (224''-215''')- disulfure avec la chaîne légère kappa (1'''-215''') [V-KAPPA humanisé (Homo sapiens IGKV1-16*01 (82.10%) -IGKJ2*01) [6.3.10] (1'''- 108''') -Homo sapiens IGKC*01, Km3 (109'''-215''')]; dimère (230-230":233-233")-bisdisulfure WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 107 cergutuzumab amunaleukina inmunoglobulina G1-kappa fusionada con IL2 (interleukina 2), anti-[Homo sapiens CEACAM5 (molécula de adhesión celular 5 relacionada con el antígeno carcinoembrionario, CEA, CD66e)], anticuerpo monoclonal humanizado fusionado IL2; cadena pesada gamma1 (1-451) [VH humanizado (Homo sapiens IGHV1-18*01 (82.70%) -(IGHD)-IGHJ6*01) [8.8.14] (1-121) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (122-219), bisagra (220-234), CH2 L1.3>A (238), L1.2>A (239), P114>G (333) (235-344), CH3 Y5>C (353), T22>S (370), L24>A (372), Y86>V (411) (345-449), CHS (450- 451)) (122-451)], (224-215')-disulfuro con la cadena ligera kappa (1’-215’) [V-KAPPA humanizado (Homo sapiens IGKV1-16*01 (82.10%) -IGKJ2*01) [6.3.10] (1'-108') - Homo sapiens IGKC*01, Km3 (109'-215')]; cadena pesada fusionada con ’IL2 (1''-598'') [VH humanizado (Homo sapiens IGHV1-18*01 (82.70%) -(IGHD)-IGHJ6*01) [8.8.14] (1''-121'') -Homo sapiens IGHG1*01, G1m17,1 (CH1 (122''-219''), bisagra (220''-234''), CH2 L1.3>A (238''), L1.2>A (239''), P114>G (333'') (235''-344''), CH3 S10>C (358''), T22>W (370''), (345''-449''), CHS K2>del (450'')) (122''-450'') -15-mer (tris(tetraglicil-seril)) espaciador (451''-465'') -Homo sapiens IL2 (Pr21-153) T23>A (468''), F62>A (507''), Y65>A (510''), L92>G (547''), C145>A (590'') (466''-598'')], (224''-215''')- disulfuro con la cadena ligera kappa (1'''-215''') [V-KAPPA humanizado (Homo sapiens IGKV1-16*01 (82.10%) -IGKJ2*01) [6.3.10] (1'''-108''') -Homo sapiens IGKC*01, Km3 (109'''-215''')]; dímero (230-230":233-233")-bisdisulfuro Heavy chain H/ Chaîne lourde H/ Cadena pesada HQVQLVQSGAE VKKPGASVKV SCKASGYTFT EFGMNWVRQA PGQGLEWMGW 50 INTKTGEATY VEEFKGRVTF TTDTSTSTAY MELRSLRSDD TAVYYCARWD 100 FAYYVEAMDY WGQGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV 150 KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ 200 TYICNVNHKP SNTKVDKKVE PKSCDKTHTC PPCPAPEAAG GPSVFLFPPK 250 PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALGAPIEKTI SKAKGQPREP 350 QVCTLPPSRD ELTKNQVSLS CAVKGFYPSD IAVEWESNGQ PENNYKTTPP 400 VLDSDGSFFL VSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG 450 K 451 Heavy chain H'' (fused to IL2) / Chaîne lourde H'' (fusionnée to IL2) / Cadena pesada H'' (fusionada con IL2) QVQLVQSGAE VKKPGASVKV SCKASGYTFT EFGMNWVRQA PGQGLEWMGW 50 INTKTGEATY VEEFKGRVTF TTDTSTSTAY MELRSLRSDD TAVYYCARWD 100 FAYYVEAMDY WGQGTTVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV 150 KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ 200 TYICNVNHKP SNTKVDKKVE PKSCDKTHTC PPCPAPEAAG GPSVFLFPPK 250 PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALGAPIEKTI SKAKGQPREP 350 QVYTLPPCRD ELTKNQVSLW CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 400 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG 450 GGGGSGGGGS GGGGSAPASS STKKTQLQLE HLLLDLQMIL NGINNYKNPK 500 LTRMLTAKFA MPKKATELKH LQCLEEELKP LEEVLNGAQS KNFHLRPRDL 550 ISNINVIVLE LKGSETTFMC EYADETATIV EFLNRWITFA QSIISTLT 598 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCKASAAVG TYVAWYQQKP GKAPKLLIYS 50 ASYRKRGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCHQ YYTYPLFTFG 100 QGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150 VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200 GLSSPVTKSF NRGEC 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 148-204 265-325 371-429 Intra-H (C23-C104) 22''-96'' 148''-204'' 265''-325'' 371''-429'' -IL2 (Pr C78-C125) 523''-570'' Intra-L (C23-C104) 23'-88' 135'-195' 23'''-88''' 135'''-195''' Inter-H-L (h 5-CL 126) 224-215' 224''-215''' Inter-H-H (h 11, h 14) 230-230'' 233-233'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 301, 301'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados Other post-translational modifications / Autres modifications post-traductionnelles / Otras modificaciones post-traduccionales H CHS K2 C-terminal lysine clipping: 451 Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 108 ciraparantagum ciraparantag N1,N1'-[piperazine-1,4-diylbis(propane-1,3-diyl)]bis- L-argininamide ciraparantag N1,N1'-[pipérazine-1,4-diylbis(propane-1,3-diyl)]bis- L-argininamide ciraparantag N1,N1'-[piperazina-1,4-diilbis(propano-1,3-diil)]bis- L-argininamida C22H48N12O2 N N N HH N O O NH2 H2N H H NH H2N NH HN HN NH2 cobitolimodum cobitolimod all-P-ambo-2'-deoxy-P-thioguanylyl-(3'→5')-2'-deoxy-P- thioguanylyl-(3'→5')-2'-deoxy-P-thioadenylyl-(3'→5')-2'- deoxyadenylyl-(3'→5')-2'-deoxycytidylyl-(3'→5')-2'- deoxyadenylyl-(3'→5')-2'-deoxyguanylyl-(3'→5')-thymidylyl- (3'→5')-thymidylyl-(3'→5')-2'-deoxycytidylyl-(3'→5')-2'- deoxyguanylyl-(3'→5')-thymidylyl-(3'→5')-2'-deoxycytidylyl- (3'→5')-2'-deoxycytidylyl-(3'→5')-2'-deoxyadenylyl-(3'→5')- P-thiothymidylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'- deoxy-P-thioguanylyl-(3'→5')-2'-deoxycytidine cobitolimod tout-P-ambo-2'-déoxy-P-thioguanylyl-(3'→5')-2'-déoxy-P- thioguanylyl-(3'→5')-2'-déoxy-P-thioadénylyl-(3'→5')-2'- déoxyadénylyl-(3'→5')-2'-déoxycytidylyl-(3'→5')-2'- déoxyadénylyl-(3'→5')-2'-déoxyguanylyl-(3'→5')-thymidylyl- (3'→5')-thymidylyl-(3'→5')-2'-déoxycytidylyl-(3'→5')-2'- déoxyguanylyl-(3'→5')-thymidylyl-(3'→5')-2'-déoxycytidylyl- (3'→5')-2'-déoxycytidylyl-(3'→5')-2'-déoxyadénylyl-(3'→5')- P-thiothymidylyl-(3'→5')-2'-déoxy-P-thioguanylyl-(3'→5')-2'- déoxy-P-thioguanylyl-(3'→5')-2'-déoxycytidine cobitolimod todo-P-ambo-2'-desoxi-P-tioguanilil-(3'→5')-2'-desoxi-P- tioguanilil-(3'→5')-2'-desoxi-P-tioadenilil-(3'→5')-2'- desoxiadenilil-(3'→5')-2'-desoxicitidilil-(3'→5')-2'- desoxiadenilil-(3'→5')-2'-desoxiguanilil-(3'→5')-timidilil- (3'→5')-timidilil-(3'→5')-2'-desoxicitidilil-(3'→5')-2'- desoxiguanilil-(3'→5')-timidilil-(3'→5')-2'-desoxicitidilil- (3'→5')-2'-desoxicitidilil-(3'→5')-2'-desoxiadenilil-(3'→5')-P- tiotimidilil-(3'→5')-2'-desoxi-P-tioguanilil-(3'→5')-2'-desoxi- P-tioguanilil-(3'→5')-2'-desoxicitidina WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 109 C185H233N73O106P18S6 (3'-5')-d-(G-G-A-A-C-A-G-T-T-C-G-T-C-C-A-T-G-G-C) Modified residues / Nucléotides modifiés / Nucleótidos modificados B = A , G , T (P-RS)-2'-deoxy-P-thionucleyl (P-RS)-2'-désoxy-P-thionucléyle (P-RS)-2'-deoxi-P-thionucleil and epimer at P et l'épimère en P y el epímero al P O OH OP S O OH C5' 3' 5' BN daprodustatum daprodustat N-[(1,3-dicyclohexylhexahydro-2,4,6-trioxopyrimidin- 5-yl)carbonyl]glycine daprodustat N-[(1,3-dicyclohexylhexahydro-2,4,6-trioxopyrimidin- 5-yl)carbonyl]glycine daprodustat N-[(1,3-diciclohexilhexahidro-2,4,6-trioxopirimidin- 5-il)carbonil]glicina C19H27N3O6 N N H N CO2H O O O O difelikefalinum difelikefalin 4-amino-1-(D-phenylalanyl-D-phenylalanyl-D-leucyl-D- lysyl)piperidine-4-carboxylic acid difélikéfaline acide 4-amino-1-(D-phénylalanyl-D-phénylalanyl- D-leucyl-D-lysyl)pipéridine-4-carboxylique difelicefalina ácido 4-amino-1-(D-fenilalanil-D-fenilalanil-D-leucil- D-lisil)piperidina-4-carboxílico C36H53N7O6 O H N N H O H N N O NH2 CO2H O H H H H2N H H2N H3C CH3 Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 110 dusquetidum dusquetide L-arginyl-L-isoleucyl-L-valyl-L-prolyl-L-alaninamide dusquétide L-arginyl-L-isoleucyl-L-valyl-L-prolyl-L-alaninamide dusquetida L-arginil-L-isoleucil-L-valil-L-prolil-L-alaninamida C25H47N9O5 Arg Ile Val Pro Ala NH2 5 H efpegsomatropinum # efpegsomatropin recombinant human growth hormone (somatropin) and human immunoglobulin G4 Fc fragment dimer, produced in Escherichia coli (nonglycosylated), linked together with polyethylene glycol derivative linker: Nα.1,N1.9'-[ω-(oxypropane-1,3-diyl)-α-(propane- 1,3-diyl)poly(oxyethylene)] human growth hormone, human immunoglobulin G4 Fc fragment (IGHG4*01 H-CH2-CH3)- (9'-229')-peptide dimer (11'-11'')-disulfide efpègsomatropine hormone de croissance humaine (somatropine) et dimère du fragment Fc de l'IgG4 humain, recombinants produits par Escherichia coli (non glycosylés), liés par un pont dérivé du polyéthylèneglycol : Nα.1,N1.9'- [ω-(oxypropane-1,3-diyl)-α-(propane- 1,3-diyl)poly(oxyéthylène)] hormone de croissance humaine, (11'-11'')-disulfure du dimère du fragment Fc de l'immunoglobuline G4 humaine (IGHG4*01 H-CH2-CH3)- (9'-229')-peptide efpegsomatropina hormona humana de crecimiento (somatropina) y dímero del fragmento Fc de la IgG4 humana, recombinantes, producidos por Escherichia coli (no glicosilados), unidos por un puente derivado del polietilenglicol : Nα.1,N1.9'- [ω-(oxipropano-1,3-diil)-α-(propano- 1,3-diil)poli(oxietileno)] hormona humana de crecimiento, (11'-11'')-disulfuro del dímero del fragmento Fc de la inmunoglobulina G4 humana (IGHG4*01 H-CH2-CH3)-(9'- 229')-péptido WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 111 elamipretidum elamipretide D-arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl- L-phenylalaninamide élamiprétide D-arginyl-2,6-diméthyl-L-tyrosyl-L-lysyl- L-phénylalaninamide elamipretida D-arginil-2,6-dimetil-L-tirosil-L-lisil-L-fenilalaninamida C32H49N9O5 CH3 H3C O H N N H O H N NH2 O H HO H2N H HN NH2 HN H2N H OH emicizumabum # emicizumab immunoglobulin G4-kappa, bispecific, anti-[Homo sapiens F9a (activated coagulation factor F9, activated coagulation factor IX) and anti-[Homo sapiens F10 (coagulation factor 10, coagulation factor X)], humanized monoclonal antibody; gamma4 heavy chain (1-448) [humanized VH (Homo sapiens IGHV3-23*04 (87.80%) -(IGHD)-IGHJ4*01 (1- 123)), IGHG4*01 (CH1 K100>Q (202) (124-221), hinge S10>P (231) (222-233), CH2 F84.3>Y (299) (234-343), CH3 E12>K (359), R88>K (412), H115>R (438), L125>P (448) (344-448), CHS>del) (124-448)], (137-214')-disulfide with kappa light chain (1’-214’) [humanized V-KAPPA (Homo sapiens IGKV1-39*01 (80.00%) -IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; gamma4 heavy chain (1-444) [VH (Homo sapiens IGHV1- 2*02 (75.50%) -(IGHD)-IGHJ6*03 Q120>E (111''), T123>L (114'') (1''-119'')), IGHG4*01 (CH1 A100>Q (198'') (120''- 217''), hinge S10>P (227'') (218''-229''), CH2 F84.3>Y (295''), (230''-339''), CH3 R88>K (408), K119>E (438), L125>P (444) (340''-444''), CHS>del) (120''-444'')], (133''- 214''')-disulfide with kappa light chain (1'''-214''') [humanized V-KAPPA (Homo sapiens IGKV1-39*01 (80.00%) -IGKJ4*01) [6.3.9] (1'''-107''') -Homo sapiens IGKC*01, Km3 (108'''-214''')]; dimer (229-225":232-228")- bisdisulfide Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 112 émicizumab immunoglobuline G4-kappa, bispécifique, anti-[Homo sapiens F9a (facteur de coagulation F9 activé, facteur de coagulation IX activé) et anti-[Homo sapiens F10 (facteur de coagulation 10, facteur de coagulation X)], anticorps monoclonal humanisé; chaîne lourde gamma4 (1-448) [VH humanisé (Homo sapiens IGHV3-23*04 (87.80%) -(IGHD)-IGHJ4*01 (1- 123)), IGHG4*01 (CH1 K100>Q (202) (124-221), S10>P (231) (222-233), CH2 F84.3>Y (299) (234-343), CH3 E12>K (359), R88>K (412), H115>R (438), L125>P (448) (344-448), CHS>del) (124-448)], (137-214')-disulfure avec la chaîne légère kappa (1’-214’) [V-KAPPA humanisé (Homo sapiens IGKV1-39*01 (80.00%) -IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; chaîne lourde gamma4 (1-444) [VH humanisé (Homo sapiens IGHV1-2*02 (75.50%) -(IGHD)-IGHJ6*03 Q120>E (111''), T123>L (114'') (1''-119'')), IGHG4*01 (CH1 A100>Q (198'') (120''-217''), charnière S10>P (227'') (218''-229''), CH2 F84.3>Y (295''), (230''-339''), CH3 R88>K (408), K119>E (438), L125>P (444) (340''-444''), CHS>del) (120''- 444'')], (133''-214''')-disulfure avec la chaîne légère kappa (1'''-214''') [V-KAPPA humanisé (Homo sapiens IGKV1- 39*01 (80.00%) -IGKJ4*01) [6.3.9] (1'''-107''') -Homo sapiens IGKC*01, Km3 (108'''-214''')]; dimère (229- 225":232-228")-bisdisulfure emicizumab inmunoglobulina G4-kappa, biespecífica, anti-[Homo sapiens F9a (factor de coagulación F9 activado, factor de coagulación IX activado) y anti-[Homo sapiens F10 (factor de coagulación 10, factor de coagulación X)], anticuerpo monoclonal humanizado; cadena pesada gamma4 (1-448) [VH humanizado (Homo sapiens IGHV3-23*04 (87.80%) -(IGHD)-IGHJ4*01 (1- 123)), IGHG4*01 (CH1 K100>Q (202) (124-221), S10>P (231) (222-233), CH2 F84.3>Y (299) (234-343), CH3 E12>K (359), R88>K (412), H115>R (438), L125>P (448) (344-448), CHS>del) (124-448)], (137-214')-disulfuro con la cadena ligera kappa (1’-214’) [V-KAPPA humanizado (Homo sapiens IGKV1-39*01 (80.00%) -IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; cadena pesada gamma4 (1-444) [VH humanizado (Homo sapiens IGHV1-2*02 (75.50%) -(IGHD)-IGHJ6*03 Q120>E (111''), T123>L (114'') (1''-119'')), IGHG4*01 (CH1 A100>Q (198'') (120''-217''),bisagra S10>P (227'') (218''-229''), CH2 F84.3>Y (295''), (230''-339''), CH3 R88>K (408), K119>E (438), L125>P (444) (340''-444''), CHS>del) (120''-444'')], (133''-214''')-disulfuro con la cadena ligera kappa (1'''- 214''') [V-KAPPA humanizado (Homo sapiens IGKV1- 39*01 (80.00%) -IGKJ4*01) [6.3.9] (1'''-107''') -Homo sapiens IGKC*01, Km3 (108'''-214''')]; dímero (229- 225":232-228")-bisdisulfuro WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 113 Heavy chain anti-F9a/ Chaîne lourde anti-F9a/ Cadena pesada anti-F9aQVQLVESGGG LVQPGGSLRL SCAASGFTFS YYDIQWVRQA PGKGLEWVSS 50 ISPSGQSTYY RREVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARRT 100 GREYGGGWYF DYWGQGTLVT VSSASTKGPS VFPLAPCSRS TSESTAALGC 150 LVKDYFPEPV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG 200 TQTYTCNVDH KPSNTKVDKR VESKYGPPCP PCPAPEFLGG PSVFLFPPKP 250 KDTLMISRTP EVTCVVVDVS QEDPEVQFNW YVDGVEVHNA KTKPREEQYN 300 STYRVVSVLT VLHQDWLNGK EYKCKVSNKG LPSSIEKTIS KAKGQPREPQ 350 VYTLPPSQKE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV 400 LDSDGSFFLY SKLTVDKSRW QEGNVFSCSV MHEALHNRYT QKSLSLSP 448 Heavy chain anti-F10/ Chaîne lourde anti-F10/ Cadena pesada anti-F10 QVQLVQSGSE LKKPGASVKV SCKASGYTFT DNNMDWVRQA PGQGLEWMGD 50 INTRSGGSIY NEEFQDRVIM TVDKSTDTAY MELSSLRSED TATYHCARRK 100 SYGYYLDEWG EGTLVTVSSA STKGPSVFPL APCSRSTSES TAALGCLVKD 150 YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY 200 TCNVDHKPSN TKVDKRVESK YGPPCPPCPA PEFLGGPSVF LFPPKPKDTL 250 MISRTPEVTC VVVDVSQEDP EVQFNWYVDG VEVHNAKTKP REEQYNSTYR 300 VVSVLTVLHQ DWLNGKEYKC KVSNKGLPSS IEKTISKAKG QPREPQVYTL 350 PPSQEEMTKN QVSLTCLVKG FYPSDIAVEW ESNGQPENNY KTTPPVLDSD 400 GSFFLYSKLT VDKSRWQEGN VFSCSVMHEA LHNHYTQESL SLSP 444 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCKASRNIE RQLAWYQQKP GQAPELLIYQ 50 ASRKESGVPD RFSGSRYGTD FTLTISSLQP EDIATYYCQQ YSDPPLTFGG 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 150-206 264-324 370-428 22''-96'' 146''-202'' 260''-320'' 366''-424'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (CH1 10-CL 126) 137-214' 133''-214''' Inter-H-H (h 8, h 11) 229-225'' 232-228'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 300, 296'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenario complejos fucosilados enasidenibum enasidenib 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]- 6-{[2-(trifluoromethyl)pyridin-4-yl]amino}- 1,3,5-triazin-2-yl)amino]propan-2-ol énasidénib 2-méthyl-1-[(4-[6-(trifluorométhyl)pyridin-2-yl]- 6-{[2-(trifluorométhyl)pyridin-4-yl]amino}- 1,3,5-triazin-2-yl)amino]propan-2-ol enasidenib 2-metil-1-[(4-[6-(trifluorometil)piridin-2-il]- 6-{[2-(trifluorometil)piridin-4-il]amino}-1,3,5-triazin- 2-il)amino]propan-2-ol C19H17F6N7O N N N HN N H N CF3 N CF3 CH3 CH3 OH enerisantum enerisant [1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)- 1H-pyrazol-4-yl](morpholin-4-yl)methanone Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 114 énérisant [1-(4-{3-[(2R)-2-méthylpyrrolidin-1-yl]propoxy}phényl)- 1H-pyrazol-4-yl](morpholin-4-yl)méthanone enerisant 1-(4-{3-[(2R)-2-metilpirrolidin-1-il]propoxi}fenil)- 1H-pirazol-4-il](morfolin-4-il)metanona C22H30N4O3 N N ON H CH3 O N O entrectinibum entrectinib N-{5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl}- 4-(4-methylpiperazin-1-yl)-2-[(oxan-4-yl)amino]benzamide entrectinib N-{5-[(3,5-difluorophényl)méthyl]-1H-indazol-3-yl}- 4-(4-méthylpipérazin-1-yl)-2-[(oxan-4-yl)amino]benzamide entrectinib N-{5-[(3,5-difluorofenil)metil]-1H-indazol-3-il}- 4-(4-metilpiperazin-1-il)-2-[(oxan-4-il)amino]benzamida C31H34F2N6O2 1108743-60-7 H N ONH N N NH N O H3C F F erdafitinibum erdafitinib N1-(3,5-dimethoxyphenyl)-N1-[3-(1-methyl-1H-pyrazol- 4-yl)quinoxalin-6-yl]-N2-(propan-2-yl)ethane-1,2-diamine erdafitinib N1-(3,5-diméthoxyphényl)-N1-[3-(1-méthyl-1H-pyrazol- 4-yl)quinoxalin-6-yl]-N2-(propan-2-yl)éthane-1,2-diamine erdafitinib N1-(3,5-dimetoxifenil)-N1-[3-(1-metil-1H-pirazol- 4-il)quinoxalin-6-il]-N2-(propan-2-il)etano-1,2-diamina WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 115 C25H30N6O2 N N N N N N H H3CO OCH3 CH3 CH3 H3C etripamilum etripamil methyl 3-(2-{[(4S)-4-cyano-4-(3,4-dimethoxyphenyl)- 5-methylhexyl](methyl)amino}ethyl)benzoate étripamil 3-(2-{[(4S)-4-cyano-4-(3,4-diméthoxyphényl)- 5-méthylhexyl](méthyl)amino}éthyl)benzoate de méthyle etripamilo 3-(2-{[(4S)-4-ciano-4-(3,4-dimetoxifenil)- 5-metilhexil](metil)amino}etil)benzoato de metilo C27H36N2O4 N CH3 CN OCH3 CH3 H3CO CH3 O O CH3 evenamidum evenamide 2-{[2-(3-butoxyphenyl)ethyl]amino}- N,N-dimethylacetamide événamide 2-{[2-(3-butoxyphényl)éthyl]amino}- N,N-diméthylacétamide evenamida 2-{[2-(3-butoxifenil)etil]amino}-N,N-dimetilacetamida C16H26N2O2 N H N O CH3 CH3 OH3C evocalcetum evocalcet {4-[(3S)-3-{[(1R)-1-(naphthalen-1-yl)ethyl]amino}pyrrolidin- 1-yl]phenyl}acetic acid évocalcet acide {4-[(3S)-3-{[(1R)-1-(naphtalén- 1-yl)éthyl]amino}pyrrolidin-1-yl]phényl}acétique Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 116 evocalcet ácido {4-[(3S)-3-{[(1R)-1-(naftalen-1-il)etil]amino}pirrolidin- 1-il]fenil}acético C24H26N2O2 H N CO2H N H CH3 H ezutromidum ezutromid 5-(ethanesulfonyl)-2-(naphthalen-2-yl)-1,3-benzoxazole ézutromid 5-(éthanesulfonyl)-2-(naphtalén-2-yl)-1,3-benzoxazole ezutromid 5-(etanosulfonil)-2-(naftalen-2-il)-1,3-benzoxazol C19H15NO3S SH3C O O N O fitusiranum fitusiran small interfering RNA (siRNA) inhibiting antithrombin liver production: duplex of [(2S,4R)-1-{30-(2-acetamido-2-deoxy-β-D- galactopyranosyl)-14,14-bis[16-(2-acetamido-2-deoxy-β-D- galactopyranosyl)-5,11-dioxo-2,16-dioxa-6,10- diazahexadecyl]-12,19,25-trioxo-16,30-dioxa-13,20,24- triazatriacontanoyl}-4-hydroxypyrrolidin-2-yl]methyl hydrogen (P-RS)-2'-deoxy-2'-fluoro-P-thioguanylyl-(3'→5')- (P-RS)-2'-O-methyl-P-thioguanylyl-(3'→5')-2'-deoxy-2'- fluorouridylyl-(3'→5')-2'-O-methyluridylyl-(3'→5')-2'-deoxy- 2'-fluoroadenylyl-(3'→5')-2'-O-methyladenylyl-(3'→5')-2'- deoxy-2'-fluorocytidylyl-(3'→5')-2'-O-methyladenylyl- (3'→5')-2'-deoxy-2'-fluorocytidylyl-(3'→5')-2'-deoxy-2'- fluorocytidylyl-(3'→5')-2'-deoxy-2'-fluoroadenylyl-(3'→5')-2'- O-methyluridylyl-(3'→5')-2'-deoxy-2'-fluorouridylyl-(3'→5')- 2'-O-methyluridylyl-(3'→5')-2'-deoxy-2'-fluoroadenylyl- (3'→5')-2'-O-methylcytidylyl-(3'→5')-2'-deoxy-2'- fluorouridylyl-(3'→5')-2'-O-methyluridylyl-(3'→5')-2'-deoxy- 2'-fluorocytidylyl-(3'→5')-2'-O-methyladenylyl-(3'→5')-2'- deoxy-2'-fluoroadenylate and WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 117 and (P-RS)-2'-O-methyl-P-thiouridylyl-(3'→5')-(P-RS)-2'- deoxy-2'-fluoro-P-thiouridylyl-(3'→5')-2'-O-methylguanylyl- (3'→5')-2'-deoxy-2'-fluoroadenylyl-(3'→5')-2'-O- methyladenylyl-(3'→5')-2'-deoxy-2'-fluoroguanylyl-(3'→5')- 2'-O-methyluridylyl-(3'→5')-2'-deoxy-2'-fluoroadenylyl- (3'→5')-2'-O-methyladenylyl-(3'→5')-2'-deoxy-2'- fluoroadenylyl-(3'→5')-2'-O-methyluridylyl-(3'→5')-2'-O- methylguanylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')-2'- deoxy-2'-fluorouridylyl-(3'→5')-2'-O-methylguanylyl-(3'→5')- 2'-deoxy-2'-fluorouridylyl-(3'→5')-2'-O-methyluridylyl- (3'→5')-2'-deoxy-2'-fluoroadenylyl-(3'→5')-2'-O- methyladenylyl-(3'→5')-2'-deoxy-2'-fluorocytidylyl-(3'→5')- (P-RS)-2'-O-methyl-P-thiocytidylyl-(3'→5')-(P-RS)-2'-O- methyl-P-thioadenylyl-(3'→5')-2'-O-methylguanosine fitusiran petit ARN interférant inhibant la production hépatique d'antithrombine: duplex de l’hydrogéno-(P-RS)-2'-deoxy-2'-fluoro-P- thioguanylyl-(3'→5')-(P-RS)-2'-O-méthyl-P-thioguanylyl- (3'→5')-2'-désoxy-2'-fluorouridylyl-(3'→5')-2'-O- méthyluridylyl-(3'→5')-2'-désoxy-2'-fluoroadénylyl-(3'→5')- 2'-O-méthyladénylyl-(3'→5')-2'-désoxy-2'-fluorocytidylyl- (3'→5')-2'-O-méthyladénylyl-(3'→5')-2'-désoxy-2'- fluorocytidylyl-(3'→5')-2'-désoxy-2'-fluorocytidylyl-(3'→5')- 2'-désoxy-2'-fluoroadénylyl-(3'→5')-2'-O-méthyluridylyl- (3'→5')-2'-désoxy-2'-fluorouridylyl-(3'→5')-2'-O- méthyluridylyl-(3'→5')-2'-désoxy-2'-fluoroadénylyl-(3'→5')- 2'-O-méthylcytidylyl-(3'→5')-2'-désoxy-2'-fluorouridylyl- (3'→5')-2'-O-méthyluridylyl-(3'→5')-2'-désoxy-2'- fluorocytidylyl-(3'→5')-2'-O-méthyladénylyl-(3'→5')-2'- désoxy-2'-fluoroadénylate de [(2S,4R)-1-{30-(2-acétamido- 2-désoxy-β-D-galactopyranosyl)-14,14-bis[16-(2- acétamido-2-désoxy-β-D-galactopyranosyl)-5,11-dioxo- 2,16-dioxa-6,10-diazahexadécyl]-12,19,25-trioxo-16,30- dioxa-13,20,24-triazatriacontanoyl}-4-hydroxypyrrolidin-2- yl]méthyle et du(P-RS)-2'-O-méthyl-P-thiouridylyl-(3'→5') (P-RS)-2'-désoxy-2'-fluoro-P-thiouridylyl-(3'→5')-2'-O- méthylguanylyl-(3'→5')-2'-désoxy-2'-fluoroadénylyl-(3'→5')- 2'-O-méthyladénylyl-(3'→5')-2'-désoxy-2'-fluoroguanylyl- (3'→5')-2'-O-méthyluridylyl-(3'→5')-2'-désoxy-2'- fluoroadénylyl-(3'→5')-2'-O-méthyladénylyl-(3'→5')-2'- désoxy-2'-fluoroadénylyl-(3'→5')-2'-O-méthyluridylyl- (3'→5')-2'-O-méthylguanylyl-(3'→5')-2'-O-méthylguanylyl- (3'→5')-2'-désoxy-2'-fluorouridylyl-(3'→5')-2'-O- méthylguanylyl-(3'→5')-2'-désoxy-2'-fluorouridylyl-(3'→5')- 2'-O-méthyluridylyl-(3'→5')-2'-désoxy-2'-fluoroadénylyl- (3'→5')-2'-O-méthyladénylyl-(3'→5')-2'-désoxy-2'- fluorocytidylyl-(3'→5')-(P-RS)-2'-O-méthyl-P-thiocytidylyl- (3'→5')-(P-RS)-2'-O-méthyl-P-thioadénylyl-(3'→5')-2'-O- méthylguanosine Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 118 fitusirán ARN pequeño de interferencia que inhibe la producción hepática de antitrombina: dúplex de hidrógeno-(P-RS)-2'-desoxi-2'-fluoro-P-tioguanilil- (3'→5')-(P-RS)-2'-O-metil-P-tioguanilil-(3'→5')-2'-desoxi-2'- fluorouridilil-(3'→5')-2'-O-metiluridilil-(3'→5')-2'-desoxi-2'- fluoroadenilil-(3'→5')-2'-O-metiladenilil-(3'→5')-2'-desoxi-2'- fluorocitidilil-(3'→5')-2'-O-metiladenilil-(3'→5')-2'-desoxi-2'- fluorocitidilil-(3'→5')-2'-desoxi-2'-fluorocitidilil-(3'→5')-2'- desoxi-2'-fluoroadenilil-(3'→5')-2'-O-metiluridilil-(3'→5')-2'- desoxi-2'-fluorouridilil-(3'→5')-2'-O-metiluridilil-(3'→5')-2'- desoxi-2'-fluoroadenilil-(3'→5')-2'-O-metilcitidill-(3'→5')-2'- desoxi-2'-fluorouridill-(3'→5')-2'-O-metiluridilil-(3'→5')-2'- desoxi-2'-fluorocitidilil-(3'→5')-2'-O-metiladenilil-(3'→5')-2'- desoxi-2'-fluoroadenilato de [(2S,4R)-1-{30-(2-acetamido-2- desoxi-β-D-galactopiranosil)-14,14-bis[16-(2-acetamido-2- desoxi-β-D-galactopiranosil)-5,11-dioxo-2,16-dioxa-6,10- diazahexadecil]-12,19,25-trioxo-16,30-dioxa-13,20,24- triazatriacontanoil}-4-hidroxipirrolidin-2-il]metil y de (P-RS)- 2'-O-metil-P-tiouridilil-(3'→5') (P-RS)-2'-desoxi-2'-fluoro-P- tiouridilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'-desoxi-2'- fluoroadenilil-(3'→5')-2'-O-metiladenilil-(3'→5')-2'-desoxi-2'- fluoroguanilil-(3'→5')-2'-O-metiluridilil-(3'→5')-2'-desoxi-2'- fluoroadenilil-(3'→5')-2'-O-metiladenilil-(3'→5')-2'-desoxi-2'- fluoroadenilil-(3'→5')-2'-O-metiluridilil-(3'→5')-2'-O- metilguanilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'-desoxi-2'- fluorouridilil-(3'→5')-2'-O-metilguanilil-(3'→5')-2'-desoxi-2'- fluorouridilil-(3'→5')-2'-O-metiluridilil-(3'→5')-2'-desoxi-2'- fluoroadenilil-(3'→5')-2'-O-metiladenilil-(3'→5')-2'-desoxi-2'- fluorocitidilil-(3'→5')-(P-RS)-2'-O-metil-P-tiocitidilil-(3'→5')- (P-RS)-2'-O-metil-P-tioadenilil-(3'→5')-2'-O-metilguanosina C520H679F21N175O309P43S6 (5'-3') G=A=C-C-A-A-U-U-G-U-G-G-U-A-A-A-U-G-A-A-G=U=U (3'-5') G=G=U-U-A-A-C-A-C-C-A-U-U-U-A-C-U-U-C-A-A-R1 . . . . . . . . . . . . . . . . . . . . . O O OH HO N H HO CH3 O = R NH HN OO O CH2 N O H NR R R H OH CH2 H=R1 OLegend X : 2'-deoyx-2'-fluoro X : 2'-O-methyl P OHO P SHO fosnetupitantum fosnetupitant {4-[5-{2-[3,5-bis(trifluoromethyl)phenyl]- N,2-dimethylpropanamido}-4-(2-methylphenyl)pyridin- 2-yl]-1-methylpiperazin-1-ium-1-yl}methyl hydrogen phosphate fosnétupitant hydrogénophosphate de {4-[5-{2-[3,5- bis(trifluorométhyl)phényl]-N,2-diméthylpropanamido}- 4-(2-méthylphényl)pyridin-2-yl]-1-méthylpipérazin-1-ium- 1-yl}méthyle WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 119 fosnetupitant hidrógenofosfato de {4-[5-{2-[3,5-bis(trifluorometil)fenil]- N,2-dimetilpropanamido}-4-(2-metilfenil)piridin-2-il]- 1-metilpiperazin-1-io-1-il}metilo C31H35F6N4O5P N CH3 CF3 CF3 N N N H3C OP O O OH O H3C CH3 H3C glembatumumabum vedotinum # glembatumumab vedotin immunoglobulin G2-kappa, anti-[Homo sapiens GPNMB (glycoprotein (transmembrane) nmb, glycoprotein transmembrane NMB, glycoprotein nonmetastatic melanoma protein B, CG56972, osteoactivin, hematopoietic growth factor inducible neurokinin-1 type, HGFIN) extracellular domain], Homo sapiens monoclonal antibody conjugated to auristatin E; gamma2 heavy chain (1-445) [Homo sapiens VH (IGHV4- 31*02 (94.90%) -(IGHD)-IGHJ4*01) [10.7.11] (1-119) - IGHG2*01, G2m.. (CH1 (120-217), hinge (218-229), CH2 (230-338), CH3 (339-443), CHS (444-445)) (120-445)], (133-215')-disulfide with kappa light chain (1'-215') [Homo sapiens V-KAPPA (IGKV3-15*01 (96.80%) -IGKJ1*01) [6.3.10] (1'-108') -IGKC*01, Km3 (109'-215')]; dimer (221- 221'':222-222'':225-225'':228-228'')-tetrakisdisulfide; conjugated, on an average of 5 cysteinyl, to monomethylauristatin E (MMAE), via a cleavable maleimidocaproyl-valyl-citrullinyl- p-aminobenzyloxycarbonyl (mc-val-cit-PABC) type linker For the vedotin part, please refer to the document “INN for pharmaceutical substances: Names for radicals, groups and others”*. glembatumumab védotine immunoglobuline G2-kappa, anti-[Homo sapiens GPNMB (glycoprotéine (transmembranaire) nmb, glycoprotéine transmembranaire NMB, protéine B glycoprotéine de mélanome non métastatique, CG56972, ostéoactivine, facteur de croissance hématopoïétique inductible type neurokinine-1, HGFIN) domaine extracellulaire], Homo sapiens anticorps monoclonal conjugué à l’auristatine E; chaîne lourde gamma2 (1-445) [Homo sapiens VH (IGHV4-31*02 (94.90%) -(IGHD)-IGHJ4*01) [10.7.11] (1- 119) -IGHG2*01, G2m.. (CH1 (120-217), charnière (218- 229), CH2 (230-338), CH3 (339-443), CHS (444-445)) (120-445)], (133-215')-disulfure avec la chaîne légère kappa (1'-215') [Homo sapiens V-KAPPA (IGKV3-15*01 (96.80%) -IGKJ1*01) [6.3.10] (1'-108') -IGKC*01, Km3 (109'-215')]; dimère (221-221'':222-222'':225-225'':228- 228'')-tétrakisdisulfure; conjugué, sur 5 cystéinyl en moyenne, au monométhylauristatine E (MMAE), via un linker clivable de type maléimidocaproyl-valyl-citrullinyl-p- aminobenzyloxycarbonyl (mc-val-cit-PABC) Pour la partie védotine, veuillez-vous référer au document “INN for pharmaceutical substances: Names for radicals, groups and others”*. Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 120 glembatumumab vedotina inmunoglobulina G2-kappa, anti-[Homo sapiens GPNMB (glicoproteína (transmembrana) nmb, glicoproteina transmembrana NMB, proteína B glicoproteína de melanoma no metastásico, CG56972, osteoactivina, factor de crecimiento hematopoyético inducible tipo neurokinina- 1, HGFIN) dominio extracelular], Homo sapiens anticuerpo monoclonal conjugado con auristatina E; cadena pesada gamma2 (1-445) [Homo sapiens VH (IGHV4-31*02 (94.90%) -(IGHD)-IGHJ4*01) [10.7.11] (1- 119) -IGHG2*01, G2m.. (CH1 (120-217), bisagra (218- 229), CH2 (230-338), CH3 (339-443), CHS (444-445)) (120-445)], (133-215')-disulfuro con la cadena ligera kappa (1'-215') [Homo sapiens V-KAPPA (IGKV3-15*01 (96.80%) -IGKJ1*01) [6.3.10] (1'-108') -IGKC*01, Km3 (109'-215')]; dímero (221-221'':222-222'':225-225'':228-228'')- tetrakisdisulfuro; conjugado, en una media de 5 restos cisteinil, con monometilauristatina E (MMAE), mediante un espaciadorescindible de tipo maleimidocaproil-valil- citrulinil-p-aminobenciloxicarbonil (mc-val-cit-PABC) La fracción vedotina, la pueden encontrar en el documento “INN for pharmaceutical substances: Names for radicals, groups and others”*. Heavy chain / Chaîne lourde / Cadena pesadaQVQLQESGPG LVKPSQTLSL TCTVSGGSIS SFNYYWSWIR HHPGKGLEWI 50 GYIYYSGSTY SNPSLKSRVT ISVDTSKNQF SLTLSSVTAA DTAVYYCARG 100 YNWNYFDYWG QGTLVTVSSA STKGPSVFPL APCSRSTSES TAALGCLVKD 150 YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSNFGTQTY 200 TCNVDHKPSN TKVDKTVERK CCVECPPCPA PPVAGPSVFL FPPKPKDTLM 250 ISRTPEVTCV VVDVSHEDPE VQFNWYVDGV EVHNAKTKPR EEQFNSTFRV 300 VSVLTVVHQD WLNGKEYKCK VSNKGLPAPI EKTISKTKGQ PREPQVYTLP 350 PSREEMTKNQ VSLTCLVKGF YPSDIAVEWE SNGQPENNYK TTPPMLDSDG 400 SFFLYSKLTV DKSRWQQGNV FSCSVMHEAL HNHYTQKSLS LSPGK 445 Light chain / Chaîne légère / Cadena ligera EIVMTQSPAT LSVSPGERAT LSCRASQSVD NNLVWYQQKP GQAPRLLIYG 50 ASTRATGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQQ YNNWPPWTFG 100 QGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150 VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200 GLSSPVTKSF NRGEC 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-97 146-202 259-319 365-423 22''-97'' 146''-202'' 259''-319'' 365''-423'' Intra-L (C23-C104) 23'-88' 135'-195' 23'''-88''' 135'''-195''' Inter-H-L (CH1 10-CL 126) 133-215' 133''-215''' Inter-H-H (h 4, h 5, h 8, h 11) 221-221'' 222-222'' 225-225'' 228-228'' *Two or three of the inter-chain disulfide bridges are not present, an average of 5 cysteinyl being conjugated each via a thioether bond to a drug linker. *Deux ou trois des ponts disulfures inter-chaînes ne sont pas présents, 5 cystéinyl en moyenne étant chacun conjugué via une liaison thioéther à un linker-principe actif. *Faltan dos o tres puentes disulfuro inter-catenarios, una media de 5 cisteinil está conjugada a conectores de principio activo. N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 295, 295'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados graunimotidum graunimotide L-lysyl-L-arginyl-L-tyrosyl-L-phenylalanyl-L-lysyl-L-leucyl- L-seryl-L-histidyl-L-leucyl-L-glutaminyl-L-methionyl- L-histidyl-L-seryl-L-arginyl-L-lysyl-L-histidine; human Wilms tumor protein (WT33) (332-347)-peptide WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 121 graunimotide L-lysyl-L-arginyl-L-tyrosyl-L-phénylalanyl-L-lysyl-L-leucyl- L-séryl-L-histidyl-L-leucyl-L-glutaminyl-L-méthionyl- L-histidyl-L-séryl-L-arginyl-L-lysyl-L-histidine; protéine tumorale Wilms humaine (WT33) (332-347)- peptide graunimotida L-lisil-L-arginil-L-tiyrosil-L-fenilalanil-L-lisil-L-leucil-L-seril- L-histidil-L-leucil-L-glutaminil-L-metionyl-L-histidil-L-seril- L-arginil-L-lisil-L-histidina; proteína de tumor de Wilms humano (WT33) (332-347)- péptido C94H150N32O21S H Lys Arg Tyr Phe Lys Leu Ser His Leu Gln Met His Ser Arg Lys His OH 10 16 guadecitabinum guadecitabine 2'-deoxy-5-azacytidylyl-(3'→5')-2'-deoxyguanosine guadécitabine 2'-déoxy-5-azacytidylyl-(3'→5')-2'-déoxyguanosine guadecitabina 2'-desoxi-5-azacitidilil-(3'→5')-2'-desoxiguanosina C18H24N9O10P O P O O OH O HO N N N O NH2 O OH N N H N N H2N O inebilizumabum inebilizumab immunoglobulin G1-kappa, anti-[Homo sapiens CD19 (B lymphocyte surface antigen B4, Leu-12)], humanized monoclonal antibody; gamma1 heavy chain (1-451) [humanized VH (Homo sapiens IGHV3-15*06 (83.70%) -(IGHD)-IGHJ4*01) [8.8.14] (1-121) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (122-219), hinge (220-234), CH2 (235-344), CH3 (345- 449), CHS (450-451)) (122-451)], (224-218')-disulfide with kappa light chain (1’-218’) [humanized V-KAPPA (Homo sapiens IGKV6-21*01 (79.80%) -IGKJ4*01) [10.3.9] (1'- 111') -Homo sapiens IGKC*01, Km3 (112'-218')]; dimer (230-230":233-233")-bisdisulfide Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 122 inébilizumab immunoglobuline G1-kappa, anti-[Homo sapiens CD19 (antigène de surface B4 des lymphocytes B, Leu-12)], anticorps monoclonal humanisé; chaîne lourde gamma1 (1-451) [VH humanisé (Homo sapiens IGHV3-15*06 (83.70%) -(IGHD)-IGHJ4*01) [8.8.14] (1-121) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (122-219), charnière (220-234), CH2 (235-344), CH3 (345- 449), CHS (450-451)) (122-451)], (224-218')-disulfure avec la chaîne légère kappa (1’-218’) [V-KAPPA humanisé (Homo sapiens IGKV6-21*01 (79.80%) -IGKJ4*01) [10.3.9] (1'-111') -Homo sapiens IGKC*01, Km3 (112'-218')]; dimère (230-230":233-233")-bisdisulfure inebilizumab inmunoglobulina G1-kappa, anti-[Homo sapiens CD19 (antígeno de superficie B4 de los linfocitos B, Leu-12)], anticuerpo monoclonal humanizado; cadena pesada gamma1 (1-451) [VH humanizada (Homo sapiens IGHV3-15*06 (83.70%) -(IGHD)-IGHJ4*01) [8.8.14] (1-121) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (122-219), bisagra (220-234), CH2 (235-344), CH3 (345- 449), CHS (450-451)) (122-451)], (224-218')-disulfuro con la cadena ligera kappa (1’-218’) [V-KAPPA humanizada (Homo sapiens IGKV6-21*01 (79.80%) -IGKJ4*01) [10.3.9] (1'-111') -Homo sapiens IGKC*01, Km3 (112'-218')]; dímero (230-230":233-233")-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaEVQLVESGGG LVQPGGSLRL SCAASGFTFS SSWMNWVRQA PGKGLEWVGR 50 IYPGDGDTNY NVKFKGRFTI SRDDSKNSLY LQMNSLKTED TAVYYCARSG 100 FITTVRDFDY WGQGTLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV 150 KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ 200 TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG GPSVFLFPPK 250 PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP 350 QVYTLPPSRE EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 400 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG 450 K 451 Light chain / Chaîne légère / Cadena ligera EIVLTQSPDF QSVTPKEKVT ITCRASESVD TFGISFMNWF QQKPDQSPKL 50 LIHEASNQGS GVPSRFSGSG SGTDFTLTIN SLEAEDAATY YCQQSKEVPF 100 TFGGGTKVEI KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV 150 QWKVDNALQS GNSQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV 200 THQGLSSPVT KSFNRGEC 218 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 148-204 265-325 371-429 22''-96'' 148''-204'' 265''-325'' 371''-429'' Intra-L (C23-C104) 23'-92' 138'-198' 23'''-92''' 138'''-198''' Inter-H-L (h 5-CL 126) 224-218' 224''-218''' Inter-H-H (h 11, h 14) 230-230'' 233-233'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 301, 301'' Afucosylated complex bi-antennary CHO-type glycans / Glycanes de type CHO bi-antennaires complexes afucosylés / Glicanos de tipo CHO biantenarios complejos no fucosilados ingenoli disoxas ingenol disoxate (1aR,2S,3Z,5R,5aS,6S,8aS,9R,10aR)-5,5a-dihydroxy- 4-(hydroxymethyl)-1,1,7,9-tetramethyl-11-oxo- 1a,2,5,5a,6,9,10,10a-octahydro-1H-2,8a- methanocyclopenta[a]cyclpropa[e][10]annulen-6-yl 3,5-diethylisoxazole-4-carboxylate WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 123 disoxate d’ingénol 3,5-diéthylisoxazole-4-carboxylate de (1aR,2S,3Z,5R,5aS,6S,8aS,9R,10aR)-5,5a-dihydroxy- 4-(hydroxyméthyl)-1,1,7,9-tétraméthyl-11-oxo- 1a,2,5,5a,6,9,10,10a-octahydro-1H-2,8a- méthanocyclopenta[a]cyclpropa[e][10]annulén-6-yle disoxato de ingenol 3,5-dietillisoxazol-4-carboxilato de (1aR,2S,3Z,5R,5aS,6S,8aS,9R,10aR)-5,5a-dihidroxi- 4-(hidroximetil)-1,1,7,9-tetrametil-11-oxo- 1a,2,5,5a,6,9,10,10a-octahidro-1H-2,8a- metanociclopenta[a]ciclpropa[e][10]anulen-6-ilo C28H37NO7 H O H3C HO HO H HO H CH3 CH3 CH3H H H O O N O H3C H3C iodinum (131I) derlotuximabum biotinum # iodine (131I) derlotuximab biotin immunoglobulin G1-kappa, anti-[Homo sapiens DNA/histone 1 (H1) complex], chimeric monoclonal antibody radiolabeled with iodine-131 and biotinylated; gamma1 heavy chain (1-450) [Mus musculus VH (IGHV2- 6-5*01 -(IGHD)-IGHJ4*01) [8.7.14] (1-120) - Homo sapiens IGHG1*01, G1m17,1 (CH1 V121>A (218) (121-218), hinge (219-233), CH2 (234-343), CH3 (344-448), CHS (449- 450)) (121-450)], (223-215')-disulfide with kappa light chain (1'-215') [Mus musculus V-KAPPA (IGKV4-57-1*01 - IGKJ1*01) [7.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (109'-215')]; dimer (229-229'':232-232'')-bisdisulfide; (131I) iodinatedwith iodine-131 covalently linked to tyrosines, and biotinylated iodine (131I) derlotuximab biotine immunoglobuline G1-kappa, anti-[Homo sapiens complexe ADN/histone 1 (H1)], anticorps monoclonal chimérique biotinylé et marqué à l’iode 131; chaîne lourde gamma1 (1-450) [Mus musculus VH (IGHV2-6-5*01 -(IGHD)-IGHJ4*01) [8.7.14] (1-120) - Homo sapiens IGHG1*01, G1m17,1 (CH1 V121>A (218) (121- 218), charnière (219-233), CH2 (234-343), CH3 (344-448), CHS (449-450)) (121-450)], (223-215')-disulfure avec la chaîne légère kappa (1'-215') [Mus musculus V-KAPPA (IGKV4-57-1*01 -IGKJ1*01) [7.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (109'-215')]; dimère (229-229'':232- 232'')-bisdisulfure; marqué à l’iode 131 (131I) lié de manière covalente à des tyrosines, et biotinylé Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 124 iodo (131I) derlotuximab biotina inmunoglobulina G1-kappa, anti-[Homo sapiens complejo ADN/histona 1 (H1)], anticuerpo monoclonal quimérico biotinilado y marcado con iodo 131; cadena pesada gamma1 (1-450) [Mus musculus VH (IGHV2-6-5*01 -(IGHD)-IGHJ4*01) [8.7.14] (1-120) - Homo sapiens IGHG1*01, G1m17,1 (CH1 V121>A (218) (121- 218), bisagra(219-233), CH2 (234-343), CH3 (344-448), CHS (449-450)) (121-450)], (223-215')-disulfuro con la cadena ligera kappa (1'-215') [Mus musculus V-KAPPA (IGKV4-57-1*01 -IGKJ1*01) [7.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (109'-215')]; dímero (229-229'':232- 232'')-bisdisulfuro; marcado con iodo 131 (131I) unido covalentemente a tirosinas, y biotinilado S H N N H O CO2HH H H biotin CO2H NH2H HO [131I] Y are partly radiolabeled 3-[131I]iodotyrosine Heavy chain / Chaîne lourde / Cadena pesada QVQLKESGPG LVAPSQSLSI TCTVSGFSLT DYGVRWIRQP PGKGLEWLGV 50 IWGGGSTYYN SALKSRLSIS KDNSKSQVFL KMNSLQTDDT AMYYCAKEKR 100 RGYYYAMDYW GQGTSVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK 150 DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT 200 YICNVNHKPS NTKVDKKAEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP 250 KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 300 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ 350 VYTLPPSRDE LTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV 400 LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPGK 450 Light chain / Chaîne légère / Cadena ligera ENVLTQSPAI MSASPGEKVT MTCRASSSVS SSYLHWYQQK SGASPKLWIY 50 STSNLASGVP ARFSGSGSGT SYSLTISSVE AEDAATYYCQ QYSGYPLTFG 100 GGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150 VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200 GLSSPVTKSF NRGEC 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-95 147-203 264-324 370-428 22''-95'' 147''-203'' 264''-324'' 370''-428'' Intra-L (C23-C104) 23'-89' 135'-195' 23'''-89''' 135'''-195''' Inter-H-L (h 5-CL 126) 223-215' 223''-215''' Inter-H-H (h 11, h 14) 229-229'' 232-232'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 300, 300'' Fucosylated complex bi-antennary NS0-type glycans / glycanes de type NS0 bi-antennaires complexes fucosylés / glicanos de tipo NS0 biantenario complejos fucosilados Modified residues / Résidus modifiés / Restos modificados isunakinrum # isunakinra human interleukin-1 beta-(1-8)-peptide fusion protein with human interleukin-1 receptor antagonist protein-(14-45)- peptide fusion protein with human interleukin-1 beta-(42- 120)-peptide fusion protein with human interleukin-1 receptor antagonist protein-(120-147)-peptide fusion protein with human interleukin-1 beta-(148-153)-peptide non-glycosylated isunakinra interleukine-1 bêta humaine-(1-8)-peptide protéine de fusion avec l’antagoniste protéique du récepteur de l’interleukine-1 humain-(14-45)-peptide protéine de fusion avec l’interleukine-1 bêta humaine-(42-120)-peptide protéine de fusion avec l’antagoniste protéique du récepteur de l’interleukine-1 humain-(120-147)-peptide protéine de fusion avec l’interleukine-1 bêta humaine-(148- 153)-peptide non-glycosylé WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 125 isunakinra interleukina-1 beta humana-(1-8)-péptido proteína de fusión con el antagonista proteíco del receptor de la interleukina-1 humana-(14-45)-péptido proteína de fusión con la interleukina-1 beta humana-(42-120)-péptido proteína de fusión con el antagonista proteíco del receptor de la interleukina-1 humana-(120-147)-péptido proteína de fusión con la interleukina-1 beta humana-(148-153)- péptido no-glicosilado APVRSLNCRI WDVNQKTFYL RNNQLVAGYL QGPNVNLEEK FSMSFVQGEE 50SNDKIPVALG LKEKNLYLSC VLKDDKPTLQ LESVDPKNYP KKKMEKRFVF 100 NKIEINNKLE FESAQFPNWF LCTAMEADQP VSLTNMPDEG VMVTKFYMQF 150 VSS 153 labetuzumabum govitecanum # labetuzumab govitecan immunoglobulin G1-kappa, anti-[Homo sapiens CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5, CEA, CD66e)], monoclonal antibody conjugated to 7-ethyl-10-hydroxycamptothecin (SN-38), active metabolite of irinotecan; gamma1 heavy chain (1-449) [humanized VH (Homo sapiens IGHV3-48*01 (75.30%) -(IGHD)-IGHJ5*01) [8.8.12] (1-119) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (120-217), hinge (218-232), CH2 (233-342), CH3 (343- 447), CHS (448-449)) (120-449)], (222-213')-disulfide with kappa light chain (1’-213’) [humanized V-KAPPA (Homo sapiens IGKV1-39*01 (85.70%) -IGKJ1*01) [6.3.8] (1'-106') -Homo sapiens IGKC*01, Km3 (107'-213')]; dimer (228- 228":231-231")-bisdisulfide; conjugated, on an average of 6 cysteinyl, to 7-ethyl-10-hydroxycamptothecin (SN-38), active metabolite of irinotecan (CPT-11, camptothecin-11), via a maleimide-type cleavable linker (carbonate group, 4-aminobenzyl alcohol and cathepsine-B-cleavable dipeptide Phe-Lys) and containing a triazoline group and a spacer PEG (n=8) labétuzumab govitécan immunoglobuline G1-kappa, anti-[Homo sapiens CEACAM5 (molécule d’adhésion cellulaire 5 apparentée à l’antigène carcinoembryonaire, CEA, CD66e)], anticorps monoclonal conjugué à la 7-éthyl- 10-hydroxycamptothécine (SN-38), métabolite actif de l’irinotécan; chaîne lourde gamma1 (1-449) [humanized VH (Homo sapiens IGHV3-48*01 (75.30%) -(IGHD)-IGHJ5*01) [8.8.12] (1-119) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (120-217), charnière (218-232), CH2 (233-342), CH3 (343- 447), CHS (448-449)) (120-449)], (222-213')-disulfure avec la chaîne légère kappa (1’-213’) [V-KAPPA humanisé (Homo sapiens IGKV1-39*01 (85.70%) -IGKJ1*01) [6.3.8] (1'-106') -Homo sapiens IGKC*01, Km3 (107'-213')]; dimère (228-228":231-231")-bisdisulfure; conjugué, sur 6 cystéinyl en moyenne, à la 7-éthyl- 10-hydroxycamptothécine (SN-38), métabolite actif de l’irinotécan (CPT-11, camptothécine-11), via un linker de type maléimide, clivable (liaison carbonate, 4-aminobenzyl alcool et dipeptide Phe-Lys clivable par la cathepsine B) et comprenant un groupe triazoline et un espaceur PEG (n=8) Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 126 labetuzumab govitecán inmunoglobulina G1-kappa, anti-[Homo sapiens CEACAM5 (molècula de adhesión celular 5 relacionada con el antígeno carcinoembrionario, CEA, CD66e)], anticuerpo monoclonal conjugado con la 7-etil- 10-hidroxicamptotecina (SN-38), metabolito activo del irinotecán; cadena pesada gamma1 (1-449) [humanizado VH (Homo sapiens IGHV3-48*01 (75.30%) -(IGHD)-IGHJ5*01) [8.8.12] (1-119) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (120-217), bisagra (218-232), CH2 (233-342), CH3 (343- 447), CHS (448-449)) (120-449)], (222-213')-disulfuro con la cadena ligera kappa (1’-213’) [V-KAPPA humanizado (Homo sapiens IGKV1-39*01 (85.70%) -IGKJ1*01) [6.3.8] (1'-106') -Homo sapiens IGKC*01, Km3 (107'-213')]; dímero (228-228":231-231")-bisdisulfuro; conjugado, en una media de 6 restos cisteinil, con la 7-etil- 10-hidroxicamptotecina (SN-38), metabolito activo del irinotecán (CPT-11, camptotecina-11), mediante un espaciador de tipo maleimida, escindible (enlace carbonato, 4-aminobencil alcohol y dipéptido Phe-Lys escindible por catepsina B) y que comprende un grupo triazolina y un espaciador PEG (n=8) ON N O O HO CH3 O CH3 OO N H Lys O O H N O O NO O H2N CO2H H NN N NH S 8 O C* 213'-213'''-222-222''- 228-228''-231-231'' * an average of 6 are substituted * en moyenne, 6 sont substitués * una media de 6 está sustituída Heavy chain / Chaîne lourde / Cadena pesada EVQLVESGGG VVQPGRSLRL SCSASGFDFT TYWMSWVRQA PGKGLEWIGE 50 IHPDSSTINY APSLKDRFTI SRDNAKNTLF LQMDSLRPED TGVYFCASLY 100 FGFPWFAYWG QGTPVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD 150 YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY 200 ICNVNHKPSN TKVDKRVEPK SCDKTHTCPP CPAPELLGGP SVFLFPPKPK 250 DTLMISRTPE VTCVVVDVSH EDPEVKFNWY VDGVEVHNAK TKPREEQYNS 300 TYRVVSVLTV LHQDWLNGKE YKCKVSNKAL PAPIEKTISK AKGQPREPQV 350 YTLPPSREEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 400 DSDGSFFLYS KLTVDKSRWQ QGNVFSCSVM HEALHNHYTQ KSLSLSPGK 449 Light chain / Chaîne légère / Cadena ligera DIQLTQSPSS LSASVGDRVT ITCKASQDVG TSVAWYQQKP GKAPKLLIYW 50 TSTRHTGVPS RFSGSGSGTD FTFTISSLQP EDIATYYCQQ YSLYRSFGQG 100 TKVEIKRTVA APSVFIFPPS DEQLKSGTAS VVCLLNNFYP REAKVQWKVD 150 NALQSGNSQE SVTEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL 200 SSPVTKSFNR GEC 213 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 146-202 263-323 369-427 22''-96'' 146''-202'' 263''-323'' 369''-427'' Intra-L (C23-C104) 23'-88' 133'-193' 23'''-88''' 133'''-193''' Inter-H-L (h 5-CL 126) * 222-213' 222''-213''' Inter-H-H (h 11, h 14) * 228-228'' 231-231'' *Three of the inter-chain disulfide bridges are not present, an average of 6 cysteinyl being conjugated each via a thioether bond to a drug linker. *Trois des ponts disulfures inter-chaînes ne sont pas présents, 6 cystéinyl en moyenne étant chacun conjugué via une liaison thioéther à un linker-principe actif. *Faltan tres puentes disulfuro inter-catenarios, una media de 6 cisteinil está conjugada a conectores de principio activo. N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 299, 299'' Fucosylated complex bi-antennary Sp2/0-type glycans / glycanes de type Sp2/0 bi-antennaires complexes fucosylés / glicanos de tipo Sp2/0 biantenarios complejos fucosilados Potential modified residues / Résidus modifiés potentiels / Restos modificados potenciales WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 127 landogrozumabum # landogrozumab immunoglobulin G4-kappa, anti-[Homo sapiens MSTN (myostatin, growth differentiation factor 8, GDF8, GDF-8)], humanized monoclonal antibody; gamma4 heavy chain (1-439) [humanized VH (Homo sapiens IGHV3-23*04 (89.80%) -(IGHD)-IGHJ4*01 [8.8.6] (1-113)) , IGHG4*01 (CH1 (114-211), hinge S10>P (221) (212-223), CH2 (224-333), CH3 (334-438), CHS K2>del (439)) (114-439)], (127-215')-disulfide with kappa light chain (1’-215’) [humanized V-KAPPA (Homo sapiens IGKV3-20*01 (89.10%) -IGKJ4*01) [7.3.9] (1'-108') -Homo sapiens IGKC*01 (109'-215')]; dimer (219-219":222-222")- bisdisulfide landogrozumab immunoglobuline G4-kappa, anti-[Homo sapiens MSTN (myostatine, facteur de croissance et de différenciation 8, GDF8, GDF-8)], anticorps monoclonal humanisé; chaîne lourde gamma4 (1-441) [VH humanisé (Homo sapiens IGHV3-23*04 (89.80%) -(IGHD)-IGHJ4*01 [8.8.6] (1-113)) , IGHG4*01 (CH1 (114-211), charnière S10>P (221) (212-223), CH2 (224-333), CH3 (334-438), CHS K2>del (439)) (114-439)], (127-215')-disulfure avec la chaîne légère kappa (1’-215’) [V-KAPPA humanisé (Homo sapiens IGKV3-20*01 (89.10%) -IGKJ4*01) [7.3.9] (1'-108') -Homo sapiens IGKC*01 (109'-215')]; dimère (219- 219":222-222")-bisdisulfure landogrozumab inmunoglobulina G4-kappa, anti-[Homo sapiens MSTN (miostatina, factor de crecimiento y de diferenciación 8, GDF8, GDF-8)], anticuerpo monoclonal humanizado; cadena pesada gamma4 (1-441) [VH humanizado (Homo sapiens IGHV3-23*04 (89.80%) -(IGHD)-IGHJ4*01 [8.8.6] (1-113)) , IGHG4*01 (CH1 (114-211),bisagra S10>P (221) (212-223), CH2 (224-333), CH3 (334-438), CHS K2>del (439)) (114-439)], (127-215')-disulfuro con la cadena ligera kappa (1’-215’) [V-KAPPA humanizado (Homo sapiens IGKV3-20*01 (89.10%) -IGKJ4*01) [7.3.9] (1'-108') -Homo sapiens IGKC*01 (109'-215')]; dímero (219-219":222- 222")-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaEVQLVESGGG LVQPGGSLRL SCAASGLTFS RYPMSWVRQA PGKGLVWVSA 50 ITSSGGSTYY SDTVKGRFTI SRDNAKNTLY LQMNSLRAED TAVYYCARLP 100 DYWGQGTLVT VSSASTKGPS VFPLAPCSRS TSESTAALGC LVKDYFPEPV 150 TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TKTYTCNVDH 200 KPSNTKVDKR VESKYGPPCP PCPAPEFLGG PSVFLFPPKP KDTLMISRTP 250 EVTCVVVDVS QEDPEVQFNW YVDGVEVHNA KTKPREEQFN STYRVVSVLT 300 VLHQDWLNGK EYKCKVSNKG LPSSIEKTIS KAKGQPREPQ VYTLPPSQEE 350 MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV LDSDGSFFLY 400 SRLTVDKSRW QEGNVFSCSV MHEALHNHYT QKSLSLSLG 439 Light chain / Chaîne légère / Cadena ligera EIVLTQSPGT LSLSPGERAT LSCRASSSVS SSYLHWYQQK PGQAPRLLIY 50 STSNLVAGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYCQ HHSGYHFTFG 100 GGTKVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150 VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200 GLSSPVTKSF NRGEC 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 140-196 254-314 360-418 22''-96'' 140''-196'' 254''-314'' 360''-418'' Intra-L (C23-C104) 23'-89' 135'-195' 23'''-89''' 135'''-195''' Inter-H-L (CH1 10-CL 126) 127-215' 127''-215''' Inter-H-H (h 8, h 11) 219-219'' 222-222'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 290, 290'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 128 lefitolimodum lefitolimod DNA based immunomodulator agent: cyclo-(3'→5')[2'-deoxy-(A-A-A-A-C-G-T-T-C-T-T-C-G-G-G- G-C-G-T-T-C-T-T-A-G-G-T-G-G-T-A-A-C-C-C-C-T-A-G-G- G-G-T-T-A-C-C-A-C-C-T-T-C-A-T-T-G-G-A-A-A-A-C-G-T- T-C-T-T-C-G-G-G-G-C-G-T-T-C-T-T-A-G-G-T-G-G-T-A-A- C-C-C-C-T-A-G-G-G-G-T-T-A-C-C-A-C-C-T-T-C-A-T-T-G- G)] léfitolimod immunomodulateur de type ADN: cyclo-(3'→5')[2'-déoxy-(A-A-A-A-C-G-T-T-C-T-T-C-G-G-G- G-C-G-T-T-C-T-T-A-G-G-T-G-G-T-A-A-C-C-C-C-T-A-G-G- G-G-T-T-A-C-C-A-C-C-T-T-C-A-T-T-G-G-A-A-A-A-C-G-T- T-C-T-T-C-G-G-G-G-C-G-T-T-C-T-T-A-G-G-T-G-G-T-A-A- C-C-C-C-T-A-G-G-G-G-T-T-A-C-C-A-C-C-T-T-C-A-T-T-G- G)] lefitolimod inmunomodulador de tipo ADN: ciclo-(3'→5')[2'-desoxi-(A-A-A-A-C-G-T-T-C-T-T-C-G-G-G- G-C-G-T-T-C-T-T-A-G-G-T-G-G-T-A-A-C-C-C-C-T-A-G-G- G-G-T-T-A-C-C-A-C-C-T-T-C-A-T-T-G-G-A-A-A-A-C-G-T- T-C-T-T-C-G-G-G-G-C-G-T-T-C-T-T-A-G-G-T-G-G-T-A-A- C-C-C-C-T-A-G-G-G-G-T-T-A-C-C-A-C-C-T-T-C-A-T-T-G- G)] CTTCGGGGCGTTCTTAGGTGGTAACCCCTAGGGGTTACCACCTTCATTGGAAAACGTT TTGCAAAAGGTTACTTCCACCATTGGGGATCCCCAATGGTGGATTCTTGCGGGGCTTC ............................ 3' 5' maralixibati chloridum maralixibat chloride 1-{[4-({4-[(4R,5R)-3,3-dibutyl-7-(dimethylamino)-4-hydroxy- 1,1-dioxo-2,3,4,5-tetrahydro-1H-1λ6-benzothiepin- 5-yl]phenoxy}methyl)phenyl]methyl}- 1,4-diazabicyclo[2.2.2]octan-1-ium chloride chlorure de maralixibat chlorure de 1-{[4-({4-[(4R,5R)-3,3-dibutyl- 7-(diméthylamino)-4-hydroxy-1,1-dioxo-2,3,4,5-tétrahydro- 1H-1λ6-benzothiépin-5-yl]phénoxy}méthyl)phényl]méthyl}- 1,4-diazabicyclo[2.2.2]octan-1-ium cloruro de maralixibat cloruro de 1-{[4-({4-[(4R,5R)-3,3-dibutil-7-(dimetilamino)- 4-hidroxi-1,1-dioxo-2,3,4,5-tetrahidro-1H-1λ6-benzotiepin- 5-il]fenoxi}metil)fenil]metil}-1,4-diazabiciclo[2.2.2]octan-1-io C40H56ClN3O4S SO O H N CH3 CH3 H3C O N N H OH H3C Cl WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 129 marzeptacogum alfa (activatum) # marzeptacog alfa (activated) recombinant DNA derived human blood coagulation factor VIIa analogue: [128-L-asparagine(T>N),129-L-alanine(P>A),286-L- arginine(Q>R),298-L-glutamine(M>Q)]activated human coagulation factor VII (proconvertine, SPCA), produced in Chinese hamster ovary (CHO) cells, glycoform alfa marzeptacog alfa (activé) analogue du facteur VIIa de coagulation sanguine humain produit à partir d’ADN recombinant : [128-L-asparagine(T>N),129-L-alanine(P>A),286-L- arginine(Q>R),298-L-glutamine(M>Q)]facteur VII de coagulation humain activé (proconvertine, SPCA), produite par des cellules ovariennes de hamster chinois (CHO), forme glycosylée alfa marzeptacog alfa (activado) análogo del factor VIIa de coagulación sanguínea humano producido a partir de ADN recombinante : [128-L-asparagina(T>N),129-L-alanina(P>A),286-L- arginina(Q>R),298-L-glutamina(M>Q)]factor VII de coagulación humano activado (proconvertina, SPCA), producida por células ováricas de hamster chino (CHO), forma glicosilada alfa HO2C CO2H NH2HHO2C CO2H NH2H HO2C HO H Light chain / Chaîne légère / Cadena ligera ANAFLEELRP GSLERECKEE QCSFEEAREI FKDAERTKLF WISYSDGDQC 50 ASSPCQNGGS CKDQLQSYIC FCLPAFEGRN CETHKDDQLI CVNENGGCEQ 100 YCSDHTGTKR SCRCHEGYSL LADGVSCNAT VEYPCGKIPI LEKRNASKPQ 150 GR 152 Heavy chain / Chaîne lourde / Cadena pesada IVGGKVCP KGECPWQVLL LVNGAQLCGG TLINTIWVVS AAHCFDKIKN 200 WRNLIAVLGE HDLSEHDGDE QSRRVAQVII PSTYVPGTTN HDIALLRLHQ 250 PVVLTDHVVP LCLPERTFSE RTLAFVRFSL VSGWGRLLDR GATALELQVL 300 NVPRLMTQDC LQQSRKVGDS PNITEYMFCA GYSDGSKDSC KGDSGGPHAT 350 HYRGTWYLTG IVSWGQGCAT VGHFGVYTRV SQYIEWLQKL MRSEPRPGVL 400 LRAPFP 406 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 17-22 50-61 55-70 72-81 91-102 98-112 114-127 135-262 159-164 178-194 310-329 340-368 Modified residues / Résidus modifiés / Restos modificados E 6-7-14-16-19 20-25-26-29-35 4-carboxyGlu D 63 3-hydroxyAsp Glycosylation sites (S or N) / Sites de glycosylation (S ou N) / Posiciones de glicosilación (S o N) Ser-52 Ser-60 Asn-128 Asn-145 Asn-322 mecapegfilgrastimum # mecapegfilgrastim [1-[N-(3-{[(3RS)-1-{3-[(2-{[ω-methoxypoly(oxyethane- 1,2-diyl)]formamido}ethyl)amino]-3-oxopropyl}- 2,5-dioxopyrrolidin-3-yl]sulfanyl}propyl)- L-methionine]]human granulocyte colony-stimulating factor (pluripoietin) isoform Short mécapegfilgrastim [1-[N-(3-{[(3RS)-1-{3-[(2-{[ω-méthoxypoly(oxyéthane- 1,2-diyl)]formamido}éthyl)amino]-3-oxopropyl}- 2,5-dioxopyrrolidin-3-yl]sulfanyl}propyl)- L-méthionine]]isoforme court (Short) du facteur de stimulation des colonies de granulocytes humain (pluripoiétine) Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 130 mecapegfilgrastim [1-[N-(3-{[(3RS)-1-{3-[(2-{[ω-metoxipoli(oxietano- 1,2-diil)]formamido}etil)amino]-3-oxopropil}- 2,5-dioxopirrolidin-3-il]sulfanil}propil)-L-metionina]]isoforma corta (Short) del factor humano de estimulación de colonias de granulocitos (pluripoyetina) OO O H3C n HN HN N O O S H O H N CO2H H SH3C Sequence / Séquence / Secuencia MTPLGPASSL PQSFLLKCLE QVRKIQGDGA ALQEKLCATY KLCHPEELVL 50 LGHSLGIPWA PLSSCPSQAL QLAGCLSQLH SGLFLYQGLL QALEGISPEL 100 GPTLDTLQLD VADFATTIWQ QMEELGMAPA LQPTQGAMPA FASAFQRRAG 150 GVLVASHLQS FLEVSYRVLR HLAQP 175 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 37-43 65-75 Modified residue / Résidu modifié / Resto modificado M 1 PEG-Met merestinibum merestinib N-(3-fluoro-4-{[1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol- 5-yl]oxy}phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo- 1,2-dihydropyridine-3-carboxamide mérestinib N-(3-fluoro-4-{[1-méthyl-6-(1H-pyrazol-4-yl)-1H-indazol- 5-yl]oxy}phényl)-1-(4-fluorophényl)-6-méthyl-2-oxo- 1,2-dihydropyridine-3-carboxamide merestinib N-(3-fluoro-4-{[1-metil-6-(1H-pirazol-4-il)-1H-indazol- 5-il]oxi}fenil)-1-(4-fluorofenil)-6-metil-2-oxo- 1,2-dihidropiridina-3-carboxamida C30H22F2N6O3 N H3C O N H O F F O N N CH3 NHN mirvetuximabum soravtansinum # mirvetuximab soravtansine immunoglobulin G1-kappa, anti-[Homo sapiens FOLR1 (folate receptor 1, folate receptor alpha, FR-alpha, adult folate-binding protein, FBP, ovarian tumor-associated antigen MOv18)], chimeric monoclonal antibody conjugated to maytansinoid DM4; WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 131 gamma1 heavy chain (1-447) [Mus musculus VH (IGHV1- 37*01 -(IGHD)-IGHJ4*01) [8.8.11] (1-118) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (119-216), hinge (217-231), CH2 (232-341), CH3 (342-446), CHS K2>del (447)) (119- 447)], (221-218')-disulfide with kappa light chain (1'-218') [Mus musculus V-KAPPA (IGKV3-9*01 -IGKJ2*01) [10.3.9] (1'-111') -Homo sapiens IGKC*01, Km3 (112'-218')]; dimer (227-227'':230-230'')-bisdisulfide;conjugated, on an average of 3 or 4 lysyl, to maytansinoid DM4 [N2'-deacetyl- N2'-(4-mercapto-4-methyl-1-oxopentyl)-maytansine] via the reducible sulfo-SPDB linker [N-succinimidyl 4-(2- pyridyldithio)-2-sulfobutanoate] mirvétuximab soravtansine immunoglobuline G1-kappa, anti-[Homo sapiens FOLR1 (réceptor 1 du folate, récepteur alpha du folate, FR-alpha, protéine de l’adulte liant le folate, FBP, antigène MOv18 associé à des tumeurs ovariennes)], anticorps monoclonal chimérique conjugué au maytansinoïde DM4; chaîne lourde gamma1 (1-447) [Mus musculus VH (IGHV1-37*01 -(IGHD)-IGHJ4*01) [8.8.11] (1-118) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (119-216), charnière (217-231), CH2 (232-341), CH3 (342-446), CHS K2>del (447)) (119-447)], (221-218')-disulfure avec la chaîne légère kappa (1'-218') [Mus musculus V-KAPPA (IGKV3- 9*01 -IGKJ2*01) [10.3.9] (1'-111') -Homo sapiens IGKC*01, Km3 (112'-218')]; dimère (227-227'':230-230'')- bisdisulfure; conjugué, sur 3 ou 4 lysyl en moyenne, au maytansinoïde DM4 [N2'-déacétyl-N2'-(4-mercapto-4- méthyl-1-oxopentyl)-maytansine] via le linker sulfo-SPDB réductible [4-(2-pyridyldithio)-2-sulfobutanoate de N- succinimidyle] mirvetuximab soravtansina inmunoglobulina G1-kappa, anti-[Homo sapiens FOLR1 (receptor 1 de folato, receptor alfa de folato, FR-alfa, proteína del adulto que liga el folato, FBP, antígeno MOv18 asociado a tumores ováricos)], anticuerpo monoclonal quimérico conjugado con el maitansinoide DM4; cadena pesada gamma1 (1-447) [Mus musculus VH (IGHV1-37*01 -(IGHD)-IGHJ4*01) [8.8.11] (1-118) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (119-216), cbisagra (217-231), CH2 (232-341), CH3 (342-446), CHS K2>del (447)) (119-447)], (221-218')-disulfuro con la cadena ligera-Homo sapiens IGKC*01, Km3 (112'-218')]; dímero (227-227'':230-230'')-bisdisulfuro; conjugado en 3-4 grupos lisil por término medio con el maitansinoide DM4 [N2'- desacetil-N2'-(4-mercapto-4-metil-1-oxopentil)-maitansina] mediante el espaciador sulfo-SPDB reducible [4-(2- piridilditio)butanoato de N-succinimidilo] Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 132 and epimer at C* et l'épimère en C* y el epímero al C* N H CH3 O N O H CH3 Cl OCH3 O H3C H OH O H3C H O O H OCH3 H N CH3H CH3 O S SC H3C H3C O HHO3S * H NIg n Ig(NH2)n = Immunoglobulin Heavy chain / Chaîne lourde / Cadena pesada QVQLVQSGAE VVKPGASVKI SCKASGYTFT GYFMNWVKQS PGQSLEWIGR 50 IHPYDGDTFY NQKFQGKATL TVDKSSNTAH MELLSLTSED FAVYYCTRYD 100 GSRAMDYWGQ GTTVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY 150 FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI 200 CNVNHKPSNT KVDKKVEPKS CDKTHTCPPC PAPELLGGPS VFLFPPKPKD 250 TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYNST 300 YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY 350 TLPPSRDELT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD 400 SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPG 447 Light chain / Chaîne légère / Cadena ligera DIVLTQSPLS LAVSLGQPAI ISCKASQSVS FAGTSLMHWY HQKPGQQPRL 50 LIYRASNLEA GVPDRFSGSG SKTDFTLTIS PVEAEDAATY YCQQSREYPY 100 TFGGGTKLEI KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV 150 QWKVDNALQS GNSQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV 200 THQGLSSPVT KSFNRGEC 218 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 145-201 262-322 368-426 22''-96'' 145''-201'' 262''-322'' 368''-426'' Intra-L (C23-C104) 23'-92' 138'-198' 23'''-92''' 138'''-198''' Inter-H-L (h 5-CL 126) 221-218' 221''-218''' Inter-H-H (h 11, h 14) 227-227'' 230-230'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 298, 298'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados soravtansine / soravtansine / soravtansina monalizumabum # monalizumab immunoglobulin G4-kappa, anti-[Homo sapiens KLRC1 (killer cell lectin-like receptor subfamily C member 1, NKG2-A, NKG2A, CD159a, CD94)],humanized monoclonal antibody; gamma4 heavy chain (1-452) [humanized VH (Homo sapiens IGHV1-18*01 (89.80%) -(IGHD)-IGHJ2*01 R120>Q (117), L123>T (130)) [8.8.18] (1-125)), IGHG4*01 (CH1 (126-223), hinge S10>P (233) (224-235), CH2 (236- 345), CH3 (346-450), CHS (451-452)) (126-452)], (139- 214')-disulfide with kappa light chain (1’-214’) [humanized V-KAPPA (Homo sapiens IGKV1-39*01 (87.40%) - IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimer (231-231":234-234")-bisdisulfide monalizumab immunoglobuline G4-kappa, anti-[Homo sapiens KLRC1 (membre 1 de la sous-famille C des récepteurs de type lectine des cellules NK, NKG2-A, NKG2A, CD159a, CD94)], anticorps monoclonal humanisé; WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 133 chaîne lourde gamma4 (1-452) [VH humanisé (Homo sapiens IGHV1-18*01 (89.80%) -(IGHD)-IGHJ2*01 R120>Q (117), L123>T (130)) [8.8.18] (1-125)), IGHG4*01 (CH1 (126-223), charnière S10>P (233) (224-235), CH2 (236-345), CH3 (346-450), CHS (451-452)) (126-452)], (139-214')-disulfure avec la chaîne légère kappa (1’-214’) [V-KAPPA humanisé (Homo sapiens IGKV1-39*01 (87.40%) -IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimère (231-231":234-234")- bisdisulfure monalizumab inmunoglobulina G4-kappa, anti-[Homo sapiens KLRC1 (miembro 1 de la subfamilia C de receptores de tipo lectina de las células NK, NKG2-A, NKG2A, CD159a, CD94)], anticuerpo monoclonal humanizado; cadena pesada gamma4 (1-452) [VH humanizado (Homo sapiens IGHV1-18*01 (89.80%) -(IGHD)-IGHJ2*01 R120>Q (117), L123>T (130)) [8.8.18] (1-125)), IGHG4*01 (CH1 (126-223), bisagra S10>P (233) (224-235), CH2 (236-345), CH3 (346-450), CHS (451-452)) (126-452)], (139-214')-disulfuro con la cadena ligera kappa (1’-214’) [V-KAPPA humanizado (Homo sapiens IGKV1-39*01 (87.40%) -IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dímero (231-231":234-234")- bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKV SCKASGYTFT SYWMNWVRQA PGQGLEWMGR 50 IDPYDSETHY AQKLQGRVTM TTDTSTSTAY MELRSLRSDD TAVYYCARGG 100 YDFDVGTLYW FFDVWGQGTT VTVSSASTKG PSVFPLAPCS RSTSESTAAL 150 GCLVKDYFPE PVTVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS 200 LGTKTYTCNV DHKPSNTKVD KRVESKYGPP CPPCPAPEFL GGPSVFLFPP 250 KPKDTLMISR TPEVTCVVVD VSQEDPEVQF NWYVDGVEVH NAKTKPREEQ 300 FNSTYRVVSV LTVLHQDWLN GKEYKCKVSN KGLPSSIEKT ISKAKGQPRE 350 PQVYTLPPSQ EEMTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP 400 PVLDSDGSFF LYSRLTVDKS RWQEGNVFSC SVMHEALHNH YTQKSLSLSL 450 GK 452 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCRASENIY SYLAWYQQKP GKAPKLLIYN 50 AKTLAEGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQH HYGTPRTFGG 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 152-208 266-326 372-430 22''-96'' 152''-208'' 266''-326'' 372''-430'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (CH1 10-CL 126) 139-214' 139''-214''' Inter-H-H (h 8, h 11) 231-231'' 234-234'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 302, 302'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados murepavadinum murepavadin cyclo[L-alanyl-L-seryl-D-prolyl-L-prolyl-L-threonyl- L-tryptophyl-L-isoleucyl-(2S)-2,4-diaminobutanoyl- L-ornithyl-(2R)-2,4-diaminobutanoyl-(2S)-2,4- diaminobutanoyl-L-tryptophyl-(2S)-2,4-diaminobutanoyl- (2S)-2,4-diaminobutanoyl] murépavadine cyclo[L-alanyl-L-séryl-D-prolyl-L-prolyl-L-thréonyl- L-tryptophyl-L-isoleucyl-(2S)-2,4-diaminobutanoyl- L-ornithyl-(2R)-2,4-diaminobutanoyl-(2S)-2,4- diaminobutanoyl-L-tryptophyl-(2S)-2,4-diaminobutanoyl- (2S)-2,4-diaminobutanoyl] Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 134 murepavadina ciclo[L-alanil-L-seril-D-prolil-L-prolil-L-treonil-L-triptofil- L-isoleucil-(2S)-2,4-diaminobutanoil-L-ornitil-(2R)-2,4- diaminobutanoil-(2S)-2,4-diaminobutanoil-L-triptofil-(2S)- 2,4-diaminobutanoil-(2S)-2,4-diaminobutanoil] C73H112N22O16 Ala Ser D-Pro Pro Thr Trp Ile NH H N H NTrp H N HHH O NH2 OO HN O O HH NH2NH2 NH2 Orn H2N nadorameranum # nadorameran an mRNA molecule encoding the rabies virus glycoprotein RAV-G containing elements for expression within eukaryotic cells; manufactured by enzymatic in vitro transcription from linearized plasmid DNA nadoraméran ARN messager codant la glycoprotéine G du virus de la rage contenant les éléments pour son expression dans des cellules eucaryotes; obtenu par transcription enzymatique in vitro à partir d'ADN de plasmide linéarisé nadoramerán ARN mensajero que codifica la glicoproteína G del virus de la rabia y contiene los elementos para su expresión en células eucariotas; obtenido por transcripción enzimática in vitro a partir de ADN de plásmido transformado en lineal nastorazepidum nastorazepide 3-({[(3R)-5-cyclohexyl-1-(3,3-dimethyl-2-oxobutyl)-2-oxo- 2,3,4,5-tetrahydro-1H-1,5-benzodiazepin- 3-yl]carbamoyl}amino)benzoic acid nastorazépide acide 3-({[(3R)-5-cyclohexyl-1-(3,3-diméthyl-2-oxobutyl)- 2-oxo-2,3,4,5-tétrahydro-1H-1,5-benzodiazépin- 3-yl]carbamoyl}amino)benzoïque nastorazepida ácido 3-({[(3R)-5-cyclohexyl-1-(3,3-dimetil-2-oxobutil)- 2-oxo-2,3,4,5-tetrahidro-1H-1,5-benzodiazepin- 3-il]carbamoil}amino)benzoico C29H36N4O5 N N N H H O H3C CH3 CH3 O N H O CO2H WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 135 natrii cinhyaluronas cinhyaluronate sodium sodium salt of hyaluronic acid partly amidified with 3-{[(2E)-3-phenylprop-2-enoyl]oxy}propan-1-amine cinhyaluronate de sodium sel sodique de l’acide hyaluronique partiellement amidifié par la 3-{[(2E)-3-phénylprop-2-énoyl]oxy}propan-1-amine cinhialuronato de sodio sal sódica del ácido hialurónico parcialmente amidificado por la 3-{[(2E)-3-fenilprop-2-enoil]oxi}propan-1-amina [(C26H34N2O12)a(C14H20NNaO11)b]nH2O O OHO NH OH O OH NaO2C HO OH O O OHO NH O OHHO O O CH3 HN O O CH3 H a b n HO O O navivumabum # navivumab immunoglobulin G1-kappa, anti-[influenza A virus hemagglutinin HA], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-456) [Homo sapiens VH (IGHV1- 18*01 (78.60%) -(IGHD)-IGHJ4*01) [8.8.19] (1-126) - IGHG1*07, G1m17,1,2 (CH1 (127-224), hinge (225-239), CH2 (240-349), CH3 (350-454), CHS (455-456)) (127- 456)], (229-215')-disulfide with kappa light chain (1'-215') [Homo sapiens V-KAPPA (IGKV3-20*01 (82.30%) - IGKJ1*01) [7.3.9] (1'-108') -IGKC*01, Km3 (109'-215')]; dimer (235-235'':238-238'')-bisdisulfide navivumab immunoglobuline G1-kappa, anti-[hémagglutinine HA du virus de la grippe A], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-456) [Homo sapiens VH (IGHV1-18*01 (78.60%) -(IGHD)-IGHJ4*01) [8.8.19] (1- 126) -IGHG1*07, G1m17,1,2 (CH1 (127-224), charnière (225-239), CH2 (240-349), CH3 (350-454), CHS (455- 456)) (127-456)], (229-215')-disulfure avec la chaîne légère kappa (1'-215') [Homo sapiens V-KAPPA (IGKV3-20*01 (82.30%) -IGKJ1*01) [7.3.9] (1'-108') -IGKC*01, Km3 (109'- 215')]; dimère (235-235'':238-238'')-bisdisulfure Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 136 navivumab inmunoglobulina G1-kappa, anti-[hemaglutinina HA del virus de la gripe A], anticuerpo monoclonal Homo sapiens; cadena pesada gamma1 (1-456) [Homo sapiens VH (IGHV1-18*01 (78.60%) -(IGHD)-IGHJ4*01) [8.8.19] (1- 126) -IGHG1*07, G1m17,1,2 (CH1 (127-224), bisagra (225-239), CH2 (240-349), CH3 (350-454), CHS (455- 456)) (127-456)], (229-215')-disulfuro con la cadena ligera kappa (1'-215') [Homo sapiens V-KAPPA (IGKV3-20*01 (82.30%) -IGKJ1*01) [7.3.9] (1'-108') -IGKC*01, Km3 (109'- 215')]; dímero (235-235'':238-238'')-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKV SCKTSGYSFS TYGVSWVRQA PGQGPEWVGW 50 ISAYTGITDY AQKFQGRVTL TTDATTATAF LDLRSLRPDD TATYFCARDK 100 VQGRVEVGSG GRHDYWGQGT LVIVSSASTK GPSVFPLAPS SKSTSGGTAA 150 LGCLVKDYFP EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSVVTVPSS 200 SLGTQTYICN VNHKPSNTKV DKKVEPKSCD KTHTCPPCPA PELLGGPSVF 250 LFPPKPKDTL MISRTPEVTC VVVDVSHEDP EVKFNWYVDG VEVHNAKTKP 300 REEQYNSTYR VVSVLTVLHQ DWLNGKEYKC KVSNKALPAP IEKTISKAKG 350 QPREPQVYTL PPSRDELTKN QVSLTCLVKG FYPSDIAVEW ESNGQPENNY 400 KTTPPVLDSD GSFFLYSKLT VDKSRWQQGN VFSCSVMHEG LHNHYTQKSL 450 SLSPGK 456 Light chain / Chaîne légère / Cadena ligera EVVLTQSPGT LALPPGERAT LSCRASHRVG STYIAWYQQK SGQAPRRLIY 50 GASNRATDIP DRFSGSGSGT DFTLTIRRLE PEDSAVYYCQ QFSVSPWTFG 100 QGTRVEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150 VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200 GLSSPVTKSF NRGEC 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 153-209 270-330 376-434 22''-96'' 153''-209'' 270''-330'' 376''-434'' Intra-L (C23-C104) 23'-89' 135'-195' 23'''-89''' 135'''-195''' Inter-H-L (h 5-CL 126) 229-215' 229''-215''' Inter-H-H (h 11, h 14) 235-235'' 238-238'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 306, 306'' Other post-translational modifications / Autres modifications post-traductionnelles / Otras modificaciones post-traduccionales H CHS K2 C-terminal lysine clipping: 456, 456'' neladenosoni bialanas neladenoson bialanate 2-{4-[2-({[2-(4-chlorophenyl)-1,3-thiazol- 4-yl]methyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin- 4-yl]phenoxy}ethyl L-alanyl-L-alaninate bialanate de néladénoson L-alanyl-L-alaninate de 2-{4-[2-({[2-(4-chlorophényl)- 1,3-thiazol-4-yl]méthyl}sulfanyl)-3,5-dicyano-6-(pyrrolidin- 1-yl)pyridin-4-yl]phénoxy}éthyle bialanato de neladenosón L-alanil-L-alaninato de 2-{4-[2-({[2-(4-clorofenil)-1,3-tiazol- 4-il]metil}sulfanil)-3,5-diciano-6-(pirrolidin-1-il)piridin- 4-il]fenoxi}etilo C35H34ClN7O4S2 N N CN CN SN S Cl O O HN O CH3 H O NH2 H CH3 WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 137 netarsudilum netarsudil {4-[(2S)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan- 2-yl]phenyl}methyl 2,4-dimethylbenzoate nétarsudil 2,4-diméthylbenzoate de {4-[(2S)-3-amino-1-(isoquinoléin- 6-ylamino)-1-oxopropan-2-yl]phényl}méthyle netarsudil 2,4-dimetilbenzoato de {4-[(2S)-3-amino-1-(isoquinolein- 6-ilamino)-1-oxopropan-2-il]fenil}metilo C28H27N3O3 O N H NO HH2N O CH3H3C obiltoxaximabum # obiltoxaximab immunoglobulin G1-kappa, anti-[Bacillus anthracis anthrax toxin protective antigen (PA)], chimeric monoclonal antibody; gamma1 heavy chain (1-449) [Mus musculus VH (IGHV1- 82*01 -(IGHD)-Homo sapiens IGHJ4*01) [8.8.12] (1-119) - Homo sapiens IGHG1*01, Gm17,1 (CH1 (120-217), hinge (218-232), CH2 (233-342), CH3 (343-447), CHS (448- 449)) (120-449)], (222-214')-disulfide with kappa light chain (1'-214') [Mus musculus V-KAPPA (IGKV10-96*01 -Homo sapiens IGKJ1*01 K127>R (107) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimer (228-228'':231- 231'')-bisdisulfide obiltoxaximab immunoglobuline G1-kappa, anti-[antigène protecteur (AP) de la toxine de Bacillus anthracis de la maladie du charbon], anticorps monoclonal chimérique; chaîne lourde gamma1 (1-449) [Mus musculus VH (IGHV1-82*01 -(IGHD)-Homo sapiens IGHJ4*01) [8.8.12] (1-119) -Homo sapiens IGHG1*01, Gm17,1 (CH1 (120- 217), charnière (218-232), CH2 (233-342), CH3 (343-447), CHS (448-449)) (120-449)], (222-214')-disulfure avec la chaîne légère kappa (1'-214') [Mus musculus V-KAPPA (IGKV10-96*01 -Homo sapiens IGKJ1*01 K127>R (107) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimère (228-228'':231-231'')-bisdisulfure obiltoxaximab inmunoglobulina G1-kappa, anti-[antigeno protector (AP) de la toxina de Bacillus anthracis, del carbunco], anticuerpo monoclonal quimérico; cadena pesada gamma1 (1-449) [Mus musculus VH (IGHV1-82*01 -(IGHD)-Homo sapiens IGHJ4*01) [8.8.12] (1-119) -Homo sapiens IGHG1*01, Gm17,1 (CH1 (120- 217), bisagra (218-232), CH2 (233-342), CH3 (343-447), CHS (448-449)) (120-449)], (222-214')-disulfuro con la cadena ligera kappa (1'-214') [Mus musculus V-KAPPA (IGKV10-96*01 -Homo sapiens IGKJ1*01 K127>R (107) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimero (228-228'':231-231'')-bisdisulfuro Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 138 Heavy chain / Chaîne lourde / Cadena pesadaQVQLQQSGPE LKKPGASVKV SCKDSGYAFS SSWMNWVRQA PGQGLEWIGR 50 IYPGDGDTNY NGKFQGRVTI TADKSSSTAY MELSSLRSED TAVYFCARSG 100 LLRYAMDYWG QGTLVTVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD 150 YFPEPVTVSW NSGALTSGVH TFPAVLQSSG LYSLSSVVTV PSSSLGTQTY 200 ICNVNHKPSN TKVDKKVEPK SCDKTHTCPP CPAPELLGGP SVFLFPPKPK 250 DTLMISRTPE VTCVVVDVSH EDPEVKFNWY VDGVEVHNAK TKPREEQYNS 300 TYRVVSVLTV LHQDWLNGKE YKCKVSNKAL PAPIEKTISK AKGQPREPQV 350 YTLPPSRDEL TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 400 DSDGSFFLYS KLTVDKSRWQ QGNVFSCSVM HEALHNHYTQ KSLSLSPGK 449 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCRASQDIR NYLNWYQQKP GKAVKLLIYY 50 TSRLLPGVPS RFSGSGSGTD YSLTISSQEQ EDIGTYFCQQ GNTLPWTFGQ 100 GTKVEIRRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 146-202 263-323 369-427 22''-96'' 146''-202'' 263''-323'' 369''-427'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 222-214' 222''-214''' Inter-H-H (h 11, h 14) 228-228'' 231-231'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 299, 299'' omaveloxolonum omaveloxolone N-(2-cyano-3,12-dioxo-28-noroleana-1,9(11)-dien-17-yl)- 2,2-difluoropropanamide omavéloxolone N-(2-cyano-3,12-dioxo-28-noroléana-1,9(11)-dién-17-yl)- 2,2-difluoropropanamide omaveloxolona N-(2-ciano-3,12-dioxo-28-noroleana-1,9(11)-dien-17-il)- 2,2-difluoropropanamida C33H44F2N2O3 CH3CH3 CH3 CH3 H3C CH3H3C O N H H NC O H H CH3 O F F opicinumabum # opicinumab immunoglobulin G1-kappa, anti-[Homo sapiens LINGO1 (leucine-rich repeat and Ig-like domain-containing nogo receptor-interacting protein 1, LINGO-1, leucine-rich repeat neuronal protein 1, LERN1, leucine-rich repeat neuronal protein 6A, LRRN6A)], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-447) [Homo sapiens VH (IGHV3- 23*01 (91.80%) -(IGHD)-IGHJ3*02) [8.8.11] (1-118) - IGHG1*01, G1m17,1 (CH1 (119-216), hinge (217-231), CH2 T85.3>A (300) (232-341), CH3 (342-446), CHS K2>del (447)) (119-447)], (221-215')-disulfide with kappa light chain (1'-215') [Homo sapiens V-KAPPA (IGKV3- 11*01 (96.80%) -IGKJ2*01) [6.3.10] (1'-108') -IGKC*01, Km3 (109'-215')]; dimer (227-227'':230-230'')-bisdisulfide WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 139 opicinumab immunoglobuline G1-kappa, anti-[Homo sapiens LINGO1 (protéine 1 interagissant avec le récepteur de nogo et contenant des répétitions riches en leucine et un domaine Ig-like, LINGO-1, protéine neuronale 1 contenant des répétitions riches en leucine, LERN1, protéine neuronale 6A contenant des répétitions riches en leucine, LRRN6A)], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-447) [Homo sapiens VH (IGHV3-23*01 (91.80%) -(IGHD)-IGHJ3*02) [8.8.11] (1- 118) -IGHG1*01, G1m17,1 (CH1 (119-216), charnière (217-231), CH2 T85.3>A (300) (232-341), CH3 (342-446), CHS K2>del (447)) (119-447)], (221-215')-disulfure avec la chaîne légère kappa (1'-215') [Homo sapiens V-KAPPA (IGKV3-11*01 (96.80%) -IGKJ2*01) [6.3.10] (1'-108') - IGKC*01, Km3 (109'-215')]; dimère (227-227'':230-230'')- bisdisulfure opicinumab inmunoglobulina G1-kappa, anti-[Homo sapiens LINGO1 (proteína 1 que interacciona con el receptor de nogo y contiene repeticiones ricas en leucina y un dominio Ig-like, LINGO-1, proteína neuronal 1, que contiene repeticiones ricas en leucina,LERN1, proteína neuronal 6A que contiene repeticiones ricas en leucina, LRRN6A)], anticuerpo monoclonal de Homo sapiens ; cadena pesada gamma1 (1-447) [Homo sapiens VH (IGHV3-23*01 (91.80%) -(IGHD)-IGHJ3*02) [8.8.11] (1- 118) -IGHG1*01, G1m17,1 (CH1 (119-216), bisagra (217- 231), CH2 T85.3>A (300) (232-341), CH3 (342-446), CHS K2>del (447)) (119-447)], (221-215')-disulfuro con la cadena ligera kappa (1'-215') [Homo sapiens V-KAPPA (IGKV3-11*01 (96.80%) -IGKJ2*01) [6.3.10] (1'-108') - IGKC*01, Km3 (109'-215')]; dímero (227-227'':230-230'')- bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaEVQLLESGGG LVQPGGSLRL SCAASGFTFS AYEMKWVRQA PGKGLEWVSV 50 IGPSGGFTFY ADSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCATEG 100 DNDAFDIWGQ GTTVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY 150 FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI 200 CNVNHKPSNT KVDKKVEPKS CDKTHTCPPC PAPELLGGPS VFLFPPKPKD 250 TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYNSA 300 YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY 350 TLPPSRDELT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD 400 SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPG 447 Light chain / Chaîne légère / Cadena ligera DIQMTQSPAT LSLSPGERAT LSCRASQSVS SYLAWYQQKP GQAPRLLIYD 50 ASNRATGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCQQ RSNWPMYTFG 100 QGTKLEIKRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150 VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200 GLSSPVTKSF NRGEC 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 145-201 262-322 368-426 22''-96'' 145''-201'' 262''-322'' 368''-426'' Intra-L (C23-C104) 23'-88' 135'-195' 23'''-88''' 135'''-195''' Inter-H-L (h 5-CL 126) 221-215' 221''-215''' Inter-H-H (h 11, h 14) 227-227'' 230-230'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 298, 298'' but no glycosylation owing to / mais pas de glycosylation dû à / pero ningún glicosilación debida a H CH2 T85.3>A (300, 300'') Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 140 osimertinibum osimertinib N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy- 5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin- 2-yl]amino}phenyl)prop-2-enamide osimertinib N-(2-{[2-(diméthylamino)éthyl](méthyl)amino}-4-méthoxy- 5-{[4-(1-méthyl-1H-indol-3-yl)pyrimidin- 2-yl]amino}phényl)prop-2-énamide osimertinib N-(2-{[2-(dimetilamino)etil](metil)amino}-4-metoxi-5-{[4-(1- metil-1H-indol-3-il)pirimidin-2-il]amino}fenil)prop-2-enamida C28H33N7O2 NH O N CH3 N CH3 CH3 OCH3 N H N NNH3C H2C pamrevlumabum # pamrevlumab immunoglobulin G1-kappa, anti-[Homo sapiens CTGF (connective tissue growth factor, CCN family member 2, CCN2, hypertrophic chondrocyte-specific protein 24, HCS24, insulin-like growth factor-binding protein 8, IGFBP- 8)], Homo sapiens monoclonal antibody; gamma1 heavy chain (1-449) [Homo sapiens VH (IGHV3- 48*03 (84.70%) -(IGHD)-IGHJ4*01) [8.7.14] (1-120) - IGHG1*03, G1m3 (CH1 (121-218), hinge (219-233), CH2 (234-343), CH3 (344-448), CHS K2>del (449)) (121-449)], (223-214')-disulfide with kappa light chain (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (100.00%) -IGKJ2*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'-214')]; dimer(229- 229'':232-232'')-bisdisulfide pamrevlumab immunoglobuline G1-kappa, anti-[Homo sapiens CTGF (facteur de croissance du tissu conjonctif, membre 2 de la famille CCN, CCN2, protéine 24 spécifique de l’hypertrophie des chondrocytes, HCS24, protéine 8 liant le facteur de croissance analogue à l’insuline, IGFBP-8)], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-449) [Homo sapiens VH (IGHV3-48*03 (84.70%) -(IGHD)-IGHJ4*01) [8.7.14] (1- 120) -IGHG1*03, G1m3 (CH1 (121-218), charnière (219- 233), CH2 (234-343), CH3 (344-448), CHS K2>del (449)) (121-449)], (223-214')-disulfure avec la chaîne légère kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (100.00%) -IGKJ2*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'-214')]; dimère (229-229'':232-232'')-bisdisulfure WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 141 pamrevlumab inmunoglobulina G1-kappa, anti-[Homo sapiens CTGF (factor de crecimiento de tejido conjunctivo, miembro 2 de la familia CCN, CCN2, proteína 24 específica de la hipertrofia de condrocitos, HCS24, proteína 8 que ligada el factor de crecimiento análogo a la insulina, IGFBP-8)], Homo sapiens anticuerpo monoclonal; cadena pesada gamma1 (1-449) [Homo sapiens VH (IGHV3-48*03 (84.70%) -(IGHD)-IGHJ4*01) [8.7.14] (1- 120) -IGHG1*03, G1m3 (CH1 (121-218), bisagra (219- 233), CH2 (234-343), CH3 (344-448), CHS K2>del (449)) (121-449)], (223-214')-disulfuro con la cadena ligera kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (100.00%) -IGKJ2*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'-214')]; dímero (229-229'':232-232'')-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaEGQLVQSGGG LVHPGGSLRL SCAGSGFTFS SYGMHWVRQA PGKGLEWVSG 50 IGTGGGTYST DSVKGRFTIS RDNAKNSLYL QMNSLRAEDM AVYYCARGDY 100 YGSGSFFDCW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK 150 DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT 200 YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPELLGG PSVFLFPPKP 250 KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 300 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ 350 VYTLPPSREE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV 400 LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPG 449 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCRASQGIS SWLAWYQQKP EKAPKSLIYA 50 ASSLQSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ YNSYPPTFGQ 100 GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-95 147-203 264-324 370-428 22''-95'' 147''-203'' 264''-324'' 370''-428'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 223-214' 223''-214''' Inter-H-H (h 11, h 14) 229-229'' 232-232'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 300, 300'' Fucosylated complex bi-antennary CHO-type glycans/ glycanes de type CHO bi-antennaires complexes fucosylés/ glicanos de tipo CHO biantenarios complejos fucosilados Other post-translational modifications / Autres modifications post-traductionnelles / Otras modificaciones post-traduccionales H VH CDR3 C117 (109, 109''): cysteinylation with either Cys, Cys-Gly, glutathione, or no cysteinylation cystéinylation avec soit Cys, Cys-Gly, glutathion, ou absence de cystéinylation / cisteinilación con Cis, o Cis-Gli, o glutatión, o ausencia de cisteinilación pegcantratinibum pegcantratinib (5'R,9S,12R)-9-methyl-3'-[α-methylpoly(oxyethane- 1,2-diyl)]-2,3,11,12-tetrahydro-1H,9H-spiro[9,12- epoxydiindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4- i][1,6]benzodiazocine-10,5'-oxazolidine]-1,2',4'-trione pegcantratinib (5'R,9S,12R)-9-méthyl-3'-[α-méthylpoly(oxyéthane- 1,2-diyl)]-2,3,11,12-tétrahydro-1H,9H-spiro[9,12- époxydiindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4- i][1,6]benzodiazocine-10,5'-oxazolidine]-1,2',4'-trione pegcantratinib (5'R,9S,12R)-9-metil-3'-[α-metilpoli(oxietano-1,2-diil)]- 2,3,11,12-tetrahidro-1H,9H-espiro[9,12-epoxidiindolo[1,2,3- fg:3',2',1'-kl]pirrolo[3,4-i][1,6]benzodiazocina- 10,5'-oxazolidina]-1,2',4'-triona Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 142 C28H20N4O5[C2H4O]n H N NN O O H N O O O CH3 CH3 n O pemafibratum pemafibrate (2R)-2-[3-({(1,3-benzoxazol-2-yl)[3-(4-methoxyphenoxy) propyl]amino}methyl)phenoxy]butanoic acid pémafibrate acide (2R)-2-[3-({(1,3-benzoxazol-2-yl)[3-(4- méthoxyphénoxy)propyl]amino}méthyl)phénoxy] butanoïque pemafibrato ácido (2R)-2-[3-({(benzoxazol-2-il)[3-(4-metoxifenoxi) propil]amino}metil)fenoxi]butanoico C28H30N2O6 O CO2H N H CH3 O N O H3CO piclidenosonum piclidenoson 1-deoxy-1-(6-{[(3-iodophenyl)methyl]amino}-9H-purin-9-yl)- N-methyl-β-D-ribofuranuronamide piclidénoson 1-déoxy-1-(6-{[(3-iodophényl)méthyl]amino}-9H-purin-9-yl)- N-méthyl-β-D-ribofuranuronamide piclidenosón 1-desoxi-1-(6-{[(3-iodofenil)metil]amino}-9H-purin-9-il)- N-metil-β-D-ribofuranuronamida C18H19IN6O4 O H N N N N N NH OHOH O H3C I WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 143 plozalizumabum # plozalizumab immunoglobulin G1-kappa, anti-[Homo sapiens CCR2 (chemokine (C-C motif) receptor 2, C-C chemokine receptor 2, CC-CKR-2, CKR-2, monocyte chemoattractant protein 1 receptor, MCP-1-R, CD192)], humanized monoclonal antibody; gamma1 heavy chain (1-447) [humanized VH (Homo sapiens IGHV3-73*01 (86.90%) -(IGHD)-IGHJ1*01) [8.10.8] (1-117) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (118-215), hinge (216-230), CH2 L1.2>A (235), G1>A (237) (231-340), CH3 (341-445), CHS (446-447)) (118- 447)], (220-219')-disulfide with kappa light chain (1’-219’) [humanized V-KAPPA (Homo sapiens IGKV2-30*01 (90.00%) -IGKJ2*01) [11.3.9] (1'-112') -Homo sapiens IGKC*01 (113'-219')]; dimer (226-226":229-229")- bisdisulfide plozalizumab immunoglobuline G1-kappa, anti-[Homo sapiens CCR2 (récepteur 2 de chimiokine (C-C motif), récepteur 2 de chimiokine C-C, CC-CKR-2, CKR-2, récepteur de la protéine 1 chimio-attractive du monocyte, MCP-1-R, CD192)], anticorps monoclonal humanisé; chaîne lourde gamma1 (1-447) [VH humanisé (Homo sapiens IGHV3-73*01 (86.90%) -(IGHD)-IGHJ1*01) [8.10.8] (1-117) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (118-215), charnière (216-230), CH2 L1.2>A (235), G1>A (237) (231-340), CH3 (341-445), CHS (446-447)) (118- 447)], (220-219')-disulfure avec la chaîne légère kappa (1’- 219’) [V-KAPPA humanisé (Homo sapiens IGKV2-30*01 (90.00%) -IGKJ2*01) [11.3.9] (1'-112') -Homo sapiens IGKC*01 (113'-219')]; dimère (226-226":229-229")- bisdisulfure plozalizumab inmunoglobulina G1-kappa, anti-[Homo sapiens CCR2 (receptor 2 de quimiokina (C-C motif), receptor 2 de quimiokina C-C, CC-CKR-2, CKR-2, receptor de la proteína 1 quimioatrayente de monocitos, MCP-1-R, CD192)], anticuerpo monoclonal humanizado; cadena pesada gamma1 (1-447) [VH humanizada (Homo sapiens IGHV3-73*01 (86.90%) -(IGHD)-IGHJ1*01) [8.10.8] (1-117) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (118-215), bisagra (216-230), CH2 L1.2>A (235), G1>A (237) (231-340), CH3 (341-445), CHS (446-447)) (118- 447)], (220-219')-disulfuro con la cadena ligera kappa (1’- 219’) [V-KAPPA humanizado (Homo sapiens IGKV2-30*01 (90.00%) -IGKJ2*01) [11.3.9] (1'-112') -Homo sapiens IGKC*01 (113'-219')]; dímero (226-226":229-229")- bisdisulfuro Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 144 Heavy chain / Chaîne lourde / Cadena pesadaEVQLVESGGG LVKPGGSLRL SCAASGFTFS AYAMNWVRQA PGKGLEWVGR 50 IRTKNNNYAT YYADSVKDRF TISRDDSKNT LYLQMNSLKT EDTAVYYCTT 100 FYGNGVWGQG TLVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF 150 PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC 200 NVNHKPSNTK VDKKVEPKSC DKTHTCPPCP APELAGAPSV FLFPPKPKDT 250 LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY 300 RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT 350 LPPSRDELTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS 400 DGSFFLYSKL TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGK 447 Light chain / Chaîne légère / Cadena ligera DVVMTQSPLS LPVTLGQPAS ISCKSSQSLL DSDGKTFLNW FQQRPGQSPR 50 RLIYLVSKLD SGVPDRFSGS GSGTDFTLKI SRVEAEDVGV YYCWQGTHFP 100 YTFGQGTRLE IKRTVAAPSV FIFPPSDEQL KSGTASVVCL LNNFYPREAK 150 VQWKVDNALQ SGNSQESVTE QDSKDSTYSL SSTLTLSKAD YEKHKVYACE 200 VTHQGLSSPV TKSFNRGEC 219 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-98 144-200 261-321 367-425 22''-98'' 144''-200'' 261''-321'' 367''-425'' Intra-L (C23-C104) 23'-93' 139'-199' 23'''-93''' 139'''-199''' Inter-H-L (h 5-CL 126) 220-219' 220''-219''' Inter-H-H (h 11, h 14) 226-226'' 229-229'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 297, 297'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados ravidasvirum ravidasvir methyl N-[(2S)-1-{(2S)-2-[5-(6-{2-[(2S)-1-{(2S)-2- [(methoxycarbonyl)amino]-3-methylbutanoyl}pyrrolidin- 2-yl]-1H-imidazol-4-yl}naphthalen-2-yl)-1H-benzimidazol- 2-yl]pyrrolidin-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate ravidasvir N-[(2S)-1-{(2S)-2-[5-(6-{2-[(2S)-1-{(2S)-2- [(méthoxycarbonyl)amino]-3-méthylbutanoyl}pyrrolidin- 2-yl]-1H-imidazol-4-yl}naphtalén-2-yl)-1H-benzimidazol- 2-yl]pyrrolidin-1-yl}-3-méthyl-1-oxobutan-2-yl]carbamate de méthyle ravidasvir N-[(2S)-1-{(2S)-2-[5-(6-{2-[(2S)-1-{(2S)-2- [(metoxicarbonil)amino]-3-metilbutanoil}pirrolidin-2-il]- 1H-imidazol-4-il}naftalen-2-il)-1H-benzoimidazol- 2-il]pirrolidin-1-il}-3-metil-1-oxobutan-2-il]carbamato de metilo C42H50N8O6 N H N NH O O N O CH3 H N N H N O HN O O CH3 H H3C H3C H H CH3 CH3 WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 145 rinucumabum # rinucumab immunoglobulin G4-kappa, anti-[Homo sapiens PDGFRB (platelet-derived growth factor receptor beta subunit, PDGFR-1, CD140b)], human monoclonal antibody; gamma4 heavy chain (1-449) [Homo sapiens VH (IGHV4- 39*01 (92.90%) -(IGHD)-IGHJ5*01) [10.7.14] (1-122) - IGHG4*01 (CH1 (123-220), hinge S10>P (230) (221-232), CH2 (233-342), CH3 (343-447), CHS (448-449)) (123- 449)], (136-215')-disulfide with kappa light chain (1’-215’) [Homo sapiens (V-KAPPA (IGKV3-20*01 (91.70%) - IGKJ3*01) [7.3.9] (1'-108') -IGKC*01, Km3 (109'-215')]; dimer (228-228":231-231")-bisdisulfide rinucumab immunoglobuline G4-kappa, anti-[Homo sapiens PDGFRB (sous-unité bêta du récepteur du facteur de croissance dérivé des plaquettes, PDGFR-1, CD140b)], anticorps monoclonal humain; chaîne lourde gamma4 (1-449) [Homo sapiens VH (IGHV4-39*01 (92.90%) -(IGHD)-IGHJ5*01) [10.7.14] (1- 122) -IGHG4*01 (CH1 (123-220), charnière S10>P (230) (221-232), CH2 (233-342), CH3 (343-447), CHS (448-449) (123-449)], (136-215')-disulfure avec la chaîne légère kappa (1’-215’) [Homo sapiens (V-KAPPA (IGKV3-20*01 (91.70%) -IGKJ3*01) [7.3.9] (1'-108') -IGKC*01, Km3 (109'- 215')]; dimère (228-228":231-231")-bisdisulfure rinucumab inmunoglobulina G4-kappa, anti-[Homo sapiens PDGFRB (subunidad beta del receptor del factor de crecimiento derivado de plaquetas, PDGFR-1, CD140b)], anticuerpo monoclonal humano; cadena pesada gamma4 (1-449) [Homo sapiens VH (IGHV4-39*01 (92.90%) -(IGHD)-IGHJ5*01) [10.7.14] (1- 122) -IGHG4*01 (CH1 (123-220), bisagra S10>P (230) (221-232), CH2 (233-342), CH3 (343-447), CHS (448-449) (123-449)], (136-215')-disulfuro con la cadena ligera kappa (1’-215’) [Homo sapiens (V-KAPPA (IGKV3-20*01 (91.70%) -IGKJ3*01) [7.3.9] (1'-108') -IGKC*01, Km3 (109'- 215')]; dímero (228-228":231-231")-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQLQLQESGPG LVKPSETLSL TCTVSGGSIT SSSYYWGWIR QPPGKGLEWI 50 GSIYYRGSTN YNPSLKSRVT ISVDSSKNQF YLKVSSVTAV DTAVYYCARQ 100 NGAARPSWFD PWGQGTLVTV SSASTKGPSV FPLAPCSRST SESTAALGCL 150 VKDYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT 200 KTYTCNVDHK PSNTKVDKRV ESKYGPPCPP CPAPEFLGGP SVFLFPPKPK 250 DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY VDGVEVHNAK TKPREEQFNS 300 TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK AKGQPREPQV 350 YTLPPSQEEM TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL 400 DSDGSFFLYS RLTVDKSRWQ EGNVFSCSVM HEALHNHYTQ KSLSLSLGK 449 Light chain / Chaîne légère / Cadena ligera EIVLTQSPDT ISLSPGERAT LSCRASQSIS SIYLAWYQQK PGQAPRLLIY 50 GASSRVTGIP DRFSVSGSGT DFTLTISRLE PEDFAVYYCQ HYGISPFTFG 100 PGTKVDIRRT VAAPSVFIFP PSDEQLKSGT ASVVCLLNNF YPREAKVQWK 150 VDNALQSGNS QESVTEQDSK DSTYSLSSTL TLSKADYEKH KVYACEVTHQ 200 GLSSPVTKSF NRGEC 215 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-97 149-205 263-323 369-427 22''-97'' 149''-205'' 263''-323'' 369''-427'' Intra-L (C23-C104) 23'-89' 135'-195' 23'''-89''' 135'''-195''' Inter-H-L (CH1 10-CL 126) 136-215' 136''-215''' Inter-H-H (h 8, h 11) 228-228'' 231-231'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 299, 299'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados Other post-translational modifications / Autres modifications post-traductionnelles / Otras modificaciones post-traduccionales H CHS K2 C-terminal lysine clipping: 449, 449'' Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 146 risankizumabum # risankizumab immunoglobulin G1-kappa, anti-[Homo sapiens IL23A (interleukin 23 subunit alpha, IL-23A, IL23 subunit p19, IL23p19)], humanized monoclonal antibody; gamma1 heavy chain (1-449) [humanized VH (Homo sapiens IGHV1-69*02 (79.40%) -(IGHD)-IGHJ5*01) [8.8.13] (1-120) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (121-218), hinge (219-233), CH2 L1.3>A (237), L1.2>A (238) (234-343), CH3 (344-448), CHS K2>del (449)) (121- 449)], (223-214')-disulfide with kappa light chain (1’-214’) [humanized V-KAPPA (Homo sapiens IGKV1-27*01 (80.00%) -IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimer (229-229":232-232")- bisdisulfide risankizumab immunoglobuline G1-kappa, anti-[Homo sapiens IL23A (interleukine 23 sous-unité alpha, IL-23A, IL23 sous-unité p19, IL23p19)], anticorps monoclonal humanisé; chaîne lourde gamma1 (1-449) [VH humanisé (Homo sapiens IGHV1-69*02 (79.40%) -(IGHD)-IGHJ5*01) [8.8.13] (1-120) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (121-218), charnière (219-233), CH2 L1.3>A (237), L1.2>A (238) (234-343), CH3 (344-448), CHS K2>del (449)) (121- 449)], (223-214')-disulfure avec la chaîne légère kappa (1’- 214’) [V-KAPPA humanisé (Homo sapiens IGKV1-27*01 (80.00%) -IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimère (229-229":232-232")- bisdisulfure risankizumab inmunoglobulina G1-kappa, anti-[Homo sapiens IL23A (interleukina 23 subunidad alfa, IL-23A, IL23 subunidad p19, IL23p19)], anticuerpo monoclonal humanizado; cadena pesada gamma1 (1-449) [VH humanizado (Homo sapiens IGHV1-69*02 (79.40%) -(IGHD)-IGHJ5*01) [8.8.13] (1-120) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (121-218), bisagra (219-233), CH2 L1.3>A (237), L1.2>A (238) (234-343), CH3 (344-448), CHS K2>del (449)) (121- 449)], (223-214')-disulfuro con la cadena ligera kappa (1’- 214’) [V-KAPPA humanizado (Homo sapiens IGKV1-27*01 (80.00%) -IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dímero (229-229":232-232")- bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGSSVKV SCKASGYTFT DQTIHWMRQA PGQGLEWIGY 50 IYPRDDSPKY NENFKGKVTI TADKSTSTAY MELSSLRSED TAVYYCAIPD 100 RSGYAWFIYW GQGTLVTVSS ASTKGPSVFP LAPSSKSTSG GTAALGCLVK 150 DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT 200 YICNVNHKPS NTKVDKRVEP KSCDKTHTCP PCPAPEAAGG PSVFLFPPKP 250 KDTLMISRTP EVTCVVVDVS HEDPEVKFNW YVDGVEVHNA KTKPREEQYN 300 STYRVVSVLT VLHQDWLNGK EYKCKVSNKA LPAPIEKTIS KAKGQPREPQ 350 VYTLPPSREE MTKNQVSLTC LVKGFYPSDI AVEWESNGQP ENNYKTTPPV 400 LDSDGSFFLY SKLTVDKSRW QQGNVFSCSV MHEALHNHYT QKSLSLSPG 449 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT ITCKASRDVA IAVAWYQQKP GKVPKLLIYW 50 ASTRHTGVPS RFSGSGSRTD FTLTISSLQP EDVADYFCHQ YSSYPFTFGS 100 GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 147-203 264-324 370-428 22''-96'' 147''-203'' 264''-324'' 370''-428'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 223-214' 223''-214''' Inter-H-H (h 11, h 14) 229-229'' 232-232'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 300, 300'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 147 rivabazumabum pegolum # rivabazumab pegol immunoglobulin Fab' G1-kappa pegylated, anti- [Pseudomonas aeruginosa type III secretion system (TTSS) PcrV protein], pegylated humanized monoclonal antibody; gamma1 heavy chain fragment VH-(CH1-hinge) (1-238) [humanized VH (Homo sapiens IGHV3-30*06 (92.90%) - (IGHD)-IGHJ6*01) [8.8.17] (1-124) -Homo sapiens IGHG1*01 (CH1 (125-222), hinge C5>S (227) (223-237), CH2 (238)) (125-238)], noncovalently associated with kappa light chain (1’-214’) [humanized V-KAPPA (Homo sapiens IGKV1-5*01 (84.60%) -IGKJ2*01) [6.3.9] (1'-107') - Homo sapiens IGKC*01 C126>S (214') (108'-214')]; conjugated via a linker of the maleimide group (thioether bond with cysteinyl H h 11 (C233) and H h 14 (236)) to two linear chains of methoxy polyethylene glycol 30 (mPEG30). rivabazumab pégol immunoglobuline Fab' G1-kappa pégylé, anti-[protéine PcrV du système de sécrétion type III (TTSS) de Pseudomonas aeruginosa], anticorps monoclonal humanisé pégylé; fragment VH-(CH1-charnière) de la chaîne lourde gamma1 (1-238) [VH humanisé (Homo sapiens IGHV3-30*06 (92.90%) -(IGHD)-IGHJ6*01) [8.8.17] (1-124) -Homo sapiens IGHG1*01 (CH1 (125-222), charnière C5>S (227) (223-237), CH2 (238)) (125-238)], associé de manière non covalente avec la chaîne légère kappa (1’-214’) [V-KAPPA humanisé (Homo sapiens IGKV1-5*01 (84.60%) - IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01 C126>S (214') (108'-214')]; conjugué via un linker du groupe maléimide (liaison thioéther avec les cystéinyl H h 11 (C233) et H h 14 (C236)) à deux chaînes linéaires de méthoxy polyéthylène glycol 30 (mPEG30). rivabazumab pegol inmunoglobulina Fab' G1-kappa pegilada, anti-[proteína PcrV del sistema de secreción tipo III (TTSS) de Pseudomonas aeruginosa], anticuerpo monoclonal humanizado pegilado; fragmento VH-(CH1-bisagra) de la cadena ligera gamma1 (1-238) [VH humanizado (Homo sapiens IGHV3-30*06 (92.90%) -(IGHD)-IGHJ6*01) [8.8.117] (1-124) -Homo sapiens IGHG1*01 (CH1(125-222), bisagra C5>S (227) (223-237), CH2 (238)) (125-238)], asociado de modo no covalente con la cadena ligera kappa (1’-214’) [V-KAPPA humanizado (Homo sapiens IGKV1-5*01 (84.60%) - IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01 C126>S (214') (108'-214')]; conjugado mediante un espaciador del grupo maleimida (unión tioéter con los cisteinil H h 11 (C233) et H h 14 (C236)) con dos cadenas lineales de metoxi polietilen glicol 30 (mPEG30). Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 148 Heavy chain / Chaîne lourde / Cadena pesadaEVQLVESGGG VVQPGRSLRL SCAASGFTFS NYPMHWVRQA PGKGLEWVAV 50 ISYDGSEKWY ADSVKGRFTI SRDNSKNTLY LEMNSLRPED TAVYYCARNR 100 GDIYYDFTYA MDIWGQGTTV TVSSASTKGP SVFPLAPSSK STSGGTAALG 150 CLVKDYFPEP VTVSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL 200 GTQTYICNVN HKPSNTKVDK KVEPKSSDKT HTCPPCPA 238 Light chain / Chaîne légère / Cadena ligera DIQLTQSPST LSASVGDSVT ITCRASEGVD RWLAWYQQKP GRAPKLLIYD 50 ASTLQSGVPS RFSGSGSGTE FSLTISSLQP DDVATYYCQH FWGTPYTFGQ 100 GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGES 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 151-207 Intra-L (C23-C104) 23'-88' 134'-194' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación None Pegylation site / Site de pegylation / Posiciones de pegilación H hinge h 11, h 14 C233, C236 ronopterinum ronopterin (1R,2S)-1-[(6RS)-2,4-diamino-5,6,7,8-tetrahydropteridin- 6-yl]propane-1,2-diol ronoptérine (1R,2S)-1-[(6RS)-2,4-diamino-5,6,7,8-tétrahydroptéridin- 6-yl]propane-1,2-diol ronopterina (1R,2S)-1-[(6RS)-2,4-diamino-5,6,7,8-tetrahidropteridin- 6-il]propano-1,2-diol C9H16N6O2 N N N H H N CH3 OHH HO H H H2N NH2 and epimer at C* et l'épimère en C* y el epímero al C* * rovalpituzumabum # rovalpituzumab immunoglobulin G1-kappa, anti-[Homo sapiens DLL3 (delta-like ligand 3)], humanized monoclonal antibody; gamma1 heavy chain (1-447) [humanized VH (Homo sapiens IGHV1-18*01 (86.700%) -(IGHD)-IGHJ4*01) [8.8.11] (1-118) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (119-216), hinge (217-231), CH2 (232-341), CH3 (342- 446), CHS K2>del (447)) (119-447)], (221-214')-disulfide with kappa light chain (1’-214’) [humanized V-KAPPA (Homo sapiens IGKV3-15*01 (87.40%) -IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimer (227-227":230-230")-bisdisulfide WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 149 rovalpituzumab immunoglobuline G1-kappa, anti-[Homo sapiens DLL3 (delta-like ligand 3)], anticorps monoclonal humanisé; chaîne lourde gamma1 (1-447) [VH humanisé (Homo sapiens IGHV1-18*01 (86.700%) -(IGHD)-IGHJ4*01) [8.8.11] (1-118) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (119-216), charnière (217-231), CH2 (232-341), CH3 (342- 446), CHS K2>del (447)) (119-447)], (221-214')-disulfure avec la chaîne légère kappa (1’-214’) [V-KAPPA humanisé (Homo sapiens IGKV3-15*01 (87.40%) -IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimère (227-227":230-230")-bisdisulfure rovalpituzumab inmunoglobulina G1-kappa, anti-[Homo sapiens DLL3 (delta-like ligando 3)], anticuerpo monoclonal humanizado; cadena pesada gamma1 (1-447) [VH humanizado (Homo sapiens IGHV1-18*01 (86.700%) -(IGHD)-IGHJ4*01) [8.8.11] (1-118) -Homo sapiens IGHG1*01 G1m17,1 (CH1 (119-216), bisagra(217-231), CH2 (232-341), CH3 (342- 446), CHS K2>del (447)) (119-447)], (221-214')-disulfuro con la cadena ligera kappa (1’-214’) [V-KAPPA humanizado (Homo sapiens IGKV3-15*01 (87.40%) - IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dímero (227-227":230-230")-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQVQLVQSGAE VKKPGASVKV SCKASGYTFT NYGMNWVRQA PGQGLEWMGW 50 INTYTGEPTY ADDFKGRVTM TTDTSTSTAY MELRSLRSDD TAVYYCARIG 100 DSSPSDYWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY 150 FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI 200 CNVNHKPSNT KVDKKVEPKS CDKTHTCPPC PAPELLGGPS VFLFPPKPKD 250 TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYNST 300 YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY 350 TLPPSRDELT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD 400 SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPG 447 Light chain / Chaîne légère / Cadena ligera EIVMTQSPAT LSVSPGERAT LSCKASQSVS NDVVWYQQKP GQAPRLLIYY 50 ASNRYTGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQQ DYTSPWTFGQ 100 GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 145-201 262-322 368-426 22''-96'' 145''-201'' 262''-322'' 368''-426'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 221-214' 221''-214''' Inter-H-H (h 11, h 14) 227-227'' 230-230'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 298, 298'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 150 rovalpituzumabum tesirinum # rovalpituzumab tesirine immunoglobulin G1-kappa, anti-[Homo sapiens DLL3 (delta-like ligand 3)], humanized monoclonal antibody conjugated to the pyrrolobenzodiazepine (PBD) dimer SCX; gamma1 heavy chain (1-447) [humanized VH (Homo sapiens IGHV1-18*01 (86.700%) -(IGHD)-IGHJ4*01) [8.8.11] (1-118) -Homo sapiens IGHG1*01 G1m17,1 (CH1 (119-216), hinge (217-231), CH2 (232-341), CH3 (342- 446), CHS K2>del (447)) (119-447)], (221-214')-disulfide with kappa light chain (1’-214’) [humanized V-KAPPA (Homo sapiens IGKV3-15*01 (87.40%) -IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimer (227-227":230-230")-bisdisulfide; conjugated, on an average of 2 cysteines, to the pyrrolobenzodiazepine (PBD) dimer SCX, via a cleavable (valine-alanine dipeptide as cathepsine B cleavage site) maleimide type linker containing a spacer PEG (n=8) rovalpituzumab tésirine immunoglobuline G1-kappa, anti-[Homo sapiens DLL3 (delta-like ligand 3)], anticorps monoclonal humanisé conjugué au dimère de pyrrolobenzodiazépine (PDB) SCX; chaîne lourde gamma1 (1-447) [VH humanisé (Homo sapiens IGHV1-18*01 (86.700%) -(IGHD)-IGHJ4*01) [8.8.11] (1-118) -Homo sapiens IGHG1*01 G1m17,1 (CH1 (119-216), charnière (217-231), CH2 (232-341), CH3 (342- 446), CHS K2>del (447)) (119-447)], (221-214')-disulfure avec la chaîne légère kappa (1’-214’) [V-KAPPA humanisé (Homo sapiens IGKV3-15*01 (87.40%) -IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimère (227-227":230-230")-bisdisulfure; conjugué, sur 2 cystéines en moyenne, au dimère de pyrrolobenzodiazépine (PBD) SCX, via un linker clivable (dipeptide valine-alanine clivable par la cathepsine B) de type maléimide et comprenant un espaceur PEG (n=8) rovalpituzumab tesirina inmunoglobulina G1-kappa, anti-[Homo sapiens DLL3 (delta-like ligando 3)], anticuerpo monoclonal humanizado conjugado con el dímero de pirrolobenzodiazepina (PDB) SCX; cadena pesada gamma1 (1-447) [VH humanizado (Homo sapiens IGHV1-18*01 (86.700%) -(IGHD)-IGHJ4*01) [8.8.11] (1-118) -Homo sapiens IGHG1*01 G1m17,1 (CH1 (119-216), bisagra(217-231), CH2 (232-341), CH3 (342- 446), CHS K2>del (447)) (119-447)], (221-214')-disulfuro con la cadena ligera kappa (1’-214’) [V-KAPPA humanizado (Homo sapiens IGKV3-15*01 (87.40%) - IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dímero (227-227":230-230")-bisdisulfuro; conjugado, en una media de 2 cisteinas, al dímero de pirrolobenzodiazepina (PBD) SCX, mediante un espaciador escindible (dipéptido valina-alanina escindible por la catepsina B) de tipo maleimida que comprende un espaciador PEG (n=8) WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 151 N CH3 NO O H3CO O N H3C N O OCH3 OH H H and epimer at C* et l'épimère en C* y el epímero al C* OO N H AlaValO HN N O O O H H S H2N CO2H H O 8 C 214',214''' ; 221,221'' ; 227,227'' ; 230,230'' "S-tesirine Cysteine" Heavy chain / Chaîne lourde / Cadena pesada QVQLVQSGAE VKKPGASVKV SCKASGYTFT NYGMNWVRQA PGQGLEWMGW 50 INTYTGEPTY ADDFKGRVTM TTDTSTSTAY MELRSLRSDD TAVYYCARIG 100 DSSPSDYWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY 150 FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI 200 CNVNHKPSNT KVDKKVEPKS CDKTHTCPPC PAPELLGGPS VFLFPPKPKD 250 TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYNST 300 YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY 350 TLPPSRDELT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD 400 SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPG 447 Light chain / Chaîne légère / Cadena ligera EIVMTQSPAT LSVSPGERAT LSCKASQSVS NDVVWYQQKP GQAPRLLIYY 50 ASNRYTGIPA RFSGSGSGTE FTLTISSLQS EDFAVYYCQQ DYTSPWTFGQ 100 GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 145-201 262-322 368-426 22''-96'' 145''-201'' 262''-322'' 368''-426'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126)* 221-214' 221''-214''' Inter-H-H (h 11, h 14)* 227-227'' 230-230'' *One or two of the inter-chain disulfide bridges are not present, an average of 2 cysteinyl being conjugated each via a thioether bond to a drug linker. *Un ou deux des ponts disulfures inter-chaînes ne sont pas présents, 2 cystéinyl en moyenne étant chacun conjugué via une liaison thioéther à un linker-principe actif. *Faltan uno o dos puentes disulfuro inter-catenarios, una media de 2 cisteinil está conjugada a conectores de principio activo. N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 298, 298'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados Potential modified residues / Résidus modifies potentiels / Restos modificados potenciales sacituzumabum govitecanum # sacituzumab govitecan immunoglobulin G1-kappa, anti-[Homo sapiens TACSTD2 (tumor-associated calcium signal transducer 2, membrane component chromosome 1 surface marker 1, M1S1, gastrointestinal tumor-associated antigen GA7331, pancreatic carcinoma marker protein GA733-1, epithelial glycoprotein-1, EGP-1, trophoblast antigen-2, cell surface glycoprotein Trop-2, TROP2)], humanized monoclonal antibody conjugated to 7-ethyl-10-hydroxycamptothecin (SN-38), active metabolite of irinotecan; gamma1 heavy chain (1-451) [humanized VH (Homo sapiens IGHV7-4-1*02 (85.70%) -(IGHD)-IGHJ2*01) [8.8.14] (1-121) -Homo sapiens IGHG1*03, Gm3 (CH1 (122-219), hinge (220-234), CH2 (235-344), CH3 (345- 449), CHS (450-451)) (122-451)], (224-214')-disulfide with kappa light chain (1’-214’) [humanized V-KAPPA (Homo sapiens IGKV1-9*01 (82.20%) -IGKJ4*01) [6.3.9] (1'-107') - Homo sapiens IGKC*01, Km3 (108'-214')]; dimer (230- 230":233-233")-bisdisulfide; conjugated, on an average of 6 cysteinyl, to 7-ethyl-10-hydroxycamptothecin (SN-38), active metabolite of irinotecan (CPT-11, camptothecin- 11),via a maleimide-type cleavable linker (carbonate group, self-immolative 4-aminobenzyl alcohol and cathepsine-B-cleavable dipeptide Phe-Lys) and containing a triazoline group and a spacer PEG (n=8). Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 152 sacituzumab govitecan immunoglobuline G1-kappa, anti-[Homo sapiens TACSTD2 (transducteur 2 de signaux calciques associé aux tumeurs, composant membranaire du chromosome 1 marqueur de surface 1, M1S1, antigène GA7331 associé aux tumeurs gastrointestinales, protéine GA733-1 marqueur de carcinomes pancréatiques, glycoprotéine épithéliale 1, EGP-1, antigène 2 du trophoblaste, glycoprotéine Trop-2 à la surface des cellules, TROP2)], anticorps monoclonal humanisé conjugué à la 7-éthyl- 10-hydroxycamptothécine (SN-38), métabolite actif de l’irinotécan; chaîne lourde gamma1 (1-451) [VH humanisé (Homo sapiens IGHV7-4-1*02 (85.70%) -(IGHD)-IGHJ2*01) [8.8.14] (1-121) -Homo sapiens IGHG1*03, Gm3 (CH1 (122-219), charnière (220-234), CH2 (235-344), CH3 (345- 449), CHS (450-451)) (122-451)], (224-214')-disulfure avec la chaîne légère kappa (1’-214’) [V-KAPPA humanisé (Homo sapiens IGKV1-9*01 (82.20%) -IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimère (230-230":233-233")-bisdisulfure; conjugué, sur 6 cystéinyl en moyenne, à la 7-éthyl-10- hydroxycamptothécine (SN-38), métabolite actif de l’irinotécan (CPT-11, camptothécine-11),via un linker de type maléimide, clivable (liaison carbonate et 4-aminobenzyl alcool et dipeptide Phe-Lys clivable par la cathepsine B) et comprenant un groupe triazoline et un espaceur PEG (n=8) sacituzumab govitecán inmunoglobulina G1-kappa, anti-[Homo sapiens TACSTD2 (transductor 2 de señales de calcio asociado a los tumores, componente de membrana del cromosoma 1 marcador de superficie 1, M1S1, antígeno GA7331 asociado a tumores gastrointestinales, proteína GA733-1 marcador de carcinomes pancreáticos glicoproteína epitelial 1, EGP-1, antígeno 2 de trofoblasto, glicoproteína Trop-2 de la superficie celular, TROP2)], anticuerpo monoclonal humanizado conjugado con la 7-etil- 10-hidroxicamptotecina (SN-38), metabolito activo del irinotecán; cadena pesada gamma1 (1-451) [VH humanizado (Homo sapiens IGHV7-4-1*02 (85.70%) -(IGHD)-IGHJ2*01) [8.8.14] (1-121) -Homo sapiens IGHG1*03, Gm3 (CH1 (122-219), bisagra(220-234), CH2 (235-344), CH3 (345- 449), CHS (450-451)) (122-451)], (224-214')-disulfuro con la cadena ligera kappa (1’-214’) [V-KAPPA humanizado (Homo sapiens IGKV1-9*01 (82.20%) -IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dímero (230-230":233-233")-bisdisulfuro; conjugado, en una media de 6 restos cisteinil, con la 7-etil- 10-hidroxicamptotecina (SN-38), metabolito activo del irinotecán (CPT-11, camptotecina-11), mediante un espaciadorde tipo maleimida, escindible (enlace carbonato y 4-aminobencil alcohol y dipéptido Phe-Lys escindible por catepsina B) y que comprende un grupo triazolina y un espaciador PEG (n=8). WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 153 ON N O O HO CH3 O CH3 OO N H Lys O O H N O O NO O H2N CO2H H NN N NH S 8 O C* 214'-214'''-224-224''- 230-230''-233-233'' * an average of 6 are substituted * en moyenne, 6 sont substitués * una media de 6 está sustituída Heavy chain / Chaîne lourde / Cadena pesada QVQLQQSGSE LKKPGASVKV SCKASGYTFT NYGMNWVKQA PGQGLKWMGW 50 INTYTGEPTY TDDFKGRFAF SLDTSVSTAY LQISSLKADD TAVYFCARGG 100 FGSSYWYFDV WGQGSLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV 150 KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ 200 TYICNVNHKP SNTKVDKRVE PKSCDKTHTC PPCPAPELLG GPSVFLFPPK 250 PKDTLMISRT PEVTCVVVDV SHEDPEVKFN WYVDGVEVHN AKTKPREEQY 300 NSTYRVVSVL TVLHQDWLNG KEYKCKVSNK ALPAPIEKTI SKAKGQPREP 350 QVYTLPPSRE EMTKNQVSLT CLVKGFYPSD IAVEWESNGQ PENNYKTTPP 400 VLDSDGSFFL YSKLTVDKSR WQQGNVFSCS VMHEALHNHY TQKSLSLSPG 450 K 451 Light chain / Chaîne légère / Cadena ligera DIQLTQSPSS LSASVGDRVS ITCKASQDVS IAVAWYQQKP GKAPKLLIYS 50 ASYRYTGVPD RFSGSGSGTD FTLTISSLQP EDFAVYYCQQ HYITPLTFGA 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 148-204 265-325 371-429 22''-96'' 148''-204'' 265''-325'' 371''-429'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) * 224-214' 224''-214''' Inter-H-H (h 11, h 14) * 230-230'' 233-233'' *Three of the inter-chain disulfide bridges are not present, an average of 6 cysteinyl being conjugated each via a thioether bond to a drug linker. *Trois des ponts disulfures inter-chaînes ne sont pas présents, 6 cystéinyl en moyenne étant chacun conjugué via une liaison thioéther à un linker-principe actif. *Faltan tres puentes disulfuro inter-catenarios, una media de 6 cisteinil está conjugada a conectores de principio activo. N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 301, 301'' Fucosylated complex bi-antennary Sp2/0-type glycans / glycanes de type Sp2/0 bi-antennaires complexes fucosylés / glicanos de tipo Sp2/0 biantenarios complejos fucosilados Potential modified residues / Résidus modifiés potentiels / Restos modificados potenciales sacubitrilatum sacubitrilat (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-(3-carboxypropanamido)- 2-methylpentanoic acid sacubitrilate acide (2R,4S)-5-([1,1'-biphényl]-4-yl)- 4-(3-carboxypropanamido)-2-méthylpentanoïque sacubitrilat ácido (2R,4S)-5-([1,1'-bifenil]-4-il)- 4-(3-carboxipropanamido)-2-metilpentanoico C22H25NO5 O H NHO2C CO2H HH3C H Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 154 selonsertibum selonsertib 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl- N-{6-[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]pyridin- 2-yl}benzamide sélonsertib 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-méthyl- N-{6-[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]pyridin- 2-yl}benzamide selonsertib 5-(4-ciclopropil-1H-imidazol-1-il)-2-fluoro-4-metil-N-{6-[4- (propan-2-il)-4H-1,2,4-triazol-3-il]piridin-2-yl}benzamida C24H24FN7O N H N O FH3C NN N N N H3C CH3 solnatidum solnatide L-cysteinylglycyl-[human tumor necrosis factor, membrane form-(178-191)-peptidyl]-L-cysteine, cyclic (1→17)-disulfide or L-cysteinylglycyl-[human tumor necrosis factor, soluble form-(102-115)-peptidyl]-L-cysteine, cyclic (1→17)-disulfide solnatide (1→17)-disulfure cyclique de L-cystéinylglycyl-[forme membranaire du facteur de nécrose tumorale humain- (178-191)-peptidyl]-L-cystéine ou (1→17)-disulfure cyclique de L-cystéinylglycyl-[forme soluble du facteur de nécrose tumorale humain-(102-115)- peptidyl]-L-cystéine solnatida (1→17)-disulfuro cíclico de L-cisteinilglicil-[forma de membrana del factor de necrosis tumoral humano-(178- 191)-peptidil]-L-cisteina o (1→17)-disulfuro cíclico de L-cisteinilglicil-[forma soluble del factor de necrosis tumoral humano-(102-115)-peptidil]- L-cisteina C82H119N23O27S2 H Cys Gly Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys Pro Trp Tyr Cys 10 17 OH WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 155 sparsentanum sparsentan 4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]- N-(4,5-dimethyl-1,2-oxazol-3-yl)-2'-(ethoxymethyl)[1,1'- biphenyl]-2-sulfonamide sparsentan 4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-én-3-yl)méthyl]- N-(4,5-diméthyl-1,2-oxazol-3-yl)-2'-(éthoxyméthyl)[1,1'- biphényle]-2-sulfonamide esparsentán 4'-[(2-butil-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-il)metil]- N-(4,5-dimetil-1,2-oxazol-3-il)-2'-(etoximetil)[1,1'-bifenilo]- 2-sulfonamida C32H40N4O5S S H NO O N O CH3 CH3NN OH3C O H3C tavilermidum tavilermide 3-{(4S,7S,10S)-7-(4-aminobutyl)- 4-[(carboxymethyl)carbamoyl]-14-nitro-6,9,12-trioxo- 3,4,5,6,7,8,9,10,11,12-decahydro-2H-1,5,8,11- benzoxatriazacyclotetradecin-10-yl}propanoic acid tavilermide acide 3-{(4S,7S,10S)-7-(4-aminobutyl)- 4-[(carboxyméthyl)carbamoyl]-14-nitro-6,9,12-trioxo- 3,4,5,6,7,8,9,10,11,12-décahydro-2H-1,5,8,11- benzoxatriazacyclotétradécin-10-yl}propanoïque tavilermida ácido 3-{(4S,7S,10S)-7-(4-aminobutil)- 4-[(carboximetil)carbamoil]-14-nitro-6,9,12-trioxo- 3,4,5,6,7,8,9,10,11,12-decahidro-2H-1,5,8,11- benzoxatriazaciclotetradecin-10-il}propanoico C24H32N6O11 O O2N HN H N O HN O H N CO2H O O H H HO2C NH2 H tegoprazanum tegoprazan 7-{[(4S)-5,7-difluoro-3,4-dihydro-2H-1-benzopyran- 4-yl]oxy}-N,N,2-trimethyl-1H-benzimidazole-5-carboxamide tégoprazan 7-{[(4S)-5,7-difluoro-3,4-dihydro-2H-1-benzopyran- 4-yl]oxy}-N,N,2-triméthyl-1H-benzimidazole-5-carboxamide Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 156 tegoprazán 7-{[(4S)-5,7-difluoro-3,4-dihidro-2H-1-benzopiran-4-il]oxi}- N,N,2-trimetil-1H-benzoimidazol-5-carboxamida C20H19F2N3O3 N HN H3C N CH3 CH3 O O H O F F tesevatinibum tesevatinib N-(3,4-dichloro-2-fluorophenyl)-6-methoxy- 7-{[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol- 5-yl]methoxy}quinazolin-4-amine tésévatinib N-(3,4-dichloro-2-fluorophényl)-6-méthoxy- 7-{[(3aR,5r,6aS)-2-méthyloctahydrocyclopenta[c]pyrrol- 5-yl]méthoxy}quinazolin-4-amine tesevatinib N-(3,4-dicloro-2-fluorofenil)- 7-{[(3aR,5r,6aS)-2- metiloctahidrociclopenta[c]pirrol-5-il]metoxi}-6-metoxi- quinazolin-4-amina C24H25Cl2FN4O2 N N HN F O Cl Cl H3CO N H H3C H H tezepelumabum # tezepelumab immunoglobulin G2-lambda, anti-[Homo sapiens TSLP (thymic stromal lymphopoietin)], Homo sapiens monoclonal antibody; gamma2 heavy chain (1-448) [Homo sapiens VH (IGHV3- 33*01 (93.90%) -(IGHD)-IGHJ3*02) [8.8.15] (1-122) - IGHG2*01, G2m.. (CH1 (123-220), hinge (221-232), CH2 (233-341), CH3 (342-446), CHS (447-448)) (123-448)], (136-213')-disulfide with lambda light chain (1'-214’) [Homo sapiens V-LAMBDA (IGLV3-21*02 (96.90%) -IGLJ2*01) [6.3.11] (1'-108') -IGLC2*01 (109'-214')]; dimer (224- 224'':225-225'':228-228'':231-231'')-tetrakisdisulfide WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 157 tézépelumab immunoglobuline G2-lambda, anti-[Homo sapiens TSLP (lymphopoïétine stromale thymique)], Homo sapiens anticorps monoclonal; chaîne lourde gamma2 (1-448) [Homo sapiens VH (IGHV3-33*01 (93.90%) -(IGHD)-IGHJ3*02) [8.8.15] (1- 122) -IGHG2*01, G2m.. (CH1 (123-220), charnière (221- 232), CH2 (233-341), CH3 (342-446), CHS (447-448)) (123-448)], (136-213')-disulfure avec la chaîne légère lambda (1'-214’) [Homo sapiens V-LAMBDA (IGLV3-21*02 (96.90%) -IGLJ2*01) [6.3.11] (1'-108') -IGLC2*01 (109'- 214')]; dimère (224-224'':225-225'':228-228'':231-231'')- tétrakisdisulfure tezepelumab inmunoglobulina G2-lambda, anti-[Homo sapiens TSLP (linfopoyetina estromal tímica)], Homo sapiens anticuerpo monoclonal; cadena pesada gamma2 (1-448) [Homo sapiens VH (IGHV3-33*01 (93.90%) -(IGHD)-IGHJ3*02) [8.8.15] (1- 122) -IGHG2*01, G2m.. (CH1 (123-220),bisagra (221-232), CH2 (233-341), CH3 (342-446), CHS (447-448)) (123- 448)], (136-213')-disulfuro con la cadena ligera lambda (1'- 214’) [Homo sapiens V-LAMBDA (IGLV3-21*02 (96.90%) - IGLJ2*01) [6.3.11] (1'-108') -IGLC2*01 (109'-214')]; dímero (224-224'':225-225'':228-228'':231-231'')-tetrakisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaQMQLVESGGG VVQPGRSLRL SCAASGFTFR TYGMHWVRQA PGKGLEWVAV 50 IWYDGSNKHY ADSVKGRFTI TRDNSKNTLN LQMNSLRAED TAVYYCARAP 100 QWELVHEAFD IWGQGTMVTV SSASTKGPSV FPLAPCSRST SESTAALGCL 150 VKDYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSNFGT 200 QTYTCNVDHK PSNTKVDKTV ERKCCVECPP CPAPPVAGPS VFLFPPKPKD 250 TLMISRTPEV TCVVVDVSHE DPEVQFNWYV DGVEVHNAKT KPREEQFNST 300 FRVVSVLTVV HQDWLNGKEY KCKVSNKGLP APIEKTISKT KGQPREPQVY 350 TLPPSREEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPMLD 400 SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK 448 Light chain / Chaîne légère / Cadena ligera SYVLTQPPSV SVAPGQTARI TCGGNNLGSK SVHWYQQKPG QAPVLVVYDD 50 SDRPSWIPER FSGSNSGNTA TLTISRGEAG DEADYYCQVW DSSSDHVVFG 100 GGTKLTVLGQ PKAAPSVTLF PPSSEELQAN KATLVCLISD FYPGAVTVAW 150 KADSSPVKAG VETTTPSKQS NNKYAASSYL SLTPEQWKSH RSYSCQVTHE 200 GSTVEKTVAP TECS 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 149-205 262-322 368-426 22''-96'' 149''-205'' 262''-322'' 368''-426'' Intra-L (C23-C104) 22'-87' 136'-195' 22'''-87''' 136'''-195''' Inter-H-L (CH1 10-CL 126) 136-213' 136''-213''' Inter-H-H (h 4, h 5, h 8, h 11) 224-224'' 225-225'' 228-228'' 231-231'' *In addition to the isoform A, isoform A/B characterized by an inter-H-H (h 4 - CH1 10) 224-136'' and an inter-H-L (h 4- CL 126) 224''-213''', instead of the inter-H-H (h 4 - h 4) 224-224'' and of one of the two inter-H-L (CH1 10-CL 126) 136''-213'''. *En plus de l'isoforme A, isoforme A/B caractérisée par un inter-H-H (h 4 - CH1 10) 224-136'' et un inter-H-L (h 4- CL 126) 224''-213''', au lieu de l'inter-H-H (h 4 - h 4) 224-224'' et de l'un des deux inter-H-L (CH1 10-CL 126) 136''-213'''. * además de la isoforma A, isoforma A/B caracterizado por un inter-H-H (h 4 - CH1 10) 224-136'' y un inter-H-L (h 4- CL 126) 224''-213''', en lugar del inter-H-H (h 4 - h 4) 224-224'' y uno de los dos inter-H-L (CH1 10-CL 126) 136''-213'''. N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 298, 298'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de typeCHO bi-antennaires complexes fucosylés / glicanosde tipo CHO biantenarios complejos fucosilados tisotumabum # tisotumab immunoglobulin G1-kappa, anti-[Homo sapiens F3 (coagulation factor III (thromboplastin, tissue factor), CD142)], Homo sapiens monoclonal antibody; Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 158 gamma1 heavy chain (1-448) [Homo sapiens VH (IGHV3- 23*01 (93.90%) -(IGHD)-IGHJ5*01) [8.8.11] (1-118) - IGHG1*03, G1m3 (CH1 (119-216), hinge (217-231), CH2 (232-341), CH3 (342-446), CHS (447-448)) (119-448)], (221-214')-disulfide with kappa light chain (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (96.80%) -IGKJ2*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'-214')]; dimer (227- 227'':230-230'')-bisdisulfide tisotumab immunoglobuline G1-kappa, anti-[Homo sapiens F3 (facteur de coagulation III (thromboplastine, facteur tissulaire), CD142)], Homo sapiens anticorps monoclonal; chaîne lourde gamma1 (1-448) [Homo sapiens VH (IGHV3-23*01 (93.90%) -(IGHD)-IGHJ5*01) [8.8.11] (1- 118) -IGHG1*03, G1m3 (CH1 (119-216), charnière (217- 231), CH2 (232-341), CH3 (342-446), CHS (447-448)) (119-448)], (221-214')-disulfure avec la chaîne légère kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (96.80%) -IGKJ2*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'- 214')]; dimère (227-227'':230-230'')-bisdisulfure tisotumab inmunoglobulina G1-kappa, anti-[Homo sapiens F3 (factor de coagulación III (tromboplastina, factor tisular), CD142)], Homo sapiens anticuerpo monoclonal ; cadena pesada gamma1 (1-448) [Homo sapiens VH (IGHV3-23*01 (93.90%) -(IGHD)-IGHJ5*01) [8.8.11] (1- 118) -IGHG1*03, G1m3 (CH1 (119-216), bisagra (217- 231), CH2 (232-341), CH3 (342-446), CHS (447-448)) (119-448)], (221-214')-disulfuro con la cadena ligera kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (96.80%) -IGKJ2*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'- 214')]; dímero (227-227'':230-230'')-bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaEVQLLESGGG LVQPGGSLRL SCAASGFTFS NYAMSWVRQA PGKGLEWVSS 50 ISGSGDYTYY TDSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARSP 100 WGYYLDSWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY 150 FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI 200 CNVNHKPSNT KVDKRVEPKS CDKTHTCPPC PAPELLGGPS VFLFPPKPKD 250 TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYNST 300 YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY 350 TLPPSREEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD 400 SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK 448 Light chain / Chaîne légère / Cadena ligera DIQMTQSPPS LSASAGDRVT ITCRASQGIS SRLAWYQQKP EKAPKSLIYA 50 ASSLQSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ YNSYPYTFGQ 100 GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 145-201 262-322 368-426 22''-96'' 145''-201'' 262''-322'' 368''-426'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 221-214' 221''-214''' Inter-H-H (h 11, h 14) 227-227'' 230-230'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 298, 298'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 159 tisotumabum vedotinum # tisotumab vedotin immunoglobulin G1-kappa, anti-[Homo sapiens F3 (coagulation factor III (thromboplastin, tissue factor), CD142)], Homo sapiens monoclonal antibody conjugated to auristatin E; gamma1 heavy chain (1-448) [Homo sapiens VH (IGHV3- 23*01 (93.90%) -(IGHD)-IGHJ5*01) [8.8.11] (1-118) - IGHG1*03, G1m3 (CH1 (119-216), hinge (217-231), CH2 (232-341), CH3 (342-446), CHS (447-448)) (119-448)], (221-214')-disulfide with kappa light chain (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (96.80%) -IGKJ2*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'-214')]; dimer (227- 227'':230-230'')-bisdisulfide; conjugated, on an average of 3 to 4 cysteinyl, to monomethylauristatin E (MMAE), via a cleavable maleimidocaproyl-valyl-citrullinyl- p-aminobenzyloxycarbonyl (mc-val-cit-PABC) type linker For the vedotin part, please refer to the document “INN for pharmaceutical substances: Names for radicals, groups and others”*. tisotumab védotine immunoglobuline G1-kappa, anti-[Homo sapiens F3 (facteur de coagulation III (thromboplastine, facteur tissulaire), CD142)], Homo sapiens anticorps monoclonal conjugué à l’auristatine E; chaîne lourde gamma1 (1-448) [Homo sapiens VH (IGHV3-23*01 (93.90%) -(IGHD)-IGHJ5*01) [8.8.11] (1- 118) -IGHG1*03, G1m3 (CH1 (119-216), charnière (217- 231), CH2 (232-341), CH3 (342-446), CHS (447-448)) (119-448)], (221-214')-disulfure avec la chaîne légère kappa (1'-214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (96.80%) -IGKJ2*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'- 214')]; dimère (227-227'':230-230'')-bisdisulfure; conjugué, sur 3 à 4 cystéinyl en moyenne, au monométhylauristatine E (MMAE), via un linker clivable de type maléimidocaproyl- valyl-citrullinyl-p-aminobenzyloxycarbonyl (mc-val-cit- PABC) Pour la partie védotine, veuillez-vous référer au document “INN for pharmaceutical substances: Names for radicals, groups and others”*. tisotumab vedotina inmunoglobulina G1-kappa, anti-[Homo sapiens F3 (factor de coagulación III (tromboplastina, factor tisular), CD142)], Homo sapiens anticuerpo monoclonal conjugado con la auristatina E; cadena pesada gamma1 (1-448) [Homo sapiens VH (IGHV3-23*01 (93.90%) -(IGHD)-IGHJ5*01) [8.8.11] (1- 118) -IGHG1*03, G1m3 (CH1 (119-216), bisagra(217-231), CH2 (232-341), CH3 (342-446), CHS (447-448)) (119- 448)], (221-214')-disulfuro con la cadena ligera kappa (1'- 214') [Homo sapiens V-KAPPA (IGKV1D-16*01 (96.80%) - IGKJ2*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'-214')]; dímero (227-227'':230-230'')-bisdisulfuro; conjugado, en 3 - 4 restos cisteinil por termino medio, con monometilauristatina E (MMAE), mediante un espaciador escindible de tipo maleimidocaproil-valil-citrulinil- p-aminobenciloxicarbonil (mc-val-cit-PABC) La fracción vedotina, la pueden encontrar en el documento “INN for pharmaceutical substances: Names for radicals, groups and others”*. Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 160 Heavy chain / Chaîne lourde / Cadena pesadaEVQLLESGGG LVQPGGSLRL SCAASGFTFS NYAMSWVRQA PGKGLEWVSS 50 ISGSGDYTYY TDSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCARSP 100 WGYYLDSWGQ GTLVTVSSAS TKGPSVFPLA PSSKSTSGGT AALGCLVKDY 150 FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI 200 CNVNHKPSNT KVDKRVEPKS CDKTHTCPPC PAPELLGGPS VFLFPPKPKD 250 TLMISRTPEV TCVVVDVSHE DPEVKFNWYV DGVEVHNAKT KPREEQYNST 300 YRVVSVLTVL HQDWLNGKEY KCKVSNKALP APIEKTISKA KGQPREPQVY 350 TLPPSREEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPVLD 400 SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK 448 Light chain / Chaîne légère / Cadena ligera DIQMTQSPPS LSASAGDRVT ITCRASQGIS SRLAWYQQKP EKAPKSLIYA 50 ASSLQSGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ YNSYPYTFGQ 100 GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 145-201 262-322 368-426 22''-96'' 145''-201'' 262''-322'' 368''-426'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126)* 221-214' 221''-214''' Inter-H-H (h 11, h 14)* 227-227'' 230-230'' *Two or three of the inter-chain disulfide bridges are not present, an average of 3 to 4 cysteinyl being conjugated each via a thioether bond to a drug linker. *Deux ou trois des ponts disulfures inter-chaînes ne sont pas présents, 3 à 4 cystéinyl en moyenne étant chacun conjugué via une liaison thioéther à un linker-principe actif. *Faltan dos o tres puentes disulfuro inter-catenarios, una media de 3 a 4 cisteinil está conjugada a conectores de principio activo. N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 298, 298'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados trevogrumabum # trevogrumab immunoglobulin G4-kappa, anti-[Homo sapiens MSTN (myostatin, growth differentiation factor 8, GDF8, GDF-8)], human monoclonal antibody; gamma4 heavy chain (1-447) [Homo sapiens VH (IGHV3- 23*01 (93.90%) -(IGHD)-IGHJ6*01 T125>I (117) [8.8.13] (1-120) -IGHG4*01 (CH1 (121-218), hinge S10>P (228) (219-230), CH2 (231-340), CH3 (341-445), CHS (446- 447)) (121-447)], (134-214')-disulfide with kappa light chain (1’-214’) [Homo sapiens (V-KAPPA (IGKV1-27*01 (90.50%) -IGKJ4*01) [6.3.9] (1'-107') -IGKC*01, Km3 (108'- 214')]; dimer (226-226":229-229")-bisdisulfide trévogrumab immunoglobuline G4-kappa, anti-[Homo sapiens MSTN (myostatine, facteur de croissance et de différenciation 8, GDF8, GDF-8)], anticorps monoclonal humain; chaîne lourde gamma4 (1-447) [Homo sapiens VH (IGHV3-23*01 (93.90%) -(IGHD)-IGHJ6*01 T125>I (117) [8.8.13] (1-120) -IGHG4*01 (CH1 (121-218), charnière S10>P (228) (219-230), CH2 (231-340), CH3 (341-445), CHS (446-447)) (121-447)], (134-214')-disulfure avec la chaîne légère kappa (1’-214’) [Homo sapiens (V-KAPPA (IGKV1-27*01 (90.50%) -IGKJ4*01) [6.3.9] (1'-107') - IGKC*01, Km3 (108'-214')]; dimère (226-226":229-229")- bisdisulfure trevogrumab inmunoglobulina G4-kappa, anti-[Homo sapiens MSTN (miostatina, factor de crecimiento y diferenciación 8, GDF8, GDF-8)], anticuerpo monoclonal humano; WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 161 cadena pesada gamma4 (1-447) [Homo sapiens VH (IGHV3-23*01 (93.90%) -(IGHD)-IGHJ6*01 T125>I (117) [8.8.13] (1-120) -IGHG4*01 (CH1 (121-218), bisagra S10>P (228) (219-230), CH2 (231-340), CH3 (341-445), CHS (446-447)) (121-447)], (134-214')-disulfuro con la cadena ligera kappa (1’-214’) [Homo sapiens (V-KAPPA (IGKV1-27*01 (90.50%) -IGKJ4*01) [6.3.9] (1'-107') - IGKC*01, Km3 (108'-214')]; dímero (226-226":229-229")- bisdisulfuro Heavy chain / Chaîne lourde / Cadena pesadaEVQVLESGGD LVQPGGSLRL SCAASGFTFS AYAMTWVRQA PGKGLEWVSA 50 ISGSGGSAYY ADSVKGRFTI SRDNSKNTVY LQMNSLRAED TAVYYCAKDG 100 AWKMSGLDVW GQGTTVIVSS ASTKGPSVFP LAPCSRSTSE STAALGCLVK 150 DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTKT 200 YTCNVDHKPS NTKVDKRVES KYGPPCPPCP APEFLGGPSV FLFPPKPKDT 250 LMISRTPEVT CVVVDVSQED PEVQFNWYVD GVEVHNAKTK PREEQFNSTY 300 RVVSVLTVLH QDWLNGKEYK CKVSNKGLPS SIEKTISKAK GQPREPQVYT 350 LPPSQEEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS 400 DGSFFLYSRL TVDKSRWQEG NVFSCSVMHE ALHNHYTQKS LSLSLGK 447 Light chain / Chaîne légère / Cadena ligera DIQMTQSPAS LSASVGDRVT ITCRASQDIS DYLAWYQQKP GKIPRLLIYT 50 TSTLQSGVPS RFRGSGSGTD FTLTISSLQP EDVATYYCQK YDSAPLTFGG 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 147-203 261-321 367-425 22''-96'' 147''-203'' 261''-321'' 367''-425'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (CH1 10-CL 126) 134-214' 134''-214''' Inter-H-H (h 8, h 11) 226-226'' 229-229'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 297, 297'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados tucatinibum tucatinib N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-N4-[3-methyl- 4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]quinazoline- 4,6-diamine tucatinib N6-(4,4-diméthyl-4,5-dihydrooxazol-2-yl)-N4-[3-méthyl- 4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phényl]quinazoline- 4,6-diamine tucatinib N6-(4,4-dimetil-4,5-dihidrooxazol-2-il)-N4-[3-metil- 4-([1,2,4]triazolo[1,5-a]piridin-7-iloxi)fenil]quinazolina- 4,6-diamina C26H24N8O2 N N HN N H O N CH3 O N N N H3C H3C vaborbactamum vaborbactam {(3R,6S)-2-hydroxy-3-[2-(thiophen-2-yl)acetamido]- 1,2-oxaborinan-6-yl}acetic acid Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 162 vaborbactam acide {(3R,6S)-2-hydroxy-3-[2-(thiophén-2-yl)acétamido]- 1,2-oxaborinan-6-yl}acétique vaborbactam ácido {(3R,6S)-2-hidroxi-3-[2-(tiofen-2-il)acetamido]- 1,2-oxaborinan-6-il}acético C12H16BNO5S B O OH N H S O H H CO2H vadastuximabum talirinum # vadastuximab talirine immunoglobulin G1-kappa, anti-[Homo sapiens CD33 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67)], chimeric monoclonal antibody conjugated to the pyrrolobenzodiazepine (PDB) dimer SGD-1882; gamma1 heavy chain (1-447) [Mus musculus VH (IGHV1- 85*01 -(IGHD)-IGHJ4*01) [8.8.10] (1-117) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (118-215), hinge (216-230), CH2 S3>C (239) (231-340), CH3 (341-445), CHS (446- 447)) (118-447)], (220-214')-disulfide with kappa light chain (1'-214') [Mus musculus V-KAPPA (IGKV14-111*01 -Homo sapiens IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimer (226-226'':229-229'')- bisdisulfide; conjugated, on two site-specific drug attachment engineered cysteines (C239, C239''), to a maximum of 2 pyrrolobenzodiazepine (PDB) dimers SGD- 1882, each via a cleavable (valine-alanine dipeptide as cathepsine B cleavage site) maleimidocaproyl type linker vadastuximab talirine immunoglobuline G1-kappa, anti-[Homo sapiens CD33 (lectine 3 de type Ig-like liant l’acide sialique, SIGLEC3, SIGLEC-3, gp67, p67)], anticorps monoclonal chimérique conjugué au dimère de pyrrolobenzodiazépine (PDB) SGD-1882; chaîne lourde gamma1 (1-447) [Mus musculus VH (IGHV1-85*01 -(IGHD)-IGHJ4*01) [8.8.10] (1-117) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (118-215), charnière (216-230), CH2 S3>C (239) (231-340), CH3 (341-445), CHS (446-447)) (118-447)], (220-214')-disulfure avec la chaîne légère kappa (1'-214') [Mus musculus V-KAPPA (IGKV14-111*01 -Homo sapiens IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimère (226- 226'':229-229'')-bisdisulfure; conjugué, sur deux cystéines sites de fixation spécifique du linker-produit actif (C239, C239''), à un maximum de 2 dimères de pyrrolobenzodiazépine (PDB) SGD-1882, chacun via un linker clivable (dipeptide valine-alanine clivable par la cathepsine B) de type maléimidocaproyle WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 163 vadastuximab talirina inmunoglobulina G1-kappa, anti-[Homo sapiens CD33 (lectina 3 de tipo Ig-like que liga el ácido siálico, SIGLEC3, SIGLEC-3, gp67, p67)], anticuerpo monoclonal quimérico conjugado con el dimero de pyirolobenzodiazepina (PDB) SGD-1882; cadena pesada gamma1 (1-447) [Mus musculus VH (IGHV1-85*01 -(IGHD)-IGHJ4*01) [8.8.10] (1-117) -Homo sapiens IGHG1*01, G1m17,1 (CH1 (118-215), bisagra (216-230), CH2 S3>C (239) (231-340), CH3 (341-445), CHS (446-447)) (118-447)], (220-214')-disulfuro con la cadena ligera kappa (1'-214') [Mus musculus V-KAPPA (IGKV14-111*01 -Homo sapiens IGKJ4*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dímero (226- 226'':229-229'')-bisdisulfuro; conjugado, en dos císteinas sitios de fijación específicos del linker-producto activo (C239, C239''), con un máximo de 2 dímeros de pirrolobenzodiazepina (PDB) SGD-1882, cada uno mediante un espaciador escindible (dipéptido valina- alanina escindible por la catepsina B) de tipo maleimidocaproil O O N NH O OCH3 H3CO N NH O OCH3 N H AlaVal O H2N CO2H H S  H N O O and epimer at C* et l'épimère en C* y el epímero al C* Heavy chain / Chaîne lourde / Cadena pesada QVQLVQSGAE VKKPGASVKV SCKASGYTFT NYDINWVRQA PGQGLEWIGW 50 IYPGDGSTKY NEKFKAKATL TADTSTSTAY MELRSLRSDD TAVYYCASGY 100 EDAMDYWGQG TTVTVSSAST KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF 150 PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC 200 NVNHKPSNTK VDKKVEPKSC DKTHTCPPCP APELLGGPCV FLFPPKPKDT 250 LMISRTPEVT CVVVDVSHED PEVKFNWYVD GVEVHNAKTK PREEQYNSTY 300 RVVSVLTVLH QDWLNGKEYK CKVSNKALPA PIEKTISKAK GQPREPQVYT 350 LPPSRDELTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS 400 DGSFFLYSKL TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGK 447 Light chain / Chaîne légère / Cadena ligera DIQMTQSPSS LSASVGDRVT INCKASQDIN SYLSWFQQKP GKAPKTLIYR 50 ANRLVDGVPS RFSGSGSGQD YTLTISSLQP EDFATYYCLQ YDEFPLTFGG 100 GTKVEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150 DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200 LSSPVTKSFN RGEC 214 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro Intra-H (C23-C104) 22-96 144-200 261-321 367-425 22''-96'' 144''-200'' 261''-321'' 367''-425'' Intra-L (C23-C104) 23'-88' 134'-194' 23'''-88''' 134'''-194''' Inter-H-L (h 5-CL 126) 220-214' 220''-214''' Inter-H-H (h 11, h 14) 226-226'' 229-229'' N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación H CH2 N84.4: 297, 297'' Fucosylated complex bi-antennary CHO-type glycans / glycanes de type CHO bi-antennaires complexes fucosylés / glicanos de tipo CHO biantenarios complejos fucosilados Modified residues / Résidus modifiés / Restos modificados C 239, 239'' velmanasum alfa # velmanase alfa human lysosomal alpha-mannosidase (Laman, EC3.2.1.24, mannosidase alpha class 2B member 1), produced in CHO (Chinese Hamster Ovary) cells, alfa glycoform Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 164 velmanase alfa alpha mannosidase lysosomiale humaine (Laman, EC3.2.1.24, membre 1 de classe 2B de la mannosidase alpha), produite par la cellule ovarienne de hamster chinois (CHO), forme glycosylée alfa velmanasa alfa alfa manosidasa lisosómica humana (Laman, EC3.2.1.24, miembro 1 de la clase 2B de la manosidasa alfa), producida por células ováricas de hamster chino (CHO), forma glicosilada alfa GGYETCPTVQ PNMLNVHLLP HTHDDVGWLK TVDQYFYGIK NDIQHAGVQY 50ILDSVISALL ADPTRRFIYV EIAFFSRWWH QQTNATQEVV RDLVRQGRLE 100 FANGGWVMND EAATHYGAIV DQMTLGLRFL EDTFGNDGRP RVAWHIDPFG 150 HSREQASLFA QMGFDGFFFG RLDYQDKWVR MQKLEMEQVW RASTSLKPPT 200 ADLFTGVLPN GYNPPRNLCW DVLCVDQPLV EDPRSPEYNA KELVDYFLNV 250 ATAQGRYYRT NHTVMTMGSD FQYENANMWF KNLDKLIRLV NAQQAKGSSV 300 HVLYSTPACY LWELNKANLT WSVKHDDFFP YADGPHQFWT GYFSSRPALK 350 RYERLSYNFL QVCNQLEALV GLAANVGPYG SGDSAPLNEA MAVLQHHDAV 400 SGTSRQHVAN DYARQLAAGW GPCEVLLSNA LARLRGFKDH FTFCQQLNIS 450 ICPLSQTAAR FQVIVYNPLG RKVNWMVRLP VSEGVFVVKD PNGRTVPSDV 500 VIFPSSDSQA HPPELLFSAS LPALGFSTYS VAQVPRWKPQ ARAPQPIPRR 550 SWSPALTIEN EHIRATFDPD TGLLMEIMNM NQQLLLPVRQ TFFWYNASIG 600 DNESDQASGA YIFRPNQQKP LPVSRWAQIH LVKTPLVQEV HQNFSAWCSQ 650 VVRLYPGQRH LELEWSVGPI PVGDTWGKEV ISRFDTPLET KGRFYTDSNG 700 REILERRRDY RPTWKLNQTE PVAGNYYPVN TRIYITDGNM QLTVLTDRSQ 750 GGSSLRDGSL ELMVHRRLLK DDGRGVSEPL MENGSGAWVR GRHLVLLDTA 800 QAAAAGHRLL AEQEVLAPQV VLAPGGGAAY NLGAPPRTQF SGLRRDLPPS 850 VHLLTLASWG PEMVLLRLEH QFAVGEDSGR NLSAPVTLNL RDLFSTFTIT 900 RLQETTLVAN QLREAASRLK WTTNTGPTPH QTPYQLDPAN ITLEPMEIRT 950 FLASVQWKEV DG 962 Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro 6-309 219-224 363-423 444-452 Glycosylation sites (potential) / Sites de glycosylation (potentiels) / Posiciones de glicosilación (potenciales) Asn-84 Asn-261 Asn-318 Asn-448 Asn-596 Asn-602 Asn-643 Asn-717 Asn-783 Asn-881 Asn-940 vesatolimodum vesatolimod 4-amino-2-butoxy-8-({3-[(pyrrolidin- 1-yl)methyl]phenyl}methyl)-7,8-dihydropteridin-6(5H)-one vésatolimod 4-amino-2-butoxy-8-({3-[(pyrrolidin- 1-yl)méthyl]phényl}méthyl)-7,8-dihydroptéridin-6(5H)-one vesatolimod 4-amino-2-butoxi-8-({3-[(pirrolidin-1-il)metil]fenil}metil)- 7,8-dihidropteridin-6(5H)-ona C22H30N6O2 N NN N H O CH3 NH2 O N vistusertibum vistusertib 3-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3- d]pyrimidin-7-yl}-N-methylbenzamide WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 165 vistusertib 3-{2,4-bis[(3S)-3-méthylmorpholin-4-yl]pyrido[2,3- d]pyrimidin-7-yl}-N-méthylbenzamide vistusertib 3-{2,4-bis[(3S)-3-metilmorfolin-4-il]pirido[2,3-d]pirimidin- 7-il}-N-metilbenzamida C25H30N6O3 N N N N N O H N O O H H3C H CH3 CH3 volanesorsenum volanesorsen all-P-ambo-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'→5')- 2'-O-(2-methoxyethyl)-P-thioguanylyl-(3'→5')-2'-O-(2- methoxyethyl)-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2- methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2- methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-deoxy-5- methyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P- thiothymidylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-P- thiothymidylyl-(3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl- (3'→5')-2'-deoxy-5-methyl-P-thiocytidylyl-(3'→5')-2'-deoxy- P-thioadenylyl-(3'→5')-2'-deoxy-P-thioguanylyl-(3'→5')-2'- deoxy-5-methyl-P-thiocytidylyl-(3'→5')-2'-O-(2- methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2- methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2- methoxyethyl)-5-methyl-P-thiouridylyl-(3'→5')-2'-O-(2- methoxyethyl)-P-thioadenylyl-(3'→5')-2'-O-(2- methoxyethyl)-5-methyluridine volanésorsen tout-P-ambo-2'-O-(2-méthoxyéthyl)-P-thioadénylyl-(3'→5')- 2'-O-(2-méthoxyéthyl)-P-thioguanylyl-(3'→5')-2'-O-(2- méthoxyéthyl)-5-méthyl-P-thiocytidylyl-(3'→5')-2'-O-(2- méthoxyéthyl)-5-méthyl-P-thiouridylyl-(3'→5')-2'-O-(2- méthoxyéthyl)-5-méthyl-P-thiouridylyl-(3'→5')-2'-déoxy-5- méthyl-P-thiocytidylyl-(3'→5')-P-thiothymidylyl-(3'→5')-P- thiothymidylyl-(3'→5')-2'-déoxy-P-thioguanylyl-(3'→5')-P- thiothymidylyl-(3'→5')-2'-déoxy-5-méthyl-P-thiocytidylyl- (3'→5')-2'-déoxy-5-méthyl-P-thiocytidylyl-(3'→5')-2'-déoxy- P-thioadénylyl-(3'→5')-2'-déoxy-P-thioguanylyl-(3'→5')-2'- déoxy-5-méthyl-P-thiocytidylyl-(3'→5')-2'-O-(2- méthoxyéthyl)-5-méthyl-P-thiouridylyl-(3'→5')-2'-O-(2- méthoxyéthyl)-5-méthyl-P-thiouridylyl-(3'→5')-2'-O-(2- méthoxyéthyl)-5-méthyl-P-thiouridylyl-(3'→5')-2'-O-(2- méthoxyéthyl)-P-thioadénylyl-(3'→5')-2'-O-(2- méthoxyéthyl)-5-méthyluridine Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 166 volanesorsén todo-P-ambo-2'-O-(2-metoxietil)-P-tioadenilil-(3'→5')-2'-O- (2-metoxietil)-P-tioguanilil-(3'→5')-2'-O-(2-metoxietil)-5- metil-P-tiocitidilil-(3'→5')-2'-O-(2-metoxietil)-5-metil-P- tiouridilil-(3'→5')-2'-O-(2-metoxietil)-5-metil-P-tiouridilil- (3'→5')-2'-desoxi-5-metil-P-tiocitidilil-(3'→5')-P-tiotimidilil- (3'→5')-P-tiotimidilil-(3'→5')-2'-desoxi-P-tioguanilil-(3'→5')- P-tiotimidilil-(3'→5')-2'-desoxi-5-metil-P-tiocitidilil-(3'→5')-2'- desoxi-5-metil-P-tiocitidilil-(3'→5')-2'-desoxi-P-tioadenilil- (3'→5')-2'-desoxi-P-tioguanilil-(3'→5')-2'-desoxi-5-metil-P- tiocitidilil-(3'→5')-2'-O-(2-metoxietil)-5-metil-P-tiouridilil- (3'→5')-2'-O-(2-metoxietil)-5-metil-P-tiouridilil-(3'→5')-2'-O- (2-metoxietil)-5-metil-P-tiouridilil-(3'→5')-2'-O-(2-metoxietil)- P-tioadenilil-(3'→5')-2'-O-(2-metoxietil)-5-metiluridina C230H320N63O125P19S19 (3'-5')(P-thio)(Amoe-Gmoe-mCmoe-Tmoe-Tmoe-dmC-dT-dT-dG-dT-dmC-dmC-dA-dG-dmC-Tmoe-Tmoe-Tmoe-Amoe-Tmoe) d (as prefix) = 2'-deoxy m (as prefix) = 5-methyl moe (as suffix) = 2'-O-[2-methoxy(ethyl)] volixibatum volixibat N-(3-O-benzyl-6-O-sulfo-β-D-glucopyranosyl)- N'-{3-[(3S,4R,5R)-3-butyl-7-(dimethylamino)-3-ethyl- 4-hydroxy-1,1-dioxo-2,3,4,5-tetrahydro- 1H-1λ6-benzothiepin-5-yl]phenyl}urea volixibat N-(3-O-benzyl-6-O-sulfo-β-D-glucopyranosyl)- N'-{3-[(3S,4R,5R)-3-butyl-7-(diméthylamino)-3-éthyl- 4-hydroxy-1,1-dioxo-2,3,4,5-tétrahydro- 1H-1λ6-benzothiépin-5-yl]phényl}urée volixibat N-(3-O-bencil-6-O-sulfo-β-D-glucopiranosil)- N'-{3-[(3S,4R,5R)-3-butil-7-(dimetilamino)-3-etil-4-hidroxi- 1,1-dioxo-2,3,4,5-tetrahidro-1H-1λ6-benzotiepin- 5-il]fenil}urea C38H51N3O12S2 SO O H3C H N H N CH3 CH3 H3C N H O O HO OH O H O S HO O O H OH voxilaprevirum voxilaprevir (1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-{(1R,2R)-2- (difluoromethyl)-1-[(1-methylcyclopropanesulfonyl) carbamoyl]cyclopropyl}-9-ethyl-18,18-difluoro-14-methoxy- 3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a- tetradecahydro-8H-7,10-methanocyclopropa[18,19] [1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline- 8-carboxamide WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 167 voxilaprévir (1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-{(1R,2R)-2- (difluorométhyl)-1-[(1-méthylcyclopropanesulfonyl) carbamoyl]cyclopropyl}-9-éthyl-18,18-difluoro-14-méthoxy- 3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a- tétradécahydro-8H-7,10-méthanocyclopropa[18,19] [1,10,3,6]dioxadiazacyclononadécino[11,12-b]quinoxaline- 8-carboxamide voxilaprevir (1aR,5S,8S,9S,10R,22aR)-5-terc-butil-N-{(1R,2R)-2- (difluorometil)-1-[(1-metilciclopropanosulfonil) carbamoil]ciclopropil}-9-etil-18,18-difluoro-14-metoxi- 3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a- tetradecahidro-8H-7,10-metanociclopropa[18,19][1,10,3,6] dioxadiazaciclononadecino[11,12-b]quinoxalina- 8-carboxamida C40H52F4N6O9S N O NHO H3C O H3C CH3 H N N O OCH3 H H FF NHO H N S F F O O O CH3 H H H H CH3 zidebactamum zidebactam (1R,2S,5R)-7-oxo-2-{2-[(3R)-piperidine- 3-carbonyl]hydrazinecarbonyl}- 1,6-diazabicyclo[3.2.1]octan-6-yl hydrogen sulfate zidébactam hydrogénosulfate de (1R,2S,5R)-7-oxo-2-{2-[(3R)- pipéridine-3-carbonyl]hydrazinecarbonyl}- 1,6-diazabicyclo[3.2.1]octan-6-yle zidebactam hidrógenosulfato de (1R,2S,5R)-7-oxo-2-{2-[(3R)- piperidina-3-carbonil]hidrazinacarbonil}- 1,6-diazabiciclo[3.2.1]octan-6-ilo C13H21N5O7S N N H OS O HO H OO O N H H N O NH H Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 168 AMENDMENTS TO PREVIOUS LISTS MODIFICATIONS APPORTÉES AUX LISTES ANTÉRIEURES MODIFICACIONES A LAS LISTAS ANTERIORES Recommended International Nonproprietary Names (Rec. INN): List 73 Dénominations communes internationales recommandées (DCI Rec.): Liste 73 Denominaciones Comunes Internacionales Recomendadas (DCI Rec.): Lista 73 (WHO Drug Information, Vol. 29, No. 1, 2015)   p. 64 albenatidum# albenatide replace the description and the structure by the following ones albénatide remplacer la description et la structure par les suivantes albenatida sustitúyase la descripción y la estructura por las siguientes S3.34-[1-(3-{[2-(2-{2-[exendin-4 Heloderma suspectum precursor-(48-86)- peptidyl (exenatidyl)-L-lysinamide-N6-yl]-2-oxo-ethoxy}ethoxy)ethyl]amino}- 3-oxopropyl)-2,5-dioxopyrrolidin-3-yl]human serum albumin. Peptide is synthetic, and human serum albumin is produced in Saccharomyces cerevisiae. S3.34-[1-(3-{[2-(2-{2-[précurseur de l’exendin-4 de Heloderma suspectum- (48-86)-peptidyl (exénatidyle)-L-lysinamide-N6-yl]-2-oxo- éthoxy}éthoxy)éthyl]amino}-3-oxopropyl)-2,5-dioxopyrrolidin-3-yl]albumine sérique humaine. Le peptide est synthétique et l'albumine sérique humaine est produite par Saccharomyces cerevisiae. S3.34-[1-(3-{[2-(2-{2-[precursor de la exendina-4 de Heloderma suspectum- (48-86)-peptidil (exenatidilo)-L-lisinamida-N6-il]-2-oxo-etoxi}etoxi)etil]amino}- 3-oxopropil)-2,5-dioxopirrolidin-3-il]albúmina sérica humana. El péptido es sintético y la albúmina sérica humana la produce el Saccharomyces cerevisiae. WHO Drug Information Vol. 30, No. 1, 2016 Recommended INN: List 75 169     p. 103 - pegvaliasum # 104 pegvaliase replace the description by the following one pegvaliase remplacer la description par la suivante pegvaliasa sustitúyase la descripción por la siguiente pegylated, recombinant DNA derived Anabaena variabilis phenylalanine ammonia lyase mutein (S 503, S 565), produced in Escherichia coli: [503-serine (C>S),565-serine (C>S)]phenylalanine ammonia-lyase (EC 4.3.1.24) Anabaena variabilis in which at least 6 lysyl residues are N6-{6-[ω-methoxypoly(oxyethylene)]hexanoyl} substituted mutéine (S 503, S 565) de phénylalanine ammoniac-lyase de Anabaena variabilis, pégylée, produite par Escherichia coli à partir d'ADN recombinant: [503-sérine (C>S),565-sérine (C>S)]phénylalanine ammoniac-lyase (EC 4.3.1.24) de Anabaena variabilis dont au moins 6 résidus lysyl sont N6-{6-[ω-méthoxypoly(oxyéthylène)]hexanoyl} substitués muteína (S 503, S 565) de la fenilalanina amoniaco-liasa de Anabaena variabilis, pegilada, producida en Escherichia coli a partir de ADN recombinante: [503-serina (C>S),565-serina (C>S)]fenilalanina amoniaco-liasa (EC 4.3.1.24) de Anabaena variabilis de cuyos restos lisil 5, por término medio, están N6-{6-[ω-metoxipoli(oxietileno)]hexanoil} substituidos     Recommended International Nonproprietary Names (Rec. INN): List 74 Dénominations communes internationales recommandées (DCI Rec.): Liste 74 Denominaciones Comunes Internacionales Recomendadas (DCI Rec.): Lista 74 (WHO Drug Information, Vol. 29, No. 3, 2015) p. 421 somapacitanum # somapacitan replace the description and the structure by the following ones somapacitan remplacer la description et la structure par les suivantes somapacitán sustitúyase la descripción y la estructura por las siguientes [101-{S-[(8S,22S,27S)-8,22,27-tricarboxy-2,10,19,24,29,38,42,42,44- nonaoxo-59-(1H-tetrazol-5-yl)-12,15,31,34-tetraoxa-42λ6-thia- 3,9,18,23,28,37,43-heptaazanonapentacontan-1-yl]-L-cysteine}]human somatropin [101-{S-[(8S,22S,27S)-8,22,27-tricarboxy-2,10,19,24,29,38,42,42,44- nonaoxo-59-(1H-tétrazol-5-yl)-12,15,31,34-tétraoxa-42λ6-thia- 3,9,18,23,28,37,43-heptaazanonapentacontan-1-yl]-L-cystéine}]somatropine humaine [101-{S-[(8S,22S,27S)-8,22,27-tricarboxi-2,10,19,24,29,38,42,42,44- nonaoxo-59-(1H-tetrazol-5-il)-12,15,31,34-tetraoxa-42λ6-tia- 3,9,18,23,28,37,43-heptaazanonapentacontan-1-il]-L-cisteina}]somatropina humana Recommended INN: List 75 WHO Drug Information Vol. 30, No. 1, 2016 170 # Electronic structure available on Mednet: http://mednet.who.int/ # Structure électronique disponible sur Mednet: http://mednet.who.int/ # Estructura electrónica disponible en Mednet: http://mednet.who.int/ * http://www.who.int/medicines/services/inn/publication/en/ Procedure and Guiding Principles / Procédure et Directives / Procedimientos y principios generales The text of the Procedures for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances and General Principles for Guidance in Devising International Nonproprietary Names for Pharmaceutical Substances will be reproduced in proposed INN lists only. Les textes de la Procédure à suivre en vue du choix de dénominations communes internationales recommandées pour les substances pharmaceutiques et des Directives générales pour la formation de dénominations communes internationales applicables aux substances pharmaceutiques seront publiés seulement dans les listes des DCI proposées. El texto de los Procedimientos de selección de denominaciones comunes internacionales recomendadas para las sustancias farmacéuticas y de los Principios generales de orientación para formar denominaciones comunes internacionales para sustancias farmacéuticas aparece solamente en las listas de DCI propuestas.