Lutikizumab

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ABT-981 is a dual-variable domain antibody that neutralizes both IL-1alpha and IL-1ß without interfering with IL-1 receptor antagonist mediated regulatory functions in the IL-1 pathway

Inn NameLutikizumab
Lab CodesABT-981
Chemical NameImmunoglobulin G1-kappa, anti-[Homo sapiens IL1A (interleukin 1 alpha) and Homo sapiens IL1B (interleukin 1 beta, IL-1B, 1L1F2)], humanized monoclonal antibody, tetravalent bispecific; gamma1 heavy chain (1-577) [humanized VH anti-IL1B (Homo sapiens IGHV3-23*04 (80.60%) -(IGHD)-IGHJ4*01) [8.8.12] (1-119) -6-mer linker (120-125) -Homo sapiens VH anti-IL1A (IGHV3 30*03 (88.80%) -(IGHD)-IGHJ1*01) [8.8.15] (126-247) -Homo sapiens IGHG1*01 (CH1 (248-345), hinge (346-360), CH2 L1.3>A (364), L1.2>A (365), (361-470), CH3 (471-575), CHS (576-577)) (248-577)], (350-327')-disulfide with kappa light chain (1’-327’) [humanized V-KAPPA anti-IL1B (Homo sapiens IGKV1-27*01 (82.10%) -IGKJ2*01) [6.3.9] (1'-106') -7-mer linker -Homo sapiens V-KAPPA anti-IL1A (IGKV1-12*01 (92.60%)-IGKJ4*01) [6.3.9] (114'-220') -Homo sapiens IGKC*01,Km3 (221'-327')]; dimer (356-356":359-359")-bisdisulfide
SequenceHeavy chain
EVQLVESGGG VVQPGRSLRL SCSASGFIFS RYDMSWVRQA PGKGLEWVAY 50
ISHGGAGTYY PDSVKGRFTI SRDNSKNTLF LQMDSLRPED TGVYFCARGG 100
VTKGYFDVWG QGTPVTVSSA STKGPQVQLV ESGGGVVQPG RSLRLSCTAS 150
GFTFSMFGVH WVRQAPGKGL EWVAAVSYDG SNKYYAESVK GRFTISRDNS 200
KNILFLQMDS LRLEDTAVYY CARGRPKVVI PAPLAHWGQG TLVTFSSAST 250
KGPSVFPLAP SSKSTSGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF 300
PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPKSC 350
DKTHTCPPCP APEAAGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED 400
PEVKFNWYVD GVEVHNAKTK PREEQYNSTY RVVSVLTVLH QDWLNGKEYK 450
CKVSNKALPA PIEKTISKAK GQPREPQVYT LPPSREEMTK NQVSLTCLVK 500
GFYPSDIAVE WESNGQPENN YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG 550
NVFSCSVMHE ALHNHYTQKS LSLSPGK 577

Light chain
DIQMTQSPSS LSASVGDRVT ITCRASGNIH NYLTWYQQTP GKAPKLLIYN 50
AKTLADGVPS RFSGSGSGTD YTFTISSLQP EDIATYYCQH FWSIPYTFGQ 100
GTKLQITRTV AAPDIQMTQS PSSVSASVGD RVTITCRASQ GISSWLAWYQ 150
QKPGKAPKLL IYEASNLETG VPSRFSGSGS GSDFTLTISS LQPEDFATYY 200
CQQTSSFLLS FGGGTKVEHK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN 250
NFYPREAKVQ WKVDNALQSG NSQESVTEQD SKDSTYSLSS TLTLSKADYE 300
KHKVYACEVT HQGLSSPVTK SFNRGEC 327

Disulfide bridges location
Intra-H (C23-C104) 22-96 147-221 274-330 391-451 497-555
22''-96'' 147''-221'' 274''-330'' 391''-451'' 497''-555''
Intra-L (C23-C104) 23'-88' 136'-201' 247'-307'
23'''-88''' 136'''-201''' 247'''-307'''
Inter-H-L (h 5-CL 126) 350-327' 350''-327'''
Inter-H-H (h 11, h 14) 356-356'' 359-359''

N-glycosylation sites
H CH2 N84.4:
427, 427''
Fucosylated complex bi-antennary CHO-type glycans
Chemical StructureLutikizumab.png
Cas Registry Number1791411-57-8
New Molecular EntityYes
OriginatorAbbott Laboratories
DeveloperAbbVie
Mechanism Of ActionInterleukin-1 (IL-1) inhibitor
Who Atc CodesL04A-C (Interleukin inhibitors)
M01A-X (Other antiinflammatory and antirheumatic agents, non-steroids)
Ephmra CodesL4 (Immunosuppressants)
M1A1 (Anti-rheumatics, non-steroidal plain)
IndicationOsteoarthritis

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