Fremanezumab

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TEV -48125 (formerly LBR-101/ RN-307) is a monoclonal antibody that binds to calcitonin gene-related peptide (CGRP), a well-validated target in migraine. CGRP signaling may be disrupted by targeting the ligand itself or its receptor. TEV-48125 is being developed for two distinct migraine indications; chronic migraine and high frequency episodic migraine.

Inn NameFremanezumab
Lab CodesLBR-101, PF-04427429, PF-4427429, RI-307, RN-307, TEV-48125
Chemical NameImmunoglobulin G2-kappa, anti-[Homo sapiens CALCA (calcitonin related polypeptide alpha) calcitonin generelated peptide 1, CGRP1, 83-119 and Homo sapiens CALCB (calcitonin related polypeptide beta) calcitonin gene-related peptide 2, CGRP2, 82-118], humanized monoclonal antibody; gamma2 heavy chain (1-448) [humanized VH (Homo sapiens IGHV3-7*01 (85.70%) -(IGHD) -IGHJ4*01) [8.10.13] (1-122) -Homo sapiens IGHG2*01, G2m..(CH1 (123-220), hinge (221-232), CH2 A115>S (331), P116>S (332) (233-341), CH3 (342-446), CHS (447-448)) (123- 448)], (136 214')-disulfide with kappa light chain (1’-214’) [humanized V-KAPPA (Homo sapiens IGKV3-11*01 (85.30%) -IGKJ2*01) [6.3.9] (1'-107') -Homo sapiens IGKC*01, Km3 (108'-214')]; dimer (224-224":225-225":228-228":231-231'')-tetrakisdisulfide
Alternate NameImmunoglobulin G2, anti-(human alpha-calcitonin gene-related peptide/beta-calcitonin gene-related peptide) (human-mus musculus monoclonal TEV-48125 heavy chain), disulfide with human-mus musculus monoclonal TEV-48125 light chain, dimer
SequenceHeavy chain
EVQLVESGGG LVQPGGSLRL SCAASGFTFS NYWISWVRQA PGKGLEWVAE 50
IRSESDASAT HYAEAVKGRF TISRDNAKNS LYLQMNSLRA EDTAVYYCLA 100
YFDYGLAIQN YWGQGTLVTV 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 SSIEKTISKT KGQPREPQVY 350
TLPPSREEMT KNQVSLTCLV KGFYPSDIAV EWESNGQPEN NYKTTPPMLD 400
SDGSFFLYSK LTVDKSRWQQ GNVFSCSVMH EALHNHYTQK SLSLSPGK 448

Light chain
EIVLTQSPAT LSLSPGERAT LSCKASKRVT TYVSWYQQKP GQAPRLLIYG 50
ASNRYLGIPA RFSGSGSGTD FTLTISSLEP EDFAVYYCSQ SYNYPYTFGQ 100
GTKLEIKRTV AAPSVFIFPP SDEQLKSGTA SVVCLLNNFY PREAKVQWKV 150
DNALQSGNSQ ESVTEQDSKD STYSLSSTLT LSKADYEKHK VYACEVTHQG 200
LSSPVTKSFN RGEC 214

Disulfide bridges location
Intra-H (C23-C104) 22-98 149-205 262-322 368-426
22''-98'' 149''-205'' 262''-322'' 368''-426''
Intra-L (C23-C104) 23'-88' 134'-194'
23'''-88''' 134'''-194'''
Inter-H-L (CH1 10-CL 126) 136-214' 136''-214'''
Inter-H-H (h 4, h 5, h 8, h 11) 224-224'' 225-225'' 228-228'' 231-231''

N-glycosylation sites
H CH2 N84.4:
298, 298''
Fucosylated complex bi-antennary CHO-type glycans

Chemical StructureFremanezumab.png
Cas Registry Number1655501-53-3
New Molecular EntityYes
OriginatorRinat Neuroscience
DeveloperTeva Pharmaceutical Industries
Mechanism Of ActionCalcitonin gene-related peptide receptor antagonist
Who Atc CodesN02C (Antimigraine Preparations)
Ephmra CodesN2C (Anti-Migraine Preparations)
IndicationMigraine

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