RESUMO
The therapeutic antibodies and their by-products (antibody fragments, conjugated, etc.) establish one of the most dynamic biopharmaceutical market segments today. Due to their intrinsic properties of specificity towards their target, towards their flexible affinity and due to their stability, antibodies became therapeutic agents of the very first choice. One of the challenges of this sector is to create antibodies of very good quality, more and more quickly, while having less and less consequent development costs in fine.
TITLE: Développabilité. ABSTRACT: Les anticorps thérapeutiques et leurs dérivés (fragments d'anticorps, conjugués, etc.) constituent aujourd'hui l'un des segments du marché biopharmaceutique les plus dynamiques. De par leurs propriétés intrinsèques de spécificité vis-à-vis de leur cible, de leur affinité modulable et de par leur stabilité, les anticorps sont devenus des agents thérapeutiques de tout premier choix. Un des challenges de ce secteur est de créer des anticorps de très bonne qualité, de plus en plus rapidement, tout en ayant des coûts de développement de moins en moins conséquents in fine.
Assuntos
Anticorpos Monoclonais , Desenvolvimento de Medicamentos , Indústria Farmacêutica , Imunoconjugados , Fragmentos de Imunoglobulinas , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/uso terapêutico , Medicamentos Biossimilares/síntese química , Medicamentos Biossimilares/química , Medicamentos Biossimilares/uso terapêutico , Desenvolvimento de Medicamentos/economia , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/normas , Indústria Farmacêutica/economia , Indústria Farmacêutica/métodos , Indústria Farmacêutica/normas , Humanos , Imunoconjugados/química , Imunoconjugados/metabolismo , Imunoconjugados/uso terapêutico , Fragmentos de Imunoglobulinas/biossíntese , Fragmentos de Imunoglobulinas/química , Fragmentos de Imunoglobulinas/uso terapêuticoAssuntos
Anticorpos , Camelídeos Americanos/imunologia , Fragmentos de Imunoglobulinas/biossíntese , Animais , Anticorpos/imunologia , Anticorpos/isolamento & purificação , Especificidade de Anticorpos , Indústria Farmacêutica/tendências , Fragmentos de Imunoglobulinas/química , Fragmentos de Imunoglobulinas/isolamento & purificaçãoRESUMO
A high affinity anti-digoxin single-chain Fv antibody fragment (scFv) was cloned from the mouse 2C2 hybridoma cell line and was functionally expressed both in the Escherichia coli periplasm as a soluble molecule and at the surface of the filamentous M13 bacteriophage as a fusion protein with the gene III minor coat protein. The 2C2 scFv sequence significantly differs from that of all the other anti-digoxin antibodies previously described. The 2C2 scFv shares with its parental monoclonal antibody a high specificity for digoxin, a cross-reactivity with active digoxin metabolites, but none with inactive metabolites. M13 phages displaying the 2C2 scFv at their surface have a high apparent affinity constant for digoxin (6.6 x 10(8) M-1) and were directly used to set up a novel type of immunoenzymatic assay for monitoring digoxin in sera of patients treated for either congestive heart failure or cardiac arrythmias. We thus report for the first time that phages displaying scFv may constitute a large source of important new reagents in the field of immunodiagnosis.