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dc.contributor.author
Cerutti, Maria Laura
dc.contributor.author
Pesce, Analía
dc.contributor.author
Bès, Cédric
dc.contributor.author
Seigelchifer, Mauricio
dc.date.available
2020-05-15T19:04:06Z
dc.date.issued
2019-03
dc.identifier.citation
Cerutti, Maria Laura; Pesce, Analía; Bès, Cédric; Seigelchifer, Mauricio; Physicochemical and biological characterization of RTXM83, a new Rituximab biosimilar; Springer; Biodrugs; 33; 3; 3-2019; 307-319
dc.identifier.issn
1173-8804
dc.identifier.uri
http://hdl.handle.net/11336/105262
dc.description.abstract
BACKGROUND: RTXM83 is a rituximab biosimilar with proven clinical safety and efficacy. It is the first rituximab biosimilar developed and approved in South America and is currently marketed in several Latin American, Middle Eastern and African countries. OBJECTIVE: The aim of this study was to present the physicochemical and biological characterization studies utilized to demonstrate the similarity between RTXM83 and its reference product. METHODS: Primary and higher order protein structures were analysed using peptide mapping with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS), fluorescence spectroscopy and circular dichroism, and micro-differential scanning calorimetry, among other techniques. Charge variants were determined by cation-exchange chromatography (CEX) and capillary isoelectric focusing (cIEF). Glycosylation and glycoforms distribution were analysed using MS, normal phase high-performance liquid chromatography (NP-HPLC) and high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD). Size variants were evaluated by size-exclusion chromatography (SEC), sedimentation velocity analytical ultracentrifugation (SV-AUC), dynamic light scattering (DLS), and capillary electrophoresis-sodium dodecyl sulfate (CE-SDS). Biological characterization included binding assays for complement C1q, CD20, and several Fc receptors (FcRs), as well as potency determination for in vitro apoptosis induction, complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). RESULTS: RTXM83 and the reference product showed identical primary sequences and disulfide bridge patterns, and similarity at higher order protein structures, post-translational modification profiles (amino acid modifications, charge variants, and glycosylation) and levels of purity and process-related impurities. Functional studies demonstrated that RTXM83 is similar to the reference product regarding the three known mechanisms of action of rituximab: CDC, ADCC, and apoptosis induction. Binding affinities to CD20, complement component C1q, and different FcRs were also equivalent. CONCLUSION: RTXM83 is similar to its reference product in all critical quality attributes.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
BIOSIMILAR
dc.subject
RITUXIMAB
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RTXM83
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COMPARABILITY
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Biotecnología relacionada con la Salud
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Biotecnología de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Physicochemical and biological characterization of RTXM83, a new Rituximab biosimilar
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-04-24T18:02:33Z
dc.identifier.eissn
1179-190X
dc.journal.volume
33
dc.journal.number
3
dc.journal.pagination
307-319
dc.journal.pais
Alemania
dc.journal.ciudad
Berlin
dc.description.fil
Fil: Cerutti, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Mabxience; España
dc.description.fil
Fil: Pesce, Analía. Mabxience; España
dc.description.fil
Fil: Bès, Cédric. Mabxience; España
dc.description.fil
Fil: Seigelchifer, Mauricio. Mabxience; España
dc.journal.title
Biodrugs
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007/s40259-019-00349-2
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s40259-019-00349-2
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