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Development of in silico models to predict viscosity and mouse clearance using a comprehensive analytical data set collected on 83 scaffold-consistent monoclonal antibodies.
Mock, Marissa; Jacobitz, Alex W; Langmead, Christopher James; Sudom, Athena; Yoo, Daniel; Humphreys, Sara C; Alday, Mai; Alekseychyk, Larysa; Angell, Nicolas; Bi, Vivian; Catterall, Hannah; Chen, Chen-Chun; Chou, Hui-Ting; Conner, Kip P; Cook, Kevin D; Correia, Ana R; Dykstra, Andrew; Ghimire-Rijal, Sudipa; Graham, Kevin; Grandsard, Peter; Huh, Joon; Hui, John O; Jain, Mani; Jann, Victoria; Jia, Lei; Johnstone, Sheree; Khanal, Neelam; Kolvenbach, Carl; Narhi, Linda; Padaki, Rupa; Pelegri-O'Day, Emma M; Qi, Wei; Razinkov, Vladimir; Rice, Austin J; Smith, Richard; Spahr, Christopher; Stevens, Jennitte; Sun, Yax; Thomas, Veena A; van Driesche, Sarah; Vernon, Robert; Wagner, Victoria; Walker, Kenneth W; Wei, Yangjie; Winters, Dwight; Yang, Melissa; Campuzano, Iain D G.
Afiliación
  • Mock M; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Jacobitz AW; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Langmead CJ; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Sudom A; Structural Biology, Amgen Research, South San Francisco, CA, USA.
  • Yoo D; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Humphreys SC; Pharmacokinetics & Drug Metabolism, Amgen Research, South San Francisco, CA, USA.
  • Alday M; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Alekseychyk L; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Angell N; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Bi V; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Catterall H; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Chen CC; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Chou HT; Structural Biology, Amgen Research, South San Francisco, CA, USA.
  • Conner KP; Pharmacokinetics & Drug Metabolism, Amgen Research, South San Francisco, CA, USA.
  • Cook KD; Pharmacokinetics & Drug Metabolism, Amgen Research, South San Francisco, CA, USA.
  • Correia AR; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Dykstra A; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Ghimire-Rijal S; Structural Biology, Amgen Research, Thousand Oaks, CA, USA.
  • Graham K; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Grandsard P; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Huh J; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Hui JO; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Jain M; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Jann V; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Jia L; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Johnstone S; Structural Biology, Amgen Research, South San Francisco, CA, USA.
  • Khanal N; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Kolvenbach C; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Narhi L; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Padaki R; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Pelegri-O'Day EM; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Qi W; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Razinkov V; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Rice AJ; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Smith R; Pharmacokinetics & Drug Metabolism, Amgen Research, South San Francisco, CA, USA.
  • Spahr C; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Stevens J; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Sun Y; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Thomas VA; Pharmacokinetics & Drug Metabolism, Amgen Research, South San Francisco, CA, USA.
  • van Driesche S; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Vernon R; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Wagner V; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Walker KW; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Wei Y; Process Development, Amgen Operations, Thousand Oaks, CA, USA.
  • Winters D; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Yang M; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
  • Campuzano IDG; Biologic Therapeutic Discovery, Amgen Research, Thousand Oaks, CA, USA.
MAbs ; 15(1): 2256745, 2023.
Article en En | MEDLINE | ID: mdl-37698932
Biologic drug discovery pipelines are designed to deliver protein therapeutics that have exquisite functional potency and selectivity while also manifesting biophysical characteristics suitable for manufacturing, storage, and convenient administration to patients. The ability to use computational methods to predict biophysical properties from protein sequence, potentially in combination with high throughput assays, could decrease timelines and increase the success rates for therapeutic developability engineering by eliminating lengthy and expensive cycles of recombinant protein production and testing. To support development of high-quality predictive models for antibody developability, we designed a sequence-diverse panel of 83 effector functionless IgG1 antibodies displaying a range of biophysical properties, produced and formulated each protein under standard platform conditions, and collected a comprehensive package of analytical data, including in vitro assays and in vivo mouse pharmacokinetics. We used this robust training data set to build machine learning classifier models that can predict complex protein behavior from these data and features derived from predicted and/or experimental structures. Our models predict with 87% accuracy whether viscosity at 150 mg/mL is above or below a threshold of 15 centipoise (cP) and with 75% accuracy whether the area under the plasma drug concentration-time curve (AUC0-672 h) in normal mouse is above or below a threshold of 3.9 × 106 h x ng/mL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Descubrimiento de Drogas / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: MAbs Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Descubrimiento de Drogas / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: MAbs Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos