Descripción del proyecto
Un enfoque innovador para mejorar el desarrollo de fármacos
Cada vez hay más fármacos nuevos basados en proteínas y, sobre todo, anticuerpos para el tratamiento de diversas enfermedades. Dado el tamaño, la heterogeneidad y la complejidad de las moléculas proteicas, resulta tecnológicamente complejo caracterizarlas al detalle y analizar su pureza durante el proceso de descubrimiento de fármacos. Los científicos del proyecto LCxLCProt, financiado con fondos europeos, proponen desarrollar un método cromatográfico con el que caracterizar biofármacos proteicos. Este nuevo método es adecuado para su uso en las primeras fases del desarrollo de fármacos y después durante su fabricación en tareas de control de calidad. Además, respalda buenas prácticas de fabricación y, por tanto, la confianza del consumidor en los productos farmacéuticos.
Objetivo
Protein biopharmaceuticals, which globally represent about 20 % of the total pharmaceutical market, are becoming increasingly popular in the treatment of various diseases. Experts forecast that over 50 % of new drug approvals in the next decade will be for biologics, especially monoclonal antibodies. Very accurate structural characterization and purity analysis is required during both the development of the new drugs, and later during manufacturing for quality control purposes. Biopharmaceutical protein molecules are very large and heterogeneous, which makes their characterization very difficult. The goal of this project is to develop novel methods for the characterization of protein biopharmaceuticals at the protein level based on comprehensive two-dimensional liquid chromatography (LC×LC). Two approaches will be explored: the use of reversed phase separation mechanism in both dimensions with parallel gradients, and application of thermally responsive stationary phases for thermal modulation of LC×LC fractions. Parallel gradients provide the greatest orthogonality when the separation mechanisms in both dimensions are correlated, and allow the use of short modulation periods, which together lead to a dramatic increase in peak capacity (as demonstrated in preliminary experiments). Thermally responsive stationary phases allow trapping of the analyte bands at elevated temperatures, and their release at low temperature. This is compatible with intact protein analysis, especially when ion exchange is used in the first dimension of the LC×LC system. It is expected that the research will result in new, cutting edge methods for the analysis and characterization of protein biopharmaceuticals that will be applicable under the good manufacturing practice (GMP) conditions, improving the quality assurance/quality control and increasing the confidence in the pharmaceuticals.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
9000 Gent
Bélgica