Paper describes detected changes in selected product attributes of three marketed biologics, both from EU and US markets. All changes had been approved by regulatory agencies (i.e. information on the drugs remained unchanged). This is very important achievement, as such changes had been only speculated about so far. Data on more than ten analysed batches of each biologics before and after detected change are presented in the paper. Based on these facts more fair discussion on approval for biosimilar drugs by regulatory agencies it is expected.
Thermodynamical model was set last year and manuscript was sent into publication last year, while it was published in the begining of this year. For the characterization of TNF and its inhibitors we carried out thermodynamic study and generated data were used to set the thermodynamic model with the purpose to understand the molecular forces involved in the recognition of TNF by the antibody with inhibitory activity. We studied the energetics of binding of a therapeutic antibody fragment (Fab) to the native and non-native forms of TNF-α by employing calorimetric and spectroscopic methods. The data were supported by structural modeling. We demonstrated that the observed high affinity binding of Fab to TNF-α is an enthalpy-driven process due mainly to specific noncovalent interactions. The study results contribute to a better understanding of the molecular mechanism of regulation of TNF activity, which will help us in designing potential inhibitors of TNF based on chemically modified analogues. The study will also assist in the development of biosimilar TNF inhibitors on the basis of mAbs.
COBISS.SI-ID: še ni vpis
This paper presents the design and characterization of different hG-CSF dimers and their PEGylated version, which would be potentially useful for therapy. In addition to the physico-chemical characterization it includes in vivo testing to determine the pharmacokinetic properties. The basis for the design of molecules has been a finding that suggests interesting PD properties of the PEGylated natural dimer. However, since it is impossible to obtain such natural dimer economically, we were looking for alternative ways of preparing molecules with similar properties. Although we were able to produce larger amounts of hG-CSF dimers, none of them showed as good properties as a natural dimer. Nevertheless, the results show the way how to continue research in the direction to descign better therapeutics.