Bio-therapeutics like monoclonal antibodies has a major share in the biopharmaceutical industry for the treatment of life-threatening chronic diseases such as cancer, skin ailments and immune disorders. A lot of instabilities are associated with these protein therapeutics which include aggregation, fragmentation, oxidation, reduction and truncation which leads to their mandatory storage at low temperatures (-80°C to -20°C). However, a disposition towards high temperature storage (25°C - 55°C) of protein drugs has been gaining in African countries where temperature reaches the highest point during summer, causing these instabilities and increases the risk to patient’s life. During forced or accelerated stability studies of the model protein, it was observed that the primary route of degradation involved both chemical as well as physical routes. Presently available therapeutic formulations contain excipients like salts, sugars, amino acids, surfactants and polymers but none of these are quite effective in providing an overall stability to these drug molecules when subjected to extreme storage conditions such as high temperature. The current work builds on this motivation, thereby focusing on application of lysine based dendrons of different generations for development of a stable formulation at high temperature. Amongst these dendrons, third generation dendrons have been identified to provide highest stability to mAbs as demonstrated by a host of analytical techniques such as Size Exclusion Chromatography (SEC), Dynamic Light Scattering (DLS), and Circular Dichroism (CD). The bio-compatibility of these dendrons was also checked by performing hemolytic activity tests. We hope that this study will stimulate utilization of such higher generation dendrons for enhancing thermal stability of mAbs.

Peptide dendrons as thermal stability amplifiers for IgG1 monoclonal antibody biotherapeutics

253rd National Meeting (2017)

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