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Physicochemical and functional characterization of trastuzumab-dkst, a trastuzumab biosimilar.
20 auth. P. Goyal, J. Iyer, L. Adhikary, Bhavesh Vats, Pradeep G. Kabadi, Harish Pai, Daniel Ranayhossaini, Shankar Gouda, M. Subbarao, G. Mehta, ...
Aims: Preclinical comparative similarity studies of trastuzumab-dkst, a Herceptin® biosimilar, are reported. Materials & methods: Primary sequence and higher-order structure and pharmacological mechanisms of action were compared using multiple techn…
Aims: Preclinical comparative similarity studies of trastuzumab-dkst, a Herceptin® biosimilar, are reported. Materials & methods: Primary sequence and higher-order structure and pharmacological mechanisms of action were compared using multiple techniques. Pharmacokinetics and repeat-dose toxicity were assessed in cynomolgus monkeys. Results: Primary structures were identical; secondary and tertiary structures were highly similar. Non-significant differences were observed for charge heterogeneity. Twelve of 13 glycan species were highly similar, with slightly higher total mannose levels in trastuzumab-dkst. FcγR and FcRn binding activity was highly similar. Each drug equally inhibited HER2+ cell proliferation, demonstrating equivalent relative potency in mediating HER2+ cell cytolysis by antibody-dependent cellular cytotoxicity. Pharmacokinetic and toxicological profiles in cynomolgus monkeys were similar. Conclusion: Trastuzumab-dkst, US-licensed trastuzumab and EU-approved trastuzumab demonstrate high structural and functional similarity.
Published in
Future Medicinal Chemistry
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0 | 2021 |
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