Fractionation of follicle stimulating hormone charge isoforms in their native form by preparative electrophoresis technology

Dallia Catzel, David Y. Chin, Peter G. Stanton, Peter Philip Gray, Stephen M. Mahler

    Research output: Contribution to journalArticleResearchpeer-review

    4 Citations (Scopus)

    Abstract

    Complex glycoprotein biopharmaceuticals, such as follicle stimulating hormone (FSH), erythropoietin and tissue plasminogen activator consist of a range of charge isoforms due to the extent of sialic acid capping of the glycoprotein glycans. Sialic acid occupies the terminal position on the oligosaccharide chain, masking the penultimate sugar residue, galactose from recognition and uptake by the hepatocyte asialoglycoprotein receptor. It is therefore well established that the more acidic charge isoforms of glycoprotein biopharmaceuticals have higher in vivo potencies than those of less acidic isoforms due to their longer serum half-life. Current strategies for manipulating glycoprotein charge isoform profile involve cell engineering or altering bioprocesss parameters to optimise expression of more acidic or basic isoforms, rather than downstream separation of isoforms. A method for the purification of a discrete range of bioactive recombinant human FSH (rhFSH) charge isoforms based on Gradiflow™ preparative electrophoresis technology is described. Gradiflow™ electrophoresis is scaleable, and incorporation into glycoprotein biopharmaceutical production bioprocesses as a potential final step facilitates the production of biopharmaceutical preparations of improved in vivo potency.

    Original languageEnglish
    Pages (from-to)73-85
    Number of pages13
    JournalJournal of Biotechnology
    Volume122
    Issue number1
    DOIs
    Publication statusPublished - 9 Mar 2006

    Keywords

    • Follicle stimulating hormone
    • Isoforms
    • Preparative electrophoresis

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