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19 - Polymer Fusions to Increase Antibody Half-Lives: PEGylation and Other Modifications

from PART VIII - PROLONGATION OF SERUM HALF-LIFE

Published online by Cambridge University Press:  15 December 2009

By
Sam P. Heywood  and
David P. Humphreys
Edited by
Melvyn Little
Melvyn Little
Affiliation:
Affimed Therapeutics AG
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Summary

PEGylation of proteins has been performed for over 30 years (Abuchowski et al., 1977a,b). Although the details such as polyethylene glycol (PEG) size, structure, synthesis, purification, and reactive chemistries have changed, the basic aims of the method remain the same. These aims are to improve the biophysical and pharmaceutical characteristics of proteins by modifying pharmacokinetics (circulating serum half-life); increasing resistance to proteolysis; reducing antigenicity and immunogenicity; and in some instances, increasing solubility and reducing propensity to aggregate. These improvements have been demonstrated successfully in the clinic with a variety of proteins including enzymes, cytokines, and antibodies. In this chapter we will introduce the aspects of PEGylation common to all proteins before dealing with their specific application to antibodies and antibody fragments.

POLYMERS FOR PROTEIN CONJUGATION

Many potential therapeutic proteins have characteristics that can be improved by conjugation to large water-soluble polymers. Tailoring of these characteristics is required in order to generate the most effective therapeutic. Alteration of a protein's characteristics may also expand its use, for example, from single use in acute indications to repeat dosing in chronic indications. Conjugation of both small molecule and protein-based drugs to a diverse range of polymers has been investigated in order to improve their therapeutic profile.

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Recombinant Antibodies for Immunotherapy , pp. 275 - 292
Publisher: Cambridge University Press
Print publication year: 2009

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