PEGylated Protein Drugs: Basic Science and Clinical Applications describes the basic technologies and the major results obtained with the PEGylation technique, the covalent binding to proteins, peptides and small organic molecules of the hydrophilic and biocompatible polymer poly(ethylene glycol) to improve their therapeutic efficacy.

The book results from the collaboration of recognized experts from academia and industry, working on various aspects of the PEGylation technology. The first chapters provide general information on the physicochemical, pharmacokinetic, immunogenic and toxicological properties of PEG and PEG-conjugates. The classical and more advanced chemical strategies for linking PEG to protein drugs are described as well as novel enzyme-catalysed approaches. Further chapters are devoted to important PEGylated products, namely PEG conjugates of enzymes, cytokines, antibodies or synthetic organic molecules already on the market or in an advanced state of clinical experimentation. Guidelines for the approval by the Health Agencies of these new nanomedicines are also reported as a last chapter.

Therefore, this book may be a unique instrument for a thorough review of the strategy, advantages and limitations of all aspects of drug PEGylation as well as a stimulation for researchers to develop new exploitations of this technology. It is of interest to physicians, biochemists, pharmacologists and chemists.

Zusammenfassung

PEGylation technology and key applications are introduced by this topical volume. Basic physical and chemical properties of PEG as basis for altering/improving in vivo behaviour of PEG-conjugates such as increased stability, improved PK/PD, and decreased immunogenicity, are discussed. Furthermore, chemical and enzymatic strategies for the coupling and the conjugate characterization are reported. Following chapters describe approved and marketed PEG-proteins and PEG-oligonucleotides as well as conjugates in various stages of clinical development.

Inhalt
Preface PEGylated protein conjugates: A new class of therapeutics for the 21st century.- Protein PEGylation, basic science and biological applications.- Reactive PEGs for protein conjugation.- Rebridging disulphides: site-specific PEGylation by sequential bis-alkylation.- Enzymatic techniques for PEGylation of biopharmaceuticals.- The site-specific TGase-mediated PEGylation of proteins occurs at flexible sites.- Protein conjugates purification and characterization.- PEG and PEG conjugates toxicity: towards an understanding of the toxicity of PEG and its relevance to PEGylated biologicals.- The occurrence, induction, specificity and potential effect of antibodies against poly(ethylene glycol).- Pegfilgrastim designing an improved form of rmetHuG-CSF.- PEGylation of human growth hormone: strategies and properties.- PEGylated ? interferons: two different strategies to achieve increased efficacy.- Development of PEGylated mammalian urate oxidase as a therapy for patients with refractory gout.- Certolizumab pegol: a PEGylated anti-tumour necrosis factor alpha biological agent.- PEG: a useful technology in anticancer therapy.- Regulatory strategy and approval processes considered for PEG-drug conjugates and other nanomedicines.