7 Engineering of Therapeutic Proteins

Protein Therapeutics versus Small Molecule Drugs .............................................. 154 Sources of Protein Therapeutics ................................................................... 155 Targets of Protein Therapeutics and Modes of Action .................................. 155 Engineering Effective Protein Therapeutics .......................................................... 156 Challenges in Pharmaceutical Translation of New Therapeutic Proteins ..... 156 Strategies for Designing Effective Protein Therapeutics .............................. 156 Strategies for Improving Pharmacokinetics ...................................... 157 Strategies for Reducing Immunogenicity ......................................... 158 Genetic Engineering ......................................................................... 159 Examples of Protein Therapeutics ......................................................................... 160 Monoclonal Antibody Therapeutics.............................................................. 161 Enzyme Therapeutics Acting on Extracellular Targets ................................. 161 Protein Therapeutics as Replacements for Defective or Deficient Proteins .....162 Protein Hormones ............................................................................. 162 Coagulation Factors .......................................................................... 163 Enzyme Replacement Therapy ......................................................... 163 Cytokines and Their Receptors as Protein Therapeutics .............................. 164 Colony Stimulating Factors .............................................................. 164 Interleukins and Their Receptors ...................................................... 164 Interferons ......................................................................................... 165 New Classes of Therapeutic Proteins under Development .................................... 167 Major Histocompatibility Complex (MHC) Proteins ................................... 167 Phage Display ................................................................................... 167 Cell Surface Display ......................................................................... 167 T Cell Receptors (TCRs) .............................................................................. 168 Protein Fusions and Rational Design ................................................ 169 Phage Display ................................................................................... 170 Yeast Surface Display ....................................................................... 170 TCR-Like Antibodies .................................................................................... 170 Conclusion and Future Prospects ........................................................................... 171 References .............................................................................................................. 171