Overview on the Use of Therapeutic Antibodies in Drug Discovery

Michael Roguska1, Zehra Kaymakcalan1, Jochen Salfeld1

1 Abbott Bioresearch Center, Worcester, Massachusetts
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 9.7
DOI:  10.1002/0471141755.ph0907s27
Online Posting Date:  January, 2005
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The number of therapeutic antibodies approved by regulatory agencies as novel drugs and the number of antibodies in development has increased significantly. The modular nature of antibody structure has enabled researchers to more predictably design therapeutic antibodies by choosing appropriate functional features most appropriate for a given antibody target and clinical indication. Advances in recombinant antibody technologies have allowed the routine generation of antibodies that can satisfy stringent drug design criteria, such as low immunogenicity, high affinity, target specificity, and commercially viable manufacturing methods. Engineering design opportunities exist for both the variable and the constant regions that encompass, in addition to antigen specificity and affinity, effector functions that mediate immune complex clearance or pharmacokinetics. These are discussed in the context of relevant in vivo and in vitro technologies, such as human IgG transgenic mice, phage display, and biologics manufacturing. Finally, therapeutic antibodies are compared with traditional drugs with respect to target class, selectivity, route of administration, intellectual property issues, and lead discovery and optimization.

Keywords: therapeutic antibodies; antibody generation; antibody engineering

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Table of Contents

  • History of Therapeutic Antibodies
  • Basic Antibody Structure
  • Technologies for Generation of Therapeutic Human Antibodies
  • Design Opportunities for an Antibody Therapeutic
  • Immunogenicity
  • Expression Technologies
  • How do Therapeutic Antibodies Compare with Traditional Drugs?
  • Summary
  • Literature Cited
  • Figures
  • Tables
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Internet Resources
  U.S. Government patent office Web site.
  European patent office Web site.
  Abgenix Web site. Developer of human antibody transgenic mice.
  Medarex Web site. Developer of human antibody transgenic mice.
  Kirin Web site. Developer of human antibody transgenic mice.
  Cambridge Antibody Technology Web site. Developer of antibody therapeutics using phage display technology.
  Domantis Web site. Developer of antibody therapeutics using phage display technology.
  Morphosys AG Web site. Developer of antibody therapeutics using phage display technology.
  Dyax Web site. Developer of antibody therapeutics using phage display technology.
  Biosite Web site. Developer of antibody therapeutics using phage display technology.
  Biovation Web site; technology provider.
  Epimmune Web site; technology provider.
  Genencor Web site; technology provider.
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