This book examines all aspects of engineering monoclonal antibodies to make more competitive antibodies and how the various genetic engineering approaches will affect candidates of the future.
Monoclonal antibodies have been used as therapeutics since Orthoclone OKT3 was first approved for marketing in 1986. Early advances in antibody engineering including chimerization and humanization technologies were used to make improved therapeutic antibodies such as Rituxan, Remicade, and Herceptin, all of which were first approved for marketing in the late 1990s. As of 2010, 28 therapeutic antibodies have been approved for marketing, generating $35.5 B in sales in 2009. Thus, therapeutic monoclonal antibodies have come of age and are now projected to become a mainstay of the ethical drug market in the coming decades.
Currently, there are more than 300 new therapeutic monoclonal antibody candidates in clinical trials crossing several therapeutic areas. Many of these target the same molecules, making for a highly competitive environment going forward. For example, there are more than eight known candidates targeting the receptor IGF1-R for oncology indications. It has become apparent that for candidates such as these to win in the upcoming crowded marketplace, they must be clearly differentiated from their competitors. Thus, the field of antibody engineering has once again become a vital and integral part of making new, improved, 'next-generation' therapeutic monoclonal antibodies that have properties better than those already on the market.
• This key book goes beyond the standard engineering issues (ADCC, CDC,
half-life engineering, etc) that are covered by most books and delves into structure-
function relationships that will help to evolve new antibody structures beyond
those already in clinical trials
• Also discusses how current and future genetic engineering of cell lines will pave the way for much higher productivity, allowing for an overall decrease in cost-of-goods
• Highlight the successes, failures, and competition in the antibody engineering field from a completely neutral standpoint
- Introduction to Antibody Engineering in the 21st century
- Historical context of Antibody Engineering, including timelines from engineering breakthroughs to successful marketing
- Compendium of all known engineered therapeutic monoclonal antibody and Fc fusion proteins on the market and in the clinic
- 21st Century Engineering of V-chains - humanization, affinity maturation, and optimization of antibody structure for solubility, lack of aggregation, and optimal behaviour
- Antibody interactions with the immune system
- Structure-Function Relationships for IgGs - details
- Modified IgG Antibodies as Therapeutics
- Fc fusion proteins, Mimetibodies, and similar Fc-related constructs
- Alternative Antibody Forms: IgAs, IgMs, Domain Antibodies and similar constructs - barriers and opportunities to develop these alternative isotpyes into therapeutic monoclonal antibodies
- Surrogate Antibody Issues and Next Generation mouse models to test human antibody function in a more human-like manner
- Engineering cell lines to produce significantly greater quantities of next generation antibodies - issues and possible solutions
- Multi-antibody approach to therapy
- Immunogenicity and other issues
- The influence of Follow-on Biologics on Therapeutic Antibodies
- Engineered Therapeutic Monoclonal Antibodies for 2020 and beyond
- Literature cited (including examples of pertinent patents)
Researchers in biotechnology and pharma industry; lecturers (and very advanced students).
Strohl, William R. Dr and Strohl, Lila M.
Dr William R. Strohl is Vice President, Biologics Research, J&J Biotechnology Center of Excellence. He has a long and distinguished academic career. From 1980 to 1997 he rose from Assistant to Full Professor in the Department of Microbiology and the Program of Biochemistry at The Ohio State University, Columbus, OH. Dr Strohl moved to Merck in 1997. From 2001 to 2008, Dr Strohl was a leader in MerckÃ?Â¯Ã?Â¿Ã?Â½s efforts to develop therapeutic monoclonal antibodies, as well as in-licensing of therapeutic targets and technologies associated with monoclonal antibodies. As part of this effort, Dr. Strohl was the scientific leader in the acquisition and integration of Abmaxis and GlycoFi into the Merck Biologics organization. In April, 2008, Dr. Strohl was named leader of Antibody Drug Discovery at Centocor (J&J). With evolution of biologics at Johnson & Johnson to serve additional therapeutic areas beyond Immunology and Oncology, Dr Strohl was recently named as VP and Head, Biologics Research, in the newly formed J&J Biotechnology Center of Excellence. Dr Strohl has over 100 publications and several patents, and has edited two books.
Lila M Strohl is a Member of the Association of Medical Illustrators and is a Certified Medical Illustrator (CMI). She has worked in the Medical Illustration field, Head of Medical Illustration at St. Anthony Medical Center, Columbus, Ohio, Medical Illustrator in Dept. of Biomedical Communications, Ohio State University Medical Center, and as owner of Medcom Graphics, an independent contractor.