Abstract
In the more than 30 years since the first process for creating monoclonal antibodies, or mAbs, was introduced, they have remained a centerpiece of the growing biotechnology industry. Twenty-four therapeutic mAbs have been approved, several of which have attained blockbuster status, with sales reaching the coveted billion-dollar mark and well beyond. Two drugs, Remicade and Rituxan, generated sales of about $4 billion each in 2006, and global sales for this entire portfolio approached $20 billion in that year. Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment reviews the broad drug development effort that is focused on bringing improved mAb-based products to the market, focusing on those used for therapeutic applications.
Specifically, the report covers:
- Discussion of the latest technologies being applied to the development of mAbs
- Profiles the major companies, drugs, and projects
- Conclusions about the future market potential for mAbs
- Discussion of some of the major challenges faced by the industry
- Analysis of the results from an online survey of industry professionals
In that survey, 81% of respondents indicated that their organization' s pipeline of mAb products has increased over the past 5 years.
Monoclonal antibodies are highly specific antibodies produced in the laboratory by a variety of methods. The first generation of mAbs were murine (derived from mice), but these were soon discovered to have several weaknesses. They were targeted for neutralization by the human immune system and also induced the formation of damaging immune complexes. The biotech industry devoted years to reducing the immunogenicity of mAbs, developing the technologies to progress from chimeric to humanized to fully human antibodies. These succeeding generations of mAbs have demonstrated incremental improvements in safety and activity, and the industry is in the middle of a major shift from murine toward humanized and human products. Much work has also been done on altering antibodies' outward form to:
- Boost their efficacy
- Enable them to more readily penetrate tumors
- Enhance their ability to stimulate beneficial immune responses
- Otherwise improve their characteristics
Into this realm fall such constructions as antibody fragments, diabodies, synthetic antibodies, bispecific antibodies, and antibody conjugates. This report looks at some of the engineered forms of antibodies and the companies that are leading the way in this research. Other complementary technologies such as PEGylation and glycosylation are also discussed.
Table of Contents
Chapter 1 BACKGROUND AND SCIENTIFIC OVERVIEW: ANTIBODIES AND MONOCLONAL ANTIBODIES
- 1.1. What Is an Antibody?
- 1.2. What Is a Monoclonal Antibody
Chapter 2 CURRENT AND EMERGING TECHNOLOGIES: IMPROVING MONOCLONAL ANTIBODY DESIGN AND PRODUCTION
- 2.1. Key Breakthroughs in the First 30 Years of Monoclonal Antibody
Production
- Murine-Derived Monoclonal Antibodies
- Chimeric Monoclonal Antibodies
- Humanized Monoclonal Antibodies
- Fully Human Monoclonal Antibodies
- Antibody Fragments
- Antibody Conjugates
- 2.2. Monoclonal Antibody Libraries and Display Technologies
- Phage Display
- Cambridge Antibody Technology
- Dyax
- Crucell
- MorphoSys
- Affitech
- Biosite
- Affimed Therapeutics
- XOMA
- Ribosome Display
- Cambridge Antibody Technology
- Discerna
- Other Library-Based Technologies
- Alexion Antibody Technologies
- BioInvent International
- MSM Protein Technologies
- Vaccinex
- Morphotek
- Phage Display
- 2.3. Other Technologies for Designing Monoclonal Antibodies
- Techniques for Improving Hybridoma Production
- Abeome
- New Technologies for Generating Animal-Derived Monoclonal Antibodies
- GENOVAC
- Epitomics
- Humanization Technology
- Abmaxis
- EvoGenix
- AERES Biomedical/Therapeutic Antibody Group
- ImmunoGen
- KaloBios Pharmaceuticals
- PDL BioPharma
- Massachusetts Institute of Technology
- XOMA
- Transgenic Mice
- Amgen
- Medarex
- AVANIR Pharmaceuticals
- XTL Biopharmaceuticals
- Regeneron Pharmaceuticals
- Human Hybridoma Technology
- Morphotek
- Techniques for Improving Hybridoma Production
- 2.4. Alternative Antibody Formats
- Antibody Fragments
- Genmab
- Synthetic Antibodies
- Ablynx
- Affibody
- Domantis
- Enzon Pharmaceuticals/Micromet
- EvoGenix
- Regeneron Pharmaceuticals
- Bispecific Antibodies
- Elusys Therapeutics
- Micromet
- TRION Pharma
- Affimed Therapeutics
- Pharmexa/Affitech
- Biotechnol
- Other Antibodies that Enhance Effector Function
- BioWa
- MacroGenics
- TolerRx
- University of Oslo
- InNexus Biotechnology
- Xencor
- TeGenero
- Antibody Fragments
- 2.5. Antibody Conjugates
- Antibody-Radioisotope Conjugates
- Affibody
- PBL Therapeutics
- Triton BioSystems
- Antibody-Drug Conjugates
- HERMES Biosciences
- Celldex Therapeutics
- Scancell
- Virexx Medical
- Antibody-Toxin Conjugates
- EvoGenix
- Antibody-Radioisotope Conjugates
- 2.6. Technologies for Improving Monoclonal Antibody Characteristics
- Protein Engineering
- Applied Molecular Evolution
- EvoGenix
- Verenium
- Morphotek
- MilleGen
- PDL BioPharma
- PEGylation
- Enzon Pharmaceuticals/Nektar Therapeutics
- Prolong Pharmaceuticals
- Ambrx
- Others
- Alternatives to PEGylation
- Glycosylation
- GlycArt Biotechnology
- GlycoFi
- Glycotope
- Neose Technologies
- LFB
- Alternative Modes of Administration
- Altus Pharmaceuticals
- Epic Therapeutics
- Protein Engineering
- 2.7. Technologies for Improving Monoclonal Antibody Production
- Increasing Yields in Mammalian Cultures
- Transgenic Animals
- Transgenic Plants
Chapter 3 MARKETED AND EMERGING MONOCLONAL ANTIBODIES: PRESENT AND FUTURE THERAPEUTICS
- 3.1. Approved Therapeutic Monoclonal Antibodies
- Profiles of Therapeutic Monoclonal Antibodies Approved for Marketing
- Orthoclone OKT3 (Muromonab-CD3) (1986)
- ReoPro (Abciximab) (1994)
- Rituxan (Rituximab) (1997)
- Zenapax (Daclizumab) (1997)
- Simulect (Basiliximab) (1998)
- Synagis (Palivizumab) (1998)
- Remicade (Infliximab) (1998)
- Herceptin (Trastuzumab) (1998)
- Mylotarg (Gemtuzumab Ozogamicin) (2000)
- Campath (Alemtuzumab) (2001)
- Zevalin (Ibritumomab Tiuxetan) (2002)
- Humira (Adalimumab) (2002)
- Xolair (Omalizumab) (2003)
- Bexxar (Tositumomab) (2003)
- Raptiva (Efalizumab) (2003)
- Erbitux (Cetuximab) (2004)
- Avastin (Bevacizumab) (2004)
- Tysabri (Natalizumab) (2006)
- Lucentis (Ranibizumab) (2006)
- Vectibix (Panitumumab) (2006)
- Soliris (Eculizumab) (2007)
- Profiles of Therapeutic Monoclonal Antibodies Approved for Marketing
- 3.2. Monoclonal Antibodies in Development for Cancer
- Unconjugated Monoclonal Antibodies for Cancer
- Genmab
- Medarex
- Biogen Idec
- Genentech
- Human Genome Sciences
- Wilex
- Immunomedics
- Regeneron Pharmaceuticals
- ImClone Systems
- Antisoma
- Micromet
- MedImmune
- GPC Biotech
- ARIUS Research
- AVEO Pharmaceuticals
- Lpath
- Northwest Biotherapeutics
- Anti-idiotype Antibodies for Cancer
- Menarini Group
- Onyvax
- Conjugated Monoclonal Antibodies for Cancer
- Viventia Biotech
- Amgen
- Active Biotech
- Antisoma
- ImmunoGen
- Immunomedics
- Cambridge Antibody Technology
- Seattle Genetics
- Merck Serono
- CuraGen
- Celldex Therapeutics
- Unconjugated Monoclonal Antibodies for Cancer
- 3.3. Monoclonal Antibodies in Development for Immunological Diseases
- UCB
- Regeneron Pharmaceuticals
- Centocor
- Human Genome Sciences
- Zymogenetics
- Amgen
- Biogen Idec/Genentech
- Cambridge Antibody Technology
- Genmab
- MedImmune
- Millennium Pharmaceuticals
- NovImmune
- Medarex
- Micromet
- BioTie Therapies
- CSL
- Glenmark Pharmaceuticals
- LigoCyte Pharmaceuticals
- 3.4. Monoclonal Antibodies in Development for Infectious Diseases
- NeuTec Pharma
- MedImmune
- Human Genome Sciences
- Progenix Pharmaceuticals
- Medarex
- XTL Biopharmaceuticals
- Elusys Therapeutics
- Genmab
- AVANIR Pharmaceuticals
- 3.5. Monoclonal Antibodies in Development for Cardiovascular Diseases
- Ablynx
- ThromboGenics/BioInvent International
- Affimed Therapeutics
- Lexicon Pharmaceuticals
- 3.6. Other Therapeutic Antibodies in Development
- Amgen
- Elan/Wyeth
- Rinat Neuroscience
- Wyeth/Cambridge Antibody Technology
Chapter 4 BUSINESS AND STRATEGIC OUTLOOK: MARKET POTENTIAL FOR MONOCLONAL ANTIBODIES AND TRENDS IN THE FIELD
- 4.1. General Trends
- 4.2. The Market for Therapeutic Monoclonal Antibodies
- Cancer: Solid Tumors
- Cancer: Non-Hodgkin' s Lymphoma
- Immune and Inflammatory Diseases
- Transplant Rejection
- Rheumatoid Arthritis
- Crohn' s Disease
- Psoriasis
- Lupus
- Multiple Sclerosis
- Asthma
- Other Emerging Markets
- Age-Related Macular Degeneration
- HIV
- Alzheimer' s Disease
