Abstract
In the nearly 35 years since the first process for creating mAbs was
introduced, they have remained a centerpiece of the growing biotechnology
industry. Thirty therapeutic mAbs have been approved around the world,
including 23 in the United States. A number of these drugs have attained
blockbuster status, with sales reaching the coveted billion-dollar mark and
well beyond. Rituxan, Remicade, Avastin, Herceptin, and Humira alone
generated sales of over $4 billion each in 2008, and global sales for this
entire sector surpassed $30 billion last year.
Key challenges and implications presented in this new report include:
- Future products and their indications
- Merits of human versus chimeric structures
- Costs of mAb therapy and the US healthcare debate
- Clinical pipeline with over 250 candidates
- A focus on "engineered" antibodies
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, concentrating on those used for therapeutic
applications. It surveys the latest technologies being applied to the
development of these compounds and profiles the major companies, drugs, and
projects. It then draws conclusions about the future market potential for mAbs
and discusses the major challenges faced by the industry.
The biotech industry devoted years to reducing the immunogenicity of mAbs,
developing the technologies - detailed in this report - 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 currently in the middle of a major shift toward
humanized and human products.
Much work has also been done on altering antibodies' outward form to boost
their efficacy, enabling them to more readily penetrate tumors, enhancing
their ability to stimulate beneficial immune responses, or otherwise improving
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
presented.
Monoclonal Antibodies: Pipeline Analysis and Competitive Assessment presents
an analysis for the current state of mAb drug development. It identifies more
than 250 therapeutic products now in clinical trials, which are largely
concentrated in the areas of cancer, immunological and inflammatory diseases,
as well as infectious diseases. Beyond these, hundreds more candidates are at
the preclinical stage of development. Reviewed here are the products that are
already available, those in clinical development, and those still at the
preclinical stage that are likely to play an important role in the advancement
of the field.
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 35 Years of Monoclonal Antibody
Development
- 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
- MedImmune (AstraZeneca)
- Dyax
- Crucell
- MorphoSys
- Affitech
- Biosite (Inverness Medical Innovations)
- Affimed Therapeutics
- XOMA
- Ribosome Display
- MedImmune (AstraZeneca)
- Discerna
- Other Library-Based Technologies
- Alexion Pharmaceuticals
- BioInvent International
- Adimab
- MSM Protein Technologies
- Vaccinex
- Morphotek (Eisai Corp. of North America)
- AnaptysBio
- Sorrento Therapeutics
- 2.3. Other Technologies for Designing Monoclonal Antibodies
- Techniques for Improving Hybridoma Production
- Abeome
- New Techniques for Generating Animal-Derived Monoclonal Antibodies
- GENOVAC (Aldevron)
- Epitomics
- North Coast Biologics
- Xori
- Chiome Bioscience
- Humanization Technology
- Abmaxis (Merck)
- Arana Therapeutics
- MRC Technology
- ImmunoGen
- KaloBios Pharmaceuticals
- PDL BioPharma
- XOMA
- Antitope
- Xencor
- Massachusetts Institute of Technology
- Transgenic Mice
- Amgen
- Medarex
- AVANIR Pharmaceuticals
- Regeneron Pharmaceuticals
- Human Hybridoma Technology
- Morphotek (Eisai Corp. of North America)
- Patrys
- Kenta Biotech
- 2.4. Alternative Antibody Formats
- Antibody Fragments
- ESBATech
- MacroGenics
- Genmab
- Synthetic Antibodies
- Ablynx
- Affibody
- Domantis (GlaxoSmithKline)
- AdAlta
- Enzon Pharmaceuticals/Micromet
- Arana Therapeutics
- Bispecific Antibodies
- Elusys Therapeutics
- Micromet
- TRION Pharma
- Affimed Therapeutics
- Affitech/Pharmexa
- Biotecnol
- Other Antibodies That Enhance Effector Function
- BioWa
- MacroGenics
- Tolerx
- Vaccibody
- InNexus Biotechnology
- Xencor
- 2.5. Antibody Conjugates
- Antibody-Radioisotope Conjugates
- Affibody
- PBL Therapeutics
- Aduro BioTech
- Antibody-Drug Conjugates
- Medarex
- HERMES Biosciences
- Celldex Therapeutics
- Scancell
- Paladin Labs
- Antibody-Toxin Conjugates
- 2.6. Technologies for Improving Monoclonal Antibody Characteristics
- Protein Engineering
- Applied Molecular Evolution (Eli Lilly)
- Arana Therapeutics
- Morphotek
- MilleGen/Accuro Biologics
- Facet Biotech
- Xencor
- Merus
- Algonomics
- f-star
- PEGylation
- Alternatives to PEGylation
- Glycosylation
- GlycArt (Roche)
- GlycoFi (Merck)
- Glycotope
- Synageva BioPharma
- LFB
- Alternative Modes of Administration
- Altus Pharmaceuticals
- Baxter BioPharma Solutions
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)
- Cimzia (Certolizumab Pegol) (2008)
- Ilaris (Canakinumab) (2009)
- 3.2. Monoclonal Antibodies in Development for Cancer
- Unconjugated Monoclonal Antibodies for Cancer
- Genmab
- Medarex
- Biogen Idec
- Genentech
- Human Genome Sciences
- Pfizer
- Wilex
- Immunomedics
- ImClone Systems (Eli Lilly)
- Morphotek (Eisai Corp. of North America)
- Antisoma
- Micromet
- UCB
- AVEO Pharmaceuticals
- Lpath
- Northwest Biotherapeutics
- Anti-idiotype Monoclonal Antibodies for Cancer
- Menarini Group
- Onyvax
- Conjugated Monoclonal Antibodies for Cancer
- Active Biotech
- Antisoma
- ImmunoGen
- Immunomedics
- MedImmune
- Seattle Genetics
- Celldex Therapeutics/Curagen
- 3.3. Monoclonal Antibodies in Development for Immunological Diseases
- Human Genome Sciences
- Novartis
- UCB
- Amgen
- Biogen Idec/Genentech
- MedImmune
- Genmab
- Millennium Pharmaceuticals (Takeda Pharmaceutical)
- Medarex
- NovImmune
- BioTie Therapies
- Micromet
- ZymoGenetics/Novo Nordisk
- Glenmark Pharmaceuticals
- CSL
- LigoCyte Pharmaceuticals
- Sanofi-Aventis/Kyowa Hakko Kirin
- 3.4. Monoclonal Antibodies in Development for Infectious Diseases
- Novartis
- MedImmune
- Human Genome Sciences
- Taimed Biologics
- Medarex
- Elusys Therapeutics
- Emergent BioSolutions
- Crucell
- Progenics Pharmaceuticals
- Roche
- Genmab
- Theraclone Sciences
- iBioPharma
- 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
- Eli Lilly
- Pfizer
- Others
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
CHAPTER 5
Survey Results and Analysis
REFERENCES
COMPANY INDEX WITH WEB ADDRESSES
