Report: Directed Molecular Evolution: Product lifecycle management for biologics TOC

CHAPTER 1 EXECUTIVE SUMMARY
- Key Findings
- Scope
- Definition of key terms
  - Small molecules
  - Biologics
  - Monoclonal antibodies
  - Therapeutic proteins
- Biologics market size
- Biologics market growth rate
- Threat to biologics - bio-similars
- DME science
- DME companies
  - Applied Molecular Evolution
  - Maxygen
  - Cambridge Antibody Technology (CAT)
  - MorphoSys
- The first DME to hit the market - Synagis/Numax
- DME-based business models
CHAPTER 2 THE COMMERCIAL CONTEXT FOR DME - THE BIOLOGICS MARKET
- Introduction
- Definition of key terms
  - Small molecules
  - Biologics
  - Monoclonal antibodies
  - Therapeutic proteins
- Biologics market size
- Biologics market growth rate
- Threat to biologics - bio-similars
  - Wave of patent expiries makes biogenerics a priority
  - High cost of biologics increases the importance of biogenerics
  - Proving equivalence of the protein
    - Recent CHMP recommendation for Omnitrope a sign of things to come?
- Threat to biologics from intensifying competition
- Current techniques for optimizing biologics
  - Current techniques for optimizing for protein therapeutics
    - Pegylation
    - Glycosylation
- Current techniques for optimizing mAbs
  - Chimeric antibodies
  - CDR grafting
- DME - a technology for the 'evolutionary' optimization of biologics
CHAPTER 3 THE SCIENCE OF DIRECTED MOLECULAR EVOLUTION
- Key findings
- Concept of DME - diversification and selection
- Application - lead optimization for biologics
- Diversification technologies
- Selection technologies
  - Cell screening
    - Display technologies
- Protein formats
- The DME technology landscape
- Amgen and Genentech - Participating in DME?
- DME intellectual property
CHAPTER 4 APPLIED MOLECULAR EVOLUTION
- Key findings
- Company history
- Eli Lilly acquisition
  - DME: providing Lilly the opportunity of accessing new markets
- AME technology
  - AME's technology: the AMEsystem
  - DirectAME
    - Antibodies
  - frAMEworks
  - ExpressAME
  - SelectAME
- AME's financial position
- AME's R&D collaborations
  - Bristol Myers-Squibb first to test AME
  - MedImmune set to benefit from AME
  - Other collaborations
- AME's internal R&D
  - AME-527
    - Overview
    - Market dynamics
    - Methodology
  - AME-133
    - Overview
    - Market dynamics
    - Methodology
  - AME-359
    - Summary
CHAPTER 5 MAXYGEN
- Key findings
- Maxygen company history
- Maxygen technology
  - Maxygen's technology: Molecular Breeding
    - DNA shuffling
- Maxygen's financial position
- Maxygen's R&D collaborations
  - Maxygen achieved industry connections and reputation through process design collaborations
  - Roche is Maxygen's biggest collaborative partner
  - Maxy-Alpha (HCV)
  - Maxy-Factor VII
  - Other collaborations
    - Antibody optimization
- Maxygen's internal R&D
  - MAXY-G34/G-CSF
  - Maxygen has a strong vaccine initiative
    - Maxy-1100
    - Maxy-1200
    - Maxy-1500
    - Maxy-201
    - Maxy-829
    - Maxy-14
  - Summary
CHAPTER 6 OTHER DME PLAYERS
- Introduction
- Cambridge Antibody Technology (CAT)
  - Phage display technology
  - Ribosome display technology
  - Partnerships
  - Product portfolio and pipeline
  - Summary
- MorphoSys
  - MorphoSys technology
  - MorphoSys proprietary candidates
  - MorphoSys collabroative agreements
  - Summary
- Dyax
  - Summary
- Crucell
  - Summary
- Diversa
- Genencor
- Direvo AG
- MilleGen
CHAPTER 7 CASE STUDY: SYNAGIS/NUMAX - THE FIRST DME PRODUCT TO REACH THE MARKET?
- Introduction
  - The facts about RSV
    - Synagis (palivizumab)
    - The role of DME in RSV
    - Numax (motavizumab)
    - DME has provided MedImmune with a successful lifecycle management strategy
CHAPTER 8 APPENDIX
- References
- List of Tables
  - Table 1: General characteristics of small molecule drugs vs. biologics
- List of Figures
  - Figure 1: Global sales by molecule class ($bn), 2001-10
  - Figure 2: Percentage contribution to global sales, 2005 and 2010 split by molecule class
  - Figure 3: CAGR trends split by product class
  - Figure 4: DME can be viewed as lead optimization for biologics
  - Figure 5: The DME concept: diversification then selection
  - Figure 6: Diversification technologies used in DME
  - Figure 7: Selection technologies used in DME
  - Figure 8: Synagis vs. Numax - schematic diagram of amino acid differences
  - Figure 9: Global sales by 2001-2010 split by molecule class
  - Figure 10: Percentage contribution to global sales, 2005 and 2010 split by molecule class
  - Figure 11: CAGR trends split by product class
  - Figure 12: The DME concept - diversification then selection
  - Figure 13: Successive diversify-select cycles drive optimization
  - Figure 14: DME is analogous to natural evolution
  - Figure 15: DME can be viewed as lead optimization for biologics
  - Figure 16: Diversification technologies used in DME
  - Figure 17: An overview of DNA shuffling/molecular breeding
  - Figure 18: Selection technologies used in DME
  - Figure 19: The range of candidate protein types eligible for DME
  - Figure 20: The DME technology landscape
  - Figure 21: The DME technology landscape
  - Figure 22: The AMEsystem
  - Figure 23: mAb optimization
  - Figure 24: AME collaborative timeline
  - Figure 25: AME's collaboration network map
  - Figure 26: Tg197 transgenic murine model of rheumatoid arthritis
  - Figure 27: AME-133 model results
  - Figure 28: Maxygen/Codexis's collaboration: process design
  - Figure 29: Maxygen's collaborations: biologic therapeutics
  - Figure 30: CAT's partnerships for its phage display technology
  - Figure 31: Diversa
  - Figure 32: Genencor
  - Figure 33: Direvo
  - Figure 34: MilleGen
  - Figure 35: Synagis vs. Numax - schematic diagram of amino acid differences
  - Figure 36: The Synagis-Numax switch

Directed Molecular Evolution: Product lifecycle management for biologics

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