Table of Contents
Chapter 1: Executive Summary 1・
Chapter 2: Biopharmaceuticals are Recombinant Products that Replicate
Functions or Antibodies that are Inhibitory 2・
- Reengineering Medicines 2・
- Humanized Chimeric Antibodies 2・Engineered Fusion Proteins謡ith and without
Fc 2・
- PEGylation 2・
- Glycosylation 2・0
- Growth Hormones and Enzymes 2・1
- Human Growth Factors and Enzymes Approved by FDA in 2004 and 2005 2・2
- Categorization of Growth Factors and Hormones 2・3
- Therapeutic Antibodies 2・6
- Economic Considerations of the Commercial Manufacture of Antibodies 2・7
- Commercialization of Antibody Production 2・9
- Purification Considerations 2・1
- Monoclonal Antibody Successes in the Clinic 2・2
- Antibodies Entering the Clinic 2・6
- FDA Approval of 18 Therapeutic Antibodies 2・6
- Therapeutic Approved Antibodies涌utside the US 2・7
- Cytokines輸 Potential $12・15 Billion 2005 Market 2・8
- Survival Factors (SCF, CNTF, BDGF) 2・9
- FDA Approved Cytokines IL-2 and interferon-alfa 2b and GM-CSF 2・0
- Interleukin-2 2・1
- Granulocyte-Monocyte Colony Stimulating Factor 2・2
- Interleukin-12 2・2
- Vaccines 2・2
- Pasteur and the Discovery of Active Immunization 2・2
- Pediatric Vaccines 2・5
- Disease Eradication 2・5
- Cancer Vaccines 2・7
- Vaccines and Bioterrorism 2・8
- A Comparison of Pharmaceutical Expression Systems 2・0
- The Emerging Industry of Plant-Made Pharmaceuticals and Biopharming 2・3
- Farming Biopharma Drugs佑rops as Bioreactors 2・6
- Plant Cell Cultures Currently in Use for Commercial Recombinant
Biopharmaceuticals 2・9
- Transgenic Animal Factories Cows, Chickens, and Rabbits 2・2
- Notable Companies Using Transgenics 2・4
- Process Development 2・5
Chapter 3: Proteins/Antibodies as Drugs 3・
- Basic Protein Biochemistry 3・
- The Amino Acids 3・
- Chaperone Proteins 3・
- Protein Structure 3・
- The Ribosome 3・1
- Post-Translational Modification 3・2
- Proteolytic Cleavage 3・3
- The Coagulation Cascade 3・4
- Protein Cross Linking 3・5
- Glycosylation 3・6
- Biochemistry of Glycosylation 3・6
- Glycosylated Precursor in the Endoplasmic Reticulum and Golgi Apparatus 3・8
- Lysosomal Targeting of Enzymes 3・2
- Clinical Significances of Glycoproteins 3・2
- Vitamin C-Dependent Modifications 3・3
- Vitamin K-Dependent Modifications 3・4
- Acetylation 3・4
- Phosphorylation 3・5
- Kinases 3・6
- Sulfation 3・6
- Prenylation, Farnesylation, and Geranylgeranylation 3・8
- Protein Degradation: The Ubiquitin Pathway 3・0
- Ubiquitin Function 3・1
- The Ubiquitin-Proteasome Pathway 3・1
- What are the degradation signals? 3・1
- How Does Ubiquitination Lead to Protein Degradation? 3・2
- The Proteasome 3・3
- The 20S Proteasome Chamber 3・3
- The Function of the Proteasome 3・4
- S Proteasome 3・4
- Proteasomes and the Immune Response 3・4
- Comparing the Proteasome and Chaperon 3・5
- Bioreactors for Synthesis of Proteins 3・5
- Prokaryotic Expression Systems裕he Earliest Bioreactor 3・6
- What is the Future for Bacterial Fermentation? 3・8
- Single Cell Eukaryotic Based Protein Synthesis 3・8
- Current Commercial Biopharmaceuticals Made in Yeast and Fungal Expression
Systems 3・0
- Glycosylation of Therapeutic Proteins 3・1
- Baculovirus and Insect Cell-Based Protein Synthesis 3・2
- Mammalian Cell-Based Protein Expression 3・5
- Hybridomas and at the Production of Monoclonal Antibodies 3・5
- To Suppress the Immune System 3・5
- To Kill or Inhibit Malignant Cells 3・5
- To Block Angiogenesis 3・6
- Protein Expression in Mammalian Cells 3・6
- Mammalian Transfection Protocols 3・8
- Electroporation 3・9
- Lipofection 3・9
- Microinjection 3・9
- Viral Expression Systems 3・9
- Transient and Stable Transfection柚ammalian CHO cells 3・0
- The Basic Antibody Response 3・1
- Protein G Based Isolation of Monoclonal Antibody 3・5
- Uses for Monoclonal Antibodies in Pathology 3・5
- Transgenic Mice and Phage Display Libraries for Antibody Production 3・6
- Problems with Monoclonal Therapy 3・8
- The Science of Transgenes, using Plants and Animals as Drug Factories 3・1
- How to Make Transgenic Plants 3・1
- Potential Uses of the Transgenic Plants 3・2
- Ethical and Political Concerns with Genetically Modified Plants 3・3
- Transgenic Animals 3・4
- Nuclear Transfer and Animal Cloning 3・6
- Nuclear Transfer Technology 3・6
- Therapeutic Cloning 3・8
Chapter 4: Quality Control and Post-translational Modifications of
Recombinant Drugs 4・
- Biopharmaceutical Formulation: Potential Post-Translational Alterations 4・
- Biotherapeutic Proteins versus Small Molecule Drugs 4・
- Drug Development Factors for Recombinant Biologicals 4・
- Critical Factors in Protein Analysis 4・
- Biologic Stability 4・0
- Process Development of Recombinant Biologicals 4・2
- Recombinant Therapeutic Systems 4・4
- Solubilization of Expressed Recombinants 4・7
- Glycosylation and Microheterogeneity Affecting Recombinant Drugs 4・8
- Erythropoietin 4・0
- Follicular Stimulating Hormone 4・1
- A Plant's N-glycans Contains ・1,3)-fucose and ・1,2)-xylose 4・3
- Protein Immunogenicity湧eoepitopes 4・4
- Prenylation and Myristoylation 4・6
- Vaccine Development 4・7
- Farensyl Transferase Inhibitors in Cancer 4・8
- Myristoylated Recombinant Proteins 4・8
- Phosphorylation of Biopharmaceuticals 4・9
- Sulfation and Disulfide Bond Formation 4・1
- Disulfide Bonds and Recombinant Protein Activity/Stability 4・1
- Thiolation and Sulfation of Therapeutic Proteins 4・3
- Metabolic Transformations of Biopharmaceuticals 4・5
- Acetylation and Acylation 4・6
- Myristyl Acylation 4・6
- Ubiquitinylation and Proteolytic Processing 4・7
- Proteolytic Processing of Biopharmaceuticals 4・9
- Degradomics 4・0
- Oxidation of Biopharmaceuticals 4・1
- Deamidation 4・3
- Glycation of Therapeutic Proteins 4・6
- Glycomics and Proteomics 4・7
- Changing Glycosylation in Protein Expression Systems 4・9
- Glycan-like Formulation Strategies for Protein Pharmaceuticals 4・0
Chapter 5: Protection of Biopharmaceutical Products 5・
- Recent Problems with Counterfeited Drugs湧ational Association of Boards of
Pharmacy Potential List of Counterfeit Medicines 5・
- Anti-Counterfeiting Measures for Biopharmaceutical Brand Protection 5・
- Financial Loss 5・
- Brand Damage 5・
- Organized Crime 5・
- Terrorism 5・
- Covert, Overt, and Forensic Solutions 5・
- Nonprinted Security Features 5・
Chapter 6: Products of the Leading Biopharmaceutical Companies 6・
- Amgen Inc. 6・
- Biogen Idec, Inc. 6・
- Genentech, Inc. 6・
- Serono, Inc. 6・
- Eli Lilly and Company 6・0
- Roche 6・2
- Biogeneric唯iopharmaceutical Generics 6・3
- The Hatch Waxman Act 6・4
- US FDA Regulations 6・4
- Invalidation of Amgen Patent for EPO in UK 6・6
- Conclusions・005 Sales Patterns 6・9
- Overview 6・1
TABLE OF EXHIBITS
- Exhibit 2.1 Biopharmaceuticals Approved and in the Market Through 2003 2・
- Exhibit 2.2 Recent Chimeric Approved Antibodies To Date 2・
- Exhibit 2.3 Humanized Antibodies in Clinical Trials in 2005 2・
- Exhibit 2.4 FDA Approved Growth Hormones and Enzymes in 2004 and 2005 2・2
- Exhibit 2.5 Summary of Growth Factors in R&D Stages 2・3
- Exhibit 2.6 Flow Chart of Fundamental Steps in a Culture/bioreactor
Product 2・1
- Exhibit 2.7 US and Europe Approved Therapeutic Antibodies Until 2005 2・3
- Exhibit 2.8 2004 and 2005 FDA-approved Antibodies 2・5
- Exhibit 2.9 Number of Therapeutic Monoclonal Antibodies Entering the
Clinic from 1984 to 2004 2・6
- Exhibit 2.10 Bacterial/Viral Infections Targets for Vaccines 2・7
- Exhibit 2.11 Types of Cancer Vaccines in Development 2・8
- Exhibit 2.12 Companies Involved in Bioterror Vaccine Production 2・0
- Exhibit 2.13 Advantages and Disadvantages of Different Expression Systems
2・2
- Exhibit 2.14 Plant-derived Pharmaceuticals Close to Commercialization 2・4
- Exhibit 2.15 Biotech Companies Specializing in Plant Made Pharmaceuticals
2・8
- Exhibit 2.16 Expression Hosts and Yields of Recombinant Proteins in
Production 2・0
- Exhibit 2.17 From a Transgenic Plants to a Commercial Product 2・2
- Exhibit 2.18 Companies Involved in the Manufacture of Biopharmaceuticals
2・5
- Exhibit 3.1 An Amino Acid 3・
- Exhibit 3.2 The Peptide Bond in a Protein 3・
- Exhibit 3.3 Amino Acids are Stereoisomers 3・
- Exhibit 3.4 The 20 Naturally Occurring Amino Acids 3・
- Exhibit 3.5 Hsp60 Chaperone Protein Crystal Structure 3・
- Exhibit 3.6 Four Levels of Protein Structure 3・
- Exhibit 3.7 Secondary Structure 3・
- Exhibit 3.8 The Central Dogma 3・0
- Exhibit 3.9 Transfer RNA 3・0
- Exhibit 3.10 The Genetic Code 3・1
- Exhibit 3.11 Protein Synthesis on the Ribosome 3・2
- Exhibit 3.12 Common Post-Translational Modifications of Proteins 3・3
- Exhibit 3.13 Cleavage Sites of Common Proteases 3・4
- Exhibit 3.14 The Coagulation Cascade 3・5
- Exhibit 3.15 The Amino Acid Cysteine Creates Disulfide Linkages 3・6
- Exhibit 3.16 The Ring Structure of Monosaccharides 3・7
- Exhibit 3.17 Common Monosaccharides and Disaccharides 3・7
- Exhibit 3.18 The Glycosidic Bond 3・8
- Exhibit 3.19 O Linked Carbohydrates 3・0
- Exhibit 3.20 N Linked Carbohydrates 3・1
- Exhibit 3.21 Dolichol Structure 3・2
- Exhibit 3.22 Enzyme Defects in Degradation of Asn-GlcNAc Type
Glycoproteins 3・3
- Exhibit 3.23 Structure of a Gla Residue 3・4
- Exhibit 3.24 The Universal PAPS Reaction 3・7
- Exhibit 3.25 Protein Prenylation 3・9
- Exhibit 3.26 The Proteasome 3・3
- Exhibit 3.27 Bioreactors for Protein Production 3・6
- Exhibit 3.28 Advantages of an Expression System Using Protozoa 3・9
- Exhibit 3.29 Yeasts S. Serevisiae and P. Pastoris Therapeutic Protein
Production 3・2
- Exhibit 3.30 Baculovirus Expression System 3・4
- Exhibit 3.31 Mammalian Transfection and Expression Protocol 3・7
- Exhibit 3.32 Mammalian Expression Vector 3・8
- Exhibit 3.33 Basic Techniques for Creating Hybridomas 3・2
- Exhibit 3.34 Monoclonal Antibodies used in Pathology 3・5
- Exhibit 3.35 Panning of Phage Libraries 3・7
- Exhibit 3.36 Basic Antibody Structure 3・8
- Exhibit 3.37 Cancer Clinical Trails using Monoclonal Antibodies till June,
2005 3・0
- Exhibit 3.38 Current Genetically Modified Plant Studies 3・2
- Exhibit 3.39 Microinjection for Creating Transgenic Animals 3・4
- Exhibit 3.40 Microinjection Process 3・5
- Exhibit 3.41 Breeding Protocol to Produce Homozygote Transgenic Animals 3・5
- Exhibit 3.42 Drugs Currently Synthesized in Transgenic Animals 3・6
- Exhibit 3.43 Cloning of Livestock 3・7
- Exhibit 3.44 Therapeutic Cloning Protocol 3・9
- Exhibit 4.1 FDA's Division of Therapeutic Proteins (DTP) Product Diversity
4・
- Exhibit 4.2 Recombinant Protein Analysis Solutions 4・
- Exhibit 4.3 Successful Isolation of a Recombinant Antitumor Immunoreagent
4・0
- Exhibit 4.4 Shelf Life of Recombinant Protein Drugs 4・1
- Exhibit 4.5 Stability-Indicating Test Methods for Recombinant Proteins 4・1
- Exhibit 4.6 Solubilization Strategies for Expressed Recombinants 4・8
- Exhibit 4.7 Microheterogeneity of FSH 4・2
- Exhibit 4.8 Ubiquitinylation of Therapeutic Protein 4・8
- Exhibit 4.9 Protein Oxidation Reactions 4・2
- Exhibit 4.10 Protein Deamidation 4・3
- Exhibit 5.1 Counterfeited Nutropin Vials 5・
- Exhibit 5.2 NABP's list of Susceptible Products 5・
- Exhibit 5.3 Anticounterfeiting Security Measures 5・
- Exhibit 6.1 Amgen's Lead Biopharmaceuticals 6・
- Exhibit 6.2 Biogen's Lead Biopharmaceuticals 6・
- Exhibit 6.3 Genentech's Lead Biopharmaceuticals 6・
- Exhibit 6.4 Serono's Lead Biopharmaceuticals 6・
- Exhibit 6.5 Lilly's Lead Biopharmaceuticals 6・1
- Exhibit 6.6 Top Biopharmaceuticals and Their Patent Positions in 2000 6・6
- Exhibit 6.7 Disease Targets for Biopharmaceuticals 6・1
View Cart
