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Selected Products of Bioprocessing

Selected Products of Bioprocessing. digging a bit deeper. Farmaceuticals. genetic modification of animals production of therapeutic proteins in milk, eggs or blood. Demand?. >100 protein based drugs are in advanced phases of clinical trials production facilities cost $200m-400m

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Selected Products of Bioprocessing

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  1. Selected Products of Bioprocessing digging a bit deeper

  2. Farmaceuticals • genetic modification of animals • production of therapeutic proteins in milk, eggs or blood

  3. Demand? • >100 protein based drugs are in advanced phases of clinical trials • production facilities cost $200m-400m • goats and cows most promising alternative

  4. Goat’a be kid’in • animals as bioreactors • milk loaded with proteins • GTC Biotherapeutics, Massachusetts engineered (transgenic) goats, producing 14 varieties of therapeutic proteins • 18 months/goat • $100m/herd

  5. Goat versus Cow • 18 months to make transgenic goat • 3 years/cow • 2 L/day milk/goat • 20 L/day/cow

  6. Cost? • mammalian cell culture: $150/gram • transgenic animals: $2/gram • don’t believe everything you read

  7. GTC goals • recombinant human anti-thrombin III (rhATIII), anti-coagulation protein found in blood • $250m worldwide market • presently $10m/year sold in US • treat hereditary difficiency

  8. GTC goals • recombinant human serus albumin (rHSA) • demand 400 tons/year • presently isolated from plasma • supply and safety concerns • bioreactors unrealistic given demand

  9. Third product? • malaria vaccine MSP-1 from goat milk • 8 goats produce enough vaccine to inoculate 20 million people

  10. Pharming Group, Leiden, Netherlands • C1 inhibitor (C1 INH) for hereditary angioendema (lack inhibitor protein) • C1 is “proenzyme” in serum complement pathway, which is controlled by inhibitor • being produced from wabbits

  11. Other Pharming products • fibrinogen and collagen produced in cows • used in wound healing and cosmetics • lactoferrin, an anti-infective • 20 cows can produce world fibrinogen supply (150 kg) • cow producing 10,000L milk/year generates 100 kg protein (10 g/L) • fermentation process, 200-300 kg/year

  12. Transgenics versus bioprocess • capital cost advantage • $40 – 200m/production facility • capital costs in farming are considerably less • relatively homogeneous medium

  13. BioProtein Technologies, Paris • proteins from rabbit milk • 4-5 months to sexual maturity • gestation 1 month • rather prolific breeders

  14. Rabbit versus CHO cells • line of transgenic rabbits in 6 months • product within year • similar time frame to CHO cells • 250 mL milk/day compared to 20L/cow • 1-10 g/L recombinant protein

  15. Potential products • antibodies, plasma proteins, hormones • some success with human growth hormone and cellular-superoxide dismutase

  16. transgenic embryo microinject transgene into fertilized oocyte recipient female breeding selection of transgenic wabbit milk extraction and purification

  17. Gala Design, Middleton, WI • focus on gene insertion using retrovirus vectors • transfection rate 50-100% in cows, pigs, monkeys • genes inserted into eggs before fertilization (transgametic), followed by in vitro culture... many transgenic embryos result, are fertilized and the rest is up to nature

  18. Consider the chicken! • eggs are sealed and sterile • protein loaded • chickens grow fast and easier than cows • occupies 1 ft2

  19. THE ANSWER IS IN THE ALBUMIN OF CHICKEN EGGS.

  20. Transgenic chickens • chimeric chickens produce 1 human antibody and 1 mouse antibody in egg albumen • low yields • working on insulin and human serum albumen

  21. express proteins in eggs at 1 mg/egg • 20 mg/kg chicken (similar productivity to cow) • laying at 5 months • produces 600-700 eggs/chicken • 100m chickens/rooster in 2 years • sterile packaging • storage without need for stabilization • 88% protein in egg white • 11 proteins make up 95% of egg white • crack and separate 200,000 eggs/h/machine • widely used in vaccine manufacture, so acceptable as transgenic medium • AviGenics is expressing interferons, antibodies and cytokines

  22. Regulatory approval • challenge • fears of bovine spongiform encephalitis (mad cow) as example • also fears of prions • some argue that milk producing animals do not harbour human viral pathogens

  23. Other cost considerations • raising animals costs 30-80% less than cell culture • $300,000/transgenic cow • $30,000/transgenic pig • cloning costs $100-200K/animal • related facilities $5-7m • but lifetime or production, plus offspring

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