Biotech Tobacco: Advantages - Agricultural Policy Analysis Center

drawerbeamerBiotechnology

Dec 6, 2012 (4 years and 6 months ago)

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Agricultural Policy
Analysis

Center
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University of Tennessee
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310 Morgan Hall
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Knoxville, TN 37996
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4519

www.agpolicy.org
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phone: (865) 974
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7407
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fax: (
865) 974
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7298

Biotech
Tobacco:

Assessing
Commercialization
Potential

42
nd

Tobacco Workers
Conference

Charleston, South Carolina

January 18, 2006

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Kelly Tiller & Marie Walsh

The University of Tennessee

This project was supported by Initiative for
Future Agriculture and Food Systems Grant
no. 2001
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52100
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11250 from the USDA
Cooperative State Research, Education,
and Extension Service.

Biotech Tobacco: Advantages


Tobacco is not in the food/feed chain


Tobacco is easily manipulated using
biotechnology tools


Fully mapped genome


Tobacco produces a lot of biomass, quickly


Tobacco grows well in a variety of locations
and conditions

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Genetic Modification


Expression of novel compounds in tobacco


The vast majority of the research identified to
date involves expression of novel compounds


Hyper
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expression of existing compounds in
tobacco


Secondary metabolites, corrosion inhibitors


Modification of existing tobacco compounds
to have new characteristics

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Biotech Tobacco Applications


Biopharmaceuticals


The vast majority of activities


The fastest growing segment of pharmaceuticals


Bioterrorist vaccines and countermeasures


Miscellaneous other compounds


Food safety


Biomaterials


Industrial enzyme production

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Biopharmaceuticals


Biopharmaceuticals (biologicals) include:


Protein and enzyme therapeutic compounds


Monoclonal antibodies


Subunit vaccines


Revenues $40b in 2003, $65b by 2008


600 biologicals currently under development
and/or in clinical trials


Potential for follow
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on biologicals (biogenerics)


Most either derived from animal tissue or produced
in mammalian cell culture systems


Usually Chinese Hamster Ovary (CHO) system

PMP: Potential Positives


Upstream costs of plant based production systems may be
70
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80% lower than mammalian cell culture


Lower capital costs and operating costs


Nearing capacity for mammalian cell culture systems??
Expensive to expand


High initial estimates of plant based system productivity


Easy scale
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up of production to kg quantities


Potential to address illnesses of little interest to large
pharmaceutical companies


PMPs may be safer than mammalian systems because they
don’t contain mammalian viruses

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Mammalian Cell Culture Capacity


Conventional wisdom that production capacity is
strained


Growth in demand for giant bioreactors due to
growth in monoclonal antibody drugs


As opposed to recombinant proteins


New facility construction costly and lengthy


May not be as bleak as thought


Expansion occurring


Mammalian cell line productivity increasing


Alternative production platforms still commercially
unproven

PMP: Advantages?


Productivity of plant systems


Cost of producing biopharmaceuticals in
plant systems


Upstream vs. downstream costs


Time to market of PMPs


Time needed to develop and scale
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up


Time needed for regulatory approval


Embrace of Big Pharma

Status of Biotech Tobacco
Pharmaceutical Production


Erythropoietein


Human Growth Factor



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Interferon


Malaria epitopes


Streptococcus Surface Antigen
IgA (Dental Caries)


Carcinoembryonic Antigen


Colon Cancer Antigens


Interleukin 10 (Chrohn’s
Disease; Inflammatory Bowel
Syndrome)


Glucocerebrosidase
(Gaucher’s Disease)


Interleukin 4


Urokinase (Breaks Blood
Clots)


Human Serum Albumin


Rabies Antigens


Hepatitis B Surface Antigen


Rotavirus VP6


Labile Eneterotoxin (Botulism)


Zonna pellucida ZB3 Protein
(Contraceptive)


Gastric Lipase (Cystic Fibrosis)


Creatine Kinase


Protein C (Anticoagulant)


Neutropenia (Granulocyte
Macrophage Colony Stimulating
Factor)


Epidermal Growth Factor


α and β Hemoglobin


Angiotensin Converting Enzyme
(Hypertension)


Insulin Like Growth Factor (Diabetes)


Tissue Necrosis Factor (Rheumatoid
Arthritis)


HIV
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1 Peptide


Lactoferrin


Substance P (Neuropeptide)


Animal Pharmaceuticals (Vaccines)


Feline Parvovirus (Panleukopenia)


Canine Parvovirus


Bovine Foot and Mouth



Measles


Aprotinin (Protease Inhibitor)


α
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Galactosidase (Fabry’s
Disease)


Interferon α 2a and 2b


Personalized Non
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Hodgkin’s
Lymphoma Vaccines


Papilloma Virus Vaccines


Lysosomal Acid Lipase (Woman’s
Disease; Atherosclerotic
Plaques)


Personalized Vaccines for
Follicular Lymphoma


α Trichosanthin (HIV)


Diagnostics for Ovarian Cancer


Diagnostics for Ecclampsia


Biomarkers for Alzheimers
Disease

Status of Biotech Tobacco
Pharmaceutical Production


Expression does not equal commercialization


Clinical trials precede commercialization


Require several years to complete (7.8 years)


Average cost of bringing a new drug to market is
$897 million


Costs for manufacturing the products only about
10
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20% of total cost


Downstream costs similar for plant and animal systems

Tobacco PMP Clinical Trials


CaroRx
TM



topical preventative intervention to
prevent tooth decay


Planet Biotechnology


Phase II/III


Personalized non
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Hodgkin’s Lymphoma cancer
vaccines


Large Scale Biology Corporation


Phase I/II


RhinoRx
TM



treatment of colds


Planet Biotechnology


Phase I

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Commercially Available PMPs


Prodigene, produced in corn


Avidin


Glycoprotein used as a diagnostic


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Glucuronidase


hydrolase used as visual marker in
transgenic plants


Trypsin (TrypZean)


Protease enzyme used in
processing pharmaceuticals


Aprotinin (Aprolizean)


Protease inhibitor used in cell
culture


Large Scale Biology Corporation, produced in
tobacco


Aprotinin


Protease inhibitor used in cell culture

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Tobacco Demand Potential


Wide range of market potential


CaroRx: 55 acres to provide one treatment
per year for every child in the U.S. and U.K.


Human blood serum albumin: 16,000 acres
to displace world production


Most human therapeutic proteins have small
markets, high value


< 10 kg/yr, > $10,000/gram

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Field Production Challenges


Farms producing biopharmaceuticals are
“manufacturing facilities” and have same
FDA requirements


FDA says, “important to dispel notions that
pharma crops are a value
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added opportunity
for a significant number of farmers.”

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Bioterrorist Vaccines &
Countermeasures


FY2004 Biodefense Research Budget: $41.3
billion


NIH
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NIAID bildefense funding increased from $0 in
2000 to $1.7 billion proposed in 2006


Tobacco transformed to produce potential
bioterrorism vaccines or countermeasures
including:


Heat labile enterotoxin (botulism), ricin (neurotoxin),
anthrax, small pox, the plague


Fraunhofer USA, University of Maryland, Thomas
Jefferson Medical Center particularly active

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Other Novel Compounds


GM tobacco used produce antibodies to detect
foodborne pathogens


Listeria, salmonella, E. coli, cryptosporidium


Toxin Alert developing food wrapping containing
antibodies to several food poisoning bacteria and some
pesticides


Working with University of Guelph and Mississippi State


Several biomaterial expressed in GM tobacco


Elastin, collagen, spider silk, polyhydroxyalkonates,
polyaspartate, modified pectin

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Cautions


Very expensive to develop and approve ANY of
these products


Estimates of cost adventages are very preliminary


Very stringent FDA regulation and oversight, even
at the farm level


The plant platform is still commercially unproven


Time to market is very long


Big Pharma vs. Little Pharma


So far, applications would not require significant
field
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grown quantity of tobacco

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What’s Driving R&D?


Not mammalian cell culture capacity


Generally not upstream cost reductions


Potential for scale
-
up


Products with very large market potential


Marginal cost savings add up


Potential for individualized applications


Products with very high market value

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Major Players (today)


U.S. firms:


Chlorogen / University of Central Florida


Large Scale Biology Corporation


Panorama Research


Planet Biotechnology


Phytomedica


SomaGenics


Non
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U.S. firms:


Center for Genetic Engineering aned Biotechnology, ERA
Plantech, Farmacule Bioindustries, Guardian
Biotechnologies/Nexgen Biotechnologies, Icon Genetics
AG, Meristem Therapeutics, Plantechno, Plantigen


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