The proposed manufacturing platform is a technology that enables the use of nontransgenic tobacco plants as biofactories of vaccines, and takes advantage of 3 different biological systems working in synergy: (1) Agrobacterium tumefaciens for effective transfer of DNA that codes for the vaccine of interest; (2) Plant virus for increased vaccine yield; (3) Non-transgenic tobacco plants as hosts for vaccine synthesis. Using tobacco as vaccine biofactories, instead of traditional manufacturing processes, is potentially significant. Capital and operating costs can be significantly reduced, up to 90%, while vaccine development time is reduced from months to weeks. The proposed technology represents an emerging trend within the biotechnology industry. FDA is now willing to approve therapeutics manufactured in non-traditional production systems that are "biobetter". Biobetter means faster, more efficient, substantially cheaper, and greener; compared to traditional technologies. The proposing team has deep experience in this field, and recent developments in optimization approaches from the group, and others, have positioned this technology on the brink of commercialization and significant societal impact.
Epidemics of recent emerging infectious diseases, such as the H1N1 pandemic, demand cost-efficient and scalable production technologies that can rapidly deliver effective therapeutics into the clinical setting. The mission of this proof-of-concept is to bring the rapid, scalable, and cost-efficient vaccine manufacturing capabilities of the technology platform outside of the research lab and closer to the market. This technology can impact diverse markets such as proteins for research use, as well as veterinary and human vaccines, and can improve the quality and affordability of animal and human health globally. Successful validation and commercialization of this manufacturing platform for recombinant proteins as reagents and/or diagnostics would demonstrate the production platform and open up new markets, which were not cost effective with previous biomanufacturing practices.
Normal 0 false false false EN-US X-NONE X-NONE Inserogen is a biotechnology startup that is commercializing intellectual property developed at UC Davis (based on work initially funded by the National Science Foundation) surrounding the use of tobacco plants as a manufacturing platform for rapid, scalable, and cost-effective production recombinant proteins. Our process uses nontransgenic (found in nature) tobacco plants, is capable of producing the target protein within a week and produces the protein in a contained facility similarly to other biomanufacturing facilities that produce therapeutic proteins, however it is less expensive because it uses the biosynthetic machinery of plants that have been grown using photosynthesis, rather than mammalian cells grown in expensive stainless steel bioreactors with expensive nutrients under stringent growth conditions. The I-Corps program gave us the opportunity to do a dry run of our startup, get out of the lab and perform a formal hypothesis-validation testing of our business strategy, and perform a "proof of concept" for our initial target market. We initially planned to demonstrate the manufacturing platform for the production of vaccines for H1N1 and other influenza strains. However, feedback from customers and partners allowed us to make a pivot to focus on rare (orphan) diseases, a market much better suited for a biotech startup. The orphan disease market will allow us to achieve the highest value for our startup, due to: need for a short development time, higher profit margins and smaller volumes of production that are required, a shorter path for regulatory approval, and because our technology provides a superior product in terms of safety, cost-effectiveness, product consistency, and reliability of supply. Our experience in the I-Corps program allowed us to size the market and provided important customer data that made clear the market opportunity for our first target product, alpha-1 antitrypsin (AAT). AAT is a 52 kDa human glycoprotein produced in the lung and liver. AAT has orphan drug designation, because there are 6,000 patients diagnosed with AAT deficiency in the United States. Patients with AAT deficiency have a genetic disorder that prevents them from producing sufficient levels of AAT in their blood and other tissues such a lung tissue, which leads to early onset emphysema. Plasma-derived AAT has been used clinically over three decades as a replacement therapy for individuals with emphysema stemming from genetic AAT deficiency, however these treatments are expensive, limited in availability, quite heterogeneous between different products and also lot-to-lot, and carry a possibility of unknown blood-borne pathogens/diseases. The current AAT market is valued at $600 million, because the cost of augmentation therapy for each AAT deficient patient is approximately $100,000 per year. However, the condition is severely underdiagnosed. Since only 3% of the patients that exhibit chronic obstructive pulmonary disorder (COPD) symptoms are positive for AAT deficiency, many physicians and hospitals neglect to test for the disease. Only 6% of individuals with AAT deficiency have been properly diagnosed, with an estimated 94% percent of affected individuals still undiagnosed. Interestingly, the popular 23andMe personal genetic testing service (at a cost now of less than $100) includes testing for AAT variants. As awareness is raised and diagnosis improves, more individuals of the total pool of affected with AAT deficiency will become patients and receive augmentation therapy. As a result, the AAT market is expected to see a substantial increase in market value well beyond a billion dollars. In addition to its well-established ability to inhibit serine proteases, such as neutrophil elastase in the lung, AAT is an acute stress responsive protein that increases during inflammation, blocks pro-inflammatory mediators, induces production of anti-inflammatory compounds and has direct anti-apoptotic effects on beta cells, which is expected to open additional markets. AAT is being investigated in clinical trials as a biologic therapeutic for type 1 diabetes and cystic fibrosis. In addition, there is evidence that low levels of AAT are associated with type 2 diabetes. As AAT demand increases due to its growing number of indications, it is clear that new scalable and cost-effective production methods will be needed given the highly constrained supply and high cost of plasma-derived AAT. Through optimization of the production process we have increased the production level of functional rAAT to a commercially relevant level of 480 mg AAT/kg FW biomass in harvested leaves at 6 days post infiltration. Using SuperPro Designer®, we have performed a preliminary analysis of our manufacturing platform for production of an H1N1 subunit vaccine from whole tobacco plants grown hydroponically, assuming the facility needed to make 75 million doses of vaccine (50 microgram of H1N1 per dose) within 34 weeks and was capable of producing 220 million doses per year. Our analysis resulted in a Cost of Goods of 9 cents per dose which was the lowest among different production hosts considered (mammalian cell culture, insect cell culture and yeast fermentation).
