Initial Market Assessment Nanoparticles for selectively harvesting pharmaceutical products from plant cells in culture [Invention Case # 2172] 1

Commercial Opportunity Summary Title: Nanoparticles for selectively harvesting pharmaceutical products from plant cells in culture Key Advantages: Green alternative to standard chemical synthesis or solvent extraction of bioactive plant metabolites Cells are able to be used for repeated harvesting Nanoparticles can be reused Market Opportunities: Many therapeutic agents have been discovered through plants containing metabolites with bioactive properties that can be used to treat certain diseases. The pharmaceutical industry has used these bioactive plant metabolites as lead compounds for chemical and pharmacological screening. Additionally, many companies use bioactive plant metabolites as prodrugs and they are commonly produced directly from plant material or are chemically synthesized for therapeutic use. When chemical synthesis proves too complex, extraction of metabolites from plant products and/or plant cell culture is achieved using solvents and chromatographic methods which are detrimental to the environment. Additionally, these extraction methods do not allow for repeated use of the same plant material and are inefficient in production of bioactive metabolites. Thus, there is a need for a more efficient and environmentally friendly process to effectively extract plant metabolites for therapeutic use. Technology Solution: Dr. Littleton and his colleagues have developed a method to harvest bioactive plant metabolites from plant cell cultures using silica nanoparticles. The desired metabolite is overexpressed in culture using gain-of-function mutations in the plant cells. Their nanoharvesting technology allows for the metabolite(s) of interest to be directly targeted via binding to specific receptors on the nanoparticles. The nanoparticles are extruded from within plant cells to the medium and the binding product can then be separated through elution and magnetization. After the metabolites are separated from the nanoparticles, the nanoparticles can then be reused. Additionally, the plant cell cultures retain their viability and can be used for repeated harvesting. This new technology does not require any solvents or harmful chemical processes for harvesting and has almost zero environmental impact.

Inventor Objectives Expected Grant; Use of Grant Proceeds/ Patent: Further develop and/or optimize a system that allows for the repeated harvesting of metabolites/biologics via a selective affinity oligonucleotide approach Inventor Timeline: Funding: NIH R44 AT008312; Naprogenix, Inc (Lexington KY) Published as NIH abstract (4/14/17) NIH needs progress report in 10 months (Feb 2018) Inventor relationships None Disclosed Inventor commercialization goals Partner with US and European pharmaceutical and biotech for commercialization License and/or sublicense technology to collaborators at UK College of Engineering Inventor is seeking a patent for the Naprogenix core technology: use of nanoparticles to harvest metabolites and biologics for biotech and pharmaceutical uses.

Technology [Nanoparticles for selectively harvesting pharmaceutical products from plant cells in culture] 4

The Problem: Current Harvesting Technologies are Inefficient Plant cells can be cultured and their metabolites harvested for pharmacological uses (eg. Anti-cancer properties, etc) Whole plants and plant cell cultures are slow growing and are unable to be used multiple times There is a need to develop an extraction system that does not alter the culture viability Uses nanoparticles to extract plant metabolites that are over expressed in plant cell culture for pharmacological uses Allows for repeated metabolite/biologic harvesting with no loss in plant cell culture viability May make it easier and faster to harvest biologics when an urgent need arises (eg. Extraction for vaccination/drug treatment during a disease epidemic Affinity separation process allows for harvested products to be semi-purified after extraction Plant Metabolite Harvesting Techniques The Solution: Nanoparticle Harvesting Nanoparticle Harvesting of Metabolites and Biologics 5

Technology Development Stage (e.g., licensed for further development; product design/development) Advanced Evaluation: (e.g., Beta prototype or working prototype in situ Evaluation: (e.g., human testing or Alpha prototype Proof-of-Concept / IP Protection: (e.g., Animal testing and/or patents filed) Discovery: Basic principles observed and reported Assessment Gather Technology development process / time Filing provisional patent Stage 1 Stage 2 Stage 3 6

Top Relevant Patent Owners Worldwide Company Name Total Assets # of Issued Patents # of Applications Avg. of Remaining Life * Avg. of Priority Year * Abbvie Inc 96 29 67 16.4 2011 Abbott Laboratories 21 4 17 12.9 2007 Allergan PLC 8 - 9 2006 Altria Group Inc 6 2002 Roche Holding Ltd 5 2 3 8.6 2004 7

Relevant Patent Landscape 1. Technology Landscape. Tools: Innography

Active Innovation Landscape 1. Technology Landscape. Tools: Innography.

Market [Nanoparticles for selectively harvesting pharmaceutical products from plant cells in culture] 10

Harvesting of bioactive plant metabolites (eg. Cancer therapeutics) Market Applications Application 1 Application 2 Harvesting of bioactive plant metabolites (eg. Cancer therapeutics) Selective harvesting of vaccines and antibodies from transgenic plant cells Considerations Nanoharvesting of flavonoids from plant cell culture has been shown; Proof of application in other plant cell cultures (eg. Phytoestrogens from licorice, alkaloids from periwinkle cells, and antibodies from transgenic tobacco cells) are in progress 11

Preliminary Market Takeaways Market Application Market Size Market Growth Rate Current Consumer Demand Potential Partners Notes Antineoplastic agent harvesting (ex. Breast cancer) 4,591 B (2017) 5.416 B (2025) 16.25%/year May be easiest to break into with proof of concept completed Antibody Harvesting Development has been limited due to high production costs; can be used to treat multiple diseases Vaccine Harvesting Production may be more cost-effective than traditional methods Key: = High/Large/many = Moderate = Low/Small/few 12