Patenting a New Form of Taxol Fermentation

Abstract

Taxol, also known as pacilitaxel, is a widely used chemotherapy drug typically extracted from the Yew tree. Mere extraction, however, does not yield sustainable returns because too-frequent extraction involves destroying the Yew tree source. Demand for Taxol has outstripped supply, and scientists have turned to developing Taxol in plant cells followed by industrial fermentation. The Duke University International Genetically Engineered Machine Project looks to go a step further, by generating Taxol in bacteria cell cultures instead of plant cell cultures. In order to use this invention to boost the market supply of Taxol, the IGEM team will eventually need a corporate or non-profit partner, and this partner will only be incentivized to participate if the IGEM team can offer exclusive licensing. Thus, the success of IGEM’s new genetically engineered bacteria largely hinges on its patentability with the United States Patent and Trademark Office. This report walks through the relevant patent requirements, analyzes the case law, and comes to the conclusion that IGEM’s new genetically engineered bacteria meets the conditions for successful patentability.

Introduction

Prior research has already shown Taxol to be an effective chemical in combatting cancer. As explained by a professor at the University of Massachusetts-Amherst, the compound “binds to micro-tubules, which are important in cell division, and prevents the cancer cells from dividing properly.”
However, just because a product is useful does not mean supply has kept pace with rising demand. Taxol is primarily obtained by extracting it from Yew trees, which naturally synthesize the product. Given the solvents and treatment necessary to do so, however, this approach also destroys the very same Yew trees in the process. As such, extraction is unlikely to achieve demand-supply equilibrium in the market. Researchers have since pivoted to modifying plant cell cultures to produce Taxol and other significant precursors found along the metabolic pathway. These plant cell cultures are in turn used in industrial processes designed to produce Taxol on a substantial scale. Even this, however, is not the most efficient solution to the current shortage—the plant cell’s complex infrastructure and subsequent energy needs have prevented the cell’s resources from being fully directed towards Taxol production. Low product yield is typically the result.
The 2016 Duke University International Genetically Engineered Machine team’s goal is to produce Taxol more efficiently, by using bacteria cell cultures rather than plant cells. The process of optimizing bacteria to produce a product for later industrial fermentation has already been demonstrated, but its application to Taxol has not. The IGEM team has worked on characterizing five enzymes involved in the natural process of Taxol production, and then merging them into one strain by genetically engineering the DNA of the bacteria culture. At the end of this process, the bacteria culture produces Taxol, with less energy expenditure than was required in plant cells and subsequently higher yield.
But a more efficient process is meaningless if the means to boost market supply are not available, which requires cooperation with a biopharmaceutical company. The Duke IGEM project does not on its own have the resources to mass produce Taxol through industrial fermentation, so licensing the new bacteria cell culture to a pharmaceutical manufacturer is the logical next step.

“A company that owns rights in a patent, know-how, or other IP asset, but cannot or does not want to be involved in the manufacturing of products, could benefit from licensing out of such IP assets by relying on the better manufacturing capacity, wider distribution outlets, greater local knowledge and management expertise of another company (the licensee)”

Details of such a licensing agreement would need to be worked out in individual contract negotiations. For example, the manufacturer might require more research by IGEM at the front-end before agreeing to commercialize the product5. Before any negotiation can take place, however, the manufacturer needs reassurance the venture will be profitable. These industries are not in the business of charity. Acquiring a patent on the new genetically engineered bacteria will provide the necessary financial incentive.
The remainder of this report will outline the fundamentals of patent law and requirements to getting a patent approved by the United States Patent and Trademark Office. It will explain out the main roadblocks towards getting approved, but will ultimately provide a case for a successful patent prosecution.

Fundamentals of Patent Law

Patent protection gives the right-holder what is known as a “negative right” to prohibit others from making, using, selling, offering to sell, or importing from elsewhere the patented invention. Because the grant of a patent removes the application of new knowledge from the public domain for 20 years from the date of filing, the criteria for patentability are strict. There are four key patent criteria—novelty, utility, nonobviousness, and disclosure.
Each of the four criteria is equally important, but some are harder to prove than others. Disclosure is the simplest. It requires that when filing for the patent, the rightseeker disclose an explanation of the product in the “best mode” possible, such that another person “reasonably skilled” in the field would be able to recreate the product. While the simplest to fulfill, disclosure is typically the most frightening for the right-seeker, because the law asks that the invention be explained to the public before the patent right has officially been granted. Careful discussion with the potential licensee and lawyers will be crucial in this stage to minimize risk. Next, the utility requirement asks that the potential usefulness of the product be proven. With the IGEM team’s documentation of the enhanced efficiency of Taxol production, the utility requirement will not pose a significant obstacle.
Novelty and non-obviousness are the strictest, and hardest to meet, criteria for patentability. The novelty requirement essentially asks whether the invention is “new” compared to prior inventions in the field that existed more than a year prior to the date of filing the patent application. The America Invents Act of 2011 sets out specific tests for novelty:

• The product cannot have been patented before.
• The product cannot have been described in a printed publication more than a year prior to the date of filing the application.
• The product cannot be in the public domain more than a year prior to the date of filing the application.
• The product cannot have been sold more than a year prior to the date of filing the application.