Patent protection, trade secrets &/or open innovation in the successful path towards personalization of medicine

Traditionally, medicine relied on information such as family history, environment, behaviors and simple tests to tailor health care to patients. New discoveries are now enabling a unique and deeper understanding of individuals on a molecular level which are increasingly being translated into inventions with the potential to prevent, manage and cure a larger number of diseases. Better known as “personalized medicine”, this trend is enabling the customization of health care for individual patients.

Objective biological indicators, commonly referred to as biomarkers, derived from molecular profiling – or “omics” data – help identify the patients most likely to respond to therapies is a key enabler of personalized medicine. Considering the high impact nature of activities in this area, there is a need to ensure stakeholders have the freedom to operate and incentives to engage in high risk/reward research. However, recent legal cases, such as Prometheus and Myriad in the US, have added some uncertainty as to what protection the law may offer and provokes a deeper exploration into available strategies to sustainably engage in biomarker related projects.

Patent Protection

A key high growth area for biomarker discovery is companion diagnostics (CDx) where a device provides information that is essential for the safe and effective use of a corresponding therapeutic product. Pharmaceutical companies may stand to benefit tremendously both from a regulatory and reimbursement perspective, however often do not possess the core capabilities to commercially develop and sell their own diagnostic kits. They therefore need to carefully evaluate whether to devote precious resources to filing patents that may not necessarily extend exclusivity for the core drug product(s) they’re developing. In these cases, devising an IP strategy requires an evaluation of the type of discovery, business objectives and associated value propositions, patentability and infringement considerations both locally and worldwide, and the need to collaborate with third parties.

The competitive landscape related to the drug, drug target and potential biomarkers could play a large part in determining whether to defer filing patent applications until more promising data is generated and more certainty emerges regarding the potential commercial value of the project. However, there is a risk that competitors working with the same drug target could discover a biomarker correlation and, if patented, could create a freedom-to-operate risk especially in the use of the biomarker(s) for the clinical trials necessary for gaining approval of the drug. Moreover, if the use of the biomarker(s) as a diagnostic is required by either a regulatory or reimbursement agency, the drug developer needs to ensure the diagnostic is available to the health care provider or patient and is unimpeded.

Freedom-to-operate risks can be reduced either by publishing relevant data or filing a patent application. Although potentially more costly, filing a provisional application is the most efficient way to create prior art for a competitor that may make a similar discovery in the future. In addition, the commercial value of the invention can be reassessed within the provisional year and the application can be updated during that time as well. If a PCT application is filed at the year date, the owner has an additional 18 months to assess the value before spending more resources to prosecute the patent globally.

With recent legal cases, such as Prometheus and Myriad in the US, some uncertainty exists as to what exactly can be patented in relation to biomarkers (to be discussed in subsequent articles). Therefore, organizations may be wise to consider alternative options when devising strategies around sustainably engaging in biomarker related projects.

Trade Secrets

At a basic level, the grant of a patent represents an exchange of benefits between the inventors and the public. Patents are granted as an incentive for inventors to disclose their inventions to the public, and, although the inventor receives a period of exclusivity, the public benefits in exchange for the disclosed information. While the patent is in force, competitors may learn from the inventor’s disclosure and develop further innovations. And, after the patent expires, anyone may freely practice the claimed invention.

The alternative to patent protection is trade secret protection. As long as an inventor is able to keep an invention a secret, the inventor can retain exclusive rights to the invention indefinitely. Because the invention is kept a secret, it is often difficult for others to use it to develop further innovations. However, trade secret protection does not prevent others from independently making the invention. But independent creation of the invention is often much more difficult than simply learning how to make the invention from the original inventor’s own disclosure.

As an example, although Myriad had their patents overturned earlier this year, the BRCA mutation data they have collected is arguably becoming more valuable than the original patents. When Myriad finds a new genetic mutation, it offers free testing to family members. These and other analyses allow it to interpret results of more variants. Gene testing by other companies finds variants of unknown significance in about 20 to 30% of cases, while Myriad’s rate is reportedly closer to 3% because it is able to assign significance to a greater variety of mutations. This means Myriad by default has a significantly superior BRCA testing that is able to provide better meaningful results. Since around 2005, mutation data and analysis algorithms have been available only to Myriad researchers via trade secret protection.

Moreover, many clinical lab developed tests (CLIA) in the US are able to exploit loopholes that enable them to meet less stringent regulatory and reporting requirements than In Vitro Medical Devices (IVDs). As a result, many such tests are often kept as closely guarded trade secrets of labs as there is less threat of others utilizing any publically available information and patenting inventions at their expense. Nevertheless, these types of tests are increasingly under scrutiny with the FDA threatening to more closely oversea and regulate these which may increase risks of closely held trade secrets being leaked into the public domain; this may encourage a greater rethink around how to best develop and protect their inventions.

Open Innovation

Precompetitive collaborative research initiatives like the Biomarkers Consortium, which includes public and private participation, share the cost and risk associated with biomarker discovery, development and qualification. Multi stakeholder partnerships leverage individual stakeholder resources, while maintaining profitable scientific and monetary returns on investment. The precompetitive consortium model provides a new and important business model for drug discovery and development as well as for biomarker research. The goal is to work collaboratively to expedite the generation of resources (for example, tools, data and specimens) that each stakeholder can use to drive the success of that organisation’s commercial products. In the setting of biomarker science, stakeholders may include any of the following: academia, industry, non-profit foundations and associations, professional societies, advocacy groups and so on.

Broad information sharing initiatives that risk exposure of valuable IP give business-minded organisations reason for scepticism. Concerns include fear of losing control of the collaboration, inability to divert sufficient resources away from ongoing operations, and lack of support from the highest levels of the organisation. Although, these issues can be mitigated through thoughtful planning and vigilant management, IP issues potentially remain most difficult.

Open sharing of information is a critical component for the success of precompetitive collaborations. As IP represents one of the (if not the most) significant assets for both pharmaceutical companies and diagnostic companies, thoughtful preparation for clear IP protection of all contributing parties is likewise critical. The Critical Path Institute (C-Path) – a non-profit collaboration between the US Food and Drug Administration (FDA), industry and academia focused on accelerating drug discovery and development – addresses this by developing a formal agreement to engage a process and set of principles for resolving IP issues that emerge for each consortium it oversees (12). The thought here is that IP issues will always emerge, and a priori agreements facilitate their clear and graceful management.

Academic institutions, less surprisingly, appear to be enthusiastic supporters of precompetitive collaboration. One reason is that through consortia may come additional sources for funding academic research. Increasing collaboration with industry also has benefits for academic investigators, providing a means to keep abreast of commercial trends and activities that may provide technology transfer opportunities. A few examples of academic participation in precompetitive consortia include: The Wellcome Trust Case Control Consortium, where academic and industry scientists search for chemical probes for epigenetics; numerous consortia supported by the Gates Foundation related to neglected and tropical diseases, HIV, and vaccine development; the Biomarkers Consortium for biomarker research; and CQDM, for drug development

Pros & cons of different strategies

Pros & cons of different strategies

 

m.s.metharu@hotmail.com'

Mandeep Metharu

Co-Founder at Medbiomarkers
Mandeep Metharu is a co-founder of Medbiomarkers, a company accelerating the translation of biomarker research via providing data and software solutions and building biomarker related consortia.. Mandeep is passionate about utilizing emerging technologies to enable start-ups to create and successfully commercialize products/services that radically improve the quality of people's lives.