Impact case study database

Impacts 1 and 2: Our research has direct application in the prevention and treatment of high blood pressure (hypertension), the number one cause of death globally, primarily from heart disease and stroke. Globally an estimated 26% of the world’s population (972 million people) have hypertension and this is expected to increase to 29% by 2025. Our research has resulted in the generation of a University Patent Portfolio entitled “Use of riboflavin in the treatment of hypertension” (C1 EP2139488A1) in collaboration with Western Health and Social Care Trust and Trinity College Dublin and in turn resulted in two Intellectual Property License Agreements (IPLAs) (C2, C3) during the current impact period. The technology is currently protected under patents in China, Mexico, Japan, Canada, Ireland, UK, Italy, Spain, France, Netherlands, Germany and Switzerland.

The health implications of these findings in preventing hypertension are considerable for the 1 in 10 adults worldwide (and much higher in some populations e.g. 32% in Mexico) who carry this genetic risk factor. In particular, patients with existing hypertension will benefit, as documented in a video investigating the patient experience showing that riboflavin intervention was not only highly effective at lowering BP, but was also very well received by patients (C4). Riboflavin supplementation thus offers a novel, non-drug treatment (and/or the potential to be combined with an antihypertensive drug) to effectively lower BP, most likely via an effect on nitric oxide ( R5) and improve BP control in genetically at-risk adults.

Two IP licensing agreements were signed during the current impact period (C2, C3).

• The first is a significant agreement for the development of a new product for eye health, Ocufolin, designed by US ophthalmologists to reduce the risk of age-related macular degeneration and diabetic retinopathy by decreasing homocysteine and consequently reducing microcirculation in eye diseases. The license with Aprofol AG, Switzerland (effective date 28-06-2016; date of variation 26-01-2018) provides exclusive use of ‘personalised nutrition’ claims related to degenerative eye disease in the European patent with the option to negotiate a patent license in China. Aprofol’s investment in Ocufolin to date is estimated at > EUR3M. Aprofol is using the license for sales of a ‘medical food’ (as defined by the US FDA) and Ocufolin products (for eye health) (C2).

The second license (C3) is with DSM Nutritional Products AG, Switzerland (effective date 06-02-2018). The license provides exclusive use of pharmaceutical claims under patent rights in China, Mexico, Japan, Canada and Europe and has realised an upfront payment to the University of EUR100,000 (02-2018) and significant company investment (additional to DSM’s research investment in grant income to the University of almost GBP1M, as detailed above). DSM has negotiated an agreement (confidential at this stage) with a global pharma company regarding the development of an antihypertensive-riboflavin combination for the prophylaxis and treatment of elevated BP, building upon the existing patent. In parallel, DSM has produced outputs focusing on hypertension treatment, including a white paper which presents an in-depth look at the science behind riboflavin as a treatment for hypertension and the latest research developments from Ulster (C5). The company has also run several promotions using both social graphics and a blog, and promoted a hypertension monograph to a global pharma audience (C6). DSM launched a campaign to promote the concept to a targeted list of pharma companies globally and has used this information successfully to attract the current pharma partner. DSM also engaged a human data science company (IQVIA) to conduct a global survey of doctors (n=736 from US, Germany, France, China) in order to understand the market potential of the concept of a riboflavin-antihypertensive combination (see Figure 1 below). As a result of our licensing agreement ( C3) with DSM, the company has filed a new international patent PCT/EP2019/077270 entitled “Medicaments containing riboflavin exhibiting improved flowability” WIPO Patent Application WO/2020/094319 (C7).

Figure 1: Global survey of physicians demonstrating their appreciation and knowledge of the proven effect of a riboflavin anti-hypertensive combination on resistant hypertension.

Impacts 3 and 4: In addition to the commercial impact, the underpinning research has impacted nutrition and health policy. Of note, the level of riboflavin (1.6 mg/day) found in our research trials to have beneficial effects on BP is within the range of what is achievable through normal dietary intakes, which is important given that our most recent research demonstrated that sub-optimal riboflavin status is associated with a three-fold increase in hypertension across adulthood (R6). Furthermore, riboflavin is entirely safe with no evidence of adverse effects, even at doses 100-fold higher than the 1.6 mg/day proven to be effective. In 2017, the European Food Safety Authority (EFSA) published its scientific opinion on “Dietary Reference Values for Riboflavin”. EFSA acknowledged for the first time among policymakers that riboflavin requirements were influenced by the MTHFR TT genotype based solely on the research from Ulster and R1-R4 were cited in the EFSA opinion (C8). Health professionals and food manufacturers in Europe use these dietary reference values daily in their work (C8). The underlying research (R1) was also cited in a health claim which was substantiated by EFSA and is authorised for use by the food / pharma industry on dietary supplements and any food product containing 15% or more of the reference dietary value for riboflavin, as well as being used by industry to promote their products.

In summary, the impacts are both commercial and health related. The patent portfolio has resulted in close engagement with global industry partners which has led to the development of a novel antihypertensive-riboflavin combination with a leading pharma company (C1-C7). The public awareness of the health benefits of riboflavin and their promotion by health professionals and industry are now on a global scale (C8-C9) through EFSA Dietary Reference Values for Riboflavin and the on-going promotion of products citing the EU generic health claim.