Dr Carolyn H. Rogers, Rushikesh S. Dasoondi and Dr Michael A. Roberts from UK and European intellectual property law firm Reddie & Grose LLP examine the intersection of personalised medicine and rare diseases and its implications for IP law.
Personalised medicine, also referred to as precision medicine, is an innovative approach which uses a patient’s genetic information in the prevention, diagnosis and/or treatment of disease. It aims to tailor healthcare strategies to the individual patient, based on a predicted risk of disease or a predicted response to a given therapeutic strategy.
In contrast to a “one size fits all” approach, personalised medicine offers the possibility of an earlier diagnosis and enhanced therapeutic response, through treatments selected to provide optimal efficacy and reduced side-effects in the patient. This not only improves patient outcomes, but also reduces overall healthcare costs. Furthermore, the stratification of patients based on their genetics can enable the discovery of new biomarkers, prompt research into previously unknown modes of pathogenesis, and identify patient sub-groups with increased responsiveness or resistance to a particular drug[1].
As such, personalised medicine represents a paradigm shift in our approach to healthcare delivery, and has already been successfully applied in several healthcare areas, including cardiology, oncology and nutrition[2]. The treatment of rare diseases presents unique commercial opportunities, and is an area of particular interest for personalised medicine, with both approaches directed to the treatment of a limited patient population. This can have important implications when seeking intellectual property (IP) protection in these fields.
Personalised medicine and the treatment of rare diseases
Personalised medicine parallels the treatment of rare diseases in at least two respects:
Firstly, rare diseases affect a small proportion of the population. Although definitions vary, the EU defines a rare disease as one that affects less than 5 in 10,000 individuals[3]. Personalised medicine is not dissimilar as it involves stratifying patients into small patient sub-groups. Secondly, the diagnosis of rare diseases is often reliant on genomic technologies, with 72% of rare diseases being genetic in origin[4]. Personalised medicine, similarly, has become increasingly reliant on genomic technologies to identify biomarkers which are used to stratify patients into sub-populations.
Given these parallels, it is perhaps unsurprising that breakthroughs in the diagnosis and treatment of rare diseases have increasingly come from personalised medicines, relying upon a precise understanding of a patients genetic characteristics to treat the underlying disease pathology. Notable examples include Kalydeco[5] (the first drug approved in the treatment of cystic fibrosis and targeted to patients with a specific CFTR gene mutation) and Casgevy[6] (the first ever CRISPR/Cas9 gene therapy to receive marketing approval [FDA and MHRA in 2023, EMA in 2024] and used in the treatment of transfusion-dependent beta thalassemia, a rare disease caused by specific mutations in the haemoglobin beta [HBB] gene).
As technological innovation continues to improve our ability to process and stratify patient derived genomic, transcriptomic and proteomic data, it is expected that personalised medicines will continue to provide breakthroughs in the treatment of rare diseases, by further enabling the identification and precise correction of genetic defects underlying these conditions.
Extended IP protection offered to “orphan drugs” for the treatment of rare diseases:
The development of drugs that treat rare diseases, also called “orphan drugs”, has seen considerable growth, with the global market share of orphan drugs increasing by almost 10% over the last decade[7]. This growth has been supported by targeted financial, and regulatory incentives introduced in several jurisdictions, the EU and UK included, to incentivise their development and counteract the inherent challenge of relatively low demand for such therapies.
Among the primary legislative incentives for orphan drug development is orphan drug exclusivity (ODE). Specifically, the EU Orphan Medicinal Products Regulation[8] and its UK counterpart provide a 10 year period of marketing exclusivity for orphan drugs for diseases that affect less than 5 in 10,000 people, provided there is no previously authorised method of diagnosis, prevention or treatment of the disease, or if the new method is significantly better. Notably, where paediatric clinical trials are also conducted (even if unsuccessful), a total 12 year period of marketing exclusivity can be obtained.
Given the overlapping approaches to treatment of rare diseases and personalised medicine, it is of particular interest to develop personalised treatments where the patient subgroup is less than 5 in 10,000 people, and ODE can be obtained. Even when this is not the case, knowledge gained from successful IP strategies used in the protection of technology directed towards the treatment of rare diseases may help to inform strategies for protecting personalised medicines.
IP protection for methods for patient stratification
Successful IP strategies for rare diseases can inform IP protection for personalised medicines, and vice versa. Patent protection for patient stratification at the European Patent Office (EPO) and UK Intellectual Property Office (UKIPO) faces two principal obstacles: diagnostic methods are not patentable, and neither are mathematical models and computer programs.
Whilst at first glance it may seem that patent protection cannot be obtained for methods for patient stratification, this is not entirely true. While the EPO and the UKIPO do have rules that exclude diagnostic methods from patent protection, these rules are quite narrow. Specifically, the EPO and UKIPO define diagnostic methods as methods performed on the body on the human body. As such, specifying that the diagnostic method is carried out ex vivo circumvents the rules of exclusion. Additionally, instead of patenting an entire diagnostic process, comprising data collection, analysis[9] and clinical attribution, it is possible to patent methods for data collection alone, or the analysis and clinical attribution of pre-collected data.
These approaches have been successful in the field of rare diseases. For example, European Patent EP3546592B1 covers a method of detecting a marker of amyotrophic lateral sclerosis (ALS) which is a rare disease. The data collection step is limited to “measuring the enzymatic activity level of acid sphingomyelinase (ASM) in the sample obtained from the subject” (emphasis added), so is not performed on the human or animal body.
In addition, the exclusion of mathematical models and computer programs is limited to when mathematical models or computer programs are claimed “as such”[10]. This exclusion does not apply if the subject matter as a whole has technical character. A claim directed to either a method involving the use of technical means (such as a computer implemented method, which involves the use of a computer) or to a device, is considered to have technical character[11]. In addition, computer programs that produce a “further technical effect”, going beyond the normal physical interactions between the program and the computer on which it is run have technical character[12].
These approaches have been successful in the field of rare diseases. For example, European Patent EP3191993B1 in the name of Illumina is directed to detecting repeat expansion of a nucleotide sequence. Diseases caused by unstable repeat expansions include fragile X syndrome, Huntington’s disease and ALS, all of which are rare diseases. The claims of EP3191993B1 are directed to computer implemented methods rather than methods of treatment.
The ability to protect computer-implemented methods is of particular importance in both rare disease and personalised medicine, given the convergence of artificial intelligence (AI) and machine learning (ML) with life sciences related innovations. This is reflected by the 12% increase in AI-related patent filings in life and medical sciences reported by WIPO between 2013 and 2016 [13]. There exists significant potential for the use of AI in the analysis of complex genetic profiles, identification of disease biomarkers, and even the prediction of patient outcomes and optimal therapeutic actions based on individual patient data. The possibility for such AI models to tangibly impact healthcare delivery makes them particularly patentable at the EPO, which requires that a claim to an AI feature “contributes to technical character”, and could also increasingly streamline personalised treatment of diseases, rare or otherwise. For example, a recently granted US patent US11366102B2 provides a model for predicting drug responsiveness based on the analysis of metabolites, particularly in breast cancer patients[14].
IP strategy for launching personalised therapeutic agents in the UK and EU
In contrast to diagnostic methods, the ability to obtain protection for first and subsequent medical uses at the EPO and UKIPO is important to consider as part of the patent strategy of a personalised medicine, not least because personalised medicine often include treatment of specific population subgroups with known therapeutic agents.
A case study on eculizumab, a drug patented by Alexion for the treatment of multiple rare diseases, revealed that the company has generated substantial profits by adopting a business model focused on extensive research into new therapeutic indications for the same drug. By continuously identifying further additional rare disease applications, Alexion has been able to file new patent applications for these indications, with the potential to effectively extend market exclusivity and maximise the drug’s commercial potential[15].
Such a strategy may not be applicable to all personalised medicines, which can be precisely targeted to the correction of specific genetic defects underlying diseases. However, patents towards personalised use (or methods enabling personalised use) of previously broadly indicated drugs, based on the identification of especially (un)responsive patient strata, has been a successful approach before the EPO. An example includes EP1831402 directed towards a method for predicting the appropriate dose range for the administration of warfarin based on a patients genetic profile, which was found to indicate their sensitivity or resistance to the drug.
This demonstrates the principle that personalised medicines, like orphan drugs, are inherently narrow in the scope of their protection. This may be an important consideration when planning how to obtain the most effective IP protection.
Outlook
The treatment of rare diseases relies on data derived from small patient sub-groups, making this area particularly amenable to treatment through personalised medicine. Both areas offer exciting commercial prospects, with the development of orphan drugs benefiting from extensions in market exclusivity, whilst personalised medicine represents a paradigm shift in healthcare delivery, set to revolutionise patient outcomes and treatment costs. As technologies advance, transformative breakthroughs in personalised medicine and orphan therapeutics are expected in the years to come, and the co-evolution of the IP landscape in each of these respective fields will be of particular interest when considering how to best protect intellectual property in these areas.
Sources
[1] https://www.sciencedirect.com/science/article/pii/S1470211824013162#cesec90
[2] https://link.springer.com/chapter/10.1007/978-3-319-67144-4_22
[3] Regulation (EC) No 141/2000
[4] https://www.eurordis.org/information-support/what-is-a-rare-disease/
[7] https://www.evaluate.com/thought-leadership/orphan-drug-report-2024/
[8] Regulation (EC) No 141/2000
[9] In this instance, the term ‘analysis’ is specifically refers to the comparison of collected data with standard values and finding of significant deviation, as per the EPO legislation
[10] Articles 52(2) and (3) EPC
[11] Guidelines for Examination in the European Patent Office, G-II, 3.3
[12] Guidelines for Examination in the European Patent Office, G-II, 3.6
[13] https://www.wipo.int/edocs/pubdocs/en/wipo_pub_1055
[14] https://www.reddie.co.uk/2025/02/04/ai-analysis-of-biological-samples-for-cancer-diagnosis/
[15] Caetano et al. (2021) Dynamics of patents, orphan drug designation, licensing, and revenues from drugs for rare diseases: The market expansion of eculizumab. PLoS ONE 16(3): e0247853.
