Systems medicine represents the transition of systems biology to a clinical paradigm. Biomedical and biological research has been significantly advanced by a holistic approach to the interaction of components within biological systems. The translation of systems biology to medical outcomes represents the field of systems medicine. Systems medicine has been defined as integrating cellular organisational data by various modelling techniques to assess pathophysiological outcomes.
One example is the diagnosis of a disease condition or state based on biomarkers. A clinical translation of such diagnosis can constitute elements of personalised medicine, where pharmacoresponsiveness of a patient is determined prior to selection of an agent or the protocol for administration of an agent. For example, the current trend in cancer care is the indivisualisation of treatment programs to provide the best care based on the possession of certain biological characteristics. The personalised aspect of systems medicine is becoming increasingly important due to its significant potential for reducing the total cost of care and to deliver improved patient outcomes. Systems medicine offers attractive commercial opportunities for those developing agents for therapies.
It is of interest to consider the impact of the US Supreme Court decision in Mayo Collaborative Services et al. v Prometheus Laboratories("Prometheus"), handed down on 20 March, 2012. The Prometheus patent claimed inter alia a method for optimising therapeutic efficacy to treat an immune-related gastrointestinal disorder by administering a known drug and measuring the level of a metabolite from that drug, wherein the level of the metabolite correlates with a need to either increase or decrease the dosage of the known drug. The US Supreme Court's analysis of the claim in question centered around whether there was sufficient application of laws of nature to render the subject matter patent-eligible. Laws of nature include physical correlations and phenomena, and in the Prometheus case, the relationship between metabolite levels and dosage efficacy. Potential application steps recited in the claim were:
- the wherein clause; and
The Supreme Court concluded that none of these application steps contributed more to laws of nature other than what is a "well-understood, routine, conventional activity, previously engaged in by the field". In essence, the Court is seeking an application step which is not "conventional or well known" to transform a law of nature into a patent-eligible application of such a phenomenon.
Impact of Prometheus on Systems Medicine
Prometheushighlights the challenge of protecting various applications of systems medicine in the US. Diamon v Diehr established that an application of a law of nature may represent patent-eligible subject matter, and Gottschalk v Benson required that the application must be inventive. Prometheus stated "to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words "apply it"". Hence, the mere application of a law of nature would, based on Prometheus, not be patent-eligible, unless this application is non-conventional. Interestingly, recent guidelines issued by the USPTO for examination of claims involving laws of nature make it clear that the transformation step need not be novel and non-obvious to carry the claim across the patentability threshold.
The Prometheus decision has caused some concern in the life science industry and diagnostic and method of treatment claims should be drafted with care. The challenge to patent drafters is to define a physical transformation step which is more than a correlation mechanism, assuming the correlation is achieved by conventional techniques. Such a step, whilst not necessarily novel nor non-obvious in its own right, needs to render the method, as a whole, novel and non-obvious. However, any adverse impact of the Prometheus decision can be mitigated to some extent by including embodiments in a patent specification supporting claim language in the US which provide an overall novel and inventive application of a method involving a putative law of nature. Such applications include the use of diagnostic platforms, interfacing with diagnostic assays, devices, use of genetically modified cells and drug design and possibly selection based on potential pharmacoresponsiveness of a subject.
Notwithstanding, the identification of novel biomarkers or the use of non-conventional techniques to identify a correlation may nevertheless go beyond Prometheus. For example, determining a pattern of biomarkers such as single nucleotide polymorphisms associated with a level of pharmacoresponsiveness creates a level of determination which is more than the use of conventional analysis. The claim then is directed to the pharmacoresponsiveness of a subject or agent rather than the treatment. It may also be worth considering if in conjunction with the natural principle, methods can be described in terms of the use of a new drug or in terms of a new use of an existing drug.
Myriad and patent eligibility
The life science industry can take heart from the Myriad decision handed down on 16 August, 2012 which noted that "patents on life-saving material and processes, involving large amounts of risky investment, would seem to be precisely the types of subject matter that should be subject to the incentives of exclusive rights". Importantly, isolated DNA molecules and methods for screening for therapeutic agents were held to represent patent-eligible subject matter. Furthermore, Myriad states that a "determination" step does not necessarily render a claim patent-ineligible, especially if it is based on an artificially created entity, e.g. genetically transformed cells.
It is important to note that Prometheus does not necessarily represent a threat to patenting applications of systems medicine in the US. Rather it provides the impetus to develop a holistic approach to protecting innovation in this area. Such innovation will likely need to be protected by claim language based on the merits of each case. Prometheus focused on a concern that permitting patents on certain subject matter defined by a correlation would prevent others using that correlation. However, Myriad confirms that a non-naturally occurring composition of matter is not a law of nature representing a rational application of Prometheus. We would suggest that Prometheus is not inconsistent with protecting innovation in systems medicine especially in the light of Myriad.
Protecting Innovation in Systems Medicine
- Systems medicine represents the transition of systems biology to a clinical paradigm.
- Prometheuson the one hand highlights the challenge of protecting various applications of system medicine, however, provides the impetus to develop a holistic approach to protecting innovation in this area. This is supported by Myriad.
- The identification of novel biomarkers or the use of non-conventional techniques to identify a correlation may be enough to go beyond Prometheus.
- Systems medicine patents need to contain language in the US which provide an overall novel and inventive application of a method involving a putative law of nature, e.g. use of diagnostic platforms, interfacing with diagnostic assays, devices, use of genetically modified cells and drug design and possibly selection based on potential pharmacoresponsiveness of a subject.