By Timo Minssen
In Part II of this blog on legal issues relating to the revival of phage therapy I discussed the US Supreme Court’s decisions in Myriad and Prometheus, which might present major obstacles to the patentability of phage-related technology (a more detailed analysis of the Myriad and Prometheus decisions is available here).
Yet, all is not lost. As indicated in Part II, Myriad does not directly affect the patentability of synthetically modified biological compounds and Prometheus would still allow patents on inventive applications of natural processes and correlations that add new features to “natural laws”. Thus there still seems to be considerable leeway for patenting within the area of page therapy.
One example, mentioned in a recent Nature article, could be the skillful selection and precise combination of different phages in order to attack one specific type of bacteria. Such selections, however, would face a tough battle to overcome the “additional features that add significantly more” and “not identical” thresholds set by Prometheus and Myriad. Another example with even better prospects for patentability relates to genetically modified phages that are – due to human intervention – enabled to target only specific bacteria. This technology was recently presented by MIT researchers at the 2014 American Society for Microbiology Meeting. The researchers led by Timothy Lu had genetically engineered phages that use a DNA-editing system called CRISPR to target and kill only antibiotic-resistant bacteria while leaving other susceptible cells untouched. The significant engineering and alteration of natural products and processes involved in such inventions would most likely meet both the Myriad and Prometheus standards.
Yet, while the USPTO has recently issued new patent eligibility guidance and the CAFC has begun to directly apply Prometheus and Myriad to reject patent claims in biotech cases (e.g. In re Roslin), many questions remain unsolved. In particular, it is still not sufficiently clear exactly how much modification is required to render a molecule or method sufficiently distinct from naturally occurring product and processes. And even if the patent-eligibility threshold could be met in extraordinarily circumstances, the claimed invention would still have to fulfil other patentability requirements such as novelty, non-obviousness and the written description-requirements. The threshold for these requirements, however, have been heightened in recent years (see e.g. KSR v. Teleflex (2007) , Nautilus (2014) etc.). Considering that phage therapy is almost a century old with a substantial common general knowledge and a state of the art employing routine methods, these crucial requirements might still prevent the patentability of many useful applications.
Consequently, much uncertainty remains within the nowadays rather blurry lines between the “patent eligibility”, novelty, and “nonobviousness” criteria. Patents are possible, but only in narrowly defined areas since the fruits are hanging low, and the number of patients in which this technology could be applied is (so far) rather limited.
So what can be done to enhance the development of phage therapies? As pointed out in an earlier blog one solution could be more governmental and public involvement, e.g. through public private partnerships (PPPs) and the funding of clinical trials through public entities (cf. the EU’s IMI and Phagoburn project). Streamlining the market approval procedure and creating specific regulatory exclusivities (cf. the US GAIN act ) might also help.
Moreover, various delinkage models could offer highly effective and sustainable solutions. These are alternative models for recovering R&D costs in drugs & devices. Delinkage relies on prizes and grants instead of patent-protected sales above marginal cost. Delinkage models can take various shapes and may be characterized by a wide array of different financial and organizational features. In his recent paper “New Business Models for Sustainable Antibiotics”, Professor Kevin Outterson delivers an excellent analysis on delinkage options in the fight against AMR. These could also be considered for phage therapy.
Finding the right balance of predictable push and pull incentives can be as complex as the problem of AMR itself. There seems to be no “one size fits all” solution, but rather a variety of options that need to be combined and optimized for various cases. But the danger is imminent and initiatives are necessary. This requires new ways of thinking including both reactive and proactive approaches. Any initiative must be coupled with preventive and conservational considerations, so that we are not only battling the symptoms but also the cause of AMR.