Precision medicine: The personal touch
As we move away from a ‘one-size-fits-all’ approach to medicine, we move towards the future: precision medicine.
This ground-breaking development also represents something else—a fundamentally different way of thinking about treatment of human suffering, says Daniel Lim, partner at the London office of Kirkland & Ellis.
“Precision medicine has the potential to yield significantly better and more reliable outcomes, with reduced side-effects, reduced waste in the healthcare system and more informed clinical decision-making,” Lim adds.
Fran Salisbury, partner at Mewburn Ellis in Manchester, UK, agrees. “It offers fantastic opportunities in terms of improving patient outcomes and improved patient experiences, but it also offers significant benefits to society as a whole,” she says.
However, despite the potential, there are myriad issues surrounding precision medicine that must be addressed before full advantage of the offering can
be taken.
"The general sense in the life sciences industry is that there is a lack of consistency in the application of section 101." - Sanjay Murthy, Morgan Lewis
First up is the patentability of diagnostic tools. Since the US Supreme Court’s 2012 decision in Mayo v Prometheus, the courts have found a series of patents claiming diagnostic methods and tools ineligible under section 101.
On the sixth anniversary of the decision, researchers at the University of Cambridge and University of Copenhagen published an examination of the impact Mayo has had on patent eligibility.
They found 21,977 patent applications that during prosecution contained a citation to Mayo in a patent eligibility rejection; 9,435 of these applications were from the USPTO’s Technology Center 1600, which deals with the biotechnology and organic chemistry fields.
John Liddicoat, senior research associate at the Centre for Law, Medicine and Life Sciences at the University of Cambridge, added that excluding pending applications, the Technology Center 1600 applications had an allowance rate of 35.9%.
Of the granted applications, 45.8% had engaged in a second round of prosecution by filing a request for continued examination (RCE) and that 30.3% of them required two or more RCEs before they were granted. These are particularly high rates of RCEs compared to the rates pre-Mayo, according to Liddicoat.
“It’s important to note that the prevalence of section 101 rejections citing Mayo has remained consistently high since the decision—indicating enduring high levels of legal uncertainty,” he adds. “Although there is an ever-present need to strike
a balance between legal certainty and flexibility, the levels of uncertainty after Mayo are substantial and ongoing.”
Brian Slater, partner and co-chair of life sciences at Pierce Bainbridge Beck Price &
Hecht in New York, adds that many of the other diagnostic method claims that have been struck down as patent-ineligible since Mayo involve important medical breakthroughs based on previously unknown laws of nature.
Patent eligibility for these types of claims raises particularly thorny issues, explains Sanjay Murthy, partner at Morgan Lewis in Chicago.
“The general sense in the life sciences industry is that there is a lack of consistency in the application of section 101. However, a lot of these cases turn on fact-specific enquiries and for this reason I am not sure how much a court revisiting this issue would help in the broader sense,” he says.
Contrast this with John Sninsky, a consultant in translational sciences and former chief scientific officer at CareDx, who believes that Congress and the courts should revisit patent eligibility of diagnostic method claims.
"The potential of the technology is exciting, but the risks if the data were misused are huge." - Frances Salisbury, Mewburn Ellis
Again, lack of clarity plays a part—Sninsky notes that landmark section 101 and 112 decisions over the last decade have “erected significant obstacles for commercialisation and stifled investment in innovation by significantly increasing uncertainty and the risk of patent issuance for medical device manufacturers”.
These issues may be addressed, if the Supreme Court decides to grant cert in Vanda Pharmaceuticals v West-Ward Pharmaceuticals.
In Vanda, the US Court of Appeals for the Federal Circuit in a 2:1 decision upheld under section 101 the validity of a patent claim to a method of treatment for schizophrenia using iloperidone at specific doses depending on whether the patient is a poor metaboliser.
The court distinguished the claim involved in Mayo as merely reciting a natural law, according to Slater, whereas the Vanda patent was eligible because it claims an application of the natural relationship discovered by the Vanda scientists.
If the Supreme Court were to uphold the Vanda decision, it would provide much-needed certainty, but it remains to be seen whether the court will take up Vanda to revisit the patent eligibility of diagnostic method claims.
“Even if the Supreme Court were inclined to revisit its decision in Mayo, the Vanda case does not appear to be a very good vehicle for doing so given the differences in the claims involved in the two cases,” says Slater.
Europe
It’s a different story in Europe. Lim says the European Patent Office’s (EPO) approach is “not as harsh” as the USPTO’s, citing the divergent outcomes in the US and Europe in relation to the Sequenom patents, which relate to the detection of paternally inherited DNA in the cell-free foetal DNA in the blood of pregnant women.
In the US, the invention was found to be invalid under section 101. But, in the UK and Europe, the equivalent patent survived a similar attack made on the basis that the claimed invention was a discovery as such.
Salisbury agrees, adding that the EPO is much more applicant-friendly than many other patent offices in this area.
“EPO examiners are often willing to allow claims that define a new biomarker—disease correlation, such as a newly identified patient subgroup, or a new clinical indication, provided this is reflected in the data in the application. Applicants can therefore often get relatively broad claims in Europe, and relatively early in development of diagnostics,” she says.
However, these inconsistencies in practice may hinder a global effort at rolling out such technologies, warns Conor McDonough, partner at Pierce Bainbridge in Boston.
“In the US, ongoing legislative efforts to revise patent eligibility standards may achieve a balance between incentivising innovation and avoiding improperly granted rights to exclude,” he adds.
Liddicoat agrees that these differences are affecting commercial decisions. In a recently accepted, interview-based paper, the university found evidence that ‘patent precarious’ organisations, such as technology transfer offices in the US, are choosing not to develop molecular tests due to patent eligibility issues.
Sninsky is more optimistic—he notes that even though landmark decisions for laws of nature and obviousness have significantly slowed patentability, innovators and patent filing firms have begun to “glean the necessary insight from past decisions to obtain at least modest patent coverage”.
He concludes: “While there is an increase in issuance of patents in the precision medicine space over the last two to four years, the limits in diagnostics needs to be addressed by Congress, the patent office or the courts if precision medicine is to reach its full potential by protecting innovator commercialisation.”
Other considerations
A host of other considerations need to be addressed—in particular, data and information security and appropriate usage.
Salisbury says: “The potential of the technology is exciting, but the risks if the data were misused are huge, and we need to ensure the ethics and regulation keep up with science.”
Murthy concurs, noting that privacy concerns for patient data, ownership and use of such data, and the ethical implications of how to use the data are of major concern.
According to Salisbury, it will be a challenge to stay ahead, and deal with these issues proactively, rather than reactively, following a data breach or misuse.
Many personalised medicine inventions arise from the analysis of samples provided by individuals for other purposes, such as for the diagnosis of another disease, or for ancestry analysis.
While Salisbury says this is fantastic for patients, as new diagnoses and treatments are expedited, without the need for fresh samples for every analysis, it can present problems.
“What other traits can also be deciphered from these samples without your knowledge?” she asks.
“What if the data could also be mined to determine your risk of developing other conditions that you don’t yet have, such alcoholism, depression or Alzheimer’s—might this information be used to deny or modify your prescription, even though you don’t yet exhibit any such symptoms?”
As we move towards a time when a doctor may be able to diagnose someone at risk of developing a disease, and begin treatment before symptoms arise, it’s important to ask whether it’s appropriate to treat a healthy patient on the basis that they might one day develop a disease.
“People may believe that they have a right to know all the information that is available about them, but is this true? There is a big difference in knowing that you are 100% more likely to develop a particular cancer than another person and understanding that this means that you have a one-in-10,000 chance of becoming sick,” says Salisbury.
She concludes that managing patient expectation and understanding will play a big part in precision medicine’s successful adoption in the clinic.
The challenge of how new precision medicine approaches and treatments will intersect with and fit alongside existing treatment protocols is an issue of utmost importance, albeit a currently overlooked one, adds Lim.
In the coming years, as the precision medicine debate grapples with new scenarios it will inevitably draw on the past for a framework. Meanwhile, rights holders will hope that areas where the IP system is holding back innovation will instead look forward, approaching protection with new thinking and finding consensus where currently there is little. The future of healthcare depends upon it.
