IP and personalised medicine: a tailor-made approach
In 2017, the US Food and Drug Administration (FDA) approved a record 16 new personalised medicines, according to the “Personalized Medicine at FDA: 2017 Progress Report”. From 2014 to 2017, more than one in every four drugs the agency approved was a personalised medicine.
“Those numbers are a sharp increase from 10 years ago, when personalised medicines accounted for less than 10% of new molecular entity approvals annually,” explained the report, released by the Personalized Medicine Coalition, which represents innovators, scientists, patients, providers and payers.
One of the challenges when discussing personalised medicine is, ironically, its broad and imprecise definition. Jason Christiansen, senior director, assistant general counsel, IP at Adamas Pharmaceuticals in Emeryville, California, views the term broadly. He argues that it can include any form of treatment, including via medical device or surgical procedure, designed to treat an individual or a subgroup of the larger population based on common characteristics of that subgroup.
Speaking to LSIPR in a personal capacity, he says such treatments for individuals or subgroups are typically based on unique characteristics or known (or expected) responses of an individual or member of the subgroup based on one or more factors.
These might include a known response to the treatment through a previous trial, plus the suspected need for and/or response to a treatment based on environmental factors such as location, living conditions, and diet.
The third factor might be membership in a group—such as being male or female or being of a certain race or ethnicity—which is known to have certain characteristics susceptible to treatment or a known response to a treatment, he says.
He adds that an individual’s genetics, including a known mutation that affects a group of people, is a potential fourth—and the most common one that people think of when they think of personalised medicine.
Christiansen also believes that medical treatments that are known to work for a group of people with a condition, but not all people with the condition, can also fit into the realm of personalised medicine even if it is not known what common characteristic the group of people have that allows the treatment to work for them.
For example, Christiansen is aware of a symptomatic treatment that only works in 30% of the patient population, and considers that treatment to be “personalised” for that group of the population. While it is likely that those 30% share some common genetic marker or markers that allow the drug to work for those patients, it is not known what makes the drug work in those patients.
But for medicines such as this that are relatively safe and that are discovered to work in a significant portion of the population, it may be acceptable to approve the medicine and then just let patients try it and see if it works for them. As long as the drug does not come with serious risks, such a method of personalising a medicine and determining which people it actually works for may be acceptable.
While this would not necessarily fall within what most people think of personalised medicine, according to Christiansen, this should be included in what everyone thinks of as personalised medicine.
Despite being active in the biopharmaceutical industry, Adamas doesn’t actually operate in the field of personalised medicine as described above. The company focuses on time-dependent biology, ie, the deliberate mapping of disease patterns and drug activity, says Christiansen, who is speaking on a panel discussing IP considerations and personalised medicine at LSPN Fall 2018, on October 16 in San Francisco.
Unlike personalised medicine, which focuses a treatment on an individual or subgroup that is typically much smaller than the entire population with a disease, time-dependent biology typically focuses on more closely personalising the treatment to the disease as it affects the majority of the population, he explains.
The aim of the time-dependent approach is to “meaningfully increase the efficacy of the treatment without compromising tolerability”.
However, while Adamas has this particular focus, the topic of personalised medicine is becoming increasingly important, according to Christiansen.
He is not alone in this view, either. Just this month, September, the CEO of National Health Service (NHS) England, Simon Stevens, announced that children and young people in England will receive a “groundbreaking cancer treatment”, a CAR-T (a chimeric antigen receptor T-cell) therapy called Kymriah.
It is the first “in what is expected to be a rapidly expanding class of personalised cancer therapies available on the NHS”, according to a statement.
In the US, where Adamas is based, the FDA has said personalised healthcare “will only be as good as the tests that guide diagnosis and treatment”, noting that Next Generation Sequencing (NGS) tests are capable of rapidly identifying or ‘sequencing’ large sections of a person’s genome and are important advances in the clinical applications of precision medicine.
The agency said it is working to ensure the accuracy of NGS tests so that patients and clinicians can receive accurate and clinically meaningful test results.
Protecting your invention
On the patenting front, one of the biggest challenges in obtaining protection for personalised medicine is avoiding the discovery being considered a ‘law of nature’, Christiansen explains.
“For example, if a patentee tries to simply claim diagnosing a patient with X disease based on a specific genetic marker, that may be an unpatentable law of nature if that genetic marker results in the patient having the disease because the prospective patentee has just discovered a relationship that exists in nature,” he says.
But if the patentee combines this diagnosis with a specific treatment based on this diagnosis, the patentee can probably avoid this being a law of nature because it has now discovered affirmative steps to take the discovery beyond just a law of nature, Christiansen adds.
While this may be a solution, it does create additional problems for the patentee, according to Christiansen.
“The patentee wants to obtain reasonable protection for what he or she has actually discovered but also avoid potential competitors from being able to easily design around his or her discovery.”
Elaborating on this by using his prior example, he imagines a case where the genetic marker indicates someone who is almost certain to get osteoporosis and the treatment is a biphosphonate, a known class of drugs for treating that condition.
Here, the patentee wants to do everything they can to ensure the claims are not limited to only treatment with biphosphonates, Christiansen says, because someone may come up with a new treatment for osteoporosis in five years and the patentee would not have protection for the relationship identified when the treatment is this new class of drugs.
Christiansen admits that such challenges cannot necessarily be overcome, but patentees have options available. For a start, they should carefully draft and prosecute their applications.
He says the most significant case on personalised medicine in recent years is Association for Molecular Pathology v Myriad Genetics, a decision handed down by the US Supreme Court in 2013. The court held that a naturally-occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but that amino acid sequences that do not exist in nature, such as cDNA, are protectable.
The case was seen as narrowing the scope of patent-eligible subject matter in the area of naturally-occurring products but, says Christiansen, it did not kill future personalised medicine IP.
Rather, Myriad provided a framework on what should be done to obtain valid and enforceable IP in this area.
“As a result of patent prosecutors fitting the prosecution into this case, it generally results in narrower claims that may not foreclose competitors from using a discovered relationship that by itself would be a law of nature.”
Another strategy for overcoming challenges in patenting personalised medicine is monitoring competitors, as “you never know when they may leave an opportunity open”, Christiansen explains.
Continuing with his earlier example of bisphosphonates, he considers that a competitor might discover a new class of drugs that treats osteoporosis and then publishes some preclinical data.
“Maybe they’ve filed a patent application by this point, but maybe they didn’t include the idea of performing your diagnostic test for the genetic marker coupled with the use of their class of drugs. Under the right circumstances, there may be an opportunity to file your own application on this if you are closely monitoring the state of the art.”
Solid patent prosecution can also help with enforcement later down the line because in many cases there will be a diagnosis step, eg, a genetic test to see if a patient has a specific marker, and a treatment step, says Christiansen.
Because these two steps are often not done by the same party, establishing inducement of infringement can be more challenging, he notes.
“Thus, it is important to prosecute the patent claims to help make establishing inducement of infringement under current law easier and to do the best you can to protect the claims from changes in the law of inducement of infringement that may occur in the future.”
Looking to the future of personalised medicine, Christiansen says while most pre-existing treatments focus on life-threatening diseases, often with relatively small populations where the treatments are very expensive, there is a great chance to develop treatments for larger groups of the population.
“With the price of genetic tests falling all the time, there is a significant opportunity to make genetic information a component of future clinical trials where post-hoc data analysis may demonstrate significant differences in efficacy or safety profiles among people with or without certain genetic markers,” he concludes.
