Thanks to improvements in next-generation sequencing techniques and other high-throughput approaches for analyzing biological samples, personalized medicine is taking a greater role in patients' treatment decisions. For example, the FDA now lists 118 approved drugs that include information about pharmacogenomic markers in their labels. But recent U.S. court decisions have altered the patent strategies companies should use to protect their investment in personalized medicine-related technologies.
Recent developments at the U.S. Supreme Court have upset settled assumptions about patents in biotechnology.
The Supreme Court recently took an interest in two cases that have particular relevance to the diagnostics industry. The first, Mayo v. Prometheus, concerned a patented method for determining the ideal dosage of thiopurine drugs in treating autoimmune diseases. The inventors discovered that the drug was most effective when the concentration of a particular metabolite in a blood sample fell within a narrow window. The patent recited method claims using a fairly typical series of steps: administer the drug, determine the level of the metabolite, and if it falls outside of the window, the next dose should be decreased or increased for optimal effectiveness.
In March of 2012, the Supreme Court held that this relationship between the metabolite concentration and the optimized dosage was a patent-ineligible "law of nature," and that more was necessary to transform it into a patent-eligible application of a natural law.
The case has raised many uncertainties about how this expanded concept of a "law of nature" will play out in practice as others attempt to patent diagnostic methods relying on correlations between a reporter compound or gene product and some physiological condition. But all is not lost. There is some guidance. For instance, if the method relies on measuring the reporter using a particular technology, this may be enough to surmount the initial barrier of patent eligibility.
The second important case involves the dispute over patents relating to the BRCA genes. People with certain mutations in these genes have a greatly increased likelihood of developing breast cancer. Some of the claims cover (1) an isolated DNA sequence encoding the BRCA1 protein, (2) the isolated cDNA corresponding to the BRCA1 gene, and (3) isolated DNA fragments that map to a gene encoding the BRCA1 protein.
The ACLU has sued the U.S. Patent & Trademark Office and exclusive licensee Myriad Genetics on behalf of a group of doctors, researchers, and others, arguing that these "composition" claims, along with some related methods, are patent-ineligible subject matter.
The Myriad claims were initially found invalid but were partly reversed on appeal by the U.S. Court of Appeals for the Federal Circuit. The Federal Circuit, following past precedent, determined that an isolated nucleic acid molecule is fundamentally different from that same sequence integrated into the chromosome, and thus the isolated BRCA1 gene is patent-eligible and not merely a product of nature. But two judges on the panel basically agreed that while the claimed cDNA and fragment probes were truly things that did not exist in nature, purification of a naturally occurring element is generally insufficient to confer patent eligibility.
In fact, one judge clarified that her agreement with the judgment as to the isolated gene was primarily based on a reluctance to upset settled expectations about the patentability of DNA sequences.
Is the lack of unanimity in the Myriad opinion a foreshadowing of things to come? The Supreme Court has clearly expressed an interest in the future of claims to DNA sequences. It vacated the initial Federal Circuit opinion, and remanded it for reconsideration in light of the Prometheus decision. The Federal Circuit, however, released an opinion with the same result. Apparently not satisfied, on November 30, 2012 the Supreme Court granted certiorari to hear the Myriad case on appeal.
There is now a nontrivial chance that the Supreme Court will make yet another foray into the patenting of biotech inventions and create law that invalidates thousands of patents relating to DNA sequences.
For example, the Court could find that claims to isolated, naturally occurring DNA sequences are ineligible for patenting, regardless of their novelty or nonobviousness. It may also find the DNA probe claims (directed to fragments of the gene of at least 15 nucleotides) cover patent-ineligible products of nature.
Now is the time for you to review your patenting strategy for many diagnostics-related technologies.
Both the Prometheus and Myriad cases affect the legal concept of subject-matter eligibility, governed under U.S. law by 35 U.S.C. § 101. This initial test for patent eligibility has historically been very broad, because to obtain a patent, the claimed material must still meet the secondary hurdles of novelty and nonobviousness, as well as certain requirements intended to ensure that a patent applicant has sufficiently demonstrated possession of the invention and has disclosed enough to enable others to make and use the invention.
These recent decisions have generally narrowed the scope of the first screen for patent eligibility for many useful life sciences technologies. But they are not without clues for how to protect newer, more complex technologies.
Diagnostics based on the presence or absence of a single genomic subsequence will now require more for patent protection. But with respect to technologies relying on genetic markers, in fact these decisions may not have as severe an impact as they initially appear.
For instance, a company attempting to commercialize a method involving a single-gene reporter involving a claim to a cDNA for the normal human gene will be confronted by a novelty rejection, as most if not all human genes have already been cloned. Work in this area is best suited to developing kits implementing the test. The patentability of diagnostic kits continues to be uncontroversial.
Identifying and commercializing diagnostic sequence profiles is an even more promising area. Rather than focusing on the correlation between a single genetic marker (or reporter compound) and a patient's condition, useful correlations between collections (or profiles) of genetic markers and a disease diagnosis, the risk of developing the disease, the predicted severity, or a preferred treatment can provide a path to patent eligibility.
One of the rationales used to reject the Prometheus claims was that every step of the method was routine and conventional, and it only served to inform doctors of the relevant correlation. But in the case of a diagnostic sequence profile, measurement of the profile can be fairly complex; there is value in identifying or developing the best mode of measurement, be it microarrays or newer technologies.
Additional complexity comes from the approach for determining whether a patient's profile is associated with a normal or abnormal state—rather than a binary decision, the result is a more nuanced estimate that depends on the combined expression or mutational differences of reporters in the profile. These additional complexities can distinguish claims to these technologies from the unpatentable method in Prometheus.
Another path to patent eligibility may be inclusion of a "man-made" sample. For example, if a patent claim includes binding a DNA probe to a biological sample and such a sample with the bound probes would not otherwise exist in nature, the existence of a man-made sample may also impart patent eligibility.
While these recent decisions may at first glance cloud the landscape of patentability in biotech, in fact the outlook may not be so grim. All one may need to consider is a little creative patent drafting.