Education, Raising Awareness and Reducing Test Turnaround Time Increases Number of Patients Treated with New Targeted Therapy
The recent Prometheus decision issued by the U.S. Supreme Court has become the talk of the personalized medicine field, generating a swarm of comments from legal and industrial pundits and influencing strategic legal and economic decisions in this growing sector. This post offers a brief synopsis of the case itself and our recommendations on how to manage your intellectual property wisely in the wake of Prometheus.
At the center of the Prometheus decision lie two patents owned by Prometheus Laboratories, Inc. (U.S. Patent Nos. 6,355,623 and 6,680,302). Generally, the patents relate to methods of monitoring and adjusting the dose of thiopurine drugs to patients being treated for conditions such as Crohn’s Disease. It is not contested that, prior to the filing date of these patents, thiopurine drugs were already being used to treat such patients. What the inventors of the Prometheus patents discovered was that after administration of a thiopurine drug, there were certain thresholds of the drug and/or its metabolites in the patient which indicated whether the subject had received a sufficient dose, an appropriate dose, or an insufficient dose, and that these thresholds could be used in order to successfully treat the disease. The claims under consideration by the Court are typified by Claim 1 of U.S. Patent 6,355,6231, which claims a method of “optimizing therapeutic efficacy” by first “administering” a thiopurine drug to a subject and then “determining the level” of the drug in the subject. The claims further describe what level of the metabolite indicates a need to increase the dosage the subject receives and what level of the metabolite indicates a need to decrease the dosage the subject receives. The claim does not require that the dose actually be adjusted.
For several years, Mayo Clinic Rochester and Mayo Collaborative Services were clients of Prometheus Laboratories, purchasing products covered by the patents in question. However, Mayo eventually began producing and using its own test, which utilized a slightly different threshold of the drug concentrations to determine efficacy. At that point, Prometheus sued Mayo, alleging that Mayo was infringing the patents.
By the time the case reached the Supreme Court, the legal wrangling had been condensed down to the question of whether the Prometheus patents were claiming patent eligible subject matter. Under U.S. patent law, a patent cannot claim a “law of nature,” “natural phenomenon,” or an “abstract idea.” For example, one cannot patent the natural phenomenon that is electricity, but various methods of conducting or using electricity are themselves patent eligible subject matter. Generally speaking, patents can only claim the works of man, not the mere recognition of pre-existing relationships or objects.
In analyzing the Prometheus patents, the Supreme Court opined, in a 9-0 decision authored by Justice Breyer, that the correlation between drug levels in the patient and the efficacy of the dose is a law of nature. In their opinion, a human body will metabolize a thiopurine drug in accordance with “entirely natural processes” and that the thresholds described in the Prometheus patents are therefore merely descriptions of a relationship that “exists in principle apart from any human action.” The recitation of the drug level thresholds was judged to merely describe a natural law.
In determining patent eligibility, the Court then conducted a novelty analysis, examining whether each step was or was not routine. The final opinion was that the claims recited only “administering” and “determining” steps, both of which were considered routine. The remaining part of the claims didn’t require any active steps, only that the clinician would or would not alter the dose when the level of thiopurine reached the stated threshold. None of the claims in question required that more of the drug be administered. In the simplest terms, the Court characterized the Prometheus claims as instructing a certain group of people (doctors) to gather information according to well-established methods and to consider the implications of a natural law when deciding upon a future course of action. In their opinion, this was not patent eligible subject matter.
So what does this decision tell us?
We now know that a claim similar to the one in Prometheus, e.g. administering a drug and determining the level of a metabolite, is not patent eligible subject matter. This has implications for more traditional diagnostics claims, which often read:
A method of determining if a subject is at risk of developing cancer, the method comprising: determining the level of an expression product of gene X in a biological sample obtained from the subject; and comparing the expression level to a reference level, wherein an increased level of gene X indicates an increased risk.
Would such a claim fall under the ruling in Prometheus? The claim only requires that the level of gene X expression be measured and that level compared to a reference level. Is the correlation between the level of gene X expression and cancer a law of nature? Justice Breyer would say so.
So what should you, if you are considering obtaining a patent on such a test, do now?
While the reactionary response would be to stop filing patent applications and rely on trade secrets, the smart response is to continue filing patent applications but to be more thoughtful in formulating claims. We simply now must recognize that patents in this area will, unavoidably, be narrower than the historic claims to which stakeholders in this field have been accustomed.
Continuing to maintain patents as part of an intellectual property strategy is particularly important in light of established customs amongst investors. In the eyes of investors, patents have value and are a well-understood form of intellectual property. Trade secrets are much more nebulous, more difficult to value, and are often not fully accessible to prospective investors due to their intrinsically confidential nature. While trade secret protection should be a key component in any intellectual property strategy, many investors simply aren’t comfortable dealing in a trade secret-only portfolio.
We will learn more about the boundaries of patent eligible subject matter as the Myriad case makes its way from the Supreme Court back to the Federal Circuit and ultimately, back to the Supreme Court.
David Resnick is the co-leader of the Patents practice group at Nixon Peabody. David’s practice is focused on patent prosecution and overall portfolio management, transactional matters, and associated client counseling. He has been entrusted with managing the patent portfolios of some of the leading U.S. research institutions and domestic and international corporations. David has extensive experience in the life sciences and is widely regarded as a thought leader in the areas of pharmacogenomics, proteomics, and disease biomarkers, and their application in the evolving field of personalized medicine. Contact him at firstname.lastname@example.org
1 Claim 1 of the 6,355,623 patent reads:
A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:
(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and
(b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder, wherein the level of 6-thioguanine less than about 230 pmol per 8×108 red blood cell indicates a need to increase the amount of said drug subsequently administered to said subject and wherein the level of 6-thioguanine greater than about 400 pmol per 8×108 red blood cell indicates a need to decrease the amount of said drug subsequently administered to said subject.