After inventing the original method for detecting fetal cell-free DNA (cfDNA), Yuk-Ming Dennis Lo, MD, and his collaborators licensed their patent exclusively to Sequenom. However, in a legal battle between Sequenom and competitor Ariosa Diagnostics (Ariosa v. Sequenom), the U.S. District Court in California invalidated the patent—a decision that was upheld by the U.S. Court of Appeals for the Federal Circuit and set in stone when, in June 2016, the U.S. Supreme Court denied Sequenom’s petition to review the lower courts’ decisions. Amelia Feulner Baur, PhD, JD, takes a look at how this case could impact diagnostic patents moving forward. 

Did Ariosa v. Sequenom clarify the distinction between patent-ineligible natural principles and their patent-eligible applications?

A:Unfortunately, we did not learn much from this case because it followed in the footsteps of Mayo v. Prometheus, a 2012 Supreme Court decision that ruled that the correlation between thiopurine metabolite levels and the efficacy of thiopurine drugs is patent ineligible. There are two steps to determining patent eligibility as laid out in Mayo. The first is whether the claim is directed to a patent-ineligible concept like a natural law, phenomenon, or product. If yes, the court then must ask whether additional elements transform the claim into something eligible. In Ariosa, the federal appeals court answered yes to part one and decided that the claim was directed to an ineligible concept: paternally inherited nucleic acid of fetal origin. Once the court determined this, many expected that the claim would fail step two, because it recited fairly routine steps for detecting this nucleic acid.

Many in the field hoped that the court would answer no to part one, namely, that the claim was not directed to an ineligible concept. The court could have found, for example, that the claim was directed to a new test for detecting a particular nucleic acid rather than the nucleic acid itself. For example, in a more recent case, Rapid Litigation Management v. CellzDirect (RLM v. CellzDirect), the claims were related to a method for preserving primary liver cells by freezing. Under Title 35 of the U.S. Code, Section 101, the district court found the claim ineligible as being directed to the natural phenomenon of the cells’ ability to survive freezing. On appeal, however, the federal appeals court found that the claims were not directed to the natural law itself but rather to a new and useful method for preserving hepatocytes. The claims were thus patent-eligible.

Did the broad claims and language of the Sequenom patent contribute to its downfall?

Some commentators have suggested that the claims in this patent were too broad and that patent drafters should introduce additional limitations into patent claims to address Section 101. I disagree. In our field, it may not be to our benefit to throw extraneous facts into our claims to overcome Section 101 issues, because additional limitations narrow the scope of the claims and can hinder our ability to block competition or use patents against potential infringers. However, we should use language that highlights the inventive piece of the invention rather than the natural law underlying it. For example, the Sequenom patent could have shied away from discussing the nucleic acid itself, and instead focused on the method of detecting it.

As a community, we should also educate the courts about the impact of their decisions and encourage them to look carefully at how they answer step one of the Mayo test. With the mindset that a claim encompasses a natural law or phenomenon, the analysis moves to step two. There, patent applicants must choose between using broad method steps (and failing step two) or narrowing their claims to recite specific method steps and leaving the routine steps open for others to practice. This Hobson’s choice tells the diagnostic industry: Find new biomarkers to benefit society, but you can only protect them if you develop new methods for testing them, and competitors can still employ old methods for testing the same new biomarkers.

Amelia Feulner Baur, PhD, JD, is a co-founder and partner at the intellectual property firm McNeill Baur PLLC. With a PhD in molecular microbiology, Dr. Baur has significant interest and expertise in patent-related matters in personalized medicine and diagnostics+Email: [email protected]