On June 12, 2015, the Federal Circuit affirmed the finding of U.S. District Court for the Northern District of California (“District Court”) that the method claims in U.S. Patent 6,258,540 (‘540 patent) for detecting paternally-inherited cell-free DNA (“cffDNA”) in maternal plasma or serum were not directed to patent eligible subject matter, and, therefore, were invalid.  See Ariosa Diagnostics, Inc. v. Sequenom, Inc., No. 2014-1139, 2014-1144, slip op. at 2, 16 (Fed. Cir., June 12, 2015).

The Federal Circuit applied the two-part test as set forth in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289 (2012), and held that the method claims in the ’540 patent “begins and ends with a natural phenomenon,” and that the additional elements in the method steps “individually and ‘as an ordered combination’” were not enough “to supply an inventive concept.”  Sequenom, slip op. at 9, 11.  The Federal Circuit also relied on Parker v. Flook, 437 U.S. 584 (1978), and refused to consider whether the method claims of the ‘540 patent would preempt, i.e., tie up the future use of the cffDNA, and stated that the questions of preemption are inherent in subject matter eligibility analysis, and when the claims fail the Mayo test, the question of preemption is moot. Sequenom, slip op. at 14-15.

Summary of the ‘540 Patent

The claims of the ‘540 patent were based on a breakthrough discovery by the Drs. Dennis Lo and James Wainscoat that cffDNA was present in the maternal plasma or serum that previously was routinely discarded as medical waste, and their subsequent implementation of a method for detecting a small fraction of paternally inherited cffDNA in the maternal plasma or serum. 

Claim 1 of the ‘540 patent recites:

A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises amplifying a paternally inherited nucleic acid from the serum or plasma sample and detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.

The method, as recited in claim 1, allowed determining fetal genetic characteristics, such as gender, without the inherent risks of then existing invasive methods that required taking samples from the fetus or placenta directly.  Sequenom, as the exclusive licensee of the ‘540 patent, commercialized this method as its MaterniT21^TM test.  Separately, Ariosa Diagnostics, Inc. (“Ariosa”), was also selling a non-invasive prenatal test, the Harmony^TM test, which uses cell-free fetal DNA circulating in the blood of a pregnant woman.

Procedural History

In December 2012, Ariosa filed a declaratory judgment action at the District Court in response to Sequenom’s letter threatening an infringement action. Ariosa sought a finding that the Harmony^TM test did not infringe any claims of the ‘540 patent. See Sequenom, slip op. at 6. Sequenom later unsuccessfully sought to enjoin Ariosa from selling the Harmony^TM Test. See id.  Ariosa and Sequenom subsequently filed cross-motions for summary judgment. See id.

The District Court granted Ariosa’s motion for summary judgment, and held that the method claims of the ‘540 patent were not drawn to patent eligible subject matter and, therefore, were invalid under 35 U.S.C. § 101. The District Court applied the Mayo test and found that the steps in the method claims “involve no more than well-understood, routine, conventional activity, previously engaged in by those in the field.”  See Ariosa Diagnostics, Inc. v. Sequenom, Inc., 19 F. Supp. 3d 938, 949, 954 (N.D. Cal. 2013).  Sequenom appealed, but the Federal Circuit agreed with the District Court. See Sequenom, slip op. at 2.

The Mayo Test

The Supreme Court’s Mayo framework provides that the first step of the analysis should be to determine whether the claims at issue are directed to a patent-ineligible concept.  If the answer is yes, then the next step is to determine whether the additional elements of the claim, both individually and as an ordered combination, transform the nature of the claim into a patent eligible application of the concept. See Sequenom, slip op. at 8.  In this case, the Federal Circuit applied the Mayo test and found that each of the method claims in the ’540 patent “begins and ends with a natural phenomenon” (slip op. at 9, 10), and that the additional elements in the method steps “individually and ‘as an ordered combination’” were not sufficient to transform the methods into patent eligible application of the natural phenomenon (see slip op. at 10-11).

First Step: Is the Invention Directed to a Natural Phenomenon?

The Federal Circuit first determined whether the claims involved a natural phenomenon, and second determined whether the inventors performed any step that could be construed as providing an “inventive concept.” Ariosa and Sequenom had agreed that the presence of cffDNA in maternal plasma or serum was a natural phenomenon. Therefore, the Federal Circuit relied on the ‘540 patent’s specification and found that because “the claims at issue . . . are generally directed to detecting the presence of a naturally occurring thing or a natural phenomenon, cffDNA in maternal plasma or serum. . . . the claimed method begins and ends with a naturally occurring phenomenon.” Slip op. at 10.

Second Step: Is there an inventive concept sufficient to “transform” the natural phenomenon to patent eligible subject matter? 

Because both Ariosa and Sequenom had agreed that the presence of cffDNA in maternal plasma or serum was a natural phenomenon, Mayo’s first part test was not dispositive in this case.  See Ariosa, 19 F. Supp. 3d at 948.  As such, the next step of the analysis was the second step of Mayo, under which the claim elements were considered both “individually” and “as an ordered combination”, to determine “whether the claim contains an inventive concept sufficient to ‘transform’ the claimed naturally occurring phenomenon into a patent-eligible application.”  Sequenom, slip op. at 10 (citing Mayo, 132 S. Ct. at 1294).  

The “ordered combination” test is from Diamond v. Diehr, 450 U.S. 175 (1981), where the Supreme Court had held that “a new combination of steps in a process may be patentable even though all the constituents of the combination were well known and in common use before the combination was made.” Id. at 188.  In contrast, in Flook the Court had held that the discovery of a natural phenomenon “cannot support a patent unless there is some other inventive concept in its application.”  Flook, 437 U.S. at 594.  The Mayo Court observed that in these two cases “the Court reached opposite conclusions about the patent eligibility that embodies the equivalent of natural laws.” Mayo, S. Ct. at 1298.  

Thus, the Mayo Court conceived a sliding scale for patent eligibility, with Diehr at one end of the scale and Flook at the other.  Holding that the claims at issue in Mayo were invalid, the Court observed that “[t]he claim before us presents a case for patentability that is weaker than the (patent-eligible) claim in Diehr and no stronger than the (unpatentable) claim in Flook.”  Mayo, S. Ct. at 1299. 

In Sequenom, neither the District Court nor the Federal Circuit found that the combination of steps in the method claims of the ‘540 patent, when considered individually and as an ordered combination, were sufficient to make the claims patent eligible.  Instead, the District Court held that the two steps in claim 1 of the ‘540 patent involving “amplifying a paternally inherited nucleic acid” and “detecting the presence . . . in the sample” were “no more than well-understood, routine, conventional activity, previously engaged in by those in the field.”  Id. at 950.  The Federal Circuit agreed.  Both courts, therefore, relied on Flook’s “inventive concept” test to conclude that the method claims of the ‘540 patent, were “not new and useful.” Sequenom, slip op. at 11.

In Judge Linn’s concurrence of the holding that the Sequenom claims were invalid due to subject matter ineligibility, Judge Linn contrasts the Sequenom facts with the Mayo facts to note that “the instructions in the [Mayo] claims … had been widely used by doctors—they had been measuring metabolites and recalculating dosages based on toxicity/inefficacy limits for years—here, the amplification and detection of cffDNA had never before been done. The new use of the previously discarded maternal plasma to achieve such an advantageous result is deserving of patent protection.”  Sequenom, slip op. at 4 (Linn, J., concurring).  

Preemption

The District Court applied the preemption test “in addition” to the Mayo tests. See Ariosa, 19 F. Supp. 3d at 953.  The Federal Circuit did not follow this sequential line of analysis. See Sequenom, slip op. at 14.  However, both the District Court and the Federal Circuit relied on Flook to clarify the preemption doctrine.  In Flook, the Supreme Court was concerned with whether limited post-solution applications of the formula would make the claim at issue patent eligible, and held that they did not.  See Sequenom, slip op. at 15. Both the District Court and the Federal Circuit analogized with the facts of Flook, where exclusive rights to a natural phenomenon (a formula) would preclude others from using the formula.  See Sequenom, slip op. at 15.  

At the District Court, Sequenom had presented scientific articles describing methods for detecting cffDNA in support of its argument that the method claims of the ‘540 patent did not preempt all other uses of cffDNA. See Ariosa, 19 F. Supp. 3d at 953. However, the District Court disagreed and observed that because “the articles … were published after the issuance of the patent and well after the date of the invention . . . . Sequenom has failed to show that any alternative methods existed at the time of the invention or at the time of issuance of the patent.” Id. at 954. 

The Federal Circuit took the approach that the question of preemption is inherent in subject matter eligibility analysis, and, as such, when the claims fail the Mayo test, the question of preemption would not arise.  Moreover, the Federal Circuit stated that although presence of preemption might preclude patent eligibility, the converse, i.e., the absence of preemption, does not “demonstrate patent eligibility.” See Sequenom, slip op. at 14. 

Conclusion

Thus, the Federal Circuit held that the claims of the ‘540 patent were not directed to patent eligible subject matter and are, therefore, invalid. In light of Mayo, Myriad, and now Sequenom, any parties involved in the diagnostic space should be mindful that scientific breakthroughs that are considered impactful may not necessarily be patentable under current jurisprudence of Section 101 case law.