Ariosa Diagnostics, Inc. v. Sequenom, Inc.: The End of Genetic Diagnostic Method Patents?

By: Andreas Baltatzis and Sandra King  |   July 16, 2015

Last month, in Ariosa Diagnostics, Inc. v. Sequenom, the Court of Appeals for the Federal Circuit found U.S. Patent No. 6,258,540 (“the ’540 patent”) invalid as not being directed to patent eligible subject matter under 35 U.S.C. § 101. --- F/3d ---, 2015 WL 3634649, at *1 (C.A.Fed. (Cal.) 2015). Despite, agreeing that the invention was a “significant human contribution” that “revolutionized pre-natal care,” the Court held that “where claims of a method patent are directed to an application that starts and ends with a naturally occurring phenomenon,” the invention is not patent eligible. Id. at *13 and *15. We believe that this decision will be an important guide to assessing the patentability and validity of patent claims directed to diagnostic methods.

The claims of the ’540 patent were directed toward the detection and amplification of cell-free fetal DNA (“cffDNA”) in maternal plasma and serum. Id. The District Court held on summary judgment and the Court agreed that the claims were directed to a natural phenomenon and, therefore, not patent eligible. Id. at *5 More specifically, the ’540 patent was directed toward cell-free fetal DNA (“cffDNA”) in maternal plasma and serum. Id. at *1. “The steps of the method of claim 1 of the ’540 patent include amplifying the cffDNA contained in a sample of a plasma or serum from a pregnant female and detecting the paternally inherited cffDNA.” Id.

The District Court had held that the claims of the ’540 patent were directed toward a natural phenomenon of “paternally inherited cffDNA and that the claims did not add enough to the natural phenomenon to make the claims patent eligible under § 101.” Id. at *3. The District Court stated that the steps of amplifying and detecting were “well-understood, routine, or conventional activity in 1997, when the application … was filed.” Id. The District Court held that the ’540 patent “was not directed to patentable subject matter because ‘the only inventive component of the processes of the ’540 patent is to apply those well-understood, routine processes to paternally inherited cffDNA, a natural phenomenon.’” Id.

The Court of Appeals for the Federal Circuit stated that it was “undisputed that the existence of cffDNA in maternal blood is a natural phenomenon.” Id. at *4. The Court further stated that the method of the ’540 patent “begins and ends with a natural phenomenon.” Id. “Thus, the claims are directed to matter that is naturally occurring.” Id. The Court asserted that because the claims were directed to a naturally occurring phenomena, it was necessary to turn to the second step of the Mayo framework to “examine the elements of the claim to determine whether the claim contains an inventive concept sufficient to ‘transform’ the claimed naturally occurring phenomenon into a patent-eligible application.” Id. The Court concluded that the practice of the method claims did not “result in an inventive concept that transforms the natural phenomenon of cffDNA into a patentable invention.” Id.

Sequenom contended that the claimed methods were patent eligible applications of a natural phenomenon as the method involved detecting paternally inherited cffDNA. Id. at *5. However, the Court stated that the method merely amounted to a “general instruction to doctors to apply routine, conventional techniques when seeking to detect cffDNA.” Id. “Because the method steps were well-understood, conventional and routine, the method of detecting paternally inherited cffDNA is not new and useful.” Id (emphasis added). The Court stated that the only subject matter that was new and useful was the “discovery of the presence of cffDNA in maternal plasma or serum.” Id. The Court ultimately concluded that the ’540 patent failed to disclose patent eligible subject matter.

In his concurrence, Judge Linn reluctantly joined the Court in invalidating the claims of the ’540 patent, stating that the Court was “bound by the sweeping language of the test set out in Mayo.” Id. at *8. Judge Linn stated, however, that, in his view, “the breadth of the second part of the test was unnecessary to the decision reached in Mayo.” Id. He stated that the instant case represents the unintended consequences of the decision wherein a meritorious invention is excluded from the patent protection it “deserves and should have been entitled to retain.” Id.

Judge Linn observed that the Supreme Court’s “blanket dismissal of conventional post-solution steps leaves no room to distinguish Mayo from this case,” even though, in contrast to Mayo, “no one was amplifying and detecting paternally-inherited cffDNA using the plasma or serum of pregnant mothers.” Id. at *9. Judge Linn noted that maternal plasma had previously been routinely discarded because “nobody thought that fetal cell-free DNA would be present.” Id.

Judge Linn went on to acknowledge the meritorious nature of Sequenom’s invention that others in the field had deemed a “paradigm shift in non-invasive prenatal diagnosis.” Id. Indeed, the commercially marketed product, i.e., the MaterniT21 test, was the first “marketed non-invasive prenatal diagnostic test for fetal aneuploidies, such as Down’s syndrome, and presented fewer risks and a more dependable rate of abnormality detection than other tests.” Id.

Based on the above points, Judge Linn concluded that the claims of the ’540 patent were nothing like Mayo, wherein the claims at issue in Mayo, had “been widely used by doctors.” Id. He further concluded that the new use of the “previously discarded maternal plasma to achieve such an advantageous result is deserving of patent protection.” Id.

In contrast, the European equivalent to the ’540 patent, i.e., European Publication No. EP 0994963 (“the ’963 patent”), contained similar claims to the ’540 patent. The ’963 patent was examined by the EPO Appeal Board in December 2011 and was found to contain an inventive step. See EPO Case Number T 0146/07- 3.3.08. Patent eligibility of the claims were not at issue, as the discussion of inventive step was limited to non-obviousness over the prior art. Id. p. 27-28. The ’963 patent was ultimately maintained with amendments. This is surprising since the EPO has generally been more conservative in determining the patent eligibility of diagnostic methods generally. Indeed, Article 53(c) EPC appears to specifically exclude certain diagnostic methods from patentability altogether. What implications this discrepancy will have on the biotech industry remains to be seen. An excellent analysis of the Ariosa decision from a European perspective is available here.

With the decision in Ariosa, it is likely that it will be extremely difficult to obtain effective patent protection for diagnostic methods involving genetic amplification and detection. For similar subject matter in the future, researchers may need to be creative in finding ways to modify “naturally occurring” genetic material into “something new,” much like the cDNA rendered patent eligible in Myriad. See Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S.Ct. 2107, 2119 (2013). In Myriad, the Supreme Court stated that the “lab technician unquestionably creates something new when cDNA is made. cDNA retains the naturally occurring exons of DNA, but it is distinct from the DNA from which it was derived.” Id. Creating similar distinction in future situations may involve subjecting DNA samples to cleavage or tagging steps to create a new chemical entity and specifically claiming such steps. Alternatively, legislative initiative may also be necessary to ensure protection for similar groundbreaking discoveries that greatly benefit modern medical science.