Can patents on diagnostic tests survive in the US?

In March 2012 it was controversially held by the US Supreme Court in Mayo Collaborative Services v Prometheus Laboratories Inc. (2012) that a “relationship” between the concentrations of blood metabolites and response to a therapeutic drug, claimed in patents owned by Prometheus Laboratories Inc was not patentable because it represented a “principle of nature”. The Court stated that to be patent eligible a claim must contain “features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself.” The Court considered that the steps defined in the “Prometheus patent” consisted of “well-understood, routine, conventional activity already engaged in by the scientific community”. Thus, the Court found that nothing of value was added to the law of nature and therefore the claimed process was not patent eligible.

The Prometheus decision prompted the USPTO to issue a memorandum to provide guidance on relevant patent subject matter eligibility. The USPTO provided a three-step process as a means to determine whether method claims define patentable subject matter as follows.

  1. Is the claimed invention directed to a process, defined as an act or a series of acts or steps?
  2. Does the claim focus on use of a law of nature, a natural phenomenon or naturally-occurring relation or correlation? In other words, is the natural principle a limiting feature of the claim?
  3. Does the claim include additional elements/steps or combination thereof that integrate the natural principle into the claimed invention such that the natural principle is practically applied and are sufficient to ensure the claim amounts to more than the natural principle itself?

Thus, from the Prometheus decision and the above guidelines, it appears that under current US law for a claim that defines a naturally-occurring principle to be patent eligible, steps making use of the principle are required that ensure the claim does not simply monopolize the naturally-occurring principle.

Ariosa Diagnostics Inc v Sequenom Inc

On 30 October 2013, the Court for the Northern District of California issued one of the first decisions to apply the “Prometheus patent eligibility standard” in Ariosa Diagnostics Inc v Sequenom Inc. The patent at issue was US Patent No 6,258,540 (the ’540 Patent), to which Sequenom is the exclusive licensee. The claims relate to the discovery that cell-free fetal DNA (“cffDNA”) is detectable in serum or plasma samples of pregnant women. This cffDNA can be used to determine fetal genetic characteristics including fetal abnormalities, for example chromosomal aneuploidies or simple mutations. The independent claims of the ’540 Patent are as follows:

1.    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.

24.    A method for detecting a paternally inherited nucleic acid on a maternal blood sample, which method comprises: removing all or substantially all nucleated and anucleated cell populations from the blood sample, amplifying a paternally inherited nucleic acid from the remaining fluid and subjecting the amplified nucleic acid to a test for the paternally inherited fetal nucleic acid.

25.    A method for performing a prenatal diagnosis on a maternal blood sample, which method comprises obtaining a non-cellular fraction of the blood sample amplifying a paternally inherited nucleic acid from the non-cellular fraction and performing nucleic acid analysis on the amplified nucleic acid to detect paternally inherited fetal nucleic acid.

Ariosa argued that the claims were not directed to patent eligible subject matter because paternally inherited cffDNA is a natural phenomenon and the claims merely add well understood, routine, conventional activity in the field to that phenomenon. In response, Sequenom argued that the claimed methods did relate to patentable subject matter because they define novel uses of a natural phenomenon rather than the natural phenomenon itself. Sequenom further argued that the claims are patent eligible because they do not preempt all uses of cffDNA. Both Ariosa and Sequenom agreed that neither the cffDNA per se nor the discovery of cffDNA in maternal plasma or serum is patentable. However, as the cffDNA was not claimed in the ’540 Patent, the major issue considered by the Court was whether the steps defined in the claimed methods applied to the naturally-occurring phenomenon were sufficient to render the claims patentable. Ultimately, the Court agreed with Ariosa that the additional limitations in the claims, for example in claim 1 of “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” were well understood routine and conventional activities and cited evidence from Sequenom’s own expert who stated that amplification and detection of DNA sequences in plasma or serum was well known in 1997. In response to Sequenom’s arguments that the claims relate to a novel and inventive method of using cffDNA, the Court found that the only potentially inventive patent eligible subject matter consisted of conventional techniques of DNA detection applied to cffDNA and that the “inventive concept” contained in the patent was the discovery of cffDNA which is not patentable.

Conclusions

The decision in Ariosa Diagnostics, Inc. v Sequenom Inc confirms that obtaining patents directed to diagnostics tests in the US will be very difficult in future unless the claims define the application of new technology or unconventional methodologies in addition to a naturally-occurring phenomenon. Christopher M. Holman, a law professor at the University of Missouri-Kansas City was prompted to say “It’s hard to imagine patents on diagnostics surviving if that approach is taken”. A statement from Sequenom indicated that they vigorously disagree with the decision and intend to lodge an appeal to the Federal Circuit Court of Appeals.