In patents for diagnostic methods, which natural phenomena the patent is directed to may be just as important as whether it is directed to a natural phenomenon at all. A January 2019 decision of the Patent Trial and Appeal Board (PTAB) suggests that which natural phenomena a court determines the patent claim is directed to under Alice step one could have significant implications for Alice step 2. The Board’s decision in Ex parte Lee stands in contrast to the Federal Circuit’s decision in Ariosa Diagnostics, Inc. v. Sequenom, Inc. And comparing the two side-by-side reveals that patent applicants have an incentive to not only argue whether their patent is directed to a natural phenomenon, but also to which natural phenomena it is directed.
Ex Parte Lee concerned an appeal from the Examiner’s determination that the diagnostic claims were patent ineligible. Claim 1 of the application was representative and describes:
1. A method of determining an increased risk of colorectal cancer or Crohn's disease in an asymptomatic human subject, comprising:
(i) collecting mucosal epithelial cells from the buccal area of the subject by swabbing the buccal area, and extracting RNA from the swab;
(ii) producing cDNA from the extracted RNA;
(iii) measuring the level of cDNA for a panel of polynucleotides comprising at least three cDNA sequences comprising SEQ ID NO: 1, 21 and 23 from the cDNA produced from the extracted RNA;
(iv) applying each of the measured cDNA levels of the panel of polynucleotides against a database of Mahalanobisdistance (M-dist) values created by analyzing measured cDNA levels of a control panel of polynucleotides from control subjects with no polyps and no family or self-history of cancer or known upper GI problems, wherein the control panel of polynucleotides and the panel of polynucleotides comprise the at least three cDNA sequences, and wherein the applying compares the same polynucleotides expression levels for each of the at least three cDNA sequences using global multivariate analysis of variance (ANOVA) and Mahalanobis-distance (M-dist), wherein the Mdist has chi-square distribution with degrees of freedom equal to the number of polynucleotides in the panel, and wherein the database comprises M-dist values for at least three cDNA sequences comprising SEQ ID NO: 1, 21 and 23, and wherein the database is stored on a computer system;
(v) determining the M-dist values for each of the at least three polynucleotides comprising SEQ ID NO: 1, 21, and 23 of the panel of polynucleotides from the asymptomatic human subject; and
(vi) indicating that the asymptomatic human subject has an increased risk of colorectal cancer or Crohn's disease if each of the M-dist values for the cDNA levels for the at least three cDNA sequences of SEQ ID NO: 1, 21 and 23 are greater than the 95% percentile of the database's M-dist values.
Ex parte Lee, Appeal 2017-011014 (Jan. 14, 2019). The Examiner determined that the claim was directed at a natural phenomenon: the correlation between the expression of SEQ ID NO: 1, 21 and 23, and the risk of Crohn’s disease or colon cancer. The Board accepted this determination under Alice step 1 but did not agree with the Examiner that the claim did not contain an inventive concept.
The Examiner cited the Spira and Hao papers papers as prior art to determine that the claim’s steps were common and routine. Spira taught the collection of RNA from a buccal swab and Hao taught the examination of SEQ ID NO: 1, 21 and 23 to assess risk of Crohn’s disease or colon cancer. However, the Board pointed out, citing Berkheimer, that just because a prior art teaches a step does not make it common and routine. The Spira paper noted that, prior to this success, no previous research team had successfully extracted RNA from mouth swabs. And while the Hao paper taught the analysis of SEQ ID NO: 1, 21 and 23, it only taught the sampling of colon cells, gave no indication of how common and routine this practice was, and noted that it was “not know[ n] which cell type is responsible for the observed altered gene expression.” Therefore, while this prior art would be useful for the question of obviousness, it did not show that the steps in the method were common and routine.
Ariosa, a Federal Circuit case, took a different view to a similar invention. In Ariosa, the patent described a method of detecting paternal DNA found in maternal plasma. Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015). Like Ex parte Lee the Court determined that the patent was directed to a natural phenomenon: the presence of paternal DNA in maternal plasma. Unlike Ex Parte Lee, however, the Court determined that the steps in Ariosa were conventional and routine. Evidence in the application as well as testimony from experts supported that the detection and then amplification of the paternal DNA could be achieved with conventional methods well known in the art. The Court further determined that the only inventive aspect was the previously unknown presence of paternal DNA in maternal plasma and that this natural phenomena could not be the inventive concept for Alice step 2.
Factually, Ex parte Lee and Ariosa share several similarities. Both paternity tests and analysis of SEQ ID NO: 1, 21 and 23 were in use prior to Ariosa and Ex parte Lee respectively. And both patents applied these known tests to a new area in the body: maternal plasma, in Ariosa, and the buccal membrane, in Ex parte Lee. However, the Board in Ex parte Lee noted that, even if the practice of analysing SEQ ID NO: 1, 21 and 23 was common and routine, the fact that Lee performed this analysis using cDNA derived from the mouth instead of the colon was enough to make the step inventive. The newly discovered presence of this biological information in the mouth could form the basis of an inventive concept, unlike in Ariosa.The difference in these results can be attributed to the fact that, in Ex parte Lee the natural law the patent was directed to was not the presence of RNA that produce SEQ ID NO: 1, 21 and 23 but rather the relationship between this cDNA and risk of Crohn’s disease and colon cancer. Because the Examiner determined that the application was directed at this natural relationship instead of the presence of the RNA of interest, it could serve as an inventive concept.
There question remains open as to whether the Board would have come to the same result had buccal swabbing for RNA been common and routine. However, the Board’s decision does suggest that applying known diagnostic tests to new areas of the body can be patent eligible when the applicant can phrase the claims to direct them to a different natural phenomenon, such as the relationship between analysis of a biological molecule and the risk of a certain disease.