The US Court of Appeals for the Federal Circuit affirmed a Patent Trial and Appeal Board (PTAB) invalidity decision in an interference proceeding, finding that the written description of the patent at issue did not describe the crucial part of the claimed method for detecting Down syndrome. Quake v. Lo, Case Nos. 18-1779, -1780, -1782 (Fed. Cir. July 10, 2019) (Chen, J).

Stanford University Professor Stephen Quake and Chinese University of Hong Kong Professor Dennis Lo both filed patent applications directed to methods for diagnosing aneuploidies using cell-free fetal DNA (cff-DNA) from mixed maternal and fetal DNA samples, using massively parallel sequencing (MPS) technology to sequence DNA fragments, identifying what chromosomes those DNA fragments come from based on their sequences, and determining if the test chromosome is over- or under-represented in the sample as compared to a reference chromosome based on statistical analyses. The claims of both patents recite a random MPS method, which means that all of the DNA in the sample is sequenced, as opposed to only specifically targeted sequences.

Quake and Lo requested an interference to determine who first invented the random MPS method and when the method was invented. The PTAB declared an interference between Quake’s patent and patent applications and Lo’s patent application, ultimately finding that the claims of Quake’s patent and patent applications were unpatentable for lack of written description because Quake’s patent specification only described detection of target sequences, not all DNA as required by the claims. Quake appealed.

The Federal Circuit affirmed, finding that substantial evidence supported the PTAB’s decision that Quake’s patent specification did not disclose a method of using random MPS to determine fetal aneuploidy. In reaching its conclusion, the Court noted that:

• The first time Quake tried to claim random MPS was after the publication of Lo’s patent application directed to random MPS.

• Quake canceled all his pending claims and replaced them with claims covering random MPS, creating a mismatch between the claims and the originally filed specification.

• The term “random MPS” is never mentioned in Quake’s patent, the process of amplifying all the DNA in a sample before sequencing is never described, and Quake admitted that there is no embodiment describing the statistical analysis needed to determine fetal aneuploidy from data generated by random MPS.

The Court also noted that Quake’s invention was directed to targeted MPS for determining fetal aneuploidy, not random MPS more broadly as recited in Quake’s patent claims. The Court also found that the Quake patents failed to reasonably convey detection of the chromosomal origin of randomly selected DNA fragments to determine the presence or absence of fetal aneuploidy, as claimed, and the step of normalization of chromosome size and statistical analysis was not sufficiently described in Quake’s patent to show possession of the claims.

Practice Note: In explaining the public policy behind the written description requirement, the Federal Circuit analogized such a disclosure as “marking trails by making blaze marks on trees to find one’s way through the woods of a specification such that a skilled artisan would be able to follow that trail and understand what the inventors had invented.” However, “the disclosure need only reasonably convey to persons skilled in the art that the inventor had possession of the subject matter in question.” Here, the inventors only left faint blaze marks—a more explicit disclosure was necessary for possession of random MPS technology.