Claims Directed to Computerized Statistical Methods for Determining Haplotype Phase Are Patent Ineligible

April 6, 2021 – Article

The Board of Trustees of the Leland Stanford Junior University (“Stanford”) appeals the final rejection of patent claims in its patent Application No. 13/486,982. The patent examiner rejected the claims as involving patent ineligible subject matter. The PTAB affirmed the examiner’s rejection. On appeal, the Federal Circuit affirmed the decision of the PTAB that the rejected claims were drawn to abstract mathematical calculations and statistical modeling, and similar subject matter that is not patent eligible.

The ’982 application is directed to computerized statistical methods for determining haplotype phase. A haplotype phase acts as an indication of the parent from whom a gene has been inherited. Haplotype phasing is a process for determining the parent from whom alleles—i.e., versions of a gene—are inherited.

Claim 1 is representative and recites:

1. A computerized method for inferring haplotype phase in a collection of unrelated individuals, comprising:
receiving genotype data describing human genotypes for a plurality of individuals and storing the genotype data on a memory of a computer system;
            imputing an initial haplotype phase for each individual in the plurality of individuals based on a statistical model and storing the initial haplotype phase for each individual in the plurality of individuals on a computer system comprising a processor a memory [sic];
            building a data structure describing a Hidden Markov Model, where the data structure contains:
            a set of imputed haplotype phases comprising the imputed initial haplotype phases for each individual in the plurality of individuals;
            a set of parameters comprising local recombination rates and mutation rates;
            wherein any change to the set of imputed haplotype phases contained within the data structure automatically results in re-computation of the set of parameters comprising local recombination rates and mutation rates contained within the data structure;
            repeatedly randomly modifying at least one of the imputed initial haplotype phases in the set of imputed haplotype phases to automatically re-compute a new set of parameters comprising local recombination rates and mutation rates that are stored within the data structure;
            automatically replacing an imputed haplotype phase for an individual with a randomly modified haplotype phase within the data structure, when the new set of parameters indicate that the randomly modified haplotype phase is more likely than an existing imputed haplotype phase;
            extracting at least one final predicted haplotype phase from the data structure as a phased haplotype for an individual; and
            storing the at least one final predicted haplotype phase for the individual on a memory of a computer system.

The PTAB applied the two-step framework established in Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208 (2014). Under Step one, the PTAB determined that representative claim 1 was directed to patent ineligible abstract ideas in the form of mathematical concepts, i.e., mathematical relationship, formulas, equations, and calculations.  Claim 1 recites an initial step of receiving genotype data, followed by the mathematical operations of building a data structure describing an HMM and randomly modifying at least one imputed haplotype to automatically re-compute the HMM’s parameters. The PTAB also determined that claim 1 recited two abstract mental processes. First, claim 1 recites the step of “imputing an initial haplotype phase for each individual in the plurality of individuals based on a statistical model,” which does not require a computer implementation. Second, claim 1 recites the step of automatically replacing an imputed haplotype phase with a randomly modified haplotype phase when the latter is more likely correct than the former. The PTAB concluded that claim 1 recited abstract ideas.

The PTAB pointed out that the additional elements in claim 1 recited generic steps of receiving and storing genotype data in a computer memory, extracting the predicted haplotype phase from the data structure, and storing it in a computer memory. Stanford argued that, here as in Enfish, the application of the steps in claim 1 resulted in improved computer functionality. Enfish, LLC v. Microsoft Corp., 822 F.3d 1327 (Fed. Cir. 2016). However, the PTAB determined that the evidence did not support that argument.  “Stanford failed to identify any specific disclosures in the specification asserting that claim 1 results in improved computer functionality.”

Stanford further argued that haplotype phasing was a computer implemented field, and that under McRO, Inc. v. Bandai Namco Games America Inc., 837 F.3d 1299, 1315 (Fed. Cir. 2016) “improvements to computer implemented fields are considered technological improvements.” The PTAB rejected Stanford’s argument and distinguished McRO on the basis that the claimed process there used “a combined order of specific rules that renders information into a specific format that is then used and applied to create desired results: a sequence of synchronized, animated characters” and noted  that here claim 1 merely recited a series of computations to produce mathematically predicted haplotype information but did not include steps that apply that information in a practical way.

The PTAB acknowledged that claim 1 “may be useful in medical or population genetics studies,” “but nonetheless claim 1 is devoid of any specific step that applies the information in a useful way, such that the claimed calculations are ‘integrated’ into a practical application and, claim 1 is directed to an abstract idea.”

Under Step two of the Alice inquiry, the PTAB reviewed whether claim 1 included additional limitations that, when taken individually or in combination, provide an inventive concept that transformed the abstract idea into patent eligible subject matter. The PTAB determined that the claim 1 steps of receiving, storing, and extracting data were well-known, routine, and conventional. The PTAB rejected Stanford’s argument that specific computational steps themselves established patent eligibility, and explained that, “although the abstract computational steps ‘might be a highly significant discovery in the field of haplotype prediction,’ that alone is insufficient to establish patent eligibility.”  The PTAB also rejected Stanford’s argument that claim 1 does not unduly preempt use of an HMM, noting that “the absence of complete preemption does not demonstrate patent eligibility.”  Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1379 (Fed. Cir. 2015). The Board affirmed the examiner’s rejection of claims 1 and 22–43 under § 101. Stanford appealed.

On appeal, the Federal Circuit (“the Court”) also used a two-step analysis under Alice.  Under the Alice Step one, the Court found that the claims were directed to the use of mathematical calculations and statistical modeling. “Courts have long held that mathematical algorithms for performing calculations, without more, are patent ineligible under § 101.” The Court further cited Parker v. Flook, 437 U.S. 584, 595 (1978); Gottschalk v.Benson, 409 U.S. 63, 71–72 (1972); In re Schrader, 22 F.3d 290, 294 (Fed. Cir. 1994).

The Court noted that claim 1 was drawn to a “computerized method of inferring haplotype phase in a collection of unrelated individuals.”  The mathematical techniques used in the method include “building a data structure describing an [HMM],” and then “repeatedly randomly modifying at least one of the imputed initial haplotype phases” to automatically re-compute the parameters of the HMM until the parameters indicate that the most likely haplotype phase is found. In addition to these mathematical steps, claim 1 recites steps of receiving genotype data, imputing an initial haplotype phase, extracting the final predicted haplotype phase from the data structure, and storing it in a computer memory. “These generic steps of implementing and processing calculations with a regular computer do not change the character of claim 1 from an abstract idea into a practical application. Claim 1 recites no application, concrete or otherwise, beyond storing the haplotype phase.”

The Court also “examined, at Alice step one, whether the claimed advance alleged in the written description demonstrates an improvement of a technological process or merely enhances an ineligible concept. See, e.g.Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743, 750 (Fed. Cir. 2019).” Stanford suggested that one claimed advance was greater efficiency in computing haplotype phase. The Court noted that “Stanford has forfeited its argument that greater computational efficiency renders claim 1 patent eligible by failing to raise it before the PTAB” and did not consider it for the first time on appeal.

Stanford separately suggested that another claimed advance was that the claim steps result in more accurate haplotype predictions and argued that the alleged increase in haplotype prediction accuracy renders claim 1 a practical application rather than an abstract idea.  However, the Court found that “Stanford’s cited cases do not support its argument because the cases involve practical, technological improvements extending beyond improving the accuracy of a mathematically calculated statistical prediction.”  “Unlike the technological improvements made in those cases, the improvement in computational accuracy alleged here does not qualify as an improvement to a technological process; rather, it is merely an enhancement to the abstract mathematical calculation of haplotype phase itself. See Athena, 915 F.3d at 750; Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1151 (Fed. Cir. 2016) (‘[A] claim for a new abstract idea is still an abstract idea.’).” The Court noted that the different use of a mathematical calculation, even one that yields different or better results, does not render patent eligible subject matter and concluded that claim 1 was directed to patent ineligible subject matter under Step one.

Under the Step two inquiry, the Court found no inventive concept that would warrant treating the use of the claimed algorithms and mathematical calculations as patent eligible subject matter. The steps of receiving, extracting, and storing data are well-known, routine, and conventional steps taken when executing a mathematical algorithm on a regular computer. “Using a conventional computer to receive, extract, and store information does not transform an abstract idea into patent eligible subject matter.” The Court pointed out that the written description further illustrated that the mathematical steps performed and the data received were conventional and well understood in the prior art. Furthermore, claim 1 does not require or result in a specialized computer or a computer with a specialized memory or processor. “Indeed, it is hard to imagine a patent claim that recites hardware limitations in more generic terms than the terms employed by claim 1.”

Stanford also argued the PTAB erred by failing to consider all the elements of claim 1 as an ordered combination and specifically that PTAB oversimplified claim 1 by characterizing it as “directed to a process of using abstract computation methods to obtain a specific type of information” and then “effectively subsumed” all the steps into that purportedly overgeneralized judicial exception. According to Stanford, “it is the specific combination of steps recited in claim 1 ‘that makes the process novel’ and ‘that provides the increased accuracy over other methods.’” However, the Court disagreed.  “The Board correctly determined that claim 1 simply appends the abstract calculations to the well-understood, routine, and conventional steps of receiving and storing data in a computer memory and extracting a predicted haplotype. The application of those elements results in the mathematical analysis itself, and therefore the claimed method subsists in “the basic tools of scientific and technological work.” “Such basic tools are not patent eligible. Nor is novelty the touchstone of patent eligibility. That a specific or different combination of mathematical steps yields more accurate haplotype predictions than previously achievable under the prior art is not enough to transform the abstract idea in claim 1 into a patent eligible application. See SAP Am., Inc. v. InvestPic, LLC, 898 F.3d 1161, 1170 (Fed. Cir. 2018) (holding that an advance in financial mathematical techniques does not constitute an inventive concept).” The Court affirmed the PTAB’s conclusion that claims 1 and 22–43 were drawn to patent ineligible subject matter under § 101.

Patent Applicants and practitioners working in the field of bioinformatics and computerized statistical and biotechnological methods continue to face unpredictability of patent eligible subject matter and patent protection under Section 101.  Recent decisions such as in Stanford CardioNet, LLC v. InfobionicInc., 955 F.3d 1358 (Fed. Cir. 2020), Ex parte Patil (PTAB January 7, 2021), are important for drafting and protecting bioinformatics and biotechnological applications.

In re Board of Trustees of the Leland Stanford Junior Univ., No. 2020-1288 (Fed. Cir. Mar. 25, 2021)

http://www.cafc.uscourts.gov/sites/default/files/opinions-orders/20-1288.OPINION.3-25-2021_1753695.pdf