In Re THE BOARD OF TRUSTEES

Case: 20-1012 Document: 38 Page: 1 Filed: 03/11/2021

United States Court of Appeals for the Federal Circuit ______________________

IN RE: BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Appellant ______________________

2020-1012 ______________________

Appeal from the United States Patent and Trademark Office, Patent Trial and Appeal Board in No. 13/445,925. ______________________

Decided: March 11, 2021 ______________________

JOEL KAUTH, KPPB LLP, Anaheim, CA, argued for ap- pellant. Also represented by DAVID BAILEY, CHRISTIAN HANS, MARK YEH.

MAUREEN DONOVAN QUELER, Office of the Solicitor, United States Patent and Trademark Office, Alexandria, VA, argued for appellee Andrew Hirshfeld. Also repre- sented by THOMAS W. KRAUSE, AMY J. NELSON. ______________________

Before PROST, Chief Judge, LOURIE and REYNA, Circuit Judges. REYNA, Circuit Judge. The Board of Trustees of the Leland Stanford Junior University appeals the final rejection of patent claims con- tained in its patent application. The patent examiner

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reviewing the application rejected the claims on grounds that they involve patent ineligible subject matter. On re- view, the Patent Trial and Appeal Board affirmed the ex- aminer’s final rejection of the claims. As discussed below, we hold that the rejected claims are drawn to abstract mathematical calculations and statistical modeling, and similar subject matter that is not patent eligible. Accord- ingly, we affirm the decision of the Patent Trial and Appeal Board. BACKGROUND The Board of Trustees of the Leland Stanford Junior University (“Stanford”) filed its Application No. 13/445,925 (“’925 application”) on April 13, 2012. The ’925 application is directed to methods and computing systems for deter- mining haplotype phase. J.A. 270, 906–07. Haplotype phasing is a process for determining the parent from whom alleles—i.e., versions of a gene—are inherited. A haplotype phase acts as an indication of the parent from whom a gene has been inherited. According to the written description of the ’925 appli- cation, improved haplotype phasing techniques “promise[] to revolutionize personalized health care by tailoring risk modification, medications, and health surveillance to pa- tients’ individual genetic backgrounds.” J.A. 269–70. Achieving the understanding necessary to accomplish those goals has long challenged scientists because it re- quires “interpretation of massive amounts of genetic data produced with each genome sequence.” J.A. 270, 296. The ’925 application purports to meet that challenge via a method for receiving certain types of genetic data and pro- cessing the data by performing mathematical calculations and statistical modeling to arrive at a haplotype phase de- termination. The claimed methods first involve using two types of information, namely genotype data and pedigree data, to determine alleles’ inheritance state using a method

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published in the prior art, namely Roach et al., Analysis of Genetic Inheritance in a Family Quartet by Whole Genome Sequencing, 328 SCIENCE 636 (2010). The Roach reference teaches the use of a hidden Markov model (“HMM”)—a sta- tistical tool used in various applications to make probabil- istic determinations of latent variables—to predict inheritance state. See J.A. 272–73, 282, 294–95, 319–20. The written description also explains that, in the prior art, methods of determining haplotype phase based on in- heritance state yielded an incomplete number of the alleles’ haplotypes. See, e.g., J.A. 297 (discussing the “trio” method that predicted haplotype phases for approximately 80 per- cent of heterozygous positions); see also J.A. 909; Appel- lant’s Br. 7 (explaining that “the inheritance state information produced by the HMM is uninformative in some regions of the allele data”). The claimed methods al- legedly increase the number of possible haplotype phase predictions. See, e.g., J.A. 298–99 (explaining that the claimed methods result in “phase resolution of 97.9% of heterozygous positions”); see also Appellant’s Br. 5 (con- trasting the inventions from the “‘trio’” method”). The increase in haplotype phase predictions is made possible by factoring additional data into the analysis. See J.A. 296–99; see also Appellant’s Br. 7. The first type of additional data, known as “linkage disequilibrium data,” could at the time be obtained from the “SNP Annotation and Proxy Search” or “SNAP” database, which launched in approximately 2008. See J.A. 283. The second type of ad- ditional data is referred to as “transition probability data.” According to the written description, transition probabili- ties are set depending on “the expected number of state transitions and the total number of allele assortments in the pedigree.” J.A. 273, 295. These two types of additional data allegedly enable haplotype phase to be inferred in re- gions where inheritance state is uninformative. See J.A. 273, 298–99; see also Appellant’s Br. 3.

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Stanford appeals the Patent Trial and Appeal Board’s (“Board”) affirmance of the examiner’s rejection of claims 1, 4–11, 14–25, and 27–30 as covering patent ineligible ab- stract mathematical algorithms and mental processes. See J.A. 871–72, 1101–10. Independent claim 1 is representa- tive and recites: 1. A method for resolving haplotype phase, com- prising: receiving allele data describing allele information regarding genotypes for a family comprising at least a mother, a father, and at least two children of the mother and the father, where the genotypes for the family contain single nucleotide variants and storing the allele data on a computer system comprising a processor and a memory; receiving pedigree data for the family describing information regarding a pedigree for the family and storing the pedigree data on a computer sys- tem comprising a processor and a memory; determining an inheritance state for the allele in- formation described in the allele data based on identity between single nucleotide variants con- tained in the genotypes for the family using a Hid- den Markov Model having hidden states implemented on a computer system comprising a processor and a memory, wherein the hidden states comprise inher- itance states, a compression fixed error state, and a[ Mendelian inheritance error]- rich fixed error state, wherein the inheritance states are mater- nal identical, paternal identical, identical, and non-identical;

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receiving transition probability data describing transition probabilities for inheritance states and storing the transition probability data on a com- puter system comprising a processor and a memory; receiving population linkage disequilibrium data and storing the population disequilibrium data on a computer system comprising a processor and a memory;

determining a haplotype phase for at least one member of the family based on the pedigree data for the family, the inheritance state for the infor- mation described in the allele data, the transition probability data, and the population linkage dise- quilibrium data using a computer system compris- ing a processor and a memory; storing the haplotype phase for at least one mem- ber of the family using a computer system compris- ing a processor and a memory; and providing the stored haplotype phase for at least one member of the family in response to a request using a computer system comprising a processor and a memory. J.A. 1101–02. 1

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In its analysis of the examiner’s rejections, the Board applied the two-step framework established by the Su- preme Court for determining patent eligibility. See Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208 (2014); J.A. 5–18. Addressing step one of the Alice inquiry, the Board determined that the eight steps in claim 1 are di- rected to either the “mental steps of receiving, storing, or providing information” or “mathematical concepts.” See J.A. 7–9. The Board reasoned that the claim recites steps for receiving and analyzing information, which humans could process in their minds, or by mathematical algo- rithms, which are mental processes within the abstract- idea category. J.A. 10. The Board concluded that the mathematical process recited in the claims is not inte- grated into a practical application. The Board specifically found that the claims, unlike those in Enfish, LLC v. Mi- crosoft Corp., 822 F.3d 1327 (Fed. Cir. 2016), do not im- prove computer technology but rather use off-the-shelf computing equipment to perform an improved mathemati- cal analysis. See J.A. 12–13. The Board explained that the claims are also unlike those covering animation of 3-D characters in McRO, Inc. v. Bandai Namco Games America Inc., 837 F.3d 1299, 1315 (Fed. Cir. 2016), which improve “the computer animation process itself.” J.A. 13–15. The Board concluded that claim 1 is directed to patent ineligible subject matter under § 101. J.A. 11, 15; 35 U.S.C. § 101. Turning to step two of the Alice inquiry, the Board con- cluded that the claims did not include additional limita- tions that, when taken individually or as a whole, provide an inventive concept that transforms the abstract idea into patent eligible subject matter. The Board found that the steps of receiving data, performing calculations using that data, storing the results, and providing the results upon request using a computer did not go beyond the well- known, routine, and conventional. See J.A. 16–17 (“We find that Appellants’ claims do not require anything other than the use of conventional and well-understood

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techniques and equipment to gather and process data ac- cording to the recited judicial exception.”). The Board ex- plained that, although the claims may provide a valuable contribution to science, that contribution does not go be- yond patent ineligible mental processes and mathematical operations. See J.A. 16. The Board addressed the remaining claims and con- cluded that the analysis applied to claim 1 also applied to claims 7, 8, 10, 11, 17, 18, 20, and 21. J.A. 17. It separately addressed claims 9 and 19, which recite certain steps cul- minating in a final step of “providing the drug for treat- ment.” The steps recited in claim 9 appear as follows and are the same as those in claim 19 in all respects material to this appeal: determining whether at least one genetic variant associated with disease is within the stored haplo- type phase by utilizing the haplotype phase to query a disease associated-single nucleotide poly- morphism database using a computer system com- prising a processor and a memory; determining a drug for treatment of at least one member of the family based on information regard- ing drug-variant-phenotype associations from a pharmacogenomics database and the determina- tion whether the at least one genetic variant asso- ciated with disease is within the stored haplotype phase using a computer system comprising a pro- cessor and a memory; storing the determined drug using a computer sys- tem comprising a processor and a memory; and providing the determined drug in response to a re- quest using a computer system comprising a pro- cessor and a memory. J.A. 1103–04, 1106–07. The Board determined that claims 9 and 19 are drawn to patent ineligible subject matter

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because they “are not directed to a specific method of treat- ment, do not identify specific patients, do not recite a spe- cific compound, do not prescribe particular doses, and do not identify the resulting outcome.” J.A. 18. The Board distinguished claims 9 and 19 from the patent eligible claims discussed in Vanda Pharmaceuticals Inc. v. West- Ward Pharmaceuticals International Ltd., 887 F.3d 1117 (Fed. Cir. 2018), because the claims in Vanda were directed to a “specific method of treatment for specific patients us- ing a specific compound at specific doses to achieve a spe- cific outcome.” J.A. 17–18. For these reasons, the Board affirmed the examiner’s rejection of claims 1, 4–11, 14–25, and 27–30 under § 101. Stanford appeals. We have juris- diction pursuant to 35 U.S.C. § 141(a) and 28 U.S.C. § 1295(a)(4)(A). STANDARD OF REVIEW We review Board decisions in accordance with the Ad- ministrative Procedure Act (“APA”), 5 U.S.C. § 706(2). Dickinson v. Zurko, 527 U.S. 150, 152 (1999). Under the APA, we review the Board’s legal conclusions de novo and its factual findings for substantial evidence. ACCO Brands Corp. v. Fellowes, Inc., 813 F.3d 1361, 1365 (Fed. Cir. 2016). Substantial evidence is “such relevant evidence as a reasonable mind might accept as adequate to support a conclusion.” In re Gartside, 203 F.3d 1305, 1312 (Fed. Cir. 2000) (quoting Consol. Edison Co. v. NLRB, 305 U.S. 197, 229 (1938)). DISCUSSION The Supreme Court has articulated a two-step analysis to determine patent eligibility under 35 U.S.C. § 101. Al- ice, 573 U.S. at 217–18. In the first step, we examine whether a claim is directed to patent ineligible subject mat- ter, such as an abstract idea. Id. If so, we turn to the sec- ond step and examine whether the claims contain an inventive concept sufficient to transform the abstract idea into patent eligible subject matter. Id. at 221. In this

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second step we consider the claim elements individually and as an ordered combination to determine whether any additional limitations amount to significantly more than the ineligible concept. Id. at 217–18, 221. A patent eligible claim must do more than simply recite the abstract idea “while adding the words ‘apply it.’” Id. at 221. We conclude that all the reviewed claims of the ’925 application are directed to patent ineligible abstract ideas. Courts have long held that mathematical algorithms for performing calculations, without more, are patent ineligi- ble under § 101. See, e.g., Parker v. Flook, 437 U.S. 584, 595 (1978) (“[I]f a claim is directed essentially to a method of calculating, using a mathematical formula, even if the solution is for a specific purpose, the claimed method is nonstatutory.” (internal citation and quotation marks omitted)); Gottschalk v. Benson, 409 U.S. 63, 72 (1972) (finding claims patent ineligible because they “would wholly pre-empt the mathematical formula and in practical effect would be a patent on the algorithm itself”); SAP Am., Inc. v. InvestPic, LLC, 898 F.3d 1161, 1167 (Fed. Cir. 2018) (explaining that the focus of the claims, namely selecting certain information, analyzing it using mathematical tech- niques, and reporting or displaying the results of the anal- ysis, “is all abstract”); Digitech Image Techs., LLC v. Elecs. for Imaging, Inc., 758 F.3d 1344, 1351 (Fed. Cir. 2014) (“Without additional limitations, a process that employs mathematical algorithms to manipulate existing infor- mation to generate additional information is not patent el- igible.”); In re Schrader, 22 F.3d 290, 294 (Fed. Cir. 1994) (holding that a data gathering step of entering bids was “insufficient to impart patentability to a claim involving the solving of a mathematical algorithm”). On its face, representative claim 1 is drawn to a “method for resolving haplotype phase.” J.A. 1101. The method first involves “receiving” allele data and pedigree data and “determining an inheritance state” based on the received data “using [an HMM].” Id. The method then

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involves “receiving” transition probability data and popu- lation linkage disequilibrium data and “determining a hap- lotype phase” based on that received data as well as the earlier-calculated inheritance state “using a computer sys- tem comprising a processor and a memory.” Id. Lastly, the method involves “storing the haplotype phase” and “provid- ing” it “in response to a request using a computer system comprising a processor and a memory.” Id. at 1101–02. Claim 1 recites no concrete application for the haplotype phase beyond storing it and providing it upon request. Stanford argues that claim 1 is not directed to an ab- stract idea because the specific application of the steps is novel and enables scientists to ascertain more haplotype information than was previously possible. See, e.g., Appel- lant’s Br. 5 (“While the ‘trio’ method may be able to provide long-range haplotype phasing for approximately 80% of heterozygous positions, the method of the present inven- tion provides accurate, long-range phasing at 97.9% of all heterozygous positions.” (citing the ’925 application at ¶¶ 91–92)). Even accepting the argument that the claimed process results in improved data, we are not persuaded that claim 1 is not directed to an abstract mathematical calculation. 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.”); SAP, 898 F.3d at 1170 (“[P]atent law does not protect such claims, without more, no matter how groundbreaking the advance.”). We have also examined, consistent with our precedent, whether the claimed advance demonstrates an improve- ment on a technological process or merely enhances an in- eligible concept. See, e.g., Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743, 750 (Fed. Cir. 2019). The claimed advance proffered by Stanford, that the process yields a greater number of haplotype phase predic- tions, may constitute a new or different use of a mathemat- ical process, but we are not persuaded that the process is an improved technological process. We therefore conclude

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that claim 1 is directed to the abstract idea of mathemati- cally calculating alleles’ haplotype phase. Because claim 1 is directed to a patent ineligible math- ematical algorithm, we turn next to Alice step two. We con- clude that claim 1 is not transformed at step two into patent eligible subject matter. Claim 1 recites no steps that practically apply the claimed mathematical algorithm; instead, claim 1 ends at storing the haplotype phase and “providing” it “in response to a request.” Simply storing information and providing it upon request does not alone transform the abstract idea into patent eligible subject matter. See, e.g., In re Greenstein, 774 F. App’x 661, 664 (Fed. Cir. 2019) (explaining that the claims at issue only invoked a computer as a generic tool to store information and record transactions). Notably, claim 1 neither requires, nor results in, a spe- cialized 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. See J.A. 1101–02 (re- citing method steps carried out by a “computer” with a “pro- cessor” and a “memory”); see also Alice, 573 U.S. at 226 (explaining that the hardware-related terms “data pro- cessing system,” “communications controller,” and “data storage unit” are “purely functional and generic”); In re TLI Commc’ns LLC Pat. Litig., 823 F.3d 607, 614 (Fed. Cir. 2016) (holding generic computer components insufficient to add an inventive concept to an otherwise abstract idea). The written description makes clear that the mathematical steps performed, and the types of data received, as claimed, are conventional and well understood in the prior art. See, e.g., J.A. 272–73, 282–83, 294–99, 319–20. Thus, taken in- dividually, the limitations of claim 1 fail to transform the claims into a patent eligible application. Although Stanford faults the Board for failing to assess the elements of claim 1 as an ordered combination,

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Stanford fails to explain how that combination of elements moves the claimed subject matter beyond the abstract and into the practical. See Appellant’s Br. 41–43; see also Af- finity Labs of Tex., LLC v. DIRECTV, LLC, 838 F.3d 1253, 1263 (Fed. Cir. 2016) (explaining that novelty does not nec- essarily avoid abstractness). That a specific or different combination of mathematical steps yields a greater num- ber of haplotype predictions than previously achievable un- der the prior art is not enough to transform claim 1 into a patent eligible application. See SAP, 898 F.3d at 1170 (holding an advance in financial mathematical techniques does not constitute an inventive concept). The alleged in- novation accomplished in claim 1 is in the mathematical analysis itself, namely, in the receipt of data, executing mathematical calculations, and storing the resulting data. The alleged innovation therefore subsists in “the basic tools of scientific and technological work.” See Alice, 573 U.S. at 216. The remaining claims contain no limitations that, when considered individually or as an ordered combina- tion, transform them into patent eligible applications. In- dependent claims 11 and 21 recite generic computer hardware for performing the calculations covered in claim 1. Such hardware by itself is insufficient to provide an in- ventive concept. See, e.g., Alice, 573 U.S. at 222–24; SAP, 898 F.3d at 1168–70. Dependent claims 4–7, 14–17, 22–25, and 27–30 recite additional calculation steps and specify certain aspects of the haplotype phase algorithm covered by claim 1. But none of these additional steps move the claims beyond patent ineligible abstract mathematical al- gorithms. See SAP, 898 F.3d at 1169 (holding dependent claims patent ineligible where they add features that “simply provide further narrowing of what are still mathe- matical operations”)). Dependent claims 8–10 and 18–20 contain limitations drawn to making non-specific determinations of a “diagno- sis,” “drug treatment,” and “prognosis” based on the

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haplotype phase calculation. Without further limitations, these claims do nothing more than recite the haplotype phase algorithm and instruct, “apply it,” as the Supreme Court has prohibited. See Alice, 573 U.S. at 221. These claims are devoid of an inventive concept that transforms the claims into a patent eligible application. CONCLUSION We have considered Stanford’s remaining arguments and find them unpersuasive. For the above reasons, the Board’s conclusion that claims 1, 4–11, 14–25, and 27–30 are drawn to patent ineligible subject matter under § 101 is affirmed. AFFIRMED

Footnotes

[1] Claims 11 and 21, the two other independent claims in the ’925 application, both recite computer hard- ware for carrying out the steps of claim 1. See J.A. 1101– 10. The claims depending from claim 1 (claims 4–10 and 22–25) recite the same substantive limitations as the cor- responding claims that depend from claim 11 (claims 14– 20 and 27–30). J.A. 1101–10. No claims depend from claim 21.