Athena Diagnostics, Inc. v. Mayo Collaborative Services, LLC

          Appeal from the United States District Court for the District of Massachusetts in No. 1:15-cv-40075-IT, Judge Indira Talwani.

          Adam Gahtan, Fenwick & West LLP, New York, NY, argued for plaintiffs-appellants. Also represented by Eric M. Majchrzak, Vanessa Park-Thompson; Andrew Joseph Kabat, Emmett J. McMahon, Robins Kaplan LLP, Minneapolis, MN; Dimitrios T. Drivas, White & Case LLP, New York, NY.

          Jonathan Elliot Singer, Fish & Richardson, PC, San Diego, CA, argued for defendants-appellees. Also represented by John Cameron Adkisson, Elizabeth M. Flanagan, Phillip Goter, Deanna Jean Reichel, Minneapolis, MN.

          Aaron Barkoff, McAndrews, Held & Malloy, Ltd., Chicago, IL, for amicus curiae The Chartered Institute of Patent Attorneys.

          Kevin Edward Noonan, McDonnell, Boehnen, Hulbert & Berghoff, LLP, Chicago, IL, for amicus curiae Five Life Sciences Patent Practitioners. Also represented by John Dominic Cravero, Aaron Vincent Gin, Michael S. Greenfield, Andrea Kay Orth.

          Melissa A. Brand, Biotechnology Innovation Organization, Washington, DC, for amicus curiae Biotechnology Innovation Organization. Also represented by Hansjorg Sauer; Brian Paul Barrett, Eli Lilly and Company, Indianapolis, IN.

          Matthew James Dowd, Dowd Scheffel PLLC, Washington, DC, for amici curiae Dan L. Burk, Richard A. Epstein, Christopher Michael Holman, Gus Hurwitz, Adam Mossoff, Kristen J. Osenga, Michael Risch, Mark F. Schultz, Ted M. Sichelman, Brenda M. Simon.

          Kathleen M. Sullivan, Quinn Emanuel Urquhart & Sullivan, LLP, New York, NY, for amicus curiae ARUP Laboratories, Inc. Also represented by Brian C. Cannon, Redwood Shores, CA.

          Before Newman, Lourie, and Stoll, Circuit Judges.

          LOURIE, CIRCUIT JUDGE.

         Athena Diagnostics, Inc., Oxford University Innovation Ltd., and the Max-Planck-Gesellschaft zur Forderung der Wissenschaften E.V. (collectively, "Athena") appeal from the order of the United States District Court for the District of Massachusetts holding that claims 6-9 of U.S. Patent 7, 267, 820 (the "'820 patent") are invalid under 35 U.S.C. § 101 and dismissing Athena's complaint under Rule 12(b)(6). Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 275 F.Supp.3d 306 (D. Mass. 2017) ("Decision"). Because the district court correctly concluded that the claims at issue are directed to a natural law and lack an inventive concept, we affirm.

         I. Background

         Athena Diagnostics is the exclusive licensee of the '820 patent, covering methods for diagnosing neurological disorders by detecting antibodies to a protein called muscle-specific tyrosine kinase ("MuSK"). '820 patent Abstract. Athena also markets a test called FMUSK that functions by evaluating those antibodies. After Mayo Collaborative Services, LLC ("Mayo") developed two competing tests that allegedly practice each step of one or more claims of the '820 patent, Athena accused Mayo of infringing its patent. Mayo moved to dismiss under Rule 12(b)(6), arguing that the asserted claims of the '820 patent were invalid under 35 U.S.C. § 101. The district court granted Mayo's motion, concluding that the claims were invalid under § 101 for claiming ineligible subject matter. This appeal solely concerns whether claims 6-9 are patent eligible under § 101.

         A.

         Myasthenia gravis ("MG") is a neurological disorder where patients experience muscle weakness and symptoms including drooping eyelids, double vision, and slurred speech. '820 patent col. 1 ll. 13-23. It was previously discovered that MG is an autoimmune disease caused by a patient generating antibodies against her own acetylcholine receptors. Id. col. 1 ll. 24-26. Antibodies which recognize a person's own proteins as foreign antigens are known as autoantibodies. Id. col. 1 ll. 42-45.

         About 80% of patients with MG produce acetylcholine receptor autoantibodies. Id. col. 1 ll. 34-36. The other 20% do not, but they do experience the same MG symptoms. Id. col. 1 ll. 36-38. The named inventors of the '820 patent discovered that many of the 20% of MG patients without acetylcholine receptor autoantibodies instead generate autoantibodies to a membrane protein called MuSK. Id. col. 1 ll. 54-61. Prior to their discovery, no disease had been associated with MuSK. Id. col. 2 ll. 35-37.

         Having discovered the association between MuSK autoantibodies and MG, the inventors of the '820 patent disclosed and claimed methods of diagnosing neurological disorders such as MG by detecting autoantibodies that bind to a MuSK epitope.^[1] Id. col. 2 ll. 61-65. Claim 1, not at issue in this appeal, is the only independent claim and reads as follows:

1. A method for diagnosing neurotransmission or developmental disorders related to [MuSK] in a mammal comprising the step of detecting in a bodily fluid of said mammal autoantibodies to an epitope of [MuSK].

Id. col. 12 ll. 31-35. Claim 7 is at issue and depends from claim 1. It recites:

7. A method according to claim 1, comprising

contacting MuSK or an epitope or antigenic determinant thereof having a suitable label thereon, with said bodily fluid,

immunoprecipitating any antibody/MuSK complex or antibody/MuSK epitope or antigenic determinant complex from said bodily fluid and

monitoring for said label on any of said antibody/MuSK complex or antibody/MuSK epitope or antigen determinant complex,

wherein the presence of said label is indicative of said mammal is suffering from said neurotransmission or developmental disorder related to [MuSK].

Id. col. 12 l. 62-col. 13 l. 5 (spacing added). Claim 8 depends from claim 7 and recites that the label is a radioactive label. Id. col. 13 ll. 6-7. Claim 9 depends from claim 8 and further recites that the radioactive label is 125I, a radioactive isotope of iodine. Id. col. 13 ll. 8-9. We focus on claim 9, the most specific one at issue, which requires: (1) contacting MuSK or an epitope thereof having a 125I label, with bodily fluid; (2) immunoprecipitating any antibody/MuSK complex; and (3) monitoring for the label on the complex, wherein the presence of the label indicates the presence of a MuSK-related disorder.

         The specification of the '820 patent further explains what the steps of iodination and immunoprecipitation entail. First, MuSK is iodinated using radioactive 125I. Id. col. 10 ll. 50-52. Then iodinated MuSK is separated from any free 125I by gel filtration. Id. col. 10 ll. 55-56. Next, the 125I-labeled MuSK is added to a small volume of the patient's bodily fluid and left overnight. Id. col. 10 ll. 56- 58. If MuSK autoantibodies are present in the patient's bodily fluid, they will bind to the 125I-labeled MuSK. Any 125I-labeled MuSK in the sample is then immunoprecipitated by adding a secondary antibody that binds to any MuSK autoantibodies present. Id. col. 10 ll. 58-60. The resulting precipitate is finally centrifuged, washed, and counted for radioactivity, which may be indicative of MG. Id. col. 10 ll. 60-61.

         It is undisputed that iodination and immunoprecipitation were known techniques at the time of the invention. The '820 patent specification states that "[t]he actual steps of detecting autoantibodies in a sample of bodily fluids may be performed in accordance with immunological assay techniques known per se in the art," such as radioimmunoassays. Id. col. 3 ll. 33-37. With respect to the relevant individual steps in the radioimmunoassay, the specification also discloses that "[i]odination and immunoprecipitation are standard techniques in the art." Id. col. 4 ll. 10- 11.

         Claim 6 is additionally at issue in this appeal and depends from claim 3. While claim 6 also involves detecting MuSK autoantibodies by contacting a patient's bodily fluid with MuSK or an epitope thereof, the labelling occurs somewhat differently than in claims 7-9. Instead of labeling MuSK with a radioisotope, claim 3 recites that the secondary antibody is "tagged or labeled with a reporter molecule." Id. col. 12 ll. 47-49. Claim 6 additionally requires that "the intensity of the signal from the [secondary] antibody is indicative of the relative amount of the anti-MuSK autoantibody in the bodily fluid when compared to a positive and negative control reading." Id. col. 12 ll. 57- 61. This claimed technique exemplifies the ELISA method, ^[2] which, like radioimmunoassays, the '820 patent specification lists as an example of "immunological assay techniques known per se in the art." Id. col. 3 ll. 33-36.

         B.

         The district court concentrated its analysis on claims 7-9. Athena did not present any arguments specific to claim 6. Applying the test for subject matter eligibility established by the Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012) and Alice Corp. v. CLS Bank International, 573 U.S. 208 (2014), the court first concluded that the claims were directed to a law of nature, Decision, 275 F.Supp.3d at 312. According to the court, the claims focused on the interaction of 125I-labeled MuSK with MuSK autoantibodies in bodily fluid, an interaction which occurs naturally. Id. at 310. The district court also determined that the claims lacked an inventive concept, as the recited steps involved only standard techniques in the art. Id. at 312-13.

         The district court thus dismissed Athena's complaint for failure to state a claim. Athena appealed. We have jurisdiction under 28 U.S.C. § 1295(a)(1).

         II. Discussion

         We review the district court's dismissal for failure to state a claim under regional circuit law. BASCOM Glob. Internet Servs., Inc. v. AT&T Mobility LLC, 827 F.3d 1341, 1347 (Fed. Cir. 2016). The First Circuit reviews such dismissals de novo, accepts all well-pleaded facts alleged in the complaint to be true, and draws all reasonable inferences in favor of the nonmovant. In re Loestrin 24 Fe Antitrust Litig., 814 F.3d 538, 549 (1st Cir. 2016). Patent eligibility under § 101 is a question of law based on underlying facts, see Aatrix Software, Inc. v. Green Shades Software, Inc., 882 F.3d 1121, 1125 (Fed. Cir. 2018); Berkheimer v. HP Inc., 881 F.3d 1360, 1364-65 (Fed. Cir. 2018), that may be resolved on a Rule 12(b)(6) motion when the undisputed facts require a holding of ineligibility, SAP Am., Inc. v. Investpic, LLC, 898 F.3d 1161, 1166 (Fed. Cir. 2018).

         Section 101 provides that "[w]hoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title." 35 U.S.C. § 101. Given the expansive terms of § 101, "Congress plainly contemplated that the patent laws would be given wide scope"; some of the legislative history likewise indicated that "Congress intended statutory subject matter to 'include anything under the sun that is made by man.'" Diamond v. Chakrabarty, 447 U.S. 303, 308-09 (1980).

         Under the law as set forth by the Supreme Court, § 101, while broad, "contains an important implicit exception. '[L]aws of nature, natural phenomena, and abstract ideas' are not patentable." Mayo, 566 U.S. at 70 (alteration in original) (quoting Diamond v. Diehr, 450 U.S. 175, 185 (1981)). These exceptions exist because monopolizing the basic tools of scientific work "might tend to impede innovation more than it would tend to promote it." Id. at 71. However, the Supreme Court has advised that these exceptions must be applied cautiously, as "too broad an interpretation of this exclusionary principle could eviscerate patent law." Id.

         Laws of nature are not patentable, but applications of such laws may be patentable. A claim to otherwise statutory subject matter does not become ineligible by its use of a law of nature. See Diehr, 450 U.S. at 187; Parker v. Flook, 437 U.S. 584, 590 (1978). But, on the other hand, adding "conventional steps, specified at a high level of generality," to a law of nature does not make a claim to the law of nature patentable. Mayo, 566 U.S. at 82.

         To distinguish claims to patent-eligible applications of laws of nature from claims that impermissibly tie up such laws, we apply the two-part test set forth by the Supreme Court. First, we examine whether the claims are "directed to" a law of nature. Alice, 573 U.S. at 217. If they are, then we proceed to the second inquiry, where we ask whether the limitations of the claim apart from the law of nature, considered individually and as an ordered combination, "'transform the nature of the claim' into a patent-eligible application." Id. (quoting Mayo, 566 U.S. at 78). To so transform the claim, the additional limitations must "ensure that the patent in practice amounts to significantly more than a patent upon the natural law itself." Mayo, 566 U.S. at 73.

         We first address claims 7-9 and then turn to claim 6.

         A.

         Athena argues that claims 7-9 are not directed to a natural law at step one because they recite innovative, specific, and concrete steps that do not preempt a natural law. Rather, Athena contends that the claims are directed to a new laboratory technique that makes use of man-made molecules.

         Mayo responds that the claims are directed to a natural law: the correlation between naturally-occurring MuSK autoantibodies and MuSK-related neurological diseases like MG. According to Mayo, the remaining steps apart from the natural law are concededly standard immunoassay techniques that still leave the claim directed to a natural law. Indeed, Mayo argues that the specificity and concreteness of the claimed steps are irrelevant to whether a claim is directed to a natural law. And, as in Mayo, Mayo contends that it makes no difference to eligibility that the claimed diagnostic method uses man-made materials.

         We ultimately agree with Mayo that, under Mayo, the claims are directed to a natural law. As an initial matter, we must identify what the relevant natural law is. Here, it is the correlation between the presence of naturally-occurring MuSK autoantibodies in bodily fluid and MuSK- related neurological diseases like MG.^[3] This correlation exists in nature apart from any human action. There can thus be no dispute that it is an ineligible natural law.

         However, as Athena correctly observes, not every claim that involves a natural law is directed to a natural law. "[A]ll inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas." Mayo, 566 U.S. at 71. The Supreme Court's two-step test thus "plainly contemplates that the first step of the inquiry is a meaningful one, i.e., that a substantial class of claims are not directed to a patent-ineligible concept." Enfish, LLC v. Microsoft Corp., 822 F.3d 1327, 1335 (Fed. Cir. 2016).

         The step one "directed to" inquiry focuses on the claim as a whole. E.g., Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016). To determine whether a claim is directed to an ineligible concept, we have frequently considered whether the claimed advance improves upon a technological process or merely an ineligible concept, based on both the written description and the claims. See Cleveland Clinic Found. v. True Health Diagnostics LLC, 859 F.3d 1352, 1361 (Fed. Cir. 2017); Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042, 1047-49 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1376 (Fed. Cir. 2015); see also McRO, Inc. v. Bandai Namco Games Am. Inc., 837 F.3d 1299, 1314-15 (Fed. Cir. 2016); Elec. Power Grp., 830 F.3d at 1354.

         For example, in CellzDirect we considered claims that covered a method for producing a preparation of a type of liver cell (called hepatocytes) that involved multiple freeze-thaw cycles. 827 F.3d at 1046, 1048. Although the inventors discovered the cells' ability to survive multiple freeze-thaw cycles, a discovery that the district court understood to be a natural law, we concluded that the claims were not directed to that natural law. Id. at 1048-50. This was because the claims as a whole recited "a new and improved way of preserving hepatocyte cells for later use," "not simply an observation or detection of the ability of hepato-cytes to survive multiple freeze-thaw cycles." Id. at 1048. The claimed advance harnessed a natural law to produce a technological improvement that was patent eligible. See id. at 1048-49; see also, e.g., Enfish, 822 F.3d at 1335-39 (holding improvement in computer-related technology not directed to abstract idea).

         In contrast, in Cleveland Clinic we reiterated that claims that merely recite observing naturally occurring biological correlations "with no meaningful non-routine steps in between" are directed to a natural law. 859 F.3d at 1361; see Ariosa, 788 F.3d at 1376. There, the specification indicated that the claimed inventors discovered a natural correlation between a molecule called MPO and cardiovascular disease. Cleveland Clinic, 859 F.3d at 1360-61. The claims at issue recited detecting MPO or other MPO-related products in a patient sample and then predicting a patient's risk of having or developing cardiovascular disease. Id. at 1361. As the claims only covered the correlation between MPO and ...