# United States **Court of Appeals**  **for the Federal Circuit**

______________________ ATHENA DIAGNOSTICS, INC., OXFORD UNIVERSITY INNOVATIO N LTD., MAX

- PLANCK

GESELLSCHAFT ZUR FOR DERUNG DER WISSENSCHAFTEN E.V., Plaintiffs

- Appellants

v.

MAYO COLLABORATIVE S ERVICES, LLC, DBA MAYO MEDICAL LABORAT ORIES, MAYO CLINIC, Defendants

- Appellees

______________________

2017

- 2508

______________________ Appeal from the United States District Court for th e District of Massachusetts in No. 1:15

- cv

- 40075

- IT, Judge Indira Talwani.

______________________

Decided: February 6 , 2019

______________________

A DAM G AHTAN , Fenwick & West LLP, New York, NY, argued for plaintiffs

- appellants. Also represented by E RIC M. M AJCHRZAK , V ANESSA P ARK -T HOMPSON ; A NDREW J OSEPH K ABAT , E MMETT J. M C M AHON , Robins Kaplan LLP, Minneapolis, MN; D IMITRIOS T. D RIVAS , White & Case LLP, New York, NY.

J ONATHAN E LLIOT S INGER , Fish & Richardson, PC, SanATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 2

Diego, CA, argued for defen dants

- appellees. Also represented by J OHN C AMERON A DKISSON , E LIZABETH M. F LANAGAN , P HILLIP G OTER , D EANNA J EAN R EICHEL , Minneapolis, MN

.

A

ARON B ARKOFF , McAndrews, Held & Malloy, Ltd., Chicago, IL, for amicus curiae The Chartered Institute of Pat ent Attorneys.

K EVIN E DWARD N OONAN , McDonnell, Boehnen, Hulbert & Berghoff, LLP, Chicago, IL, for amicus curiae Five Life Sciences Patent Practitioners. Also represented by J OHN D OMINIC C RAVERO , A ARON V INCENT G IN , M ICHAEL S. G REENFIELD , A NDREA K AY O RTH

.

M ELISSA A. B RAND , Biotechnology Innovation Organization, Washington, DC, for amicus curiae Biotechnology Innovation Organization. Also represented by H ANSJORG S AUER ; B RIAN P AUL B ARRETT , Eli Lilly and Company, Indianapolis, IN.

M ATTHEW J AMES D OWD , 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.

K

ATHLEEN M. S ULLIVAN , Quinn Emanuel Urquhart &Sullivan, LLP, New York, NY, for amicus curiae ARUP Laboratories, Inc. Also represented by B RIAN C. C ANNON , Redwood Shores, CA.

______________________
Before N EWMAN , L OURIE , and S TOLL , Circuit Judges.
Opinion for the court filed by Circuit Judge L OURIE

. Dissenting opinion filed by Circuit Judge N EWMAN

.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 3

L OURIE , Circuit Judge

. A thena Diagnostics, Inc., Oxford University Innovation Ltd., and the Max

- Planck

- Gesellschaft zur Forderung d er 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 a re directed to a natural law and lack an inventive concept, we affirm.

I. B ACKGROUND
Athena Diagnostics is the exclusive licensee of the ’820 patent, covering methods for diagnosing neurological disorders by detecting antibodies to a protein called muscl especific 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, conclud ing 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 aATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 4

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 autoantibodi es. 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, i s the only independent claim and reads as follows : 1. A method for diagnosing neurotransmission or developmental disorders related to [MuSK] in amammal 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:

1 An epitope, also known as an antigenic determinant, is a segment of a protein recognized by an antibody. See Bruce Alberts, Molecular Biology of the Cell 449

– 50(6th ed. 2015). The specification of the ’820 patent disclosed that autoantibodies in MG patients recognize a MuSK epitope located on the protein’s extracellular amino

terminal domain. ’820 patent col. 1 ll. 54

– 57.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 5

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 complexor 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,

whe rein the presence of said label is indicative ofsaid mammal is suffering from said neurotransmission or developmental disorder related to [MuSK]

. Id. col. 12 l. 62

– col. 13 l. 5 ( spacing added). Cl aim 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 recite s 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 o f the label indicates the presence of a MuSK

- related disorder.
The specification of the ’820 patent further explainswhat the steps of iodination and immunoprecipitation entail

. First, MuSK is iodinated using radioactive 125I. Id. col. 10 ll. 50

– 52. T hen 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 pres ent 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 anyATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 6

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.

I t is undisputed that iodination and immunoprecipitation were known techniques a t 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 immun oprecipitation 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 wit h 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 speci fication lists as an example of “immunological assay techniques known per se in the art.” Id. col. 3 ll. 33

– 36.

2 ELISA stands for enzyme

- lin ked immunosorbent assay. The technical details of this assay are not relevant to this appeal.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 7

B.

The district court concentrated its analysis on claims 7– 9. Athena did not present any arguments specific to claim 6. Applying the test fo r 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), t he 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

. I d. 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. D ISCUSSION
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. 20 16). 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 non

- movant

. In re Loestrin 24 Fe Antitrust Litig. , 814 F.3d 538, 549 (1st Cir. 2016). Patent eligibility u nder § 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).ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 8

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 improvementthereof, may obtain a patent therefor, subject to the conditions and requirements of this title.” 35 U.S.C. § 101. Given t he 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 C ourt, § 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 thebasic 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 o f such laws may be patentable. A claim to otherwise statutory subject matter do es not beco me 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 st eps, 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, thenATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 9

we proceed to the second inquiry, where we ask w hether 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 cla im, 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

- mad e 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 , a s i n 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,

w e must identif y what the relevant natural law is. Here, it is the correlation between the presence of naturally

- occurring MuSK autoantibodies in bodily fluid and MuSK

-ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 10

related neurological diseases like MG

. 3 T his correlation exists in nature apart from any human action

. There can thus be no dispute that it is a n 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, restupon, or apply laws of nature, natural phenomena, or abstract ideas.” Mayo , 566 U.S. at 71. T he 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 ineligibl e 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); Arios a Diagnostics, Inc. v. Sequenom, Inc.

, 788 F.3d 1371, 1376 (Fed. Cir. 2015); see also McRO, Inc. v.

3 We note that the district court held that the “focusof the claims” was the binding of MuSK to MuSK antibodies in bodily fluid. Decision , 275 F. Supp. 3d a t 310. Our cases have not described a claim to the binding of two molecules during a sequence of chemical manipulations (here, after MuSK labeling and before immunoprecipitation) as a claim to a natural law, even if such binding occurs according to natura l laws. We need not resolve that issue here, as we agree with Mayo’s identification of the natural law.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 11

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 multipl e freeze

thaw cycles, a discover y 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

, ” “notsimply an observation or detection of the ability of hepatocytes 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, t he 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

- relate d products in a patient sample and thenpredicting a patient’s risk of having or developing cardiovascular disease. Id. at 1361. As the claims only covered the correlation between MPO and cardiovascular disease

, a n ineligible discovery, together with “well

- known techniques to execute the claimed method,” we held that the claims were directed to a natural law. Id.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 12

The claims at issue here involve both the discovery of a natural law and certain concrete steps to observe its operation

. Claim 9, the most specific claim at issue, recites the following method to detect MuSK autoantibodies : (1) mixing MuSK or an epitope there of having a 125I label with bodily fluid; (2) immunoprecipitating any resulting antibody/MuSK complex; and (3) monitoring for the label on the complex. ’820 patent col. 12 l. 62

– col. 13 l. 9. The claim then concludes in the wherein clause with a statement of the natural law

, i.e.

, the discovery that MuSK auto antibodies naturally present in a patient sample

, detected with the 125I label bound to the MuSK/antibody complex, i ndicate that the patient is suf fering from a MuSK

- related neurological disorder. Id. col. 13 ll. 2

– 5.

A s in Cleveland Clinic and Ariosa

, we conclude that claims 7

– 9 are directed to a natural law because the claimed advance was only in the discovery of a natural law, and that the addit ional recited steps only apply conventional techniques to detect that natural law. T he specification of the ’820 patent highlights the discovery of thenatural law, explaining that “[t]he present inventors surprisingly found that many of the 20% of MG pat ients [who]do not exhibit any autoantibodies to [the acetylcholine receptor], instead have .

. . antibodies directed against the extracellular [amino]

- terminal domains of MuSK.” Id. col. 1 ll. 54

– 57. Further , the specification describes the claimedconcrete steps for observing the natural law as conventional. It teaches 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,” includi ng radioimmunoassays and ELISA. Id. col. 3 ll. 33

– 37. Likewise, the specification identifies “[i]odination and immunoprecipitation” as “standard techniques in the art.” Id. col. 4 ll. 10

– 12. T he ’820 patent thus describes the claimed invention principa lly as a discovery of a natural law

, not as an improvement in the underlying immunoassay technology

.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 13

Consistent with the specification

, the claims are directed to that law

. Athena argues that the claims at issue, like the claims in CellzDirect , are dire cted to an innovative laboratory technique, not a law of nature. However, Athena does notpoint to any innovation other than its discovery of the natural law. CellzDirect did not suggest that appending standard techniques to detect a natural law rendered claims not directed to a natural law; rather, we expressly distinguished the eligible claims in that case from ineligible claims that “amounted to nothing more than observing or identifying the ineligible concept itself.” 827 F.3d at 1048. In that case , w e concluded that the “end result” of the claims at issue was “not simply an observation or detection” of a natural law. Id. We cannot so conclude here

, since the claims before us only involve detecting a natural law “with no meaningful non

- routine step s.” Cleveland Clinic , 859 F.3d at 1361

. Athena also points to the specificity of the claimed concrete steps , contending that they preempt no natural law and therefore the claims cannot be directed to a natural law

. Although w e agree that claim 9 leaves open to the public other ways of interro gating the correlation between MuSK autoantibodies and MuSK

- related disorders without practicing the claim’s concrete steps , that does not disturb our conclusion at step one

. P reemption is sufficient to render a cl aim ineligible under § 101, but it is not necessary. Flook , 409 U.S. at 71

– 72 (holding claim involving mathematical formula invalid under § 101 that did not preempt a mathematical formula); Ariosa , 788 F.3d at 1379 ; In re BRCA1 - & BRCA2

- Based Hereditary Cancer Test Patent Litig. , 774 F.3d 755, 764 n.4 (Fed. Cir. 2014)

. The claims here are directed to a natural law because they recite only the natural law together with standard techniques for observing it. That the routine steps are set forth with some s pecificity is not enough to change that conclusion

.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 14

Finally, Athena argues that the claims at issue differ from prior diagnostic claims we have held ineligible under § 101 because they require labeling MuSK with a man

made substance. We disagree. As Ma yo argues, the use of

a man

- made molecule is not decisive if it amounts to onlya routine step in a conventional method for observing a natural law . For example, Mayo involved claims requiring administering a man

- made molecule (a drug “providing” 6

- thioguanine) to a patient. 566 U.S. at 74

– 75. Some of the claims in Ariosa likewise required amplification through the polymerase chain reaction, which makes use of man

made reagents, see U.S. Patent 6,258,540 col. 5 ll. 6

– 26, or using a specific probe that bi nds to DNA, 788 F.3d at 1374. And the claims in BRCA1 also involved hybridizing a synthetic DNA probe to a DNA strand. BRCA1 , 774 F.3d at 763

– 64 . Nonetheless, in each of these cases either the Supreme Court or this court held the claims directed to a na tural law and invalid under § 101. Mayo , 566 U.S. at 92; Ariosa , 788 F.3d at 1380; BRCA1 , 774 F.3d at 765. We thus reaffirm that use of a man

- made molecule in a method claim employing standard techniques to detect or observe a natural law may still leave the claim directed to a natural law.

We co nsider it important at this point to note the difference between the claims before us here, which recite a natural law and conventional means for detecting it , and applications of natural laws, which are patent

- eligible

. See Vanda Pharm. Inc. v. West

- Ward Pharm. Int’l Ltd. , 887 F.3d 1117, 1133

– 36 (Fed. Cir. 2018) (holding that method of treatment by administering drug at certain dosage ranges based on a patient ’s genotype was not directed to a natural law )

. Claiming a natural cause of an ailment and well- known means of observing it is not eligible for patent because such a claim in effect only encompasses the natural law itself . But claiming a new treat ment for an ailment, albeit using a natural law, is not claiming the natural law.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 15

As we conclude that claims 7–9 are directed to a natural law, we turn to the second step of the Mayo/ Alice test. 4

B. At step two, “we consider the elements of each claim both individual ly and ‘as an ordered combination’ to de termine whether the additional elements ‘transform the nature of the claim’ into a patent

- eligible application.” Alice

,

4 The dissent states much that one can agree with from the standpoint of policy, and history , including that “the public interest is poorly served by adding disincentive to the development of new diagnostic methods .” Dissent at 12

. We would add further that, in our view, providing patent protection to novel and non -obvious diagnostic methods would promote the progress of science and useful arts. But, w hether or not we as individual judges might agree or not that these claims only recite a natural law, cf. Berkheimer v. HP Inc. , 890 F.3d 1369, 1374 (Fed. Cir. 2018) (Lourie, J., concurring in the denial of rehea ring en banc ) (discussing traditional laws of nature such as “Ohm’s Law, Boyle’s Law, [and] the equivalence of matter and energy”), the Supreme Court has effectively told us in Mayo that correlations between the presence of a biological material and a disease are laws of nature, see 566 U.S. a t 77, and “[p]urely ‘ conventional or obvious ’ ‘ [pre]

- solution activity ’ is normally not sufficient to transform an unpatentable law of nature into a patent

- eligible application of such a law ,” id. at 79 (second alteration in original) (quoting Flook , 437 U .S. at 590)

. We have since confirmed that applying somewhat specific yet conventional techniques ( such as the polymerase chain reaction ) to detect a newly discover ed natural law does not confer eligibility under § 101. Ariosa

, 788 F.3d at 1377; see also Cleveland Clinic , 859 F.3d at 1356, 1362 (addressing other conventional techniques such as flow cytometry)

. Our precedent leaves no room for a different outcome here.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 16

573 U.S. at 217 (quoting Mayo , 566 U.S. at 78, 79). “Purely ‘conventional or obvious’ ‘[pre]

- solution activity’ is normally not sufficient to transform an unpatentable law of nature into a patent

- eligible application of such a law.” Mayo , 566 U.S. at 79 ( second alteration in original) (quoting Flook

, 437 U.S. at 590). The transformative “inventiveconcept” supplied by the claim elements not drawn to ineligible subject matter must be “sufficient to ensure that thepatent in practice amounts to significantly more than a patent upon the [ineligible conc ept] itself.” Alice

, 573 U.S. at 217

– 18 (quoting Mayo , 566 U.S. at 73).

1. Athena argues that the claims provide an inventive concept: an innovative sequence of steps involving man

made molecules. Prior to its discovery, Athena contends that there was no disclosed method to detect MuSK autoantibodies. In addition, Athena argues that the existence of factual disputes precluded dismissal under Rule 12(b)(6).
Mayo responds that the claims lack an inventive concept because the specification describes the steps for detecting MuSK autoantibodies as standard techniques in the art. Furthermore, Mayo argues that no factual issues precluded the district court’s dismissal under Rule 12(b)(6). We agree with Mayo that the steps of the claims not drawn to inel igible subject matter , whether viewed individually or as an ordered combination, only require standard techniques to be applied in a standard way. As previously discussed, t he specification of the ’820 patent plainly states that “[t]he actual steps of det ecting 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. ’820 patent col. 3 ll. 33

– 37

. Iodination and immunoprecipitation are likewise described as standard techniques. Id. col. 4 ll. 9

– 12. Because the specification defines the individual immunoprecipitation and iodination steps and the overallATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 17

radioimmunoassay as conventional techniques

, the claims fail to provide an inventive concept. Cleveland Clinic , 859 F.3d at 1362; Ariosa , 788 F.3d at 1378

. Our decisions in CellzDirect and BASCOM are consistent with the principle that applying standard techniques in a standard way to observe a nat ural law does not provide an inventive concept. In CellzDirect , we considered a combination of claimed steps involving two freeze/thaw cycles. 827 F.3d at 1051. We held that this combination of steps was not conventional because the prior art methods

on ly disclosed using one freeze/thaw cycle and , in fact, taught away from using multiple freeze/thaw cycles. Id. Similarly, in BASCOM we held that the ordered combination of claim limitations was not routine and conventional because they placed a filtering tool at a specific location that improved on prior art technology. 827 F.3d at 1350. The inventive concept was “found in the non

- conventional and non

- generic arrangement of known, conventional pieces .” Id. In contrast, c laims 7–9 of the ’820 patent employ a conventional technique for detecting autoantibodies

, a radioimmunoassay, which the specification acknowledges was “known per se in the art.” ’820 patent col. 3 ll. 33

– 37. The individual constituent steps of that technique, iodination and immunop recipitation

, are similarly described as standard. Id. col. 4 ll. 9

– 12. Thus, u nlike the claimed limitations at issue in CellzDirect and BASCOM

, t he recited steps here were conventional both as an ordered combination and individually

. Athena also arg ues that the claimed steps were unconventional because they had not been applied to detect MuSK autoantibodies prior to Athena’s discovery of the correlation between MuSK autoantibodies and MG

. Even accepting that fact, we cannot hold that performing stan dard techniques in a standard way to observe a newly discovered natural law provides an inventive concept. This is because “[t]he inventive concept necessary at step two

. . . cannot be furnished by the unpatentable law of natureATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 18

. . . itself.” Genetic Techs. Ltd. v. Merial L.L.C. , 818 F.3d 1369, 1376 (Fed. Cir. 20 16) ; see Mayo , 566 U.S. at 73 (considering whether the “claimed processes (apart from the natural laws themselves)” were routine and conventional)

. Rather, to supply an inventive con cept the sequence of claimed steps must do more than adapt a conventional assay to a new ly discovered natural law; it must represent an inventive application beyond the discovery of the natural law itself

. Because claims 7

– 9 fail to recite such an application, they do not provide an inventive concept

. Similar to its step one argument, Athena further argues that the claims recite an inventive concept because they use a man

- made molecule, i.e.

, labeled MuSK. Athena analogizes its methods involving labeled MuSK t o the composition claims involving cDNA held eligible in Association for Molecular Pathology v. Myriad Genetics, Inc. , 569 U.S. 576, 594

– 95 (2013). However, the method claims at issue here are unlike the claims held eligible in Myriad , which recited a new composition of matter that was not a natural product. Id. For the same reason s that we have concluded that attaching a label to MuSK did not make the claims directed to an eligible concept at step one, we conclude that appending labeling techniques to a natural law does not provide an inventive concept where, as here, the specification describes 125I labeling as a standard practice in a well- known assay

. 2. Athena also argues that the district court needed to conduct fact

- finding be fore resolving the § 101 issue. But

, u nlike in Aatrix

, 882 F.3d at 1128, Athena directs us to no factual allegations in its complaint

— amended three times

— that the radioimmunoassay technique recited in claims 7

– 9 is anything other than standard and “known per se in the art.” ’820 patent, col. 3 ll. 33

– 37. Instead, Athena relies on an expert declaration submitted with its opposition to Mayo’s motion to dismiss, assert ing that iodinationATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 19

and immunoprecipitation were not routine as applied to the claimed inv ention. In dismissing Athena’s complaint under Rule 12(b)(6), the district court did not consider the declaration. Athena argues that was error. We disagree.
In the First Circuit, under Rule 12(b)(6) a district court
may generally “consider only facts and documents that arepart of or incorporated into the complaint; if matters outside the pleadings are considered, the motion must be decided under the more stringent standards applicable to a Rule 56 motion for summary judgment.” Tr ans

- Spec Truck Serv., Inc. v. Caterpillar Inc. , 524 F.3d 315, 321 (1st Cir. 2008). Certain documents

, like the ’820 patent here

, are also considered to “merge[] into the pleadings” where the “complaint’s factual allegations are expressly linked to” and de pendent upon a document, the authenticity of which is undisputed. Id. (quoting Beddall v. State St. Bank & Trust Co. , 137 F.3d 12, 16

– 17 (1st Cir. 1998) )

. District courts in the First Circuit have discretion whether to convert a motion to dismiss into a motion for summary judgment. Id. (citing Fed. R. Civ. P. 12(d)). “[I]f the district court chooses .

. . to ignore supplementary materials submitted with the motion papers and determine the motion under the Rule 12(b)(6) standard, no conversion

occurs an d the supplementary materials do not become part of the record for purposes of the Rule 12(b)(6) motion.” Id.

We conclude that the district court did not abuse itsdiscretion in declining to consider Athena’s expert declaration and convert the motion into one for summary judgment

. The declaration does not “merge into the pleadings

, ” as the complaint does not reference it or otherwise depend on it. Nor is the declaration an official public record , another type of document a court may consider with the pleadings

. See Watterson v. Page , 987 F.2d 1, 3

– 4 (1st Cir. 1993).ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 20

Athena does not expressly argue that the district court abused its discretion, but does contend, primarily citing

non

- binding authority, that the plaintiff may freely allege facts with out support in responding to a motion to dismiss

as long as those facts ar e consistent with the complaint, s ee Early v. Bankers Life & Casualty Co. , 95 9 F.2d 75, 79 (7th C ir. 1992), and that its expert declaration alleged such consistent facts that create a dispute of material fact.
Even assuming this general principle applies in the First Circuit

— an assumption that Athena meagerly supports

— the district court did not need to consider the allegations in the expert declaration because they were not consis tent with the complaint read in light of the ’820 patent

. These technical allegations include : (1) that detecting MuSK autoantibodies required the “creative step” of breaking up MuSK into smaller fragments, J.A. 623 , 625 ; (2) that identifying a specific site on MuSK to label would not have been routine because many factors contribute to whether a binding site for a label is adequate , J.A. 626

– 28; and (3) that immunoprecipitation is generally uncertain and not routine, J.A. 630. Non e of these details are recited in the claims of the ’820 patent : no claim requires breaking MuSK into fragments as opposed to using the entire MuSK protein; no claim is limited to a particular MuSK binding site; and no claim recites any detail with respec t to immunoprecipitation. Th ose omissions are consistent withthe specification’s description of iodination, immunoprecipitation, and the overall radioimmunoassay as standard techniques

. Because Athena’s expert declaration made allegations inconsistent w ith the ’820 patent, the district court was not obliged to accept them as true. For these

reasons, the district court did not err in dismissing Athena’s complaint under Rule 12(b)(6)

. C.Claim 6 recites a method for detecting MuSK autoantibodies different from claims 7

– 9. While claims 7

– 9 reciteATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 21

a radioimmunoassay, claim 6 recites an ELISA method. Like radioimmunoassays, the specification describes ELISA as an “immunological assay technique[] known per se in the art.” ’820 patent col. 3 ll. 32

– 36. The main technical difference pertinent to this appeal between an ELISA and a radioimmunoassay is that in an ELISA, the secondary antibody rather than the antigen is labeled.
Athena argues that since the district court did not specifically analyze cl aim 6 , which involves a different technology, and implicitly treated claims 7

– 9 as representative, we should remand at least with respect to claim 6. Mayo responds that the district court properly grouped claim 6 with claims 7

– 9 because Athena grouped the m together

, and that Athena waived any separate arguments regarding claim 6 by not specifically addressing that claim in its briefing

.During the district court proceedings, Athena represented that it would not assert claims 1

– 5 and 10

– 12, and Mayo then moved to dismiss Athena’s complaint, specifically addressing claims 6

– 9. In its response, Athena did not make any particularized arguments regarding claim 6, and

, in an earlier response

, indicated that the same arguments pertaining to claims 7

– 9 were also applicable to claim 6. See J.A. 180 (“While the claim does not requireradioactive MuSK or complexes, many other arguments relating to claims 7

- 9 apply to claim 6.”). The district court did not address claim 6 in its order beyond listing it among the ot her claims. Decision , 275 F. Supp. 3d at 309

– 10.

Given this history , w e agree with Mayo that Athena waived its arguments specific to claim 6 by not making them before the district court

. We apply regional circuit law to the issue of waiver, as it is not unique to patent law. Riverwood Int’l Corp. v. R.A. Jones & Co. , 324 F.3d 1346, 1352 (Fed. Cir. 2003) (citing Midwest Indus., Inc. v. Karavan Trailers, Inc. , 175 F.3d 1356, 1359 (Fed. Cir. 1999) (en banc in relevant part) )

. In the First Circuit, an argum entATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 22

may be deemed waived that was not presented to the district court. Butler v. Deutsche Bank Tr. Co. Ams. , 748 F.3d 28, 36 (1st Cir. 2014). Although Athena recognized that claim 6 was at issue, it concededly did not present any specific arguments conce rning the eligibility of claim 6. Appellant’s Br. 15. It was not incumbent on the district court to address arguments that Athena did not make. We thus find no error in the district court considering claims 7

– 9 as representative of claim 6. Even if we had reached the issue, we would hold claim 6 ineligible. T he specification describes ELISA as an “immunological assay technique[] known per se in the art.” ’820 patent col. 3 ll. 32

– 36. Claim 6 merely recites the application of this standard techniqueto observe a natural law. This does not provide an inventive concept under step two

. C ONCLUSION We have considered Athena’s remaining arguments but find them unpersuasive. Because claims 6

– 9 of the ’820 patent recite only a natural law together with conventional steps to detect that law, they are ineligible under § 101. For the foregoing reasons, we affirm the judgment of the district court.

AFFIRMED

# United States **Court of Appeals**  **for the Federal Circuit**

______________________ ATHENA DIAGNOSTICS, INC., OXFORD UNIVERSITY INNOVATIO N LTD., MAX

- PLANCK

GESELLSCHAFT ZUR FOR DERUNG DER WISSENSCHAFTEN E.V., Plaintiffs

- Appellants

v.

MAYO COLLABORATIVE S ERVICES, LLC, DBA MAYO MEDICAL LABORAT ORIES, MAYO CLINIC, Defendants

- Appellees

______________________

2017

- 2508

______________________ Appeal from the United States District Court for th e District of Massachusetts in No. 1:15

- cv

- 40075

- IT, Judge Indira Talwani.

______________________ N EWMAN , Circuit Judge, dissenting.

Until discovery of the diagnostic method described in U.S. Patent No. 7,267,820 (“the ’820 patent ”)

, some 20% of patients s uffering from the neurological disorder Myasthenia G ravis were not capable of being diagnosed

. My colleagues rule that this new diagnostic method is not patent

eligible, although new and unobvious. However, “[t]his new and improved technique, for producing a tangible anduseful result, falls squarely outside those categories of inventions that are ‘directed to’ patent

- ineligible concepts.” Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc. , 827 F.3d 1042,ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 2

1050 (Fed. Cir. 2016). The court again depart s from the cautious restraints in the Supreme Court’s Mayo / Alice application of laws of nature and abstract ideas.

Th is court’ s decisions on the patent

- in eligibility of diagnostic methods are not consistent, and my colleagues today enlarge the inconsistenc ies and exacerbate the judge

made disincentive s to development of new diagnostic methods , with no public benefit

. I respectfully dissent.
The claims are for a mul ti

- step method of diagnosis, not a law of nature
The ’820 inventors did not patent their scientific discovery of MuSK autoantibodies. Rather, they applied this discovery to create a new method of diagnosis, for a previously undiagnosable neurological condition. The district court summarized this new diagnostic method as follows:
For the 20% of Myasthenia Gravis patients who do not have the AChR [acetylcholine receptor] autoantibod ies, the ’ 820 patent inventors discovered that they had IgG [immunoglobulin G] anti bodies that attack the N

- terminal domains of muscle specific tyrosine kinase (“MuSK” ), a receptor that is located on the surface of neuromuscular junctions. . . . [A]radioactive label is attached to MuSK (or a fragment thereof) and is then introduced to a sample of bodily fluid. . . . [T]he MuSK auto antibodies, if present, attach to the labeled fragment

. . . [and] is immunoprecipitated , the presence of the radioactive label on any antibody indicates that the person is suf fering from Myasthenia Gravis.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 3

D ist

. Ct. Order, at 307

– 08 1 (citing ’82 0 patent, col. 1, ll. 55

– 61). The claims recite the method, including preparation of the new radioactive entities and their chemical reactions to detect autoantibodies to the protein muscle

- specific tyrosine kinase (MuSK). At issue are patent c laims 7

– 9, shown with claim 1 (not in suit) from which they depend:
1. A method for diagnosing neurotransmission or developmental disorders related to muscle specific tyrosine kinase (MuSK) in a mammal comprising the step of de tecting in a bodily fluid of said mammal autoantibodies to an epitope of muscle specific tyrosine kinase (MuSK).
7. A method according to claim 1, comprising

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

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

monitoring for said label on any of said antibody/MuSK complex or antibody/MuSK epitope or antig en determi nant complex,

wherein the presence of said label is indicative ofsaid mammal is suffering from said neurotransmission or developmental disorder related to muscle specific tyrosine kinase ( MuSK).
8. A method according to claim 7 wherein said la bel is a radioactive label.

1 Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC , 275 F. Supp. 3d 306 (D. Mass. 2017) (“Dist. Ct. Order”).ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 4

9. A method according to claim 8 wherein said label is 125I [iodine isotope 125].

The reaction between the antibody and the MuSK proteinwas not previously known, nor was it known to form a labeled MuSK or its epitope, nor to fo rm the antibody /MuSK complex, immunoprecipitate the complex, and monitor for radioactivity , thereby diagnos ing these previously undiagnosable neurotransmission disorders.

Claim s 7–9 require specific steps by which the diagnostic method is performed. The panel majority ignores these steps, and instead holds that “claims 7

– 9 are directed to a natural law because the claimed advance was only in the discovery of a natural law, and that the additional recited steps only apply conventional techniques to detect t hat n atural law.” Maj. Op. at 1 2. T his analysis of patent

- eligibility is incorrect, for the claim is for a multi

- step method of diagnosing neurotransmission disorders related to muscle specific tyrosine kinase

, by detecting autoantibodies using a series of chemical and biological steps as set forth in the claim s . Eligibility is determined for the claim considered as a whole

, including all its elements and l imitations. C laim limitations cannot be discarded when dete rmining eligibility under Section 101, a s explained in Diamond v. Diehr , 450 U.S. 175 (1981):
In determining the eligibility of respondents ’ claimed process for patent protection under § 101, their claims must be considered as a whole

. It is inapprop riate to dissect the claims into old and new elements and then to ignore the presence of the old elements in t he analysis.

Id. at 188 ; s ee Parker v. Flook , 437 U.S. 584, 594 (1978) (“ [A] patent claim must be considere d as a whole.”); see also Aro Mfg. Co. v. Convertible Top Replacement Co ., 365 U.S. 336, 344 (1961) (“ [I] f anything is settled in the patent law, it is that the combination patent covers only the totality of the elements in the claim and that no element, separatelyATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 5

viewed, is within t he grant .” ); Mercoid Corp. v. Minneapolis

- Honeywell Regulator Co ., 320 U.S. 680, 684 (1944) (“ [A] patent on a combination is a patent on the assembled or functioning whole, not on the separate parts.”).

The requirement that a claim is considered as a whole was not changed by the Ma yo/Alice protocol of search ing for an inventive concept within a claim that is directed to a law of nature or an abstract idea. It is incorrect to excise from the claims any step s that are performed by conventional procedures

. This is misconstruction of claims

, a nd misapplication of Section 101 . A s reiterated in Bilski v. Kappos , 561 U.S. 593 (2010) :Section 101 is a dynamic provision designed to encompass new and unforeseen inventions. A categorical rule denying patent protection for inventions in areas not contemplated by Congress

. . . would frustrate the purposes of the patent law.

Id. at 605 (internal citations and quotation marks omitted).
Applied to the ’820 patent, the claimed me thod is a new method of diagnosing Myasthenia G ra vis

. After eliminating the “conventional” procedures, my colleagues rule that this new method is a “ law of nature .” However, these inventors are not claiming the scientific fact of a newly described auto antibody ; they are claiming a new multi

- step diagnostic method

. This is not a law of na ture, but a man

made reaction sequence employing new components in a new combination to perform a new diagnostic procedure

. Section 101 describes patent

- eligible subjec t matter in broad and general terms
Section 101 does not exclude new methods of diagnosis of human ailments.
35 U.S.C. § 101 Inventions P atentable
Whoever invents or discovers any new and useful process, machine, manufacture, or composition ofATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 6

matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.

Section 101 recites the subject matter of patent law, as disti nguished from copyright law, which is also authorized by Article I

, Section 8

. This framework is “ cast in bro ad
terms ,” as the Court observed in Diamond v. Chakrabarty

, 447 U.S. 303 (1980):
The subject

- matter provisions of the patent lawhave been cast in broad terms to fulfill the constitutional and statutory goal of promoting “the Progress of Science and the useful Arts” with all thatmeans for the social and economic benefits envisioned by Jefferson. Broad general language is notnecessarily ambiguous when congressional objectives require broad terms.

Id. at 315.

Th e Court has often discussed the exceptions to patent eligibility , stating that : “P henomena of nature, though justdiscovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technologic al work.” Gottschalk v. Benson , 409 U.S. 63, 67 (1972). “Thus, a new mineral discovered in the earth or a new plant found in the wild is not patentable subject matter

. Likewise, Einstein could not patent his celebrated law that E=mc 2 ; nor could Newton h ave patented the law of gravity. Such discoveries are ‘manifestations of . . . nature, free to all men and reserved exclusively to none’

. ” Chakrabarty , 447 U.S. at 309 (quoting Funk Bros. Seed Co. v. Kalo Inoculant Co. , 333 U.S. 127, 130 (1948) )

. In Funk Brothers the Court explained:
The qualities of these bacteria, like the heat of the sun, electricity, or the qualities of metals, are part of the storehouse of knowledge of all men. They are manifestations of laws of nature, free to all menATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 7

and reserved exclusively to none. He who discovers a hitherto unknown phenomenon of nature has no claim to a monopoly of it which the law recognizes. If there is to be invention from such a disco very, it must come from the application of the law of nature to a new and useful end.

Id

. at 130.

T he C ourt early drew the d istinction between scientific knowledge and its technological application

. An oft

- cited example is the case of O’ Reilly v. Morse

, 56 U.S. 62 (15 How.) ( 185 4 ), where the Court declined patent

- eligibility of Morse’ s claim 8 to “ electro

- magnetism, however developed for ma r king or printing intelligible characters, signs, or letters, at any distance s ,” id. at 112

– 13
, but sustained Morse’ s claims to “ us [ ing ] [] the motive power of magnetism . . . as means of operating or giving motion to machinery

, whichmay be used to imprint signals . . . for the purpose of telegraphic communication at any distance s .” Id. at 8 5 ; see id. at 112

. The Court criticized the breadth of Morse’s claim 8 , and stated:
In fine he claims an exclusive right to use a manner and process which he has not described and indeed had not invented, and therefore could not describe when he obtained his patent.

Id. at 1 13 ; s ee Adam Mos s off, O’ Reilly v. Morse

, Georg e Mason Law & Econ. Research Pap er No. 14

- 22 (Aug. 18, 2014 )

, available at http://ssrn.com/abstract=2448363

. In Mackay Radio & Tel egraph Co. v. Radio Corp. of Am erica , 306 U.S. 86 (1939) , the C ourt explained that : “While a scientifictruth, or the mathematical expression of it, is not patentable invention, a novel and useful structure created with the aid of knowledge of scientific truth may be.” Id. at 94. These principles are the foundation of the truism t hat natural phenomena and abstract ideas are not patent

- eligible

.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 8

As science and its applications advanced, particularly in the new fields of digital electronics and biotechnology, the jurisprudence kept pace. I n Chakrabarty the Court considered a man

- made bacterium, and held that eligibility under Section 101 applies to “ anything under the sun that is made b y man.” 447 U.S. at 309

. The most recent Court updates are Mayo Collaborative Services v. Prometheus Lab oratories , Inc.

, 566 U.S. 66 (2012) (b iotechnology), and Alice Corp. Pty. Ltd. v. CLS Bank Int’ l

, 573 U.S. 2 08 (2014) (digital electronics)

. The Court reviewed Section 101 eligibility in these new fields

, building on the vast body of jurisprudence since the first patent was analyzed by Thomas Jefferson as Secretary of State in 1790

. See generally Ten Law Professors Br. ; 2 Five Life Sciences Patent Practitioners Br. 3 These amici curiae explain the policy concern for preemption of scientific principles, and apply this concern to the case at bar, advising that the scientific information of the new autoantibody and its protein reactivity is available to all , and that the ’820 patent claims 7

– 9 “ did not preempt any ‘law of nature’ upon wh ich the claim ed diagnostic method relied .” Five Life Sciences Patent Practitioners Br. at 1

. In Alice

, the Court summarized the procedural framework for eligibility for patenting:
First, we determine whether the claims at issue are directed to one of those patent

- ineligi ble concepts. 132 S. Ct., at 1296

– 1297. If so, we then ask, “[w]hat else is there in the claims before us?” 132

2 Amici Curiae Ten Law Professors, ECF No. 54 (Nov. 13, 2017) (“Ten Law Professors Br.”).

3 Amici Curiae Five Life Sciences Patent Practitioners, ECF No. 52 (Nov. 13, 2017) (“Five Life Sciences Patent Practitioners Br .”).ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 9

S. Ct., at 1297. To answer that question, we consider the elements of each claim both individually and “as an ordered combination” to determine whether the additional elements “transform the nature of the claim” into a patent

- eligible application

. 132 S. Ct., at 1298, 12 97.

Alice

, 573 U.S. at 217 (quoting Mayo)

. T his analysis comports with precedent, and the Court reiterated its caution that “too broad an interpretation of this exclusionary principle could eviscerate patent law. For all inventions at some level embody, use, reflect, restupon, or apply laws of nature, natural phenomena, or abstract ideas.” Mayo , 566 U.S. at 71; see Alice

, 573 U.S. at 217 (“At the same time, we tread carefully in construing this exclusionary principle lest it swallow all of patent law

. ”). We have echoed th is concern, stating in Rapid Litig ation Managemen t , 827 F.3d at 1050 , “[a] t step one, therefore, it is not enough to merely identify a patent

- ineligible concept underlying the claim; we must determine whether that patent

- ineligible co ncept is wha t the claim is ‘directed to

, ’” (quoting Alice , 573 U.S. at 217).

Th e panel majority departs from this guidance , for the claimed diagnostic method as a whole satisfies s tep one

. The majority does not distinguish between the question of whether the claimed method as a whole is eligible, and the question of whether the separate steps use conven tional procedures. Instead, my colleagues hold that since the separate p rocedures are convent ional, it is irrelevant that the method as a whole is a new method. The majority misconstrues the claims, in holding that claims 7

– 9 are directed
to the “ concept ” of “the correlation between the presence of naturally

- occurring MuSK autoantibodies in bodil y fluid and MuSK

- related neurological diseases like MG.” Maj. Op. at 9– 10. The claimed method determines whet her this correlation is present

, for diagnostic pur pose s , but the concept itself is not claimed

.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 10

It is incorrect to separate the claim steps into whether

a step is performed by conventional techniques, and then
to remo ve tho se steps from the claims and their “ conjunction with all of the other steps ” for the purpose of Section 101 analysis. Diehr

, 450 U.S. at 18 7 . All of the claim steps must be considered in the claimed combination

. “ It is inappropriate to dissect the cl aims into old and new elements and then to ignore the presence of the old elements in the analysis .” Id. at 188. T he Court explained that a new process may be a combination of known steps:

This is particularly true in a process claim becausea new combination of steps in a process may be patentable even though all the constituents of the combination were well known and in common use before the combination was made.

Id. The Court stated that: The “novelty” of any element or steps in a process, or even of the process itself, is of no relevance in determining whether the subject matter of a claimfalls within the § 101 categories of possibly patentable subject matter

. Id. at 18 8– 89. The Court again recognized this principle in KSR Int’ l Co. v. Teleflex Inc.

, 550 U.S. 398 (2007), stating that : [I] nventions in most, if not all, instances rely upon building blocks long since uncovered, and claimed discoveries almost of necessity will be combinations of what, in some sense, is already known.

Id. at 418

– 19. This court applied this principle in McRO, Inc. v. Ba ndai Namco Games Am erica Inc. , 837 F.3d 1299, 1313 (Fed. Cir. 2016) (internal quotation marks omitted) and cautioned that “ courts must be careful to avoid oversimplifying the claims by looking at them generally and failing to account for the specific requi rements of the claims”

— a caution disregarded today.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 11

The panel majority contravenes the requirements of precedent, now holding that all of the steps of claims 7 –9— that is, radioactive labelling, complexing, precipitating, and monitoring

— are removed from consideration in the Section 101 analysis because they use conven tional procedures ; the majority holds that “[t]he ’820 patent thus describes the claimed invention principally as a discovery of a natural law, not as an improvement in the underlying immunoa ssay technology.” Maj. Op. at 1 2. However, that is not the claimed invention

. I n Mayo

, 566 U.S. at 71, the Court cautioned that “too broad an interpretation of this exclusionary principle could eviscerate patent law . F or all inventions at some level em body, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas.”
Applying the Mayo/Alice protocol of two

- step claim analysis, claims 7

– 9 of the ’820 patent are patent

- eligible under Step 1, for this method of diagnosing Myasthenia G ravis is not a law of nature, but a man

- made chemical

biomedical procedure

. Claims 7

– 9 recite a combination of technologic steps
, all of which are limitations to the claims and cannot be disregarded whether for patentability or patent

- eligibility or infringement. The court today violates this rule, in holding t hat because “the

. . . individual steps . . . [ of] ‘[i] odination and immunoprecipitation are standard techniques in the art ,’ ” Maj. Op. at 6, these steps do not count under Section 101

. Id

. at 12

– 13.

Section 101 does not turn on whether any claim steps

are “ standard t echniques .” The appropriate analysis of the role of conventional process steps in claims to a new method is under S ections 102 and 103, not S ection 101.

The amici curiae raise strong concerns for the
consequences for biomedical diagnostic s
This court ’ s decisions have not been consistent. Today’s decision is not consistent with, for example, Rapid Litigation Management

, 827 F.3d at 1048, where the courtATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 12

held that although the general type of cell was known, and the manipulation of these specific cells w as conducted in a conventional manner, the overall method was eligible under Section 101

. A mici curiae point out that t he public interest i s poorly served b y adding disincentive to the development of new diagnostic methods. This is a severe criticism; and when presented by the entire industry, and stressed by thoughtful scholars, it warrants judicial attention.

The Biotec hnology In novation Organization 4 pleads for consistency in judge

- made law , citing the
unabated uncertainty about the patent

- eligibilityof many biotechnological inventions, with diagnostic and prognostic methods being particularly affected. The unstable state of patent

- eligibilityjurisprudence affects modern biotechnologies ranging from b iomarker- assisted methods of drug treatment to companion diagnostic tests, fermentation

p roducts, industrial enzyme technology, and marker

- assis ted methods of plant breeding.

BIO Br. at 1. I nternational concern s are presented by T he Chartered Institute of Patent Attorneys

, 5 an organization of the United Kingdom, stat ing that this decision conflicts with the eligibility of diagnostic methods under the Patent Cooperation Treaty and the European Patent Con vention, and is inconsistent wi th the obligations of the United States under Article 27 and Note 5 of the Agreement on Trade

- Related Aspects of Intellectual Property Rights

4 Amicus Curiae Biotechnology Innovation Organization, ECF No. 53 (Nov. 13, 2017) (“BIO Br.”).

5 Amicus Curiae The Chartered Institute of Patent Attorneys, ECF No. 51 (Nov. 13, 2017) (“CIPA Br.”).ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 13

(TRIPS) administered by the World Trade Organization. CIPA Br . a t 2.

A mici curiae Five Life Sciences Paten t Practitioners point out that “ The S upr eme C ourt has recognized that patent ineligibility de t erminations (by courts or the Patent Office) have the potential to inhibit innovation ,” Five Life Sciences Patent Practitioners Br. at 6 (citing Bilski v. Kappos , 5 61 U.S. 593, 605 (2010)). They state concerns of the inventing/investing communities with respect to the future of diagnostic s, because “[ medical ] diagnostic methods . . .are so tightly bound to underlying natural laws and phenomen[a] , they are especiall y susceptible to undue expansion of the eligibility standar ds implemented to protect the judicial exceptions as they have been explicated by the S upreme Court.” Id. a t 6

– 7.

A mici curiae Ten Law Professors direct us to the cost to develop and commercialize a new diagnostic

, reported as $50

- 100 million, see Ten Law Professors Br. at 18

– 19 ( citing Diaceutics Group, Mystery Solved! What is the Cost to Develop and Launch a Diagnostic? (2013) , available at https://www.diaceutics.com/?expert

- insight=mystery

solve d- what

- is

- the

- cost

- to -develop- and

- launch -a- diagnostic )

. Undoubtedly there are a variety of interests in diagnostic procedures , and we take not e that a micus curiae A RUP Laboratories 6 states that diagnostic tests should not be patentable at all

. See general ly ARUP Br. However, for procedures that require extensive development and federal approval, unpredictability of patent support is a

6 Amicus Curiae ARUP Laboratories, ECF No. 76 (Feb. 6, 2018) (“ARUP Br.”)

.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 14

disincentive to development of new diagnostic methods. 7 The loser is the afflicted public , for diagnostic methods that

are not developed benefit no one. 8
The judicial obligation is to provide stable, consistent application of statute and precedent , to implement the legislative purpose. With all respect to my colleagues on this panel, they misapply precedent and misin terpret the statute , adding discrepancies and disincentives to this important area of biomedicine

. Claims 7

– 9 meet the Section 101 eligibility rules, for the claims are to a new and useful method.
Applying the statute correctly, diagnostic claims should be evaluated for novelty and unobviousness, specificity and enablement. A method that meets these statutory criteria is w i thin the system of patents, whether the diagnosed event occurs in the human body or in an

7 This court has invalidated patents on new diagnostic methods in Roche Molecular Sys.

, Inc. v. CEPHEID , 905 F.3d 1363, 1374 (Fed. Cir. 2018); Cleveland Clinic Found. v. True Health Diagnostics LLC , 859 F.3d 1352, 1363 (Fed. Cir. 2017); Genetic Techs. Ltd. v. Merial L.L.C. , 818 F.3d 1369, 1380 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc. , 788 F.3d 1371, 1378 (Fed. Cir. 2015); In re BRCA1 - & BRCA2

- Based Hereditary Cancer Test Paten t Litig. , 774 F.3d 755, 765 (Fed. Cir. 2014).

8 It is estimated that 66% of all medical treatment decisions are based on the results of in vitro diagnostic testing. U lrich -Peter Roh r, et al., Th e V al ue of In V itro D iagnostic Testing in M edical Practice: A Status R eport , 11 PL oS O ne 1, 2, 11, 13 (2016),https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778800/pdf/pone.0149856.pdf

. See Ten Law Professors Br. at 18.ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES 15

extra n eous device. From my co ll ea gues’ co ntrary conclusion

, I respectfully dissent

.