Court Opinion

ID: 4365062
Source: CourtListenerOpinion
Date Created: 2019-02-06 17:00:38.620742+00
Date Added: 2024-06-11T14:49:19.574744
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
                 ______________________

    ATHENA DIAGNOSTICS, INC., OXFORD
 UNIVERSITY INNOVATION LTD., MAX-PLANCK-
    GESELLSCHAFT ZUR FORDERUNG DER
          WISSENSCHAFTEN E.V.,
             Plaintiffs-Appellants

                            v.

 MAYO COLLABORATIVE SERVICES, LLC, DBA
MAYO MEDICAL LABORATORIES, MAYO CLINIC,
           Defendants-Appellees
          ______________________

                       2017-2508
                 ______________________

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

               Decided: February 6, 2019
                ______________________

   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
2      ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

Diego, CA, argued for defendants-appellees. Also repre-
sented by JOHN CAMERON ADKISSON, ELIZABETH M.
FLANAGAN, PHILLIP GOTER, DEANNA JEAN REICHEL, Minne-
apolis, 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 Organi-
zation, Washington, DC, for amicus curiae Biotechnology
Innovation Organization. Also represented by HANSJORG
SAUER; BRIAN PAUL BARRETT, Eli Lilly and Company, Indi-
anapolis, IN.

    MATTHEW JAMES DOWD, Dowd Scheffel PLLC, Wash-
ington, DC, for amici curiae Dan L. Burk, Richard A. Ep-
stein, 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 La-
boratories, Inc. Also represented by BRIAN C. CANNON,
Redwood Shores, CA.
                 ______________________

    Before NEWMAN, LOURIE, and STOLL, Circuit Judges.
    Opinion for the court filed by Circuit Judge LOURIE.
    Dissenting opinion filed by Circuit Judge NEWMAN.
ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES          3

LOURIE, Circuit Judge.
     Athena Diagnostics, Inc., Oxford University Innova-
tion 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 Collabora-
tive Servs., LLC, 275 F. Supp. 3d 306 (D. Mass. 2017) (“De-
cision”). 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 dis-
orders 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 con-
cerns 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 dis-
covered that MG is an autoimmune disease caused by a
4       ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

patient generating antibodies against her own acetylcho-
line receptors. Id. col. 1 ll. 24–26. Antibodies which recog-
nize 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 au-
toantibodies 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 au-
toantibodies and MG, the inventors of the ’820 patent dis-
closed 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 bod-
    ily 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 determi-
nant, 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 dis-
closed 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 deter-
    minant thereof having a suitable label thereon,
    with said bodily fluid,
    immunoprecipitating any antibody/MuSK complex
    or antibody/MuSK epitope or antigenic determi-
    nant complex from said bodily fluid and
    monitoring for said label on any of said anti-
    body/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 neurotransmis-
    sion or developmental disorder related to [MuSK].
Id. col. 12 l. 62–col. 13 l. 5 (spacing added). Claim 8 de-
pends from claim 7 and recites that the label is a radioac-
tive 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 anti-
body/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 en-
tail. 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 immunoprecipi-
tated by adding a secondary antibody that binds to any
6       ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

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 immunoprecipita-
tion 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 radioimmuno-
assays. Id. col. 3 ll. 33–37. With respect to the relevant
individual steps in the radioimmunoassay, the specifica-
tion also discloses that “[i]odination and immunoprecipita-
tion are standard techniques in the art.” Id. col. 4 ll. 10–
11.
    Claim 6 is additionally at issue in this appeal and de-
pends 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 label-
ing MuSK with a radioisotope, claim 3 recites that the sec-
ondary antibody is “tagged or labeled with a reporter
molecule.” Id. col. 12 ll. 47–49. Claim 6 additionally re-
quires 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.

    2    ELISA stands for enzyme-linked 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 for subject matter eligibility es-
tablished by the Supreme Court in Mayo Collaborative Ser-
vices 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 di-
rected to a law of nature, Decision, 275 F. Supp. 3d at 312.
According to the court, the claims focused on the interac-
tion 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 ju-
risdiction 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 dis-
missals de novo, accepts all well-pleaded facts alleged in
the complaint to be true, and draws all reasonable infer-
ences in favor of the non-movant. In re Loestrin 24 Fe An-
titrust Litig., 814 F.3d 538, 549 (1st Cir. 2016). Patent
eligibility under § 101 is a question of law based on under-
lying facts, see Aatrix Software, Inc. v. Green Shades Soft-
ware, 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).
8      ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

    Section 101 provides that “[w]hoever invents or discov-
ers 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 condi-
tions and requirements of this title.” 35 U.S.C. § 101.
Given the expansive terms of § 101, “Congress plainly con-
templated that the patent laws would be given wide scope”;
some of the legislative history likewise indicated that “Con-
gress intended statutory subject matter to ‘include any-
thing 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 excep-
tion. ‘[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 innova-
tion more than it would tend to promote it.” Id. at 71. How-
ever, 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 statu-
tory 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 na-
ture 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
ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES           9

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 “en-
sure 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, spe-
cific, 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 immunoas-
say techniques that still leave the claim directed to a natu-
ral 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-oc-
curring MuSK autoantibodies in bodily fluid and MuSK-
10       ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

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 ab-
stract 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 con-
cept.” 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 fre-
quently considered whether the claimed advance improves
upon a technological process or merely an ineligible con-
cept, 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.

     3   We note that the district court held that the “focus
of the claims” was the binding of MuSK to MuSK antibod-
ies in bodily fluid. Decision, 275 F. Supp. 3d at 310. Our
cases have not described a claim to the binding of two mol-
ecules 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 accord-
ing to natural 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 inven-
tors 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 be-
cause 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 bi-
ological 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 indi-
cated that the claimed inventors discovered a natural cor-
relation 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 cardio-
vascular disease. Id. at 1361. As the claims only covered
the correlation between MPO and cardiovascular disease,
an ineligible discovery, together with “well-known tech-
niques to execute the claimed method,” we held that the
claims were directed to a natural law. Id.
12     ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

     The claims at issue here involve both the discovery of a
natural law and certain concrete steps to observe its oper-
ation. Claim 9, the most specific claim at issue, recites the
following method to detect MuSK autoantibodies: (1) mix-
ing MuSK or an epitope thereof having a 125I label with
bodily fluid; (2) immunoprecipitating any resulting anti-
body/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 autoantibod-
ies naturally present in a patient sample, detected with the
125I label bound to the MuSK/antibody complex, indicate
that the patient is suffering from a MuSK-related neuro-
logical disorder. Id. col. 13 ll. 2–5.
     As 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 additional recited steps only apply conven-
tional techniques to detect that natural law. The specifica-
tion of the ’820 patent highlights the discovery of the
natural law, explaining that “[t]he present inventors sur-
prisingly found that many of the 20% of MG patients [who]
do not exhibit any autoantibodies to [the acetylcholine re-
ceptor], instead have . . . antibodies directed against the ex-
tracellular [amino]-terminal domains of MuSK.” Id. col. 1
ll. 54–57. Further, the specification describes the claimed
concrete steps for observing the natural law as conven-
tional. It teaches that “[t]he actual steps of detecting auto-
antibodies in a sample of bodily fluids may be performed in
accordance with immunological assay techniques known
per se in the art,” including 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. The
’820 patent thus describes the claimed invention princi-
pally as a discovery of a natural law, not as an improve-
ment 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 directed to an innovative laboratory
technique, not a law of nature. However, Athena does not
point to any innovation other than its discovery of the nat-
ural 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 ineligi-
ble claims that “amounted to nothing more than observing
or identifying the ineligible concept itself.” 827 F.3d at
1048. In that case, we concluded that the “end result” of
the claims at issue was “not simply an observation or de-
tection” 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 steps.” Cleveland
Clinic, 859 F.3d at 1361.
    Athena also points to the specificity of the claimed con-
crete steps, contending that they preempt no natural law
and therefore the claims cannot be directed to a natural
law. Although we agree that claim 9 leaves open to the
public other ways of interrogating the correlation between
MuSK autoantibodies and MuSK-related disorders with-
out practicing the claim’s concrete steps, that does not dis-
turb our conclusion at step one. Preemption is sufficient to
render a claim ineligible under § 101, but it is not neces-
sary. 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 tech-
niques for observing it. That the routine steps are set forth
with some specificity is not enough to change that conclu-
sion.
14     ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

    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 Mayo argues, the use of
a man-made molecule is not decisive if it amounts to only
a routine step in a conventional method for observing a nat-
ural law. For example, Mayo involved claims requiring ad-
ministering 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 binds to DNA, 788 F.3d at 1374.
And the claims in BRCA1 also involved hybridizing a syn-
thetic DNA probe to a DNA strand. BRCA1, 774 F.3d at
763–64. Nonetheless, in each of these cases either the Su-
preme Court or this court held the claims directed to a nat-
ural 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 consider it important at this point to note the dif-
ference 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 natu-
ral law itself. But claiming a new treatment 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 natu-
ral 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 individually and ‘as an ordered combination’ to deter-
mine whether the additional elements ‘transform the na-
ture 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 pa-
tent protection to novel and non-obvious diagnostic meth-
ods would promote the progress of science and useful arts.
But, whether or not we as individual judges might agree or
not that these claims only recite a natural law, cf. Berk-
heimer v. HP Inc., 890 F.3d 1369, 1374 (Fed. Cir. 2018)
(Lourie, J., concurring in the denial of rehearing 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 cor-
relations between the presence of a biological material and
a disease are laws of nature, see 566 U.S. at 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 some-
what specific yet conventional techniques (such as the pol-
ymerase chain reaction) to detect a newly discovered
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 dif-
ferent outcome here.
16     ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES
573 U.S. at 217 (quoting Mayo, 566 U.S. at 78, 79). “Purely
‘conventional or obvious’ ‘[pre]-solution activity’ is nor-
mally 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) (quot-
ing Flook, 437 U.S. at 590). The transformative “inventive
concept” supplied by the claim elements not drawn to inel-
igible subject matter must be “sufficient to ensure that the
patent in practice amounts to significantly more than a pa-
tent upon the [ineligible concept] 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 auto-
antibodies. 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 con-
cept because the specification describes the steps for de-
tecting 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 ineligible subject matter, whether viewed individ-
ually or as an ordered combination, only require standard
techniques to be applied in a standard way. As previously
discussed, the specification of the ’820 patent plainly 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. ’820 patent col. 3 ll. 33–
37. Iodination and immunoprecipitation are likewise de-
scribed as standard techniques. Id. col. 4 ll. 9–12. Because
the specification defines the individual immunoprecipita-
tion    and     iodination    steps     and     the    overall
ATHENA 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 con-
sistent with the principle that applying standard tech-
niques in a standard way to observe a natural 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
only 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 combina-
tion 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, claims 7–9 of the ’820 patent em-
ploy a conventional technique for detecting autoantibodies,
a radioimmunoassay, which the specification acknowl-
edges was “known per se in the art.” ’820 patent col. 3 ll.
33–37. The individual constituent steps of that technique,
iodination and immunoprecipitation, are similarly de-
scribed as standard. Id. col. 4 ll. 9–12. Thus, unlike the
claimed limitations at issue in CellzDirect and BASCOM,
the recited steps here were conventional both as an ordered
combination and individually.
      Athena also argues that the claimed steps were uncon-
ventional 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 stand-
ard techniques in a standard way to observe a newly dis-
covered 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 nature
18     ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

. . . itself.” Genetic Techs. Ltd. v. Merial L.L.C., 818 F.3d
1369, 1376 (Fed. Cir. 2016); see Mayo, 566 U.S. at 73 (con-
sidering whether the “claimed processes (apart from the
natural laws themselves)” were routine and conventional).
Rather, to supply an inventive concept the sequence of
claimed steps must do more than adapt a conventional as-
say to a newly 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 appli-
cation, they do not provide an inventive concept.
    Similar to its step one argument, Athena further ar-
gues 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 to the com-
position 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 reasons 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 specifica-
tion 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 before resolving the § 101 issue. But,
unlike 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 opposi-
tion to Mayo’s motion to dismiss, asserting that iodination
ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES          19

and immunoprecipitation were not routine as applied to
the claimed invention. 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 are
part of or incorporated into the complaint; if matters out-
side the pleadings are considered, the motion must be de-
cided under the more stringent standards applicable to a
Rule 56 motion for summary judgment.” Trans-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 dependent 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 ma-
terials submitted with the motion papers and determine
the motion under the Rule 12(b)(6) standard, no conversion
occurs and 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 its
discretion in declining to consider Athena’s expert declara-
tion and convert the motion into one for summary judg-
ment. 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, an-
other type of document a court may consider with the
pleadings. See Watterson v. Page, 987 F.2d 1, 3–4 (1st Cir.
1993).
20     ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

    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 without support in responding to a motion to dismiss
as long as those facts are consistent with the complaint, see
Early v. Bankers Life & Casualty Co., 959 F.2d 75, 79 (7th
Cir. 1992), and that its expert declaration alleged such con-
sistent facts that create a dispute of material fact.
     Even assuming this general principle applies in the
First Circuit—an assumption that Athena meagerly sup-
ports—the district court did not need to consider the alle-
gations in the expert declaration because they were not
consistent with the complaint read in light of the ’820 pa-
tent. These technical allegations include: (1) that detect-
ing 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. None 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 respect to im-
munoprecipitation. Those omissions are consistent with
the specification’s description of iodination, immunoprecip-
itation, and the overall radioimmunoassay as standard
techniques. Because Athena’s expert declaration made al-
legations inconsistent with 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 autoanti-
bodies different from claims 7–9. While claims 7–9 recite
ATHENA 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 tech-
nical difference pertinent to this appeal between an ELISA
and a radioimmunoassay is that in an ELISA, the second-
ary antibody rather than the antigen is labeled.
     Athena argues that since the district court did not spe-
cifically analyze claim 6, which involves a different tech-
nology, 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 them together,
and that Athena waived any separate arguments regard-
ing claim 6 by not specifically addressing that claim in its
briefing.
    During the district court proceedings, Athena repre-
sented that it would not assert claims 1–5 and 10–12, and
Mayo then moved to dismiss Athena’s complaint, specifi-
cally 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 argu-
ments pertaining to claims 7–9 were also applicable to
claim 6. See J.A. 180 (“While the claim does not require
radioactive MuSK or complexes, many other arguments re-
lating to claims 7-9 apply to claim 6.”). The district court
did not address claim 6 in its order beyond listing it among
the other claims. Decision, 275 F. Supp. 3d at 309–10.
    Given this history, we 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. Kara-
van Trailers, Inc., 175 F.3d 1356, 1359 (Fed. Cir. 1999) (en
banc in relevant part)). In the First Circuit, an argument
22     ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

may be deemed waived that was not presented to the dis-
trict 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 spe-
cific arguments concerning the eligibility of claim 6. Ap-
pellant’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 is-
sue, we would hold claim 6 ineligible. The specification de-
scribes 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 technique
to observe a natural law. This does not provide an in-
ventive concept under step two.
                       CONCLUSION
    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 INNOVATION LTD., MAX-PLANCK-
    GESELLSCHAFT ZUR FORDERUNG DER
          WISSENSCHAFTEN E.V.,
             Plaintiffs-Appellants

                             v.

 MAYO COLLABORATIVE SERVICES, LLC, DBA
MAYO MEDICAL LABORATORIES, MAYO CLINIC,
           Defendants-Appellees
          ______________________

                        2017-2508
                  ______________________

    Appeal from the United States District Court for the
District of Massachusetts in No. 1:15-cv-40075-IT, Judge
Indira Talwani.
                 ______________________
NEWMAN, 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 suffering from the neurological disorder Myasthe-
nia Gravis were not capable of being diagnosed. My col-
leagues 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 and
useful result, falls squarely outside those categories of in-
ventions that are ‘directed to’ patent-ineligible concepts.”
Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042,
2      ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

1050 (Fed. Cir. 2016). The court again departs from the
cautious restraints in the Supreme Court’s Mayo/Alice ap-
plication of laws of nature and abstract ideas.
    This court’s decisions on the patent-ineligibility of di-
agnostic methods are not consistent, and my colleagues to-
day enlarge the inconsistencies and exacerbate the judge-
made disincentives to development of new diagnostic meth-
ods, with no public benefit. I respectfully dissent.
    The claims are for a multi-step method of di-
    agnosis, not a law of nature
    The ’820 inventors did not patent their scientific dis-
covery of MuSK autoantibodies. Rather, they applied this
discovery to create a new method of diagnosis, for a previ-
ously 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] autoan-
    tibodies, the ’820 patent inventors discovered that
    they had IgG [immunoglobulin G] antibodies 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 frag-
    ment thereof) and is then introduced to a sample of
    bodily fluid. . . . [T]he MuSK autoantibodies, if pre-
    sent, attach to the labeled fragment . . . [and] is im-
    munoprecipitated, the presence of the radioactive
    label on any antibody indicates that the person is
    suffering from Myasthenia Gravis.
ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES              3

Dist. Ct. Order, at 307–08 1 (citing ’820 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 ty-
rosine kinase (MuSK). At issue are patent claims 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 detecting in a bodily fluid of said mam-
    mal 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 deter-
    minant thereof having a suitable label thereon,
    with said bodily fluid,
     immunoprecipitating any antibody/MuSK com-
    plex or antibody/MuSK epitope or antigenic deter-
    minant complex from said bodily fluid and
     monitoring for said label on any of said anti-
    body/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 neurotransmis-
    sion or developmental disorder related to muscle
    specific tyrosine kinase (MuSK).
    8. A method according to claim 7 wherein said label
    is a radioactive label.

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

    9. A method according to claim 8 wherein said label
    is 125I [iodine isotope 125].
The reaction between the antibody and the MuSK protein
was not previously known, nor was it known to form a la-
beled MuSK or its epitope, nor to form the antibody/MuSK
complex, immunoprecipitate the complex, and monitor for
radioactivity, thereby diagnosing these previously undiag-
nosable neurotransmission disorders.
     Claims 7–9 require specific steps by which the diagnos-
tic 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 that nat-
ural law.” Maj. Op. at 12. This analysis of patent-eligibil-
ity 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
claims. Eligibility is determined for the claim considered
as a whole, including all its elements and limitations.
Claim limitations cannot be discarded when determining
eligibility under Section 101, as 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
    inappropriate to dissect the claims into old and new
    elements and then to ignore the presence of the old
    elements in the analysis.
Id. at 188; see Parker v. Flook, 437 U.S. 584, 594 (1978)
(“[A] patent claim must be considered 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, separately
ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES           5

viewed, is within the grant.”); Mercoid Corp. v. Minneap-
olis-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 Mayo/Alice protocol of searching
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 steps that are performed by conven-
tional procedures. This is misconstruction of claims, and
misapplication of Section 101. As reiterated in Bilski v.
Kappos, 561 U.S. 593 (2010):
    Section 101 is a dynamic provision designed to en-
    compass new and unforeseen inventions. A cate-
    gorical 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 method is a new
method of diagnosing Myasthenia Gravis. After eliminat-
ing the “conventional” procedures, my colleagues rule that
this new method is a “law of nature.” However, these in-
ventors are not claiming the scientific fact of a newly de-
scribed autoantibody; they are claiming a new multi-step
diagnostic method. This is not a law of nature, but a man-
made reaction sequence employing new components in a
new combination to perform a new diagnostic procedure.
    Section 101 describes patent-eligible subject
    matter in broad and general terms
    Section 101 does not exclude new methods of diagnosis
of human ailments.
    35 U.S.C. § 101 Inventions Patentable
    Whoever invents or discovers any new and useful
    process, machine, manufacture, or composition of
6      ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

    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 dis-
tinguished from copyright law, which is also authorized by
Article I, Section 8. This framework is “cast in broad
terms,” as the Court observed in Diamond v. Chakrabarty,
447 U.S. 303 (1980):
    The subject-matter provisions of the patent law
    have been cast in broad terms to fulfill the consti-
    tutional and statutory goal of promoting “the Pro-
    gress of Science and the useful Arts” with all that
    means for the social and economic benefits envi-
    sioned by Jefferson. Broad general language is not
    necessarily ambiguous when congressional objec-
    tives require broad terms.
Id. at 315.
     The Court has often discussed the exceptions to patent
eligibility, stating that: “Phenomena of nature, though just
discovered, mental processes, and abstract intellectual con-
cepts are not patentable, as they are the basic tools of sci-
entific and technological 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 cel-
ebrated law that E=mc2; nor could Newton have 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 men
ATHENA 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 discovery, it
    must come from the application of the law of nature
    to a new and useful end.
Id. at 130.
    The Court early drew the distinction 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.) (1854), where the Court declined patent-eligibility of
Morse’s claim 8 to “electro-magnetism, however developed
for marking or printing intelligible characters, signs, or let-
ters, at any distances,” 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, which
may be used to imprint signals . . . for the purpose of tele-
graphic communication at any distances.” Id. at 85; 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 113; see Adam Mossoff, O’Reilly v. Morse, George Ma-
son Law & Econ. Research Paper No. 14-22 (Aug. 18, 2014),
available at http://ssrn.com/abstract=2448363. In Mackay
Radio & Telegraph Co. v. Radio Corp. of America, 306 U.S.
86 (1939), the Court explained that: “While a scientific
truth, or the mathematical expression of it, is not patenta-
ble 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 that nat-
ural phenomena and abstract ideas are not patent-eligible.
8       ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

    As science and its applications advanced, particularly
in the new fields of digital electronics and biotechnology,
the jurisprudence kept pace. In Chakrabarty the Court
considered a man-made bacterium, and held that eligibility
under Section 101 applies to “anything under the sun that
is made by man.” 447 U.S. at 309.
    The most recent Court updates are Mayo Collaborative
Services v. Prometheus Laboratories, Inc., 566 U.S. 66
(2012) (biotechnology), and Alice Corp. Pty. Ltd. v. CLS
Bank Int’l, 573 U.S. 208 (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 prin-
ciples, 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
which the claimed diagnostic method relied.” Five Life Sci-
ences Patent Practitioners Br. at 1.
   In Alice, the Court summarized the procedural frame-
work for eligibility for patenting:
    First, we determine whether the claims at issue are
    directed to one of those patent-ineligible 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 Practition-
ers, 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 con-
    sider 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 applica-
    tion. 132 S. Ct., at 1298, 1297.
Alice, 573 U.S. at 217 (quoting Mayo).
     This 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, rest
upon, or apply laws of nature, natural phenomena, or ab-
stract 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 this concern, stating in Rapid Lit-
igation Management, 827 F.3d at 1050, “[a]t step one,
therefore, it is not enough to merely identify a patent-inel-
igible concept underlying the claim; we must determine
whether that patent-ineligible concept is what the claim is
‘directed to,’” (quoting Alice, 573 U.S. at 217).
    The panel majority departs from this guidance, for the
claimed diagnostic method as a whole satisfies step 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 conventional
procedures. Instead, my colleagues hold that since the sep-
arate procedures are conventional, it is irrelevant that the
method as a whole is a new method. The majority miscon-
strues 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 bodily fluid
and MuSK-related neurological diseases like MG.” Maj.
Op. at 9–10. The claimed method determines whether this
correlation is present, for diagnostic purposes, but the con-
cept itself is not claimed.
10      ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

    It is incorrect to separate the claim steps into whether
a step is performed by conventional techniques, and then
to remove those steps from the claims and their “conjunc-
tion with all of the other steps” for the purpose of Section
101 analysis. Diehr, 450 U.S. at 187. All of the claim steps
must be considered in the claimed combination. “It is in-
appropriate to dissect the claims into old and new elements
and then to ignore the presence of the old elements in the
analysis.” Id. at 188. The Court explained that a new pro-
cess may be a combination of known steps:
     This is particularly true in a process claim because
     a new combination of steps in a process may be pa-
     tentable 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 claim
     falls within the § 101 categories of possibly patent-
     able subject matter.
Id. at 188–89. 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. Bandai Namco Games America Inc., 837 F.3d 1299,
1313 (Fed. Cir. 2016) (internal quotation marks omitted)
and cautioned that “courts must be careful to avoid over-
simplifying the claims by looking at them generally and
failing to account for the specific requirements 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 conventional proce-
dures; the majority holds that “[t]he ’820 patent thus de-
scribes the claimed invention principally as a discovery of
a natural law, not as an improvement in the underlying
immunoassay technology.” Maj. Op. at 12. However, that
is not the claimed invention. In Mayo, 566 U.S. at 71, the
Court cautioned that “too broad an interpretation of this
exclusionary principle could eviscerate patent law. For all
inventions at some level embody, 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
Gravis 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 pa-
tent-eligibility or infringement. The court today violates
this rule, in holding that 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 techniques.” The appropriate analysis of the
role of conventional process steps in claims to a new
method is under Sections 102 and 103, not Section 101.
    The amici curiae raise strong concerns for the
    consequences for biomedical diagnostics
    This court’s decisions have not been consistent. To-
day’s decision is not consistent with, for example, Rapid
Litigation Management, 827 F.3d at 1048, where the court
12       ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

held that although the general type of cell was known, and
the manipulation of these specific cells was conducted in a
conventional manner, the overall method was eligible un-
der Section 101.
     Amici curiae point out that the public interest is poorly
served by adding disincentive to the development of new
diagnostic methods. This is a severe criticism; and when
presented by the entire industry, and stressed by thought-
ful scholars, it warrants judicial attention.
    The Biotechnology Innovation Organization 4 pleads for
consistency in judge-made law, citing the
     unabated uncertainty about the patent-eligibility
     of many biotechnological inventions, with diagnos-
     tic and prognostic methods being particularly af-
     fected. The unstable state of patent-eligibility
     jurisprudence affects modern biotechnologies rang-
     ing from biomarker-assisted methods of drug treat-
     ment to companion diagnostic tests, fermentation
     products, industrial enzyme technology, and
     marker-assisted methods of plant breeding.
BIO Br. at 1. International concerns are presented by The
Chartered Institute of Patent Attorneys, 5 an organization
of the United Kingdom, stating that this decision conflicts
with the eligibility of diagnostic methods under the Patent
Cooperation Treaty and the European Patent Convention,
and is inconsistent with 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 Organi-
zation, 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. at 2.
    Amici curiae Five Life Sciences Patent Practitioners
point out that “The Supreme Court has recognized that pa-
tent ineligibility determinations (by courts or the Patent
Office) have the potential to inhibit innovation,” Five Life
Sciences Patent Practitioners Br. at 6 (citing Bilski v. Kap-
pos, 561 U.S. 593, 605 (2010)). They state concerns of the
inventing/investing communities with respect to the future
of diagnostics, because “[medical] diagnostic methods . . .
are so tightly bound to underlying natural laws and phe-
nomen[a], they are especially susceptible to undue expan-
sion of the eligibility standards implemented to protect the
judicial exceptions as they have been explicated by the Su-
preme Court.” Id. at 6–7.
      Amici 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 (cit-
ing Diaceutics Group, Mystery Solved! What is the Cost to
Develop and Launch a Diagnostic? (2013), available at
https://www.diaceutics.com/?expert-insight=mystery-
solved-what-is-the-cost-to-develop-and-launch-a-diagnos-
tic).
     Undoubtedly there are a variety of interests in diagnos-
tic procedures, and we take note that amicus curiae ARUP
Laboratories6 states that diagnostic tests should not be pa-
tentable at all. See generally ARUP Br. However, for pro-
cedures 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.”).
14       ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES

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 leg-
islative purpose. With all respect to my colleagues on this
panel, they misapply precedent and misinterpret the stat-
ute, adding discrepancies and disincentives to this im-
portant 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, speci-
ficity and enablement. A method that meets these statu-
tory criteria is within the system of patents, whether the
diagnosed event occurs in the human body or in an

     7   This court has invalidated patents on new diagnos-
tic 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. Se-
quenom, Inc., 788 F.3d 1371, 1378 (Fed. Cir. 2015); In re
BRCA1- & BRCA2-Based Hereditary Cancer Test Patent
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 test-
ing. Ulrich-Peter Rohr, et al., The Value of In Vitro
Diagnostic Testing in Medical Practice: A Status Report, 11
PLoS        One       1,     2,      11,       13      (2016),
https://www.ncbi.nlm.nih.gov/pmc/arti-
cles/PMC4778800/pdf/pone.0149856.pdf. See Ten Law
Professors Br. at 18.
ATHENA DIAGNOSTICS v. MAYO COLLABORATIVE SERVICES   15

extraneous device. From my colleagues’ contrary conclu-
sion, I respectfully dissent.