ATHENA DIAGNOSTICS, INC., OXFORD UNIVERSITY INNOVATION LTD., MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN E. V., Plaintiffs-Appellants
MAYO COLLABORATIVE SERVICES, LLC, DBA MAYO MEDICAL LABORATORIES, MAYO CLINIC, Defendants-Appellees
from the United States District Court for the District of
Massachusetts in No. 1:15-cv-40075-IT, Judge Indira Talwani.
Gahtan, Fenwick & West LLP, New York, NY, argued for
plaintiffs-appellants. Also represented by Eric M. Majchrzak,
Vanessa Park-Thompson; Andrew Joseph Kabat, Emmett J.
McMahon, Robins Kaplan LLP, Minneapolis, MN; Dimitrios T.
Drivas, White & Case LLP, New York, NY.
Jonathan Elliot Singer, Fish & Richardson, PC, San Diego,
CA, argued for defendants-appellees. Also represented by John
Cameron Adkisson, Elizabeth M. Flanagan, Phillip Goter,
Deanna Jean Reichel, Minneapolis, MN.
Barkoff, McAndrews, Held & Malloy, Ltd., Chicago, IL, for
amicus curiae The Chartered Institute of Patent Attorneys.
Edward Noonan, McDonnell, Boehnen, Hulbert & Berghoff,
LLP, Chicago, IL, for amicus curiae Five Life Sciences Patent
Practitioners. Also represented by John Dominic Cravero,
Aaron Vincent Gin, Michael S. Greenfield, Andrea Kay Orth.
Melissa A. Brand, Biotechnology Innovation Organization,
Washington, DC, for amicus curiae Biotechnology Innovation
Organization. Also represented by Hansjorg Sauer; Brian Paul
Barrett, Eli Lilly and Company, Indianapolis, IN.
Matthew James Dowd, Dowd Scheffel PLLC, Washington, DC, for
amici curiae Dan L. Burk, Richard A. Epstein, Christopher
Michael Holman, Gus Hurwitz, Adam Mossoff, Kristen J. Osenga,
Michael Risch, Mark F. Schultz, Ted M. Sichelman, Brenda M.
Kathleen M. Sullivan, Quinn Emanuel Urquhart & Sullivan,
LLP, New York, NY, for amicus curiae ARUP Laboratories, Inc.
Also represented by Brian C. Cannon, Redwood Shores, CA.
Newman, Lourie, and Stoll, Circuit Judges.
LOURIE, CIRCUIT JUDGE.
Diagnostics, Inc., Oxford University Innovation Ltd., and the
Max-Planck-Gesellschaft zur Forderung der Wissenschaften E.V.
(collectively, "Athena") appeal from the order of
the United States District Court for the District of
Massachusetts holding that claims 6-9 of U.S. Patent 7, 267,
820 (the "'820 patent") are invalid under 35
U.S.C. § 101 and dismissing Athena's complaint under
Rule 12(b)(6). Athena Diagnostics, Inc. v. Mayo
Collaborative Servs., LLC, 275 F.Supp.3d 306 (D. Mass.
2017) ("Decision"). Because the district
court correctly concluded that the claims at issue are
directed to a natural law and lack an inventive concept, we
Diagnostics is the exclusive licensee of the '820 patent,
covering methods for diagnosing neurological disorders by
detecting antibodies to a protein called muscle-specific
tyrosine kinase ("MuSK"). '820 patent Abstract.
Athena also markets a test called FMUSK that functions by
evaluating those antibodies. After Mayo Collaborative
Services, LLC ("Mayo") developed two competing
tests that allegedly practice each step of one or more claims
of the '820 patent, Athena accused Mayo of infringing its
patent. Mayo moved to dismiss under Rule 12(b)(6), arguing
that the asserted claims of the '820 patent were invalid
under 35 U.S.C. § 101. The district court granted
Mayo's motion, concluding that the claims were invalid
under § 101 for claiming ineligible subject matter. This
appeal solely concerns whether claims 6-9 are patent eligible
under § 101.
gravis ("MG") is a neurological disorder where
patients experience muscle weakness and symptoms including
drooping eyelids, double vision, and slurred speech. '820
patent col. 1 ll. 13-23. It was previously discovered that MG
is an autoimmune disease caused by a patient generating
antibodies against her own acetylcholine receptors.
Id. col. 1 ll. 24-26. Antibodies which recognize a
person's own proteins as foreign antigens are known as
autoantibodies. Id. col. 1 ll. 42-45.
80% of patients with MG produce acetylcholine receptor
autoantibodies. Id. col. 1 ll. 34-36. The other 20%
do not, but they do experience the same MG symptoms.
Id. col. 1 ll. 36-38. The named inventors of the
'820 patent discovered that many of the 20% of MG
patients without acetylcholine receptor autoantibodies
instead generate autoantibodies to a membrane protein called
MuSK. Id. col. 1 ll. 54-61. Prior to their
discovery, no disease had been associated with MuSK.
Id. col. 2 ll. 35-37.
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. Id. col. 2 ll. 61-65. Claim 1,
not at issue in this appeal, is the only independent claim
and reads as follows:
1. A method for diagnosing neurotransmission or developmental
disorders related to [MuSK] in a mammal comprising the step
of detecting in a bodily fluid of said mammal autoantibodies
to an epitope of [MuSK].
Id. col. 12 ll. 31-35. Claim 7 is at issue and
depends from claim 1. It recites:
7. A method according to claim 1, comprising
contacting MuSK or an epitope or antigenic determinant
thereof having a suitable label thereon, with said bodily
immunoprecipitating any antibody/MuSK complex or
antibody/MuSK epitope or antigenic determinant complex from
said bodily fluid and
monitoring for said label on any of said antibody/MuSK
complex or antibody/MuSK epitope or antigen determinant
wherein the presence of said label is indicative of said
mammal is suffering from said neurotransmission or
developmental disorder related to [MuSK].
Id. col. 12 l. 62-col. 13 l. 5 (spacing added).
Claim 8 depends from claim 7 and recites that the label is a
radioactive label. Id. col. 13 ll. 6-7. Claim 9
depends from claim 8 and further recites that the radioactive
label is 125I, a radioactive isotope of iodine. Id.
col. 13 ll. 8-9. We focus on claim 9, the most specific one
at issue, which requires: (1) contacting MuSK or an epitope
thereof having a 125I label, with bodily fluid; (2)
immunoprecipitating any antibody/MuSK complex; and (3)
monitoring for the label on the complex, wherein the presence
of the label indicates the presence of a MuSK-related
specification of the '820 patent further explains what
the steps of iodination and immunoprecipitation entail.
First, MuSK is iodinated using radioactive 125I. Id.
col. 10 ll. 50-52. Then iodinated MuSK is separated from any
free 125I by gel filtration. Id. col. 10 ll. 55-56.
Next, the 125I-labeled MuSK is added to a small volume of the
patient's bodily fluid and left overnight. Id.
col. 10 ll. 56- 58. If MuSK autoantibodies are present in the
patient's bodily fluid, they will bind to the
125I-labeled MuSK. Any 125I-labeled MuSK in the sample is
then immunoprecipitated by adding a secondary antibody that
binds to any MuSK autoantibodies present. Id. col.
10 ll. 58-60. The resulting precipitate is finally
centrifuged, washed, and counted for radioactivity, which may
be indicative of MG. Id. col. 10 ll. 60-61.
undisputed that iodination and immunoprecipitation were known
techniques at the time of the invention. The '820 patent
specification states that "[t]he actual steps of
detecting autoantibodies in a sample of bodily fluids may be
performed in accordance with immunological assay techniques
known per se in the art," such as radioimmunoassays.
Id. col. 3 ll. 33-37. With respect to the relevant
individual steps in the radioimmunoassay, the specification
also discloses that "[i]odination and
immunoprecipitation are standard techniques in the art."
Id. col. 4 ll. 10- 11.
is additionally at issue in this appeal and depends from
claim 3. While claim 6 also involves detecting MuSK
autoantibodies by contacting a patient's bodily fluid
with MuSK or an epitope thereof, the labelling occurs
somewhat differently than in claims 7-9. Instead of labeling
MuSK with a radioisotope, claim 3 recites that the secondary
antibody is "tagged or labeled with a reporter
molecule." Id. col. 12 ll. 47-49. Claim 6
additionally requires that "the intensity of the signal
from the [secondary] antibody is indicative of the relative
amount of the anti-MuSK autoantibody in the bodily fluid when
compared to a positive and negative control reading."
Id. col. 12 ll. 57- 61. This claimed technique
exemplifies the ELISA method,  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.
district court concentrated its analysis on claims 7-9.
Athena did not present any arguments specific to claim 6.
Applying the test for subject matter eligibility established
by the Supreme Court in Mayo Collaborative Services v.
Prometheus Laboratories, Inc., 566 U.S. 66 (2012) and
Alice Corp. v. CLS Bank International, 573 U.S. 208
(2014), the court first concluded that the claims were
directed to a law of nature, Decision, 275 F.Supp.3d
at 312. According to the court, the claims focused on the
interaction of 125I-labeled MuSK with MuSK autoantibodies in
bodily fluid, an interaction which occurs naturally.
Id. at 310. The district court also determined that
the claims lacked an inventive concept, as the recited steps
involved only standard techniques in the art. Id. at
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).
review the district court's dismissal for failure to
state a claim under regional circuit law. BASCOM Glob.
Internet Servs., Inc. v. AT&T Mobility LLC, 827 F.3d
1341, 1347 (Fed. Cir. 2016). The First Circuit reviews such
dismissals de novo, accepts all well-pleaded facts
alleged in the complaint to be true, and draws all reasonable
inferences in favor of the nonmovant. In re Loestrin 24
Fe Antitrust Litig., 814 F.3d 538, 549 (1st Cir. 2016).
Patent eligibility under § 101 is a question of law
based on underlying facts, see Aatrix Software, Inc. v.
Green Shades Software, Inc., 882 F.3d 1121, 1125 (Fed.
Cir. 2018); Berkheimer v. HP Inc., 881 F.3d 1360,
1364-65 (Fed. Cir. 2018), that may be resolved on a Rule
12(b)(6) motion when the undisputed facts require a holding
of ineligibility, SAP Am., Inc. v. Investpic, LLC,
898 F.3d 1161, 1166 (Fed. Cir. 2018).
101 provides that "[w]hoever invents or discovers any
new and useful process, machine, manufacture, or composition
of matter, or any new and useful improvement thereof, may
obtain a patent therefor, subject to the conditions and
requirements of this title." 35 U.S.C. § 101. Given
the expansive terms of § 101, "Congress plainly
contemplated that the patent laws would be given wide
scope"; some of the legislative history likewise
indicated that "Congress intended statutory subject
matter to 'include anything under the sun that is made by
man.'" Diamond v. Chakrabarty, 447 U.S.
303, 308-09 (1980).
the law as set forth by the Supreme Court, § 101, while
broad, "contains an important implicit exception.
'[L]aws of nature, natural phenomena, and abstract
ideas' are not patentable." Mayo, 566 U.S.
at 70 (alteration in original) (quoting Diamond v.
Diehr, 450 U.S. 175, 185 (1981)). These exceptions exist
because monopolizing the basic tools of scientific work
"might tend to impede innovation more than it would tend
to promote it." Id. at 71. However, the Supreme
Court has advised that these exceptions must be applied
cautiously, as "too broad an interpretation of this
exclusionary principle could eviscerate patent law."
nature are not patentable, but applications of such laws may
be patentable. A claim to otherwise statutory subject matter
does not become ineligible by its use of a law of nature.
See Diehr, 450 U.S. at 187; Parker v.
Flook, 437 U.S. 584, 590 (1978). But, on the other hand,
adding "conventional steps, specified at a high level of
generality," to a law of nature does not make a claim to
the law of nature patentable. Mayo, 566 U.S. at 82.
distinguish claims to patent-eligible applications of laws of
nature from claims that impermissibly tie up such laws, we
apply the two-part test set forth by the Supreme Court.
First, we examine whether the claims are "directed
to" a law of nature. Alice, 573 U.S. at 217. If
they are, then we proceed to the second inquiry, where we ask
whether the limitations of the claim apart from the law of
nature, considered individually and as an ordered
combination, "'transform the nature of the
claim' into a patent-eligible application."
Id. (quoting Mayo, 566 U.S. at 78). To so
transform the claim, the additional limitations must
"ensure that the patent in practice amounts to
significantly more than a patent upon the natural law
itself." Mayo, 566 U.S. at 73.
first address claims 7-9 and then turn to claim 6.
argues that claims 7-9 are not directed to a natural law at
step one because they recite innovative, specific, and
concrete steps that do not preempt a natural law. Rather,
Athena contends that the claims are directed to a new
laboratory technique that makes use of man-made molecules.
responds that the claims are directed to a natural law: the
correlation between naturally-occurring MuSK autoantibodies
and MuSK-related neurological diseases like MG. According to
Mayo, the remaining steps apart from the natural law are
concededly standard immunoassay techniques that still leave
the claim directed to a natural law. Indeed, Mayo argues that
the specificity and concreteness of the claimed steps are
irrelevant to whether a claim is directed to a natural law.
And, as in Mayo, Mayo contends that it makes no
difference to eligibility that the claimed diagnostic method
uses man-made materials.
ultimately agree with Mayo that, under Mayo, the
claims are directed to a natural law. As an initial matter,
we must identify what the relevant natural law is. Here, it
is the correlation between the presence of
naturally-occurring MuSK autoantibodies in bodily fluid and
MuSK- related neurological diseases like MG. This correlation
exists in nature apart from any human action. There can thus
be no dispute that it is an ineligible natural law.
as Athena correctly observes, not every claim that involves a
natural law is directed to a natural law. "[A]ll
inventions at some level embody, use, reflect, rest upon, or
apply laws of nature, natural phenomena, or abstract
ideas." Mayo, 566 U.S. at 71. The Supreme
Court's two-step test thus "plainly contemplates
that the first step of the inquiry is a meaningful one, i.e.,
that a substantial class of claims are not directed
to a patent-ineligible concept." Enfish, LLC v.
Microsoft Corp., 822 F.3d 1327, 1335 (Fed. Cir. 2016).
step one "directed to" inquiry focuses on the claim
as a whole. E.g., Elec. Power Grp., LLC v.
Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016). To
determine whether a claim is directed to an ineligible
concept, we have frequently considered whether the claimed
advance improves upon a technological process or merely an
ineligible concept, based on both the written description and
the claims. See Cleveland Clinic Found. v. True Health
Diagnostics LLC, 859 F.3d 1352, 1361 (Fed. Cir. 2017);
Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827
F.3d 1042, 1047-49 (Fed. Cir. 2016); Ariosa Diagnostics,
Inc. v. Sequenom, Inc., 788 F.3d 1371, 1376 (Fed. Cir.
2015); see also McRO, Inc. v. Bandai Namco Games
Am. Inc., 837 F.3d 1299, 1314-15 (Fed. Cir. 2016);
Elec. Power Grp., 830 F.3d at 1354.
example, in CellzDirect we considered claims that
covered a method for producing a preparation of a type of
liver cell (called hepatocytes) that involved multiple
freeze-thaw cycles. 827 F.3d at 1046, 1048. Although the
inventors discovered the cells' ability to survive
multiple freeze-thaw cycles, a discovery that the district
court understood to be a natural law, we concluded that the
claims were not directed to that natural law. Id. at
1048-50. This was because the claims as a whole recited
"a new and improved way of preserving hepatocyte cells
for later use," "not simply an observation or
detection of the ability of hepato-cytes to survive multiple
freeze-thaw cycles." Id. at 1048. The claimed
advance harnessed a natural law to produce a technological
improvement that was patent eligible. See id. at
1048-49; see also, e.g., Enfish, 822 F.3d
at 1335-39 (holding improvement in computer-related
technology not directed to abstract idea).
contrast, in Cleveland Clinic we reiterated that
claims that merely recite observing naturally occurring
biological correlations "with no meaningful non-routine
steps in between" are directed to a natural law. 859
F.3d at 1361; see Ariosa, 788 F.3d at 1376. There,
the specification indicated that the claimed inventors
discovered a natural correlation between a molecule called
MPO and cardiovascular disease. Cleveland Clinic,
859 F.3d at 1360-61. The claims at issue recited detecting
MPO or other MPO-related products in a patient sample and
then predicting a patient's risk of having or developing
cardiovascular disease. Id. at 1361. As the claims
only covered the correlation between MPO and ...