United States Court of Appeals 

for the Federal Circuit ______________________

ATHENA DIAGNOSTICS, INC., OXFORD 

UNIVERSITY INNOVATION LTD., MAX-PLANCKGESELLSCHAFT 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.

______________________

ON PETITION FOR REHEARING EN BANC

______________________

ADAM GAHTAN, Fenwick & West, New York, NY, filed a 

petition for rehearing en banc for plaintiffs-appellants. 

Also represented by ERIC M. MAJCHRZAK, VANESSA PARKTHOMPSON; 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 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

2

Diego, CA, filed a response to the petition for defendantsappellees. Also represented by JOHN CAMERON ADKISSON,

ELIZABETH M. FLANAGAN, PHILLIP GOTER, DEANNA JEAN 

REICHEL, Minneapolis, MN. 

 

 MELISSA A. BRAND, Biotechnology Innovation Organization, Washington, DC, for amici curiae Biotechnology Innovation Organization, CropLife International, 

Pharmaceutical Research and Manufacturers of America, 

Wisconsin Alumni Research Foundation. Also represented 

by HANSJORG SAUER. Amicus curiae Biotechnology Innovation Organization also represented by BRIAN PAUL 

BARRETT, Eli Lilly and Company, Indianapolis, IN. Amicus 

curiae Pharmaceutical Research and Manufacturers of 

America also represented by DAVID EVAN KORN, Pharmaceutical Research and Manufacturers Association of America, Washington, DC. 

 MATTHEW JAMES DOWD, Dowd Scheffel PLLC, Washington, DC, for amici curiae Richard A. Epstein, Christopher Michael Holman, Adam Mossoff, Kristen J. Osenga, 

Michael Risch, Ted M. Sichelman, Brenda M. Simon. Also 

represented by ROBERT JAMES SCHEFFEL. 

 SHERRY M. KNOWLES, Knowles Intellectual Property 

Strategies, LLC, Atlanta, GA, for amici curiae Freenome 

Holdings Inc., Achillion Pharmaceuticals, Inc. Also represented by MEREDITH MARTIN ADDY, AddyHart P.C., Atlanta, GA. 

______________________

Before PROST, Chief Judge, NEWMAN, LOURIE, DYK, MOORE, 

O’MALLEY, REYNA, WALLACH, TARANTO, CHEN, HUGHES,

and STOLL, Circuit Judges.

LOURIE, Circuit Judge, with whom REYNA and CHEN, 

Circuit Judges, join, concurs in the denial of the petition 

for rehearing en banc.
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

3

HUGHES, Circuit Judge, with whom PROST, Chief 

Judge, and TARANTO, Circuit Judge, join, concurs in the 

denial of the petition for rehearing en banc.

DYK, Circuit Judge, with whom HUGHES, Circuit 

Judge, joins, and with whom CHEN, Circuit Judge, joins as 

to Parts IV, V, and VI, concurs in the denial of the petition for rehearing en banc.

CHEN, Circuit Judge, concurs in the denial of the petition for rehearing en banc.

MOORE, Circuit Judge, with whom O’MALLEY,

WALLACH, and STOLL, Circuit Judges, join, dissents from 

the denial of the petition for rehearing en banc.

NEWMAN, Circuit Judge, with whom WALLACH, Circuit Judge, joins, dissents from the denial of the petition 

for rehearing en banc.

STOLL, Circuit Judge, with whom WALLACH, Circuit 

Judge, joins, dissents from the denial of the petition for 

rehearing en banc.

O’MALLEY, Circuit Judge, dissents from the denial of the 

petition for rehearing en banc.

PER CURIAM.

O R D E R

A petition for rehearing en banc was filed by appellants 

Athena Diagnostics, Inc., Oxford University Innovation

Ltd., and the Max-Planck-Gesellschaft zur Forderung der 

Wissenschaften E.V. A response to the petition was invited 

by the court and filed by appellees Mayo Collaborative Services, LLC and Mayo Clinic. Several motions for leave to 

file amici curiae briefs were filed and granted by the court. 

The petition for rehearing, response, and amici curiae 

briefs were first referred to the panel that heard the appeal, and thereafter, to the circuit judges who are in regular active service. A poll was requested, taken, and failed. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

4

Upon consideration thereof, 

IT IS ORDERED THAT:

1) The petition for panel rehearing is denied. 

2) The petition for rehearing en banc is denied. 

3) The mandate of the court will issue on July 10, 

2019.

FOR THE COURT

 July 3, 2019 /s/ Peter R. Marksteiner

 Date Peter R. Marksteiner

 Clerk of Court
United States Court of Appeals 

for the Federal Circuit ______________________

ATHENA DIAGNOSTICS, INC., OXFORD 

UNIVERSITY INNOVATION LTD., MAX-PLANCKGESELLSCHAFT 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.

______________________

LOURIE, Circuit Judge, with whom REYNA and CHEN, Circuit Judges, join, concurring in the denial of the petition 

for rehearing en banc.

I concur in the court’s decision not to rehear this case 

en banc. In my view, we can accomplish little in doing so, 

as we are bound by the Supreme Court’s decision in Mayo. 

Some of us have already expressed our concerns over current precedent. E.g., Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743, 753 n.4 (Fed. Cir. 

2019); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 809 F.3d 

1282, 1284 (Fed. Cir. 2015) (Lourie, J., concurring in the 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

2

denial of rehearing en banc); id. at 1287 (Dyk, J., concurring in the denial of rehearing en banc). 

If I could write on a clean slate, I would write as an 

exception to patent eligibility, as respects natural laws, 

only claims directed to the natural law itself, e.g., E=mc2, 

F=ma, Boyle’s Law, Maxwell’s Equations, etc. I would not 

exclude uses or detection of natural laws. The laws of anticipation, obviousness, indefiniteness, and written description provide other filters to determine what is 

patentable.

But we do not write here on a clean slate; we are bound 

by Supreme Court precedent. In Mayo Collaborative Services v. Prometheus Laboratories, Inc., the claims at issue 

were held by the Court to be directed to the relationship 

between the concentration of metabolites in the blood and 

the likelihood that a drug dose will be ineffective, which it 

referred to as a law of nature. 566 U.S. 66, 74–75, 77 

(2012). The other steps—administering a drug and detecting the level of a specific metabolite—added only “[p]urely 

‘conventional or obvious’ ‘[pre]-solution activity’” that was 

“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 Parker v. Flook, 437 

U.S. 584, 590 (1978)); see Bilski v. Kappos, 561 U.S. 593, 

610–11 (2010) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by attempting to limit 

the use of the formula to a particular technological environment’ or adding ‘insignificant postsolution activity.’” 

(quoting Diamond v. Diehr, 450 U.S. 175, 191–92 (1981))); 

Flook, 437 U.S. at 590 (“The notion that post-solution activity, no matter how conventional or obvious in itself, can 

transform an unpatentable principle into a patentable process exalts form over substance.”). Because the claims recited only what the Court called a natural law together 

with well-understood, conventional activity, the Court concluded the claims were ineligible under § 101. Mayo, 566 

U.S. at 73, 79–80. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

3

In applying Mayo, we have accordingly held claims focused on detecting new and useful natural laws with conventional steps to be ineligible. E.g., Cleveland Clinic 

Found. v. True Health Diagnostics LLC, 859 F.3d 1352, 

1363 (Fed. Cir. 2017), cert. denied, 138 S. Ct. 2621 (2018); 

Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 

1378 (Fed. Cir. 2015), cert. denied, 136 S. Ct. 2511 (2016). 

In Cleveland Clinic, the claims recited a specific assay to 

detect the protein MPO, the enzyme-linked immunosorbent assay. 859 F.3d at 1357–58, 1362. Ariosa similarly 

involved a specific technique to amplify and detect DNA, 

the polymerase chain reaction. 788 F.3d at 1377. But in 

both cases, the patents’ specifications described these techniques as well-understood and conventional. Cleveland 

Clinic, 859 F.3d at 1355; Ariosa, 788 F.3d at 1377. We concluded that using these routine assays to detect new natural phenomena did not transform the claims into patent 

eligible applications. Cleveland Clinic, 859 F.3d at 1362–

63; Ariosa, 788 F.3d at 1376–77. 

In contrast, new method of treatment patents do not 

fall prey to Mayo’s prohibition. E.g., Vanda Pharm. Inc. v. 

West-Ward Pharm. Int’l Ltd., 887 F.3d 1117, 1136 (Fed. 

Cir. 2018). Nor have unconventional arrangements of 

known laboratory techniques, even if directed to a natural 

law. Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 

1042, 1051 (Fed. Cir. 2016). But this case involves neither

scenario. Athena’s claims recite observing a natural law 

using a radioimmunoassay that the specification describes 

as “standard” and “known per se in the art.” U.S. Patent 

7,267,820 col. 3 ll. 33–37, col. 4 ll. 10–12. The claims do not 

recite a new method of treatment or an unconventional 

combination of steps to detect the natural law. The only 

unconventional aspect is the inventors’ discovery of what 

the Supreme Court would call the natural law—the correlation between MuSK autoantibodies and the neurological 

disorder myasthenia gravis—but we cannot premise eligibility solely on the natural law’s novelty. Mayo, 566 U.S. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

4

at 73 (concluding that “the steps in the claimed processes 

(apart from the natural laws themselves) involve well-understood, routine, conventional activity previously engaged 

in by researchers in the field” (emphasis added)); Flook, 

437 U.S. at 591–92 (“[T]he novelty of the mathematical algorithm is not a determining factor at all” and “is treated 

as though it were a familiar part of the prior art.”). Under 

Supreme Court precedent, I do not believe that specific yet 

purely conventional detection steps impart eligibility to a 

claim that otherwise only sets forth what the Court has 

held is a natural law. That is the situation presented in 

Ariosa, Cleveland Clinic, and now Athena. Accordingly, as 

long as the Court’s precedent stands, the only possible solution lies in the pens of claim drafters or legislators. We 

are neither. 

Amici and others have complained that our eligibility 

precedent is confused. However, our cases are consistent. 

They have distinguished between new method of treatment 

claims and unconventional laboratory techniques, on the 

one hand, and, on the other hand, diagnostic methods that 

consist of routine steps to observe the operation of a natural law, a clear line. Beyond that, I do not see a way clear 

to distinguish Mayo in a useful, principled, fashion. Software is another matter, but such patents are not before us 

here. 

I therefore concur in the decision of the court not to

take this case en banc because I do not believe we can convincingly distinguish Mayo in this case.
United States Court of Appeals 

for the Federal Circuit ______________________

ATHENA DIAGNOSTICS, INC., OXFORD 

UNIVERSITY INNOVATION LTD., MAX-PLANCKGESELLSCHAFT 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.

______________________

HUGHES, Circuit Judge, with whom PROST, Chief Judge, 

and TARANTO, Circuit Judge, join, concurring in the denial 

of the petition for rehearing en banc. 

The multiple concurring and dissenting opinions regarding the denial of en banc rehearing in this case are illustrative of how fraught the issue of § 101 eligibility, 

especially as applied to medical diagnostics patents, is. I 

agree that the language in Mayo, as later reinforced in Alice, forecloses this court from adopting an approach or 

reaching a result different from the panel majority’s. I also 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

2

agree, however, that the bottom line for diagnostics patents 

is problematic. But this is not a problem that we can solve. 

As an inferior appellate court, we are bound by the Supreme Court.

I, for one, would welcome further explication of eligibility standards in the area of diagnostics patents. Such 

standards could permit patenting of essential life saving 

inventions based on natural laws while providing a reasonable and measured way to differentiate between overly 

broad patents claiming natural laws and truly worthy specific applications. Such an explication might come from the 

Supreme Court. Or it might come from Congress, with its 

distinctive role in making the factual and policy determinations relevant to setting the proper balance of innovation 

incentives under patent law.
United States Court of Appeals 

for the Federal Circuit ______________________

ATHENA DIAGNOSTICS, INC., OXFORD 

UNIVERSITY INNOVATION LTD., MAX-PLANCKGESELLSCHAFT 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.

______________________

DYK, Circuit Judge, with whom HUGHES, Circuit Judge,

joins, and with whom CHEN, Circuit Judge, joins as to Parts 

IV, V, and VI, concurring in the denial of the petition for 

rehearing en banc. 

I

In the realm of abstract ideas, the Mayo/Alice framework has successfully screened out claims that few would 

contend should be patent eligible, for example, those that 

merely apply well-known business methods and other
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

2

processes using computers or the Internet.1 The Mayo/Alice framework has thus proven to be both valuable and effective at invalidating overly broad, non-inventive claims 

that would effectively “grant a monopoly over an abstract 

idea.” Alice Corp. v. CLS Bank Int’l, 573 U.S. 208, 216 

(2014) (quoting Bilski v. Kappos, 561 U.S. 593, 611–612 

(2010)). As the Supreme Court has recognized, the concern 

with such patents is that they would “‘inhibit further 

 

1 See, e.g., Trading Techs. Int’l, Inc. v. IBG LLC, 921 

F.3d 1378, 1384–85 (Fed. Cir. 2019) (invalidating claims 

directed to “providing a trader with additional financial information to facilitate market trades” using “a generic computer”); SAP Am., Inc., v. Investpic, LLC, 898 F.3d 1161, 

1167–69 (Fed. Cir. 2018) (invalidating claims directed to 

“the selection and mathematical analysis of [investment] 

information, followed by reporting or display of the results” 

using “off-the-shelf computer technology”); Credit Acceptance Corp. v. Westlake Servs., 859 F.3d 1044, 1054–57 

(Fed. Cir. 2017) (invalidating claims directed to “processing 

an application for financing a purchase” using “generic 

computer components”); Elec. Power Grp., LLC v. Alstom 

S.A., 830 F.3d 1350, 1353–55 (Fed. Cir. 2016) (invalidating 

claims directed to “collecting information, analyzing it, and 

displaying certain results” using “off-the-shelf, conventional computer, network, and display technology”); Intellectual Ventures I LLC v. Capital One Bank, 792 F.3d 1363, 

1369–70 (Fed. Cir. 2015) (invalidating claims directed to 

tailoring advertising to individual customers using a “generic web server with attendant software”); Ultramercial, 

Inc. v. Hulu, LLC, 772 F.3d 709, 715–16 (Fed. Cir. 2014) 

(invalidating a claim directed to “using advertising as an 

exchange or currency” “on the Internet”); buySAFE, Inc. v. 

Google, Inc., 765 F.3d 1350, 1355 (Fed. Cir. 2014) (invalidating a claim directed to “creating a contractual relationship” through “online transactions” using “generic” 

computer functionality). 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

3

discovery by improperly tying up the future use of’ these 

buildings blocks of human ingenuity.” Id. (quoting Mayo 

Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 

85 (2012)). At the same time, our § 101 precedent has allowed room for claims that do more than recite conventional applications of abstract concepts.2 

II

Despite assertions to the contrary, the doctrines of novelty under § 102, obviousness under § 103, and enablement 

and written description under § 112 cannot adequately 

guard against the dangers of overclaiming. In Mayo, the 

Supreme Court rejected the argument that “other statutory provisions”—specifically §§ 102, 103, and 112—could 

adequately “perform th[e] screening function” served by 

§ 101. 566 U.S. at 89. Although the Court recognized that 

the § 101 patent eligibility inquiry “might sometimes overlap” with considerations of novelty and non-obviousness 

under §§ 102 and 103, it concluded that “to shift the patenteligibility inquiry entirely to these later sections risks creating significantly greater legal uncertainty, while assuming that those sections can do work that they are not 

equipped to do.” Id. at 90. Those sections and § 112 do not 

adequately address “the risk that a patent on the [natural]

 

2 See, e.g., Ancora Techs., Inc. v. HTC Am., Inc., 908 

F.3d 1343, 1348–49 (Fed. Cir. 2018) (holding that claim to 

a specific technique for improving computer security 

against unauthorized use of a program was not directed to 

an abstract idea); Finjan, Inc. v. Blue Coat Sys., Inc., 879 

F.3d 1299, 1303–04 (Fed. Cir. 2018) (holding that claims to 

a “behavior-based virus scan” allowing for more flexible 

and nuanced virus filtering were not directed to an abstract 

idea); Enfish, LLC v. Microsoft Corp., 822 F.3d 1327, 1336–

38 (Fed. Cir. 2016) (holding that claims to self-referential 

tables that allowed for more efficient launching and adaptation of databases were not directed to an abstract idea). 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

4

law would significantly impede future innovation.” Id. at 

90–91; see also Mark Lemley et al., Life After Bilski, 63 

Stan. L. Rev. 1315, 1329–32 (2011) (outlining differences 

between §§ 101 and 112). Nor do these other provisions 

typically allow early stage resolution of the “threshold” issue of patent eligibility, Bilski, 561 U.S. at 602, necessary 

to avoid the costs of lengthy litigation. Thus, § 101 serves 

an important purpose not served by these other provisions 

in the Patent Act.

A simple example in the area of diagnostic patents illustrates this point. If the first person to identify the relationship between a genetic abnormality and a disease had 

sought a broad patent on a method of searching for genetic 

abnormalities and determining their relationship to disease, the claims would have been neither anticipated nor 

obvious. Nor is it likely that they would they have been 

invalid for lack of enablement (since a representative species was disclosed) or written description (the overall conception being in the mind of the inventor). The only barrier 

to such broad patent claiming is § 101. 

In fact, one of the diagnostic patents that we have held 

unpatentable under § 101 had exactly that problem of overbreadth. In In re BRCA1- & BRCA2-Based Hereditary 

Cancer Test Patent Litigation, 774 F.3d 755 (Fed. Cir. 

2014), we held that genetic testing claims were directed to 

the “patent-ineligible abstract idea of comparing BRCA sequences and determining the existence of alterations” of 

the gene. Id. at 763. We noted the breadth of the claims, 

explaining that they “are not restricted by the purpose of 

the comparison or the alteration being detected,” nor “limited to the detection of risk of breast or ovarian cancer.” Id. 

at 763–64. Indeed, the claims encompassed “comparisons 

for purposes other than detection of cancer.” Id.; see also 

Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 

1373–74, 1378 (Fed. Cir. 2015) (invalidating claims to 

methods of detecting cffDNA in maternal serum or plasma 

that encompassed any diagnosis of any disease). What was 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

5

claimed was a broad concept, and we therefore held the 

claims ineligible under § 101, though the claims may well 

have survived challenge under §§ 102, 103, and 112. 

III

The problem with § 101 arises not in implementing the 

abstract idea approach of Alice, but rather in implementing 

the natural law approach of Mayo. Although Mayo’s framework is sound overall, I share the concerns expressed by 

my dissenting colleagues that the Mayo test for patent eligibility should leave room for sufficiently specific diagnostic patents. But it is the Supreme Court, not this court, 

that must reconsider the breadth of Mayo. 

Although the Supreme Court’s decision in Mayo did not 

make all diagnostic claims patent ineligible, as we previously held in Ariosa, 788 F.3d at 1376–77, Mayo left no

room for us to find typical diagnostic claims patent eligible, 

absent some inventive concept at Mayo step two. The panel 

here correctly concluded that Mayo controls. 

The inventors of U.S. Patent 7,267,820 (“the ’820 patent”) discovered that myasthenia gravis (“MG”), a neurological disorder, can be diagnosed by detecting the presence 

of MuSK autoantibodies in bodily fluid. See Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 

743, 747 (Fed. Cir. 2019). At Mayo step one, the claims are 

directed to a natural law: “the correlation between the 

presence of naturally-occurring MuSK autoantibodies in 

bodily fluid” and certain neurological diseases like MG. Id. 

at 750. This is similar to the correlation between “concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove 

ineffective or cause harm,” which the Supreme Court held 

“sets forth a natural law” in Mayo, 566 U.S. at 77. 

So too as in Mayo, at step two, the additional steps of

the claims here, though “set forth with some specificity,”

Athena, 915 F.3d at 752, “only require standard techniques 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

6

to be applied in a standard way” and thus do not supply the 

requisite inventive concept, id. at 753. The specification 

explains 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.” Id. at 753–54 (alteration in original). Similarly, 

in Mayo, adding steps “to determine the level of the relevant metabolites in the blood” was held “not sufficient to 

transform an unpatentable law of nature into a patent-eligible application” because those steps were “well known in 

the art.” 566 U.S. at 79. Therefore, the panel here correctly 

held that under the Mayo framework, the claims are not 

patent eligible under § 101. Athena, 915 F.3d at 746, 756. 

And the Supreme Court has instructed us to follow its precedent until the Court itself chooses to expressly overrule 

it.3 

IV

It is nonetheless appropriate to point out that there is 

tension between Mayo and the Supreme Court’s later decision in Association for Molecular Pathology v. Myriad 

 

3 See, e.g., Hohn v. United States, 524 U.S. 236, 252–

53 (1998) (“Our decisions remain binding precedent until 

we see fit to reconsider them, regardless of whether subsequent cases have raised doubts about their continuing vitality.”); State Oil Co. v. Khan, 522 U.S. 3, 20 (1997) (“The 

Court of Appeals was correct in applying that principle despite disagreement with [the precedent], for it is this 

Court’s prerogative alone to overrule one of its precedents.”); Rodriguez de Quijas v. Shearson/Am. Express, 

Inc., 490 U.S. 477, 484 (1989) (“If a precedent of this Court 

has direct application in a case, yet appears to rest on reasons rejected in some other line of decisions, the Court of 

Appeals should follow the case which directly controls, 

leaving to this Court the prerogative of overruling its own 

decisions.”).
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

7

Genetics, Inc., 569 U.S. 576 (2013), and that the holding of 

Mayo may be overbroad. The language of § 101 does cover 

“discover[ies],” 35 U.S.C. § 101, and there is no doubt that 

determining the relationship between specific genetic abnormalities and specific diseases constitutes an important 

discovery with proven utility. There is much to be said for 

the patentability of claims to such discoveries, if not 

drafted overbroadly. And Myriad suggests that such discoveries may be patent eligible. There, the patent applicant discovered a previously unknown natural 

phenomenon: the location and sequence of the BRCA1 and 

BRCA2 genes and their connection to cancer. Myriad, 569 

U.S. at 582–83. Although the Court held ineligible the 

claims to naturally occurring DNA sequences, it suggested 

that “new applications of knowledge about the BRCA1 and 

BRCA2 genes” could be eligible and referred to various “unchallenged claims” discussed in Judge Bryson’s concurrence to our court’s decision below. Id. at 596 (emphasis in 

original) (citing Ass’n for Molecular Pathology v. U.S. Patent & Trademark Office, Inc., 689 F.3d 1303, 1349 (Fed. 

Cir. 2012) (Bryson, J. concurring)). One of these “unchallenged claims” was claim 21 of Myriad’s U.S. Patent No. 

5,753,441, which covered a method of detecting (using conventional methods) any of several specific mutations in the 

BRCA1 gene, newly discovered by the patent applicant and 

shown to increase a person’s risk of developing particular 

cancers (a far narrower claim than the claims held unpatentable in BRCA1- & BRCA2). 

By suggesting that such a claim could be patent eligible, Myriad thus recognized that an inventive concept can 

sometimes come from the discovery of an unknown natural 

phenomenon and its application for a diagnostic purpose. 

This appears to be in tension with Mayo. Under Mayo, a 

natural phenomenon itself, no matter how narrow and specific, cannot supply the requisite “inventive concept.” See 

Mayo, 566 U.S. at 77–78, 88–89. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

8

Thus, it would be desirable for the Supreme Court to 

refine the Mayo framework to allow for sufficiently specific 

diagnostic patent claims with proven utility. In the life sciences, development of new diagnostic methods is often 

based on researching complex biological systems. The inventive concepts in this area may lie primarily in the application of a natural law. 

V

At the same time, Mayo’s central concern was both important and consistent with the Patent Act. There is a substantial risk that overbroad claims involving natural laws 

may “preempt the use of a natural law” and thus “inhibit 

further discovery by improperly tying up the future use of 

laws of nature.” Id. at 72, 85. In other words, there is a 

risk that granting overbroad patents could reward a mere 

concept rather than the work subsequently done by the actual inventor. The risks associated with such overbreadth 

are shown by the examples discussed earlier. 

In my view, the Mayo framework should be refined in 

limited respects. First, at step one of Mayo, the natural 

law cannot be claimed as such. See Gottschalk v. Benson, 

409 U.S. 63, 67 (1972). As Mayo noted, “Einstein could not 

patent his celebrated law that E=mc2.” 566 U.S. at 71 

(quoting Diamond v. Chakrabarty, 447 U.S. 303, 309 

(1980)); see also Parker v. Flook, 437 U.S. 584, 591 (1978). 

Nor could a patent claimant “simply recite a law of nature 

and then add the instruction ‘apply the law,’” such as if 

Einstein had claimed “a process consisting of simply telling 

linear accelerator operators to refer to the law.” Mayo, 566 

U.S. at 78. Where the natural law itself is so broadly 

claimed, there is no reason to address step 2 (the inventive 

concept). The claims are simply ineligible. 

At the same time, “all inventions at some level embody, 

use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas.” Id. at 71. Thus, a sufficiently 

specific “application of a law of nature or mathematical 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

9

formula to a known structure or process may well be deserving of patent protection.” Id. (emphasis in original) 

(quoting Diamond v. Diehr, 450 U.S. 175, 187 (1981)). 

For there to be a patent eligible application of a natural 

law, there must be a “discover[y],” 35 U.S.C. § 101, and the 

claims must recite a specific application of that “discovery” 

with established utility. Otherwise, the natural law may 

be entirely preempted, even as to those aspects where the 

patent claimant has done no more than claim a broad conception. Requiring a specific application mitigates against 

the risk of granting patents too early—that is, before the 

patent applicant has devised a specific application of the 

natural law—and thereby prevents monopolization of the 

“basic tools of scientific and technological work.” Mayo, 566 

U.S. at 71 (quoting Benson, 409 U.S. at 67); Brenner v. 

Manson, 383 U.S. 519, 534–35 (1966) (noting that before a 

claimed invention is sufficiently “refined and developed,” 

granting a patent “may confer power to block off whole areas of scientific development”); see generally Lemley, supra, 

at 1337–38 (arguing for a focus on claim scope under § 101 

and noting that overly broad claims “make later improvements more costly or even impossible”). 

The Supreme Court’s opinion in O’Reilly v. Morse, 56 

U.S. (15 How.) 62 (1854), the foundation of the Court’s jurisprudence on patent eligibility, appears to make this very 

distinction. There, the Court allowed Morse’s narrower 

claims, which were tied specifically to his discovery: the telegraph. See id. at 112.4 The Court reasoned that Morse 

 

4 For example, Morse’s second claim recited “the employment of the machinery called the register or recording 

instrument, composed of the train of clock-wheels, cylinders, and other apparatus, or their equivalent, for removing the material upon which the characters are to be 

imprinted, and for imprinting said characters, 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

10

“discover[ed] a method by which intelligible marks or signs 

may be printed at a distance” and that “for the [particular] 

method or process thus discovered, he is entitled to a patent.” Id. at 117. But the Court held unpatentable Morse’s 

claim to all “marking or printing [of] intelligible characters, 

signs, or letters, at any distances” via electric currents, because “the claim is too broad, and not warranted by law.” 

Id. at 112–13. As in Mayo, the Court was particularly concerned about preempting use of the natural phenomenon: 

“For aught that we now know some future inventor, in the 

onward march of science, may discover a [different] mode 

of writing or printing at a distance by means of the electric 

or galvanic current . . . . But yet if it is covered by this patent the inventor could not use it, nor the public have the 

benefit of it without the permission of this patentee.” Id. 

at 113. 

More recent opinions of the Supreme Court are also 

consistent with a focus on claims that sweep too broadly. 

In Benson, the Court observed that the claims were “so abstract and sweeping as to cover both known and unknown 

uses of” the mathematical formula at issue, and so held the 

claims ineligible. 409 U.S. at 67–68. Similarly, in Flook, 

the claims to “a formula for computing an updated alarm 

limit” could “cover a broad range of potential uses” and 

were also held ineligible. 437 U.S. at 586. By contrast, in 

Diehr, the Court held eligible claims that used a wellknown mathematical equation in a process of curing synthetic rubber. 450 U.S. at 191–92. The patent claimants 

did “not seek to pre-empt the use of th[e] equation,” but rather sought “only to foreclose from others the use of that 

equation in conjunction with all of the other steps in their 

claimed process” for curing rubber. Id. at 187. Thus, the 

 

substantially as set forth in the foregoing description of the 

second principal part of my invention.” Morse, 56 U.S. at 

85. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

11

Supreme Court’s precedents support a requirement of specific application as part of the patent eligibility inquiry as 

to natural laws. 

To ensure against overbroad claims, the scope of the 

§ 101 natural law exception is necessarily informed by the 

utility requirement of § 101. The utility requirement has 

its origins in the constitutional grant of Congressional authority, which contemplated that the “discoveries” entitled 

to patents would be limited to those of proven utility. See 

U.S. Const. art. I, § 8, cl. 8; Sean M. O’Connor, The Overlooked French Influence on the Intellectual Property Clause, 

82 U. Chi. L. Rev. 733, 792–93 (2015). And the statutory 

requirement of utility has been held by the Supreme Court 

to require that the claimed invention have established utility, not merely the prospect of future utility. Brenner, 383 

U.S. at 534–36. In Brenner, the Supreme Court held that 

a patent claiming an allegedly novel process for making 

certain known steroids was ineligible for lack of utility. Id. 

The Court reasoned that without a showing of utility, “the 

metes and bounds of th[e] monopoly are not capable of precise delineation,” and “[s]uch a patent may confer power to 

block off whole areas of scientific development, without 

compensating benefit to the public.” Id. at 534. “Unless 

and until a process is refined and developed to this point—

where specific benefit exists in currently available form—

there is insufficient justification for permitting an applicant to engross what may prove to be a broad field.” Id. at 

534–35. It follows that the scope of patents involving the 

application of natural laws should not extend beyond established utility, and that claims that extend further are 

not patent eligible. Under this approach, because of their 

breadth, the claims in Mayo would not be eligible at step 

one. See Mayo, 566 U.S. at 87 (explaining that the claim 

steps were “set forth in highly general language covering 

all processes that make use of the correlations after measuring metabolites, including later discovered processes 

that measure metabolite levels in new ways”). 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

12

However, if the claim is sufficiently tied to a specific 

and useful application of a natural law at Mayo step one, 

that application itself should serve as the necessary inventive concept at Mayo step two. Yet at step two, the application must be more than determining the precise 

correlation of a known relationship using prior art processes, as was the case in Mayo itself. In Mayo, “scientists 

already understood that the levels in a patient’s blood of 

certain metabolites, including [those involved in the 

claims] were correlated with the likelihood that a particular dosage of a thiopurine drug could cause harm or prove 

ineffective.” Id. at 73–74. And “scientists routinely measured metabolites as part of their investigations into the relationships between metabolite levels and efficacy and 

toxicity of thiopurine compounds.” Id. at 79. “But those in 

the field did not know the precise correlations between metabolite levels and likely harm or ineffectiveness.” Id. at 

74. Thus, Mayo’s claims only involved determining the precise correlations of a law of nature that was already well 

known. The asserted application of the natural law was 

therefore no more than determining “the precise correlations between metabolite levels and likely harm or ineffectiveness” of a drug dosage and thus was patent ineligible. 

Requiring specific and useful application for the entire 

scope of the claim at Mayo step one, and more than determining precise correlations of a known natural law using 

prior art processes at Mayo step two, would ensure that the 

claims truly recite an “inventive application” of the natural 

law that should be eligible under § 101. This approach 

would help ensure that the reward of a patent goes to those 

who have actually done the work to develop a specific application of a natural law, not those who are the first to the 

patent office with broad, conceptual claims lacking proven 

utility in many applications.
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

13

VI

Finally, this case may involve claims that could be patent eligible under this suggested approach. First, claims 

7–9 do not claim the natural law itself—the relationship 

between MuSK autoantibodies and MG, a rare neurological 

disorder—but rather claim specific methods of diagnosing 

neurological disorders like MG by detecting MuSK autoantibodies. See Athena, 915 F.3d at 747.5 Second, unlike in 

 

5 Claims 7–9 depend from claim 1, not at issue in this 

appeal, which recites:

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]. 

’820 patent, col. 12, ll. 31–35.

Claim 7 recites:

7. A method according to claim 1, comprising

contacting MuSK or an epitope or antigenic determinant thereof having a suitable label thereon, 

with said bodily fluid, immunoprecipitating any 

antibody/MuSK complex or antibody/MuSK 

epitope or antigenic determinant complex from 

said bodily fluid and

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

antigen determinant complex,

wherein the presence of said label is indicative of 

said mammal is suffering from said neurotransmission or developmental disorder related to [MuSK].

Id. col. 12, l. 62–col 13, l. 5 (indentation added). 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

14

Mayo, this case involves a “discovery” of the relationship, 

not mere determination of the precise correlations of a 

known natural law using prior art processes. As the panel 

noted, “[p]rior to the[] discovery [by the named inventors], 

no disease had been associated with MuSK.” Id. 

Because at least some of the claims here recite specific 

applications of the newly discovered law of nature with 

proven utility, this case could provide the Supreme Court 

with the opportunity to refine the Mayo framework as to 

diagnostic patents. 

 

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. Id. col 13, ll. 8–9. 
United States Court of Appeals 

for the Federal Circuit ______________________

ATHENA DIAGNOSTICS, INC., OXFORD 

UNIVERSITY INNOVATION LTD., MAX-PLANCKGESELLSCHAFT 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.

______________________

CHEN, Circuit Judge, concurring with denial of the petition 

for rehearing en banc.

“Congress plainly contemplated that the patent laws 

would be given wide scope.” Bilski v. Kappos, 561 U.S. 593, 

601 (2010) (quoting Diamond v. Chakrabarty, 447 U.S. 303, 

308 (1980)). As the Court observed, “Congress took this 

permissive approach to patent eligibility to ensure that ‘ingenuity should receive a liberal encouragement.’” Id. Consistent with that mandate, the Court in Diamond v. Diehr, 

450 U.S. 175 (1981) adopted a relatively narrow and more 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

2

administrable version of the judicial exceptions to the statutory text of 35 U.S.C. § 101 compared to what the Court 

articulated three years earlier in Parker v. Flook, 437 U.S. 

584 (1978). Under Diehr’s “claim as a whole” principle, 

which does not divide the claim into new versus old elements, Athena’s claims, particularly claims 7 and 9, likely 

would have been found to be directed to a patent-eligible 

process comprising a set of technical, transformative steps 

to test a patient for a particular medical condition. But in 

Mayo Collaborative Services v. Prometheus Laboratories, 

Inc., 566 U.S. 66 (2012), the Court set forth an inventive 

concept/point of novelty framework, which is a more farreaching, aggressive version of the judicial exceptions to 

the statute and is largely incompatible with Diehr’s core 

rationale. At the same time, nothing in Mayo suggests that 

it sought to repudiate Diehr’s analysis. While I believe our 

court would benefit from the Supreme Court’s guidance as 

to whether it intended to override central tenets of Diehr,

Mayo’s reasoning is clear and we are bound by it. Because 

that analysis requires the affirmance of the district court’s 

decision to invalidate Athena’s claims, I concur with this 

court’s decision to deny the petition for rehearing en banc.

I. FLOOK AND DIEHR

In Flook, the Court articulated the notion that something else beyond an algorithm or law of nature recited in 

a claim must provide the key “inventive concept” to make 

a claim patent-eligible. 437 U.S. at 594. There, the claims 

recited a formula for computing an updated alarm limit, a 

number that signals the presence of an abnormal temperature, pressure, and flow rate combination indicating inefficiency or perhaps danger during catalytic conversion 

processes. Id. at 585. While the Court recognized that “a 

process is not unpatentable simply because it contains a 

law of nature or a mathematical algorithm,” id. at 590, it 

also declared that “the discovery of such a phenomenon 

cannot support a patent unless there is some other inventive concept in its application.” Id. at 594. Because the 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

3

recited field of use of catalytic conversion of hydrocarbons 

was “well known,” and the formula received no credit in the 

analysis, the Court concluded that Flook’s claim “contains 

no patentable invention.” Id. The Court indicated that it 

had considered the claim “as a whole,” but it did so by reviewing the claim on an element-by-element basis in 

search of something new and inventive, discounting the 

formula as “assumed to be within the prior art.” Id. In so 

doing, the Court found no novel “inventive concept” in the 

claim. Id.

The Court advanced a very different analytic approach 

for the judicial exceptions in Diamond v. Diehr, 450 U.S. 

175 (1981), one that is difficult to reconcile with much of 

Flook’s reasoning. The Court held patent-eligible under 

§ 101 a claim for a process of constantly measuring the 

temperature inside a molding press to determine when to 

remove a cured rubber product. Id. at 192–93. The relationship between temperature and cure relied on a known 

mathematical equation, but the Court found that, when the 

overall patent claim was considered as a whole, the respondents did “not seek to patent a mathematical formula,”

but instead “[sought] protection for a process of curing synthetic rubber.” Id. at 187. Rejecting a point of novelty inquiry for § 101, the Court stated: “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 

patentable subject matter.” Id. at 188–89; id. at 193 n.15

(“The fact that one or more of the steps in [a claimed] process may not, in isolation, be novel or independently eligible for patent protection is irrelevant to the question of 

whether the claims as a whole recite subject matter eligible 

for patent protection under § 101.”) (emphasis in original); 

see also id. at 190 (“The question therefore of whether a 

particular invention is novel is ‘wholly apart from whether 

the invention falls into a category of statutory subject 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

4

matter.’” (quoting In re Bergy, 596 F.2d 952, 961 (C.C.P.A.

1979))).

Furthermore, Bilski recognized the interplay between 

Diehr and Flook, pointing out that Diehr “established a 

limitation on the principles articulated in [Gottschalk v.] 

Benson and Flook” in that “Diehr emphasized the need to 

consider the invention as a whole, rather than ‘dissect[ing] 

the claims into old and new elements . . . in the analysis.’” 

Bilski, 561 U.S. at 611 (quoting Diehr, 450 U.S. at 188). 

Thus, as recently as Bilski, the Court understood Diehr as 

requiring consideration of the claim as a whole, including 

any mathematical formula or scientific principle, in the 

§ 101 inquiry, and as rejecting any dissection of the claim 

in search of novel or unconventional components. 

Aside from reaffirming the result in Flook, the Diehr

Court addressed Flook’s takeaway meaning at two different points in the opinion. First, Diehr observed: “Our recent holdings in Gottschalk v. Benson, supra, and Parker v. 

Flook, supra, both of which are computer-related, stand for 

no more than [the] long-established principles” that 

“[e]xcluded from such patent protection are laws of nature,

natural phenomena, and abstract ideas.” 450 U.S. at 185 

(citing Flook and other cases describing the judicial exceptions, e.g., “[a] principle[] in the abstract . . . cannot be patented.”). Second, Diehr explained the defect in the Flook

claim in the following way: “A mathematical formula does 

not suddenly become patentable subject matter simply by 

having the applicant acquiesce to limiting the reach of the 

patent for the formula to a particular technological 

use . . . . All the application provided was a ‘formula for 

computing an updated alarm limit.’” Id. at 192 n.14 (quoting Flook, 437 U.S. at 586). The Diehr Court thus regarded 

the Flook claim as merely reciting a formula that would be 

applicable in an industrial process, but not reciting an 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

5

industrial process itself.1 Aside from these two points, 

Diehr did not restate any other principles expressed in 

Flook.

That Diehr established a limitation on Flook and rejected the point of novelty/inventive concept approach to 

patent eligibility is underscored by the protests within the 

Diehr dissent. See Diehr, 450 U.S. at 204–16. “Proper 

analysis,” in the dissent’s view, “must start with an understanding of what the inventor claims to have discovered—

or phrased somewhat differently—what he considers his 

inventive concept to be.” Id. at 212. Because the claim had 

“no other inventive concept” other than the addition of a 

mathematical algorithm to the otherwise conventional 

claimed process for curing rubber, the dissent would have 

found the Diehr claim ineligible. Id. at 213–14. The Diehr

majority responded: “In order for the dissent to reach its 

conclusion it is necessary for it to read out of respondents’ 

patent application all the steps in the claimed process 

which it determined were not novel or ‘inventive.’ That is 

not the purpose of the § 101 inquiry and conflicts with the 

proposition recited above that a claimed invention may be 

entitled to patent protection even though some or all of its 

elements are not ‘novel.’” Id. at 193 n.15.

Given Diehr’s evident disagreement with Flook’s analysis, Diehr, as the later opinion, was widely understood to 

be the guiding, settled precedent on § 101 for three decades. See, e.g., Arrhythmia Research Tech., Inc. v. Corazonix Corp., 958 F.2d 1053, 1057 n.4 (Fed. Cir. 1992) 

 

1 Citing Flook, the Diehr Court also stated that “insignificant post-solution activity will not transform an unpatentable principle into a patentable process.” Id. at 191–

92. What that meant (pre-Mayo) was not clear, but, at the 

time, it could be read to refer to the fact that Flook’s claim 

did nothing more than “limit the use of the formula to a 

particular technological environment.” Id. at 191. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

6

(“Although commentators have differed in their interpretations of Benson, Flook, and Diehr, it appears to be generally 

agreed that these decisions represent evolving views of the 

Court, and that the reasoning in Diehr not only elaborated 

on, but in part superseded, that of Benson and Flook.”) (citing R.L. Gable & J.B. Leaheey, The Strength of Patent Protection for Computer Products, 17 Rutgers Computer & 

Tech. L.J. 87 (1991); D. Chisum, The Patentability of Algorithms, 47 U. Pitt. L. Rev. 959 (1986)); see also Edward W. 

Roush, Jr., Patent Law-Patentable Subject Matter-Manufacturing Process Which Includes Use of Mathematical Formula and Computer Program Constitutes Patentable 

Subject Matter, 13 St. Mary’s L.J. 420, 428–29 (1981) (“The 

Diehr Court’s holding is entirely consistent with title 35, 

section 101 subject matter standards. Although both the 

majority and dissent acknowledged that Diehr presented a 

section 101 statutory subject matter question, the dissent 

improperly injected considerations of section 102 novelty 

into its analysis. The majority in Flook employed the same 

rationale.”).

II. MAYO AND ALICE

Three decades after Diehr, Mayo provided a framework 

for the judicial exceptions that strongly tracked the reasoning of Flook and the Diehr dissent. Mayo Collaborative 

Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012). The 

claims in Mayo were for a method of optimizing the treatment of an immune-mediated gastrointestinal disorder 

comprising two physical steps: (1) administering a synthetic drug to a patient, and (2) determining the concentration level of certain metabolic byproducts in the patient’s 

bloodstream. The claims also included two “wherein” 

clauses, reciting that the measured level indicates whether 

the patient has received a safe and effective dose. Id. at 

74–75. The Court found that the “wherein” clauses incorporate a law of nature: the relationship between concentrations of certain metabolites in the blood and the likelihood 

that a thiopurine drug dosage will prove ineffective or 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

7

cause harm. Id. at 78. Because the two physical steps were 

well-known in the prior art, the Mayo Court characterized 

these claims as adding to that law of nature nothing more 

than “well-understood, routine, conventional activity.” Id. 

at 73, 79–80. 

Citing primarily to Flook, as well as Bilski, the Court 

stated that its prior decisions “insist that a process that focuses upon the use of a natural law also contain other elements or a combination of elements, sometimes referred to 

as an ‘inventive concept,’ sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the natural law itself.” Id. at 72–73. Because, 

in the Court’s view, “the steps in the claimed processes 

(apart from the natural laws themselves) involve well-understood, routine, conventional activity previously engaged 

in by researchers in the field,” the claims lacked any inventive concept. Id. at 73. Moreover, the Court did not 

share the concerns Diehr expressed as to preserving a doctrinal distinction between §§ 101 and 102; instead, the 

Court noted: “We recognize that, in evaluating the significance of additional steps [beyond the law of nature] the 

§ 101 patent eligibility inquiry and, say, the § 102 novelty 

inquiry might sometimes overlap.” Id. at 90. Mayo’s rationale thus follows the point of novelty/inventive concept

reasoning of Flook and the Diehr dissent. 

As such, Mayo is in considerable tension with Diehr’s 

instruction to consider claims “as a whole” and Diehr’s disapproval of dissecting claims into elements and ignoring 

non-novel elements in the § 101 analysis. 450 U.S. at 188. 

The Mayo Court indicated that it considered the claimed 

steps “as an ordered combination,” but it excluded the law 

of nature from that review and concluded that the “ordered 

combination adds nothing to the laws of nature that is not 

already present when the steps are considered separately.” 

566 U.S. at 79. In other words, after setting aside the law 

of nature, “any additional steps consist[ed] of well-understood, routine, conventional activity already engaged in by 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

8

the scientific community; and those steps, when viewed as 

a whole, add[ed] nothing significant beyond the sum of 

their parts taken separately.” Id. at 79–80. The Court 

found support for this understanding of the judicial exceptions in Flook, observing that, for the Flook claim, the steps 

of monitoring a catalytic conversion process “were all ‘well 

known,’ to the point where, putting the formula to the side, 

there was no ‘inventive concept’ in the claimed application 

of the formula.” Id. at 82. That type of “ordered combination” review (“putting the formula to the side”), however, is

fundamentally different from Diehr’s “claim as whole” principle, which does not carve out the judicial exception from 

the patent eligibility inquiry, nor does it dismiss elements 

that lack novelty.2 See Diehr, 450 U.S. at 188–93.

 

2 Both Mayo and Flook rely on an 1841 English case, 

Neilson v. Harford, 1 Web. P. C. 295 (1841), as supporting 

an “inventive concept” requirement in which a law of nature is treated as something well-known. Mayo, 566 U.S. 

at 82–83; Flook, 437 U.S. at 592. There is reason to believe, 

however, that the decision in Neilson did not turn on such 

a premise. See Tilghman v. Proctor, 102 U.S. 707, 723–25 

(1880) (describing Neilson’s reasoning as drawing “the true 

distinction between a mere principle . . . and a process by 

which a principle is applied to effect a useful result.”); see 

also Brief of Professors Jeffrey A. Lefstin and Peter S. Menell as Amici Curiae in Support of Petition for Writ of Certiorari at 15–21, Sequenom, Inc. v. Ariosa Diagnostics, Inc. 

(2016) (No. 15-1182) (Lefstin and Menell Br.). Moreover, 

no Supreme Court patent eligibility case for a process claim 

prior to Flook relied on an inventive concept inquiry or assumption that a scientific discovery should be regarded as 

well-known. See, e.g., Gottschalk v. Benson, 409 U.S. 63 

(1972); Expanded Metal Co. v. Bradford, 214 U.S. 366 

(1909); Dolbear v. Am. Bell Tel. Co., 126 U.S. 1 (1888); 

Tilghman, 102 U.S. ; Cochrane v. Deener, 94 U.S. 780 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

9

In Alice, the Court reaffirmed this reversion to Flook,

reiterating that, if the claims at issue are directed to laws 

of nature, natural phenomena, or abstract ideas, then we 

must ask “what else is there in the claims before us?” And 

in doing so, we must “consider the elements of each claim 

individually and ‘as an ordered combination’ to determine 

whether the additional elements ‘transform the nature of 

the claim’ into a patent-eligible application.” Alice Corp. 

Pty. v. CLS Bank Int’l, 573 U.S. 208, 217 (2014) (quoting 

Mayo, 566 U.S. at 78–79) (emphases added). As in Mayo, 

Alice described the second step of this analysis “as a search 

for an ‘inventive concept’” that discounts the law of nature 

or abstract idea from that inquiry. Id. (quoting Mayo, 566 

U.S. at 72–73); see also id. at 221 (“A claim that recites an 

abstract idea must include ‘additional features’ to ensure 

‘that the [claim] is more than a drafting effort designed to 

 

(1876); Corning v. Burden, 56 U.S. 252 (1853); Le Roy v. 

Tatham, 55 U.S. 156 (1853) (“A patent will be good, though 

the subject of the patent consists in the discovery of a great, 

general, and most comprehensive principle in science or 

law of nature, if that principle is by the specification applied to any special purpose, so as thereby to effectuate a 

practical result and benefit not previously attained.” (quoting Househill Coal & Iron Co. v. Neilson, 1 Web. P. C. 673, 

683 (1843))); see also O’Reilly v. Morse, 56 U.S. 62, 114–

15,118 (1853) (quoting same passage from Neilson quoted 

in Mayo and Flook, and then stating that “we see nothing” 

in Neilson “which would sanction the introduction of any 

new principle in the law of patents” and relying on “established principles in the American courts”). Importantly, 

Diehr’s reasoning, which post-dates Flook and was controlling authority for 30 years, is incompatible with the inventive concept approach. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

10

monopolize the [abstract idea].’” (quoting Mayo, 566 U.S.

at 77)).3 

When it comes to applying the judicial exceptions, it 

bears noting that the Mayo analytical approach is considerably harder to apply consistently than the Diehr framework, and more aggressive in its reach. Consider the claim 

in Mayo. If that claim had recited just the single step of

administering a synthetic drug to a patient, that singlestep claim would be patent-eligible, but lack novelty under 

§ 102. And if that claim added a second step for determining the subsequent level of a non-naturally occurring metabolite in a patient, that claim also would pass muster 

under § 101, but lack novelty. But when the claim further 

recites a relationship between a metabolite level and its efficacy in a patient, that claim suddenly would be invalid 

under § 101 for violating the law of nature exception. In 

other words, steps 1 and 2 now get pushed aside and declared insignificant, and the last step is designated as the 

“focus” of the claim, i.e., the heart of the invention. The 

notion that adding claim language can convert an otherwise patent-eligible claim into a patent-ineligible claim is 

counterintuitive and a very difficult thing to explain to 

8,000 patent examiners.4 Moreover, the process of 

 

3 The Alice Court, like Mayo and Flook, states that 

its approach is consistent with the rule that patent claims 

must be considered as a whole, because it considers the 

claim elements separately as well as in combination. Alice, 

573 U.S. at 218 n.3. But, as explained supra, this approach 

is wholly unlike Diehr’s understanding of evaluating the 

claim “as a whole.”

4 That is not to say that the Mayo claim should have 

been upheld as valid. The “wherein” clauses simply identified a mental inference from practicing a prior art process, which is insufficient to distinguish the claim from the 

prior art. See Brief for United States as Amicus Curiae, at 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

11

determining what the claim is “really about” when the 

claim is viewed in pieces, rather than as a whole, can be

highly subjective and impressionistic. This approach puts

courts and examiners in the position of assigning value 

judgments to individual limitations, designating some as

“significant” and others as “insignificant,” and hoping everyone else reaches the same conclusion as to whether the 

claim contains a truly meritorious inventive contribution 

as opposed to a judicial exception embellished with insignificant window dressing. And all this just to resolve the 

threshold question of whether an invention is eligible for 

the patent system. 

As written, Mayo requires a patent claim to have an 

inventive concept apart from the recitation of a natural 

law. That requirement has consequences that go beyond 

the facts of Mayo and is certainly clear enough that we are 

obliged to follow it. But, as explained above, Mayo’s framework is in tension on its face with Diehr, which was equally 

clear in requiring that a patent claim be considered as a 

whole, without putting aside any natural law or otherwise 

dissecting a claim into new versus old elements. Moreover, 

nothing in Mayo suggests that it sought to repudiate anything in Diehr; it instead suggests that it sought to maintain continuity with the Court’s prior cases in this area. As 

for Flook, the Court in Bilski acknowledged that Diehr had 

“established a limitation” on Flook by “emphasiz[ing] the 

need to consider the invention as a whole, rather than ‘dissect[ing] the claims into old and new elements . . . in the 

analysis.’” Bilski, 561 U.S. at 611 (quoting Diehr, 450 U.S. 

at 188). Importantly, Mayo does not say that it nullified 

this key “limitation” expressed in Diehr. Furthermore, as 

Judge Dyk points out in his concurrence, the Court’s opinion in Ass’n for Molecular Pathology v. Myriad Genetics, 

 

26–28, Mayo v. Prometheus, 566 U.S. 66 (2012) (No. 10-

1150).
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

12

Inc., 569 U.S. 576 (2013), which issued after Mayo, could 

be read as potentially maintaining an open door for diagnostic claims such as Athena’s, because they may be regarded as applications of knowledge of discovered natural 

laws. See Dyk Concurrence at 7. Myriad thus could suggest that Mayo should not go as far as its language indicates.

Through it all, there is a serious question today in patent law as to what extent Diehr remains good law in light 

of Mayo. We are not in a position to resolve that question, 

but the Supreme Court can. Resolution of the present confusion is important because if Mayo in fact overruled the 

principles in Diehr (as reiterated in Bilski), then that 

would be a significant incursion on the settled expectations 

that had existed for 30 years since Diehr. Relying on the 

Diehr framework, the Patent Office examined and granted 

many patents for medical diagnostic methods, establishing 

settled expectations in those granted property rights, and 

prompted companies and research institutions to organize 

their conduct and choices accordingly. Many of these diagnostic claims, including the ones at issue here, do not hold 

up well against Mayo’s more searching, claim dissection

scrutiny. 

III. ATHENA’S CLAIMS

Judge Newman, Judge Moore, the petitioner, and the 

amici raise several valid concerns. But I believe the reasoning underlying recent Supreme Court decisions compels

us to affirm the district court’s invalidity determination 

here. While Diehr long established that we must evaluate 

“the claim as a whole” for § 101 purposes, that principle has 

been considerably undermined, for we’ve been recently instructed to ask for claims such as Athena’s, “do the patent 

claims add enough to their statements of the correlations 

to allow the processes they describe to qualify as patenteligible processes that apply natural laws?” Mayo, 566 

U.S. at 77 (emphases in original). Moreover, “[p]urely 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

13

‘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.

It appears to me that, per Mayo, because the association of an antibody and a medical disorder is deemed to be 

a law of nature rather than an application of a law of nature, detecting that law of nature, by using data gathering 

steps or devices that can be said to be basic, conventional, 

or obvious, fails § 101. This is in contrast to examples, such 

as Diehr and Neilson, in which, as characterized by Mayo,

the claimed inventions included unconventional steps beyond reliance on an abstract scientific principle. Mayo, 566 

U.S. at 80–81, 83–84. In other words, the Supreme Court 

has made clear that detecting a law of nature (without 

more than conventional steps for accessing the law of nature) does not qualify as a patent-eligible application of a 

law of nature.

Here, the inventors of Athena’s U.S. Patent No. 

7,267,820 discovered an association between the disorder 

myasthenia gravis and the presence of muscle specific tyrosine kinase (MuSK) autoantibodies in a patient’s blood. 

At issue are claims 7–9 reciting: 

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 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 

thereon, with said bodily fluid,
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

14

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

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

or antigen determinant complex,

wherein the presence of said label is indicative 

of said mammal is suffering from said neurotransmission or developmental disorder related 

to [MuSK].

8. A method according to claim 7 wherein said label is a radioactive label.

9. A method according to claim 8 wherein said label is 125I.

’820 patent, col. 12 ll. 31–35, col. 12 l. 62 – col. 13 l. 9.

We must accept that the association between the antibody and the disorder is a law of nature. Here, as in Mayo, 

data first must be gathered in order to access and observe 

the newly-discovered law of nature, and the claimed steps 

“simply tell doctors to gather data from which they may 

draw an inference in light of the correlations.” Mayo, 566 

U.S. at 79. That claims 7 and 9 do not preempt all ways of 

observing the law of nature isn’t decisive, as none of the 

steps recited therein add anything inventive to the 

claims. Claim 7’s label-adding and immunoprecipitating 

steps are conventional, standard techniques in the art of 

detecting the presence of a law of nature such as a protein; 

the panel majority opinion notes that these steps do not recite any improvement in the underlying immunoassay 

technology. Athena Diagnostics, Inc. v. Mayo Collaborative 

Servs., LLC, 915 F.3d 743, 751 (Fed. Cir. 2019).

Claim 9 recites use of a particular label, but one that 

was standard to use in the art. This cannot provide the 

inventive concept under Mayo. As an analogy, we would
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

15

not find that a claim directed to an abstract idea of communicating information through a device passes muster 

under § 101 simply because it limits the claimed device to, 

say, a Samsung Galaxy® smartphone. Nor would the Mayo

claim be considered to possess an inventive concept if it had 

recited that the initial step of “administering a drug” be 

performed in a conventional way, such as orally or intravenously.

One amicus brief points out that § 101 provides that 

“[w]hoever invents or discovers” a new or useful process, 

manufacture, machine or composition of matter may be entitled to a patent, and that § 100(a) defines “invention” to 

mean “invention or discovery.” Brief of Freenome Holdings 

Inc. and Achillion Pharm., Inc. as Amici Curiae in Support 

of Neither Party, Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743 (2019) (No. 17-2508). 

Section 100 also defines “process” to include “a new use of 

a known process, machine, manufacture, composition of

matter, or material.” § 100(b). Arguably, Athena’s invention is a claim for a new use (diagnosing myasthenia gravis) 

of a known composition of matter (MuSK autoantibodies). 

Moreover, given that the dual “invention or discovery” 

structure consistently has been part of every Patent Act 

since 1790, this statutory provision suggests that at least 

some discoveries, including Athena’s “discovery” of how to 

diagnose myasthenia gravis, have always been contemplated as patentable subject matter. See Lefstin and Menell Br. at 4–14. However, I am not aware of the Supreme 

Court ever addressing the meaning of “discovers” in § 101

separately from “invents,” and it must be the Supreme 

Court, and not this court, that speaks to that statutory 

question, because the Court already proclaimed that 

“[g]roundbreaking, innovative, or even brilliant discovery 

does not by itself satisfy the section 101 inquiry.” Myriad, 

569 U.S. at 591.
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

16

In sum, I do not think the claims here can withstand 

Mayo’s scrutiny.5 But perhaps when read “as a whole” under Diehr, claims such as claims 7 and 9 in this case could 

be viewed as methods of testing for a specific medical condition, employing a sequence of steps that physically transform materials. By no means do the claims cover a natural 

principle in the abstract. Rather, this sounds like a contribution to the “useful arts” stated in Article I, Section 8, 

Clause 8 of the U.S. Constitution. That those physical, 

transformative steps may apply conventional techniques 

for locating an antibody in a sample would not be disregarded in the threshold inquiry of whether the claimed invention qualifies as subject matter eligible for the patent 

system.

New methods for diagnosing medical conditions, as a 

general matter, intuitively seem to be the kind of subject 

matter the patent system is designed for: to encourage the 

risky, expensive, unpredictable technical research and development that people would not otherwise pursue in the 

hope that if they discover something of great medical value, 

then they will be protected and rewarded for that successful effort with a patent. This category of invention, after 

all, is not the same as methods of entering into contracts, 

or horse whispering, or speed dating or other methods that 

animated many of the concerns underlying Bilski. The 

kind of lab work undertaken in discovering new diagnostics 

 

5 While this court is bound by Mayo, I do not believe 

this court has turned Mayo into a “per se rule” that bars all 

medical diagnostic claims from patent protection. Moore 

Dissent at 4. Diagnostic claims grounded in novel, non-obvious techniques that render a given diagnosis possess an 

inventive concept continue to be granted. As to the difference in outcomes so far in our § 101 decisions between diagnostic and treatment claims, I agree with the analysis in 

Judge Lourie’s concurrence. Lourie Concurrence at 3–4.
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

17

and performing the steps of such claimed inventions can 

only be described as being technical in nature. For several 

decades before Mayo, this has been the basis for why the 

Patent Office granted patents for many medical diagnostics—not just for the law of nature in the abstract, but as 

applied in the real-world medical context to diagnose patient health conditions. In any meaningful sense, this represents a practical application of the discovered law of 

nature, that is, it is applied science in every sense of that 

term. And it should be patentable subject matter in a wellfunctioning patent system.

CONCLUSION

The most recent Supreme Court opinions are clear in 

my view on how to address claims like Athena’s. Even 

though Athena’s claims likely would be found patent-eligible under Diehr’s framework, it is not an inferior court’s 

role to dodge the clear, recent direction of the Supreme 

Court. Accordingly, I concur with denial of the petition for 

rehearing en banc.
United States Court of Appeals 

for the Federal Circuit ______________________

ATHENA DIAGNOSTICS, INC., OXFORD 

UNIVERSITY INNOVATION LTD., MAX-PLANCKGESELLSCHAFT 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.

______________________

MOORE, Circuit Judge, with whom O’MALLEY, WALLACH,

and STOLL, Circuit Judges, join, dissenting from the denial 

of the petition for rehearing en banc.

This is not a case in which the judges of this court disagree over whether diagnostic claims, like those at issue in 

Athena, should be eligible for patent protection. They 

should. None of my colleagues defend the conclusion that 

claims to diagnostic kits and diagnostic techniques, like 

those at issue, should be ineligible. The only difference 

among us is whether the Supreme Court’s Mayo decision 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

2

requires this outcome. The majority of my colleagues believe that our hands are tied and that Mayo requires this 

outcome. I believe Mayo does not. The Patent Act renders 

eligible the invention or discovery of any new and useful 

process. 35 U.S.C. § 101. And the patent system exists to 

promote exactly this sort of specific, targeted application of 

a life-saving discovery, which is characterized by extraordinarily high initial market entry costs. The claims in this 

case should be held eligible, and they are distinguishable

from Mayo.

DIAGNOSTICS ARE PER SE INELIGIBLE

Since Mayo, we have held every single diagnostic claim 

in every case before us ineligible. See Cleveland Clinic 

Found. v. True Health Diagnostics LLC, 760 F. App’x 1013 

(Fed. Cir. 2019) (“Cleveland Clinic II”); Athena Diagnostics, 

Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743 (Fed. 

Cir. 2019); Roche Molecular Sys., Inc. v. CEPHEID, 905 

F.3d 1363 (Fed. Cir. 2018); Cleveland Clinic Found. v. True 

Health Diagnostics LLC, 859 F.3d 1352 (Fed. Cir. 2017) 

(“Cleveland Clinic I”); Genetic Techs. Ltd. v. Merial L.L.C.,

818 F.3d 1369 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. 

Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015); In re 

BRCA1- and BRCA2-Based Hereditary Cancer Test Patent 

Litig., 774 F.3d 755 (Fed. Cir. 2014); PerkinElmer, Inc. v. 

Intema Ltd., 496 F. App’x 65 (Fed. Cir. 2012).1 Despite the 

 

1 The district courts are following our lead, holding 

diagnostic methods ineligible. See, e.g., Illumina, Inc. v. 

Ariosa Diagnostics, Inc., 356 F. Supp. 3d 925 (N.D. Cal. 

2018); Genetic Veterinary Scis., Inc. v. LABOklin GmbH & 

Co., 314 F. Supp. 3d 727 (E.D. Va. 2018); Mallinckrodt 

Hosp. Prods. IP Ltd. v. Praxair Distribution, Inc., No. 15–

170–GMS, 2017 WL 3867649 (D. Del. Sept. 5, 2017); Esoterix Genetic Labs. LLC v. Qiagen Inc., No. 14–CV–13228–

ADB, 2016 WL 4555613 (D. Mass. Aug. 31, 2016); Esoterix 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

3

significance of these diagnostic inventions and the high 

costs of developing them, we have held, because of Mayo,

every one of these life-changing inventions and discoveries 

ineligible. For example, we held a method for assessing a 

patient’s risk of having cardiovascular disease by detecting

a specific enzyme, based on the discovery of the correlation 

between the enzyme and the disease, ineligible. Cleveland 

Clinic I, 859 F.3d at 1363. Cardiovascular disease is the 

number one cause of death in the United States, killing 

more than 600,000 people per year, and costing over $200 

billion annually.2 The diagnostic invention in Cleveland 

Clinic I allowed for early diagnosis of cardiovascular disease and had a better predictive value than the clinically 

used risk factors employed by physicians at the time. 

There can be no argument but that such early diagnoses 

will save lives and reduce future treatment costs. But because of Mayo, such claims were held ineligible. We also 

held ineligible claims to a method of screening for alterations in genes linked to hereditary breast and ovarian cancer. In re BRCA1, 774 F.3d at 765. It is estimated that

breast cancer will kill more than 40,000 people in 2019.3 

Again, there is no reasonable dispute that early diagnoses 

save lives and future medical costs. To be clear, the method

claims were not to the gene itself which is found in nature, 

but rather to a use of the discovered correlation between 

 

Genetic Labs. LLC v. Qiagen Inc., 133 F. Supp. 3d 349 (D. 

Mass. 2015); Genetic Veterinary Scis., Inc. v. Canine EIC 

Genetics, LLC, 101 F. Supp. 3d 833 (D. Minn. 2015). 2 CTRS. FOR DISEASE CONTROL AND PREVENTION, 

Heart Disease Fact Sheet (Aug. 23, 2017), 

https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_

heart_disease.htm. 3 NAT’L CANCER INSTITUTE, Cancer Stat Facts: Female Breast Cancer, https://seer.cancer.gov/statfacts/html/

breast.html.
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

4

certain mutations and breast cancer for diagnostic purposes. In re BRCA1, 774 F.3d at 758. We held ineligible a

method for detecting tuberculosis, one of the world’s deadliest diseases.4 Roche, 905 F.3d at 1374. And claims to 

diagnostic methods related to fetal health, characteristics, 

and genetic disorders, such as Down syndrome, fared no 

better. Ariosa, 788 F.3d at 1378; PerkinElmer, 496 F. App’x 

at 73. The Ariosa method of detecting fetal abnormalities 

based on a simple blood test was an absolute game changer. 

Prior to the Ariosa discovery, such abnormalities were detected with higher cost and higher risk procedures such as 

amniocenteses which had the potential to harm all involved. That brings us to the Athena claims, which are directed to a method of diagnosing patients with an 

autoimmune disease using a protein that had never before 

been associated with the disease. Athena, 915 F. 3d at 747. 

One of every five patients with the autoimmune disease experienced symptoms but did not produce the type of autoantibodies previously associated with the disease, and thus 

were unable to be diagnosed and properly treated at an 

early stage. Id. The claimed diagnostic method in Athena

solved that problem through a specific, narrowly tailored 

diagnostic process but was nonetheless held ineligible. 

None of these diagnostic claims survived because we concluded we had no choice because of Mayo. 

We have turned Mayo into a per se rule that diagnostic 

kits and techniques are ineligible. That per se rule is “too 

broad an interpretation of this exclusionary principle

[which] could eviscerate patent law.” Mayo Collaborative 

Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 

(2012). The Supreme Court has repeatedly cautioned 

against rigid or per se rules. See, e.g., Halo Elecs., Inc. v. 

 

4 CTRS. FOR DISEASE CONTROL AND PREVENTION, Tuberculosis (TB) Data and Statistics (Dec. 31, 2018), 

https://www.cdc.gov/tb/statistics/default.
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

5

Pulse Elecs., Inc., 136 S. Ct. 1923, 1932 (2016) (rejecting 

test which “is unduly rigid”); Octane Fitness, LLC v. ICON 

Health & Fitness, Inc., 572 U.S. 545, 551 (2014) (rejecting 

test as “unduly rigid”); KSR Int’l Co. v. Teleflex Inc., 550 

U.S. 398, 419–20 (2007) (cautioning against “[r]igid preventative rules”); Festo Corp. v. Shoketsu Kinzoku Kogyo 

Kabushiki Co., 535 U.S. 722, 738 (2002) (preferring that 

rules be interpreted “in a flexible way, not a rigid one”); 

Warner-Jenkinson Co., Inc. v. Hilton Davis Chem. Co., 520 

U.S. 17, 32 (1997) (declining to adopt a “rigid rule”); Diamond v. Chakrabarty, 447 U.S. 303, 315 (1980) (declining 

to create a rule that “inventions in areas not contemplated 

by Congress when the patent laws were enacted are unpatentable per se”). 

In his opening statement during The State of Patent

Eligibility in America Senate hearings, Senator Coons recognized that “for medical diagnostics, . . . [there is] a presumption against eligibility that is nearly impossible to 

overcome.” The State of Patent Eligibility in America, Part 

I: Hearing Before the Subcomm. on Intellectual Property of 

the S. Comm. on the Judiciary, 116th Cong. 15:36–45 

(2019) (opening statement of Sen. Coons). And testimony 

from industry representatives confirmed that industry 

members and scholars think “it is unclear whether diagnostic methods are patentable in any meaningful way.” 

See, e.g., The State of Patent Eligibility in America, Part II, 

116th Cong. 7 (2019) (written testimony of Hans Sauer, 

Ph.D., Deputy General Counsel and Vice President for Intellectual Property, Biotechnology Innovation Organization (BIO)).

Our fervor for clarity and consistency has resulted in a

per se rule that excludes all diagnostics from eligibility. I 

do not agree with my colleagues that Mayo requires that 

all of these claims in all of these cases be held ineligible. 

But that is where we are. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

6

I do not fault my colleagues, who under protest have 

concluded that they have no choice but to hold the claims

in Athena ineligible because of Mayo. See Athena, 915 F.3d 

at 753 n.4 (“[W]hether or not we as individual judges might 

agree or not that these claims only recite a natural law . . . 

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 also Ariosa Diagnostics, 

Inc. v. Sequenom, Inc., 809 F.3d 1282, 1287 (Fed. Cir. 2015) 

(Lourie, J., concurring with denial of reh’g en banc) (“[I]t is 

unsound to have a rule that takes inventions of this nature 

out of the realm of patent-eligibility . . . [b]ut I agree that 

the panel did not err in its conclusion that under Supreme 

Court precedent it had no option other than to affirm the 

district court.”). There is surely some broad language in 

Mayo which could lead to this conclusion. I, however, think 

we have extended Mayo too far. Reading the entirety of 

Mayo and the subsequent Myriad decision, the Supreme 

Court did not intend Mayo to be the “sweeping” decision my 

colleagues have concluded it is. See, e.g., Ariosa, 788 F.3d 

at 1380 (Linn, J., concurring) (“I join the court’s opinion invalidating the claims . . . only because I am bound by the 

sweeping language of the test set out in [Mayo].”); Ariosa, 

809 F.3d at 1290 n.3 (Dyk, J., concurring) (stating that we 

must “respect the sweeping precedent of Mayo”); see also 

id. at 1289 (“[T]here is a problem with Mayo insofar as it 

concludes that inventive concept cannot come from discovering something new in nature . . . . Mayo did not fully 

take into account the fact that an inventive concept can 

come not just from creative, unconventional application of 

a natural law, but also from the creativity and novelty of 

the discovery of the law itself.”). It is the role of this court 

to both faithfully follow Mayo and to determine its reach 

when facts and circumstances differ. I dissent from my colleagues’ refusal to rethink our interpretation of Mayo.
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

7

DIAGNOSTICS DESERVE PATENT INCENTIVES

“Diagnosis is the foundation of medicine,” and diagnostic techniques and kits when narrowly claimed are precisely the type of innovation the patent system exists to 

promote.5 Diagnostic techniques, while accounting for less 

than 2.5% of healthcare expenses, “guide[] approximately 

66% of clinical decisions.”6 Diagnostics are an essential 

category of medical technologies, critical to treating illnesses and saving lives. Diagnostic medicine saves lives 

and money through early detection and reduces the need 

for high cost pharmaceuticals or curative procedures, but 

developing diagnostic kits and techniques is expensive and 

time consuming. Development of a new diagnostic test is 

estimated to cost up to $100 million and to take nearly 10 

years.7 

 

5 NAT’L RESEARCH COUNCIL, TOWARD PRECISION 

MEDICINE: BUILDING A KNOWLEDGE NETWORK FOR 

BIOMEDICAL RESEARCH AND A NEW TAXONOMY OF DISEASE, 

Epilogue, (2011) https://www.ncbi.nlm.nih.gov/books/

NBK92141/. 6 UP Rohr et al., The Value of In Vitro Diagnostic 

Testing in Medical Practice: A Status Report, PLOS ONE 

(March 2016), https://journals.plos.org/plosone/article?id=

10.1371/journal.pone.0149856. 7 I. Okeke et al., Diagnostics as Essential Tools for 

Containing Antibacterial Resistance, 14 DRUG RESISTANCE 

UPDATES 95, 101 (April 2011), https://www.sciencedirect.com/science/article/pii/S1368764611000185?via%3Dihub; see also Mystery Solved! What is the Cost to Develop 

and Launch a Diagnostic, DIACEUTICS (Jan. 15, 2013),

https://www.diaceutics.com/?expert-insight=mysterysolved-what-is-the-cost-to-develop-and-launch-a-diagnostic (2013) (The average cost of developing a diagnostic in 

the U.S. is $50–75 million with development of expansion 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

8

Diagnostics economically depend on strong patent protection. Because they are typically characterized as “very 

expensive to develop but relatively cheap to reproduce,” patent protection is required to make it financially viable for 

continued investment in their development.8 As Senator 

Tillis explained in his opening statement during The State 

of Patent Eligibility in America Senate hearings, “[w]hy 

would anyone in their right mind risk millions if not billions of dollars to develop a product when they have no idea 

if they’re eligible for protection? From a business perspective, it simply isn’t worth the risk for many endeavors.”9 

Without the possibility of patent protection to recoup the 

high costs of research and development associated with diagnostic techniques and kits, the impact can only be that 

there will be fewer advances in diagnostic medicine.10 Industry leaders make clear that absent dependable patent 

 

assays on existing platforms costing $10–15 million and development of new platforms costing over $100 million.). 

8 A. Krattiger, Promoting Access to Medical Innovation, WORLD INTELLECTUAL PROPERTY ORGANIZATION (Sept. 

2013), https://www.wipo.int/wipo_magazine/en/2013/05/article_0002.html. 9 The State of Patent Eligibility in America, Part I, 

116th Cong. 3:32–47 (2019) (opening statement of Sen. Tillis). 

10 The State of Patent Eligibility in America, Part II, 

116th Cong. 1–2 (2019) (written testimony of Rick Brandon, Associate. General Counsel, University of Michigan

representing Association of American Universities) 

(“[I]nventors and investors often require the protection of a 

period of exclusivity in order to assume the substantial risk 

of investing the significant resources needed in order to 

bring a product to the public. In the case of products that 

require FDA approval, including diagnostics, this can take 

years and millions of dollars. The public benefits from both 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

9

protection, companies will not move forward with diagnostic innovations.11 As investors routinely recognize, once 

patent protection over medical technologies is lost, these 

innovations essentially become gifts to society and the companies that developed them cannot recoup the time and 

money they spent to do so.12 It is these life-saving fields

though, with such high costs to the initial market investor, 

where patent protection is critical. 

The importance of diagnostics and their cost-reducing 

effects on patient treatment cannot reasonably be questioned. We are hard-pressed to identify facets of modern 

medicine that do not employ or rely on diagnostics. Diagnostics are “crucial in mitigating the effect of disease outbreaks.”13 For example, had diagnostic techniques been 

 

public disclosure and a greater assurance of new products 

and services.”).

11 The State of Patent Eligibility in America, Part III, 

116th Cong. 3 (2019) (written testimony of Peter O’Neill, 

Executive Director of Cleveland Clinic Innovations) (The 

“[a]bility to get protectable intellectual property (usually in 

the form of a patent) is the first, and most influential factor 

in our assessment. If an invention can’t get intellectual 

property protection, usually that is a fatal flaw and the invention is abandoned at that point.”). 

12 M. Rosenblatt, The Real Cost of “High-Priced” 

Drugs, HARVARD BUSINESS REVIEW (Nov. 17, 2014), 

https://hbr.org/2014/11/the-real-cost-of-high-priced-drugs; 

The State of Patent Eligibility in America, Part I, 116th 

Cong. 1–2 (2019) (written testimony of Patrick Kilbride, 

Senior Vice President of the Global Innovation Policy Center at the U.S. Chamber of Commerce).

13 M. Perkins et al., Diagnostic Preparedness for Infectious Disease Outbreaks, 390 SCIENCEDIRECT 2211 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

10

developed before the 2015 Ebola outbreak, and applied to 

patients early enough, the population-attack rate of Ebola 

could have been reduced from 80% to 0%. Id. Ebola is only 

one example. “Poor diagnostic preparedness has [also] contributed to significant delays in the identification of . . . 

Lassa Fever, yellow fever, and Zika.”14 Disease epidemics 

are not the only life-threatening conditions to which diagnostics provide a meaningful response. Diagnostics are 

pivotal to addressing the advent and increase in drug-resistant infections. Current estimates project that by 2050,

drug-resistant infections will “lead to 10 million people dying every year and . . . would cost the world up to 100 trillion” dollars.15 Diagnostic tests are a critical component of 

the answer to this problem. Methicillin-Resistant Staphylococcus Aureus (“MRSA”) is an example of an antibioticresistant infection that burdens American hospitals in 

terms of morbidity, mortality, and healthcare costs.16 Its 

treatment, and the outcome of that treatment, depends on 

appropriate diagnosis and antibiotic administration. Id. 

And the effects of diagnostics in improving the detection 

and treatment of cancer, human immunodeficiency virus, 

 

(2017), https://www.thelancet.com/journals/lancet/article/

PIIS0140-6736(17)31224-2/fulltext. 14 C. Kelly-Cirino et al., Importance of Diagnostics in 

Epidemic and Pandemic Preparedness, 4 BMJ GLOBAL 

HEALTH (2019), https://gh.bmj.com/content/4/Suppl_2/

e001179. 15 J. O’Neill, Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations, THE REV. ON 

ANTIMICROBIAL RESISTANCE, 6 (Dec. 2014). 16 K. Bauer et al., An Antimicrobial Stewardship Program’s Impact with Rapid Polymerase Chain Reaction 

Methicillin-Resistant Staphylococcus Aureus/S. aureus 

Blood Culture Test in Patients with S. aureus Bacteremia, 

51 CLINICAL INFECTIOUS DISEASES 1074 (2010).
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

11

as well as in vitro care should not be overlooked. See Rohr, 

supra note 6. For example, diagnostics improved medical 

approaches to cancer care, and will continue supporting 

progress in a field that cost an estimated $125 billion in the 

United States in 2010.17 Development of diagnostics plays 

a central role in American medical innovation as we face 

increasingly robust medical challenges, with a goal to save 

lives and improve the quality of those lives. 

Not only do diagnostics save lives, they reduce the cost

of treatment. The diagnostic industry drives medical costs 

down, not up. People suffering from illness or disease will 

do whatever they can to find a cure. Proper diagnoses allow for earlier detection of illness and targeted treatment. 

But without proper diagnosis, patients have to endure numerous unsuccessful and costly treatments. Both the financial burden of continued testing and treatment and the 

emotional and physical tolls associated with suffering from 

symptoms, but not knowing the cause, can be reduced or 

even prevented thanks to diagnostics. And when there are 

specific advances, discoveries, or inventions in the diagnostics industry, they must be eligible for patent protection.18 

 

17 A. Mariotto et al., Projections of the Cost of Cancer 

Care in the United States: 2010-2020, 103 J. NAT’L CANCER 

INST. 117, 122 (2011), https://www.ncbi.nlm.nih.gov/pmc/

articles/PMC3107566/.

18 See R. Davis, Senate Scrutinizes Patent Bill’s Effect 

on Drug Prices, Genes, LAW360 (June 6, 2019), 

https://www.law360.com/ip/articles/1164262/senate-scrutinizes-patent-bill-s-effect-on-drug-prices-genes?nl_pk=

c4844ff4-19ab-48d7-b2f9-9fa06ce87648&utm_source=

newsletter&utm_medium=email&utm_campaign=ip (discussing Senator Tillis’ explanation that patent eligibility 

uncertainty “has undermined investment in new medical 

research and could prevent new drugs from being created, 

making it a moot point how much they cost”).
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

12

Unless one opposes the notion of patent protection entirely, it cannot be reasonably disputed that claims to diagnostic kits and techniques, like pharmaceuticals, which 

require enormous initial investments in terms of both time 

and money, are the reason we suffer the promise of a monopoly. As many have explained, without patent protection, there will be little incentive for companies to invest 

the monumental amount of time and money necessary to 

develop diagnostic kits, tools and techniques. A recent article, co-written by Paul Michel, former Chief Judge of the 

Federal Circuit, and David Kappos, former Director of the 

PTO, states:

This uncertain patent climate has a chilling effect 

on innovation in biosciences to the detriment of 

public health. . . . [I]nvestors are less interested in 

funding costly new biomarker diagnostic research. 

As a result, diseases will go undiagnosed, and patients will suffer the consequences. . . . Investment 

in diagnostics goes to the core of containing spiraling health care costs, improving patient outcomes 

and treating illnesses before they become debilitating to suffering Americans.19

This sentiment was echoed by industry leaders during The 

State of Patent Eligibility in America Senate hearings held 

on June 4–5 & 11, 2019. See The State of Patent Eligibility 

in America, Part II, 116th Cong. 6–7 (2019) (written testimony of Hans Sauer, Ph.D., Deputy General Counsel and 

Vice President for Intellectual Property, BIO) (“Absent the 

ability to protect their discoveries with valid patents . . .

 

19 D. Kappos & P. Michel, Supreme Court Patent Decisions are Stifling Health Care Innovation, MORNING 

CONSULT (Oct. 29, 2018), https://morningconsult.com/opinions/supreme-court-patent-decisions-stifling-health-careinnovation/. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

13

companies would lack the necessary incentive to make the 

risky, expensive, and time-consuming investments in research and development often required to bring new technologies to market.”); The State of Patent Eligibility in 

America, Part II, 116th Cong. 9 (2019) (written testimony

of Henry Hadad, President, IPO) (“[C]onfusion about what 

is patent-eligible discourages inventors from pursuing 

work in certain technology areas, including discovering 

new genetic biomarkers and developing diagnostic and artificial intelligence technologies. [This] uncertainty disincentivizes the enormous investment in research and 

development that is necessary to fuel the innovation cycle.”); The State of Patent Eligibility in America, Part I, 

116th Cong. 14:46–15:05 (2019) (opening statement of Sen. 

Coons) (“I worry that this continuing lack of clarity . . . has 

led to reduced investment in the expensive and intensive 

research and development necessary to develop next generation cures . . . .”); The State of Patent Eligibility in America, Part III, 116th Cong. 1:22:12–1:22:35 (2019) (testimony 

of Peter O’Neill, Executive Director of Cleveland Clinic Innovations) (“The work of translating discovery into commercial products requires [patent] protection to justify the 

investment into those discoveries. And absent clarity . . . 

we are not moving forward diagnostic discoveries to translate them into commercial products the way we would do 

otherwise.”); The State of Patent Eligibility in America, 

Part III, 116th Cong. 1:42:12–1:42:28 (2019) (testimony of 

Corey Salsberg, Vice President and Global Head Intellectual Property Affairs for Novartis) (“Make no mistake 

about section 101, this is the gateway to the patent system. 

So what that means in practical terms is it’s a guide as to 

which fields of technologies can support sustained investment, and which ones likely cannot, and that’s why we 

have such deep concerns about the status quo.”); The State 

of Patent Eligibility in America, Part III, 116th Cong. 1

(2019) (written testimony of Robert Deberardine, Chief Intellectual Property Counsel, Johnson & Johnson) (“It is 

only because of the United States patent system, and the 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

14

predictability that it has historically provided, that we 

have been able to make the investments, conduct the research, and take the risks required to develop these treatments. And only with predictability will we be able [to] 

solve today’s most challenging healthcare problems and develop the groundbreaking treatments of tomorrow. Unfortunately, the patent system in the United States today is 

anything but predictable.”). 

The math is simple, you need not be an economist to 

get it: Without patent protection to recoup the enormous 

R&D cost, investment in diagnostic medicine will decline. 

To put it simply, this is bad. It is bad for the health of the 

American people and the health of the American economy. 

And it is avoidable depending on our interpretation of the 

Supreme Court’s holding in Mayo. I have no doubt that my 

colleagues agree with the sentiments herein that diagnostics are important, and that patent protection of such diagnostics is critical to incentivizing their very existence. The 

only point upon which we disagree is over the breadth of 

the Mayo holding. 

ATHENA’S SPECIFICALLY CLAIMED METHOD IS ELIGIBLE

While Mayo did not require the result the panel 

reached in this case, the panel could not disregard our 

binding precedent of cases like Ariosa, Cleveland Clinics, 

and Roche which have interpreted Mayo as requiring this 

per se rule. Thus, the only hope was en banc action. 

It is my view that § 101 and Mayo, when read together 

and in their entireties, compel the holding that the claims 

in Athena are eligible. Under the Patent Act, “[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. Our decisions have ignored the truth that 

claims to specific, narrow processes, even if those processes 

involve natural laws, are not directed to the natural laws
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

15

themselves. And contrary to the “elementary principle

that . . . [we must] ‘give effect, if possible, to every clause 

and word of a statute,’” our § 101 jurisprudence has largely 

ignored Congress’ explicit instruction that a discovery can 

be the basis for a patentable invention. King v. Burwell, 

135 S. Ct. 2480, 2498 (2015) (quoting Montclair v. 

Ramsdell, 107 U.S. 147, 152 (1883)). Section 101 refers to 

both “invent[ion] or discover[y],” and § 100(a) expressly defines invention as any “invention or discovery.” We have 

misread Mayo and how it fits within the framework of the 

judicially-created exceptions to § 101 for laws of nature, 

natural phenomena, and abstract ideas. 

Laws of nature, natural phenomena, and abstract 

ideas are considered “the basic tools of scientific and technological work.” Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 

573 U.S. 208, 216 (2014) (quoting Assoc. for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589

(2013)). The Supreme Court excepted these categories 

from § 101 to ensure that patent law does not “‘inhibit further discovery by improperly tying up the future use of’

these building blocks of human ingenuity.” Id. (quoting 

Mayo, 566 U.S. at 85). Accordingly, “patents cannot issue 

for the discovery” of a law of nature. Funk Bros. Seed Co. 

v. Kalo Inoculant Co., 333 U.S. 127, 130 (1948). Nor can a 

claim to the law of nature become patentable by simply 

“adding the words ‘apply it.’” Mayo, 566 U.S. at 72 (citing 

Gottschalk v. Benson, 409 U.S. 63, 71–72 (1972)). But “an 

application of a law of nature . . . to a known structure or 

process may well be deserving of patent protection.” Id. at 

71 (quoting Diamond v. Diehr, 450 U.S. 175, 187 (1981)). 

We have chosen to ignore the legal space between these 

principles in favor of a swiftly executing, per se rule that 

all diagnostic claims are ineligible. That conclusion is incorrect. 

By distinguishing between claims that recite a law of 

nature and simply add the words “apply it,” and claims that 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

16

recite a concrete application of a law of nature, the Supreme Court suggests we should consider the level of specificity in the claims to determine whether the claim is even 

directed to the natural law. See Alice, 573 U.S. at 223 (“[I]f 

a patent’s recitation of a computer amounts to a mere instruction to implement an abstract idea on a computer, 

that addition cannot impart patent eligibility.”)); Mayo, 

566 U.S. at 72 (“[T]o transform an unpatentable law of nature into a patent-eligible application of such a law, one 

must do more than simply state the law of nature while 

adding the words ‘apply it.’”); Diehr, 450 U.S. at 192 

(“[W]hen a claim recites a mathematical formula (or scientific principle or phenomenon of nature), an inquiry must 

be made into whether the claim is seeking patent protection for that formula in the abstract. . . . [W]hen a claim 

containing a mathematical formula implements or applies 

that formula in a structure or process which, when considered as a whole, is performing a function which the patent 

laws were designed to protect (e.g., transforming or reducing an article to a different state or thing), then the claim 

satisfies the requirements of § 101.”).

The law of nature at issue in Mayo was the “relationship between concentrations of certain metabolites in the 

blood and the likelihood that a dosage of a thiopurine drug 

will prove ineffective or cause harm.” 566 U.S. at 77. Importantly, this relationship was not a new discovery. “At 

the time the discoveries embodied in the patents were 

made, scientists already understood that the levels in a patient’s blood of certain metabolites . . . were correlated with 

the likelihood that a particular dosage of thiopurine drug 

could cause harm or prove ineffective.” Id. at 73. While 

the inventors characterized the precise correlation, they 

could not be said to have discovered the relationship in the 

first place. 

The Court began its analysis with the statement that 

“[i]f a law of nature is not patentable, then neither is a pro-
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

17

cess reciting a law of nature, unless that process has additional features that provide practical assurance that the 

process is more than a drafting effort designed to monopolize the law of nature itself.” Id. at 77–78. It examined the 

limitations of the representative claim, which recited:

A method of optimizing therapeutic efficacy for 

treatment of an immune-mediated gastrointestinal 

disorder, comprising:

(a) administering a drug providing 6-thioguanine to a subject having said immunemediated gastrointestinal disorder; and

(b) determining the level of 6-thioguanine 

in said subject having said immune-mediated gastrointestinal disorder,

wherein the level of 6-thioguanine less 

than about 230 pmol per 8×108 red blood 

cells indicates a need to increase the 

amount of said drug subsequently administered to said subject and

wherein the level of 6-thioguanine greater 

than about 400 pmol per 8×108 red blood 

cells indicates a need to decrease the 

amount of said drug subsequently administered to said subject.

Id. at 74–75.

This claim in its entirety did nothing more than describe the natural relationship between metabolite concentrations and the effective dose of a thiopurine drug. Id. at 

77. “Unlike, say, a typical patent on a new drug or a new 

way of using an existing drug, the patent claims d[id] not 

confine their reach to particular applications of those 

laws.” Id. at 87. The claimed steps were set forth in “highly 

general language covering all processes that make use of 

the correlations . . . including later discovered processes 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

18

that measure metabolite levels in new ways.” Id. at 87. 

Due to their breadth, the Supreme Court concluded that 

upholding the claims “would risk disproportionately tying 

up the use of the underlying natural laws, inhibiting their 

use in the making of further discoveries.” Id. at 73; see also 

id. at 87 (holding that “the basic underlying concern that 

these patents tie up too much future use of laws of nature”

reinforced the holding of ineligibility). “[S]imply appending conventional steps, specified at a high level of generality,” to the law of nature did not make that law patentable.

Id. at 82 (emphasis added). 

The breadth and generality of the Mayo claims led to 

their demise, as they recited nothing more than the natural 

law. We have since ignored these considerations, treating 

every claim that includes a law of nature as directed to that 

law, even if the claim as a whole recites a specific way of 

applying that law of nature to a new and useful end. We 

should not ignore the considerations related to claim 

breadth articulated in Mayo in our § 101 analysis. 

The Athena claims differ significantly from the Mayo

claims. In 1960, before the invention claimed in U.S. Patent No. 7,267,820 (“the ’820 patent”), scientists identified

a specific category of autoantibodies that bind to and interfere with the acetyl choline receptor (AChR)—which is responsible for the transmission of signals from neurons to 

muscle cells—cause Myasthenia gravis (“MG”). ’820 patent

at 1:24–26. The presence of these anti-AChR antibodies 

thus indicates that the patient suffers from MG. However, 

20% of patients who manifested MG-like symptoms did not

have the anti-AChR antibodies. Id. at 1:34–40. It was unknown if this 20%, “have the same or a distinct and separate MG condition,” id. at 1:41–42, and there was “no basis 

for providing an immediate clinical diagnosis for such patients,” id. at 4:20–22. 

The inventors of the ’820 patent discovered that a different type of autoantibody that binds to and interferes 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

19

with muscle-specific tyrosine kinase (MuSK)—another receptor also known to help transmit signals from neurons to 

muscles—can also cause MG. Id. at 1:54–61 (“The present 

inventors surprisingly found that many of the 20% of MG 

patients which do not exhibit any autoantibodies to AChR, 

instead have IgG antibodies . . . indicating that they are 

afflicted with a form of MG which has a different etiology . 

. . .”). The inventors in Athena discovered that these MG 

sufferers produced the anti-MuSK antibody, and created a 

process for diagnosing MG using methods that detect the 

presence of that antibody. These methods had never before 

been used to diagnose MG. Claims 7 and 9, on which the 

majority focused in Athena, require the use of specific laboratory techniques to diagnose a patient based on the natural law that 20% of people having MG produce

autoantibodies to the MuSK protein. Claim 7 recites:

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 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 thereon, with 

said bodily fluid, immunoprecipitating any antibody/MuSK complex or antibody/MuSK epitope or 

antigenic determinant complex from said bodily 

fluid and monitoring for said label on any of said 

antibody/MuSK complex or antibody/MuSK 

epitope or antigen determinant complex, wherein 

the presence of said label is indicative of said mammal is suffering from said neurotransmission or developmental disorder related to muscle specific 

tyrosine kinase (MuSK).

’820 patent at Claims 1, 7. 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

20

The claims provide for a method of diagnosing patients 

with MG using the following concrete steps: (1) contacting 

the patient’s bodily fluid with labeled MuSK, MuSK 

epitope, or other antigenic determinant that binds any 

anti-MuSK antibodies that may be present in the bodily 

fluid; (2) immunoprecipitating any resulting complexes 

from the bodily fluid; and (3) detecting the presence of the 

anti-MuSK antibody by monitoring for the label, whereby 

the presence of the label indicates a diagnosis of MG. Id.

These steps are not set out at the “high level of generality” 

that concerned the Court in Mayo, and they specifically 

confine their reach to a specific application of the relationship between anti-MuSK antibodies and MG. While the 

combination of steps in Mayo amounted to little “more than 

an instruction to doctors to apply the applicable laws when 

treating their patients,” 566 U.S. at 79, claim 7 in Athena 

is a single, specific method for applying the applicable law. 

Indeed, the majority in this case repeatedly acknowledged that the claims in Athena, unlike the claims in Mayo, 

contain specific, concrete steps applying the law of nature. 

See, e.g., Athena, 915 F.3d at 751 (“The claims at issue here 

involve both the discovery of a natural law and certain concrete steps to observe its operation.”). As the majority further acknowledged, claim 9, which depends on claim 7,

“leaves open to the public other ways of interrogating the 

correlation between MuSK autoantibodies and MuSK-related disorders without practicing the claim’s concrete 

steps.” Id. at 752. In fact, the ’820 patent identifies alternate methods for detecting antibodies, such as MuSK-related antibodies. See ’820 patent at 3:33–4:12. The claims 

do not “broadly preempt the use of a natural law,” and do 

not prevent any scientist from using the natural law in association with other common processes. Mayo, 566 U.S. at 

72; see Myriad, 569 U.S. at 595–96. The concreteness and 

specificity of the claims in Athena moves them from reciting a law of nature to a particular application of a law of 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

21

nature. The claims are not directed to a natural law or 

phenomenon. 

The inventiveness of the claimed discovery in the process steps should also be considered when assessing eligibility. New and useful discoveries, such as the before 

unknown relationship between anti-MuSK autoantibodies 

and MG, when applied in a “process,” should pass muster

as eligible under the statutory text of § 101. Our decision 

to entirely disregard the discovery incorporated in the 

claims is a misapplication of the statute. This is not to say 

that a claim on the discovery of a law of nature itself or a 

natural phenomenon should be eligible. I agree it should 

not. But to wholly ignore the inventiveness of the discovery 

when assessing patent eligibility closes our eyes to the statute enacted by Congress. Athena discovered that 20% of 

people suffering from MG generate autoantibodies that 

bind to a MuSK protein. Its claims recite concrete steps to 

detect the presence of autoantibodies to MuSK to diagnose 

MG. These antibody/MuSK complexes had never been 

used by prior art MG diagnostic tests. In contrast, the 

claims in Mayo recited a generic “determining” step, with 

no laboratory test at all specified by the claims, and the 

specification itself stated that the methods were “well-understood, routine, and conventional activity already engaged in by the scientific community.” 566 U.S. at 79. 

Moreover, the Court explained that scientists had routinely performed that very step on thiopurine metabolites, 

the metabolite being detected in the claim. Id. at 78. This 

is not at all the case in Athena. The claims are directed to 

a new and useful process of specific, concrete steps for diagnosing MG using a particular immunoassay that had 

never been previously used to diagnose MG. The claims 

should be held patent eligible under § 101 and Mayo. 

I do not believe that the Supreme Court intended Mayo

to be the sweeping decision it has become. Indeed, it 

warned us that “too broad an interpretation of” its judicial 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

22

exceptions to eligibility “could eviscerate patent law” because “all 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. I do not understand 

Mayo to render ineligible a claim which covers a specific, 

concrete application of a natural law simply because such 

a claim is diagnostic as opposed to therapeutic. Both 

should be eligible. The last word on this from the Supreme 

Court came in Myriad where the Court made clear “patents 

on new applications of knowledge about BRCA1 and 

BRCA2 genes” could be eligible. 569 U.S. at 596. To the 

extent that this Court has read Mayo so broadly that it precludes exactly that sort of patent, we have erred. Doing so 

leaves Mayo at odds with the patent statutes and the later 

Myriad decision. 

CONCLUSION

“It’s important for the judiciary to first recognize that 

there is a problem that needs to be addressed . . . 101 remains the most important substantive patent law issue in 

the United States today. And it’s not even close.” R. Davis, 

Courts Can Resolve Patent Eligibility Problems, Iancu 

Says, LAW 360 (Apr. 11, 2019) (quoting U.S. Patent and 

Trademark Office Director Iancu). In the wake of Mayo, 

we have painted with a broad brush, suggesting that improved diagnostic techniques are not patent eligible. Mayo

did not go so far, and given the import of diagnostic techniques, we should reconsider this case and clarify our precedent. Because my colleagues have declined to do so, there 

are no more options at this court for diagnostic patents. My 

colleagues’ refusal deflates the Amici’s hopeful suggestion

that our precedent leaves the eligibility of a diagnostic 

claim in front of the Federal Circuit “uncertain.” It is no

longer uncertain. Since Mayo, every diagnostic claim to 

come before this court has been held ineligible. While we 

believe that such claims should be eligible for patent protection, the majority of this court has definitively concluded 

that the Supreme Court prevents us from so holding. No 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

23

need to waste resources with additional en banc requests. 

Your only hope lies with the Supreme Court or Congress. I 

hope that they recognize the importance of these technologies, the benefits to society, and the market incentives for 

American business. And, oh yes, that the statute clearly 

permits the eligibility of such inventions and that no judicially-created exception should have such a vast embrace. 

It is neither a good idea, nor warranted by the statute. I 

dissent. 
United States Court of Appeals 

for the Federal Circuit ______________________

ATHENA DIAGNOSTICS, INC., OXFORD 

UNIVERSITY INNOVATION LTD., MAX-PLANCKGESELLSCHAFT 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, with whom WALLACH, Circuit 

Judge, joins, dissenting from denial of the petition for rehearing en banc.

The majority of the court has voted not to rehear this 

case en banc. I write again in dissent because of the importance of medical diagnosis and the critical role of the 

patent system in achieving new diagnostic methods. Diagnostic methods are costly in research and development,

from scientific discovery through federal approval, and are

of substantial public benefit—exemplified by Athena’s
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

2

method of diagnosing Myasthenia Gravis in persons previously undiagnosable. The patent system provides the economic foundation for the cycle of experimental study, 

clinical evaluation and proof, and implementation in commerce. This foundation applies to diagnosis as well as to 

treatment.

The panel majority held that the new diagnostic 

method in U.S. Patent No. 7,267,820 (“the ’820 patent”)

was not eligible for patenting under section 101 of the Patent Act. Athena Diagnostics, Inc. v. Mayo Collaborative 

Servs., LLC, 915 F.3d 743 (Fed. Cir. 2019) (Newman, J., 

dissenting). The panel majority stated that “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,” and therefore methods for determining 

previously unknown correlations for diagnostic purposes 

are not patent-eligible. Id. at 753 n.4.

The majority’s position is a flawed interpretation of the 

Court’s decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012). The Court did 

not hold that methods of diagnosis are subject to unique

patent-eligibility rules. We have mistakenly enlarged the 

Court’s holding, in substance and in application. Rehearing en banc is warranted.

I summarize the reasons for concern:

I

The Supreme Court’s Mayo decision did not convert diagnostic methods into laws of nature

Until Athena’s invention of the diagnostic method described in the ’820 patent, some 20% of patients suffering 

from Myasthenia Gravis were not capable of being diagnosed. The ’820 patent describes and claims a multi-step 

method wherein for such patients the presence in bodily 

fluid of autoantibodies to a protein, muscle-specific tyrosine kinase (MuSK), is detected by “binding of a MuSK or 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

3

its epitope, together with a revealing label, to the autoantibodies in the serum or bodily fluid.” ’820 patent, col. 3, 

l. 66–col. 4, l. 2. The ’820 patent explains that “[t]he present inventors surprisingly found that many of the 20% of 

MG patients which do not exhibit any autoantibodies to 

AChR [acetyl choline receptor] instead have IgG [immunoglobulin] antibodies directed against the extracellular Nterminal domains of MuSK.” Id., col. 1, ll. 54–57.

These antibodies and their reaction with the MuSK 

protein were not known, nor the use of this procedure to 

diagnose Myasthenia Gravis. The separate chemical steps

of radioactive labelling, reaction of an antibody with a protein, separation of the reaction product, and analysis of radioactivity, are described in the specification as conducted 

by conventional methods. However, the panel majority 

held that this new diagnostic method is not patent-eligible, 

stating 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 natural law.” 

Athena, 915 F.3d at 751. This statement is a misapplication of the patent statute, and a misperception of the 

Court’s decision in Mayo.

At issue are patent claims 7–9, shown with claim 1 

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 

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 thereon, 

with said bodily fluid,
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

4

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

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

antigen determinant complex,

wherein the presence of said label is indicative 

of said mammal is suffering from said neurotransmission or developmental disorder related to muscle specific tyrosine kinase (MuSK).

8. A method according to claim 7 wherein said 

label is a radioactive label.

9. A method according to claim 8 wherein said 

label is 125I [iodine isotope 125].

The reaction between the specified antibodies and the 

MuSK protein was not previously known, and the specified

claim steps had not previously been performed, separately 

or in combination. This method of diagnosing Myasthenia 

Gravis and related disorders is conceded to be new and unobvious.

The ’820 patent specification teaches that each claim 

step is conducted by conventional procedures, that is, procedures for creating a radioactively labelled compound, reacting an antibody with a protein, separating any 

antibody-protein complex, and monitoring the radioactivity of the product. The panel majority holds that since the

separate steps are “conventional,” they do not count in the 

section 101 analysis, leaving claims 7–9 with only the general “concept” of “the correlation between the presence of 

naturally-occurring MuSK autoantibodies in bodily fluid 

and MuSK-related neurological diseases like MG.” Athena, 

915 F.3d at 750. The panel majority concluded that “[t]he 

’820 patent thus describes the claimed invention principally as a discovery of a natural law, not as an 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

5

improvement in the underlying immunoassay technology.” 

Id. at 751.

The Court in Mayo admonished against “too broadly 

preempt[ing] the use of a natural law.” 566 U.S. at 72. 

Claims 7–9 claim a new multi-step method of diagnosis; it 

is incorrect to omit from the claims the steps by which the 

method is performed, leaving only the “concept” of the general purpose. En banc review is needed to provide consistent and correct application of statute and precedent to 

methods of medical diagnosis.

II

Statute and precedent require that the claimed

invention is considered as a whole 

The Court explained this principle in KSR Int’l Co. v. 

Teleflex Inc., 550 U.S. 398 (2007):

[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. The Court had explored this principle 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.

Id. at 188. The Court stressed that:

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. The Court further explained that this rule applies to 

patent eligibility as it does to patentability:

The “novelty” of any element or steps in a process, 

or even of the process itself, is of no relevance in 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

6

determining whether the subject matter of a claim 

falls within the § 101 categories of possibly patentable subject matter.

Id. at 188–89; see also, e.g., Parker v. Flook, 437 U.S. 584, 

594 (1978) (“[A] patent claim must be considered as a 

whole.”); 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 viewed, is within the grant.”).

This established rule does not evaporate when the subject matter is a diagnostic method. The Mayo Court did not 

effect such a change. The Court reiterated in Alice Corp. 

Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 217 (2014), that 

“an invention is not rendered ineligible for patent simply 

because it involves an abstract concept” in some of its claim 

elements. There is no support in the Court’s precedent for 

our abandonment of the invention-as-a-whole in determining eligibility under section 101.

The purpose of section 101 is to provide a broad statutory scope to inventive activity. See Bilski v. Kappos, 561 

U.S. 593, 605 (2010) (“Section 101 is a dynamic provision 

designed to encompass new and unforeseen inventions.”

(internal quotation marks omitted)); Diehr, 450 U.S. at 187 

(“[A]n application of a law of nature or mathematical formula to a known structure or process may well be deserving of patent protection.”). In Diamond v. Chakrabarty, 

447 U.S. 303 (1980), the Court observed that “Congress employed broad general language in drafting § 101 precisely 

because such inventions are often unforeseeable,” id. at 

316, and that the legislative history of the 1952 Patent Act 

showed that “Congress intended statutory subject matter 

to ‘include anything under the sun that is made by man,’”

id. at 309 (quoting S. Rep. No. 1979, 82d Cong., 2d Sess., 5 

(1952); H.R. Rep. No. 1923, 82d Cong., 2d Sess., 6 (1952)). 

The Mayo Court cautioned that 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

7

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.

566 U.S. at 71.

The Federal Circuit has respected this long-standing 

principle in contexts other than for diagnostic methods. 

See, e.g., McRO, Inc. v. Bandai Namco Games America Inc., 

837 F.3d 1299, 1313 (Fed. Cir. 2016) (“[C]ourts must be 

careful to avoid oversimplifying the claims by looking at 

them generally and failing to account for the specific requirements of the claims.” (internal quotation marks omitted)). However, we have strayed in our rulings on 

diagnostic methods; our flawed analysis is summarized by 

the majority in Athena, 915 F.3d at 753 n.4 (“We have since 

confirmed that applying somewhat specific yet conventional techniques . . . to detect a newly discovered natural 

law does not confer eligibility under § 101.”).

When viewed on correct law and precedent, Athena’s

diagnostic method meets the requirements of section 101. 

The appropriate analysis of patentability is under sections 

102, 103, and 112; not section 101.

III

The Court in Mayo did not create a section 101

distinction between diagnostic methods and 

therapeutic methods

In Mayo the Court discussed the method at issue in 

that case, and concluded that “upholding the patents would 

risk disproportionately tying up the use of the underlying 

natural laws, inhibiting their use in the making of further 

discoveries.” 566 U.S. at 73. The Court did not hold that 

every diagnostic method ties up a natural law, and the 

Athena panel majority acknowledged that “we agree that 

claim 9 leaves open to the public other ways of 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

8

interrogating the correlation between MuSK autoantibodies and MuSK-related disorders without practicing the 

claim’s concrete steps.” 915 F.3d at 752.

Athena’s diagnostic method is not a law of nature; it is 

a novel man-made method of diagnosis of a neurological

disorder. The Athena diagnostic method, a multi-step 

method performed by a combination of specific chemical 

and biological steps, was unknown in the prior art. The 

Court in Mayo did not exclude such methods from eligibility for patenting.

Following is an outline of this court’s inconsistent rulings between diagnosis and treatment of disease:

A. Methods of diagnosis, held ineligible under 

section 101 

1. In re BRCA1- & BRCA2-Based Hereditary Cancer 

Test Patent Litigation, 774 F.3d 755 (Fed. Cir. 2014). The

claimed invention is a method for screening for genes 

linked to inherited breast and ovarian cancer, by analyzing 

for certain mutations in the DNA. The court held the 

claims ineligible under section 101 as directed to a law of 

nature, and also held that identifying genetic mutations is 

an ineligible abstract idea.

2. Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 

1371 (Fed. Cir. 2015). The claimed invention is a method 

for detecting paternally-inherited fetal abnormalities by 

analyzing the blood or serum of a pregnant female. The 

court held the claims ineligible under section 101, while 

recognizing that “detecting cffDNA in maternal plasma or 

serum that before was discarded as waste material is a positive and valuable contribution to science.” Id. at 1380.

3. Genetic Technologies Ltd. v. Merial L.L.C., 818 F.3d 

1369 (Fed. Cir. 2016). The claimed invention is a method 

for detecting a coding region of DNA based on its relationship to non-coding regions, by amplifying genomic DNA 

with a primer spanning a non-coding sequence in genetic 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

9

linkage to an allele to be detected. The court stated that 

“the patent claim focuses on a newly discovered fact about 

human biology,” id. at 1376, and that this is a law of nature 

and is ineligible subject matter under section 101.

4. Cleveland Clinic Foundation v. True Health Diagnostics LLC, 859 F.3d 1352 (Fed. Cir. 2017). The claimed 

invention is a method for diagnosing risk of cardiovascular 

disease by analyzing for the enzyme myeloperoxidase 

(“MPO”). The court held that even though prior methods 

for detecting MPO were inferior, the discovery of how to 

directly analyze for MPO, and discovery of the relation to 

the risk of cardiovascular disease, although “groundbreaking, ‘even such valuable contributions can fall short of statutory patentable subject matter.’” Id. at 1363 (quoting 

Ariosa, 788 F.3d at 1380). 

5. Roche Molecular Systems, Inc. v. CEPHEID, 905 

F.3d 1363 (Fed. Cir. 2018). The claimed invention is a 

method for detecting the pathogenic bacterium Mycobacterium tuberculosis (“MTB”), based on nucleotide content

and a novel method of analysis. The court stated that the 

method is new, unobvious, and “both faster and more accurate than the traditional MTB detection methods,” id. at 

1366, but held that the method is ineligible under section 

101.

6. Cleveland Clinic Foundation v. True Health Diagnostics LLC, 760 F. App’x 1013 (Fed. Cir. 2019). The 

claimed invention is the novel immunoassay to detect the 

correlation between blood MPO levels and cardiovascular 

disease. The court held that the claims are for a law of 

nature and ineligible under section 101.

In all of these diagnostic cases the claims were held ineligible under section 101, whether or not the method of 

diagnosis was new and unobvious, and independent of patentability under sections 102, 103, and 112.
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

10

B. Methods of treatment, held eligible under 

section 101

1. Rapid Litigation Management Ltd. v. CellzDirect, 

Inc., 827 F.3d 1042 (Fed. Cir. 2016). The claimed invention 

is a “method of producing a desired preparation of multicryopreserved hepatocytes [liver cells].” Id. at 1047. The 

court stated that “the natural ability of the subject matter 

to undergo the process does not make the claim ‘directed to’ 

that natural ability,” id. at 1049 (emphasis omitted), and 

“[t]his type of constructive process, carried out by an artisan to achieve ‘a new and useful end,’ is precisely the type 

of claim that is eligible for patenting,” id. at 1048 (quoting 

Alice, 573 U.S. at 217).

2. Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals Int’l Ltd., 887 F.3d 1117 (Fed. Cir. 2018). The 

claimed invention is a method of treating schizophrenia 

with the known drug iloperidone, where the dose is adjusted based on whether the patient is a “CYP2D6 poor metabolizer.” Id. at 1121. The method uses genetic testing to 

determine CYP2D6 metabolism. The court held that this 

is “a specific method of treatment for specific patients using 

a specific compound at specific doses to achieve a specific 

outcome,” id. at 1136, and is eligible under section 101.

3. Natural Alternatives Int’l, Inc. v. Creative Compounds, LLC, 918 F.3d 1338 (Fed. Cir. 2019). The claimed 

invention is a method of increasing athletic performance by 

administering beta-alanine in larger quantities. The court 

held the method eligible under section 101, although the 

mechanism was a natural effect.

4. Endo Pharmaceuticals Inc. v. Teva Pharmaceuticals

USA, Inc., 919 F.3d 1347 (Fed. Cir. 2019). The claimed invention is a method of treating patients with oxymorphone, 

based on the discovery that patients with impaired kidney 

function need less oxymorphone for pain relief. The court

stated that the method was patent-eligible, for “the claims 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

11

here are directed to a treatment method, not a detection 

method.” Id. at 1356 (emphasis in original).

IV

The amici curiae advise on the consequences of 

our rulings1

The major biotech industry organizations advise that 

our court’s application of Mayo “has caused great uncertainty to the industry, and . . . has called into doubt innumerable biotech patents.” Biotechnology Innovation 

Organization (BIO) Br. at 3. BIO discusses the inconsistency of our section 101 rulings, and points out that 

“[t]he panel decision reflects a troubling divergence in this 

court’s section 101 jurisprudence between software and biotech inventions,” explaining that in software cases the 

threshold analysis focuses on whether the claims contain a 

technical improvement over the prior art, whereas this aspect is absent from our biotech analyses. Id. at 9.

The amici discuss the adverse effect of our section 101 

rulings on advances in medical diagnosis. Seven Law Professors state that “diagnostic tests form[] the basis of 60%–

70% of all medical treatment decisions,” and “[d]iagnostic 

tests have immense benefits for patient care and greatly 

reduce associated costs, including decreasing hospitalization and avoiding unnecessary treatment.” Profs. Br. at 11 

(citing The Value of Diagnostics Innovation, Adoption and 

Diffusion into Health Care (July 2005), available at

 

1 Amicus curiae briefs were filed by the Biotechnology Innovation Organization, Pharmaceutical Research 

and Manufacturers of America, Croplife International, 

Wisconsin Alumni Research Foundation, Seven Law Professors, and Freenome Holdings Inc. and Achillion Pharmaceuticals, Inc.
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

12

https://dx.advamed.org/sites/dx.advamed.org/files/resource/

Lewin%20Value%20of%20Diagnostics%20Report.pdf). 

The Law Professors state that “[t]he economics of the 

R&D and commercialization of innovative diagnostic tests 

reflect the core economic justification for the patent system: The marginal cost of making a diagnostic test is relatively low, but the ex ante R&D costs can be enormous,” 

stating that the cost of commercializing a diagnostic test is 

between $50-$100 million. Id. at 11–12 (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-solved-what-is-thecost-to-develop-and-launch-a-diagnostic). The Law Professors state that by “creat[ing] an unduly restrictive patent 

eligibility doctrine under § 101, the majority decision and 

many other court decisions send the wrong message to innovators that groundbreaking diagnostic tests born of the 

biotechnological arts in the modern biopharmaceutical industry are virtually per se unpatentable under § 101.” Id.

at 13.

Amici curiae Freenome Holdings and Achillion Pharmaceuticals suggest that our jurisprudence contravenes

“promot[ing] the Progress of Science and useful Arts.” U.S. 

Const. art. I, § 8, cl. 8. These amici point to the judicial

duty to construe section 101 to include both inventions and 

discoveries, and that discovery of a new diagnostic method 

is within the constitutional purpose.

I repeat 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 thoughtful scholars, 

it warrants judicial attention.” Athena, 915 F.3d at 762 

(Newman, J., dissenting).
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

13

The need for en banc action

The judicial responsibility is to provide clear and consistent law in conformity with statute. Our holdings on 

medical diagnostics contravene the admonition that courts 

“should not read into the patent laws limitations and conditions which the legislature has not expressed.” 

Chakrabarty, 447 U.S. at 308. 

The legislative plan is for an incentive system that supports advances in useful technologies by enabling innovators to benefit economically. The patent statute requires 

that the new knowledge is disclosed to the public, where it 

adds to the body of knowledge and, in turn, may be studied

and built upon. No benefit has been suggested by excluding medical diagnostic methods from the patent incentive 

system. 

This case presents an opportunity for judicial review

and judicial remedy. Although diagnostic methods are not 

the only area in which section 101 jurisprudence warrants 

attention, Federal Circuit precedent is ripe for reconsideration specific to diagnostic methods, to correct our application of the Mayo decision and to restore the necessary 

economic incentive. As summarized by Senators Chris 

Coons and Thom Tillis, co-chairs of the Senate Subcommittee that is conducting hearings on proposed remedial legislation, “courts have clouded the line to exclude critical 

medical advances like life-saving precision medicine and 

diagnostics,” and “studies showed that investors familiar 

with the current lack of clarity invest less in critical research and development in areas like medical diagnostics.” 

The Senators stated that “[e]ven some witnesses advocating against broad reform conceded that there are problems 

with the current system, particularly in the life sciences.” 

Report available at https://www.law360.com/articles/1171672/

what-coons-and-tillis-learned-at-patent-reform-hearings

(June 21, 2019). 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

14

From my colleagues’ denial of en banc review, I respectfully dissent.
United States Court of Appeals 

for the Federal Circuit ______________________

ATHENA DIAGNOSTICS, INC., OXFORD 

UNIVERSITY INNOVATION LTD., MAX-PLANCKGESELLSCHAFT 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.

______________________

STOLL, Circuit Judge, with whom WALLACH, Circuit 

Judge, joins, dissenting from the denial of the petition for 

rehearing en banc.

In a series of cases since the Supreme Court’s decision 

in Mayo Collaborative Services v. Prometheus Laboratories, 

Inc., 566 U.S. 66 (2012), we have established a bright-line 

rule of ineligibility for all diagnostic claims. See, e.g., Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 

1377 (Fed. Cir. 2015) (rejecting a diagnostic claim because 

the “only subject matter new and useful as of the date of 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE

SERVICES

2

the application was the discovery of the presence of cffDNA 

in maternal plasma or serum”). This rule as applied to the 

facts of this case dictated that the majority panel find the 

claimed invention ineligible. But, because this court’s 

bright-line rule is based on an over-reaching and flawed 

test for eligibility, a test that undermines the constitutional rationale for having a patent system—promoting the 

progress of science and useful arts—the court should take 

this opportunity to correct its erroneous rule. So, while I 

stand by the panel decision in this case, I write separately 

to dissent from the denial of en banc rehearing because the

question of the eligibility of diagnostic inventions is exactly 

the type of exceptionally important issue that warrants full 

consideration by this court.

Federal Rule of Appellate Procedure 35 directs us to 

order rehearing en banc when “the proceeding involves a 

question of exceptional importance.” Fed. R. App. P.

35(a)(2). A question is of exceptional importance if it creates “important systemic consequences for the development of the law and the administration of justice.” Watson 

v. Geren, 587 F.3d 156, 160 (2d Cir. 2009). As Judge Newman and Judge Moore aptly describe, a wholesale bar on 

patent eligibility for diagnostic claims has far-reaching and 

long-ranging implications for the development of life-saving diagnostic methods. The eligibility of life-saving inventions is not only one of the most important issues of patent 

law, but of human health. Thus, the importance of the issue here mandates that we consider it en banc.

Interpreting Mayo, our prior opinions seem to take for 

granted that the Supreme Court has foreclosed all avenues 

of patent protection for diagnostic claims. As Judge Moore 

points out, we have held every diagnostic claim in every 

case before us ineligible. Dissent Op. at 2 (Moore, J.). Our 

inflexible following of Mayo has created flawed decisions 

that are inconsistent with the precepts of Mayo and our patent system as a whole. The Mayo test was guided by 

broad-sweeping principles that are not applicable to every 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

3

individual diagnostic claim. For example, Mayo emphasizes that patent eligibility cannot apply to “processes that 

too broadly preempt the use of a natural law.” 566 U.S. at 

72. Certain diagnostic claims, such as the ones at issue in 

this case, are so narrowly tailored that preemption is not a 

reasonable concern.

Given the importance of this question, I would urge the

en banc court to take the opportunity to entertain the 

thoughtful argument and fully developed record that such

review would provide, and reconsider this critically important issue. As Congress’s recent interest in § 101 legislation has demonstrated, there are a variety of 

stakeholders that consider this issue to be vitally important. En banc rehearing would not only permit us to 

have a more extensive view of the various considerations 

underlying Mayo, but it would also allow us to create judicial doctrine geared toward the practical application of 

Mayo’s principles. At the very least, en banc review would 

help the court develop an articulable standard for its § 101 

jurisprudence moving forward.

In my view, by consistently bypassing en banc review 

of a critical issue that goes to the heart of this court’s jurisdiction, we are abdicating our responsibility. For this reason, I respectfully dissent.
United States Court of Appeals 

for the Federal Circuit ______________________

ATHENA DIAGNOSTICS, INC., OXFORD 

UNIVERSITY INNOVATION LTD., MAX-PLANCKGESELLSCHAFT 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.

______________________

O’MALLEY, Circuit Judge, dissenting from the denial of the 

petition for rehearing en banc.

I agree with all aspects of Judge Moore’s thoughtful 

dissent. Indeed, I agree with all my dissenting colleagues 

that our precedent applies the Supreme Court’s holding in 

Mayo Collaborative Services v. Prometheus Laboratories, 

Inc., 566 U.S. 66 (2012) too broadly. I write separately, 

however, because I believe that confusion and disagreements over patent eligibility have been engendered by the 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

2

fact that the Supreme Court has ignored Congress’s direction to the courts to apply 35 U.S.C. sections 101, et seq

(“Patent Act”) as written. Specifically, the Supreme Court 

has instructed federal courts to read into Section 101 an

“inventive concept” requirement—a baffling standard that 

Congress removed when it amended the Patent Act in 

1952. I encourage Congress to amend the Patent Act once 

more to clarify that it meant what it said in 1952.

I begin with some historical perspective. After World 

War II, federal courts were invalidating patents at breakneck speed. Lawrence Baum, The Federal Courts and Patent Validity: An Analysis of the Record, 56 J. Patent Office

Soc’y 758, 760 tbl. 1 (1974) (showing that federal appellate 

courts, on average, invalidated patents at a rate of 77% between 1941–1945), 777 tbl. 5 (showing that the Supreme 

Court invalidated patents at a rate higher than 81% from 

1921–1973, except during 1953–1964 when the Court did 

not issue any decisions on patent validity). As Justice 

Jackson wrote, it seemed the only valid patent was “one 

which [the Supreme Court] ha[d] not been able to get its 

hands on.” Jungersen v. Ostby & Barton Co., 335 U.S. 560, 

572 (1949) (Jackson, J., dissenting). This was due, in large 

part, to what became known as the “invention requirement”—itself “invented” by the Supreme Court rather than 

Congress or the Constitution. Applying this requirement 

meant asking whether a patent evidenced “invention.” 

Prominent jurists of that time remarked that the requirement was unworkable. Judge Learned Hand opined 

that, under this requirement, “‘invention’ became perhaps 

the most baffling concept in the whole catalogue of judicial 

efforts to provide postulates for indefinitely varying occasions.” Lyon v. Bausch & Lomb Optical Co., 224 F.2d 530, 

536 (2d Cir. 1955). According to Judge Giles Rich, because 

inventiveness “is an unmeasurable quantity having different meanings for different persons,” the invention requirement “left every judge practically scott-free to decide this 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

3

often controlling factor according to his personal philosophy of what inventions should be patented.” Giles S. Rich, 

The Vague Concept of Invention as Replaced by Sec. 103 of 

the 1952 Patent Act, 46 J. Patent Office Soc’y 855, 865 

(1964) (internal quotations and citations omitted). If the 

invention requirement and its criticisms sound familiar, 

that is because they are. 

Congress attempted to address these criticisms by

amending the Patent Act to replace the ill-defined and judicially-created invention requirement with the more 

workable anticipation and obviousness tests codified in 

Sections 102 and 103. Patent Act of 1952, Pub. L. No. 82-

593, § 103, 66 Stat. 792, 798 (1952); see, e.g., H.R. 4061, 

80th Cong. (1947) (as introduced to the H. Comm. on the 

Judiciary, July 1, 1947) (“A BILL To establish a criterion 

of invention with respect to patent applications and issued 

patents[.]”); Nat’l Patent Planning Comm’n, The American 

Patent System, June 18, 1943, H.R. Doc. 78-239, at 10 

(“One of the greatest technical weaknesses of the patent 

system is the lack of a definitive yardstick as to what is 

invention.”); id. at 5 (“The most serious weakness in the 

present patent system is the lack of a uniform test or standard for determining whether the particular contribution of 

an inventor merits the award of the patent grant. . . . The 

difficulty in applying this statute arises out of the presence 

of the words ‘invented’ and ‘discovered.’ Novelty alone is 

not sufficient, nor is utility, nor is the final accomplishment. There must also be present some mysterious ingredient connoted in the term ‘invented.’”). 

But although Congress so amended the Act decades 

ago, we continue to apply the invention requirement today

under a new name—the “inventive concept” requirement. 

Early cases applying § 101 after the 1952 amendment, 

such as Parker v. Flook, 437 U.S. 584 (1978), drew heavily 

from cases decided under the “invention” requirement. 

Compare Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 

U.S. 127, 131 (1948) (concluding that the “aggregation of 
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

4

species” at issue “fell short of invention” because “[i]f 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”), with Flook, 437 U.S. at 591 (“Mackay Radio and 

Funk Bros. point to the proper analysis for this case.”). 

Flook therefore forged a two-part test, with respect to 

§ 101, that is seemingly indistinguishable from the one 

that had been applied in many “invention” cases over 

twenty-five years earlier. First, Flook treated the natural 

law as part of “the prior art.” Flook, 437 U.S. at 594. Second, Flook asked whether what remained—apart from the 

prior art, i.e. the natural law—constituted “invention.” Id. 

(“Respondent’s process is unpatentable under § 101, not because it contains a mathematical algorithm as one component, but because once that algorithm is assumed to be 

within the prior art, the application, considered as a whole, 

contains no patentable invention.”); see also Diamond v. 

Diehr, 450 U.S. 175, 204 (1981) (“Under this procedure, the 

algorithm is treated for § 101 purposes as though it were a 

familiar part of the prior art; the claim is then examined to 

determine whether it discloses ‘some other inventive concept.’”) (quoting Flook, 437 U.S. at 594)). Against this backdrop, the search for an inventive concept—now enshrined 

in the § 101 inquiry via Mayo—calls back to the invention 

requirement that Congress quite deliberately abrogated 

through the Patent Act of 1952.

In fact, the disagreement here centers on whether the 

additional limitations in the claims, either individually or 

as an ordered combination, satisfy the inventive concept 

requirement. Compare Lourie Op. at 4 (“Under Supreme 

Court precedent, I do not believe that specific yet purely 

conventional detection steps impart eligibility to a claim 

that otherwise only sets forth what the Court has held is a 

natural law.” (internal quotations omitted)), with Moore 

Op. at 20 (“These [additional] steps are not set out at the 

‘high level of generality’ that concerned the Court in Mayo,
ATHENA DIAGNOSTICS, INC. v. MAYO COLLABORATIVE 

SERVICES

5

and they specifically confine their reach to a specific application of the relationship between anti-MuSK antibodies 

and MG.”). Had the Supreme Court not disregarded Congress’s wishes for a second time, perhaps the outcome in 

this case would be different. See Lourie Op. at 2 (“If I could 

write on a clean slate, . . . I would not exclude uses or detection of natural laws.”). Indeed, claims directed to uses 

of natural laws rather than the natural laws themselves

would be eligible under § 101 as written. Because the Supreme Court judicially revived the invention requirement 

and continues to apply it despite express abrogation, I dissent to encourage Congress to clarify that there should be 

no such requirement read into § 101; to clarify that concepts of novelty and “invention” are to be assessed via application of other provisions of the Patent Act Congress 

designed for that purpose.