United States Court of Appeals 

for the Federal Circuit ______________________ 

ARIOSA DIAGNOSTICS, INC., NATERA, INC., 

Plaintiffs-Appellees

DNA DIAGNOSTICS CENTER, INC.,

Counterclaim Defendant-Appellee

v.

SEQUENOM, INC., SEQUENOM CENTER FOR 

MOLECULAR MEDICINE, LLC,

Defendants-Appellants

ISIS INNOVATION LIMITED,

Defendant

______________________ 

2014-1139, 2014-1144

______________________ 

Appeals from the United States District Court for the 

Northern District of California in Nos. 3:11-cv-06391-SI, 

3:12-cv-00132-SI, Judge Susan Y. Illston.

______________________ 

ON PETITION FOR REHEARING EN BANC

______________________ 

MICHAEL J. MALECEK, Kaye Scholer LLP, Palo Alto, 

CA, filed a petition for rehearing en banc for defendantsappellants. Also represented by PETER E. ROOT; ATON 

ARBISSER, Los Angeles, CA; THOMAS GOLDSTEIN, ERIC F.

CITRON, Goldstein & Russell, P.C., Bethesda, MD.
2 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

DAVID ISAAC GINDLER, Irell & Manella LLP, Los Angeles, CA, filed a response to the petition for plaintiffappellee Ariosa Diagnostics, Inc. Also represented by 

ANDREI IANCU, JOSHUA GORDON; AMIR NAINI, Russ August 

& Kabat, Los Angeles, CA.

MARK ANDREW PERRY, Gibson, Dunn & Crutcher LLP, 

Washington, DC, filed a response to the petition for 

plaintiff-appellee Natera, Inc. Also represented by TRACEY 

B. DAVIES, BRETT ROSENTHAL, MICHAEL A. VALEK, Dallas, 

TX. 

WILLIAM PAUL SCHUCK, Bartko, Zankel, Bunzel & Miller, San Francisco, CA, for counterclaim defendantappellee DNA Diagnostics Center, Inc.

GIDEON A. SCHOR, Wilson Sonsini Goodrich & Rosati, 

PC, New York, NY, for amici curiae Amarantus Bioscience Holdings, Inc., Personalis, Inc., Population Diagnostics, Inc. Also represented by MAYA SKUBATCH, Palo Alto, 

CA; RICHARD TORCZON, CHARLES J. ANDRES, JR., Washington, DC.

LANA GLADSTEIN, Nutter McClennen & Fish LLP, 

Boston, MA, for amicus curiae Bioindustry Association. 

Also represented by KONSTANTIN M. LINNIK, ISAAC A.

HUBNER. 

CHRISTOPHER MICHAEL HOLMAN, University of Missouri-Kansas City, Kansas City, MO, for amici curiae 

Biotechnology Industry Organization, Pharmaceutical 

Research and Manufacturers of America. Biotechnology 

Industry Organization also represented by BRIAN P.

BARRETT, Eli Lilly and Company, Indianapolis, IN; LI 

WESTERLUND, Bavarian Nordic, Inc., Redwood City, CA.
ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 3

BENJAMIN JACKSON, Myriad Genetics, Inc., Salt Lake 

City, UT, for amicus curiae The Coalition for 21st Century 

Medicine. Also represented by DAVID CARTER HOFFMAN, 

Genomic Health, Inc., Redwood City, CA.

DONALD LOUIS ZUHN, JR., McDonnell Boehnen Hulbert & Berghoff LLP, Chicago, IL, for amicus curiae Paul 

Gilbert Cole.

TEIGE P. SHEEHAN, Heslin, Rothenberg, Farley & Mesiti, P.C., Albany, NY, for amicus curiae Intellectual 

Property Owners Association. Also represented by PHILIP 

STATON JOHNSON, Johnson & Johnson, New Brunswick, 

NJ; KEVIN H. RHODES, 3M Innovative Properties Company, St. Paul, MN; HERBERT CLARE WAMSLEY, JR., Intellectual Property Owners Association, Washington, DC.

MATTHEW JAMES DOWD, Andrews Kurth LLP, Washington, DC, for amicus curiae JYANT Technologies, Inc. 

Also represented by ROBERT A. GUTKIN, SUSHILA 

CHANANA. 

JEFFREY LEFSTIN, University of California Hastings 

College of Law, San Francisco, CA, for amici curiae Jeffrey Lefstin, Peter S. Menell.

JOHN D. MURNANE, Fitzpatrick, Cella, Harper & Scinto, New York, NY, for amicus curiae New York Intellectual Property Law Association. Also represented by ALICIA 

ALEXANDRA ROSE RUSSO, ERIN AUSTIN; DOROTHY R. AUTH, 

Cadwalader, Wickersham & Taft LLP, New York, NY; 

IRENA ROYZMAN, Patterson Belknap Webb & Tyler LLP, 

New York, NY; DAVID F. RYAN, Croton-on-Hudson, NY.

COREY A. SALSBERG, Novartis International AG, Basel, Switzerland, for amicus curiae Novartis AG.
4 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

KEVIN EDWARD NOONAN, McDonnell Boehnen Hulbert 

& Berghoff LLP, Chicago, IL, for amici curiae TwentyThree Law Professors. 

DAN L. BAGATELL, Perkins Coie LLP, Phoenix, AZ, for 

amici curiae Wisconsin Alumni Research Foundation, 

Marshfield Clinic, MCIS, Inc. Also represented by 

MICHELLE MARIE UMBERGER, Madison, WI; MICHAEL 

ROBERT OSTERHOFF, Chicago, IL.

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

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

HUGHES, and STOLL, Circuit Judges.

LOURIE, Circuit Judge, with whom MOORE, Circuit 

Judge, joins, concurs with the denial of the petition for 

rehearing en banc.

DYK, Circuit Judge, concurs with the denial of the petition for rehearing en banc.

NEWMAN, 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 defendants-appellants Sequenom, Inc. and Sequenom Center for 

Molecular Medicine, LLC. The petition for rehearing was

first referred to the panel that heard the appeal, and 

thereafter, to the circuit judges who are in regular active 

service. A response was invited by the court and filed by 

plaintiffs-appellees Ariosa Diagnostics, Inc. and Natera, 

Inc. A poll was requested, taken, and failed.

Upon consideration thereof,

IT IS ORDERED THAT: 
ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 5

(1) The petition for rehearing en banc is denied.

(2) The mandate of the court will issue on December 

9, 2015.

 FOR THE COURT

December 2, 2015 /s/ Daniel E. O’Toole 

 Date Daniel E. O’Toole

 Clerk of Court 
United States Court of Appeals 

for the Federal Circuit ______________________ 

ARIOSA DIAGNOSTICS, INC., NATERA, INC., 

Plaintiffs-Appellees

DNA DIAGNOSTICS CENTER, INC.,

Counterclaim Defendant-Appellee

v.

SEQUENOM, INC., SEQUENOM CENTER FOR 

MOLECULAR MEDICINE, LLC,

Defendants-Appellants

ISIS INNOVATION LIMITED,

Defendant

______________________ 

2014-1139, 2014-1144

______________________ 

Appeals from the United States District Court for the 

Northern District of California in Nos. 3:11-cv-06391-SI, 

3:12-cv-00132-SI, Judge Susan Y. Illston. 

______________________ 

LOURIE, Circuit Judge, with whom MOORE, Circuit Judge, 

joins, concurring in the denial of the petition for rehearing 

en banc.

I concur in the court’s denial of rehearing en banc in 

this case, based on the precedent of Mayo Collaborative 

Services v. Prometheus Laboratories, Inc., 566 U.S. __, 132 

S. Ct. 1289 (2012). I do so because I find no principled 
2 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

basis to distinguish this case from Mayo, by which we are 

bound. I write separately to express some thoughts

concerning laws of nature and abstract ideas, which seem 

to be at the heart of patent-eligibility issues in the medical sciences. 

Since the Supreme Court’s decision in Bilski v. Kappos, 561 U.S. __, 130 S. Ct. 3218 (2010), the issue of 

patent eligibility under § 101 has been of key importance 

in the adjudication of patent cases, particularly in the 

field of software. The Court’s decisions in Mayo, Association for Molecular Pathology v. Myriad Genetics, Inc., 569 

U.S. __, 133 S. Ct. 2107 (2013), and Alice Corp. v. CLS 

Bank International, 573 U.S. __, 134 S. Ct. 2347 (2014), 

have further brought the focus onto the field of medical 

diagnostics.

The Supreme Court in Mayo determined that the 

claims in that patent “set forth laws of nature.” It further 

held in Mayo that steps additional to those setting forth 

laws of nature in a claimed process must add something 

“that in terms of patent law’s objectives ha[ve] significance” to the natural laws, such that those steps transform the process into an inventive application of those 

laws. Mayo, 132 S. Ct. at 1299. Moreover, the Court 

rejected “post-solution activity that is purely conventional 

or obvious” as not significant enough to bring a claimed 

invention within the realm of patent-eligible subject 

matter. Id. (internal quotation marks and alteration 

omitted).

Alice relates to the third specific exception to eligibility—abstract ideas—and its discussion also incorporates

the requirement of an “inventive concept” beyond “conventional steps.” It held that claims that amount to 

nothing more than instruction to apply an abstract idea 

are not patent eligible, although application of the abstract idea may be. In my view, neither of the traditional 
ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 3

preclusions of laws of nature or of abstract ideas ought to 

prohibit patenting of the subject matter in this case.

Laws of nature are exact statements of physical relationships, deduced from scientific observations of natural 

phenomena. They are often represented by equations, 

and include such laws as the relationship between energy 

and mass (E=mc2), the relationship between current and 

resistance (Ohm’s Law), that between force, mass, and 

acceleration (F=ma), Maxwell’s equations, Newton’s laws 

of motion, and many more. Those laws, all agree, are not 

and should not be patent-eligible subject matter. But 

methods that utilize laws of nature do not set forth or 

claim laws of nature. All physical steps of human ingenuity utilize natural laws or involve natural phenomena. 

Thus, those steps cannot be patent-ineligible solely on 

that basis because, under that reasoning, nothing in the 

physical universe would be patent-eligible.

Abstract steps are, axiomatically, the opposite of tangible steps; that which is not tangible is abstract. But 

steps that involve machines, which are tangible, steps 

that involve transformation of tangible subject matter, or 

tangible implementations of ideas or abstractions should 

not be considered to be abstract ideas. In Bilski, the 

Supreme Court supported this proposition when it described our earlier machine-or-transformation test as a 

useful clue, albeit not the only test, for eligibility. 

Conversely, abstract ideas are essentially mental 

steps; they are not tangible even if they are written down 

or programmed into a physical machine. Alice, in affirming this court, held that claims that amount to nothing 

significantly more than instruction to apply an abstract 

idea are not patent eligible. But the fact that steps are 

well-known, although relevant to other statutory sections 

of the patent law, does not necessarily make them abstract.
4 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

The claims at issue in Sequenom’s patent are directed 

to methods for detecting paternally-inherited fetal DNA 

in maternal blood samples, and performing a prenatal 

diagnosis based on such DNA. Following Mayo, which 

held that certain steps merely recite natural laws and 

that the remaining steps must be sufficiently innovative

apart from the natural laws, the panel in this case held

that the claims do not involve patent-eligible subject 

matter. Appellants and amici have argued before us in 

briefs that a broad range of claims of this sort appear to 

be in serious jeopardy. It is said that the whole category 

of diagnostic claims is at risk. It is also said that a crisis 

of patent law and medical innovation may be upon us, and 

there seems to be some truth in that concern. 

The claims in this case perhaps should be in jeopardy, 

not because they recite natural laws or abstract ideas, but 

because they may be indefinite or too broad. But they 

should not be patent-ineligible on the ground that they set 

forth natural laws or are abstractions.

Claim 1 is directed to a method for detecting a paternally inherited nucleic acid of fetal origin from a pregnant 

female comprising amplifying a paternally inherited 

nucleic acid and detecting the presence of a paternally 

inherited nucleic acid. Claim 21 is directed to a method of 

performing a prenatal diagnosis comprising providing a 

maternal blood sample, separating the sample into a 

cellular and non-cellular fraction, detecting the presence 

of a nucleic acid, and providing a diagnosis. Both of these 

claims contain the nucleus of patent-eligible subject 

matter. 

As the panel noted, the natural phenomenon here is 

the presence of cell-free fetal DNA (“cffDNA”) in maternal 

plasma, which, when subjected to certain conventional 

steps, has led to an important new development: diagnosis of possible birth defects without using highly intrusive 

means. Applications of natural phenomena or laws to a 
ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 5

known process “may well be deserving of patent protection.” Diehr, 450 U.S. at 187. And it is not disputed that 

this scientific work on its own seems like an important 

discovery and a valuable contribution to the medical field, 

although no one asserts that a claim directed to the mere 

existence of cffDNA is patent-eligible. But neither of the 

representative claims here merely recites a law of nature, 

a natural phenomenon, or an abstract idea. The claims 

rely on or operate by, but do not recite, a natural phenomenon or law. The claimed invention involves taking 

maternal serum, separating it, amplifying the genetic 

material to detect cffDNA, and running tests to identify 

certain genes or genetic defects; these are all physical, 

and not insignificant, steps requiring human intervention.

The claims might be indefinite or too broad in that 

they do not specify how to amplify and detect, or how to 

separate, detect, and diagnose. Or they perhaps attempt 

to claim all known methods of carrying out those steps. 

But the finer filter of § 112 might be better suited to 

treating these as questions of patentability, rather than 

reviewing them under the less-defined eligibility rules. 

It is not disputed that fractionating blood, amplifying 

DNA, and analyzing DNA to detect specific gene sequences are known techniques in the art. As all other steps in 

the claims are individually well-known, the innovative 

aspect of the claims appears to be the improvement in the 

method of determining fetal genetic characteristics or 

diagnosing abnormalities of fetal DNA, consisting of use of 

the non-cellular fraction of fetal DNA obtained from a 

maternal blood sample.

The claim to this invention, then, might have been 

better drafted as a so-called Jepson claim, which recites 

what is in the prior art and what is the improvement. 

Such a claim might read, perhaps with more details 

added: “In a method of performing a prenatal diagnosis

using techniques of fractionation and amplification, the 
6 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

improvement consisting of using the non-cellular fraction 

of a maternal blood sample.” 

Regardless, we are not experts in drafting claims to 

protect new biological procedures and we are not in a 

position to rewrite claims or review a hypothetical claim. 

But against the accusation that such a claim to the invention might be considered mere draftsmanship and thus 

still ineligible under the seemingly expansive holding of 

Mayo, it must be said that a process, composition of 

matter, article of manufacture, and machine are different

implementations of ideas, and differentiating among them 

in claim drafting is a laudable professional skill, not 

necessarily a devious device for avoiding prohibitions. 

This is true despite the Supreme Court’s affirmance of 

this court in Alice, where we had held, by a 7–3 vote, that 

method and media claims in inventions of the type 

claimed there were essentially the same.

But focusing on the claims we have rather than those 

we might have had, the claims here are directed to an 

actual use of the natural material of cffDNA. They recite

innovative and practical uses for it, particularly for diagnostic testing: blood typing, sex typing, and screening for 

genetic abnormalities. And it is undisputed that before 

this invention, the amplification and detection of cffDNA 

from maternal blood, and use of these methods for prenatal diagnoses, were not routine and conventional. But

applying Mayo, we are unfortunately obliged to divorce 

the additional steps from the asserted natural phenomenon to arrive at a conclusion that they add nothing innovative to the process. 

Moreover, the claims here are not abstract. There is 

nothing abstract about performing actual physical steps 

on a physical material. And if the concern is preemption 

of a natural phenomenon, this is, apparently, a novel 

process and that is what patents are intended to incentivize and be awarded for. The panel here also noted that 
ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 7

there were other uses for cffDNA and other methods of 

prenatal diagnostic testing using cffDNA that do not 

involve the steps recited in the various claims. That fact 

should sufficiently address the concern of improperly 

tying up future use of natural phenomena and laws. 

In sum, it is unsound to have a rule that takes inventions of this nature out of the realm of patent-eligibility

on grounds that they only claim a natural phenomenon 

plus conventional steps, or that they claim abstract concepts. But 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. 
United States Court of Appeals 

for the Federal Circuit ______________________ 

ARIOSA DIAGNOSTICS, INC., NATERA, INC., 

Plaintiffs-Appellees

DNA DIAGNOSTICS CENTER, INC.,

Counterclaim Defendant-Appellee

v.

SEQUENOM, INC., SEQUENOM CENTER FOR 

MOLECULAR MEDICINE, LLC,

Defendants-Appellants

ISIS INNOVATION LIMITED,

Defendant

______________________ 

2014-1139, 2014-1144

______________________ 

Appeals from the United States District Court for the 

Northern District of California in Nos. 3:11-cv-06391-SI, 

3:12-cv-00132-SI, Judge Susan Y. Illston.

______________________ 

DYK, Circuit Judge, concurring in the denial of the petition for rehearing en banc. 

I concur in the court’s denial of rehearing en banc. In 

my view the framework of Mayo and Alice is an essential 

ingredient of a healthy patent system, allowing the inval-
2 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

idation of improperly issued and highly anticompetitive 

patents without the need for protracted and expensive 

litigation. Yet I share the concerns of some of my colleagues that a too restrictive test for patent eligibility 

under 35 U.S.C. § 101 with respect to laws of nature 

(reflected in some of the language in Mayo) may discourage development and disclosure of new diagnostic and 

therapeutic methods in the life sciences, which are often 

driven by discovery of new natural laws and phenomena. 

This leads me to think that some further illumination as 

to the scope of Mayo would be beneficial in one limited 

aspect. At the same time I think that we are bound by 

the language of Mayo, and any further guidance must 

come from the Supreme Court, not this court. 

I 

The language of Mayo is clear. The Mayo Court found 

that prior Supreme Court 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.” Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289, 

1294 (2012) (quoting Parker v. Flook, 437 U.S. 584, 594 

(1978)). Patent claims directed to laws of nature are 

ineligible under 35 U.S.C. § 101 when, “(apart from the 

natural laws themselves) [they] involve well-understood, 

routine, conventional activity previously engaged in by 

researchers in the field.” Id. (emphasis added). Reviewing the Court’s earlier Flook decision, the Mayo Court 

determined that Flook’s claim to a chemical process 

applying an “apparently novel mathematical algorithm,” 

id. at 1298, was ineligible under § 101 because the steps

of the 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 
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 3

1299 (quoting Flook, 437 U.S. at 594) (emphasis added). 

“[S]imply appending conventional steps, specified at a 

high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, 

phenomena, and ideas patentable.” Id. at 1300. In other 

words, Mayo states that the inventive concept necessary 

for eligibility must come in the application analyzed at 

step two, rather than from the discovery of the law of 

nature itself. 

Alice subsequently confirmed that the two-step 

framework articulated in Mayo is a unitary rule that 

applies equally “for distinguishing patents that claim 

laws of nature, natural phenomena, and abstract ideas 

from those that claim patent-eligible applications of those 

concepts.” Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. 

Ct. 2347, 2355 (2014) (citing Mayo). Alice explained,

First, we determine whether the claims at issue 

are directed to one of those patent-ineligible concepts. If so, we then ask, what else is there in the 

claims before us? . . . We have described step two of 

this analysis as a search for an inventive concept—

i.e., an element or combination of elements that is 

sufficient to ensure that the patent in practice 

amounts to significantly more than a patent upon 

the ineligible concept itself. 

Id. (emphasis added) (alterations, citations, and quotation 

marks omitted). “At Mayo step two, we must examine the 

elements of the claim to determine whether it contains an 

‘inventive concept’ sufficient to ‘transform’ the claimed 

abstract idea into a patent-eligible application.” Id. at 

2357 (emphasis added) (quotation marks omitted). Thus 

Alice also holds that inventive concept must be found at 

step two of the framework. 

Mayo has unambiguously announced a generally applicable test for determining subject-matter eligibility 
4 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

under § 101 with respect to laws of nature, and we are 

bound to follow it. We cannot confine Mayo to its facts or 

otherwise cabin a clear statement from the Supreme 

Court. “[O]nce the Court has spoken, it is the duty of 

other courts to respect that understanding of the governing rule of law.” Rivers v. Roadway Express, Inc., 511 

U.S. 298, 312 (1994). A court of appeals must not “confus[e] the factual contours of [a Supreme Court decision] 

for its unmistakable holding” to arrive at a “novel interpretation” of that decision. Thurston Motor Lines, Inc. v. 

Jordan K. Rand, Ltd., 460 U.S. 533, 534–35 (1983) (per 

curiam). As we have recognized, “[a]s a subordinate 

federal court, we may not so easily dismiss [the Supreme 

Court’s] statements as dicta but are bound to follow 

them.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 

1336, 1347 (Fed. Cir. 2010) (en banc) (citing Stone Container Corp. v. United States, 229 F.3d 1345, 1349–50 

(Fed. Cir. 2000)). 

The panel thus held correctly that Mayo is controlling 

precedent that governs the outcome here. The panel’s

opinion aptly states and applies the two-step framework 

of Mayo. “First, we determine whether the claims at issue 

are directed to a patent-ineligible concept.” Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1375 (Fed. 

Cir. 2015) (citing Mayo, 566 U.S. at 1292). “[T]he claims 

at issue, as informed by the specification, are generally 

directed to detecting the presence of a naturally occurring 

thing or a natural phenomenon, cffDNA in maternal 

plasma or serum. . . . [T]he claimed method begins and 

ends with a naturally occurring phenomenon.” Id. at 

1376. At the second step of the Mayo framework, the

panel determined that “[t]he method at issue here 

amounts to a general instruction to doctors to apply 

routine, conventional techniques when seeking to detect 

cffDNA.” Id. at 1377. The panel therefore found that the 

claims were not patent eligible under § 101. Id. at 1378. 
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 5

II

The Mayo/Alice framework works well when the abstract idea or law of nature in question is well known and 

longstanding, as was the situation in Mayo itself (as 

discussed below), earlier Supreme Court cases,1 and in

many of our own recent cases where we have found claims 

patent ineligible under § 101.2 Where the abstract idea or 

1 See, e.g., Bilski v. Kappos, 561 U.S. 593, 611 

(2010) (“Hedging is a fundamental economic practice long 

prevalent in our system of commerce and taught in any 

introductory finance class.”) (quoting In re Bilski, 545 

F.3d 943, 1013 (Fed. Cir. 2008) (Rader, J., dissenting)) 

(emphasis added); Diamond v. Diehr, 450 U.S. 175, 177 

n.2 (1981) (noting that the Arrhenius equation “has long 

been used to calculate the cure time in rubber-molding 

processes”) (emphasis added); Funk Bros. Seed Co. v. Kalo 

Inoculant Co., 333 U.S. 127, 129 (1948) (“Methods of 

selecting the strong strains [of nitrogen-fixing root-nodule 

bacteria] and of producing a bacterial culture from them 

have long been known.”) (emphasis added); see also the 

influential English patent case discussed in Mayo, 132 S. 

Ct. at 1300, Neilson v. Harford, Webster’s Patent Cases 

295, 371 (1841) (“We think the case must be considered as 

if the principle [that hot air promotes ignition better than 

cold air is] well known . . . .”) (emphasis added). 2 See, e.g., Intellectual Ventures I LLC v. Capital 

One Bank, 792 F.3d 1363, 1369 (Fed. Cir. 2015) (invalidating claims that applied an abstract idea—tailoring of 

advertising to individual customers—which “had often 

been” used before); OIP Techs., Inc. v. Amazon.com, Inc., 

788 F.3d 1359, 1362, 1364 (Fed. Cir. 2015) (invalidating 

claims to computerized methods of offer-based price 

optimization and noting that the abstract idea implicated 

was a “fundamental economic concept[]”); Ultramercial, 

 
6 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

law of nature is well known and longstanding, there is no 

basis for attributing novelty to that aspect of the claimed 

invention. 

Also, it seems to me that the Mayo/Alice framework 

works well with respect to abstract ideas. In my view, 

claims to business methods and other processes that 

merely organize human activity should not be patent 

eligible under any circumstances. See Alice, 134 S. Ct. at 

2360 (Sotomayor, J., concurring); In re Bilski, 545 F.3d 

943, 972 (Fed. Cir. 2008) (en banc) (Dyk, J., concurring). 

In any event, departing from the Mayo/Alice framework 

with respect to abstract ideas (as opposed to discoveries of 

natural laws and phenomena) would create serious risks 

of undue preemption because of the difficulty in distinguishing between new and established abstract ideas. 

But, as I see it, there is a problem with Mayo insofar 

as it concludes that inventive concept cannot come from 

discovering something new in nature—e.g., identification 

of a previously unknown natural relationship or property. 

In my view, Mayo did not fully take into account the fact 

that an inventive concept can come not just from creative, 

Inc. v. Hulu, LLC, 772 F3d 709, 715 (Fed. Cir. 2014) 

(invalidating a claim to routine, conventional application 

of the abstract idea of “using advertising as an exchange 

or currency” and rejecting the patentee’s argument that 

the idea was new); buySAFE, Inc. v. Google, Inc., 765 F.3d 

1350, 1351, 1355 (Fed. Cir. 2014) (invalidating a claim to 

a method of guaranteeing a party’s performance in an 

online transaction and finding that the abstract idea 

implicated was “beyond question of ancient lineage”); 

SmartGene, Inc. v. Advanced Biological Labs., SA, 555 F. 

App’x 950 (Fed. Cir. 2014) (invalidating a claim to computerized application of a mental process for treating

medical patients that “doctors do routinely”). 

 
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 7

unconventional application of a natural law, but also from 

the creativity and novelty of the discovery of the law

itself. This is especially true in the life sciences, where 

development of useful new diagnostic and therapeutic 

methods is driven by investigation of complex biological 

systems. I worry that method claims that apply newly 

discovered natural laws and phenomena in somewhat 

conventional ways are screened out by the Mayo test. In 

this regard I think that Mayo may not be entirely consistent with the Supreme Court’s decision in Myriad.3 

In Myriad the patent applicant discovered a previously unknown natural phenomenon: the sequences of the 

BRCA1 and BRCA2 genes and their connection with 

cancer. Ass’n for Molecular Pathology v. Myriad Genetics, 

Inc., 133 S. Ct. 2107, 2112–13 (2013). While the Court 

found ineligible Myriad’s claims to naturally occurring 

gDNA sequences, it suggested that “new applications of 

knowledge about the BRCA1 and BRCA2 genes” could

generally be eligible, with reference to claim 21 of U.S. 

Patent No. 5,753,441 (discussed further below).4 Id. at 

2120. Myriad thus appeared to recognize that an inventive concept can sometimes come from discovery of an 

3 Any tension between Mayo and Myriad does not, 

of course, change our obligation to respect the sweeping 

precedent of Mayo, as the panel did. Supreme Court 

“decisions remain binding precedent until [the Court] 

see[s] fit to reconsider them, regardless of whether subsequent cases have raised doubts about their continuing 

vitality.” Hohn v. United States, 524 U.S. 236, 252–53 

(1998) (citation omitted). 4 The “new applications” referred to by the Court 

must have meant applications of the newly discovered 

genes rather than inventive concepts at step two of the 

Mayo/Alice framework. 

 
8 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

unknown natural phenomenon, not just from unconventional application of a phenomenon. As Myriad emphasized, the first party with knowledge of a law of nature, 

natural phenomenon, or abstract idea should be “in an 

excellent position to claim applications of that 

knowledge.” Id. (quoting Ass’n. for Molecular Pathology v. 

USPTO, 689 F.3d 1303, 1349 (Fed. Cir. 2012) (Bryson, J., 

concurring in part and dissenting in part)).

III

Of course, I do not suggest that a newly discovered 

law of nature should be patent eligible in its entirety. 

Laws of nature are never patentable as such, even when 

first discovered by the patent applicant. As Mayo recognized, “Einstein could not patent his celebrated law that 

E=mc2.” 132 U.S. at 1293 (quoting Diamond v. 

Chakrabarty, 447 U.S. 303, 309 (1980)); see also Flook, 

437 U.S. at 591; Gottschalk v. Benson, 409 U.S. 63, 72

(1972) (holding that claims to methods of using a new 

mathematical algorithm were unpatentable because they

“in practical effect would be a patent on the algorithm 

itself”). Myriad itself reminded us that 

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

does not by itself satisfy the § 101 inquiry.” Myriad, 133 

S. Ct. at 2117; see also Ariosa, 788 F.3d at 1379. 

The primary concern with a patent on a law of nature 

is undue preemption—the fear that others’ innovative 

future applications of the law will be foreclosed. See 

O’Reilly v. Morse, 56 U.S. 62, 113 (1853); Mayo, 132 S. Ct. 

at 1301. As Mayo emphasized, “there is a danger that the 

grant of patents that tie up the[] use [of laws of nature] 

will inhibit future innovation premised upon them . . . .” 

132 S. Ct. at 1301; see also id. at 1304 (highlighting “the 

kind of risk that underlies the law of nature exception, 

namely the risk that a patent on the law would significantly impede future innovation”). 
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 9

As far back as O’Reilly v. Morse, the Supreme Court 

found unpatentable Morse’s sweeping claim to all “marking or printing [of] intelligible characters, signs, or letters, 

at any distances” via “the use of the motive power of the 

electric or galvanic current, which I call electromagnetism,” holding that “the claim is too broad, and not 

warranted by law.” 56 U.S. at 112, 113. Morse, like 

Mayo, was concerned with undue preemption of the 

building blocks of human ingenuity. “[W]hile he shuts the 

door against inventions of other persons, the patentee 

would be able to avail himself of new discoveries in the 

properties and powers of electro-magnetism which scientific men might bring to light.” Id. at 113. 

Similarly, in an aspect of our original Myriad decision 

that was not reversed by the Supreme Court, Ass’n for 

Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 

694 (2012), and again in our court’s recent In re BRCA1- 

& BRCA2-Based Hereditary Cancer Test decision, we

found genetic testing claims that sought to capture “all 

comparisons between the patient’s BRCA genes and the 

wild-type BRCA genes” to be overbroad and thus ineligible under § 101, noting that “[t]he covered comparisons 

are not restricted by the purpose of the comparison or the 

alteration being detected.” 774 F.3d 755, 763, 765 (Fed. 

Cir. 2014). 

However, if the breadth of the claim is sufficiently 

limited to a specific application of the new law of nature

discovered by the patent applicant and reduced to practice, I think that the novelty of the discovery should be 

enough to supply the necessary inventive concept. My 

proposed approach would require that the claimed application be both narrow in scope and actually reduced to 

practice, not merely “constructively” reduced to practice 

by filing of a patent application replete with prophetic 

examples. 
10 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

In my view, the breadth of the claim should be critical. Even when a patent applicant has demonstrated 

some particular utility for a newly discovered law of 

nature and reduced it to practice, the claim should be

invalid unless narrowly tailored to the particular application of the law that has been developed. Claims that 

extend far beyond the utility demonstrated by the patent 

applicant and reduced to practice should be invalid, as 

they “too broadly preempt the use” of the underlying idea 

by others. Mayo, 132 S. Ct. at 1294; see also Diamond v. 

Diehr, 450 U.S. 175, 191–92 (1981). But, so long as a 

claim is narrowly tailored to what the patent applicant 

has actually invented and reduced to practice, there is 

limited risk of undue preemption of the underlying idea. 

In Myriad the Court noted, 133 S. Ct. at 2120, that an 

example of a meritorious claim might be claim 21 of 

Myriad’s U.S. Patent No. 5,753,441 (“the ’441 patent”),

which was not at issue in the case and which Judge 

Bryson discussed in his concurring opinion on our court’s 

decision below, Ass’n for Molecular Pathology, 689 F.3d at

1348 (Bryson, J., concurring). Claim 21 of the ’441 patent 

covers a method of detecting 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, using conventional methods. 

See In re BRCA1 & BRCA2, 774 F.3d at 765. 

This approach appears also to be supported by Morse. 

The Supreme Court established in Morse that the extent 

to which a patentee can claim is the extent to which he 

has actually made some concrete use of the discovery and 

reduced it to practice. “The specification of this patentee 

describes his invention or discovery, and the manner and 

process of constructing and using it; and his patent . . . covers nothing more.” Morse, 56 U.S. at 119. 

Limiting patentees to narrow applications they have 

actually developed and reduced to practice would be in 
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 11

keeping with Mayo’s commandment that “simply appending conventional steps, specified at a high level of generality, to laws of nature, natural phenomena, and abstract 

ideas cannot make those laws, phenomena, and ideas 

patentable.” Mayo, 132 S. Ct. at 1300 (emphasis added). 

This proposed approach, limiting the scope of patents 

based on new discoveries to narrow claims covering 

applications actually reduced to practice, would allow the 

inventor to enjoy an exclusive right to what he himself 

has invented and put into practice, but not to prevent new 

applications of the natural law by others.5 This would 

ensure that the scope of the patent claims would not 

“foreclose[] more future invention than the underlying 

5 It has been suggested that the requirements of 

enablement and written description will guard against 

the dangers of overclaiming a law of nature. Those doctrines, important as they are, generally require only that 

one or a handful of representative embodiments be described by the patentee. See, e.g., Donald S. Chisum, 

Chisum on Patents, § 7.03 at 7-15 (2015) (“An enabling 

disclosure is all that is required [for enablement]. The 

applicant need not describe actual embodiments or examples. Indeed, an applicant need not have reduced the 

invention to practice prior to filing.”); Id. § 7.04[1][e] at 

7-309–7-310.1 (“In Ariad Pharmaceuticals, Inc. v. Eli Lilly 

& Co. (2010), the Federal Circuit, sitting en banc, reaffirmed that written description of the invention is a 

requirement distinct from enablement . . . . [The court] 

declined to set forth ‘bright-line rules,’ including rules on 

the number of species needed to support a generic claim.”) 

(citing and quoting Ariad, 598 F.3d at 1351–52). Therefore, the doctrines of enablement and written description 

would not entirely prevent claims that preempt future 

applications of the law of nature by others. 

 
12 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

discovery could reasonably justify.” Id. at 1301. Limiting 

the scope of the patent also would avoid the problem that 

“the more abstractly [a process patent’s] claims are stated, the more difficult it is to determine precisely what 

they cover.” Mayo, 132 S. Ct. at 1302 (quoting Christina

Bohannan & Herbert Hovenkamp, Creation without 

Restraint: Promoting Liberty and Rivalry in Innovation

112 (2012)). 

To be sure, determination of whether a claim applying 

a new law of nature is overbroad could present difficulties

of definition and line drawing. But allowing narrow 

claims that have been actually reduced to practice when 

those claims embody an inventive, newly discovered law 

of nature would promote the fundamental policies underlying § 101. Requiring narrow claims and actual reduction to practice would be a reasonable accommodation in 

return for a more permissive inventive concept requirement. The approach would, I think, ensure that only 

diagnostic and therapeutic method patents limited in 

their claim scope would survive. These patents would 

provide the world with disclosure and useful applications 

of previously unknown natural laws, and the opportunity 

to obtain such patents would help to restore the incentive 

to make those discoveries that the patent system has 

historically provided. 

IV

To be clear, I do not suggest that Mayo was incorrectly decided on its particular facts. The claims at issue in 

Mayo contributed only routine application to a law of 

nature that was already well known. “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, including, in particular, [the individual metabolites measured in the claimed methods], were 

correlated with the likelihood that a particular dosage of a 
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 13

thiopurine drug could cause harm or prove ineffective.” 

132 S. Ct. at 1295 (emphasis added). While “those in the 

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

“scientists routinely measured metabolites as part of their 

investigations into the relationships between metabolite 

levels and efficacy and toxicity of thiopurine compounds,” 

id. at 1298 (emphasis added). In Mayo, the application of 

the natural law was merely routine optimization of drug

dosage to maximize therapeutic effect.6 As discussed 

above, Mayo thus forms part of a long line of Supreme 

Court decisions invalidating patent claims to conventional 

applications of well-known laws of nature. 

V 

Finally, it seems to me that the approach I suggest 

would not change the result in this case. Sequenom’s 

challenged claims embody a newly discovered natural 

phenomenon, the presence of paternally inherited cell-free 

fetal DNA (cffDNA) in a mother’s bloodstream. Judge 

Linn’s concurrence notes that “the amplification and 

detection of cffDNA had never before been done.” Ariosa, 

788 F.3d at 1381 (Linn, J., concurring). But the major 

defect is not that the claims lack inventive concept but 

rather that they are overbroad. See Mayo, 132 S. Ct. at 

1294. 

6 Cf. Pfizer, Inc., v. Apotex, Inc., 480 F.3d 1348, 

1368 (Fed. Cir. 2007) (“[D]iscovery of an optimum value of 

a variable in a known process is usually obvious.”); In re 

Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) (noting that 

generally, in the context of obviousness, “it is not inventive to discover the optimum or workable ranges by 

routine experimentation”) (quoting In re Aller, 220 F.2d 

454, 456 (CCPA 1955)).

 
14 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

For example, claim 1 of the ’540 patent broadly covers 

any method of detecting paternally inherited cffDNA from 

maternal serum or plasma via amplification and detection 

of that cffDNA. ’540 patent, col. 23, ll. 61–67. Even the 

somewhat narrower claim 21 of the ’540 patent, which 

recites a method of performing a prenatal diagnosis based 

on the presence, quantity, or sequence of paternally 

inherited cffDNA detected by the method of claim 1, still 

broadly encompasses any diagnosis of any disease, disorder, or condition. ’540 patent, col. 26, ll. 4–14. Such 

claims appear to be impermissible attempts to capture the 

entire natural phenomenon of cffDNA rather than any 

particular applications thereof developed and actually 

reduced to practice by the inventors. 

A future case is likely to present a patent claim where 

the inventive concept resides in a newly discovered law of 

nature or natural phenomenon, but the claim is narrowly 

drawn and actually reduced to practice. That case will, I 

hope, provide the Supreme Court with an opportunity to 

revisit the Mayo/Alice framework in this one limited 

aspect. 
United States Court of Appeals 

for the Federal Circuit ______________________ 

ARIOSA DIAGNOSTICS, INC., NATERA, INC.,

Plaintiffs-Appellees 

DNA DIAGNOSTICS CENTER, INC.,

Counterclaim Defendant-Appellee

v.

SEQUENOM, INC., SEQUENOM CENTER FOR 

MOLECULAR MEDICINE, LLC,

Defendants-Appellants

ISIS INNOVATION LIMITED,

Defendant

______________________ 

2014-1139, 2014-1144

______________________ 

Appeals from the United States District Court for the 

Northern District of California in Nos. 3:11-cv-06391-SI, 

3:12-cv-00132-SI, Judge Susan Y. Illston.

______________________ 

NEWMAN, Circuit Judge, dissenting from denial of the 

petition for rehearing en banc.

I agree with my colleagues that this case is wrongly 

decided. However, I do not share their view that this

incorrect decision is required by Supreme Court precedent. The facts of this case diverge significantly from the 
2 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

facts and rulings in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S. Ct. 1289 (2012), and in 

Association for Molecular Pathology v. Myriad Genetics, 

133 S. Ct. 2107 (2013). 

In Mayo, both the medicinal product and its metabolites were previously known, leaving sparse room for

innovative advance in using this information as a diagnostic dosage tool. Nonetheless, the Court recognized the 

principle that patent eligibility is not disabled when 

science is put to practical use, stating that “a new way of 

using an existing drug” is patent-eligible under Section 

101. 132 S. Ct. at 1302.

Whether or not Mayo drew an appropriate line in that 

case, particularly in view of the specificity of the diagnostic method that was developed, this decision does not 

require the drawing of a different line on quite different 

facts. In the case now before us, the claimed method was 

not previously known, nor the diagnostic knowledge and 

benefit implemented by the method.

Similar caveats accompanied the Court’s decision in

Association for Molecular Pathology v. Myriad Genetics, 

with the Court stating that “this case does not involve 

patents on new applications of knowledge about the 

BRCA1 and BRCA2 genes.” 133 S. Ct. at 2120 (emphasis 

original). The Court further explained its holding, stating 

that: “We merely hold that genes and the information 

they encode are not patent eligible under § 101 simply 

because they have been isolated from the surrounding 

genetic material.” Id.

In the case at bar, the inventors are not claiming the 

scientific fact of the discovery of paternal DNA in the 

blood of a pregnant woman; they are claiming the discovery and development of a new diagnostic method of using 

this information. As the panel recognized, this is a 

“breakthrough,” for this information can now be learned 

not only earlier in the gestation period than was previous-
ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 3

ly available, but without the risks of the previously required invasive procedures of penetrating the amniotic 

sac. 

Precedent does not require that all discoveries of natural phenomena or their application in new ways or for 

new uses are ineligible for patenting; the Court has 

cautioned against such generalizations. Such caution 

takes hold for the case at bar. The new diagnostic method 

here is novel and unforeseen, and is of profound public 

benefit—“a significant contribution to the medical field,” 

Panel Maj. Op. at 16—a “breakthrough,” Panel Conc. Op. 

at 5. The panel’s decision to withhold access to patenting, 

now endorsed by the en banc court’s refusal to rehear the 

case, is devoid of support.

Nor does patenting of this new diagnostic method preempt further study of this science, nor the development of 

additional applications. Patenting does, however, facilitate the public benefit of provision of this method through 

medical diagnostic commerce, rather than remaining a 

laboratory curiosity.

This subject matter is not ineligible under Section 

101, but warrants standard legal analysis for compliance 

with the requirements of patentability, that is, novelty, 

unobviousness, specificity of written description, enablement, etc., and whether the claims are appropriately 

limited, as discussed many years ago in O’Reilly v. Morse, 

56 U.S. 62, 112 (1853) (“We perceive no well-founded 

objection to the description which is given of the whole 

invention and its separate parts, nor to his right to a 

patent for the first seven inventions set forth in the 

specification of his claims.”).

I respectfully dissent from my colleagues’ conclusion 

that Supreme Court precedent on Section 101 excludes 

this invention from eligibility for patenting. The subject 

matter should be reviewed for compliance with Sections 
4 ARIOSA DIAGNOSTICS, INC. v. SEQUENOM, INC. 

102, 103, and 112, and any other relevant provisions of 

the patent law.