Document ID: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-14-01144/USCOURTS-ca13-14-01144-0/pdf.json

Parties Involved:
DNA Diagnostics Center, Inc.
Appellee
Isis Innovation Limited
Not party
Natera, Inc.
Appellee
Sequenom, Inc.
Appellant

Document Text:

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.

______________________ 

Decided: June 12, 2015

______________________ 

DAVID ISAAC GINDLER, Irell & Manella LLP, Los Angeles, CA, argued for plaintiff-appellee Ariosa Diagnostics, 

Inc. Also represented by ANDREI IANCU; AMIR NAINI, Russ 

August & Kabat, Los Angeles, CA. 

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2 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 

WILLIAM PAUL SCHUCK, Bartko, Zankel, Bunzel & Miller, San Francisco, CA, for plaintiff-appellee Natera, Inc., 

counterclaim defendant-appellee DNA Diagnostics Center, Inc. 

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

CA, argued for defendants-appellants. Also represented 

by PETER E. ROOT, Menlo Park, CA; ATON ARBISSER, Los 

Angeles, CA. 

RICHARD L. BLAYLOCK, Pillsbury Winthrop Shaw 

Pittman LLP, San Diego, CA, for amicus curiae Invitae 

Corporation. Also represented by KIRKE M. HASSON, 

COLIN TRAVERS KEMP, San Francisco, CA. 

KEVIN EDWARD NOONAN, McDonnell, Boehnen Hulbert & Berghoff, LLP, Chicago, IL, for amicus curiae 

Biotechnology Industry Organization. 

WILLIAM LARRY RESPESS, I, Sheppard, Mullin, Richter, 

& Hampton LLP, San Diego, CA, for amicus curiae The

San Diego Intellectual Property Law Association. 

______________________ 

Before REYNA, LINN, and WALLACH, Circuit Judges.

Opinion for the court filed by Circuit Judge REYNA. 

Concurring Opinion filed by Circuit Judge LINN. 

REYNA, Circuit Judge.

This appeal is from a grant of summary judgment of 

invalidity of the asserted claims of U.S. Patent No. 

6,258,540 (“the ’540 patent”). The United States District 

Court for the Northern District of California found that 

the asserted claims of the ’540 patent are not directed to 

patent eligible subject matter and are therefore invalid 

under 35 U.S.C. § 101. For the reasons explained below, 

we affirm. 

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ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 3

I 

In 1996, Drs. Dennis Lo and James Wainscoat discovered cell-free fetal DNA (“cffDNA”) in maternal plasma 

and serum, the portion of maternal blood samples that 

other researchers had previously discarded as medical 

waste. cffDNA is non-cellular fetal DNA that circulates 

freely in the blood stream of a pregnant woman. Applying 

a combination of known laboratory techniques to their 

discovery, Drs. Lo and Wainscoat implemented a method 

for detecting the small fraction of paternally inherited 

cffDNA in maternal plasma or serum to determine fetal 

characteristics, such as gender. The invention, commercialized by Sequenom as its MaterniT21 test, created an 

alternative for prenatal diagnosis of fetal DNA that 

avoids the risks of widely-used techniques that took 

samples from the fetus or placenta. In 2001, Drs. Lo and 

Wainscoat obtained the ’540 patent, which relates to this 

discovery. 

The parties agree that the patent does not claim 

cffDNA or paternally inherited cffDNA. Instead, the ’540 

patent claims certain methods of using cffDNA. The steps 

of the method of claim 1 of the ’540 patent include amplifying the cffDNA contained in a sample of a plasma or 

serum from a pregnant female and detecting the paternally inherited cffDNA. Amplifying cffDNA results in a 

single copy, or a few copies, of a piece of cffDNA being 

multiplied across several orders of magnitude, generating 

thousands to millions of copies of that particular DNA 

sequence. In the amplification step, DNA is extracted 

from the serum or plasma samples and amplified by 

polymerase chain reaction (“PCR”) or another method. 

PCR exponentially amplifies the cffDNA sample to detectable levels. 

In the detecting step, the lab technician adds the amplified cffDNA to an agarose gel containing ethidium 

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4 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 

bromide to stain and visualize the paternally inherited 

cffDNA. 

The ’540 patent also provides for making a diagnosis 

of certain fetal characteristics based on the detection of 

paternally inherited cffDNA. The specification explains 

that analysis of cffDNA permits more efficient determination of genetic defects and that a pregnant woman carrying a fetus with certain genetic defects will have more 

cffDNA in her blood than will a woman with a normal 

fetus. ’540 patent col. 3 ll. 30-43. 

Claims 1, 2, 4, 5, 8, 19-22, 24, and 25 of the ’540 patent are at issue in this appeal.1 Independent claim 1 

requires:

1. A method for detecting a paternally inherited 

nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises

amplifying a paternally inherited nucleic acid 

from the serum or plasma sample and

detecting the presence of a paternally inherited 

nucleic acid of fetal origin in the sample.

’540 patent col. 23 l. 61-67.

For comparison, independent claims 24 and 25 require:

24. A method for detecting a paternally inherited 

nucleic acid on a maternal blood sample, which 

method comprises:

1 The parties have stipulated that for the purposes 

of this appeal claims 1, 2, 4, 5, 8, 9-22, 24 and 25 are 

representative of claims 6, 7, 12, 13, 15, and 18 of the ‘540 

patent. J.A. 24-25, 30-31.

 

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removing all or substantially all nucleated and 

anucleated cell populations from the blood sample,

amplifying a paternally inherited nucleic acid 

from the remaining fluid and subjecting the amplified nucleic acid to a test for the Paternally [sic] 

inherited fetal nucleic acid.

25. A method for performing a prenatal diagnosis 

on a maternal blood sample, which method comprises

obtaining a non-cellular fraction of the blood sample

amplifying a paternally inherited nucleic acid 

from the non-cellular fraction

and performing nucleic acid analysis on the amplified nucleic acid to detect paternally inherited fetal nucleic acid.

Id. at 26 ll. 20-36. 

The remaining claims explain how the method of detection occurs or how it can be used. For example, claim 2 

depends from claim 1 and claims amplification by polymerase chain reaction. Id. at col. 24 ll. 60-61. Claim 4 

similarly depends from claim 1 and claims detection via a 

sequence specific probe. Id. col. 24 ll. 65-67. Claim 21 

also depends from claim 1, but instead of focusing solely 

on a method for detecting, it focuses on a method for 

performing a prenatal diagnosis, using claim 1’s method 

for detecting. Id. col. 26 ll. 4-14. 

II

Appellee Ariosa Diagnostics, Inc. (formerly known as 

“Aria Diagnostics, Inc.”) makes and sells the Harmony 

Test, a non-invasive test used for prenatal diagnosis of 

certain fetal characteristics. Natera, Inc. makes and sells 

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6 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 

the Non-Invasive Paternity Test, which is intended to 

confirm the paternity or non-paternity of a gestating fetus 

from genetic information in fetal DNA available in the 

blood of the pregnant female. Diagnostics Center, Inc. is 

a licensee of Natera.

In response to letters threatening claims of infringement, Ariosa Diagnostics, Inc., Natera, Inc. and Diagnostics Center, Inc. each filed separate declaratory judgment 

actions from December 2011 through early 2012 against 

Sequenom alleging that they did not infringe the ’540 

patent. Sequenom counterclaimed alleging infringement 

in each case. The district court related the three actions 

for pretrial purposes. 

In the Ariosa action, Sequenom filed a motion seeking 

to preliminarily enjoin Ariosa from selling the accused 

Harmony Prenatal Test. In July 2012, the district court 

issued an order denying Sequenom’s motion for a preliminary injunction. In the context of doing so, the district 

court found that there was a substantial question over 

whether the subject matter of the asserted claims was 

directed to eligible subject matter. Sequenom appealed to 

this court. 

On August 9, 2013, this court vacated and remanded 

the case, holding that the district court erred in certain 

respects not relevant to this appeal. Aria Diagnostics, 

Inc. v. Sequenom, Inc., 726 F.3d 1296, 1305 

(Fed. Cir. 2013). In addition, this Court noted that it 

offered no opinion “as to whether there is or is not a 

substantial question regarding the subject matter eligibility of the asserted claims” of the ’540 patent, but remanded “for the district court to examine subject matter 

eligibility . . . . in light of [Ass’n for Molecular Pathology v. 

Myriad Genetics, Inc., 569 U.S. ___, 133 S. Ct. 2107, 2117 

(2013)].” Id. at 1304. 

After remand, the parties filed cross motions for 

summary judgment regarding invalidity under 35 U.S.C. 

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§ 101. The district court agreed with Ariosa’s argument 

that the claims of the ’540 patent were directed to the 

natural phenomenon of paternally inherited cffDNA and 

that the claims did not add enough to the natural phenomenon to make the claims patent eligible under § 101. 

The district court determined that the steps of amplifying 

and detecting were well-understood, routine, or conventional activity in 1997, when the application for the ’540 

patent was filed. The district court concluded that the 

’540 patent was not directed to patentable subject matter 

because “the only inventive component of the processes of 

the ’540 patent is to apply those well-understood, routine 

processes to paternally inherited cffDNA, a natural phenomenon.” J.A. 18. The district court also found that the 

claimed processes posed a risk of preempting a natural 

phenomenon. Sequenom appeals.

We have jurisdiction under 28 U.S.C. § 1295(a)(1).

III

We review the grant of summary judgment under the 

law of the regional circuit, in this case the Ninth Circuit. 

Charles Mach. Works, Inc. v. Vermeer Mfg. Co., 723 F.3d 

1376, 1378 (Fed. Cir. 2013). The Ninth Circuit reviews 

the grant or denial of summary judgment de novo. Leever 

v. Carson City, 360 F.3d 1014, 1017 (9th Cir. 2004). We 

also review de novo the question of whether a claim is 

invalid under section 101. In re BRCA1- and BRCA2-

Based Hereditary Cancer Test Patent Litig., 774 F.3d. 755, 

759 (Fed. Cir. 2014).

Section 101 of the Patent Act defines patent eligible 

subject matter:

Whoever 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.

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35 U.S.C. § 101. The Supreme Court has long held that 

there are certain exceptions to this provision: laws of 

nature, natural phenomena, and abstract ideas. Alice 

Corp. v. CLS Bank Int’l, ___ U.S. ___, 134 S. Ct. 2347, 

2354 (2014) (collecting cases). 

In Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. ___, 132 S. Ct. 1289 (2012), the 

Supreme Court set forth a framework for distinguishing 

patents that claim laws of nature, natural phenomena, 

and abstract ideas from those that claim patent-eligible 

applications of those concepts. First, we determine 

whether the claims at issue are directed to a patentineligible concept. Id. at 1297. If the answer is yes, then 

we next consider the elements of each claim both individually and “as an ordered combination” to determine 

whether additional elements “transform the nature of the 

claim” into a patent-eligible application. Id. at 1298. The 

Supreme Court has described the second step 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. at 1294; see also Digitech Image Techs., LLC v. Elecs.

For Imaging, Inc., 758 F.3d 1344, 1351 (Fed. Cir. 2014) 

(“Without additional limitations, a process that employs 

mathematical algorithms to manipulate existing information to generate additional information is not patent 

eligible.”).

The claims of the ’540 patent that are at issue in this 

appeal are method claims. Methods are generally eligible 

subject matter. In this case, the asserted claims of the 

’540 patent are directed to a multistep method that starts 

with cffDNA taken from a sample of maternal plasma or 

serum—a naturally occurring non-cellular fetal DNA that 

circulates freely in the blood stream of a pregnant woman. 

See, e.g., ’540 patent claims 1, 24, 25. It is undisputed 

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ral phenomenon. Sequenom does not contend that Drs. 

Lo and Wainscoat created or altered any of the genetic 

information encoded in the cffDNA, and it is undisputed 

that the location of the nucleic acids existed in nature 

before Drs. Lo and Wainscoat found them. The method 

ends with paternally inherited cffDNA, which is also a 

natural phenomenon. The method therefore begins and 

ends with a natural phenomenon. Thus, the claims are 

directed to matter that is naturally occurring. 

The written description supports the conclusion that 

the claims of the ’540 patent are directed to a naturally 

occurring thing or natural phenomenon. In the Summary 

and Objects of the Invention section of the ’540 patent, the 

patent states that “[i]t has now been discovered that

foetal DNA is detectable in maternal serum or plasma 

samples.”2 ’540 patent col. 1 ll. 50-51. The patent goes on 

to state that “[t]his is a surprising and unexpected finding; maternal plasma is the very material that is routinely discarded by investigators studying noninvasive 

prenatal diagnosis using foetal cells in maternal blood.” 

Id. col. 1 ll. 51-55. In the discussion, the patent notes:

In this study we have demonstrated the feasibility 

of performing non-invasive foetal RhD genotyping 

from maternal plasma. This represents the first 

description of single gene diagnosis from maternal 

plasma. 

Id. col. 10 ll. 53-58. Further, the description of the invention notes: “[w]e have demonstrated that foetal DNA is 

present in maternal plasma and serum,” id. col. 13 ll. 6-7, 

and “[t]hese observations indicate that maternal plasma/serum DNA may be a useful source of material for the 

2 The term “fetal” and “foetal” are used interchangeably in the ’540 patent and by the parties. 

 

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non-invasive prenatal diagnosis of certain genetic disorders,” id. col. 13 ll. 11-13. The patent also states: “[t]he 

most important observation in this study is the very high 

concentration of foetal DNA in maternal plasma and 

serum.” Id. col. 16 ll. 12-14. Thus, the 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. As we noted above, the claimed method begins 

and ends with a naturally occurring phenomenon. 

Because the claims at issue are directed to naturally 

occurring phenomena, we turn to the second step of 

Mayo’s framework. In the second step, we examine the 

elements of the claim to determine whether the claim

contains an inventive concept sufficient to “transform” the 

claimed naturally occurring phenomenon into a patenteligible application. 132 S. Ct. at 1294. We conclude that 

the practice of the method claims does not result in an 

inventive concept that transforms the natural phenomenon of cffDNA into a patentable invention. 

Mayo made clear that transformation into a patenteligible application requires “more than simply stat[ing] 

the law of nature while adding the words ‘apply it.’” Id. at 

1294. A claim that recites an abstract idea, law of nature, 

or natural phenomenon must include “additional features” to ensure “that the [claim] is more than a drafting 

effort designed to monopolize the [abstract idea, law of 

nature, or natural phenomenon].” Id. at 1297. For process claims that encompass natural phenomenon, the 

process steps are the additional features that must be 

new and useful. See Parker v. Flook, 437 U.S. 584, 591 

(1978) (“The process itself, not merely the mathematical 

algorithm, must be new and useful.”). 

In Mayo, the patents at issue claimed a method for 

measuring metabolites in the bloodstream in order to 

calibrate the appropriate dosage of thiopurine drugs in 

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the treatment of autoimmune diseases. 132 S. Ct. at 

1294. The respondent contended that the claimed method 

was a patent eligible application of a natural law that 

described the relationship between the concentration of 

certain metabolites and the likelihood that the drug 

dosage will be harmful or ineffective. Methods for determining metabolite levels, however, were already “well 

known in the art.” Id. at 1298. Further, the process at 

issue amounted to “nothing significantly more than an 

instruction to doctors to apply the applicable laws when 

treating their patients.” Id. In that case, “[s]imply appending conventional steps, specified at a high level of 

generality,” was not enough to supply an inventive concept. Id. at 1300. 

Like the patentee in Mayo, Sequenom contends that 

the claimed methods are patent eligible applications of a 

natural phenomenon, specifically a method for detecting 

paternally inherited cffDNA. Using methods like PCR to 

amplify and detect cffDNA was well-understood, routine, 

and conventional activity in 1997. The method at issue 

here amounts to a general instruction to doctors to apply 

routine, conventional techniques when seeking to detect 

cffDNA. Because the method steps were well-understood, 

conventional and routine, the method of detecting paternally inherited cffDNA is not new and useful. The only 

subject matter new and useful as of the date of the application was the discovery of the presence of cffDNA in 

maternal plasma or serum. 

The specification of the ’540 patent confirms that the 

preparation and amplification of DNA sequences in plasma or serum were well-understood, routine, conventional 

activities performed by doctors in 1997. The ’540 patent 

provides that “[t]he preparation of serum or plasma from 

the maternal blood sample is carried out by standard 

techniques.” ’540 patent col. 2 ll. 27-28. It also provides 

that “[s]tandard nucleic acid amplification systems can be 

used, including PCR, the ligase chain reaction, nucleic 

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12 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 

acid sequence based amplification (NASBA), branched 

DNA methods, and so on.” Id. col. 2 ll. 44-47. 

Other evidence supports this conclusion. For example, Sequenom’s expert, Dr. Evans, testified at deposition 

that PCR and other methodologies for amplifying DNA 

were “already well known in science [in 1997].” J.A. 1092-

93, 1995-96. Similarly, in a declaration filed during 

prosecution of the ’540 patent, Dr. Lo testified that 

“[s]uitable amplification techniques can be ordinary PCR 

or more sophisticated developments thereof, but these 

techniques were all known in the literature before the 

date of my invention.” J.A. 1109. 

The detecting step was similarly well-understood, 

routine, and conventional. During prosecution of the 

application that became the ’540 patent, the applicant 

stated:

[O]ne skilled in the art is aware of a variety of 

techniques which might be used to detect different 

nucleic acid species. For example, there are numerous techniques which might be used to detect 

repeat expansions, single gene mutations, deletions or translocations. These techniques are a 

matter of routine for one skilled in the art for the 

analysis of DNA.

J.A. 1052. The applicant went on to note:

[O]ne skilled in the art is readily able to apply the 

teachings of the present application to any one of 

the well-known techniques for detection of DNA 

with a view to analysis of foetal DNA in paternal

[sic] plasma or serum. 

J.A. 1055. Similarly, the applicant later added that “[t]he 

person skilled in the art has a broad range of techniques 

available for the detection of DNA in a sample.” 

J.A. 1057. 

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The dependent claims are broad examples of how to 

detect cffDNA in maternal plasma. The dependent claims 

are focused on the use of the natural phenomenon in 

combination with well-understood, routine, and conventional activity. For example, claim 2 identifies the polymerase chain reaction as the amplification technique to be 

used in the detection method of claim 1. As noted above, 

this technique was well-understood, routine, and conventional in 1997, as specified by the patent itself. Like 

claim 1, claims 5 and 8 focus on detecting a specific chromosome within the cffDNA—a natural phenomenon—

again, adding no inventive concept to the limitations of 

claim 1. None of the remaining asserted dependent or 

independent claims differ substantially from these claims. 

Thus, in this case, appending routine, conventional steps 

to a natural phenomenon, specified at a high level of 

generality, is not enough to supply an inventive concept. 

Where claims of a method patent are directed to an application that starts and ends with a naturally occurring 

phenomenon, the patent fails to disclose patent eligible 

subject matter if the methods themselves are conventional, routine and well understood applications in the art. 

The claims of the ’540 patent at issue in this appeal are 

not directed to patent eligible subject matter and are, 

therefore, invalid.

IV

In its opinion, the district court addressed the principle of preemption. The district court noted:

It is important to note that the ’540 patent does 

not merely claim uses or applications of cffDNA, it 

claims methods for detecting the natural phenomenon. Because generally one must be able to find 

a natural phenomenon to use it and apply it, 

claims covering the only commercially viable way 

of detecting that phenomenon do carry a substantial risk of preempting all practical uses of it.

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J.A. 19. 

Sequenom argues that there are numerous other uses 

of cffDNA aside from those claimed in the ’540 patent, 

and thus, the ’540 patent does not preempt all uses of 

cffDNA, as shown by evidence in the record before the 

district court. Sequenom also argues that “a method 

applying or using a natural phenomenon in a manner that 

does not preclude alternative methods in the same field is 

non-preemptive, and, by definition, patent-eligible under 

Section 101.” Appellants’ Br. 30. Similarly, Sequenom 

and amici argue that because the particular application of 

the natural phenomena that the ’540 patent claims embody are narrow and specific, the claims should be upheld. 

Ariosa argues that the principle of preemption does not 

alter the analysis. Ariosa argues that the claimed methods are not, as Sequenom asserts, limited and specific. 

The Supreme Court has made clear that the principle 

of preemption is the basis for the judicial exceptions to 

patentability. Alice, 134 S. Ct at 2354 (“We have described the concern that drives this exclusionary principal 

as one of pre-emption”). For this reason, questions on 

preemption are inherent in and resolved by the § 101 

analysis. The concern is that “patent law not inhibit 

further discovery by improperly tying up the future use of 

these building blocks of human ingenuity.” Id. (internal 

quotations omitted). In other words, patent claims should 

not prevent the use of the basic building blocks of technology—abstract ideas, naturally occurring phenomena, and 

natural laws. While preemption may signal patent ineligible subject matter, the absence of complete preemption 

does not demonstrate patent eligibility. In this case, 

Sequenom’s attempt to limit the breadth of the claims by 

showing alternative uses of cffDNA outside of the scope of 

the claims does not change the conclusion that the claims 

are directed to patent ineligible subject matter. Where a 

patent’s claims are deemed only to disclose patent ineligible subject matter under the Mayo framework, as they are 

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in this case, preemption concerns are fully addressed and 

made moot. 

Sequenom and amici encourage us to draw distinctions among natural phenomena based on whether or not 

they will interfere significantly with innovation in other 

fields now or in the future. The Supreme Court cases, 

however, have not distinguished among different laws of 

nature or natural phenomenon according to whether or 

not the principles they embody are sufficiently narrow. 

See, e.g., Parker v. Flook, 437 U.S. 584 (1978) (holding 

narrow mathematical formula unpatentable). In Parker 

v. Flook, the Supreme Court stated the issue in the case 

as follows: “The question in this case is whether the 

identification of a limited category of useful, though 

conventional, post-solution applications of such a formula 

makes respondent’s method eligible for patent protection.” 

Id. at 585. The answer to that question was “no” because 

granting exclusive rights to the mathematical formula 

would be exempting it from any future use. 

V 

For completeness, we address Sequenom’s remaining 

arguments. Sequenom argues that “before the ’540 patent, no one was using the plasma or serum of pregnant 

mothers to amplify and detect paternally-inherited

cffDNA.” Appellants’ Br. 49 (emphasis original). This 

argument implies that the inventive concept lies in the 

discovery of cffDNA in plasma or serum. Even if so, this 

is not the invention claimed by the ’540 patent. 

Sequenom further argues that “[o]ne simple measure 

of [Drs.] Lo and Wainscoat’s contribution is that their 

1997 Lancet publication has been cited over a thousand 

times.” Appellants’ Br. 25. Sequenom also notes that “the 

method reflects a significant human contribution in that 

[Drs.] Lo and Wainscoat combined and utilized man-made 

tools of biotechnology in a new way that revolutionized 

prenatal care.” Id. We agree but note that the Supreme 

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16 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 

Court instructs that “[g]roundbreaking, innovative, or 

even brilliant discovery does not by itself satisfy the § 101 

inquiry.” Myriad Genetics, Inc., 133 S. Ct. at 2117. The 

discovery of the BRCA1 and BRCA2 genes was a significant contribution to the medical field, but it was not 

patentable. Id. at 2117. While Drs. Lo and Wainscoat’s 

discovery regarding cffDNA may have been a significant 

contribution to the medical field, that alone does not make 

it patentable. We do not disagree that detecting cffDNA 

in maternal plasma or serum that before was discarded as 

waste material is a positive and valuable contribution to 

science. But even such valuable contributions can fall 

short of statutory patentable subject matter, as it does 

here. 

VI 

For each of the reasons stated above, we affirm the 

district court’s summary judgment ruling.

AFFIRMED

COSTS

No costs.

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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.

______________________ 

LINN, Circuit Judge, concurring. 

I join the court’s opinion invalidating the claims of 

the ’540 patent only because I am bound by the sweeping 

language of the test set out in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. ___, 132 

S. Ct. 1289 (2012). In my view, the breadth of the second 

part of the test was unnecessary to the decision reached 

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2 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 

in Mayo. This case represents the consequence—perhaps 

unintended—of that broad language in excluding a meritorious invention from the patent protection it deserves 

and should have been entitled to retain. 

It has long been established that “[l]aws of nature, 

natural phenomena, and abstract ideas are not patentable.” Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 

(2014) (citations omitted). In Mayo, the Supreme Court 

set forth a two-step framework for distinguishing patents 

that claim laws of nature, natural phenomena, and abstract ideas from those that claim patent-eligible applications of those concepts. The first step looks to determine 

whether claims are directed to a patent-ineligible concept. 

Mayo, 132 S. Ct. at 1297. If they are, the second step is to 

consider whether the additional elements recited in the 

claim “transform the nature of the claim” into a patenteligible application by reciting an “inventive concept” that 

is “sufficient to ensure that the patent in practice 

amounts to significantly more than a patent upon the 

[ineligible concept] itself.” Id. at 1294. 

In applying the second part of the test, the Supreme 

Court in Mayo discounted, seemingly without qualification, any “[p]ost-solution activity that is purely conventional or obvious,” id. at 1299 (original alterations 

omitted). This was unnecessary in Mayo, because doctors 

were already performing in combination all of the claimed 

steps of administering the drug at issue, measuring 

metabolite levels, and adjusting dosing based on the 

metabolite levels, id. 

In Diamond v. Diehr, the Supreme Court held that “a 

new combination of steps in a process may be patentable 

even though all the constituents of the combination were 

well-known and in common use before the combination 

was made.” 450 U.S. 175, 188 (1981). As Mayo explained: 

Diehr “pointed out that the basic mathematical equation, 

like a law of nature, was not patentable. But [Diehr] 

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ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 3

found the overall process patent eligible because of the 

way the additional steps of the process integrated the 

equation into the process as a whole.” Mayo 132 S. Ct. at 

1298. Despite that recognition, Mayo discounted entirely 

the “conventional activity” recited in the claims in that 

case because the steps “add nothing specific to the laws of 

nature other than what is well-understood, routine, 

conventional activity, previously engaged in by those in 

the field.” Id. at 1299. While that conclusion might have 

been warranted in that case, given the fact that the 

“conventional activities” in Mayo were the very steps that 

doctors were already doing—administering the drug at 

issue, measuring metabolite levels, and adjusting dosing 

based on the metabolite levels—the Supreme Court did 

not limit its ruling to those particular facts and circumstances. 

The Supreme Court’s blanket dismissal of conventional post-solution steps leaves no room to distinguish

Mayo from this case, even though here no one was amplifying and detecting paternally-inherited cffDNA using the 

plasma or serum of pregnant mothers. Indeed, the maternal plasma used to be “routinely discarded,” ’540 

patent col.1 ll.50–53, because, as Dr. Evans testified,

“nobody thought that fetal cell-free DNA would be present.”

It is hard to deny that Sequenom’s invention is truly 

meritorious. Prior to the ’540 patent, prenatal diagnoses 

required invasive methods, which “present[ed] a degree of 

risk to the mother and to the pregnancy.” Id. at col.1 

ll.16–17. The available “techniques [we]re timeconsuming or require[d] expensive equipment.” Id. at 

col.1 ll.17–37. Dr. Mark Evans testified that “despite 

years of trying by multiple methods, no one was ever able 

to achieve acceptable success and accuracy.” In a groundbreaking invention, Drs. Lo and Wainscoat discovered 

that there was cell-free fetal DNA in the maternal plasma. The Royal Society lauded this discovery as “a paraCase: 14-1144 Document: 29-2 Page: 19 Filed: 06/12/2015
4 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 

digm shift in non-invasive prenatal diagnosis,” and the 

inventors’ article describing this invention has been cited 

well over a thousand times. The commercial embodiment 

of the invention, the MaterniT21 test, was the first marketed non-invasive prenatal diagnostic test for fetal 

aneuploidies, such as Down’s syndrome, and presented

fewer risks and a more dependable rate of abnormality 

detection than other tests. Unlike in Mayo, the ’540 

patent claims a new method that should be patent eligible. While the instructions in the claims at issue in Mayo

had been widely used by doctors—they had been measuring metabolites and recalculating dosages based on toxicity/inefficacy limits for years—here, the amplification and 

detection of cffDNA had never before been done. The new 

use of the previously discarded maternal plasma to 

achieve such an advantageous result is deserving of 

patent protection. Cf. Rebecca S. Eisenberg, Prometheus 

Rebound: Diagnostics, Nature, and Mathematical Algorithms, 122 Yale L.J. Online 341, 343–44 (2013) (noting 

that despite Mayo’s declaration that a claim to “a new 

way of using an existing drug” is patentable, Mayo, 132 S. 

Ct. at 1302, it is unclear how a claim to new uses for 

existing drugs would survive Mayo’s sweeping test).

In short, Sequenom’s invention is nothing like the invention at issue in Mayo. Sequenom “effectuate[d] a 

practical result and benefit not previously attained,” so its 

patent would traditionally have been valid. Le Roy v. 

Tatham, 63 U.S. 132, 135–36 (1859) (quoting Househill 

Coal & Iron Co. v. Neilson, Webster’s Patent Case 673, 

683 (House of Lords 1843)); Le Roy v. Tatham, 55 U.S. 

156, 175 (1852) (same); see generally Jeffrey A. Lefstin, 

Inventive Application: a History, 67 Fla. L. Rev. (forthcoming 2015), available at

http://ssrn.com/abstract=2398696 (last visited June 10, 

2015) (analyzing traditional notions of patent eligibility of 

newly discovered laws of nature). But for the sweeping 

language in the Supreme Court’s Mayo opinion, I see no 

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ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 5

reason, in policy or statute, why this breakthrough invention should be deemed patent ineligible.

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