Ariosa Diagnostics, Inc. v. Sequenom, Inc. , 788 F.3d 1371 ( 2015 )

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 Ange-
les, CA, argued for plaintiff-appellee Ariosa Diagnostics,
Inc. Also represented by ANDREI IANCU; AMIR NAINI, Russ
August & Kabat, Los Angeles, CA.
2 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC.
WILLIAM PAUL SCHUCK, Bartko, Zankel, Bunzel & Mil-
ler, San Francisco, CA, for plaintiff-appellee Natera, Inc.,
counterclaim defendant-appellee DNA Diagnostics Cen-
ter, 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 Hul-
bert & 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.
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 3
I
In 1996, Drs. Dennis Lo and James Wainscoat discov-
ered 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, commer-
cialized 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 ampli-
fying the cffDNA contained in a sample of a plasma or
serum from a pregnant female and detecting the paternal-
ly 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 de-
tectable levels.
In the detecting step, the lab technician adds the am-
plified cffDNA to an agarose gel containing ethidium
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 determina-
tion of genetic defects and that a pregnant woman carry-
ing 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 pa-
tent 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 mater-
nal serum or plasma sample from a pregnant fe-
male, 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 re-
quire:
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.
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 5
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 am-
plified 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 com-
prises
obtaining a non-cellular fraction of the blood sam-
ple
amplifying a paternally inherited nucleic acid
from the non-cellular fraction
and performing nucleic acid analysis on the ampli-
fied nucleic acid to detect paternally inherited fe-
tal nucleic acid.
Id. at 26 ll. 20-36.
The remaining claims explain how the method of de-
tection occurs or how it can be used. For example, claim 2
depends from claim 1 and claims amplification by poly-
merase 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
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 infringe-
ment, Ariosa Diagnostics, Inc., Natera, Inc. and Diagnos-
tics 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 prelimi-
nary 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 eligibil-
ity of the asserted claims” of the ’540 patent, but remand-
ed “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.
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 7
§ 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 phe-
nomenon to make the claims patent eligible under § 101.
The district court determined that the steps of amplifying
and detecting were well-understood, routine, or conven-
tional 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 phe-
nomenon.” 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.
8 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC.
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 Labora-
tories, 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 patent-
ineligible concept. Id. at 1297. If the answer is yes, then
we next consider the elements of each claim both individ-
ually 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 significant-
ly 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 infor-
mation 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
that the existence of cffDNA in maternal blood is a natu-
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 9
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 find-
ing; maternal plasma is the very material that is routine-
ly 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 inven-
tion 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 plas-
ma/serum DNA may be a useful source of material for the
2 The term “fetal” and “foetal” are used inter-
changeably in the ’540 patent and by the parties.
10 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC.
non-invasive prenatal diagnosis of certain genetic disor-
ders,” 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 patent-
eligible 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 phenome-
non of cffDNA into a patentable invention.
Mayo made clear that transformation into a patent-
eligible 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 fea-
tures” 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 pro-
cess 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
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 11
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 deter-
mining 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 ap-
pending conventional steps, specified at a high level of
generality,” was not enough to supply an inventive con-
cept. 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 pater-
nally inherited cffDNA is not new and useful. The only
subject matter new and useful as of the date of the appli-
cation 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 plas-
ma 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
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 exam-
ple, 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 nu-
merous techniques which might be used to detect
repeat expansions, single gene mutations, dele-
tions 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.
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 13
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 conven-
tional activity. For example, claim 2 identifies the poly-
merase 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 conven-
tional in 1997, as specified by the patent itself. Like
claim 1, claims 5 and 8 focus on detecting a specific chro-
mosome 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 appli-
cation that starts and ends with a naturally occurring
phenomenon, the patent fails to disclose patent eligible
subject matter if the methods themselves are convention-
al, 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 princi-
ple 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 phenom-
enon. 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 substan-
tial risk of preempting all practical uses of it.
14 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC.
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 em-
body 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 meth-
ods 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 de-
scribed 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 technol-
ogy—abstract ideas, naturally occurring phenomena, and
natural laws. While preemption may signal patent ineli-
gible 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 ineligi-
ble subject matter under the Mayo framework, as they are
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 15
in this case, preemption concerns are fully addressed and
made moot.
Sequenom and amici encourage us to draw distinc-
tions 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 pa-
tent, 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
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 signifi-
cant 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.
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 Ser-
vices 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
2 ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC.
in Mayo. This case represents the consequence—perhaps
unintended—of that broad language in excluding a meri-
torious 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 patenta-
ble.” 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 ab-
stract ideas from those that claim patent-eligible applica-
tions 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 patent-
eligible 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 qualifica-
tion, any “[p]ost-solution activity that is purely conven-
tional 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]
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 circum-
stances.
The Supreme Court’s blanket dismissal of conven-
tional post-solution steps leaves no room to distinguish
Mayo from this case, even though here no one was ampli-
fying and detecting paternally-inherited cffDNA using the
plasma or serum of pregnant mothers. Indeed, the ma-
ternal 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 pre-
sent.”
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 time-
consuming 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 ground-
breaking invention, Drs. Lo and Wainscoat discovered
that there was cell-free fetal DNA in the maternal plas-
ma. The Royal Society lauded this discovery as “a para-
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 mar-
keted 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 eligi-
ble. While the instructions in the claims at issue in Mayo
had been widely used by doctors—they had been measur-
ing metabolites and recalculating dosages based on toxici-
ty/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 Algo-
rithms, 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 in-
vention 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. (forth-
coming 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
ARIOSA DIAGNOSTICS, INC v. SEQUENOM, INC. 5
reason, in policy or statute, why this breakthrough inven-
tion should be deemed patent ineligible.