Filed: Aug. 03, 2020
Latest Update: Aug. 03, 2020
Summary: Case: 19-1419 Document: 64 Page: 1 Filed: 08/03/2020 United States Court of Appeals for the Federal Circuit _ ILLUMINA, INC., SEQUENOM, INC., Plaintiffs-Appellants v. ARIOSA DIAGNOSTICS, INC., ROCHE SEQUENCING SOLUTIONS, INC., ROCHE MOLECULAR SYSTEMS, INC., Defendants-Appellees _ 2019-1419 _ Appeal from the United States District Court for the Northern District of California in No. 3:18-cv-02847-SI, Senior Judge Susan Y. Illston. _ OPINION ISSUED: March 17, 2020 OPINION MODIFIED: August 3, 2020
Summary: Case: 19-1419 Document: 64 Page: 1 Filed: 08/03/2020 United States Court of Appeals for the Federal Circuit _ ILLUMINA, INC., SEQUENOM, INC., Plaintiffs-Appellants v. ARIOSA DIAGNOSTICS, INC., ROCHE SEQUENCING SOLUTIONS, INC., ROCHE MOLECULAR SYSTEMS, INC., Defendants-Appellees _ 2019-1419 _ Appeal from the United States District Court for the Northern District of California in No. 3:18-cv-02847-SI, Senior Judge Susan Y. Illston. _ OPINION ISSUED: March 17, 2020 OPINION MODIFIED: August 3, 2020 *..
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Case: 19-1419 Document: 64 Page: 1 Filed: 08/03/2020
United States Court of Appeals
for the Federal Circuit
______________________
ILLUMINA, INC., SEQUENOM, INC.,
Plaintiffs-Appellants
v.
ARIOSA DIAGNOSTICS, INC., ROCHE
SEQUENCING SOLUTIONS, INC., ROCHE
MOLECULAR SYSTEMS, INC.,
Defendants-Appellees
______________________
2019-1419
______________________
Appeal from the United States District Court for the
Northern District of California in No. 3:18-cv-02847-SI,
Senior Judge Susan Y. Illston.
______________________
OPINION ISSUED: March 17, 2020
OPINION MODIFIED: August 3, 2020 *
______________________
EDWARD R. REINES, Weil, Gotshal & Manges LLP, Red-
wood Shores, CA, argued for plaintiffs-appellants. Also
represented by CHRISTOPHER SHAWN LAVIN, DEREK C.
WALTER; ZACHARY TRIPP, Washington, DC.
* This opinion has been modified and reissued fol-
lowing a petition for rehearing filed by Defendants-Appel-
lees.
Case: 19-1419 Document: 64 Page: 2 Filed: 08/03/2020
2 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
DARALYN JEANNINE DURIE, Durie Tangri LLP, San
Francisco, CA, argued for all defendants-appellees. De-
fendant-appellee Ariosa Diagnostics, Inc. also represented
by DAVID FLOYD MCGOWAN, LAURA MILLER.
ROBERT J. GUNTHER, JR., Wilmer Cutler Pickering Hale
and Dorr LLP, New York, NY, for defendants-appellees
Roche Sequencing Solutions, Inc., Roche Molecular Sys-
tems, Inc. Also represented by OMAR KHAN, CHRISTOPHER
R. NOYES; THOMAS SAUNDERS, Washington, DC.
______________________
Before LOURIE, MOORE, and REYNA, Circuit Judges.
Opinion for the court filed by Circuit Judge LOURIE.
Dissenting opinion filed by Circuit Judge REYNA.
LOURIE, Circuit Judge.
Illumina, Inc. and Sequenom, Inc. (collectively, “Illu-
mina”) appeal from a decision of the United States District
Court for the Northern District of California that claims 1–
2, 4–5, and 9–10 of U.S. Patent 9,580,751 (the “’751 pa-
tent”) and claims 1–2 and 10–14 of U.S. Patent 9,738,931
(the “’931 patent”) are invalid under 35 U.S.C. § 101 as di-
rected to an ineligible natural phenomenon. Illumina, Inc.
v. Ariosa Diagnostics, Inc., 356 F. Supp. 3d 925 (N.D. Cal.
2018) (“Decision”). Because we conclude that the claims
are directed to patent-eligible subject matter, we reverse.
BACKGROUND
“In 1996, Drs. Dennis Lo and James Wainscoat discov-
ered cell-free fetal DNA in maternal plasma and serum, the
portion of maternal blood samples that other researchers
had previously discarded as medical waste.” Ariosa Diag-
nostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1373 (Fed.
Cir. 2015). They applied for a patent, and, in 2001, they
obtained U.S. Patent 6,258,540, which claimed a method
Case: 19-1419 Document: 64 Page: 3 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 3
for detecting the small fraction of paternally inherited cell-
free fetal DNA in the plasma and serum of a pregnant
woman.
Id. In 2015, we held that the claims of that patent
were invalid under 35 U.S.C. § 101 because they were di-
rected to “matter that is naturally occurring”—i.e., the nat-
ural phenomenon that cell-free fetal DNA exists in
maternal blood.
Id. at 1376.
The present case involves two patents that are unre-
lated to the patent held invalid in Ariosa, but rather claim
priority from a European patent application filed in 2003.
The ’751 and ’931 patents at issue in this case, which are
related to each other and have largely identical specifica-
tions, begin by acknowledging the natural phenomenon
that was at issue in Ariosa: “[I]t has been shown that in the
case of a pregnant woman extracellular fetal DNA is pre-
sent in the maternal circulation and can be detected in ma-
ternal plasma . . . .” ’751 patent col. 1 ll. 23–25. The
patents then identify a problem that was the subject of fur-
ther research on cell-free fetal DNA in maternal blood:
[T]he major proportion (generally >90%) of the ex-
tracellular DNA in the maternal circulation is de-
rived from the mother. This vast bulk of maternal
circulatory extracellular DNA renders it difficult, if
not impossible, to determine fetal genetic alterna-
tions [sic] . . . from the small amount of circulatory
extracellular fetal DNA.
Id. col. 1 ll. 42–50. In simple terms, the problem that the
inventors encountered was that, although it was known
that cell-free fetal DNA existed in the mother’s blood-
stream, there was no known way to distinguish and sepa-
rate the tiny amount of fetal DNA from the vast amount of
maternal DNA.
The inventors of the ’751 and ’931 patents attempted to
find a solution to that problem. First, they made a discov-
ery:
Case: 19-1419 Document: 64 Page: 4 Filed: 08/03/2020
4 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
An examination of circulatory extracellular fetal
DNA and circulatory extracellular maternal DNA
in maternal plasma has now shown that, surpris-
ingly, the majority of the circulatory extracellular
fetal DNA has a relatively small size of approxi-
mately 500 base pairs or less, whereas the majority
of circulatory extracellular maternal DNA in ma-
ternal plasma has a size greater than approxi-
mately 500 base pairs.
Id. col. 1 ll. 54–61. To arrive at that discovery, the inven-
tors examined five pregnancies and found that cell-free fe-
tal DNA fragments “were almost completely of sizes
smaller than 500 base pairs.” ’751 patent col. 4 ll. 50–53.
Moreover, the inventors found that 70% of all DNA frag-
ments smaller than 300 base pairs were fetal.
Id.
Having made that discovery regarding the relative size
distributions of cell-free fetal and maternal DNA frag-
ments in a pregnant mother’s bloodstream, the inventors
used their discovery to develop a solution to the identified
problem of distinguishing the fetal DNA from the maternal
DNA:
This surprising finding forms the basis of the pre-
sent invention according to which separation of cir-
culatory extracellular DNA fragments which are
smaller than approximately 500 base pairs pro-
vides a possibility to enrich for fetal DNA se-
quences from the vast bulk of circulatory
extracellular maternal DNA.
Id. col. 2 ll. 1–6.
The claims of the ’751 and ’931 patents are directed to
that solution. Specifically, they claim methods of prepar-
ing a fraction of cell-free DNA that is enriched in fetal
DNA. The methods of preparation include size discrimina-
tion of the DNA based on size parameters that the inven-
tors selected to balance the need to remove enough longer
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ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 5
maternal DNA fragments to enrich the sample but also
leave behind enough shorter fetal DNA fragments to allow
for testing. As explained in the patent, “depending on the
downstream application” of the enriched mixture, the size
parameter is not fixed at either 500 or 300 base pairs but
can be even smaller. See ’751 patent col. 4 ll. 57–59.
Claim 1 of the ’751 patent, the only independent claim,
includes an inventor-chosen size parameter of 500 base
pairs to allow for selective removal of longer DNA frag-
ments from the mixture:
1. A method for preparing a deoxyribonucleic
acid (DNA) fraction from a pregnant human female
useful for analyzing a genetic locus involved in a
fetal chromosomal aberration, comprising:
(a) extracting DNA from a substantially cell-free
sample of blood plasma or blood serum of a preg-
nant human female to obtain extracellular circula-
tory fetal and maternal DNA fragments;
(b) producing a fraction of the DNA extracted in
(a) by:
(i) size discrimination of extracellular circula-
tory DNA fragments, and
(ii) selectively removing the DNA fragments
greater than approximately 500 base pairs,
wherein the DNA fraction after (b) comprises a
plurality of genetic loci of the extracellular circula-
tory fetal and maternal DNA; and
(c) analyzing a genetic locus in the fraction of
DNA produced in (b).
’751 patent col. 7 l. 54–col. 8 l. 57. In contrast, claim 1 of
the ’931 patent imposes a different size parameter, namely,
300 base pairs:
1. A method, comprising:
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6 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
(a) extracting DNA comprising maternal and fe-
tal DNA fragments from a substantially cell-free
sample of blood plasma or blood serum of a preg-
nant human female;
(b) producing a fraction of the DNA extracted in
(a) by:
(i) size discrimination of extracellular circula-
tory fetal and maternal DNA fragments, and
(ii) selectively removing the DNA fragments
greater than approximately 300 base pairs,
wherein the DNA fraction after (b) comprises ex-
tracellular circulatory fetal and maternal DNA
fragments of approximately 300 base pairs and less
and a plurality of genetic loci of the extracellular
circulatory fetal and maternal DNA fragments; and
(c) analyzing DNA fragments in the fraction of
DNA produced in (b).
’931 patent col. 7 l. 58–col. 8 l. 63.
Dependent claims in each patent place further limita-
tions on the size discrimination and selective removal pro-
cesses recited in step (b) of the method claims. For
example, dependent claim 7 of the ’751 patent recites that
“the size discrimination in (b) comprises centrifugation,”
and claim 8 further limits it to “density gradient centrifu-
gation.” ’751 patent col. 9 ll. 1–4. Likewise, dependent
claims 4–10 of the ’931 patent recite that step (b) can com-
prise “chromatography,” “electrophoresis,” “centrifuga-
tion,” and/or “nanotechnological means.” ’931 patent col. 9
ll. 1–14.
Illumina filed suit against Ariosa Diagnostics, Inc.,
Roche Sequencing Solutions, Inc., and Roche Molecular
Systems, Inc. (collectively, “Roche”) alleging infringement
of the ’751 and ’931 patents. Roche moved for summary
judgment that the asserted claims are invalid under 35
Case: 19-1419 Document: 64 Page: 7 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 7
U.S.C. § 101. The district court granted Roche’s motion for
summary judgment, holding that the claims of the ’751 and
’931 patents are directed to ineligible subject matter. De-
cision, 356 F. Supp. 3d at 935. The court entered judgment
in favor of Roche, and Illumina appealed. We have juris-
diction under 28 U.S.C. § 1295(a)(1).
DISCUSSION
We review a grant of summary judgment according to
the law of the regional circuit. Kaneka Corp. v. Xiamen
Kingdomway Grp. Co., 790 F.3d 1298, 1303 (Fed. Cir. 2015)
(citing Halo Elecs., Inc. v. Pulse Elecs., Inc.,
769 F.3d 1371,
1377 (Fed. Cir. 2014)). In the Ninth Circuit, a grant of
summary judgment is reviewed de novo. Leever v. Carson
City,
360 F.3d 1014, 1017 (9th Cir. 2004) (citing Hargis v.
Foster,
312 F.3d 404, 409 (9th Cir. 2002)). Summary judg-
ment is appropriate when “there is no genuine dispute as
to any material fact and the movant is entitled to judgment
as a matter of law.” Fed. R. Civ. P. 56.
I
Section 101 provides that “Whoever invents or discov-
ers any new and useful process, machine, manufacture, or
composition of matter, or any new and useful improvement
thereof, may obtain a patent therefor . . . .” 35 U.S.C. § 101.
Given the expansive terms of § 101, “Congress plainly con-
templated that the patent laws would be given wide scope”;
the legislative history likewise indicated that “Congress in-
tended statutory subject matter to ‘include anything under
the sun that is made by man.’” Diamond v. Chakrabarty,
447 U.S. 303, 308–09 (1980) (internal citation omitted).
The Supreme Court has held that § 101 “contains an
important implicit exception. ‘[L]aws of nature, natural
phenomena, and abstract ideas’ are not patentable.” Mayo
Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66,
70 (2012) (alteration in original) (quoting Diamond v.
Diehr,
450 U.S. 175, 185 (1981)). These exceptions exist
Case: 19-1419 Document: 64 Page: 8 Filed: 08/03/2020
8 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
because monopolizing the basic tools of scientific work
“might tend to impede innovation more than it would tend
to promote it.”
Id. at 71.
However, the Supreme Court has
advised that these exceptions must be applied cautiously,
as “too broad an interpretation of this exclusionary princi-
ple could eviscerate patent law.”
Id.
Laws of nature and natural phenomena are not patent-
able, but applications and uses of such laws and phenom-
ena may be patentable. A claim to otherwise statutory
subject matter does not become ineligible by its use of a law
of nature or natural phenomenon. See
Diehr, 450 U.S. at
187; Parker v. Flook,
437 U.S. 584, 590 (1978). On the other
hand, adding “conventional steps, specified at a high level
of generality,” to a law of nature or natural phenomenon
does not make a claim to the law or phenomenon patenta-
ble.
Mayo, 566 U.S. at 82.
To distinguish claims to patent-eligible applications of
laws of nature and natural phenomena from claims that
impermissibly tie up such laws and phenomena, we apply
the two-part test set forth by the Supreme Court. First, we
examine whether the claims are “directed to” a law of na-
ture or natural phenomenon. Alice Corp. Pty. Ltd. v. CLS
Bank Int’l, 573 U.S. 208, 217 (2014). If—and only if—they
are, then we proceed to the second inquiry, where we ex-
amine whether the limitations of the claim apart from the
law of nature or natural phenomenon, considered individ-
ually and as an ordered combination, “‘transform the na-
ture of the claim’ into a patent-eligible application.”
Id.
(quoting Mayo, 566 U.S. at 78).
II
This is not a diagnostic case. And it is not a method of
treatment case. It is a method of preparation case.
Under Mayo, we have consistently held diagnostic
claims unpatentable as directed to ineligible subject mat-
ter. See Athena Diagnostics, Inc. v. Mayo Collaborative
Case: 19-1419 Document: 64 Page: 9 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 9
Servs., LLC, 927 F.3d 1333, 1352 (Fed. Cir. 2019) (Moore,
J., dissenting from denial of rehearing en banc) (“Since
Mayo, we have held every single diagnostic claim in every
case before us ineligible.”); see also, e.g., Athena Diagnos-
tics, Inc. v. Mayo Collaborative Servs., LLC,
915 F.3d 743
(Fed. Cir. 2019); Cleveland Clinic Found. v. True Health
Diagnostics LLC,
859 F.3d 1352 (Fed. Cir. 2017); Cleveland
Clinic Found. v. True Health Diagnostics LLC, 760 F. App’x
1013 (Fed. Cir. 2019). In contrast, we have held that
method of treatment claims are patent-eligible. See Endo
Pharm. Inc. v. Teva Pharm. USA, Inc.,
919 F.3d 1347 (Fed.
Cir. 2019); Natural Alternatives Int’l, Inc. v. Creative Com-
pounds, LLC,
918 F.3d 1338 (Fed. Cir. 2019); Vanda
Pharm. Inc. v. West-Ward Pharm. Int’l Ltd.,
887 F.3d 1117
(Fed. Cir. 2018). The claims in this case do not fall into
either category, and we consider the claims under the Al-
ice/Mayo test.
Here, it is undisputed that the inventors of the ’751 and
’931 patents discovered a natural phenomenon. But at step
one of the Alice/Mayo test, “it is not enough to merely iden-
tify a patent-ineligible concept underlying the claim; we
must determine whether that patent-ineligible concept is
what the claim is ‘directed to.’” Rapid Litig. Mgmt. Ltd. v.
CellzDirect, Inc., 827 F.3d 1042, 1050 (Fed. Cir. 2016). The
focus of the dispute in this case is whether the claims of the
’751 and ’931 patents are “directed to” the natural phenom-
enon, i.e., whether they claim the discovered natural phe-
nomenon itself versus eligible subject matter that exploits
the discovery of the natural phenomenon.
As an initial matter, there are differences between the
district court and the parties about how to articulate the
natural phenomenon that the inventors discovered. The
district court appeared to find that the relevant natural
phenomenon is either the “testable quantity” of fetal DNA
or “test results” obtained from that fetal DNA. Decision,
356 F. Supp. 3d at 933. Roche’s articulation of the natural
phenomenon was a moving target throughout its briefing
Case: 19-1419 Document: 64 Page: 10 Filed: 08/03/2020
10 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
and at oral argument, but appears to be the “size distribu-
tion” of fetal to maternal cell-free DNA in a mother’s blood
reflected in Table 1 of the specification, with a particular
focus on the number “500 base pairs” as the critical divid-
ing line between the two. See Appellee’s Br. 14, 18, 21; Oral
Arg. 27:58, 28:35, 29:16. And Illumina asserts more simply
that the inventors’ discovery was that “fetal cell-free DNA
tends to be shorter than maternal cell-free DNA.” Appel-
lant’s Br. 24; see also
id. at 8
(“[I]n a sample of cell-free
DNA from a pregnant woman, the DNA that arises from
the fetus is smaller on average than the DNA that arises
from the mother.”).
We take note of Roche’s inability—despite its status as
the party challenging the validity of the patents—to
clearly identify the natural phenomenon that forms the ba-
sis of its challenge. But, ultimately, we find that the par-
ties’ respective articulations reflect distinctions without
differences. For simplicity, we adopt Illumina’s articula-
tion of the natural phenomenon, i.e., that cell-free fetal
DNA tends to be shorter than cell-free maternal DNA in a
mother’s bloodstream. We thus turn to the crucial question
on which this case depends: whether the claims are “di-
rected to” that natural phenomenon. We conclude that the
claims are not directed to that natural phenomenon but ra-
ther to a patent-eligible method that utilizes it.
The claims in this case are directed to methods for pre-
paring a fraction of cell-free DNA that is enriched in fetal
DNA. The methods include specific process steps—size dis-
criminating and selectively removing DNA fragments that
are above a specified size threshold—to increase the rela-
tive amount of fetal DNA as compared to maternal DNA in
the sample. ’751 patent col. 7 ll. 63–67. The size thresholds
in the claims—500 base pairs in the ’751 patent and 300
base pairs in the ’931 patent—are not dictated by any nat-
ural phenomenon, particularly because the size distribu-
tions of fetal and maternal cell-free DNA overlap each
other (i.e., there are maternal DNA fragments shorter than
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ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 11
300 base pairs). The claimed size thresholds are human-
engineered parameters that optimize the amount of mater-
nal DNA that is removed from the mixture and the amount
of fetal DNA that remains in the mixture in order to create
an improved end product that is more useful for genetic
testing than the original natural extracted blood sample.
Moreover, the claimed methods achieve more than
simply observing that fetal DNA is shorter than maternal
DNA or detecting the presence of that phenomenon. The
claims include physical process steps that change the com-
position of the mixture, resulting in a DNA fraction that is
different from the naturally occurring fraction in the
mother’s blood. The dependent claims further illustrate
the concrete nature of the claimed process steps. For ex-
ample, claims 7–8 of the ’751 patent and claims 8–9 of the
’931 patent require that the size discrimination step com-
prise “centrifugation,” and specifically “density gradient
centrifugation.” ’751 patent col. 9 ll. 1–4; ’931 patent col. 9
ll. 9–12. Other dependent claims in the ’931 patent com-
prise other discrimination and separation means, such as
“high performance liquid chromatography” (claims 4–5),
“capillary electrophoresis” (claims 6–7), or “nanotechnolog-
ical means” (claim 10). These dependent claims are sup-
ported by the specification’s description of the physical
means by which the size discrimination and selective re-
moval step of the claims can be achieved:
The size separation of the extracellular DNA in
said serum or plasma sample can be brought about
by a variety of methods, including but not limited
to: chromatography or electrophoresis such as chro-
matography on agarose or polyacrylamide gels, ion-
pair reversed-phase high performance liquid chro-
matography [], capillary electrophoresis in a self-
coating, low-viscosity polymer matrix [], selective
extraction in microfabricated electrophoresis de-
vices [], microchip electrophoresis on reduced vis-
cosity polymer matrices [], adsorptive membrane
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12 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
chromatography [] and the like; density gradient
centrifugation []; and methods utilising [sic] nano-
technological means such as microfabricated en-
tropic trap arrays [] and the like.
’931 patent col. 2 l. 61–col. 3 l. 18 (citations omitted); see
also id. col. 4 ll. 15–22 (“3. The gel was electrophoresed at
80 Volt for 1 hour. 4. The Gel [sic] was cut into pieces cor-
responding to specific DNA sizes . . . .”). As described by
the specification, the inventors used these concrete process
steps, not merely to observe the presence of the phenome-
non that fetal DNA is shorter than maternal DNA, but ra-
ther to exploit that discovery in a method for preparation
of a mixture enriched in fetal DNA.
Roche insists that the claims in this case are no more
eligible than the claims at issue in Ariosa. We disagree. In
Ariosa, the relevant independent claims were directed to a
method “for detecting a paternally inherited nucleic acid”
(claims 1 and 24) or a method “for performing a prenatal
diagnosis” (claim 25). See Ariosa, 788 F.3d at 1373–74.
The only operative steps in the claims were “amplifying”
(i.e., making more of) the cell-free fetal DNA and then “de-
tecting [it],” “subjecting [it] . . . to a test,” or “performing
nucleic acid analysis on [it] to detect [it].”
Id. We found
those claims ineligible because, like the invalid diagnostic
claims at issue in Mayo, Athena, and Cleveland Clinic, they
were directed to detecting a natural phenomenon after a
sample has been prepared or extracted. In essence, the in-
ventors in Ariosa discovered that cell-free fetal DNA exists,
and then obtained patent claims that covered a method di-
rected to starting with a sample that contains cell-free fetal
DNA and seeing that that the cell-free fetal DNA exists.
Here, in contrast, the claims are directed to more than
just the correlation between a DNA fragment’s size and its
tendency to be either fetal or maternal, a correlation which
is not even mentioned in the claims. The claims do not
cover a method for detecting whether a cell-free DNA
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ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 13
fragment in a previously-prepared sample is fetal or ma-
ternal based on the natural size distribution of cell-free
DNA fragments; rather, the claimed methods exploit that
natural size distribution during the sample preparation
steps to remove some maternal DNA from the mother’s
blood. Even the “analyzing” step of the claims is not di-
rected to analyzing the discovered natural phenomenon,
but to analyzing something else entirely, namely, “fetal
chromosomal aberrations.” See ’751 patent col. 7 ll. 55–56,
col. 8 ll. 56–57, col. 9 ll. 5–8; ’931 patent col. 9 ll. 17–24.
Thus, the claims in this case are different from the claims
that we held invalid in Ariosa.
Roche also argues, based on the Supreme Court’s deci-
sion in Association for Molecular Pathology v. Myriad Ge-
netics, Inc., that “a naturally occurring DNA segment is a
product of nature and not patent eligible merely because it
has been isolated.” 569 U.S. 576, 580 (2013). But the
claims here are not directed to the cell-free fetal DNA itself.
The Supreme Court in Myriad expressly declined to extend
its holding to method claims reciting an innovative process
used to isolate DNA. See
id. at 595–96.
The Court stated:
It is important to note what is not implicated by
this decision. First, there are no method claims be-
fore this Court. Had Myriad created an innovative
method of manipulating genes while searching for
the BRCA1 and BRCA2 genes, it could possibly
have sought a method patent. But the processes
used by Myriad to isolate DNA were well under-
stood by geneticists at the time of Myriad’s patents,
were well understood, widely used, and fairly uni-
form insofar as any scientist engaged in the search
for a gene would likely have utilized a similar ap-
proach, and are not at issue in this case.
Id. (internal quotation marks omitted). Thus, in Myriad,
the claims were ineligible because they covered a gene that
Case: 19-1419 Document: 64 Page: 14 Filed: 08/03/2020
14 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
the inventors isolated but did not invent, rather than an
innovative process for isolating a gene.
Here, we encounter the opposite situation, i.e., the
claims do not cover separated cell-free fetal DNA itself but
rather a process for selective removal of non-fetal DNA to
enrich a mixture in fetal DNA. That process includes size
parameters that the inventors engineered to balance the
practicalities of the specific problem that they were facing,
namely, removing enough cell-free maternal DNA to enrich
the mixture while leaving enough cell-free fetal DNA to al-
low for testing. Thus, the Supreme Court’s decision in Myr-
iad is not on point in this case where the inventors claimed
to have conceived and reduced to practice, not the sepa-
rated DNA, but a method that uses unconventional size pa-
rameters to perform the separation.
In our view, CellzDirect, while not directly on point, is
instructive. In CellzDirect, the inventors discovered the
natural phenomenon “that some fraction of hepatocytes are
capable of surviving multiple freeze-thaw cycles.” 827 F.3d
at 1045. Having made that discovery, they patented an
“improved process of preserving hepatocytes,” that com-
prises freezing hepatocytes, thawing the hepatocytes, re-
moving the non-viable hepatocytes, and refreezing the
viable hepatocytes.
Id. We found that their claimed inven-
tion was patent-eligible because it was “not simply an ob-
servation or detection of the ability of hepatocytes to
survive multiple freeze-thaw cycles. Rather, the claims are
directed to a new and useful method of preserving hepato-
cyte cells.”
Id. at 1048.
The inventors in CellzDirect did not invent hepatocytes
or impart to hepatocytes an ability to survive cycles of
freezing and thawing.
Id. at 1045.
Rather, they discovered
that hepatocytes naturally have that ability, and they ex-
ploited that phenomenon in a patent-eligible method. So
too here, the inventors of the ’751 and ’931 patents obvi-
ously did not invent cell-free fetal DNA or the relative size
Case: 19-1419 Document: 64 Page: 15 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 15
distribution of fetal and maternal cell-free DNA in mater-
nal blood. And, like in CellzDirect, the inventors used their
discovery to invent a method of preparing a fraction of DNA
that includes physical process steps with human-engi-
neered size parameters to selectively remove some mater-
nal DNA in blood to produce a mixture enriched in fetal
DNA.
Roche argues that the techniques for size discriminat-
ing and selectively removing DNA fragments that are used
to practice the invention were well-known and conven-
tional. And we recognize, of course, that the inventors of
the ’751 and ’931 patents did not invent centrifugation,
chromatography, electrophoresis, or nanotechnology. 1 But
conventional separation technologies can be used in uncon-
ventional ways. And Roche, the party challenging the va-
lidity of the patents and thus bearing the burden of proof
on its § 101 challenge, has presented no evidence that
thresholds of 500 base pairs and 300 base pairs were con-
ventional for separating different types of cell-free DNA
fragments. Thus, the claims are directed to a human-engi-
neered method rather than the natural size distributions
of cell-free DNA. Moreover, while such conventionality
considerations may be relevant to the inquiry under Al-
ice/Mayo step two, or to other statutory considerations such
as obviousness that are not at issue before us in this case,
they do not impact the Alice/Mayo step one question
whether the claims themselves are directed to a natural
phenomenon. Again, CellzDirect is instructive, where we
acknowledged that the inventors had not invented the well-
known processes of “freezing” and “thawing,” but only in
1 We note, without deciding, that Illumina argues
that claim 11 of the ’931 patent requires the use of micro-
arrays, which it claims was a methodology not previously
used with cell-free DNA. Appellant’s Br. 40.
Case: 19-1419 Document: 64 Page: 16 Filed: 08/03/2020
16 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
the context of the Alice/Mayo step two inquiry. 827 F.3d at
1050–51.
Rather than focusing on what the inventors of the ’751
and ’931 patents did not invent, we focus our Alice/Mayo
step one analysis on what the inventors did purport to in-
vent and what they claimed in their patents: methods for
preparing a fraction of cell-free DNA by the physical pro-
cess of size discriminating and selectively removing DNA
fragments longer than a specified human-engineered
threshold. Those methods are “directed to” more than
merely the natural phenomenon that the inventors discov-
ered. Accordingly, we conclude at step one of the Al-
ice/Mayo test that the claims are not directed to a patent-
ineligible concept, and we need not reach step two of the
test.
III
In Ariosa, we recognized that the inventors had made
a discovery with implications that would allow what had
previously been discarded as medical waste to be used as a
tool for determining fetal characteristics. 788 F.3d at 1373.
We acknowledged the profound impact that the discovery
had on the field of prenatal medicine, including that it “cre-
ated an alternative for prenatal diagnosis of fetal DNA that
avoids the risks of widely-used techniques that took sam-
ples from the fetus or placenta.”
Id. Nevertheless, under
guidance from the Supreme Court, we determined that the
discovery of that natural phenomenon, no matter how sig-
nificant it was to the medical field, was not itself patenta-
ble, and neither was a method for detecting it.
Id. at 1379–
80.
The invention in this case is the product of further re-
search on cell-free fetal DNA. This time, the inventors dis-
covered that, not only does the fetal DNA exist in the
bloodstream of a pregnant mother, but it has characteris-
tics that make it distinguishable, and therefore separable,
from the maternal DNA. Again, regardless how
Case: 19-1419 Document: 64 Page: 17 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 17
groundbreaking this additional discovery may have been,
the inventors were not entitled to patent the natural phe-
nomenon that cell-free fetal DNA tends to be shorter than
cell-free maternal DNA. “Groundbreaking, innovative, or
even brilliant discovery does not by itself satisfy the § 101
inquiry.”
Myriad, 569 U.S. at 591. Thus, they could not
claim a method directed to the natural phenomenon, e.g., a
method for determining whether a fragment of cell-free
DNA is fetal or maternal based on its length. And they did
not attempt to patent such a method.
The inventors here patented methods of preparing a
DNA fraction. The claimed methods utilize the natural
phenomenon that the inventors discovered by employing
physical process steps and human-engineered size param-
eters to selectively remove larger fragments of cell-free
DNA and thus enrich a mixture in cell-free fetal DNA.
Though we make no comment on whether the claims at is-
sue will pass muster under challenges based on any other
portion of the patent statute, under § 101 the claimed
methods are patent-eligible subject matter.
CONCLUSION
We conclude that the claims of the ’751 and ’931 pa-
tents are directed to patent-eligible subject matter under
35 U.S.C. § 101. We therefore reverse the district court’s
grant of summary judgment and remand for further pro-
ceedings.
REVERSED AND REMANDED
Case: 19-1419 Document: 64 Page: 18 Filed: 08/03/2020
United States Court of Appeals
for the Federal Circuit
______________________
ILLUMINA, INC., SEQUENOM, INC.,
Plaintiffs-Appellants
v.
ARIOSA DIAGNOSTICS, INC., ROCHE
SEQUENCING SOLUTIONS, INC., ROCHE
MOLECULAR SYSTEMS, INC.,
Defendants-Appellees
______________________
2019-1419
______________________
Appeal from the United States District Court for the
Northern District of California in No. 3:18-cv-02847-SI,
Senior Judge Susan Y. Illston.
______________________
REYNA, Circuit Judge, dissenting.
The claims, written description, and legal precedent
converge to a conclusion that the ’751 and ’931 patents 1
cover patent ineligible subject matter. The asserted claims
are directed to a natural phenomenon, the patents’ sole
claimed advance is the discovery of that natural
1 U.S. Patent Nos. 9,580,751 and 9,738,931. The pa-
tents contain nearly identical written descriptions and
claims. For economy, this opinion will reference only the
’751 patent.
Case: 19-1419 Document: 64 Page: 19 Filed: 08/03/2020
2 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
phenomenon, and the application of the natural phenome-
non utilizes routine steps and conventional procedures that
are well known in the art.
The patents in this appeal proclaim a surprising dis-
covery that has advanced the medical arts in an area of
great need. Without doubt, scientists are entitled to great
credit and recognition for such a discovery. But, under U.S.
patent law, they are not entitled to a patent.
DISCUSSION
I. The Claims are Directed to a Natural Phenomenon
At the time of the invention, skilled artisans were
aware that cell-free fetal DNA (“cff-DNA”) existed; that cff-
DNA could be detected in a sample of a pregnant woman’s
blood or serum; and that cff-DNA was useful for reliably
analyzing fetal genetic markers (for detecting certain dis-
eases and disorders). ’751 patent at col. 1 ll. 22–34. But
for some genetic markers found in the genomes of both the
mother and the fetus, skilled artisans faced a problem: the
relatively small amount of cff-DNA compared to the
amount of maternal extracellular DNA in the mother’s
blood made it difficult to identify and analyze genetic alter-
ations in the fetus. Id. at col. 1 ll. 41–50.
The patent informs us that the problem was overcome
when the inventors made a “surprising” discovery. Id. at
col. 1 ll. 54–61. The inventors discovered that cff-DNA
tends to be shorter than cell-free maternal DNA in a
mother’s blood. See ’751 patent at col. 1 ll. 54–67; see also
Maj. Op. at 3–4, 8. The written description explains that
the majority of cff-DNA in the mother’s blood plasma “has
a relatively small size of approximately 500 base pairs or
less, whereas the majority of circulatory extracellular ma-
ternal DNA in maternal plasma has a size greater than ap-
proximately 500 base pairs.”
Id. at col. 1 ll. 54–61. The
written description states that “[t]his surprising finding
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ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 3
forms the basis of the present invention.”
Id. at col. 2 ll. 1–
2 (emphasis added).
As explained in detail below, it is to this precise sur-
prising discovery of size discrepancy of cff-DNA in a
mother’s blood—an undisputed natural phenomenon—
that the claims at issue are directed. These claims, thus,
do not escape Alice step one.
A. The Claimed Method Steps
Involve a Natural Phenomenon
The first step of the Alice test requires that we deter-
mine whether the claims at issue are “directed to” a natural
phenomenon. Alice Corp. Pty. Ltd. v. CLS Bank Intern, 573
U.S. 208, 217–18 (2014). To make this determination, the
Supreme Court has analyzed whether the claims “in-
volved” patent-ineligible subject matter.
Id. at 219; see also
id. at 218–20
(citing Gottschalk v. Benson,
409 U.S. 63, 71–
72 (1972), and Bilski v. Kappos,
561 U.S. 593, 599 (2010)).
In Alice, the Court determined that the claims were di-
rected to an abstract idea because the claims “involve” the
abstract idea of “intermediated settlement,” a concept the
Court deemed a “fundamental economic practice.”
Alice,
573 U.S. at 219. Like in Alice, the claims here are directed
to a natural phenomenon because they involve a funda-
mental natural phenomenon, that cff-DNA tends to be
shorter than cell-free maternal DNA in a mother’s blood, to
produce a “mixture” of naturally-occurring substances.
For example, the preamble of claim 1 of the ’751 patent
informs us that the patent claims a method for preparing a
DNA “fraction” from a pregnant human female that can be
used for diagnostic purposes. 2 The remainder of claim 1
2 Claim 1 recites:
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4 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
recites the method steps for producing the fraction and an-
alyzing it. Each step involves the DNA taken from the
blood plasma or serum of a pregnant human female. The
DNA itself is not changed or altered.
The first step is achieved by (a) extracting DNA from a
substantially cell-free sample of blood plasma or blood se-
rum taken from a pregnant female. That sample is then
A method for preparing a deoxyribonucleic acid
(DNA) fraction from a pregnant human female use-
ful for analyzing a genetic locus involved in a fetal
chromosomal aberration, comprising:
(a) extracting DNA from a substantially
cell-free sample of blood plasma or blood se-
rum of a pregnant human female to obtain
extracellular circulatory fetal and mater-
nal DNA fragments;
(b) producing a fraction of the DNA ex-
tracted in (a) by:
(i) size discrimination of extracellu-
lar circulatory DNA fragments,
and
(ii) selectively removing the DNA
fragments greater than approxi-
mately 500 base pairs, wherein the
DNA fraction after (b) comprises a
plurality of genetic loci of the extra-
cellular circulatory fetal and ma-
ternal DNA; and
(c) analyzing a genetic locus in the fraction
of DNA produced in (b).
’751 patent at col. 7 ll. 54-67, col. 8 ll. 53-57; cf. ’931 patent
at col. 7 ll. 58-67, col. 8 ll. 57-63 (claim 1).
Case: 19-1419 Document: 64 Page: 22 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 5
used to (b) produce a “fraction” of the DNA extracted in the
first step (a). The fraction is produced via (i) size discrimi-
nation of the extracellular circulatory DNA fragments, and
(ii) selective removal of DNA fragments greater than ap-
proximately 500 base pairs. Claim 1 states that after the
extraction, size discrimination, and selection and removal
steps are completed, the fraction comprises “a plurality of
genetic loci of the extracellular circulator fetal and mater-
nal DNA.” ’751 patent at col. 8 ll. 53–55. The Majority
describes the resulting fraction as “a mixture enriched in
fetal DNA.” Maj. Op. at 12. But this mixture is made of
the same natural substances present in the original sam-
ple.
In sum, the claimed method begins with extracting a
sample of blood plasma or serum from a pregnant mother
that consists wholly of various naturally occurring sub-
stances, including cff-DNA. ’751 patent at col. 7. ll. 58–61.
The claimed method separates those naturally occurring
substances by size, leaving a “fraction” of the original sam-
ple that is predominantly cff-DNA. Id. at col. 7 ll. 63–67,
col. 8 ll. 53–55. The claimed method ends with analyzing
the components of the “fraction,” which contains cff-DNA.
Id. at col. 8 ll. 56–57. The substances present throughout
the process are naturally occurring substances, and the
claimed method steps do not alter those substances. Thus,
under the Supreme Court’s step-one analysis, the claimed
method steps “involve” natural phenomenon and are,
therefore, directed to a natural phenomenon. 3
3 The dependent claims add detail such as tech-
niques for conducting each method step and the detection
of specific chromosomal aberrations. For example, claim 7
of the ’751 patent specifies centrifugation for the size dis-
crimination step and claim 10 specifies for the detection of
a fetal chromosomal aberration causing Down Syndrome.
’751 patent at col. 9 ll. 1-2, 7-8.
Case: 19-1419 Document: 64 Page: 23 Filed: 08/03/2020
6 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
B. The Claimed Advance is a Natural Phenomenon
My conclusion that the method steps are directed to a
natural phenomenon is bolstered by our precedent that
looks to the “claimed advance” for determining whether a
claim is directed to patent ineligible subject matter. E.g.,
Athena, 915 F.3d 743, 750 (Fed. Cir. 2019) (Lourie, J.); Ge-
netic Techs. Ltd. v. Merial L.L.C.,
818 F.3d 1369, 1375 (Fed.
Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc.,
788
F.3d 1371 (Fed. Cir. 2015).
In Ariosa, we concluded that the claims were directed
to a natural phenomenon relying, in part, on the patent’s
disclosure that the natural phenomenon was a “surprising
and unexpected finding.” 788 F.3d at 1376 (citation and
quotation omitted). In Athena, we concluded that the
claimed advance was “only in the discovery of the natural
law” by relying, in part, on the patent’s disclosure that the
inventors “surprisingly found” the natural
law. 915 F.3d
at 751 (citation and quotation omitted). In Cleveland
Clinic, we concluded that the claims were directed to a nat-
ural law relying, in part, on the patent’s disclosure that
“the inventions are ‘based on the discovery’” of the natural
law. 859 F.3d at 1360–61 (citation omitted).
Here, the claimed advance is the inventors’ “surpris-
ing[]” discovery of a natural phenomenon—that cff-DNA
tends to be shorter than cell-free maternal DNA in a
mother’s bloodstream. See ’751 patent at col. 1 ll. 54–61.
Like in Ariosa and Athena, the patent’s written description
identifies only the natural phenomenon as the “surprising
finding.” Id. at col. 1 l. 54–col. 2 l. 6. And the patent ex-
plains that the natural phenomenon “forms the basis of the
present invention,” like the patent in Cleveland Clinic.
Id.
at col. 2 ll. 1–6. It is undisputed that the surprising discov-
ery is a natural phenomenon. See Maj. Op. at 3–4, 9. The
claimed advance is, therefore, the discovery of the natural
phenomenon.
Case: 19-1419 Document: 64 Page: 24 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 7
The conclusion that the claimed advance is the discov-
ery of a natural phenomenon is supported by the fact that
the claimed method steps begin and end with a naturally
occurring substance. See Ariosa, 788 F.3d at 1376. In Ari-
osa, we found ineligible process claims directed to a method
of detecting paternally inherited cff-DNA.
Id. The claimed
method steps began with a naturally occurring blood sam-
ple and ended with cff-DNA, itself a naturally occurring
substances.
Id. In this case, as in Ariosa, the inventors did
not create or alter via the claimed method steps any of the
genetic information encoded in the cff-DNA in the claimed
method steps.
Id.
The Majority avoids our claimed advance precedent by
reasoning that these claims belong in a distinct category of
process claims for “method[s] of preparation.” 4 See Maj.
Op. at 8. But characterizing the claims as a “method of
preparation” does not render inapplicable this court’s prec-
edent including Athena, Roche Molecular, Cleveland
Clinic, Genetic Techs., and Ariosa. 5
Id. Our precedent does
not support such cherry picking. A “method of prepara-
tion” is treated no differently than any other process claim
under our law. The statute provides that the term “pro-
cess” in § 101 encompasses all “process, art or method”
4 Cf. Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827
F.3d 1042, 1050 (Fed. Cir. 2016) (reciting in claim 1’s pre-
amble “[a] method of producing a desired preparation”).
5 Athena Diagnostics, Inc. v. Mayo Collaborative
Servs., LLC, 915 F.3d 743 (Fed. Cir. 2019); Roche Molecu-
lar Sys., Inc. v. Cepheid,
905 F.3d 1363 (Fed. Cir. 2018);
Cleveland Clinic Found. v. True Health Diagnostics LLC,
859 F.3d 1352 (Fed. Cir. 2017); Genetic Techs. Ltd. v.
Merial L.L.C.,
818 F.3d 1369 (Fed. Cir. 2016); Ariosa Diag-
nostics, Inc. v. Sequenom, Inc.,
788 F.3d 1371 (Fed.
Cir. 2015).
Case: 19-1419 Document: 64 Page: 25 Filed: 08/03/2020
8 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
claims. 35 U.S.C. § 100(b). It makes no distinction based
on how the process or method is characterized.
Here, the Majority fails to adequately address the
claimed advance inquiry. E.g., Maj. Op. at 8–13. Yet, the
Majority maintains that the claimed methods are not di-
rected to the natural phenomenon—under the Alice/Mayo
step-one inquiry—because they “include physical process
steps” that “achieve more than simply observing that fetal
DNA is shorter than maternal DNA or detecting the pres-
ence of that phenomenon.” Maj. Op. at 11. The problem
with this approach is that it conflates the Alice/Mayo step-
one analysis with the step-two analysis by focusing on
whether and how the claimed “physical process steps”
transform the invention into more than an observation of
the natural phenomenon. See Alice, 573 U.S. 217–18. The
Supreme Court describes step two of the analysis as “a
search for an ‘inventive concept’—i.e., an element or com-
bination of elements that is ‘sufficient to ensure that the pa-
tent in practice amounts to significantly more than a patent
upon the [ineligible concept] itself.’”
Id. (emphasis added)
(quoting Mayo Collaborative Services v. Prometheus Labor-
atories, Inc.,
566 U.S. 66, 72–73 (2012)).
The Majority also suggests that the claimed advance is
an improvement in “size discriminat[ion]” and “selective[]
remov[al]” techniques. See Maj. Op. at 9–11. The Majority
reasons that the inventors used “specific process steps” of
“size discriminating and selectively removing DNA frag-
ments that are above a specified size threshold” and that
these “concrete process steps . . . exploit [the natural phe-
nomenon] in a method for preparation of a mixture en-
riched in fetal DNA.” Id. at 9–10, 12. But whether the
claimed method steps are specific and concrete is not the
point of analysis for the “directed to” inquiry or for deter-
mining the claimed advance at step one. See
Athena, 915
F.3d at 752 (concluding that the claims’ specific and con-
crete nature “does not disturb our conclusion at step one”).
Case: 19-1419 Document: 64 Page: 26 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 9
The claimed advance suggested by the Majority, an im-
provement in the underlying DNA-processing technology,
is not supported by the claims or the written description.
As discussed below, the written description identifies the
claimed method steps as well-known or performed using
commercially available tools or kits. See ’751 patent at col.
2 l. 49–col. 3 l. 18, col. 3 ll. 49–50, col. 3 l. 65–col. 4 l. 13,
col. 5 ll. 45–50. Where a written description identifies a
technology as well-known or performed using commercially
available tools or kits, that technology cannot logically con-
stitute a claimed advance. Ariosa, 788 F.3d at 751; see also
Athena, 915 F.3d at 751 (identifying the claimed “immuno-
logical assay techniques [as] known per se in the art” and
therefore not the claimed advance); Cleveland
Clinic, 859
F.3d at 1361 (relying on the patent’s disclosure of “commer-
cially available testing kits” for detecting the natural law).
Table 1, below, highlights the commercially available
tools and kits that are identified in the written description
as used to perform each claimed method step.
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10 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
Table 1: Performance of Claimed Method Steps
Commercially Available
Claimed Method Step
Tool or Kit
QIAgen Maxi kit
Claim 1(a), “extracting
(’751 patent at col. 3 ll. 49–
DNA”
50)
Invitrogen 1% agarose gel
(’751 patent at col. 3 ll. 66–
67)
New England Biolabs 100
Claim 1(b)(i), “size dis- base pair ladder
crimination” (id. at col. 4 ll. 4–5)
Claim 1(b)(ii), “selec- Lamda Hind III digest
tively removing” (’751 patent at col. 4 ll. 5–
6)
QIAEX Gel Extraction
kit
(id. at col. 4 ll. 10–12)
Applied Biosystems (ABI)
7000 Sequence Detection
System
(’751 patent at col. 4 ll. 14-
Step (c), “analyzing a ge- 38)
netic locus”
TaqMan System and
TaqMan Minor Groove
Binder
(id. at col. 4 ll. 19–38)
The Majority turns to attorney argument to save these
claims. It reasons that Roche “has presented no evidence
that thresholds of 500 base pairs and 300 base pairs were
conventional for separating different types of cell-free DNA
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ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 11
fragments.” Maj. Op. at 15. But whether a claim is di-
rected to patent ineligible subject matter depends on the
claims and the written description, and not attorney argu-
ment. The absence, or silence, of conventionality of an as-
pect of an invention in the written description does not
render that aspect unconventional. There is nothing in the
patent itself to indicate that size selection based on 500 and
300 base pairs was an unconventional human engineered
parameter or that this aspect of the invention is the
claimed advance. This explains why the Majority’s re-
peated statements concerning human engineered parame-
ters are unsupported by citations to the specification. See
Maj. Op. at 10, 14–17. The claimed DNA-processing tech-
nologies do not, therefore, constitute the claimed advance.
See Cleveland Clinic, 859 F.3d at 1361.
The Majority relies on CellzDirect. See Maj. Op. at 14–
15. But CellzDirect is distinct from this case. In CellzDi-
rect, the inventors created a new and useful cryopreserva-
tion technique comprising multiple free-thaw cycles. 827
F.3d at 1048. The claimed invention went beyond applying
a known laboratory technique to a newly discovered natu-
ral phenomenon and, instead, created an entirely new la-
boratory technique.
Id. Unlike in CellzDirect, the claimed
method steps here are not new, nor are the claimed tech-
niques used in a new or unconventional way. The method
steps do not recite or recognize the creation of a new labor-
atory technique. The Majority recognizes that the inven-
tors “did not invent centrifugation, chromatography,
electrophoresis, or nanotechnology”—the claimed tech-
niques described in the written description. Maj. Op. at 15.
The Majority further reasons that the claimed method
steps of size discrimination and selective removal “change
the composition of the mixture, resulting in a DNA fraction
that is different from the naturally-occurring fraction in
the mother’s blood.” Id. at 9–10. On this basis, the Major-
ity concludes that the claimed method in the patent
“achieves more than simply observing that fetal DNA is
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12 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
shorter than maternal DNA, or detecting the presence of
that phenomenon.”
Id.
The Majority’s position is declaratory, but not logical.
That the claimed process changes the composition of a sam-
ple of naturally occurring substances, but does not alter the
naturally occurring substances themselves, is not suffi-
cient to render the claimed process patent eligible. See Ge-
netic
Techs., 818 F.3d at 1374 (holding ineligible the
claimed process for using PCR to amplify genomic DNA in
a sample before detecting it);
Ariosa, 788 F.3d at 1373
(holding ineligible the claimed process for using PCR to
amplify cff-DNA in a sample before detecting it).
Here, the claimed method steps of size discrimination
and selective removal do not alter the naturally occurring
substances in the sample of blood plasma or serum from a
pregnant mother. Importantly, the majority correctly un-
derstands that the patent does not claim the fraction in
terms of chemical composition, as a naturally occurring
substance that has been chemically altered by the method
steps. Cf. Association for Molecular Pathology v. Myriad
Genetics, Inc., 569 U.S. 576, 593 (2013) (“Myriad’s claims
are simply not expressed in terms of chemical composition,
nor do they rely in any way on the chemical changes that
result from the isolation of a particular section of DNA.”).
The Majority also suggests that the claimed methods
are not directed to the natural phenomenon because the
“correlation” that “a DNA fragment’s size and its tendency
to be either fetal or maternal” is not recited in the claim.
Maj. Op. at 12–13. Neither our precedent nor that of the
Supreme Court imposes such a requirement. Requiring a
recitation of the natural phenomenon leads to the “drafts-
man’s art” problem, where a claim drafter has written a
claim that is devoted to an ineligible concept, but the
drafter managed to avoid reciting the ineligible concept it-
self. It was this recognition of “the draftsman’s art” that
motivated the Supreme Court to adopt the step-two,
Case: 19-1419 Document: 64 Page: 30 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 13
inventive concept inquiry. Mayo, 566 U.S. at 72 (citing
Parker v. Flook,
437 U.S. 584, 593 (1978)); see also Dia-
mond v. Diehr,
450 U.S. 175, 188–89 (1981).
The Majority’s category-based approach also allows
claim draftsmanship to evade § 101’s safeguard at the step-
one inquiry. In Myriad, the Court concluded that the
claims at issue were “concerned primarily” with a patent-
ineligible product of nature and recognized that “separat-
ing [a] gene from its surrounding genetic material is not an
act of invention.” 569 U.S. at 591. Here, the separation of
genetic material from its surroundings is plainly the focus
of the claims at issue. Yet, the Majority distinguishes Myr-
iad on the sole ground that these claims have been drafted
as method claims rather than composition of matter
claims. In any event, whether a patent claim recites a pro-
cess or a composition of matter does not impact the step-
one, “directed to” inquiry because this inquiry applies
equally to composition of matter and process claims. 6 I see
no principled reason why under the facts of this case Myr-
iad should or should not apply simply because this case
presents a method claim and not a composition of matter
claim. Regardless of whether the asserted claims are to a
composition of matter or a “method of preparation,” the
purpose of § 101 remains the same: to safeguard against
6 E.g., Myriad, 569 U.S. at 591 (analyzing the “focus”
of the relevant composition of matter claims),
Mayo, 566
U.S. at 72-73 (analyzing the “focus” of the relevant process
claims);
Bilski, 561 U.S. at 609–13 (analyzing whether the
process claims involved an abstract idea);
Diehr, 450 U.S.
at 192 (analyzing whether the process claims were “drawn
to” a mathematical formula or a patent-eligible process ap-
plying that formula); Funk Bros. Seed Co. v. Kalo Inoculant
Co.,
333 U.S. 127, 132 (1948) (analyzing eligibility of “prod-
uct claims”).
Case: 19-1419 Document: 64 Page: 31 Filed: 08/03/2020
14 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
claims that monopolize a law of nature, natural phenome-
non, or abstract idea. See
Alice, 573 U.S. at 216.
II. The Claims Do Not Survive Step Two
Step two of the Alice inquiry is a search for other ele-
ments that transform ineligible claims into significantly
more than a patent upon the natural law or phenomenon.
See Mayo, 566 U.S. at 72–73. Mayo made clear that trans-
formation into a patent eligible application requires “more
than simply stat[ing] the law of nature while adding the
words ‘apply it.’”
Id. at 72.
In step two, we ask: “[w]hat else is there in the claims
before us?” Id. at 78. This question is a lifeline, one that
is limited to “additional features” of the claim that trans-
forms the nature of the claim into a patent-eligible appli-
cation.
Id. at 77;
Ariosa, 788 F.3d at 1377.
For method claims that encompass natural phenom-
ena, the method 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 al-
gorithm, must be new and useful.”). We must assess
whether the additional features are new and useful within
the field generally, not in the context of their particular ap-
plication to the newly discovered phenomenon. See Roche
Molecular, 905 F.3d at 1372; see also
Athena, 915 F.3d at
754.
The method steps under review do not transform the
nature of the claims into patent-eligible applications. The
three claimed method steps of (a) extracting DNA, (b) pro-
ducing a fraction of DNA by size discrimination, and (c) an-
alyzing a genetic locus are not new, either alone or in
combination. As illustrated above in Table 1, the written
description indicates that the laboratory techniques of the
claimed method are commercially available. And the writ-
ten description explains that step (b)’s requirement of pro-
ducing a fraction by size discrimination “can be brought
Case: 19-1419 Document: 64 Page: 32 Filed: 08/03/2020
ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 15
about by a variety of methods.” ’751 patent at col. 2 ll. 49–
51.
Contrary to the majority’s belief, that the size discrim-
ination and selective removal method steps were applied
for the first time to the newly discovered natural phenom-
enon does not render those steps transformative, new and
useful, under the Alice/Mayo step-two inquiry. See Roche
Molecular, 905 F.3d at 1372; see also
Athena, 915 F.3d at
754. In Roche Molecular, we held that the method claims
at issue, which involved PCR amplification of DNA, did not
contain an inventive concept even though the inventors
were the first to use PCR to detect the claimed natural phe-
nomenon. 905 F.3d at 1372. We reasoned that the claims
did not contain an inventive concept because they did not
“disclose any ‘new and useful’ improvement to PCR proto-
cols or DNA amplification techniques in general.” Id. see
also
Athena, 915 F.3d at 754 (noting that “to supply an in-
ventive concept, the sequence of claimed steps must do
more than adapt a conventional assay to a newly discov-
ered natural law”).
Like in Roche Molecular, the claimed method steps
here do not disclose any new and useful improvement to
DNA separation techniques. And they do not disclose an
unconventional assay to apply the newly discovered natu-
ral phenomenon. As noted above in the step-one discus-
sion, the Majority reasons that Roche has presented “no
evidence that thresholds of 500 base pairs and 300 base
pairs were conventional for separating different types of
cell-free DNA fragments.” Maj. Op. at 15. But, like in
Roche, the addition of these so-called thresholds—which
are claimed as approximations conforming to the natural
phenomenon—are nothing more than an adaptation of
commercially available DNA separation techniques to the
natural phenomenon.
The dependent claims also fail to transform the nature
of the claims because they too rely on the same
Case: 19-1419 Document: 64 Page: 33 Filed: 08/03/2020
16 ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC.
commercially available, routine, and conventional tech-
niques as claim 1, only they provide more specificity on
which techniques to use (e.g., ’751 patent, claim 7, identi-
fying “density gradient centrifugation” for the size discrim-
ination method).
For example, the written description describes two ex-
amples where experiments illustrate the application of the
natural phenomenon. ’751 patent at col. 3 l. 30–col. 6 l. 46.
The results of Example 1, as captured in Table 1, demon-
strate that “DNA fragments originating from the fetus
were almost completely of sizes smaller than 500 base pairs
with around 70% being of fetal origin for sizes smaller than
300 base pairs.” Id. at col. 4 l. 50–col. 5 l. 7. The results of
Example 2 demonstrate that fetal alleles for “D21S11,” a
genetic marker found in the human chromosome related to
Down Syndrome, could be detected in cell-free DNA sam-
ples from which fragments greater than 500 base pairs or
300 base pairs had been removed. The patent explains that
both experiments were conducted using known laboratory
techniques and commercially available testing kits. E.g.
,
id. at col. 3 ll. 49–50, col. 3 l. 65–col. 4 l. 13, col. 5 ll. 45–50;
see also
id. at col. 2 l. 61–col. 3 l. 18.
Simply appending routine, conventional steps to a nat-
ural phenomenon, specified at a high level of generality, is
not enough to supply an inventive concept. Thus, the
claims of the patent in this appeal that are directed to pa-
tent ineligible subject matter are not transformed into sig-
nificantly more than a patent upon the natural law or
phenomenon. See Mayo, 566 U.S. at 72–73.
III. Preemption
The Supreme Court has made clear that the principle
of preemption is the basis for the judicial exceptions to pa-
tentability. Alice, 573 U.S. at 216–17. As Mayo empha-
sized, “there is a danger that the grant of patents that tie
up the[] use [of laws of nature] will inhibit future innova-
tion premised upon
them.” 566 U.S. at 86.
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ILLUMINA, INC. v. ARIOSA DIAGNOSTICS, INC. 17
Here, the claims are drafted in a manner that tie up
future innovations premised upon the natural phenomenon
because no skilled artisan would be entitled to rely on the
natural phenomenon to isolate cff-DNA. That a skilled ar-
tisan could isolate or enrich cff-DNA using some unclaimed
technique is not dispositive for preemption. See Athena Di-
agnostics, Inc. v. Mayo Collaborative Servs., 927 F.3d 1333,
1351 (Fed. Cir. 2019) (Chen, J., concurring in the denial of
the petition for rehearing en banc) (“That claims 7 and 9 do
not preempt all ways of observing the law of nature isn’t
decisive, as none of the steps recited therein add anything
inventive to the claims.”). As in Athena, the only claimed
advance here is the discovery of the natural phenomenon,
and as drafted, these claims significantly preempt use of
that natural phenomenon.
CONCLUSION
Much of what we are as humans has its source in our
respective DNA, including particular genetic aberrations.
The development of medical and scientific procedures to de-
tect and diagnose genetic aberrations, like those involved
in the patents in this appeal, count among the great discov-
eries of modern medicine. Such procedures may qualify for
a patent, but DNA itself, or a segment of DNA that dis-
closes an aberration, like the entirety of the human ge-
nome, does not.
I dissent because while I do not doubt that process
claims that are directed to natural phenomenon could be
patent eligible subject matter, this is not such a case.
