Roland Stoughton et al.

Patent Trials and Appeals Board

Sep 13, 2019

13863992 - (D) (P.T.A.B. Sep. 13, 2019)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/863,992 04/16/2013 Roland Stoughton 26101-0027002 7457
150985 7590 09/13/2019
FISH & RICHARDSON P.C. (ILLUMINA)
P.O. BOX 1022
MINNEAPOLIS, MN 55440-1022
EXAMINER
STRZELECKA, TERESA E
ART UNIT PAPER NUMBER
1637
NOTIFICATION DATE DELIVERY MODE
09/13/2019 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
PATDOCTC@fr.com
illuminadocket@illumina.foundationip.com
PTOL-90A (Rev. 04/07)
1
UNITED STATES PATENT AND TRADEMARK OFFICE
____________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________________

Ex parte ROLAND STOUGHTON, RAVI KAPUR,
MEHMET TONER, RONALD DAVIS, and
BARB ARIEL COHEN1
____________________

Appeal 2018-006149
Application 13/863,992
Technology Center 1600
____________________

Before JEFFREY N. FREDMAN, TAWEN CHANG, and DAVID COTTA,
Administrative Patent Judges.

CHANG, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of determining a likelihood of aneuploidy in a fetus, which have
been rejected as being directed to a judicial exception to patent-eligible
subject matter without significantly more. We have jurisdiction under 35
U.S.C. § 6(b).
We AFFIRM.

1 Appellants states that, although “[a]ssignments from the inventors have not
yet been recorded in this application, . . . the inventors are under an
obligation to assign to Verinata Health Inc. . . . , The General Hospital
Corporation . . . , and GPB Scientific LLC.” (Br. 2.)
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STATEMENT OF THE CASE
According to the Specification, certain methods currently available for
prenatal tests, such as amniocentesis and chorionic villus sampling (CVS),
are “potentially harmful to the mother and to the fetus.” (Spec. ¶ 2.) The
Specification states that “[t]he presence of fetal cells within the blood of
pregnant women offers the opportunity to develop a prenatal diagnostic that
. . . eliminates the risk of today’s invasive diagnosis.” (Id. ¶ 5.) However,
the Specification explains that, because “fetal cells represent a small number
of cells against the background of a large number of maternal cells in the
blood,” prenatal tests based on analyses of maternal blood may be “time
consuming and prone to error.” (Id.) Further according to the Specification,
[t]he methods of the present invention allow for the detection of fetal cells
and fetal abnormalities when fetal cells are mixed with a population of
maternal cells, even when the maternal cells dominate the mixture.” (Id. ¶
4.)
Claims 1–4, 9–15, 17, 20–24, 26–28, 32, 33, and 36 are on appeal.2
Claim 1 is illustrative and reproduced below:
1. A method of determining a likelihood of a presence or
absence of a fetal aneuploidy in a fetus using a maternal blood sample
derived from a pregnant human female comprising fetal and maternal
DNA, the method comprising:
(a) selectively amplifying a plurality of single nucleotide
polymorphism (SNP) sites of a first chromosome selected from the
group consisting of chromosomes 13, 18, 21, X, and Y in the maternal
blood sample comprising fetal and maternal DNA;
(b) sequencing the amplified plurality of SNP sites of the
fetal and maternal DNA of (a) and determining abundances of

2 Claims 29–31, 34, 35, and 37 have been cancelled. (Amendment under 37
C.F.R. § 41.33(b)(1) (Mar. 16, 2018); Office Communication (May 14,
2018).)
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sequence reads of alleles at the plurality of SNP sites, wherein the
sequencing comprises sequencing millions of molecules in parallel;
(c) selectively amplifying the plurality of SNP sites of the
first chromosome in a maternal-only sample comprising maternal
DNA, wherein the maternal-only sample is essentially free of fetal
DNA;
(d) sequencing the amplified plurality of SNP sites of the
first chromosome of the maternal DNA of (c) and determining
abundances of sequence reads of alleles at the plurality of SNP sites,
wherein the sequencing of step (d) comprises sequencing millions of
molecules in parallel;
(e) creating models corresponding to a plurality of fetal
ploidy states based on the abundances of sequence reads of alleles at
the plurality of SNP sites of (d);
(f) comparing the abundances of sequence reads of alleles at
the plurality of SNP sites of (b) to the models and selecting from the
models a model that provides a best fit to the abundances of sequence
reads of alleles at the plurality of SNP sites of (b); and
(g) determining the likelihood of the presence or absence of
a fetal aneuploidy of the first chromosome using the selected model.
(Br. 21–22 (Claims App.).)
The Examiner rejects claims 1–4, 9–15, 17, 20–24, 26–28, 32, 33, and
36 under 35 U.S.C. § 101 as being directed to a judicial exception (i.e., a law
of nature, a natural phenomenon, or an abstract idea) without significantly
more.3 (Ans. 3.)

3 The Examiner withdrew the rejection of claims 32, 33, and 36 under 35
U.S.C. ¶ 112, first paragraph. (Ans. 14.) The Examiner also rejects claims
29–31, 34, 35, and 37 under 35 U.S.C. § 101 as being directed to a judicial
exception without more, as well as under 35 U.S.C. § 112(a) or 35 U.S.C.
§ 112 (pre-AIA), first paragraph, as failing to comply with the written
description requirement. (Id. at 3, 9.) However, as discussed above, claims
29–31, 34, 35, and 37 have been cancelled. See supra n. 2.
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DISCUSSION
Issue
The Examiner finds that the claims on appeal are directed to “an
abstract idea of a correlation between the likelihood of fetal aneuploidy and
the number of sequencing reads of SNPs obtained in maternal plus fetal
DNA and maternal-only samples.” (Ans. 7.) The Examiner further finds
that the claims do not include additional elements that amount to
significantly more than the judicial exception, because the claims “do not
provide improvement to another technology,” “do not effect a
transformation of a particular article to a different state or thing,” and “do
not add specific limitations other than what was well-understood, routine
and conventional in the field.” (Id. at 8, emphasis omitted.)
Appellants contend that the Examiner has not established that the
claims are directed to an abstract idea. (Br. 10.) Appellants contend that the
claims are in fact directed to a patent-eligible improvement in fetal
aneuploidy detection. (Id. at 7–8.) Appellants contend that the claims do
not preempt the field of fetal aneuploidy detection. (Id. at 8–9). Appellants
further contend that the claims are patent-eligible because they contain
additional elements that, when considered separately or in an ordered
combination, are not conventional, well-understood, or routine and “make
the claims amount to significantly more than a judicial exception.” (Id. at
10–14.)
Appellants do not separately argue the claims. We therefore limit our
analysis to claim 1 as representative. The issues with respect to this
rejection are (1) whether claim 1 is directed to a patent-ineligible concept
(i.e., a law of nature, a natural phenomenon, or an abstract idea) and, if so,
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(2) whether claim 1 contains elements that, individually or as an ordered
combination, transform the nature of the claim into a patent-eligible
application.
Analysis
Unless otherwise noted, we adopt the Examiner’s findings of fact and
reasoning regarding the Examiner’s rejection of claim 1 under 35 U.S.C. §
101 (Final Act. 2–12, 18–20, 22–24; Ans. 3–4, 7–8, 20–28) and agree that
claim 1 is unpatentable as being directed to a judicial exception without
significantly more. Only those arguments timely made by Appellants in the
Appeal Brief (no Reply Brief was submitted) have been considered;
arguments not so presented in the Brief are waived. See 37 C.F.R. §
41.37(c)(1)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474
(BPAI 2010) (informative) (“Any bases for asserting error, whether factual
or legal, that are not raised in the principal brief are waived.”). We highlight
the following points for emphasis.
We analyze this case under the framework set forth by the Supreme
Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566
U.S. 66 (2012), and applied by our reviewing court in Ariosa Diagnostics,
Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015). As the Ariosa court
explained:
In Mayo . . . , 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. . . . If the answer is yes, then
we next consider the elements of each claim both
individually and “as an ordered combination” to determine
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whether additional elements “transform the nature of the
claim” into a patent-eligible application. . . . The Supreme
Court has described the second step of this analysis as a
search for an “inventive concept”—i.e., an element or
combination of elements that is “sufficient to ensure that
the patent in practice amounts to significantly more than a
patent upon the [ineligible concept] itself.”
Id. at 1375.
Whether Claim 1 Is Directed to Patent-Ineligible Concept
We begin with the first step of the Mayo test, namely whether a claim
is “directed to” a patent-ineligible concept. On January 7, 2019, the Director
of the USPTO issued the “2019 Revised Patent Subject Matter Eligibility
Guidance” (“Revised Guidance”), which provides further details regarding
how the Patent Office analyzes patent-eligibility questions under 35 U.S.C. §
101. 84 Fed. Reg. 50–57 (Jan. 7, 2019). Under the Revised Guidance, the
first step of the Mayo test (i.e., Step 2A of the Revised Guidance) is “a two-
pronged inquiry.” Id. at 54. In prong one, we evaluate whether the claim
recites a judicial exception, such as laws of nature, natural phenomena, or
abstract ideas. Id. If the claim recites a judicial exception, the claim is
further analyzed under prong two, which requires “evaluat[ion of] whether
the claim recites additional elements that integrate the exception into a
practical application of that exception.” Id. The Revised Guidance explains
that, “[i]f the recited exception is integrated into a practical application of
the exception, then the claim is eligible at Prong Two of . . . Step 2A [of the
Revised Guidance].” Id.
Prong One of Step 2A of Revised Guidance
With respect to the first prong of Step 2A of the Revised Guidance,
we agree with the Examiner that claim 1 recites a patent-ineligible law of
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nature or natural phenomenon, specifically, the correlation between (1) “the
abundances of sequence reads of alleles at . . . SNP sites” of certain
chromosomes in a maternal blood sample comprising fetal and maternal
DNA as compared to a “maternal-only sample . . . essentially free of fetal
DNA” and (2) “the likelihood of the presence or absence of a fetal
aneuploidy” of the chromosomes. (Br. 21–22 (Claims App.), claim 1, steps
(b) and (d)–(g); see also Spec. ¶¶ 6–11 (explaining that “invention relates to
methods for detecting a fetal abnormality by determining the ratio of the
abundance of one or more maternal alleles to . . . paternal alleles” or by
comparing “a ratio of the abundance of the maternal alleles in [a] first
genomic region to . . . [a] second genomic region” to the ratio in a control
sample); see also id. ¶¶ 107, 110–112, 113, 121.)
In Mayo, the Supreme Court found that a claim was directed to a
natural law, where the claim required administering a drug and determining
the levels of a metabolite following administration and where the level of
metabolite was indicative of a need to increase or decrease the dosage of the
drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S.
66, 74 (2012). In Ariosa, the Federal Circuit found that a method for
performing a prenatal diagnosis was directed to matter that is naturally
occurring, where the method comprised “obtaining a non-cellular fraction of
[a maternal] blood sample[,] amplifying a paternally inherited nucleic acid
from the . . . fraction[,] and performing nucleic acid analysis on the
amplified nucleic acid to detect paternally inherited fetal nucleic acid.”
Ariosa, 788 F.3d at 1374, 1376. In particular, the Ariosa court reasoned that
both the existence of cell-free fetal DNA (cffDNA) in maternal blood and
paternally inherited cffDNA are natural phenomena. Id. at 1376.
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Here, similar to the claims in Mayo that correlate a physiological
parameter of a subject to the need to increase or decrease dosage of a drug,
claim 1 recites correlating genetic parameters (i.e., abundances of sequence
reads of alleles at certain SNP sites of different samples) to the likelihood of
the presence or absence of a condition (i.e., fetal aneuploidy). Likewise,
claim 1 recites “determining the likelihood of the presence or absence of a
fetal aneuploidy of [a] chromosome” (i.e., performing a prenatal diagnosis as
in Ariosa) comprising, among other things, amplifying certain nucleic acid
from a maternal blood sample containing fetal DNA—the existence of
which is a natural phenomenon as explained in Ariosa—and then performing
nucleic acid analysis. Under the reasoning set forth in Mayo and Ariosa,
therefore, claim 1 recites a patent-ineligible natural law or natural
phenomenon.
Claim 1 further recites mathematical concepts and/or mental steps in
steps (e)–(g), namely “creating models corresponding to a plurality of fetal
ploidy states based on the abundances of sequence reads of alleles at . . .
SNP sites of [maternal-only sample . . . essentially free of fetal DNA],”
“comparing the abundances of sequence reads of alleles at . . . SNP sites of
[fetal and maternal DNA] to the models and selecting . . . a model that
provides a best fit,” and “determining the likelihood of the presence or
absence of a fetal aneuploidy of the [selected] chromosome using the
selected model.” (Br. 21–22 (Claims App.), claim 1, steps (e)–(g).)
For instance, the Specification provides examples of “model[s] for
SNP data in the context of fetal diagnosis” where the presence or absence of
aneuploidy is determined by mathematical equations that may take into
account factors such as “efficiencies of amplification, hybridization, and
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readout common to the alleles” at a particular locus k, “amplification
differences between different primer pairs,” “fraction of fetal cells in the
mixture,” and “unit data contributions” of maternal and paternal alleles at
locus k. (Spec. ¶¶ 115–119.) Furthermore, creating such models, selecting a
model that provides a best fit, and determining the likelihood of the presence
or absence of fetal aneuploidy based on the model are all activities that may
be performed in the human mind and thus also fall within the “mental step”
category of abstract ideas.
Appellants contend that “[t]he Examiner has not cited an appropriate
court decision that supports the identification of the subject matter recited in
the claim language as an abstract idea.” (Br. 10.) We are not persuaded. As
discussed above, claim 1 recites a diagnostic method based on a natural law
or natural phenomenon as well as a mathematical concept and/or mental
step. Mayo and Ariosa both held that such diagnostic methods are, without
more, directed to patent-ineligible subject matter. Similarly, both Supreme
Court and Federal Circuit case law make clear that mental steps and
mathematical concepts as such are abstract ideas. See, e.g., Bilski v. Kappos,
561 U.S. 593, 611 (2010) (explaining that “[t]he concept of hedging . . .
reduced to a mathematical formula . . . is an unpatentable abstract idea”);
Parker v. Flook, 437 U.S. 584, 594 (1978) (stating that “the discovery of [a
mathematical formula] cannot support a patent unless there is some other
inventive concept in its application”); SAP America, Inc. v. InvestPic, LLC,
898 F.3d 1161, 1163 (Fed. Cir. 2018) (holding that claims to a “series of
mathematical calculations based on selected information” are directed to an
abstract idea); In re BRCA1 & BRCA2-Based Hereditary Cancer Test Patent
Litig., 774 F.3d 755, 763 (Fed. Cir. 2014) (holding that “comparing BRCA
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sequences and determining the existence of alterations” is a patent-ineligible
abstract idea).
Prong Two of Step 2A of Revised Guidance
The second prong of Step 2A asks whether the claims as a whole
integrates the judicial exception into a practical application of the exception.
Revised Guidance, 84 Fed. Reg. at 54. We find that claim 1 does not recite
additional elements that integrate the recited law of nature, mathematical
concept, and/or mental steps into a practical application.
In particular, the only elements of claim 1 that are not either a
statement of the natural law, a mathematical concept, or a mental step are (1)
“selectively amplifying a plurality of . . . SNP . . . sites of a first
chromosome selected from the group consisting of chromosomes 13, 18, 21,
X, and Y in the maternal blood sample comprising fetal and maternal DNA”
(Appeal Br. 21 (Claims App.), claim 1, step (a)), (2) “selectively amplifying
the plurality of SNP sites of the first chromosome in a . . . maternal-only
sample . . . essentially free of fetal DNA” (id. at step (c)), and (3)
“sequencing the amplified plurality of SNP sites” from the two samples
wherein the sequencing comprises “sequencing millions of molecules in
parallel” (id. at steps (b), (d)).
These steps, however, merely collect the data (i.e., the abundance of
sequence reads) needed for determining the likelihood of fetal aneuploidy.
Similar to the step of “determining the level of [relevant metabolite] in [a]
subject,” which the Supreme Court found in Mayo to be insufficient to
transform a law of nature into a patent-eligible application of the law, 566
U.S. at 77, they are insignificant pre-solution activities that do not serve to
integrate a judicial exception into a practical application. 84 Fed. Reg. at 55.
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Appellants contend that, “[c]onsidered as a whole and in light of the
specification, the instant claims are directed to a noninvasive technological
process that improves the field of fetal aneuploidy detection by reducing the
risk of induced abortion.” (Br. 7.) In particular, Appellants contend that
“[t]he claimed invention improves on . . . amniocentesis and chorionic villus
sampling (CVS), which tend to be dangerously invasive, insufficiently
sensitive, and limited to late in pregnancy.” (Id.) Similarly, Appellants
contend that “[t]he steps of the claims . . . reduce the amount of sequence
information generated relative to sequence information generated by whole
genome amplification, improving the cost effectiveness of fetal aneuploidy
detection.” (Id.)
We are not persuaded. We agree that a judicial exception may be
integrated into a practical application where “[a]n additional element reflects
. . . an improvement to [a] technology or technical field” when the claim is
considered as a whole. 84 Fed. Reg. 55 (emphasis added) (explaining that
“additional elements” refers to “claim features, limitations, and/or steps that
are recited in the claim beyond the identified judicial exception).
In this case, however, the improvement that Appellants point to are
the natural law and/or the mathematical concepts themselves. That is, the
alleged improvement (over amniocentesis, CVS, and whole genome
amplification) is the discovery of the correlation between fetal aneuploidy
and the abundance of sequence reads of alleles at SNPs of maternal blood
samples with and without fetal DNA, and/or the mathematical models based
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on the abundances of these sequence reads.4 Such an improvement does not
suffice to render claim 1 patent-eligible.
In Ariosa, for example, our reviewing court rejected a similar
argument by appellant Sequenom that its claimed methods are “patent
eligible applications of a natural phenomenon, specifically a method for
detecting paternally inherited cffDNA,” because the court found that “[t]he
only subject matter new and useful . . . was the discovery of the presence of
cffDNA in maternal plasma or serum.” Ariosa, 788 F.3d 1377; see also
Assoc. for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 591
(2013) (explaining that “[g]roundbreaking, innovative, or even brilliant
discovery does not by itself satisfy the § 101 inquiry”); Flook, 437 U.S. at
591 (explaining that, to be patentable, “[t]he process itself, not merely the
mathematical algorithm, must be new and useful”).
Appellants compare the claims to those in Rapid Litig. Mgmt. v.
CellzDirect Inc., 827 F.3d 1042 (Fed. Cir. 2016), where “the process steps
were focused on manipulating hepatocytes to achieve [a] desired outcome
[of multi-cryopreserved viable hepatocytes] in accordance with the natural
ability of the cells to survive multiple freeze-thaw cycles, rather than simply
observing or detecting the ability of hepatocytes to survive multiple freeze-
thaw cycles.” (Br. 8.) Appellants argue that, similarly, the claims on appeal
“are drawn to a process that involves numerous steps that manipulate DNA

4 For instance, we note that Dhallan, which similarly teaches a correlation
between (1) ratio for alleles at a locus of interest and (2) presence or absence
of a chromosomal abnormality, also requires sequencing “only the desired
bases or loci of interest” rather than sequencing the entire genome. Dhallan,
US 2004/0137470, published July 15, 2004, ¶ 202.
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in blood samples to achieve the desired outcome of creating an improved
and noninvasive technological process that detects fetal aneuploidy.” (Id.)
We are not persuaded. As explained by the CellzDirect court, while
“[t]he inventors [in CellzDirect] certainly discovered the cells’ ability to
survive multiple freeze-thaw cycles, . . . that is not where they stopped, nor
is it what they patented.” CellzDirect, 827 F.3d at 1048. Instead, the
inventors in CellzDirect “employed their natural discovery to create a new
and improved way of preserving hepatocyte cells for later use.” Id. Once
again, in this case Appellants arguably discovered the natural correlation
between fetal aneuploidy and the abundance of sequence reads of alleles at
SNPs of maternal blood samples with and without fetal DNA. Unlike the
claims in CellzDirect, however, claim 1 not directed to a method of using the
natural correlation: While the end result of the method in CellzDirect is a
preparation of multi-cryopreserved hepatocytes, the end result of the method
of claim 1 is a diagnosis, i.e., a statement of the correlation itself.5
Finally, citing McRO, Inc. v. Bandai Namco Games Am. Inc., 837
F.3d 1299, 1315 (Fed. Cir. 2016), Appellants contend that the claims are not
directed to a patent-ineligible law of nature or abstract idea because they do

5 Appellants contend that, although the last step of claim 1 is to “determin[e]
the likelihood of the presence or absence of a fetal aneuploidy of the first
chromosome using the selected model,” a skilled artisan would understand
that the invention is in fact directed to “detecting fetal aneuploidy . . . .” (Br.
10.) We are not persuaded. Assuming for the sake of argument that
Appellants’ claims recite a method for “detecting” fetal aneuploidy rather
than “determining a likelihood of a presence or absence of a fetal
aneuploidy,” such a method does not do more than “state the law of nature
while adding the words ‘apply it,’” which would not suffice to “transform
unpatentable law of nature into patent-eligible application of such law.”
Mayo, 566 U.S. at 72.
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not preempt “the field of fetal aneuploidy detection” or “the alleged,
narrower judicial exception of an ‘abstract idea of a correlation between the
likelihood of fetal aneuploidy and the number of sequencing reads of SNPs
obtained in maternal plus fetal DNA and maternal-only samples.’” (Br. 8–
9.) Appellants contend that fetal aneuploidy may be detected via non-
claimed processes such as amniocentesis and CVS. (Id. at 9.) Appellants
likewise contend that the allegedly abstract correlation may be determined
using chromosomes or maternal samples not recited in the claims and
without “sequencing millions of molecules in parallel” as required by, e.g.,
independent claims 1 and 27. (Id.)
We are not persuaded. “While preemption may signal patent
ineligible subject matter, the absence of complete preemption does not
demonstrate patent eligibility.” Ariosa, 788 F.3d at 1379. In Ariosa, for
instance, our reviewing court held various dependent claims to be invalid as
directed to patent-ineligible subject matter, even though these claims are
limited to specific techniques of amplifying and detecting nucleic acid. See
id. at 1374, 1378 (finding invalid dependent claims requiring amplification
of nucleic acid by polymerase chain reaction or detection of nucleic acid via
a sequence specific probe because they are “focused on the use of the natural
phenomenon in combination with well-understood, routine, and
conventional activity”).
Whether Claim 1 Amounts to “Significantly More”
Having determined that claim 1 is directed to a patent-ineligible law
of nature, we next consider whether claim 1 recites “an element or
combination of elements that is ‘sufficient to ensure that the patent in
practice amounts to significantly more than a patent upon the [ineligible
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concept] itself.’” Ariosa, 788 F.3d at 1375 (citation omitted). We agree
with the Examiner that it does not. (Ans. 7–8, 21–27.)
As discussed above, the only elements of claim 1 that are not either a
statement of the natural law, a mathematical concept, or a mental step,
involve the data gathering steps of “selectively amplifying a plurality of . . .
SNP . . . sites” of one of the recited chromosomes in maternal blood samples
either comprising fetal DNA or essentially free of fetal DNA, and then
“sequencing the amplified plurality of SNP sites” from the two samples
wherein the sequencing comprises “sequencing millions of molecules in
parallel.” (Appeal Br. 21 (Claims App.), claim 1, steps (a)–(d).)
The Examiner finds, and we agree, that these “data collection steps
are well-understood, common and routine in the art.” (Ans. 21.) For
instance, as the Examiner points out, the Specification teaches that
amplifying and sequencing DNA are known to those skilled in the art, and
prior art also teaches amplifying and sequencing DNA for purposes of
detecting chromosomal abnormalities in a fetus. (Id. at 21–28; see also
Dhallan Abstract (describing non-invasive method for detecting fetal
chromosomal abnormalities by determining sequence of alleles of a locus of
interest and quantitating a ratio for the alleles), ¶ 208 (“[a]ny method that
provides information on the sequence of a nucleic acid” may be used to
determine the sequence of a locus of interest, including among others DNA
sequencing), ¶ 46 (wherein loci of interest is suspected of containing an SNP
and wherein loci of interest can be amplified), ¶¶ 48–49, 59–60, 64–65, 67–
70, 72–73 (amplifying alleles of locus of interest), ¶¶ 46, 62, 64–65, 67–70
(describing methods of amplification), ¶ 204 (any number of loci of interest
can be analyzed and processed).)
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Appellants do not dispute that amplifying and sequencing DNA,
including sequencing millions of molecules in parallel, are routine and
conventional techniques in DNA analysis. (See, e.g., Tr. 10:12–11:3.)
However, Appellants contend that the Examiner has not established that “at
least sequencing millions of molecules and using both a maternal blood
sample comprising fetal and maternal DNA and a maternal-only sample
essentially free of fetal DNA” was conventional, well-understood, and
routine in the field of fetal aneuploidy detection, which Appellants contend
to be the subject of the invention and thus the relevant field of art for
determining whether additional claim elements are well-known, routine, and
conventional. (Br. 10–11; Tr. 13:4–19.)
We are not persuaded. Appellants improperly rely on the patent-
ineligible natural law or phenomenon in their arguments for patent
eligibility. As the Supreme Court has explained, in determining patent
eligibility of a claim that recites a natural law or mathematical formula,
“th[e] case must . . . be considered as if the principle or mathematical
formula were well known.” Flook, 437 U.S. at 592. Thus, the relevant
question in step 2 of the Mayo test is not whether, e.g., sequencing millions
of molecules in parallel is well-known, routine, and conventional in the field
of fetal aneuploidy detection;6 rather, it is whether such a technique is well-

6 As evidenced by Dhallan, the prior art in fact does teach using similar
DNA amplification and sequencing steps in detecting fetal aneuploidy. (See,
e.g., Dhallan Abstract (describing non-invasive method for detecting fetal
chromosomal abnormalities by determining sequence of alleles of a locus of
interest and quantitating a ratio for the alleles), ¶ 208 (“[a]ny method that
provides information on the sequence of a nucleic acid” may be used to
determine the sequence of a locus of interest, including among others DNA
sequencing), ¶ 46 (wherein loci of interest is suspected of containing an SNP
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known, routine, and conventional for sequencing DNA and determining
abundances of sequence reads of alleles. We agree with the Examiner that
they are. Appellants’ argument that using samples comprising fetal and
maternal DNA as well as maternal-only samples is not routine in fetal
aneuploidy detection is flawed for the same reason: the correlation between
the likelihood of fetal aneuploidy and the abundances of SNP sequence reads
in the two different samples is the recited natural law and cannot form the
basis for patent eligibility.
The Federal Circuit’s analysis in Ariosa also supports the rejection.
The claims in that case included methods for “detecting a paternally
inherited nucleic acid of fetal origin performed on a maternal serum or
plasma sample from a pregnant female,” comprising the steps of, e.g.,
“amplifying a paternally inherited nucleic acid” from the sample using
methods such as PCR. Ariosa, 788 F.3d at 1373–74. The claims also
included “[a] method for performing a prenatal diagnosis on a maternal
blood sample.” Id.

and wherein loci of interest can be amplified), ¶¶ 48–49, 59–60, 64–65, 67–
70, 72–73 (amplifying alleles of locus of interest), ¶¶ 46, 62, 64–65, 67–70
(describing methods of amplification), ¶ 204 (any number of loci of interest
can be analyzed and processed).) Citing the USPTO’s May 4, 2016
Memorandum on subject matter eligibility, Appellants contend that “‘mere
knowledge of the particular laboratory technique or use of the particular
laboratory techniques by a few scientists is not sufficient to make the use of
the particular laboratory technique routine or conventional in the relevant
field.’” (Br. 11.) While this is true, Dhallan nevertheless supports the
finding that DNA amplification and sequencing are well-known, routine, and
conventional techniques in the field of DNA analysis and diagnostics,
regardless of the specific purpose for which DNA is analyzed.
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In applying the second step of the Mayo test, the Federal Circuit
acknowledged that the discovery of the presence of cell-free fetal DNA in
maternal plasma or serum is new and useful. Id. at 1377. Thus, while
techniques like PCR may have been well-understood, routine, and
conventional in amplifying and detecting DNA generally, it presumably was
not well-understood, routine, and conventional for the specific purposes of
“detecting a paternally inherited nucleic acid of fetal origin performed on a
maternal serum or plasma sample from a pregnant female.” Nevertheless,
and despite appellant Sequenom’s argument that before its patent “no one
was using the plasma or serum of pregnant mothers to amplify and detect
paternally-inherited cffDNA,” the Federal Circuit found the claims in Ariosa
to be patent-ineligible, because “[t]he method at issue here amounts to a
general instruction to doctors to apply routine, conventional techniques
when seeking to detect [cell-free fetal DNA (cffDNA)].” Id. at 1377, 1379.
Similarly, in this case, there is no dispute that amplifying and
sequencing SNP sites is conventional, well-understood, and routine in DNA
analysis. What is allegedly new is only the discovery that the likelihood of
fetal aneuploidy correlates to the abundance of sequence reads of SNPs in
maternal plus fetal DNA versus maternal-only samples. Thus, as in Ariosa,
“[t]he method at issue here amounts to a general instruction to doctors to
apply routine, conventional techniques when seeking to [determine the
likelihood of fetal aneuploidy].” Id. at 1377.
Appellants argue that the pending claims are not analogous to the
claims at issue in Ariosa because the pending claims are not directed to
determining the presence of a nucleic acid but rather to an improved method
of fetal aneuploidy detection. (Br. 12.) We are not persuaded. As discussed
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above, the claims at issue in Ariosa also included claim 25, which recites
“[a] method for preforming a prenatal diagnosis” similar to Appellants’
claim to “[a] method of determining a likelihood of a presence or absence of
a fetal aneuploidy.” 788 F.3d at 1374. Neither do Appellants provide any
persuasive explanation why a diagnostic method is necessarily more patent
eligible than a method for detecting the presence of a nucleic acid.7
Appellants contend that the claims at issue are analogous to the patent
eligible claim 3 in Example 29 of USPTO’s May 2016 Subject Matter
Eligibility Examples: Life Sciences (“May 2016 Examples”), which is set
forth below:
3. A method of diagnosing julitis in a patient, said method
comprising:
a. obtaining a plasma sample from a human patient;
b. detecting whether JUL-1 is present in the plasma sample by
contacting the plasma sample with a porcine anti-JUL-1
antibody and detecting binding between JUL-1 and the porcine
antibody; and
c. diagnosing the patient with julitis when the presence of JUL-1
in the plasma sample is detected.
(Br. 11; May 2016 Examples 10.)
Appellants contend that “[t]he example indicates that use of a porcine
anti-JUL antibody ‘in veterinary therapeutics was known to most scientists
in the field’” and further contend that, therefore, claim 3 must have been

7 To the extent Appellant’s argument is based on the statement in Ariosa that
“[u]sing methods like PCR to amplify and detect cffDNA was well-
understood, routine and conventional activity in 1997” (Br. 12), we are not
persuaded. As discussed above, although “the preparation and amplification
of DNA sequences in plasma or serum were well-understood, routine,
conventional,” there appears to be no disagreement that the discovery of the
presence of cffDNA in maternal plasma or serum was new as of the time of
Sequenom’s invention. Ariosa, 788 F.3d at 1377.
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patent-eligible because “[t]he use of the porcine anti-JUL antibody in the
claimed field is unconventional.” (Br. 11.)
We are not persuaded. The analysis with respect to Example 29
explains that claim 3 is patent eligible because “there is no evidence that
porcine antibodies were routinely or conventionally used to detect human
proteins such as JUL-1.” (May 2016 Examples 13 (emphasis added).) In
contrast, as discussed above, the Specification and Dhallan show that
amplifying and sequencing DNA from blood samples are well-known,
routine and conventional techniques. Unlike claim 3 of Example 29,
therefore, pending claim 1 does not include significantly more than the
judicial exceptions recited therein.
Indeed, Example 29 supports the Examiner’s rejection of the claims
on appeal. The analysis accompanying the example explains that claim 2 of
Example 29, which detects whether JUL-1 is present by detecting binding
between JUL-1 and an anti-JUL-1 antibody, is patent-ineligible because
detecting a protein using an antibody to that protein is a routine and
conventional technique. (Id. at 9–10, 12.) In other words, claim 2 was
patent-ineligible, despite the fact that it would not have been routine and
conventional to use the anti-JUL-1 antibody “in the field of julitis diagnosis”
because the correlation between the presence of JUL-1 protein and the
presence of julitis in the patient was not previously known.
Appellants contend that “[t]he pending claims are also patent eligible
because the ordered combination of the elements in the instant claims was
not conventional, well-understood, and routine in fetal aneuploidy
detection.” (Br. 12 (emphasis added).) Appellants contend that “a patent
eligible ‘process’ includes a ‘new use of a known process, machine,
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manufacture, composition of matter, or material’” and that the Examiner
“attest[ed] to [the] nonconventional nature [of the claims]” by withdrawing
earlier anticipation and obviousness rejections. (Id. at 12–13.)
We are not persuaded. The additional elements as a combination
merely use well-understood, routine, and conventional techniques to gather
the data necessary to apply the recited judicial exception(s). Thus, they add
no meaningful limitations to the exception not already present when the
elements are considered separately. To the extent Appellants’ argument is
that the combination of elements is not well-understood, routine, and
conventional in fetal aneuploidy detection, we are not persuaded for the
reasons discussed above.
Neither are we persuaded by Appellants’ apparent argument that
claim 1 must be patent eligible because the Examiner withdrew earlier
rejections based on prior art. A claim may recite a “[g]roundbreaking,
innovative, or even brilliant discovery” — and thus be nonobvious — and
nevertheless fail to satisfy the § 101 inquiry. Myriad, 569 U.S. at 591. As
the Supreme Court explained in the context of mathematical algorithms,
[t]he process itself, not merely the mathematical
algorithm, must be new and useful. Indeed, the novelty of
the mathematical algorithm is not a determining factor at
all. Whether the algorithm was in fact known or unknown
at the time of the claimed invention, as one of the “basic
tools of scientific and technological work,” it is treated as
though it were a familiar part of the prior art.
Parker v. Flook, 437 U.S. 584, 591–592 (1978).
Finally, Appellants contend that claim 1 is patent eligible under the
second step of the Mayo inquiry because it recites “specific meaningful
limitations” such as a specific type of disease, nucleic acid, samples, loci of
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interest, sequencing, chromosomes, requirements for creating models, and
comparison step. (Br. 13.)
We are not persuaded. As already discussed, limitations that merely
recite a judicial exception or insignificant pre-solution activities performed
using well-known, routine, and conventional techniques are insufficient to
transform a claim into a patent-eligible application of the judicial exception.
Likewise, limiting a claim to a particular technological environment (e.g.,
specific type of disease, chromosomes, etc.) is, without more, insufficient to
transform the claim into a patent-eligible application of the judicial
exception. Bilski, 561 U.S. at 610–611 (explaining that “the prohibition
against patenting abstract ideas ‘cannot be circumvented by attempting to
limit the use of [the abstract idea] to a particular technological
environment’”) (citation omitted).
Accordingly, we affirm the Examiner’s rejection of claim 1. Claims
2–4, 9–15, 17, 20–24, 26–28, 32, 33, and 36, which are not separately
argued, fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv).
SUMMARY
For the reasons above, we affirm the Examiner’s decision rejecting
claims 1–4, 9–15, 17, 20–24, and 26–28, 32, 33, and 36.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED