Wen Luo

Patent Trials and Appeals Board

Oct 23, 2020

2020000934 (P.T.A.B. Oct. 23, 2020)

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.
13/982,470 10/14/2013 Wen Luo 4594-2000100 5604
128144 7590 10/23/2020
Rimon PC
One Embarcadero Center
Suite 400
San Francisco, CA 94111
EXAMINER
WOITACH, JOSEPH T
ART UNIT PAPER NUMBER
1631
NOTIFICATION DATE DELIVERY MODE
10/23/2020 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):
docketing.rimonlaw@clarivate.com
eofficeaction@appcoll.com
patentdocketing@rimonlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte WEN LUO
__________

Appeal 2020-000934
Application 13/982,470
Technology Center 1600
__________

Before FRANCISCO C. PRATS, TAWEN CHANG, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL

Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1, 12, 15, 16, 30, 35, 36, 51, 73, 74, 76–
78, 80, and 81. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

STATEMENT OF THE CASE
“The present invention relates to a method of discovering
pharmacogenomic biomarkers which can be developed into companion

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies Denovo Biomarkers, Inc.,
6404 Nancy Ridge Dr., San Diego, CA 92121, as the real party in interest.
Appeal Br. 3.
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diagnostic tests to predict varied individual responses (efficacy, adverse
effect, or other) to therapeutic agents.” Spec. ¶ 2.
Appellant’s claim 1, the only independent claim on appeal, is
representative, and reads as follows:
1. A method to identify one or more pharmacogenomic
biomarkers, which method comprises:
a) isolating DNA from archived clinical plasma samples of at
least two patients exhibiting different values in a drug response;
b) amplifying said isolated DNA using whole-genome
amplification (WGA) to generate whole-genome amplified
DNA (wgaDNA);
c) performing whole-genome genotyping of said wgaDNA to
obtain high-density genotyping data, using an array set
comprising about 500,000 single nucleotide polymorphisms
(SNPs) and a genome-wide genotype calling algorithm,
wherein said genome-wide genotype calling algorithm is a
Robust Linear Model with the Mahalanobis Distance Classifier
(RLMM) algorithm or an imputation algorithm, and wherein
the call rate cut-off value of the genome-wide genotype calling
algorithm is less than about 80%; and
d) performing association analysis based on said whole-genome
genotyping data and said different values in said drug response,
thereby identifying said one or more pharmacogenomic
biomarkers for the drug response.
Appeal Br. 15.2
The sole rejection before us for review is the Examiner’s rejection of
claims 1, 12, 15, 16, 30, 35, 36, 51, 73, 74, 76–78, 80, and 81, under
35 U.S.C. § 101, as being directed to subject matter not eligible for
patenting. Final Act. 3–4;3 Ans. 4–7.4

2 Appeal Brief entered May 23, 2019.
3 Final Office Action entered July 27, 2018.
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ELIGIBILITY FOR PATENTING
Principles of Law
An invention is patent-eligible if it claims a “new and useful process,
machine, manufacture, or composition of matter.” 35 U.S.C. § 101. The
Supreme Court has long interpreted 35 U.S.C. § 101 to include implicit
exceptions, however: “[l]aws of nature, natural phenomena, and abstract
ideas” are not patentable. Alice Corp. v. CLS Bank Int’l, 573 U.S. 208, 216
(2014).
In determining whether a claim falls within an excluded category, we
are guided by the Supreme Court’s two-step framework, described in Mayo
Collaborative Services v. Prometheus Laboratories., Inc., 566 U.S. 66
(2012) and Alice, 573 U.S. at 217–18 (citing Mayo, 566 U.S. at 75–77). In
accordance with that framework, we first determine what concept the claim
is “directed to.” See Alice, 573 U.S. at 219 (“On their face, the claims
before us are drawn to the concept of intermediated settlement, i.e., the use
of a third party to mitigate settlement risk.”).
Concepts determined to be abstract ideas, and thus patent ineligible,
include certain methods of organizing human activity, such as fundamental
economic practices (Alice, 573 U.S. at 219–20; Bilski v. Kappos, 561 U.S.
593, 611 (2010)); mathematical formulas (Parker v. Flook, 437 U.S. 584,
594–95 (1978)); and mental processes (Gottschalk v. Benson, 409 U.S. 63,
69 (1972)).
If the claim is “directed to” an abstract idea, we turn to the second
step of the Alice and Mayo framework, where “we must examine the
elements of the claim to determine whether it contains an ‘inventive

4 Examiner’s Answer entered September 20, 2019.
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concept’ sufficient to ‘transform’ the claimed abstract idea into a patent-
eligible application.” Alice, 573 U.S. at 221 (quotation marks omitted).
Early in 2019, the USPTO published revised guidance on the
application of § 101. USPTO, 2019 Revised Patent Subject Matter
Eligibility Guidance, 84 Fed. Reg. 50 (January 7, 2019) (“2019 Office
Guidance” or “Office Guidance”). In light of comments received in
response to the Office Guidance, the USPTO subsequently issued the
October 2019 Patent Eligibility Guidance Update (“October 2019
Update”).5 “All USPTO personnel are, as a matter of internal agency
management, expected to follow the guidance.” Id. at 51; see also October
2019 Update at 1.
Following the Office Guidance and the October 2019 Update, under
Revised Step 2A, we first look to whether the claim recites the following:
(1) any judicial exceptions, including certain groupings of
abstract ideas (i.e., mathematical concepts, certain methods of
organizing human activity such as a fundamental economic
practice, or mental processes); and
(2) additional elements that integrate the judicial exception into
a practical application (see MPEP § 2106.05(a)–(c), (e)–(h)).
Only if a claim (1) recites a judicial exception and (2) does not
integrate that exception into a practical application, do we then look, under
Step 2B of the Office Guidance, to whether the claim:
(3) adds specific limitations beyond the judicial exception that
are not “well-understood, routine, conventional” in the field
(see MPEP § 2106.05(d)); or

5 https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_
update.pdf.
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(4) simply appends well-understood, routine, conventional
activities previously known to the industry, specified at a high
level of generality, to the judicial exception.
See Office Guidance (84 Fed. Reg. at 56).
The Examiner’s Position
The 2019 Office Guidance issued after the Examiner’s Final
Rejection, but before the Examiner’s Answer. In restating the § 101
rejection in the Answer, the Examiner initially summarized the claimed
subject matter, noting the changes resulting from Appellant’s amendments.
Ans. 4–5. The Examiner also noted that the limitations added to the claims
by Appellant’s amendments were features of conventional genotyping
techniques. Id. at 5.
Turning to the 2019 Office Guidance, the Examiner determined “[f]or
step 1 of the 101 analysis, the claims are found to be directed to a statutory
category as [a] method that isolates and analyzes DNA data obtained from
plasma.” Ans. 5.
The Examiner determined that, “[f]or step 2A of the 101 analysis, the
judicial exception of the claim are the steps of associating sequence data
with drug response data for patients.” Ans. 5. In particular, the Examiner
determined that,
[u]nder prong 1, the judicial exception is a set of instructions
for analysis of sequence data that was obtained from the array,
and appears to fall into both Mathematical Concepts, that is the
use of mathematical formulas or equations as specifically
recited for the use of RLMN/imputations algorithms and into
the category of Mental Processes, that is concepts performed in
the human mind (including an observation, evaluation,
judgment, opinion) in this case making a correlation with
presence or absence of a SNP and a drug response that was
observed in the patient.
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Id.
The Examiner then turned to the “second prong” of Revised Step 2A
of the 2019 Office Guidance, and determined that the claims do not integrate
the judicial exceptions into a practical application because the judicial
exceptions recite steps “at [a] high level of generality for the correlation of
a[n] SNP and drug response.” Ans. 6. In particular, the Examiner
determined, “there does not appear to be any evidence in the specification or
of record that the results feed-back or affect the previous steps where a
sample is amplified and analyzed on an array.” Id. The Examiner
determined, in addition, that the “physical steps of the claims” are “data
gathering steps which are not a practical application of the recited judicial
exception; i.e. they do not apply the mathematical and/or mental steps which
follow the data gathering steps to anything in any practical manner.” Id. at
8. The Examiner also noted that the claims’ physical steps are “conventional
steps of obtaining sequence information based on the guidance of the
specification and art of record which subsequently can be used in further
analysis to associate genotype data with observed phenotype data.” Id.
Turning to “step 2B of the 101 analysis,” the Examiner determined
that, beyond the recited judicial exceptions, the claims “provide additional
physical steps for isolating and amplifying DNA from a sample by whole
genome amplification and assessing a genotype with a SNP array.” Ans. 6.
The Examiner determined that the physical steps recited in Appellant’s
claims involved conventional molecular biology techniques, and that the
data analysis involved the use of known software. Id. at 7 (citing Spec.
¶¶ 25, 69).
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Analysis
Appellant’s representative claim 1 recites a “[a] method to identify
one or more pharmacogenomic biomarkers.” Appeal Br. 15. We find,
therefore, that the subject matter recited in claim 1 is a process, which falls
within one of the broad statutory categories of patent-eligible subject matter
under 35 U.S.C. § 101. Accordingly, we proceed to Step 2A, Prong One, of
the Office Guidance to determine the claim’s subject matter eligibility in
accordance with guidance under Mayo/Alice.
Office Guidance—Revised Step 2A, Prong 1
Applying Revised Step 2A, Prong 1, of the 2019 Office Guidance, we
agree with the Examiner that Appellant’s claim 1 recites judicial exceptions,
in the form of mathematical concepts and mental processes, both of which
are abstract ideas. See Office Guidance (84 Fed. Reg. at 52 (abstract ideas
include “(a) Mathematical concepts—mathematical relationships,
mathematical formulas or equations, mathematical calculations”)); id.
(abstract ideas include “(c) Mental processes—concepts performed in the
human mind (including an observation, evaluation, judgment, opinion”)).
The first two steps of Appellant’s claim 1 recite (a) isolating DNA
from archived clinical plasma samples of at least two patients that exhibit
different responses to a drug, and (b) amplifying the isolated DNA to
generate whole-genome amplified DNA (wgaDNA). Appeal Br. 15.
Step (c) of Appellant’s claim 1 recites using an array having about
500,000 single nucleotide polymorphisms (SNPs) “to obtain high-density
genotyping data.” Appeal Br. 15. The step of obtaining the genotyping data
uses specific algorithms, either a Robust Linear Model with the Mahalanobis
Distance Classifier (RLMM) algorithm or an imputation algorithm. Id. The
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algorithms employed in the step of obtaining the genotyping data use “a call
rate cut-off value of . . . less than about 80%.” Id.
Appellant does not persuade us of error in the Examiner’s
determination that obtaining genotyping data in the manner recited in step
(c) of claim 1 recites mathematical relationships. Appellant initially
contends that it is “untenable” to find that step (c) recites a judicial
exception. Appeal Br. 8.
Responding to the Examiner’s application of the 2019 Office
Guidance, however, Appellant expressly states that claim 1 “specifies . . . the
particular mathematical algorithms to apply for analysis, and an upper limit
on the call rate cutoff value to be used in the algorithm.” Reply Br. 5.
Appellant’s Specification explains, moreover, that the call rate cut-off value
(less than about 80% in claim 1) is a calculation that governs whether data
from a particular patient’s DNA sample will be included in the ultimate
analysis (step (d) of claim 1) that determines whether a particular genotype
is associated with a response to a drug. See, e.g., Spec. ¶ 116 (“After
removing the samples having call rates lower than the optimal cut-off
criteria, the genotype results are analyzed using genetic data analysis
software PLINK (Purcell et al., Am J Hum Genet (2007) 81:559-5752) to
calculate associated p-value of each polymorphic locus with the relevant
phenotype.”).
Accordingly, because obtaining genotyping data in the manner
provided in step (c) of claim 1 concededly recites specific mathematical
algorithms, and also recites a specific calculation that governs whether data
from a particular patient’s DNA sample will be included in the ultimate
analysis recited in the claim, we agree with the Examiner that claim 1 recites
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mathematical relationships, which are abstract ideas. See Office Guidance
(84 Fed. Reg. at 52).
Step (d) of Appellant’s representative claim 1 recites “performing
association analysis based on said whole-genome genotyping data and said
different values in said drug response.” Appeal Br. 15. Appellant does not
assert, nor do we discern, specific error in the Examiner’s determination that
step (d) of Appellant’s claim 1 recites an abstract idea, in the form of a
mental process. In particular, as the Examiner found, nothing in the
language of step (d) excludes making a straightforward mental determination
as to whether, “based on” the genotyping data (Appeal Br. 15), an identified
SNP is associated with a patient’s response (or non-response) to a drug.
Accordingly, because step (d)’s analysis encompasses an observation,
evaluation, judgment, and/or an opinion that can be made in the human
mind, we agree with the Examiner that claim 1 recites a mental process,
which is an abstract idea. See Office Guidance (84 Fed. Reg. at 52 (abstract
ideas include “(c) Mental processes—concepts performed in the human
mind (including an observation, evaluation, judgment, opinion”))).
We note, in addition, that step (d) of claim 1 recites an analysis that
associates a particular genotype with a patient’s response (or non-response)
to a drug, thereby ultimately “identifying . . . one or more pharmacogenomic
biomarkers for the drug response.” Appeal Br. 15. Because claim 1,
therefore, recites determining the natural relationship between a condition of
a patient (genotype) and the patient’s response to a drug, we find that claim
1 also recites a judicial exception, in the form of a law of nature. See Mayo,
566 U.S. at 77 (“Prometheus’ patents set forth laws of nature—namely,
relationships between concentrations of certain metabolites in the blood and
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the likelihood that a dosage of a thiopurine drug will prove ineffective or
cause harm.”); see also Genetic Technologies Ltd. v. Merial LLC, 818 F.3d
1369, 1374 (Fed. Cir. 2016) (finding claims reciting analysis of amplified
DNA as being “directed to the relationship between non-coding and coding
sequences in linkage disequilibrium and the tendency of such non-coding
DNA sequences to be representative of the linked coding sequences—a law
of nature”).
Office Guidance—Revised Step 2A, Prong 2
Having determined under Revised Step 2A, Prong 1, of the Office
Guidance that Appellant’s claim 1 recites judicial exceptions, we turn to
Revised Step 2A, Prong 2, to determine whether Appellant’s representative
claim 1 recites additional elements that integrate the judicial exceptions into
a practical application. See Office Guidance (84 Fed. Reg. at 54–55).
Appellant does not persuade us that the Examiner erred in determining that
claim 1 does not recite additional elements sufficient to integrate the judicial
exceptions into a practical application.
As to the abstract elements of claim 1, as noted above, step (c) of
Appellant’s claim 1 recites using abstract mathematical relationships to
obtain genotyping data from an array of SNPs, and step (d) recites an
abstract mental process of analyzing the data to determine an association
between the data and a patient’s response (or non-response) to a drug. See
Appeal Br. 15.
As also noted above, the first two steps of Appellant’s claim 1 recite
(a) isolating DNA from archived clinical plasma samples of at least two
patients that exhibit different responses to a drug, and (b) amplifying the
isolated DNA to generate whole-genome amplified DNA. Appeal Br. 15.
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As seen in claim 1, the steps of isolating and amplifying the patients’ DNA
provide the information required to generate the genotyping data, which in
turn is used to perform the abstract mental process of analyzing the data to
determine an association between the data and a patient’s response (or non-
response) to a drug. We therefore discern no error in the Examiner’s
determination that steps (a) and (b) of claim 1 involve mere data gathering,
which is not sufficient to integrate the recited judicial exceptions into
practical application. See Office Guidance (84 Fed. Reg. at 55 n.31
(additional element that merely adds insignificant extra-solution activity to a
judicial exception includes “mere data gathering such as a step of obtaining
information about credit card transactions so that the information can be
analyzed in order to detect whether the transactions were fraudulent”)).
Appellant does not specifically assert error in the Examiner’s
determination that claim 1’s DNA isolation and amplification steps are data
gathering steps that are central to performing the subsequent abstract steps
recited in the claim. Rather, Appellant contends that specific elements of
steps (a), (b), and (c) of claim 1’s process are sufficient to integrate the
claimed judicial exceptions into a practical application. See Appeal Br. 9–
11; Reply Br. 7–8. We are not persuaded.
In particular, we are not persuaded that claim 1’s requirement of
isolating DNA from “archived clinical plasma samples” is sufficient to
integrate the judicial exceptions recited in the claim into a practical
application. See Appeal Br. 9, 11; Reply Br. 7. While claim 1 specifies a
particular source from which the DNA must be isolated, isolating DNA from
patient samples is a step that necessarily must be performed when collecting
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information for performing the abstract data analyses recited later in the
claim.
We are not persuaded that selecting a particular source of genetic
information, in this case archived clinical plasma samples, for subsequent
abstract data manipulation is sufficient to integrate the recited judicial
exceptions into a practical application. See MPEP § 2106.05(g) (listing
“examples of activities that the courts have found to be insignificant extra-
solution activity” including “[s]electing a particular data source or type of
data to be manipulated” (collecting cases)); see also Electric Power Group,
LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (finding claims at
issue to be directed to abstract idea despite the fact that information analyzed
in claims was “of a specified content” (cited in MPEP § 2106.05(g))).
We are also unpersuaded that, in reciting that the DNA isolating step
uses “archived clinical plasma samples” (Appeal Br. 15), Appellant’s
claim 1 places a meaningful limitation on the claimed judicial exceptions.
To perform the abstract mental process of determining whether a particular
SNP or genotype is associated with a patient’s response (or non-response) to
a drug, one must necessarily obtain DNA from the patient, and plasma was a
known source of genomic DNA. See Spec. ¶ 6. In addition, the
Specification’s definition of “clinical sample” does not meaningfully limit
the source of the DNA. See Spec. ¶ 30 (“‘clinical sample’ . . . refer[s] to any
sample obtained from a subject of interest that would be expected or is
known to contain the cellular and/or molecular entity, such as a biomarker,
that is to be characterized” (emphasis added)).
Appellant, moreover, does not direct us to a specific definition for the
claim term “archived” in the Specification, or elsewhere in the record. We
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acknowledge the Specification’s disclosure that archived clinical plasma
samples may “often be[]processed and stored inappropriately” such that the
“DNA quality [i]s . . . poor.” Spec. ¶ 6 (internal quotations and citations
omitted).
As currently drafted, however, Appellant’s claim 1 contains no
specific language limiting the DNA-containing plasma sample to any
particular storage conditions or DNA quality. Given the absence of a
specific definition for the term “archived,” and given the absence of any
language in claim 1 limiting the archived plasma sample to a specific storage
duration, conditions, or DNA quality, Appellant’s representative claim 1
encompasses obtaining DNA from clinical plasma samples that were stored
for any period of time, and comprised of any quality DNA. We are not
persuaded, therefore, that claim 1 as currently drafted places a meaningful
limitation on the recited plasma sample, notwithstanding presence of the
term “archived.”
We are also not persuaded that claim 1’s use, in step (c), of an array of
about 500,000 SNPs is sufficient to integrate the claimed judicial exceptions
into a practical application. While claim 1’s step (c) employs data
manipulation processes conceded by Appellant to involve mathematical
relationships, the ultimate result of step (c) is “obtain[ing] high-density
genotyping data.” Appeal Br. 15. Thus, based on its express language,
claim 1’s step (c) is a data gathering step, although it involves mathematical
relationships. As noted above, mere data gathering is insignificant extra-
solution activity that is insufficient to integrate a judicial exception into a
practical application. See MPEP § 2106.05(g). Although the selection of
the 500,000 SNP array recited in claim 1 affects how much genotyping data
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can be obtained for the subsequent abstract mathematical manipulation and
analysis recited in the claim, the specific size of the array does not change
the fact that claim 1’s step (c) is ultimately a data gathering step.
We are not persuaded, therefore, that claim 1’s recitation of an array
of about 500,000 SNPs is sufficient to integrate the claimed judicial
exceptions into a practical application. Similarly, the fact that DNA
isolation and amplification might involve transformations of substances into
different substances (see Appeal Br. 10), does not negate the fact that the
isolation and amplification steps are steps of gathering data for use in the
ultimate abstract mental determination recited in claim 1.
We are also not persuaded that, when viewed in combination with the
other claim elements, the call rate cut-off value of less than about 80% in
claim 1 is sufficient to integrate the remainder of the claimed process into a
practical application. See Appeal Br. 11. As noted above, Appellant’s
Specification explains that the call rate cut-off value is a percentage
calculation (i.e., mathematical relationship) that governs whether data from a
particular patient’s DNA sample will be included in the ultimate analysis
(step (d) of claim 1) that determines whether a particular genotype is
associated with a response to a drug. See, e.g., Spec. ¶ 116 (disclosing that
genotyping data is analyzed “[a]fter removing the samples having call rates
lower than the optimal cut-off criteria”).
We acknowledge the Specification’s disclosure that the call rate cut-
off value of less than about 80% in claim 1 is lower than conventional cut-
off values, and that using a lower than conventional cut-off value allows
consideration of DNA-containing samples that would not be included in
normal genotype analyses, such as samples having poor quality DNA. See
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Spec. ¶¶ 63–64. As discussed above, however, we are not persuaded that
claim 1’s recitation of an archived clinical sample requires the use of
samples that contain poor quality DNA. We are not persuaded, therefore,
that the call rate cut-off value of less than about 80% in claim 1 is sufficient
to integrate the claimed process into a practical application, even when
viewed alongside the other elements in the claim 1. To the contrary, because
claim 1’s call rate cut-off value is merely a calculation that governs whether
data from a particular patient’s DNA sample will be included in the ultimate
analysis recited in the claim, the call rate cut-off value is part of the
genotype data gathering step, and therefore is insignificant extra-solution
activity, in addition to being an abstract mathematical relationship.
Lastly, we acknowledge, but are unpersuaded by, Appellant’s
argument that “[i]dentifying . . . biomarkers is certainly a useful and
practical result.” Appeal Br. 9. While it may be true that the process of
claim 1 can be used to uncover highly useful genetic information about
patients that have received a drug, as seen above, none of the non-abstract
elements recited in claim 1 apply that information in practical manner, such
as treating a specific disease or disorder. See Office Guidance (84 Fed. Reg.
at 55 (additional element that integrates a judicial exception into a practical
application includes “an additional element that applies or uses a judicial
exception to effect a particular treatment or prophylaxis for a disease or
medical condition”) (citing Classen Immunotherapies, Inc. v. Biogen IDEC,
659 F.3d 1057, 1066–68 (Fed. Cir. 2011); Vanda Pharm. Inc. v. West-Ward
Pharm. Int’l Ltd., 887 F.3d 1117, 1135 (Fed. Cir. 2018). Indeed, as our
reviewing court has explained, even if Appellant “made a ‘[g]roundbreaking,
innovative, or even brilliant discovery,’ . . . that is not enough” to establish
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patent eligibility. In re BRCA1- and BRCA2-Based Hereditary Cancer Test
Patent Litigation, 774 F.3d 755, 759 (Fed. Cir. 2014) (citing Association for
Molecular Pathology v. Myriad, 133 S.Ct. 2107, 2117 (2013)).
In sum, for the reasons discussed, considering the various claim
elements individually and in combination, we are not persuaded that the
additional elements recited in Appellant’s representative claim 1 are
sufficient to integrate the claimed judicial exceptions into a practical
application.
Office Guidance—Step 2B
Having determined that Appellant’s representative claim 1 recites
judicial exceptions under Revised Step 2A, Prong 1, of the 2019 Office
Guidance, and does not integrate those judicial exceptions into a practical
application under Revised Step 2A, Prong 2, we turn to Step 2B of the
Office Guidance to determine whether (a) claim 1 recites specific limitations
beyond the judicial exceptions that are not well-understood, routine, or
conventional in the field, or (b) whether claim 1 simply appends well-
understood, routine, conventional activities previously known to the
industry, specified at a high level of generality, to the judicial exception.
See Office Guidance (84 Fed. Reg. at 56).
In the present case, the limitations recited in representative claim 1
beyond the judicial exceptions are the steps of (a) isolating DNA from
“archived clinical plasma samples” of at least two patients exhibiting
different drug responses, (b) amplifying the DNA using whole-genome
amplification, and (c) applying the amplified DNA to an array having about
500,000 SNPs. Appeal Br. 15.
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As discussed above, the current language in claim 1 does not
expressly limit the archived plasma samples to specific storage durations,
conditions, or DNA quality. As also discussed above, there is no definition
of “archived” in the Specification or elsewhere in the record that
distinguishes the plasma samples of Appellant’s representative claim 1 from
plasma samples stored for short periods of time, or under optimal conditions
that would provide high quality DNA. To the contrary, as noted above, the
Specification broadly defines a “clinical sample” as essentially any sample
obtained from a patient of interest. See Spec. ¶ 30 (“‘clinical sample’ . . .
refer[s] to any sample obtained from a subject of interest that would be
expected or is known to contain the cellular and/or molecular entity, such as
a biomarker, that is to be characterized” (emphasis added)).
We conclude, therefore, that the term “archived clinical plasma
samples” in claim 1 encompasses any plasma samples that were previously
obtained from patients of interest. As evidenced by Appellant’s
Specification, as well as publications in the record, plasma was a well-
known source of isolatable genomic DNA. See Spec. ¶ 6 (citing Sjoholm,6
Lu7); see also Croft8 (cited by the Examiner at Ans. 8 and Final Act. 5).
Because plasma was a well-known source of isolatable genomic DNA, we
agree with the Examiner that the source of the patients’ DNA recited in

6 Malin L.L. Sjöholm et al., Comparison of Archival Plasma and Formalin-
Fixed Paraffin-Embedded Tissue for Genotyping in Hepatocellular
Carcinoma, 14 CANCER EPIDEMIOL. BIOMARKERS PREV. 251–255 (2005).
7 Yanhui Lu et al., Use of whole genome amplification to rescue
DNA from plasma samples, 39 BIOTECHNIQUES 511–515 (2005).
8 Daniel T. Croft, Jr., et al., Performance of Whole-Genome Amplified DNA
Isolated from Serum and Plasma on High-Density Single Nucleotide
Polymorphism Arrays, 10 J. MOL. DIAGNOSTICS 249–257 (2008).
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Appellant’s representative claim 1 does not add an inventive concept to the
judicial exceptions recited in the claim, but instead merely appends well-
understood elements to the judicial exception. See Office Guidance (84 Fed.
Reg. at 56); see also Appeal Br. 14 (arguing that isolating DNA from
archived clinical samples is not conventional); Reply Br. 8 (same argument).
As to the DNA isolation and amplification steps of Appellant’s
representative claim 1, Appellant’s Specification states expressly that the
“practice of the present invention will employ, unless otherwise indicated,
conventional techniques of molecular biology (including recombinant
techniques), microbiology, cell biology, biochemistry, and immunology,
which are within the skill of the art.” Spec. ¶ 25. We note, moreover, that
arrays with about 500,000 SNPs were commercially available. See id. ¶ 116
(describing use of “the Affymetrix GeneChip 500K Mapping Array Set
containing 500,000 SNPs following Affymetrix standard protocol (Santa
Clara, CA, USA)”).
Accordingly, for the reasons discussed, we conclude that the
additional elements beyond the judicial exceptions recited in Appellant’s
representative claim 1 simply append well-understood, routine, conventional
activities previously known in the field, to the judicial exceptions. We are
not persuaded by Appellant’s argument that claim 1’s allegedly
unconventional call rate cut-off value of less than about 80%, when
combined with claim 1’s archived clinical plasma samples, provides
unconventional inventive concept sufficient to transform the claimed
abstract idea into a patent-eligible application. See Appeal Br. 14; Reply Br.
8.
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19
It might be true, as Appellant contends, that using a relatively low call
rate cut-off value would allow inclusion, in claim 1’s biomarker analysis, of
samples having low quality DNA, such as might be found in archived
clinical plasma samples that were stored under poor conditions, or for a
relatively long time. The analysis under Step 2B of the Office Guidance,
however, relates to whether the “additional elements” beyond the judicial
exceptions add an inventive concept to the claim. Office Guidance (84 Fed.
Reg. at 56) (emphasis added).
As discussed above, the call rate cut-off value of less than about 80%
recited in representative claim 1 is itself an abstract mathematical
calculation, and intimately involved in the abstract data collecting and
manipulation features of claim 1. We are not persuaded, therefore, that
claim 1’s call rate cut-off value, even if unconventional, is sufficient to
provide an inventive concept to the process recited in claim 1. See BSG
Tech LLC v. BuySeasons, Inc., 899 F.3d 1281, 1290 (Fed. Cir. 2018) (“It has
been clear since Alice that a claimed invention’s use of the ineligible concept
to which it is directed cannot supply the inventive concept that renders the
invention ‘significantly more’ than that ineligible concept.”).
As also discussed above, the current language of claim 1 does not
distinguish the claimed archived clinical plasma samples from samples
stored for short periods of time, under optimal conditions providing high
quality DNA. Accordingly, even assuming that the call rate cut-off value in
claim 1 would allow inclusion of samples having low quality DNA in claim
1’s biomarker analysis, the current language of claim 1 does not reflect, or
even require, a combination of features that provide the alleged inventive
concept.
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20
In sum, for the reasons discussed, we conclude that the additional
elements beyond the judicial exceptions recited in Appellant’s representative
claim 1, viewed individually and as an ordered combination, simply append
well-understood, routine, conventional activities previously known in the
field, to the judicial exceptions.
Eligibility for Patenting—Conclusion
As discussed above, we are persuaded that Appellant’s claim 1 recites
judicial exceptions under Revised Step 2A, Prong 1, of the 2019 Office
Guidance, and does not integrate those judicial exceptions into a practical
application under Revised Step 2A, Prong 2. As also discussed above, we
are persuaded that claim 1 simply appends well-understood, routine,
conventional activities previously known to the industry, specified at a high
level of generality, to the judicial exception.
We acknowledge, as Appellant contends (see Reply Br. 3–4), that in
restating the § 101 rejection in the Answer, the Examiner initially
summarized the claimed subject matter, noted the changes resulting from
Appellant’s amendments, and subsequently applied the 2019 Office
Guidance to the claims as amended. Ans. 4–5. However, because the
Examiner ultimately applied the principles set forth in the 2019 Office
Guidance to the claims (see id. at 5–7), we are not persuaded that the
Examiner’s initial discussion regarding the individual claim elements added
in the amendment process rises to the level of reversible error.
In sum, applying the principles set forth in the 2019 Office Guidance
and October 2019 Update, we find that the preponderance of the evidence
supports the Examiner’s determination that Appellant’s claim 1 is directed to
subject matter that is ineligible for patenting. We, therefore, affirm the
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Examiner’s rejection of claim 1 on that ground. Because they were not
argued separately, claims 12, 15, 16, 30, 35, 36, 51, 73, 74, 76–78, 80, and
81 fall with claim 1. See 37 C.F.R. § 41.37(c)(1)(iv).

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 12, 15,
16, 30, 35,
36, 51, 73,
74, 76–78,
80, 81
101 Ineligibility 1, 12, 15,
16, 30, 35,
36, 51, 73,
74, 76–78,
80, 81

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED