Somalee Datta et al.

Patent Trials and Appeals Board

Aug 9, 2019

14414688 - (D) (P.T.A.B. Aug. 9, 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.
14/414,688 01/13/2015 Somalee Datta GP317-03.UT 6187
13837 7590 08/09/2019
Alston & Bird LLP/ Gen-Probe Incorporated
Bank of America Plaza
101 South Tryon Street, Suite 4000
Charlotte, NC 28280-4000
EXAMINER
WISE, OLIVIA M.
ART UNIT PAPER NUMBER
1631
NOTIFICATION DATE DELIVERY MODE
08/09/2019 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):
patentdept@hologic.com
usptomail@alston.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte SOMALEE DATTA, BRETT BOWMAN, XIANQUN WANG,
and MINGJIE WANG
____________

Appeal 2018-0083271
Application 14/414,688
Technology Center 1600
____________

Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
DAVID COTTA, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
The claims in this appeal are directed to a method of detecting a
minority genotype of a target nucleic acid of a virus in a population of
patients undergoing a drug treatment regime.
The Examiner rejected the claims under 35 U.S.C. § 101 as reciting a
judicial exception to patent eligibility. Pursuant to 35 U.S.C. § 134(a),
Appellants appeal the Examiner’s determination that the claims are
unpatentable. We have jurisdiction for the appeal under 35 U.S.C. § 6(b).
The Examiner’s decision is affirmed.

1 The Appeal Brief (“Appeal Br.” entered Apr. 18, 2018) lists Gen-Probe
Inc. as the Real Party in Interest. Appeal Br. 2.
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The Examiner rejected claim 1, under 35 U.S.C. § 101 as directed to a
judicial exception to patent eligibility. Final Act. 2.
Claim 1, the only independent claim on appeal, is reproduced below:
1. A method for detecting a minority genotype of a
target nucleic acid of a virus in a population of patients
undergoing a treatment regime, the treatment regime
comprising receiving a drug for treating an infection by the
virus, the patients being monitored to provide efficacy and/or
resistance data of the drug, the method comprising:
(a) deep sequencing at least a portion of the target nucleic
acid, wherein the deep sequencing is selected from the group
consisting of: single molecule real time sequencing, ion semi-
conductor sequencing, and bridge polymerase chain reaction
sequencing,
(b) detecting, using the deep sequencing results of (a), a
presence of variant nucleobases at one or more nucleotide
reference positions within the target nucleic acid;
(c) calculating p-values of the variants detected in step
(b) and selecting statistically significant variants with the
lowest p-values or for which the p-values are below a threshold;
(d) clustering, using non-negative matrix factorization,
the statistically significant variants of step (c) into clusters; and
(e) correlating the clusters of statistically significant
variants with the efficacy and/or drug resistance data.

REJECTION UNDER § 101
The Examiner found that the claims are directed to “the abstract idea
of an algorithm for correlating nucleic acid variants with efficacy and/or
drug resistance data” and “the concept of a correlation between a natural
product and a specific outcome” which are judicial exceptions to patent
eligibility under § 101. Final Act. 3.
Under 35 U.S.C. § 101, an invention is patent-eligible if it claims a
“new and useful process, machine, manufacture, or composition of matter.”
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However, not every discovery is eligible for patent protection. Diamond v.
Diehr, 450 U.S. 175, 185 (1981). “Excluded from such patent protection are
laws of nature, natural phenomena, and abstract ideas.” Id. (citations
omitted). The Supreme Court articulated a two-step analysis to determine
whether a claim falls within an excluded category of invention. Alice Corp.
v. CLS Bank Int’l, 573 U.S. 208, 216 (2014); Mayo Collaborative Servs. v.
Prometheus Labs., Inc., 566 U.S. 66, 75–77 (2012).
In the first step, it is determined “whether the claims at issue are
directed to one of those patent-ineligible concepts.” Alice, 566 U.S. at 217
(citation omitted). If it is determined that the claims are directed to an
ineligible concept, then the second step of the two-part analysis is applied in
which it is asked “‘[w]hat else is there in the claims before us?’” Id.
(citation omitted). The Court explained that this step involves:
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.”

Alice, 566 U.S. at 217–18 (citing from Mayo, 566 U.S. at 75–77).
Alice, relying on the analysis in Mayo of a claim directed to a law of
nature, stated that in the second part of the analysis “the elements of each
claim both individually and ‘as an ordered combination’” must be
considered “to determine whether the additional elements ‘transform the
nature of the claim’ into a patent-eligible application.” Alice, 566 U.S. at
217.
The PTO recently published revised guidance on the application of
§ 101. USPTO’s January 7, 2019 Memorandum, 2019 Revised Patent
Subject Matter Eligibility Guidance, 84 Fed. Reg. 50, 51–57 (2019) (“2019
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Guidelines”). This guidance provides direction on how to implement the
two-part analysis of Mayo and Alice.
The 2019 Guidelines implement the first step of the Alice/Mayo test as
Step 2A. 84 Fed. Reg. 51 (col. 1). Step 2A, Prong One, of the 2019
Guidelines, looks at the specific limitations in the claim to determine
whether the claim recites a judicial exception to patent eligibility. 84 Fed.
Reg. 54 (“1. Prong One”). In Step 2A, Prong Two, the claims are examined
to identify whether there are additional elements in the claims that integrate
the exception in a practical application, namely, is there a “meaningful limit
on the judicial exception, such that the claim is more than a drafting effort
designed to monopolize the judicial exception.” 84 Fed. Reg. 54 (“2. Prong
Two”).
If the exception is not integrated into a practical application, then as in
the Alice/Mayo framework, Step 2B of the 2019 Guidelines asks whether
there is an inventive concept to ensure that the patent is significantly more
than a patent on the ineligible concept, itself. 84 Fed. Reg. 56. In making
this determination, it must be considered whether there are specific
limitations or elements recited in the claim “that are not well-understood,
routine, conventional activity in the field, which is indicative that an
inventive concept may be present” or whether the claim “simply appends
well-understood, routine, conventional activities previously known to the
industry, specified at a high level of generality, to the judicial exception,
which is indicative that an inventive concept may not be present.” 84 Fed.
Reg. 56.
With these guiding principles, we proceed to determine whether the
claimed subject matter in this appeal is eligible for patent protection under
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35 U.S.C. § 101. As explained in more detail below, we conclude that the
claims are directed to patent-ineligible subject matter.

Step 2A, Prong One
In Step 2A, Prong One, of the 2019 Guidelines, the specific
limitations in the claim are examined to determine whether the claim recites
a judicial exception to patent eligibility, i.e., whether the claim recites an
abstract idea, law of nature, or natural phenomenon. The Examiner found
that the claim recites both an abstract idea and a law of nature. Ans. 3.
The 2019 Eligibility Guidance identifies three groupings (a)–(c) as
abstract ideas. 84 Fed. Reg. 52. As explained in more detail below, the
claim recites subject matter which fits into grouping (a), “Mathematical
concepts—mathematical relationships, mathematical formulas or equations,
mathematical calculation,” and also into grouping (c), “Mental processes–
concepts performed in the human mind (including an observation,
evaluation, judgment, opinion).” Id.
Claim 1 is directed to a “method for detecting a minority genotype of
a target nucleic acid of a virus in a population of patients undergoing a
treatment regime.” The Specification does not define “minority genotype,”
but describes an example of one as a “rare or as yet unknown” viral
genotypes. Spec. ¶ 6. The Specification discloses, with respect to the
hepatitis C virus (HCV), that the virus mutates rapidly giving rise to
“extreme genetic heterogeneity” that includes “a dominant majority species
and a cloud of genetically distinct minority species.” Spec. ¶ 3. The
Specification explains that such genotypes “are indicative of disease
prognosis and can influence viral response to drugs.” Id. Thus, the purpose
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of the claimed method is to identify minority/rare/unknown viral genotypes.
The method uses conventional nucleotide sequencing platforms to do so.
Spec. ¶ 7.
The patients are recited in the claim preamble as “being monitored to
provide efficacy and/or resistance data of the drug.” While the patients are
also recited in the claim preamble as “receiving a drug for treating an
infection by the virus,” the preamble identifies the claim as a whole as a
genotype detection method (“A method for detecting a minority genotype of
a target nucleic acid of a virus”), and does not indicate how the detected
genotype is used to treat the patients having the infection.
With regard to the detection method, step (b) of the claim is directed
to “detecting” a variant nucleotide base (“nucleobase”) with respect to a
reference sequence. Appellants’ cited paragraph 45 of the Specification for
support for the “detecting” step. Appeal Br. 2. This paragraph does not
explain how the detecting is performed. However, paragraphs 67–70
describe aligning nucleotide sequence reads with a consensus sequence and
then identifying the variants. The detecting step would also be understood to
be a mental process because the identified variants produced by the sequence
alignment are observed. Thus, this step recites an abstract idea comprising
“Mathematical Concepts” and “Mental processes.” See 84 Fed. Reg. 52
Steps (c) and (d) are “calculating p-values” of variants and
“clustering” the variants of step (c), respectively. Step (c) involves a
calculation and therefore is a mathematical operation. The “clustering” in
step (d) is described in the example in the Specification as performed by the
NMF algorithm described, for example, in Gaujoux, R., and Seoighe, C.,
BMC Bioinformatics, 2010, 11:367 (“Gaujoux”). Spec. ¶ 77. Gaujoux
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discloses “a mathematical formulation of the general NMF approach.”
Gaujoux 2 (in section titled “Formal definition”). The “clustering” is
therefore also a mathematical operation.
The last step of the claim is “correlating the clusters of statistically
significant variants with the efficacy and/or drug resistance data.” The
“correlating” step results in the discovery of a law of nature, namely, the
relationship between the naturally-occurring virus and its corresponding
sequence and how the patient infected with the virus responds to a drug.
The determination of a naturally-occurring viral sequence and its
relationship to drug efficacy and drug resistance is a law of nature which is a
judicial exception to patent eligibility. Mayo is similar in that naturally-
occurring levels of a drug metabolite were used to determine how much of
the drug to subsequently administer to a patient (Mayo, 566 U.S. at 74–75)
analogously to how naturally-occurring sequence variants are correlated in
the rejected claims in this appeal to drug response. In both cases, a natural
relationship is used to inform the doctor about how to treat the patient. As
stated by the Court in Mayo, the combination of steps in the claim “amounts
to nothing significantly more than an instruction to doctors to apply the
applicable laws when treating their patients.” Mayo, 566 U.S. at 79. The
Court found that steps of the claim “simply tell doctors to gather data from
which they may draw an inference in light of the correlations.” Id.
In claim 1, the naturally-occurring sequence variants are subjected to
mathematical operations (steps (c) and (d)) and then correlated statistically
“with the efficacy and/or drug resistance data.” A naturally-occurring
product – the metabolite in Mayo and “variant nucleobases” in rejected
claim 1 – is used to tell the doctor something about the patient’s response to
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a drug. For this reason, the Mayo Court’s conclusion that the claims at issue
in that case “set forth laws of nature — namely, relationships between
concentrations of certain metabolites in the blood and the likelihood that a
dosage of a thiopurine drug will prove ineffective or cause harm” is
applicable here. Mayo, 566 U.S. at 77. That is, rejected claim 1 sets forth a
law of nature, namely, a natural relationship or natural correlation between
the sequence variants of a naturally-occurring virus and drug treatment.
For these reasons, we conclude that, under the first step of the Alice/Mayo
test, step (e) of claim 1 on appeal recites a law of nature.
In summary, steps (a) and (b) of claim 1 recite mental processes, steps
(c) and (d) recite mathematical operations, and step (e) recites a law of
nature. Accordingly we conclude that claim 1 recites multiple judicial
exceptions.
Appellants argue that “there may be previous cases finding that a
genetic analysis constitutes a natural principle or a statistical analysis
constitutes an abstract idea, there has been no case holding that the
combination of both was also an abstract idea and thus patent-ineligible.”
Appeal Br. 4. We find this argument unpersuasive because Mayo found that
the correlation between metabolite and drug, which necessarily requires
calculations to be performed, recites a natural law. Appellants did not
explain why reciting mathematical operations in a claim involving the
discovery of a natural law transforms an ineligible judicial exception into an
eligible one.
Appellants contend that Cleveland Clinic Foundation v. True Health
Diagnostics LLC, 859 F.3d 1352, 1356 (Fed. Cir. 2017) is “suggesting that a
combination of a natural principle and abstract idea in the form of a novel
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statistical analysis is patent eligible subject matter.” Appeal Br. 4.
Appellants state that “implication” of statements in Cleveland Clinic is
that statistical steps as detection steps are taken into account in
assessing whether the claim includes significantly more than a
natural principle, and if the claims had assessed disease risk by
a novel statistical analysis of metabolite levels rather than a
conventional and generic comparison with control levels,
subject eligibility would have been found.
Appeal Br. 6.
It was stated in Cleveland Clinic:
Here, the testing patents here do not extend their discovery that
MPO correlates to cardiovascular risk to a patentable method.
They require only conventional MPO detection methods and
compare those values to predetermined or control values
derived from conventional statistical methods.
Cleveland Clinic, 859 F.3d at 1362.
We do not agree with Appellants that Cleveland Clinic stands for the
principle that “statistical steps” could confer patent eligibility on a natural
principle. Parker v. Flook, 437 U.S. 584 (1978) clearly articulated that it is
the process that is the focus of patent eligibility, and not the mathematical
operations performed in the claim.
In Flook, 437 U.S. at 594–95, claims to updating alarm limits were
found to be ineligible for patent, despite providing “a new and presumably
better method for calculating alarm limit values.” In Flook, the claim was
directed to a “method for updating the value of at least one alarm limit on at
least one process variable involved in a process comprising the catalytic
chemical conversion of hydrocarbons.” Flook, 437 U.S. at 596–97
(Appendix to Opinion). The steps comprised determining a new alarm base
using a mathematical algorithm, using the alarm base to update an alarm
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limit, and then adjusting the alarm limit to the updated value. Id. The Court
found the claim to be a judicial exception to subject matter ineligibility. The
Court held that “[t]he process itself, not merely the mathematical algorithm,
must be new and useful.” Id. at 591.
For this reason, we decline to find that mathematical operations used
to derive a correlation are sufficient to confer eligibility on the claims.

Step 2A, Prong Two
In the second step of the analysis, when the claim is found to recite a
judicial exception, the 2019 Guidelines directs us to “evaluate whether the
claim as a whole integrates the recited judicial exception into a practical
application of the exception.” 84 Fed. Reg. 54 (in section titled “2. Prong
Two”). Thus, because claim 53 recited several judicial exceptions, we
proceed to the second step of the analysis. The 2019 Guidelines explains:
A claim that integrates a judicial exception into a practical
application will apply, rely on, or use the judicial exception in
a manner that imposes a meaningful limit on the judicial
exception, such that the claim is more than a drafting effort
designed to monopolize the judicial exception.
84 Fed. Reg. 54.
The body of the claim recites the steps necessary to implement the
method of “detecting a minority genotype of a target nucleic acid of a virus.”
The first step of the claim is “deep sequencing.” The Specification defines
“deep sequencing” as “nucleic acid sequencing to a depth that allows each
base to be read hundreds of times, typically at least about 500 times, more
typically at least about 1000 times, and even more typically at least about
1500 times.” Spec. ¶ 29. The deep sequencing is performed using a
sequencing platform selected from a list of specific sequencing technologies.
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As discussed above, this step is properly understood as mental process, i.e., a
judicial exception, and is thus not a practical application of a judicial
exception. To the extent these steps are considered to require one to perform
physical steps, it would not change the results of our analysis, because those
steps involve the collection of information that is necessary to perform the
detection of the minority genotype and subsequent correlation, i.e. mere data
gathering.2
The steps of the claim, as described above, result in the detection of
nucleotide variants of naturally-occurring viruses. This information is used
to make a correlation between the sequence and response to a drug used to
treat the virus. Significantly, the claim does not include a step requiring one
to act upon the correlation like the claim in Vanda Pharms. Inc. v. West-
Ward Pharms. Int’l Ltd., 887 F.3d 1117, 1135 (Fed. Cir. 2018). In Vanda,
the claim was found to be a patent-eligible application because the claimed
step of identifying a patient’s CYP2D6 genotype was used to determine how
much of a drug to actually administer to the patient experiencing
schizophrenia, i.e., the claim was directed to treating a patient rather than the
natural correlation. The court in Vanda found that the genotype of the
patient (a naturally-occurring phenomenon) was integrated into a new way
of using an existing drug to treat a patient and thus was patent-eligible. Id.
Rejected claim 1 appreciates the natural occurring nucleotide
sequence and its association with a drug response, but unlike Vanda, the

2 The collection of information in the context of analyzing it and displaying
the result was still found to be an abstract idea in Electric Power Grp., LLC
v. Alstom S.A., 830 F.3d 1350, 1354–55 (Fed. Cir. 2016); see also, 84 Fed.
Reg. 55 n.31.
.
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appealed claim does not require this result to be applied in a practical way,
such as drug administration or treatment. Thus, like Mayo, the “ordered
combination [of steps] adds nothing to the laws of nature that is not already
present when the steps are considered separately.” Mayo, 566 U.S. at 79.
The claims provide no instruction to the skilled artisan who wants to use the
correlation between the nucleobase variant and drug response.
Appellants contend that “the claims contain many additional
limitations constituting a specific application of this law of nature,” stating
that the claims are limited to “the field” of “patients receiving drug treatment
for a viral infection” and that “[v]ariants are identified by a combination of
three steps.” Appeal Br. 8. This argument does not persuade us that the
claims recite a practical application because the steps used to identify the
variants are mathematical operations and the results of those operations are
not applied in a useful way to treat the patients as they were in Vanda. In
reaching this determination, we are not ignoring the claims “as a whole” as
asserted by Appellants (Appeal Br. 10), but rather we find that the recited
judicial exceptions are not integrated into a practical application.
Appellants cite to McRO, Inc. v. Bandai Namco Games Am. Inc., 837
F.3d 1299, 1313 (Fed. Cir. 2016) (Appeal Br. 10), but the claims are clearly
distinguishable from those in McRO because, while the McRO claims
involved the manipulation of data, e.g., generating morph weight sets to
animate lip and facial expressions of three dimensional characters, the court
found that “the automation goes beyond merely ‘organizing [existing]
information into a new form’ or carrying out a fundamental economic
practice.” McRO, 837 F.3d at 1315 (citation omitted). Instead, the court
found that the “claimed process uses a combined order of specific rules that
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renders information into a specific format that is then used and applied to
create desired results: a sequence of synchronized, animated characters.” Id.
The rejected claims in this case are different because the data is not used to
produce a new patent eligible result, but rather to obtain a correlation which
is not applied in the claim to achieve a useful result, such as treating patients
with a drug. To the contrary, the patients are already receiving drug
treatment and the correlation is not used to modify the treatment protocol.

Step 2B
As explained in the 2019 Guidelines, if the exception is not integrated
into a practical application, then Step 2B of the 2019 Guidelines, as in the
Mayo/Alice framework, asks whether there is an inventive concept. To
determine whether an unpatentable law of nature has been transformed “into
a patent-eligible application of such law,” the Court in Mayo held that the
claim as a whole must be examined to determine whether it “also contain[s]
other elements or a combination of elements, sometimes referred to as an
‘inventive concept,’ sufficient to ensure that the patent in practice amounts
to significantly more than a patent upon the natural law itself.” Mayo, 566
U.S. at 72–73. Under this step, we are directed to ask whether an additional
element or combination of elements recited in the claims:
• Adds a specific limitation or combination of
limitations that are not well-understood, routine,
conventional activity in the field, which is indicative that
an inventive concept may be present; or
• simply appends well-understood, routine,
conventional activities previously known to the industry,
specified at a high level of generality, to the judicial
exception, which is indicative that an inventive concept
may not be present.
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84 Fed. Reg. 56.
The first step of claim 1 is of deep sequencing a portion of nucleic
acid using a sequencing platform selected from a group of sequencing
technologies. Appellants state that “the deep sequencing techniques recited
by claim 1 are a recently emerging field still subject to problems and rapid
innovation rather than well-understood, routine and conventional
techniques.” Reply Br. 7. To support this argument, Appellants cite a
review article by Bazon, Int. J. Mol. Sci., 2011, 12, 7861–84, which
discloses that the field is in “rapid expansion and novel and improved
platforms are continuously being developed and released” and that “[n]ext-
generation high throughput sequencing technologies have become available
in the last few years and are in continuous development and improvement.”
Reply Br. 7–8.
This argument is not supported by persuasive evidence. Wang, J.
Virol., 2010, 84(12):6218–28, cited by the Examiner, describes identifying
sequencing of HCV virus variants by “deep sequencing.” Wang 6219
(“Using the deep-sequencing data, we estimate that only one or a few viral
variants seeded initial infection, but after that, viral variants could expand to
> 100 in a single individual.”) Thus, deep sequencing had been used for the
same purpose as in the rejected claims, to identify sequence variants in a
virus, supporting the Examiner’s determination that deep sequencing is well-
understood and routine.
While it may be true that improvements were still being made to deep
sequencing technology, this fact does not undermine the finding that deep
sequence was well-understood, routine, and conventional in the art at the
time of the invention. As held in In re Peterson, 315 F.3d 1325, 1329–30
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(Fed. Cir. 2003), there is a “normal desire of scientists or artisans to improve
upon what is already generally known.” The fact that scientists sought to
improve “deep sequencing” does not, alone, establish that such technology
was not routine and conventional at the time of the invention. Appellants
have not directed our attention to anything in the claims or the Specification
that establish that Appellants have used deep sequencing in an inventive way
that adds significantly more to the judicial exception, itself.
Appellants further argue that combination of steps recited in claim 1 is
novel. Appeal Br. 6. Appellants state that “claim 1 does not simply recite
non-negative matrix factorization [clustering] but also has the step of
determining p-values of variants (which serves to remove sequencing errors,
i.e., statistical noise) before the non-negative matrix factorization is
performed.” Appeal Br. 6. As held in Flook, “[v]ery simply, our holding
today is that a claim for an improved method of calculation, even when tied
to a specific end use, is unpatentable subject matter under § 101.” Flook,
437 U.S. at 595 n.18. Thus, step (c) of “calculating” and step (d) of
“clustering,” even if novel when combined, do not make the claim eligible
for a patent under § 101.

SUMMARY
For the foregoing reasons, the rejection of claim 1 under 35 U.S.C.
§ 101 is affirmed. Claims 5, 7–11, 14, 15, 22, 32 and 35 were not argued
separately and thus fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv).

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TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).

AFFIRMED