Douglas A. Levine

Patent Trials and Appeals Board

Jul 22, 2019

13624922 - (D) (P.T.A.B. Jul. 22, 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.
13/624,922 09/22/2012 Douglas A. Levine 2003080-0477 2733
63411 7590 07/22/2019
CHOATE, HALL & STEWART LLP/MSKCC
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH
TWO INTERNATIONAL PLACE
BOSTON, MA 02110
EXAMINER
AEDER, SEAN E
ART UNIT PAPER NUMBER
1642
NOTIFICATION DATE DELIVERY MODE
07/22/2019 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):
jnease@choate.com
patentdocket@choate.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte DOUGLAS A. LEVINE
____________

Appeal 2018-000311
Application 13/624,9221
Technology Center 1600
____________

Before DONALD E. ADAMS, ERIC B. GRIMES, and
FRANCISCO C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims directed to a
method of using a uterine manipulator device to collect a uterine wash
sample that contains biomarkers indicative of ovarian cancer. The Examiner
rejected the claims for obviousness and as being directed to subject matter
ineligible for patenting.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm the obviousness rejection, but reverse the ineligibility
rejection.

1 Appellant states that “[t]he real party in interest is the owner and assignee
of the present application, MEMORIAL SLOAN-KETTERING CANCER
CENTER.” Appeal Br. 2.
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STATEMENT OF THE CASE
The Specification discloses that, contrary to earlier teachings,
“[r]ecent studies have demonstrated that the majority of presumed ovarian
carcinoma likely develops within the fallopian tube.” Spec. ¶ 60; see also
id. ¶¶ 54–55 (citing publications supporting fallopian tube lesion termed
“STIC” (serous tubal intraepithelial carcinoma) as most likely ovarian
cancer precursor).
The Specification explains that, because “[t]he fallopian tube lies in
direct continuity with the endometrial/uterine cavity, [it] can serve as a
proximal anatomic site for the detection of tissue specific biomarkers.” Id.
¶ 60.
Appellant’s invention involves detecting ovarian cancer biomarkers in
uterine washings in subjects with early stage ovarian cancer. See id. ¶ 62.
As explained in the Specification, “[t]his novel approach to early ovarian
cancer detection capitalizes on recent knowledge that the putative cell of
origin for ovarian cancer is the fallopian tubal secretory epithelium and not
the ovarian surface epithelium, as had been thought for decades.” Id.
The Specification explains that the CA-125 antigen, which is
associated with the MUC16 polypeptide, is a known biomarker for ovarian
cancer and “is present in the vast majority of serous ovarian cancers.” Id.
¶ 58.
In addition to CA-125, the Specification discloses that “[t]hose of
ordinary skill in the art are familiar with a variety of biomarkers whose
presence, and/or level correlates with presence and/or type of ovarian cells
and/or with ovarian cancer. To give but a few examples, biomarkers such as
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HE4, mesothelin, and/or YKL-40 may be detected and/or measured.” Id.
¶ 63.
The Specification states that the “present disclosure surprisingly
demonstrates that CA-125 measurements obtained from uterine washings
and/or in situ can be used to identify and/or characterize individuals
suffering from ovarian carcinoma or known precursor lesion such as, for
example, STIC.” Id. ¶ 62; see also id. ¶ 3 (“[T]he present invention
encompasses the surprising finding that ovarian washes can contain material
and/or markers that permit detection and/or characterization of cancer, and
particularly of ovarian cancer, including ovarian cancer that arises or exists
in fallopian tubes.”).
In that regard, Example 3 of the Specification describes a study of 25
women. Id. ¶ 89. Eleven of the women in the study had stage IIIC or IV
high-grade serous carcinoma (ovarian cancer termed “HGSC”), and fourteen
of the women, serving as non-cancer controls, were undergoing bilateral
salpingo-oophorectomy (BSO) for benign indications. Id.
“Serum, uterine washings, and peritoneal washings were collected
from each patient and analyzed for CA-125, YKL-40, HE4 and mesothelin
(MSLN).” Id. The results showed that CA-125, YKL-40, HE4, and MSLN
levels were significantly elevated in uterine washings from cancerous
patients, as compared to non-cancer control patients. Id. ¶ 90.
Based on the results, the Specification concludes that “[c]ommon
ovarian biomarkers are elevated in the uterine washings from HGSC patients
in this pilot study. Though this study was restricted to advanced stage
HGSC patients, it provides a foundation to explore a new approach to
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ovarian cancer screening considering a putative precursor lesion within the
distal fallopian tube.” Id. ¶ 91.
Appellant’s claim 1, the sole independent claim on appeal, is
representative and reads as follows:
1. A method of using a uterine manipulator device, the
method comprising a step of:
operating the device while present in a uterine cavity of a
subject suffering from early stage ovarian cancer so that:
(a) the device obtains a uterine wash sample, wherein the
uterine wash sample comprises cells, cellular fragments,
proteins and/or nucleic acids from the ovary or fallopian tube;
and
(b) the device detects an ovarian cancer biomarker level
for one or more of CA-125, HE4, mesothelin, and YKL-40,
and/or combinations thereof in the uterine wash sample,
wherein the ovarian cancer biomarker level is or comprises
level of a protein.
Appeal Br. 45.
The following rejections are before us for review:
(1) Claims 1–3, 6, 8–10, 22–24, 26–28, and 31, rejected under 35
U.S.C. § 103(a) as being unpatentable over Monahan,2 Lopata,3 and Palena4
(Ans. 2–5); and
(2) Claims 1–3, 6, 8–10, 22–24, 26–28, and 31, rejected under 35
U.S.C. § 101 as being directed to a judicial exception without significantly
more (Ans. 5–8).

2 US 2003/0087250 A1 (published May 8, 2003).
3 US 6,607,894 B1 (issued Aug. 19, 2003).
4 US 2009/0220382 A1 (published Sept. 3, 2009).
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OBVIOUSNESS
The Examiner’s Rejection
The Examiner cited Monahan as evidence that it was known in the art
to detect ovarian cancer biomarkers, among them mesothelin and CA-125, in
uterine washes, and noted in particular Monahan’s teaching that it was
desirable to detect ovarian cancer as early as possible. Ans. 2–3.
The Examiner found that Monahan differed from the process recited
in Appellant’s claims in that Monahan did not “specifically state the
biomarkers are to be detected in a uterine wash with a detection device
operating in vivo.” Id. at 3.
The Examiner cited Lopata as teaching methods of performing uterine
washes for measuring biomarker levels. Id. The Examiner cited Palena as
evidence that it was known in the art to implant antibody-containing
“nano-getter” devices into subjects to detect ovarian cancer biomarkers. Id.
at 3–4.
Based on the references’ combined teachings the Examiner concluded
that a skilled artisan would have considered it obvious to implant Palena’s
nano-getter device in a subject’s uterine cavity to detect levels of the
mesothelin and/or CA-125 biomarkers in uterine washes taught by Monahan
as being indicative of ovarian cancer. Id. at 4.
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
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Having carefully considered the arguments and evidence advanced by
Appellant and the Examiner, we find that that the preponderance of the
evidence supports the Examiner’s conclusion of obviousness.
As recited in Appellant’s claim 1, Monahan discloses testing subjects
to determine the presence of early stage ovarian cancer. See Monahan ¶ 13
(“[A] pressing need exists for methods of detecting ovarian cancer as early
as possible. . . . The present invention satisfies th[is] need[].”)
Monahan discloses that the presence of ovarian cancer can be
diagnosed by ascertaining whether a subject, including a subject with stage I
ovarian cancer, overexpresses one or more of the cancer markers identified
in Tables 1–3 of the reference. Id. ¶ 14–16.
As recited in Appellant’s claim 1, Monahan discloses that mesothelin
and the CA-125-associated protein MUC16 are ovarian cancer biomarkers
detectable by its methods. See id. at pp. 8–9.
As recited in Appellant’s claim 1, Monahan discloses detecting
biomarkers for ovarian cancer in uterine washes:
[T]he samples or patient samples comprise cells obtained
from the patient. . . . In one embodiment . . . the cells may be
found in a fluid selected from the group consisting of a fluid
collected by peritoneal rinsing, a fluid collected by uterine
rinsing, a uterine fluid, a uterine exudate, a pleural fluid, and an
ovarian exudate.
Id. ¶ 54 (emphasis added).
Monahan explains that the presence of ovarian cancer can be
ascertained using antibodies that bind to overexpressed protein biomarkers.
Id. ¶¶ 55–56 (disclosing “detecting the presence in the sample of . . . the
corresponding marker protein or a fragment of the protein (e.g. by using a
reagent, such as an antibody”); see also id. ¶ 129 (describing the use of
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immunological methods to detect ovarian cancer biomarkers on cancerous
cells present in “fluids collected by uterine rinsing”).
Although Monahan does not describe using an implanted device to
perform its antibody-based detection of the biomarkers, Palena discloses the
use of an internally implanted “nano-getter device” that contains antibodies
for detecting ovarian cancer biomarkers:
The nano-getter device 10 facilitates the in vivo
diagnostic methods and applications disclosed herein (e.g.,
detection of ovarian cancer) because it is very small and
innocuous, so that one or more nano-getter devices 10 may be
injected as a dialysate suspension into the patient’s abdominal
cavity, disperse into the peritoneum cavity, and reside for
subsequent interrogation by external sensing probes, including
but not limited to microwave, ultrasonic, and/or Raman
spectroscopy.
Palena ¶ 17 (emphasis added); see also id. ¶ 27 (“Once individual
biomarkers have been identified and characterized, the generally-accepted
approach is to generate antibodies that will bind specifically to each
biomarker. . . . Several biomarkers (or antigens) have been identified for
ovarian cancer, including CA125.”).
We acknowledge Palena’s disclosure of implanting its device in the
patient’s abdominal cavity. Id. ¶ 17. As discussed above, however,
Monahan discloses that ovarian cancer biomarkers can be detected in uterine
fluids, including uterine washes. Monahan ¶ 54. We therefore discern no
error in the Examiner’s determination that a skilled artisan would have been
motivated to, and had a reasonable expectation of success in, operating
Palena’s device so that it obtains a uterine wash sample, as recited in
Appellant’s claim 1. Indeed, as the Examiner found, Lopata describes
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techniques suitable for generating uterine washes useful for biomarker
analysis. See Lopata 6:17–23.
Accordingly, for the reasons discussed, we agree with the Examiner
that a skilled artisan had a good reason for, and a reasonable expectation of
success in, performing a process having all of the steps and features recited
in Appellant’s claim 1. We therefore agree with the Examiner’s
determination that the process recited in Appellant’s claim 1 would have
been obvious to a skilled artisan, based on the cited prior art.
Appellant contends that, despite Monahan’s express disclosure that
ovarian cancer biomarkers can be detected in uterine washes, and despite
Monahan’s express disclosure that mesothelin and CA-125 are useful
biomarkers for ovarian cancer, a skilled artisan would not have had
motivation or a reasonable expectation of success in detecting those
biomarkers in uterine washes. See Appeal Br. 9–21, 26–27 (citing Levine
Decl.);5 Reply Br. 4–17, 20–22.
It might be true that Monahan did not provide a working example
demonstrating that each and every biomarker listed in the reference was
detectable in uterine washes. See Appeal Br. 9 (citing Levine Decl. ¶ 6);
Reply Br. 10–11. It might also be true that Monahan focused on detecting
biomarkers by transcriptional profiling of the nucleic acids encoding the
proteins. See Appeal Br. 10–11; Reply Br. 10–11.
It is well settled, however, that when considering the obviousness of
claimed subject matter, “[a]ll the disclosures in a reference must be
evaluated, including nonpreferred embodiments, and a reference is not

5 Declaration under 37 C.F.R. § 1.132 of Douglas A. Levine, MD (signed
October 25, 2016).
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limited to the disclosure of specific working examples.” In re Mills, 470
F.2d 649, 651 (CCPA 1972) (emphasis added; citations omitted).
In the present case, as discussed above, Monahan expressly discloses
that two of the proteins recited in Appellant’s claim 1 (mesothelin and CA-
125) were known biomarkers for ovarian cancer. Monahan, pp. 8–9.
Monahan also expressly discloses that ovarian cancer biomarkers can be
detected in uterine washes. Id. ¶¶ 54, 129. Monahan expressly discloses
that antibodies (in addition to transcriptional profiling) can be used to detect
the biomarkers. Id. ¶¶ 55–56. And Monahan also expressly states that its
methods are useful for detecting early stage ovarian cancer. Id. ¶¶ 13, 16.
Because Monahan expressly identified uterine washes as a useful
sample material for analysis, and because Monahan expressly identified
mesothelin and CA-125 as useful biomarkers for diagnosing ovarian cancer,
the fact that Monahan may have disclosed a number of other useful sample
materials and biomarkers does not persuade us that Monahan failed to
provide sufficient blaze marks suggesting the sample material and
biomarkers recited in Appellant’s claim 1. See Appeal Br. 10–12; see also
Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989)
(species claim held obvious where it recited one of 1200 possible
combinations of embodiments disclosed by reference and where reference
suggested no preference for claimed embodiment); see also id. at 808 (That
a reference “discloses a multitude of effective combinations does not render
any particular formulation less obvious.”). Indeed, absent some objective
evidence in the record persuasively contradicting the express disclosures in
Monahan, we agree with the Examiner that Monahan provided a good
reason for, and a reasonable expectation of success in, using antibodies to
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detect mesothelin and/or CA-125 in uterine washes in subjects with early
stage ovarian cancer, as recited in Appellant’s claim 1.
While we acknowledge the statements in the Levine Declaration6
asserting lack of motivation and reasonable expectation of success in the
cited prior art, it is well settled that, to be persuasive of nonobviousness, an
expert’s opinion must be supported by objective evidence. See Ashland Oil,
Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 294 (Fed. Cir. 1985)
(“Lack of factual support for expert opinion going to factual determinations
. . . may render the testimony of little probative value in a validity
determination.”) (citing In re Altenpohl, 500 F.2d 1151, 1158 (CCPA
1974)).
In the present case, we are not persuaded that the Levine Declaration
identifies objective factual evidence sufficient to support the opinions
expressed therein. In particular, we are not persuaded that the Levine
Declaration identifies objective factual evidence that specifically contradicts
or questions the teachings in Monahan, such that a skilled artisan would
have ignored or failed to credit Monahan’s express disclosure that ovarian
cancer biomarkers may be detected in uterine washes. Although the
Monahan reference itself might have included certain disclosures consistent
with the view that ovarian cancer originates in the ovarian epithelium (see
Appeal Br. 11 (citing Levine Decl. ¶ 9)), Monahan nevertheless expressly
discloses that uterine washes are samples in which biomarkers may be
detected, as discussed above.

6 Dr. Levine is also the sole inventor of the present application.
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Indeed, rather than identifying objective factual evidence that
specifically contradicts or undercuts Monahan, Appellant acknowledges in
the Specification that a number of prior art publications include teachings
consistent with the view of fallopian tubes as the origin of ovarian cancer, a
view which Appellant argues (see Appeal Br. 14 (citing Levine Decl. ¶ 15))
is consistent with the expectation that ovarian cancer biomarkers would be
present in uterine washes, as taught in Monahan:
Two important findings from the published literature emerge:
1) that a lesion resembling ovarian HGSC [high grade serous
carcinoma] is rarely reported in CICs [cortical inclusion cysts]
and OSE [ovarian surface epithelium] compared to STICs
[serous tubal intraepithelial carcinoma] and 2) that there is
evidence for and against the role of CICs and OSE as
precursors whereas all the papers describing STICs support
that it is a precursor lesion.
Spec. ¶ 54 (emphasis added); see also id. ¶ 55 (listing papers describing
STICs).
Although we acknowledge Appellant’s citation of the Erickson,7
Flesken-Nikitin,8 and Dubeau9 references (Appeal Br. 11–13 (citing Levine
Decl. ¶¶ 10–12)), we first note that each of those articles has a publication
date after the 2011 priority date of the present application. In any event,
Appellant does not identify any disclosure in any of those references
explaining specifically whether biomarkers for ovarian cancer can be

7 Dr. Britt K. Erickson et al., The role of the fallopian tube in the origin of
ovarian cancer, 209 AM. J. OBSTET. GYNECOL. 409–414 (2013).
8 Andrea Flesken-Nikitin, Role of the stem cell niche in the pathogenesis of
epithelial ovarian cancers, 1 MOLECULAR & CELLULAR ONCOLOGY
e963435-1– e963435-7 (2014).
9 L. Dubeau & R. Drapkin, Coming into focus: the nonovarian origins of
ovarian cancer, 24 ANNALS OF ONCOLOGY vii28–vii35 (2013).
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detected in uterine washes. Absent some teaching that explains specifically
why a skilled artisan would not have expected biomarkers for ovarian cancer
to be detectable in uterine washes, the fact that Erickson, Flesken-Nikitin,
and Dubeau might or might not be consistent with the view of fallopian
tubes as the origin of ovarian cancer does not persuade us that those
references would have led a skilled artisan to ignore or question Monahan’s
express disclosure that ovarian cancer biomarkers are detectable in uterine
washes.
Moreover, contrary to Appellant’s contention that Monahan fails to
provide teachings specific to early stage cancer (see Appeal Br. 13–14
(citing Levine Decl. ¶¶ 14–16)), Monahan states expressly that its invention
“satisfies the[] need[]” “for methods of detecting ovarian cancer as early as
possible” and discloses that, “[i]n a preferred embodiment of the diagnostic
method, the marker is over-expressed by at least two-fold in at least about
20% of stage I ovarian cancer patients.” Monahan ¶¶ 13, 16.
We acknowledge Appellant’s contention that it was unexpected that
ovarian cancer biomarkers would be detectable in uterine washes. See
Appeal Br. 14 (citing Spec. ¶ 62, Levine Decl. ¶ 15), see also id. at 21–24;
see also Reply Br. 14–17. Again, however, Monahan expressly discloses
that ovarian cancer biomarkers are detectable in uterine washes, as noted
above. See Monahan ¶¶ 54, 129. Accordingly, given the express disclosures
in Monahan, and given Appellant’s failure to identify any objective factual
evidence specifically contradicting Monahan’s disclosures, Appellant’s
detection of ovarian cancer biomarkers in uterine washes is an expected
result, rather than an unexpected result.
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We acknowledge Appellant’s more specific contention that it was
unexpected to be able to detect ovarian cancer biomarkers in uterine washes
from subjects with early stage ovarian cancer, as recited in Appellant’s
claim 1. See Appeal Br. 22–24. Appellant, however, fails to provide
objective evidence supporting that contention.
To the contrary, the sole objective evidence advanced by Appellant to
show detection of ovarian cancer biomarkers in uterine washes is conceded
by the Specification to be limited to advanced stage ovarian cancer patients.
See Spec. ¶ 91 (“Though this study was restricted to advanced stage HGSC
patients, it provides a foundation to explore a new approach to ovarian
cancer screening considering a putative precursor lesion within the distal
fallopian tube.”). Because the alleged evidence of unexpectedness advanced
by Appellant is not commensurate in scope with the claimed subject matter,
we are not persuaded that that evidence demonstrates the nonobviousness of
the claimed subject matter.
We acknowledge, as Appellant contends (Appeal Br. 15–16; Reply
Br. 18–20), that Lopata is directed to obtaining samples to be examined for
endometrial cancer (see Lopata, abstract). It is well settled, however, that
“[n]on-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references. . . . [The reference] must be read, not in
isolation, but for what it fairly teaches in combination with the prior art as a
whole.” In re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986)
Here, the Examiner relied on Lopata merely as evidence that methods
of obtaining uterine wash samples were known in the art. See Ans. 3. Thus,
the fact that Lopata might not be directed to detecting ovarian cancer
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biomarkers in uterine washes does not address whether it would have been
obvious to use Lopata’s methods to obtain a uterine wash to determine the
presence of ovarian cancer biomarkers, as expressly taught in Monahan.
We acknowledge, as Appellant contends (see Appeal Br. 16–21, 24–
25; Reply Br. 17–18), that Palena describes deploying its nano-getter
sensing device in the abdominal cavity (see, e.g., Palena ¶ 17), rather than in
the uterine cavity as recited in Appellant’s claim 1.
As the Supreme Court has explained, however, in determining
whether the prior art supplies a reason for practicing the claimed subject
matter, the analysis “need not seek out precise teachings directed to the
specific subject matter of the challenged claim, for a court can take account
of the inferences and creative steps that a person of ordinary skill in the art
would employ.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007);
see also id. at 421 (“A person of ordinary skill is . . . a person of ordinary
creativity, not an automaton.”). In the present case, given Monahan’s
disclosure that ovarian cancer biomarkers were detectable in uterine washes,
we agree with the Examiner that a skilled artisan would have reasonably
inferred that it would be useful to deploy Palena’s biomarker-detecting
device at the actual location where the biomarkers could be found, i.e. the
uterine cavity.
As evidence that Palena’s device would have been expected to
function in the uterine cavity, the Examiner noted that, in addition to the
abdominal cavity, “Palena further teaches a ‘nano-getter’ device may be
inserted into numerous body cavities, e.g., oral, rectal, and vaginal cavity
(see [0030], in particular).” Ans. 17. Appellant does not dispute the
Examiner’s finding. See Reply Br. 18 (“Palena refers to oral, rectal, and
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vaginal cavities as examples . . . .”). While the Levine Declaration states
that there was no reasonable expectation of success in deploying Palena’s
device in the uterine cavity, the Declaration does not cite any objective
factual evidence in support of that opinion. See Levine Decl. ¶¶ 23–15.
Given Palena’s undisputed disclosure that its device functions in a
number of distinct body cavities, we agree with the Examiner that, when
deploying the device in the uterine cavity as suggested by Monahan, a
skilled artisan had a reasonable expectation that the device would function
there as well. See In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009)
(“Obviousness does not require absolute predictability of success. . . . For
obviousness under § 103, all that is required is a reasonable expectation of
success.”) (quoting In re O’Farrell, 853 F.2d 894, 903–04 (Fed. Cir. 1988)
(emphasis removed). Given Palena’s undisputed disclosure that its device
functions in a number of distinct body cavities, we are also unpersuaded that
Palena teaches away from the claimed invention. See Appeal Br. 32.
We acknowledge, but are unpersuaded by, Appellant’s contention that
because claim 1 recites a new use for an old product (deployment of
Palena’s nano-getter device in the uterine cavity), claim 1 is necessarily
nonobvious. See Appeal Br. 30–32. As discussed above, because Monahan
discloses that ovarian cancer biomarkers were detectable in uterine washes,
we agree with the Examiner that a skilled artisan would have reasonably
inferred that it would be useful to deploy Palena’s biomarker-detecting
device at the actual location where the biomarkers could be found, i.e. the
uterine cavity.
That the process recited in Appellant’s claim 1 is not entirely
disclosed in either Monahan or Palena simply demonstrates that there are
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differences between claim 1 and those references. As the Supreme Court
has explained, however, “the mere existence of differences between the prior
art and an invention does not establish the invention’s nonobviousness.”
Dann v. Johnston, 425 U.S. 219, 230 (1976)
In sum, for the reasons discussed, we find that the preponderance of
the evidence supports the Examiner’s conclusion that the process recited in
Appellant’s claim 1 would have been obvious in view of the teachings of
Monahan, Lopata, and Palena. We, therefore, affirm the Examiner’s
rejection of that claim over those references. Because they were not argued
separately, claims 2, 3, 6, 8–10, 22–24, 26–28, and 31 fall with claim 1.
ELIGIBILITY FOR PATENTING
The Examiner’s Rejection
The Examiner found that Appellant’s claims are directed to a natural
phenomenon, which is the fact that the “recited proteins are present in the
uterine cavity of patients with early stage ovarian cancer.” Ans. 5 (emphasis
omitted).
The Examiner found that claims do not recite significantly more than
the natural phenomenon because the claims’ additional elements are limited
to “well-understood, routine and conventional steps of detecting known
ovarian cancer biomarker proteins in uterine fluid and optionally
administering generic ovarian cancer treatments to subjects with ovarian
cancer.” Id. at 5–6. In particular, the Examiner reasoned, the “device used
to detect recited biomarker proteins is not required to be any particular
device and the specification does not demonstrate the claimed method with
any device encompassed by the claims.” Id. at 6.
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Based on reasoning similar to that advanced in the obviousness
rejection discussed above, the Examiner urged that the process recited in
Appellant’s claims merely recited a conventional and routine process using
known elements. Id. at 6–7. The Examiner reasoned, therefore, that the
claimed processes were analogous to those found ineligible for patenting in
Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015).
Ans. 7–8.
Analysis
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.”).
If the claim is “directed to” a judicial exception, we turn to the
second step of the Alice and Mayo framework, where we examine the
elements of the claim to determine whether it contains an “inventive
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concept” sufficient to “transform” the claimed judicial exception into a
patent-eligible application. Alice, 573 U.S. at 221.
The PTO published revised guidance earlier this year on the
application of § 101. USPTO, 2019 Revised Patent Subject Matter
Eligibility Guidance, 84 Fed. Reg. 50 (January 7, 2019) (“Memorandum” or
“Office Guidance”).10 Following the Office Guidance, 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 a specific limitation beyond the judicial
exception that are not “well-understood, routine, conventional”
in the field (see MPEP § 2106.05(d)); or
(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 Memorandum.
In the present case, the Examiner does not persuade us that
Appellant’s claims are directed to subject matter that is ineligible for
patenting.

10 Available at https://www.govinfo.gov/content/pkg/FR-2019-01-
07/pdf/2018-28282.pdf.
Appeal 2018-000311
Application 13/624,922

19
As to Revised Step 2A, Prong 1 of the Office Guidance (see 84 Fed.
Reg. at 54), we agree with the Examiner that claim 1, the only independent
claim on appeal, includes a recitation of natural phenomena. Specifically,
claim 1 recites detecting at least one of CA-125, HE4, mesothelin, and YKL-
40, which are undisputedly naturally occurring proteins indicative of the
presence of ovarian cancer. See Appeal Br. 45.
However, as to Revised Step 2A, Prong 2 of the Office Guidance (see
84 Fed. Reg. at 54–55), we find that claim 1 includes additional elements
sufficient to integrate the judicial exception into a practical application.
Specifically, as Appellant argues (see Appeal Br. 35, 39), claim 1 recites
using a specific device—a device that is capable of deployment in the
uterine cavity and is configured to detect the particular biomarkers recited in
the claim. See id. at 45. As explained in Appellant’s Specification, one
example of such a device is a nano-getter device that contains antibodies to
the claim-recited protein biomarkers. Spec. ¶¶ 83–86 (Example 2).
Because Appellant’s claim 1 thus includes additional elements that
implement the judicial exception in conjunction with “a particular machine
or manufacture that is integral to the claim,” see Office Guidance, 84 Fed.
Reg. at 55, we are persuaded that claim 1 integrates the judicial exception
into a practical application.
Indeed, because Appellant’s claim 1 is limited to using a specific
device having a particularized combination of features, we agree with
Appellant that, in addition to the natural phenomena, claim 1 recites
elements sufficient to apply the judicial exceptions in a meaningful way
beyond a mere drafting effort designed to monopolize the exceptions
(naturally occurring proteins indicative of ovarian cancer) recited in the
Appeal 2018-000311
Application 13/624,922

20
claim. See id. The fact that the prior art cited in the obviousness rejection
(Palena) might teach or suggest devices similar to those recited in the claims
does not persuade us that the claims are ineligible for patenting. See id. at
54 (“[A] claim that includes conventional elements may still integrate an
exception into a practical application, thereby satisfying the subject matter
eligibility requirement of Section 101.”).
In sum, for the reasons discussed, we conclude that although
Appellant’s independent claim 1 recites natural phenomena, claim 1 recites
additional elements that integrate the natural phenomena into a practical
application. Because we conclude, therefore, that claim 1 is not directed to
subject matter that is ineligible for patenting, we reverse the Examiner’s
rejection of claim 1, and its dependent claims, on that ground.

SUMMARY
For the reasons discussed, we affirm the Examiner’s rejection of
claims 1–3, 6, 8–10, 22–24, 26–28, and 31, for obviousness over Monahan,
Lopata, and Palena.
For the reasons discussed, we reverse the Examiner’s rejection of
claims 1–3, 6, 8–10, 22–24, 26–28, and 31, as being directed to subject
matter ineligible for patenting.

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).

AFFIRMED