Makoto Watanabe et al.

Patent Trials and Appeals Board

Aug 5, 2019

14852308 - (D) (P.T.A.B. Aug. 5, 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.
14/852,308 09/11/2015 Makoto Watanabe OKA-0320/DIV 5757
74384 7590 08/05/2019
Cheng Law Group, PLLC
1133 13th St. N.W.
Suite C2
Washington, DC 20005
EXAMINER
AEDER, SEAN E
ART UNIT PAPER NUMBER
1642
MAIL DATE DELIVERY MODE
08/05/2019 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
_____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_____________

Ex parte MAKOTO WATANABE, EIICHI MATSUO, NAOKI KANEKO,
TOSHIYA MATSUBARA, OSAMU NISHIMURA, MASAKI MORI,
HIDEO MATSUDA, SHIGETO SENO, and ICHIRO TAKEMASA
_____________

Appeal 2018-004691
Application 14/852,308
Technology Center 1600
_____________

Before JEFFREY N. FREDMAN, JOHN G. NEW, and JAMIE T. WISZ,
Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL

Appellants1,2 appeal under 35 U.S.C. § 134 from the Final Rejection
of claims 5 and 9–14, which are all the claims pending in the present
application. We have jurisdiction over the appeal under 35 U.S.C. § 6(b).
We affirm.

1 Appellants identify Shimadzu Corporation and Osaka University as the real
parties in interest. App. Br. 2.
2 We have considered and herein refer to the Specification of Sept. 11, 2015
(“Spec.”); Final Office Action of June 19, 2017 (“Final Act.”); Appeal Brief
of Dec. 17, 2017 (“App. Br.”); Examiner’s Answer of Jan. 31, 2018
(“Ans.”), and Reply Brief of Mar. 30, 2018 (“Reply Br.”).

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CLAIMED SUBJECT MATTER
“As typical colon cancer markers, Carcinoembryonic antigen-related
cell adhesion molecule 5 (CEA) and Carbohydrate Antigen 19-9 (CA19-9)
are known.” Spec. 1:21–23. The prior art “reports that Galectin-1, Galectin-
3, and Galectin 4 are effective as plasma markers for colon cancer.” Spec.
2:3–5.
The present invention relates generally to techniques for “clinical
diagnosis and screening of colon cancer” using a “multiplex colon cancer
marker panel.” Spec. 1:13–15. Independent claim 5 is illustrative of the
claims on appeal and recites:
5. A method of detecting colon cancer comprising the steps
of:
preparing a blood plasma sample by treating whole blood
collected from an individual,
measuring the blood plasma sample by an assay based on
biospecific affinity or a quantitative mass spectrometry method
to acquire respective measured values of five colon cancer
markers of Carcinoembryonic antigen-related cell adhesion
molecule 5, Carbohydrate antigen 19-9, Galectin-4, APEX
nuclease, and Actin-related protein 2 in the blood plasma
sample;
normalizing the respective measured values of the five
colon cancer markers sigmoidally based on an extreme-value
distribution to derive respective probability scores of the five
colon cancer markers and deriving an average of the probability
scores; and
detecting the presence or absence of the colon cancer for
the individual based on whether the average of the probability
scores is higher or lower than a criterion value for the five colon
cancer markers.
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REJECTIONS ON APPEAL
Claims 5 and 9–14 stand rejected under 35 U.S.C. § 101 as directed to
judicial exceptions of abstract idea and law of nature. Final Act. 2–6.

ANALYSIS
Appellants appeal the Examiner’s rejection of claims 5 and 9–14 as
ineligible subject matter under § 101. App. Br. 5–9. All of the rejected
claims are argued together as a group. See App. Br. 9 (“claims 9–14 are
allowable for the same reasons noted above with regard to claim 5”). As
such, we select claim 5 as representative of the rejected claims, and we
decide the appeal of the rejection of all of the rejected claims on the basis of
claim 5. See 37 C.F.R. § 41.37(c)(1)(iv).
In analyzing patent-eligibility questions under the judicial exceptions
to 35 U.S.C. § 101, the Supreme Court instructs us to “first determine
whether the claims at issue are directed to a patent-ineligible concept.” Alice
Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 218 (2014). The Court
found that “[p]henomena of nature, though just discovered, mental
processes, and abstract intellectual concepts are not patentable, as they are
the basic tools of scientific and technological work.” Mayo Collaborative
Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71 (2012) (quoting Gottschalk
v. Benson, 409 U.S. 63, 67 (1972)). If the claims are determined to be
directed to an ineligible concept we then move to a second step and
“consider the elements of each claim both individually and ‘as an ordered
combination’ to determine whether the additional elements ‘transform the
nature of the claim’ into a patent-eligible application.” Alice at 217 (quoting
Mayo, 566 U.S. at 97).
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In addition to this direction by the Supreme Court, the U.S. Patent and
Trademark Office published revised guidance on the application of § 101.
USPTO’s January 7, 2019 Memorandum, 2019 Revised Patent Subject
Matter Eligibility Guidance (“2019 Guidance Memorandum”). Under this
guidance, in step one of the Mayo/Alice framework, we first look to whether
the claim recites:
(Prong 1) any judicial exceptions, including “[l]aws of nature,
natural phenomena, and abstract ideas,” (quoting Alice, 573
U.S. at 216) and/or 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) (Guidance Step 2A, Prong 1); and
(Prong 2) additional elements that integrate the judicial exception
into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)),
i.e., considering the claim as a whole, does it impose a
meaningful limit on the judicial exception so as to be more than
a drafting effort to circumvent patent-ineligibility for a judicial
exception.
Furthermore, under the guidance, regarding step two of the Mayo/Alice
framework, only if a claim is determined to (1) recite a judicial exception
and (2) not integrate that exception into a practical application, do we then
look to whether the claim:
(3) adds a specific limitation beyond the judicial exception that
is 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.
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The Board is required to adhere to the 2019 Guidance as a matter of
Office policy. Id. at 51.3
2019 Guidance Step 1
First, under “Step 1,” we consider whether the claimed subject matter
falls within the four statutory categories set forth in § 101, namely
“[p]rocess, machine, manufacture, or composition of matter.” 2019
Guidance 53–54; see 35 U.S.C. § 101. Claim 5 recites a “method” and, thus,
falls within the “process” category. Consequently, we proceed to the next
step of the analysis.
2019 Guidance Step 2A Prong 1
Second, under “Step 2A [] Prong One,” we evaluate “whether the
claim recites a judicial exception, i.e., an abstract idea, a law of nature, or a
natural phenomenon.” 2019 Guidance 54; see Alice, 573 U.S. at 216. The
Examiner determined that the rejected claims recite a law of nature or
natural phenomenon because they recite the natural phenomenon that “levels
of recited markers mathematically correlate with [] the presence and absence
of colon cancer.” Ans. 6. Additionally, the Examiner determined that the
mathematical “normalizing step is merely an abstract idea. Ans. 6. We
agree with these conclusions, and Appellants’ arguments to the contrary are
unpersuasive for the following reasons.
Appellants contend that the steps of claim 5 “do not recite or describe
any recognized exception. [See, e.g.,] Mayo . . . (recited steps of

3 Although the Office Action at issue, as well as all the briefing for this
appeal, was completed before the 2019 Guidance was issued, the 2019
Guidance “applies to all applications . . . filed before, on, or after January 7,
2019.” 2019 Guidance at 50.
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administering a drug to a patient and determining the resultant level of 6-
thioguanine in the patient ‘are not themselves natural laws’).” App. Br. 6.
Appellants further contend “in the present invention method, measured
values of five specific colon cancer markers are transformed to respective
probability scores. Accordingly, it is clear that the essential features of the
invention of claim 5 are not directed to a natural product itself, an abstract
idea or a natural phenomenon.” App. Br. 7.
We find this argument unpersuasive because Mayo stated that the
patents at issue “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.” Mayo,
566 U.S. at 77. Claim 5 also sets forth a natural relationship between the
amounts of five colon cancer markers and the presence or absence of colon
cancer in a patient. In the portion of Mayo referred to by Appellants
regarding administering, determining, and wherein steps, Mayo explains that
“[t]hese additional steps are not themselves natural laws but neither are they
sufficient to transform the nature of the claim.” Id. at 78.
Claim 5 is similar to the claim held to recite a law of nature in
Cleveland Clinic Foundation v. True Health Diagnostics LLC, 859 F.3d
1352 (Fed. Cir. 2017). In that case, the Federal Circuit examined a claim to
a method wherein the amount of “myeloperoxidase [(MPO)] in a bodily
sample” is determined and compared to MPO levels in control subjects,
which indicates “the extent of the test subject’s risk of having atherosclerotic
cardiovascular disease.” Id. at 1356. Similarly, claim 5 recites, “detecting
the presence or absence of the colon cancer,” and comparing that value to
“whether the average of the probability scores is higher or lower than a
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criterion value for the five colon cancer markers,” which indicates whether
the subject has “colon cancer.” Just as the Federal Circuit determined the
claims in Cleveland Clinic to be directed to a natural law (i.e., the
correlation between MPO and heart disease), we determine claim 5 here to
recite a natural law, namely the correlation between five particular colon
cancer markers and the presence or absence of colon cancer in a patient. See
Cleveland Clinic, 859 F.3d at 1361.
We also agree with the Examiner that claim 5 recites an abstract idea,
specifically a mathematical concept. Specifically, as the Examiner found,
claim 5 recites, “normalizing the respective measured values of the five
colon cancer markers sigmoidally based on an extreme-value distribution to
derive respective probability scores of the five colon cancer markers and
deriving an average of the probability scores,” which is a mathematical
analysis of the law of nature data. Final Act. 5. As such, claim 5 recites a
mathematical concept, which is one of the three groupings of subject matter
that the 2019 Guidance designates as meeting the abstract idea exception.
2019 Guidance 52. While the Federal Circuit has “recognize[d] that
defining the precise abstract idea of patent claims in many cases is far from a
‘straightforward’ exercise.” Synopsys, Inc. v. Mentor Graphics Corp., 839
F.3d 1138, 1150 (Fed. Cir. 2016), the Federal Circuit explained that “we
continue to ‘treat[] analyzing information by steps people [could] go through
in their minds, or by mathematical algorithms, without more, as essentially
mental processes within the abstract-idea category.’” Id. at 1146–47
(citation omitted).
We find the mathematical concept in claim 5 is similar to that in
SmartGene, where the Federal Circuit held that claims directed to
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“comparing new and stored information and using rules to identify medical
options” did not satisfy Alice step one. See SmartGene, Inc. v. Advanced
Biological Labs., SA, 555 F. App’x 950, 951–52, 955–56 (Fed. Cir. 2014)
(nonprecedential). As in SmartGene, the “normalizing” and “deriving” steps
do not rely on an inventive device or technique for displaying information or
new techniques for obtaining biological information, but rather constitute a
recitation of steps for mathematically manipulating data associated with a
natural phenomenon. See SmartGene, 555 Fed. Appx. at 954 (holding
claims were patent ineligible because they did “no more than call on a
‘computing device,’ with basic functionality for comparing stored and input
data and rules, to do what doctors do routinely.”).

3. 2019 Guidance Step 2A Prong 2
Having determined that claim 5 recites a law of nature/natural
phenomenon and a mathematical concept, we proceed to “Step 2A[] Prong
Two” of the 2019 Guidance, which requires that we evaluate whether “the
claim as a whole integrates the recited judicial exception into a practical
application of that exception.” Id. at 54. “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.” Id.; see Mayo, 566 U.S. at 78.
The 2019 Guidance specifies that this evaluation is conducted by first
“[i]dentifying whether there are any additional elements recited in the claim
beyond the judicial exception(s)”, then “evaluating those additional elements
individually and in combination to determine whether they integrate the
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exception into a practical application.” 2019 Guidance 54–55. The
Examiner determined that, aside from the recited judicial exceptions, claim 5
did
not include additional elements that are sufficient to amount to
significantly more than the judicial exception because the
additional elements (common methods of detecting proteins)
are routinely performed in the art to obtain data regarding
protein levels. The claims do not recite something
“significantly more” than the judicial exception(s); rather, the
claims “simply inform” the natural phenomenon to one
performing routine active method steps and do not amount to
significantly more than the judicial exception(s).
Final Act. 3. According to the Examiner, measuring CEACAM5,
CA 19-9, LGALS4, APEX1, and ACTR2 by quantitative mass spectrometry
was an established, common technique. Id. at 3. Further, the Examiner
cited two references, Mackay4 and Spetzler,5 to establish that “measuring
proteins in plasma samples using methods such as biospecific
affinity assays” and that “detecting each recited marker in samples such as
plasma and using either biospecific affinity or mass spectrometry
techniques” were routine and conventional. Id. Based on the above, the
Examiner concluded that the claim does not integrate the recited judicial
exceptions into a practical application. Id. We agree even considering
Appellants’ arguments, as explained further below.
Step 2A Prong 2 of the 2019 Guidance is a change from prior
guidance from the Office regarding § 101 that was in effect at the time

4 Mackay et al., Role of Serial Plasma C.E.A. Assays in Detection of
Recurrent and Metastatic Colorectal Carcinomas, 4 British Medical J. 382–
385 (1974).
5 Spetzler et al., US 2014/0148350 A1, published May 29, 2014.
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Appellants submitted their briefing in this appeal. See 2019 Guidance 54
(“Prong Two represents a change from prior guidance.”). Nonetheless, as
the 2019 Guidance applies to applications filed before it was issued (id. at
50), we consider arguments presented by Appellants addressing issues
relevant to Step 2A Prong 2.
Appellants contend
claim 5 recites, “normalizing the respective measured values of
the five colon cancer markers sigmoidally based on an extreme-
value distribution to derive respective probability scores of the
five colon cancer markers and deriving an average of the
probability scores” and Applicant submits that this step, and
more particularly, this step in combination with the measuring
step of claim 5, is “significantly more” than a natural
correlation between biomarkers and colon cancer diagnosis.
App. Br. 8.
We are not persuaded that the combination includes elements beyond
the judicial exceptions. Step 2A Prong 2 requires that only “any additional
elements recited in the claim beyond the judicial exception(s)” be
considered. 2019 Guidance 54–55 (emphasis added). As discussed above,
both the correlation between the five colon cancer markers and the presence
or absence of colon cancer and the mathematical method of normalizing the
correlation values are subject matter falling under judicial exceptions to
§ 101. Thus, the only remaining elements recited in claim 5 are “preparing a
blood sample” and “measuring the blood plasma sample by an assay based
on biospecific affinity or a quantitative mass spectrometry”. The Examiner
expressly considered these elements, individually and in combination. Ans.
4–5.
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Appellants also contend that the “five markers have markedly
different characteristics based on structure, function and/or properties
than other product of nature, as demonstrated in Reference Example 3 in the
present [S]pecification.” App. Br. 7.
We find this unpersuasive because, as an initial matter, the
relationship between these five markers and the presence or absence of colon
cancer (i.e., the recited correlation) is not an additional element because it
recites a natural law, as discussed above. Further, the Examiner found that
determining CEACAM5, CA 19-9, LGALS4, APEX1, and ACTR2 levels
using either bioaffinity or mass spectrometry methods as recited in claim 5
were established techniques, citing specific prior art literature including
Mackay and Spetzler as evidence. Final Act. 3. Thus, the Examiner
considered the combination of elements Appellants rely on, and Appellants
do not explain why these findings are inadequate.
Moreover, we note that “add[ing] insignificant extra-solution activity
to the judicial exception” is insufficient to integrate the exception into a
practical application (2019 Guidance 55). Data gathering steps typically
constitute such insignificant extra-solution activity. See Mayo Collaborative
Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 79 (2012) (concluding that
additional element of measuring metabolites of a drug administered to a
patient was insignificant extra-solution activity); OIP Techs., Inc. v.
Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015) (holding that mere
data gathering is insufficient to confer patent eligibility). Here, the
“preparing” and “measuring” steps, including the recited bioaffinity or mass
spectrometry methods, gather the data (i.e., determine levels of the five
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markers) necessary to conduct the recited comparing and correlating (i.e.,
the judicial exceptions).
Moreover, “generally link[ing] the use of a judicial exception to a
particular technological environment or field of use” is insufficient to
integrate a judicial exception into a practical application. 2019 Guidance 55.
See Parker v. Flook, 437 U.S. 584, 595 (1978) (determining that limiting an
ineligible alarm limit calculation to specific process variables in a chemical
process was insufficient for patent eligibility).
In addition, we note that Appellants did not demonstrate error in the
Examiner’s conclusion that “methods encompassed by the instant claims are
well-known, routine, and conventional.” Final Act. 3. Nor did Appellants
argue, much less demonstrate, that claim 5 “uses a judicial exception to
effect a particular treatment or prophylaxis for a disease or medical
condition,” implements or uses a judicial exception with “a particular
machine or manufacture that is integral to the claim,” or “effects a
transformation or reduction of a particular article to a different state or
thing.” 2019 Guidance 55; see MPEP 2106.05(a)–(c), (e).
For the above reasons, Appellants have not shown that the Examiner
erred in concluding that claim 5 does not integrate the recited judicial
exceptions into a practical application.
4. 2019 Guidance Step 2B
Having concluded that claim 5 recites judicial exceptions but does not
integrate them into a practical application—i.e., that the claim is “directed
to” those exceptions (2019 Guidance 54)—we finally turn to whether the
claim provides an “inventive concept,” i.e., whether the additional elements
beyond the exceptions, individually and in combination, amount to
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“significantly more” than the exceptions themselves. Id. at 56. According
to the 2019 Guidance, “[a]dd[ing] a specific limitation or combination of
limitations that are not well-understood, routine, conventional activity in the
field” may indicate an inventive concept is present. Id. Conversely, “simply
append[ing] well-understood, routine, conventional activities previously
known to the industry, specified at a high level of generality,” typically
indicates an inventive concept is absent. Id.
As discussed above, the Examiner correctly determined that the only
“additional” elements recited in claim 5 are the “preparing” and “measuring”
steps. Final Act. 3. The Examiner further found that the “methods
encompassed by the instant claims are well-known, routine, and
conventional.” Id. Specifically, the Examiner found that claim 5 does “not
recite something ‘significantly more’ than the judicial exception(s); rather,
the claims ‘simply inform’ the natural phenomenon to one performing
routine active method steps and do not amount to significantly more than the
judicial exception(s)”. Ans. 4–5.
In addition, the Examiner found that
Even the instant specification acknowledges that mass
spectrometry and biospecific affinity assays are routine and
conventional in the art by disclosing: “The assay based on
biospecific affinity is well-known to those skilled in the art [. . .
] an immunoassay is preferred [. . . . ]A specific protocol of the
immunoassay can be easily selected by those skilled in the art [.
. . . ]Alternatively, the colon cancer markers may be measured
based on mass spectrometry. A method of mass spectrometry [.
. . ]can be appropriately selected by those skilled in the art”
([see] pages 14[–]15 of the instant specification).
Ans. 4. The Examiner also notes “the additional elements (common
methods of detecting proteins) are routinely performed in the art to obtain
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data regarding protein levels.” Ans. 4. We agree and find Appellants’
arguments unpersuasive, as explained below.
Appellants contend that
in the normalizing step of the present invention, measured
values of the specific five colon cancer markers are transformed
to respective probability scores. This transformation of
measured values of the specific five colon cancer markers to
respective probability scores is not disclosed in the prior art and
therefore, is not a well-known, conventional and routine step
performed in the art.
App. Br. 8. Appellants further contend “the essential features of the
present invention (i.e., both the measuring step, and the subsequent
normalizing step) are not well-understood, routine, conventional activities
and amount to ‘significantly more’ than a natural correlation between
biomarkers and colon cancer diagnosis.” App. Br. 9.
We find these arguments unpersuasive for similar reasons as for Step
2A Prong 2. The addition of the abstract mathematical analysis of
“normalizing” to the natural correlation of five colon cancer markers and
colon cancer does not add significantly more because “[a]dding one abstract
idea . . . to another abstract idea . . . does not render the claim non-abstract.”
RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327 (Fed. Cir. 2017).
“A claim directed to an abstract idea does not automatically become eligible
merely by adding a mathematical formula. . . . The addition of a
mathematical equation that simply changes the data into other forms of data
cannot save it.” Id. at 1328. The mathematical analysis recited in claim 5
converts measured values of the five colon cancer markers into an average
of probability scores.
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Appellants point to no additional steps that could not be performed
mentally or without using a generic computer. The use of a generic
computer to perform generic computer functions that are “well-understood,
routine, conventional activit[ies]” previously known in the industry is not
enough to transform the abstract idea into a patent-eligible invention. See
Alice, 573 U.S. at 225–26.
As noted above, the Examiner cited specific evidence to support the
findings that the additional elements of claim 5 were well-understood,
routine and conventional. See Final Act. 4–5. Moreover, we note the
Specification itself states that the “assay based on biospecific affinity is
well-known to those skilled in the art and is not particularly limited.” Spec.
14:9–11. According to the Specification, the “method of mass spectrometry
is not particularly limited as long as it can perform quantitative analysis, and
can be appropriately selected by those skilled in the art.” Spec. 15:7–10.
The Specification, thus, supports the Examiner’s finding that the recited
detection and quantitation of colon cancer markers using affinity assays or
mass spectrometry was well-understood, routine and conventional.
Thus, for the reasons explained above, we agree with the Examiner
that claim 5 “simply appends well-understood, routine, conventional
activities previously known to the industry, specified at a high level of
generality,” and, thus, fails to present an “inventive concept” because the
claim does not recite additional elements that provide “significantly more”
than the recited judicial exceptions. See 2019 Guidance 56. Therefore, we
sustain the Examiner’s rejection of claim 5 as ineligible subject matter under
§ 101. As a result, we also sustain the rejection of claims 9–14 under § 101.
See 37 C.F.R. § 41.37(c)(1)(iv).
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DECISION
We affirm the Examiner’s rejection of claims 5 and 9–14 under
35 U.S.C. § 101.

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