Joseph Sung et al.

Patent Trials and Appeals Board

Nov 15, 2021

2021001155 (P.T.A.B. Nov. 15, 2021)

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.
12/646,839 12/23/2009 Joseph Jao Yiu Sung 080015-0780481-000200US 1846
20350 7590 11/15/2021
Kilpatrick Townsend & Stockton LLP - West Coast
Mailstop: IP Docketing - 22
1100 Peachtree Street
Suite 2800
Atlanta, GA 30309
EXAMINER
POHNERT, STEVEN C
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
11/15/2021 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):
KTSDocketing2@kilpatrick.foundationip.com
ipefiling@kilpatricktownsend.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JOSEPH JAO YIU SUNG, JUN YU, and KIN FAI
____________

Appeal 2021-001155
Application 12/646,839
Technology Center 1600
____________

Before DONALD E. ADAMS, ERIC B. GRIMES, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 1, 6, 7, 12, and 21–24 (Appeal Br. 3). We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as “The Chinese
University of Hong Kong, Hong Kong Special Administrative Region,
CHINA” (Appellant’s May 22, 2020, Appeal Brief (Appeal Br.) 3).
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STATEMENT OF THE CASE
Appellant’s disclosure relates to “markers for gastric cancer, and
methods for the inhibition of gastric cancer” (Spec.2 1). Appellant’s claim 1,
the only independent claim on appeal, is reproduced below:
1. A method for assessing likelihood of mortality from gastric
cancer, the method comprising the steps of:
(a) treating genomic DNA isolated from a gastric cancer sample
with a bisulfite, wherein the gastric cancer sample is taken from
a human patient diagnosed with stage I-III gastric cancer;
(b) performing a polymerase chain reaction (PCR) to amplify
the treated genomic DNA following step (a) with primers
consisting of the nucleotide sequences of SEQ ID NO:43 and
SEQ ID NO:44;
(c) determining nucleotide sequence of the amplified DNA
from step (b) to detect DNA that has been amplified from a
methylated version of the genomic DNA; and
(d) determining, based on the presence of the amplified
methylated genomic DNA from step (c), a higher likelihood of
mortality for the patient compared with another stage I-III
gastric cancer human patient whose gastric cancer sample
shows absence of amplified methylated genomic DNA after
being processed through steps (a) to (c).
(Appeal Br. 10.)

2 Appellant’s December 23, 2009, Specification.
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Grounds of rejection before this Panel for review:
I. Claims 1, 6, 7, and 243 stand rejected under 35 U.S.C. § 103(a)
as unpatentable over Cheung,4 Freije,5 Dieffenbach,6 and
Roux.7
II. Claims 12, 21, and 22 stand rejected under 35 U.S.C. § 103(a)
as unpatentable over Cheung, Freije, Dieffenbach, Roux, and
Hogan.8
III. Claim 23 stands rejected under 35 U.S.C. § 103(a) as
unpatentable over Cheung, Freije, Dieffenbach, Roux, Hogan,
and Yao.9

3 Examiner’s statement of the rejection includes a harmless typographical
error, listing Appellant’s claim 23, instead of claim 24, as part of this
rejection (see Examiner’s October 7, 2020, Answer (Ans.) 3; cf. Ex parte
Sung et al., 2019 WL 2208890 (PTAB April 25, 2019) (Decision) n.2;
Appeal Br. 3, n. 1). We, therefore, address the merits of this rejection as it
relates to claims 1, 6, 7, and 24.
4 Cheung et al., Epigenetic Characterization of a Novel Tumor Suppressor
Gene, Rnf180, in Gastric Cancer and Its Application in Noninvasive Cancer
Detection, 134 GASTROENTEROLOGY A-382 (2008).
5 Freije et al., WO 2007/102891 A2, published Sept. 13, 2007.
6 Dieffenbach et al., General Concepts for PCR Primer Design, 3 PCR
METHODS APPL. 30–37 (1993).
7 Roux, Optimization and Troubleshooting in PCR, 4 PCR METHODS
APPL. 185–194 (1995).
8 Hogan et al., US 5,541,308, issued July 30, 1996.
9 Yao et al., Evaluation of Minor Groove Binding Probe and Taqman Probe
PCR Assays: Influence of Mismatches and Template Complexity on
Quantification, 20 MOLECULAR & CELLULAR PROBES 311–316
(2006).
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This is the second Appeal of Appellant’s claimed invention (see
Decision *1). The prior art rejections before this Panel are the same as those
affirmed by the prior Panel (see id. at *1–*4). The “prosecution history is
not disputed” (Reply Br.10 2). The only difference between this Appeal and
the prior Appeal is “the Rule 132 declaration that was signed by inventor Dr.
Jun Yu [(Yu Decl.)] and submitted with Appellant’s response of June 24,
2019, to provide information not before the PTAB at the time of the appeal
and therefore not considered during the [prior] appeal process (Appeal Br. 6
(emphasis omitted)).

ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?

ANALYSIS
We adopt the prior Panel’s factual findings and reasoning as it relates
to the combination of references set forth in each of Rejections I–III on this
record. For emphasis we note that the prior Panel found:
Frieje [sic] as a whole explores the correlation between
methylation of certain genes and cancer, as indicated by its title:
“Materials and Methods for Assaying for Methylation of CpG
Islands Associated with Genes in the Evaluation of Cancer.”
Further, as the Examiner explains, addressing both Frieje [sic]
and Cheung:
the prior art of Cheung specifically teaches RNF180 is a tumor
suppressor in gastric cancer and implicates the methylation of
the RNF180 core promoter (sequence amplified by claimed
primers) as a biomarker, while Freije teach SEQ ID NO 183

10 Appellant’s December 1, 2020, Reply Brief.
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which comprises the RNF180 core promoter and the sequences
or complement of SEQ ID NO 43 and SEQ ID NO 44. Further
Frieje [sic] teaches, “The invention also provides methods of
prognosticating cancer by assaying for the methylation of one
or more genes that are indicative of the grade or stage of the
cancer, and/or the length of disease-free survival following
treatment for cancer” (0025, page 10 of Frieje).
Ans. 16. Thus, the combination of references relied upon by
the Examiner provides a reasonable expectation of successfully
predicting the likelihood of patient mortality relative to another
stage I-III gastric cancer human patient based on methylation
state of the amplified genomic DNA.
(Decision *3–*4.)
Yu declares:
The Board’s reasoning is incorrect because it fails to take into
consideration an important scientific fact: albeit somewhat
related, the initial onset of a disease and its progression are two
biological processes involving substantially different molecular
mechanisms. At or just prior to the initial stage of disease
emergence, a series of relevant molecular events take place in
an environment that is still relatively normal or under near
physiological conditions. In contrast, at a later stage of disease
development a different set of molecule events contribute to
disease progression, up to and including mortality, under
severely abnormal or pathological conditions. The divergence
of diagnostic markers and prognostic markers can be better
understood considering how different subpopulations of
patients emerge after the initial diagnosis: while these patients
may share some of the common molecular events responsible
for the disease occurrence, they undergo different subsequent
molecular changes, which are responsible for different courses
of disease progression, e.g., differences in mortality. As such,
there is a substantial likelihood that a biomarker useful for
diagnosing gastric cancer cannot serve as a suitable biomarker
for predicting patient mortality.
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(Yu Decl. ¶ 5; see also Appeal Br. 7 (citing Yu Decl. ¶ 5); Reply Br. 4
(citing Yu Decl. ¶ 5.)) Declarant failed to direct attention to an evidentiary
basis supporting the foregoing statements. Nonetheless, even if we assume,
for the purposes of this Appeal, that Yu’s statements are factually correct,
we find that the preponderance of evidence on this record falls in favor of
Examiner’s rejections.
As Examiner explains, “the declaration provides no evidence that
RNF180 promoter methylation detection in gastric cancer[, as is suggested
by the combination of prior art relied upon by Examiner,] is not correlated
with mortality” (Ans. 12; cf. Decision *4 (The prior Panel found that “the
combination of references relied upon by the Examiner provides a
reasonable expectation of successfully predicting the likelihood of patient
mortality relative to another stage I-III gastric cancer human patient based
on methylation state of the amplified genomic DNA”)). Stated differently,
even if Yu’s broad generic statements regarding molecular modifications
that may generically occur during disease progression are correct, Yu’s
testimony fails to specifically address the specific disclosures of the prior art
relating to, and making obvious, the specific method set forth in Appellant’s
claimed invention.
Similarly, Yu’s generic unsupported statements regarding “observed
diagnostic markers [that] turn out to be very poor or completely unusable as
prognostic markers” and discussion of markers that are outside the scope of
the combination of prior art on this record fails to outweigh Examiner’s
prima facie case of obviousness that relies on a combination of prior art that
addresses and makes obvious the use of the specific marker required by
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Appellant’s claimed method (see Yu Decl. ¶ 6; see also Appeal Br. 7 (citing
Yu Decl. ¶ 6);Reply Br. 4 (citing Yu Decl. ¶ 6); cf. Decision *1–*4).
For the foregoing reasons, having reconsidered the evidence relied
upon by Examiner, and the prior Panel, in the context of the Yu Declaration,
we find that the preponderance of evidence on this record fails to support
Yu’s statement that “there is no reasonable expectation that RNF180 will
turn out to be a suitable marker for predicting mortality. Only actual
experimentation can provide the definitive answer whether or not RNF180 is
a usable marker for predicting gastric cancer mortality” (Yu Decl. ¶ 7; see
also Appeal Br. 7–8; Reply Br. 4–5; cf. Decision *4 (The prior Panel found
that “the combination of references relied upon by the Examiner provides a
reasonable expectation of successfully predicting the likelihood of patient
mortality relative to another stage I-III gastric cancer human patient based
on methylation state of the amplified genomic DNA”)). “Appellant agrees
that the law does not require absolute predictability” (Reply Br. 3).
Having found no deficiency in the combination of Cheung, Freije,
Dieffenbach, and Roux, we are not persuaded by Appellant’s contention that
Hogan or Yao fail to make up for Appellant’s asserted deficiency in Cheung,
Freije, Dieffenbach, and Roux (see Appeal Br. 8).
We decline to address arguments presented for the first time in
Appellant’s Reply Brief. See Ex parte Borden, 93 USPQ2d 1473, 1474
(BPAI 2010) (informative) (“[T]he reply brief [is not] an opportunity to
make arguments that could have been made in the principal brief on appeal
to rebut the Examiner’s rejections, but were not.”).

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CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness.
Rejection I: The rejection of claim 1 under 35 U.S.C. § 103(a) as
unpatentable over Cheung, Freije, Dieffenbach, and Roux is affirmed.
Claims 6, 7, and 24 are not separately argued and fall with claim 1.
Rejection II: The rejection of claim 12 under 35 U.S.C. § 103(a) as
unpatentable over Cheung, Freije, Dieffenbach, Roux, and Hogan is
affirmed. Claims 21 and 22 are not separately argued and fall with claim 12.
Rejection III: The rejection of claim 23 under 35 U.S.C. § 103(a) as
unpatentable over Cheung, Freije, Dieffenbach, Roux, Hogan, and Yao is
affirmed.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 6, 7, 24 103 Cheung, Freije,
Dieffenbach, Roux
1, 6, 7, 24
12, 21, 22 103 Cheung, Freije,
Dieffenbach,
Roux, Hogan
12, 21, 22
23 103 Cheung, Freije,
Dieffenbach,
Roux, Hogan, Yao
23
Overall
Outcome
1, 6, 7, 12,
21–24

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Application 12/646,839

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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) (2019).

AFFIRMED