Eiken Kagaku Kabushiki Kaisha

Patent Trials and Appeals Board

Dec 3, 2021

2021000598 (P.T.A.B. Dec. 3, 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.
15/537,121 06/16/2017 Satoru Michiyuki 046124-5451 8226
9629 7590 12/03/2021
Morgan, Lewis & Bockius LLP (WA)
1111 Pennsylvania Avenue, N.W.
Washington, DC 20004
EXAMINER
SISSON, BRADLEY L
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
12/03/2021 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):
karen.catalano@morganlewis.com
patents@morganlewis.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SATORU MICHIYUKI
Appeal 2021-000598
Application 15/537,121
Technology Center 1600
Before JEFFREY N. FREDMAN, TIMOTHY G. MAJORS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims to a probe for single nucleotide
polymorphism detection and a method of its use. We have jurisdiction under
35 U.S.C. § 6(b).
We Affirm In Part.

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 Eiken Kagaku
Kabushiki Kaisha. (Appeal Br. 1.)
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Application 15/537,121

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STATEMENT OF THE CASE
Appellant’s Specification explains that “a polymorphism caused by
replacement of one base in a [nucleotide] sequence is particularly designated
as a single nucleotide polymorphism [SNP].” (Spec. ¶ 3.) The appearance
frequency of SNPs “is the highest among those of mutations found in the
human genome.” (Id.)
Appellant’s Specification explains that “[v]arious detection methods
and detection probes for the SNP have been developed so far,” including “a
fluorescence labeled probe method.” (Id. ¶ 5.) “In this method, it is
determined whether or not the SNP is present in a sequence of a target
nucleic acid depending on a difference in the hybridization efficiency
attained when a fluorescence labeled probe is perfectly matched or
mismatched with the target nucleic acid.” (Id.) “[F]luorescence labeled
probe[s] comprising a region for detecting the SNP, a region for recognizing
a sequence in the vicinity of the SNP and a region for connecting these two
regions to each other ha[ve] been developed.” (Id.) For example, the
Specification describes the following prior art probes:
an oligonucleotide comprising: a switch domain comprising (a)
a nucleic acid region complementary to a first sequence of
nucleic acid residues of a target nucleic acid and (b) at least one
cross-linking domain and at least one binding domain, in which
the switch domain is capable of distinguishing (i) a second
sequence of the nucleic acid residues of the target nucleic acid
complementary to the binding domain from (ii) a second
sequence of the nucleic acid residues of the target nucleic acid
comprising at least one nucleic acid residue not complementary
to the binding domain under a condition where the region (a)
forms a stable double strand together with the first sequence of
the nucleic acid residues of the target nucleic acid.
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(Id. ¶¶ 6, 8 (citing Japanese Unexamined Patent Publication No. 2006-
525027).) The “cross-linking domain comprises a universal base, a non-
hydrogen bonding natural base or an analog of any of these, or a mixture of
a universal base and a non-hydrogen bonding natural base or an analog of
any of these.” (Id.)
The Specification also describes the following prior art probes:
a detectably labeled probe, comprising an anchor nucleic acid
domain and a reporter nucleic acid domain, in which the anchor
and reporter domains are linked to each other via a non-
nucleoside linker, neither the anchor domain nor the reporter
domain forms a stem loop in the absence of a target nucleic
acid, (i) the probe is not extended by polymerase, (ii) the linker
is bound to the anchor domain within two nucleotides at the 3'-
end of the anchor domain, and is bound to the reporter domain
within two nucleotides at the 5'-end of reporter domain, and the
anchor domain is not bound to a detectable label.
(Id. ¶¶ 7, 8 (citing Japanese Unexamined Patent Publication No. 2013-
501508).) The Specification identifies the following problems with the prior
art probes just described. (Id. ¶ 9.) In particular, it is stated that where the
cross-linking domain is required to have a universal base of the like for
forming a prescribed structure, the problem is “that it lacks flexibility with
respect to probe design, and in addition, . . . it is more expensive than a case
where usual bases alone are used in the oligonucleotide synthesis.” (Id.)
And, where the probe includes a non-nucleotide linker, the problem is that
“it is necessary to prepare the linker separately from the anchor nucleic acid
domain and the reporter nucleic acid domain, and to synthesize these
thereafter,. . . [which] synthesis of the probe is troublesome.” (Id.)
Appellant’s invention is directed to a probe for detecting SNPs that is
different from the foregoing designs. (Id. ¶¶ 10–11.)
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Claims 1–13 and 20–29 are on appeal. Claim 1, reproduced below, is
illustrative of the claimed subject matter:
1. A probe for single nucleotide polymorphism detection to
be used for a target nucleic acid sequence where a single
nucleotide polymorphism is present, wherein the target nucleic
acid sequence comprises a first target sequence corresponding
to a region comprising the single nucleotide polymorphism, and
a second target sequence positioned on a 3' or 5' side of the first
target sequence and corresponding to a region without the
single nucleotide polymorphism,
the probe comprises a reporter region for detecting the
single nucleotide polymorphism, an anchor region, and a linker
region,
the reporter region comprises nucleotides consisting of a
sequence perfectly matching with the first target sequence when
a nucleotide of the single nucleotide polymorphism is a first
nucleotide, and mismatching with the first target sequence
when the nucleotide is a nucleotide other than the first
nucleotide; and a fluorescent dye quenching when the first
target sequence and the reporter region hybridize,
the anchor region comprises nucleotides consisting of a
sequence complementary to the second target sequence, and
the linker region links the reporter region and the anchor
region to each other, and comprises nucleotides consisting of a
sequence non-complementary to a sequence between the first
target sequence and the second target sequence in the target
nucleic acid sequence.
(Appeal Br. Appendix A: Claims, A1)

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The prior art relied upon by the Examiner is:
Name Reference Date
Hirai et al. US 2009/0176231 A1 July 9, 2009
Chun et al. US 2012/0220468 A1 Aug. 30, 2012
Wangh et al. US 2013/0295570 A1 Nov. 7, 2013
Cobb US 2014/0227683 A1 Aug. 14, 2014

DISCUSSION
The Examiner found that Cobb teaches probes and methods for their
use in detecting polymorphisms, and that in one embodiment, the probe
includes a reporter and an anchor sequence which are separated from each
other by a linker sequence. (Final Action 31 (citing Cobb Abstr.).) The
Examiner found that polymorphism “is deemed to fairly suggest detection of
single nucleotide polymorphisms.” (Id.) The Examiner found that, in fact,
Cobb teaches that a probe with a reporter “is used to report the presence of a
specific sequence or sequence variants (eg, SNPs, insertions, deletions,
etc.).” (Ans. 14 (citing Cobb ¶ 80).) The Examiner further found that Cobb
teaches the reporter sequence includes a label, such as a fluorescent label.
(Final Action 31 (citing Cobb ¶ 17).)
The Examiner found that Cobb does not specifically teach using a
fluorescent label that is quenched upon binding/hybridization (id.), but “is
deemed to provide a variety of options as to how the probe can be designed
and used” (Ans. 14). In particular, the Examiner noted that Cobb teaches
that nucleic acid probes that include first and second regions where a
quencher molecule is included in one of the regions and the other region
includes a reporter molecule were known in the art. (Ans. 6 (citing Cobb
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¶ 6).) The Examiner further found that Cobb includes a dependent claim
(claim 6) that states as its only further limitation of independent claim 1 that
“the probe does not comprise a quencher moiety.” (Id. at 13.) Thus, the
Examiner concluded that claim 1 of Cobb necessarily embodies a probe that
includes a quencher moiety or that does not include a quencher moiety. (Id.)
In addition, the Examiner found that Hirai teaches using labeled
quenching probes, including guanine quenching probes, which “is known as
so-called QProbe.” (Final Action 33 (citing Hirai ¶ 32).) The Examiner also
found that Hirai teaches the advantage of using such a guanine quenching
probe: “The use of such a probe makes it possible to verify hybridization and
dissociation easily according to a change in the signal.” (Id.) The Examiner
further found that Hirai teaches using labeled probes for detection of single
nucleotide polymorphisms. (Id. (citing Hirai ¶¶ 2, 21).)
Lastly, the Examiner found that Applicant’s Specification admits to a
number of specific examples of fluorescent dyes that are “comprised in the
QProbe.” (Final Action 34 (citing Spec. ¶ 34).)
The Examiner concluded from the foregoing teachings that it would
have been obvious to modify the Cobb probe label with
the commercially-available fluorescent dyes that are quenched
upon hybridization of probe to target for in using same, one
only has to use one label, not both fluorophore and quencher.
By using only one, and that which is commercially available,
the amount of time and resources involved in producing labeled
probes is effectively cut in half.
(Final Action 34.)
With respect to the linker required by dependent claims 3, 4, 7–9, 11,
and 12, the Examiner stated Cobb “has not been found to teach that the
linker does not comprise a universal base, or that it can be but only one kind
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of base.” (Final Action 32.) However, the Examiner concluded that such
would have been obvious from the teachings of Chun. (Id.) In particular,
the Examiner found that Chun teaches a linker “which serves to link two
probe sequences” “can be a poly(T)7 sequence.” (Id.)

Obviousness: Claims 1, 5, 22, 25, 26, and 27
Appellant does not address the method claims separately from the
composition claims. We select the composition of claim 1 as representative.
We agree with the Examiner’s conclusion that claim 1 would have been
obvious from the teachings of Cobb, Hirai, and the admitted prior art. In
affirming a multiple reference rejection under 35 U.S.C. § 103, the Board
may rely on fewer than all of the references relied on by the Examiner in an
obviousness rationale without designating it as a new ground of rejection. In
re Bush, 296 F.2d 491, 496 (CCPA 1961). Thus, that we do not rely on the
teachings of Chun to affirm the Examiner does not require that we designate
the rejection as a new ground.
Appellant argues that “[a] critical feature of the claims is fluorescence
dye quenching when the first target sequence and the reporter region
hybridize to the target nucleic acid” and that Cobb teaches away from
quenching. (Appeal Br. 14 (citing Cobb ¶ 17).) We do not find this
argument persuasive for the reasons articulated by the Examiner in the
Answer. (Ans. 13–14.) As the Examiner explained, paragraph 17 of Cobb
merely indicates a preference to not use a quencher. There is no discussion
as to why the known quenchers of the prior art (see Cobb ¶ 6) and the well-
known technique of using quenching in target sequence detection would not
work in the Cobb system. “[A] patentee preferably omits from the
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disclosure any routine technology that is well known at the time of
application.” Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254 (Fed.
Cir. 2004). And Hirai, a reference that predates Cobb, demonstrates that
fluorescent quenching probes, indeed QProbes, were known in the art well
prior to Cobb’s filing date. Thus, we do not find persuasive of error,
Appellant’s argument that Cobb does not provide an exemplification of a
probe with a quencher (Reply Br. 2).
Moreover, we agree with the Examiner’s claim differentiation
argument in light of the foregoing, and we do not find persuasive
Appellant’s argument that the Examiner has improperly “expand[ed] the
scope and contents of the prior art” (Reply Br. 2) or suggested a
modification that is unintended (Appeal Br. 18). Dependent claim 6 of Cobb
recites that the probe does not include a quencher and that is the only
difference from claim 1. Thus, claim 1 is reasonably understood to embrace
a probe that includes a quencher.
For the foregoing reasons, we affirm the Examiner’s rejection of
claims 1, 6, and 25 as being obvious from Cobb and Hirai.
Appellant does not argue claims 5, 22, or 27 separately. Thus, these
claims fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv).
Appellant also does not separately argue the rejection of claim 26,
where the Examiner added Wangh to address the obviousness of the
limitations recited in that claim. Thus, we summarily affirm the Examiner’s
rejection of claim 26 as being obvious over Cobb, Hirai, and Wangh. Hyatt
v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008) (“When the appellant fails to
contest a ground of rejection to the Board, . . . the Board may treat any
argument with respect to that ground of rejection as waived.”)
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Obviousness: Claims 2, 10, and 13
Regarding claim 2’s requirement that the length of the nucleotide
sequence of the reporter region is shorter than a length of the nucleotide
sequence of the anchor region, the Examiner found that Cobb teaches a
variety of nucleotide lengths for the anchor region, e.g., between 20 and 200
nucleotides, and a variety of lengths for the reporter region, e.g., between 15
and 200 nucleotides, and that a number of the identified anchor region
lengths are longer than the identified reporter region lengths. (Final Action
32.) In particular, the Examiner noted the following teachings about the
anchor length from Cobb:
The anchor region is preferably at least 50 nt in length, more
preferably at least 60, 70, 80, 90, 100, 125, 150 nt. The anchor
region is preferably no more than 200 nt in length and no less
than 20 nt in length.
(Id. (citing Cobb ¶ 26).) The Examiner noted the following teachings about
the reporter length from Cobb:
The reporter region is preferably 15-200 nt in length, more
preferably 15-150, more preferably still 15-100, or 20-100, 30-
80, 40-60, or around 50 nt in length.
(Id. (citing Cobb ¶ 18).) Accordingly, the Examiner concluded that Cobb
discloses the limitation that the anchor sequence is longer than the reporter
sequence. (Id.)
We agree with the Examiner’s conclusion of obviousness. The
relevant paragraphs of Cobb are set forth above. Those paragraphs indicate,
for example, an anchor length could be selected to be 125 or 150
nucleotides, and a reporter region could be a nucleotide length of “15-100,
or 20-100, 30-80, 50-60 or around 50.” (Cobb ¶¶ 18, 26.) As such the
anchor length being longer than the reporter region is a probe possibility
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reasonably suggested by Cobb’s teachings. And for this reason, we do not
agree with Appellant that Cobb “does not disclose . . . the feature that
reporter region is shorter than the anchor region.” (Appeal Br. 15.)
Consequently, we affirm the Examiner’s rejection of claim 2 (and
claim 13 which has the same requirements as claim 2) as being obvious from
the teachings of Cobb and Hirai.
Appellant does not argue claim 10, which depends from claim 2
separately. Thus, claim 10 falls with claim 2. 37 C.F.R. § 41.37(c)(1)(iv).

Obviousness: Claims 23 and 24
Regarding the requirement that the fluorescent dye is selected from a
particular group of dyes, the Examiner noted that Appellant’s Specification
admits that the fluorescent dyes named in the claims that quench on
hybridization were known and commercially available “in the QProbe”
series manufactured by Nippon Steel & Sumikin Eco-Tech Corporation.
(Final Action 34 (citing Spec. ¶ 34).) The Examiner concluded that it would
have been obvious to use such commercially available dyes in the Cobb
probe and in light of the teachings of Hirai. (Id.) The Examiner stated:
It would have also been obvious to one off ordinary skill in the
art to have employed the commercially-available fluorescent
dyes that are quenched upon hybridization of probe to target for
in using same, one only has to use one label, not both
fluorophore and quencher. By using only one, and that which is
commercially available, the amount of time and resources
involved in producing labeled probes is effectively cut in half.
(Id.)
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We agree with the Examiner’s conclusion that the Specification is an
admission that the fluorescent dyes of claims 23 and 24 were commercially
available and known to be used with the QProbe series.
Appellant argues that the Specification statement is not an admission
that the fluorescent dyes are commercially available, just that the QProbe
reagent is commercially available. (Appeal Br. 4–5.) We do not find this
argument persuasive. The attorney argument in the Appeal Brief that the
Specification’s statement is not an admission that the fluorescent dyes are
commercially available is not evidence. Icon Health & Fitness v. Strava
Inc., 849 F.3d 1034, 1043 (Fed. Cir. 2017); see also, Gemtron Corp. v.
Saint-Gobain Corp., 572 F.3d 1371, 1380 (Fed. Cir. 2009) (“[U]nsworn
attorney argument . . . is not evidence and cannot rebut . . . other
admitted evidence . . . .”) The Specification clearly states that “Examples of
the fluorescent dye having such a characteristic [that quenches when the first
target sequence and the reporter region hybridize] include QProbe series
(manufactured by Nippon Steel & Sumikin Eco-Tech Corporation).” (Spec.
¶ 34.) In other words, the Specification states that a fluorescent dye is
included in the QProbe series that are commercially available. And the
Specification states “Specific examples of the fluorescent dye comprised in
the QProbe include FITC, TMR, 6-joe, Bodipy-FL/C6 and Bodipy-FL/C3.”
(Id.)
Indeed, the Specification admission appears consistent with the
teachings of Hirai. In particular, Hirai teaches a number of commercially
available dyes that can be used with QProbe, including Bodipy-FL,
TAMRA, and FAM. (Hirai ¶¶ 32–33).

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Thus, we affirm the Examiner’s rejection of claims 23 and 24 as being
obvious from the teachings of Cobb, Hirai, and the admitted evidence at
paragraph 34 of the Specification.

Non-Obviousness: Claims 3, 4, 7, 8, 9, 11, 12, 20, 21, 28, and 29
The Examiner relied on the teachings of Chun to address the
obviousness of the requirement of claim 3 that the linker region does not
include a universal base, and claim 4, that the linker region consists of only
one kind of base selected from adenine, guanine, cytosine, and thymine.
(See Final Action 32; Ans. 15–16.) We do not affirm the Examiner’s
rejection for the reasons expressly noted by Appellant in the Appeal Brief.
(See Appeal Br. 15–16.) Chun’s specified linker sequence that can be a
poly(T)7 sequence is not a linker between two probe sequences, but is used
to link a probe to a substrate. (See, e.g., Chun Figures 5A–7, ¶¶ 156, 409.)
The linker that separates hybridization portions of the probe from each other
is the sequence Y’q. (Id. ¶ 36.) And Chun explains that the linker between
probe sections is “at least three universal bases.” (Id.) Thus, given the art of
record relied on by the Examiner, we cannot agree that a prima facie case of
obviousness has been established with respect to the requirements of
dependent claims 3 and 4, which are also requirements of claims 7, 8, 9, 11,
12, 20, 21, 28, and 29.
Consequently, we reverse the Examiner’s rejection of claims 3, 4, 7,
8, 9, 11, 12, 20, 21, 28, and 29 as being obvious from the teachings of Cobb,
Chun, Hirai, and the admitted prior art.
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–13, 20–
25, 27, 28
103 Cobb, Chun, Hirai,
Admitted Prior Art
1, 2, 5, 6,
10, 13, 22,
23, 24, 25,
27
3, 4, 7–9,
11, 12, 20,
21, 28
26, 29 103 Cobb, Chun, Hirai,
Admitted Prior
Art, Wangh
26 29
Overall
Outcome
1, 2, 5, 6,
10, 13, 22,
23, 24, 25–
27
3, 4, 7–9,
11, 12, 20,
21, 28, 29

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