SYSMEX CORPORATION

Patent Trials and Appeals Board

Dec 9, 2021

2021001498 (P.T.A.B. Dec. 9, 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.
15/245,426 08/24/2016 Chikayuki TSURUNO Q228493 6706
23373 7590 12/09/2021
SUGHRUE MION, PLLC
2000 PENNSYLVANIA AVENUE, N.W.
SUITE 9000
WASHINGTON, DC 20006
EXAMINER
MARCSISIN, ELLEN JEAN
ART UNIT PAPER NUMBER
1641
NOTIFICATION DATE DELIVERY MODE
12/09/2021 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):
PPROCESSING@SUGHRUE.COM
USPTO@sughrue.com
sughrue@sughrue.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte CHIKAYUKI TSURUNO, SHINYA NAGAI, MINAKO TERAO,
CHIKA MIZUTA, and TAKUYA KYOUTOU
__________

Appeal 2021-001498
Application 15/245,426
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, RACHEL H. TOWNSEND, and
JAMIE T. WISZ, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a method
for detecting a target substance comprising a sugar chain that binds with a
lectin of Wisteria floribunda. The Examiner rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

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 SYSMEX
CORPORATION (see Appeal Br. 3). We have considered the Specification
of Aug. 24, 2016 (“Spec.”); Final Office Action of Oct. 15, 2019 (“Final
Action”); Appeal Brief of May 15, 2020 (“Appeal Br.”); Examiner’s Answer
of Oct. 29, 2020 (“Ans.”); and Reply Brief of Dec. 29, 2020 (“Reply Br.”).
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Statement of the Case
Background
The lectin of Wisteria floribunda (WFA) “binds with a sugar chain
having a GalNAc residue at its terminal . . . WFA (tetrameric WFA) also
binds with a sugar chain having a galactose (Gal) residue at its terminal”
(Spec. ¶ 27). The “inventors found that dimeric WFA that is obtained by
altering tetrameric WFA into dimer also has an activity of binding with the
sugar chain” and that when “the dimeric WFA is immobilized [it] shows
higher reactivity than the reagent involving a solid phase carrier on which
tetrameric WFA is immobilized” (id.). In addition, the “inventors found that
the storage stability of the present reagent is significantly higher than the
storage stability of the reagent involving tetrameric WFA” (id.).
The Claims
Claims 6–11 are on appeal. Claim 6 is an independent claim, is
representative and reads as follows:
6. A method for detecting a target substance comprising a
sugar chain that binds with lectin of Wisteria floribunda
(WFA), comprising the steps of:
(A) bringing a dimeric WFA immobilized carrier
comprising a solid phase carrier and a dimeric WFA which is
immobilized on the solid phase carrier, a sample comprising the
target substance, and a labeling substance that specifically binds
with the target substance into contact with each other to form a
complex comprising the dimeric WFA, the target substance and
the labeling substance on the solid phase carrier, and
(B) measuring the labeling substance in the complex
obtained in the step (A) to detect the target substance.

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The Rejections
A. The Examiner rejected claims 6–11 under 35 U.S.C. § 103(a) as
obvious over Narimatsu,2 Wolf,3 and Kurokawa4 (Final Act. 3–5).
B. The Examiner provisionally rejected claims 6–11 on the ground of
nonstatutory double patenting as being unpatentable over claims 1–14 of
copending Application No. 15/809,160, Wolf, and Kurokawa (Final Act. 6–
8).

A. 35 U.S.C. § 103(a) over Narimatsu, Wolf, and Kurokawa
The Examiner finds Narimatsu teaches “detecting a target substance
comprising a sugar chain that binds WFA” but does not “specify dimeric
WFA immobilized at the solid phase carrier” (Final Act. 3). The Examiner
finds Wolf teaches “most lectins are oligomeric proteins, existing as
tetramers or dimers” and “low valency binding ligands can be generated
from oligomeric protein, by modification of binding site or by reducing the
number of carbohydrate binding site containing subunits in the molecule”
(id.). The Examiner finds “Wolf teach[es] reduced valency ligands are
advantageous because lower numbers of binding sites reduces aggregation,
thereby improving assay performance and sensitivity” (id. at 3–4). The
Examiner finds Kurokawa teaches “WFA appeared as a dimer composed of
two identical subunits” (id. at 4) (emphasis omitted).

2 Narimatsu et al., US 2012/0172247 A1, published July 5, 2012.
3 Wolf, US 6,232,130 B1, issued May 15, 2001.
4 Kurokawa et al., Purification and Characterization of a Lectin from
Wistaria floribunda Seeds, 251 J. Biol. Chem. 5686–93 (1976).
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The Examiner finds it would have been obvious
to have used/immobilized dimeric WFA (as taught by both
Wolf and Kurokawa) at the solid support [of Narimatsu] for
capture and assay of the targeted analyte (AGP or M2PB)
because Wolf teach, with respect to the use of lectin as ligand in
binding assay, that reduced valency ligands are advantageous
because of lower numbers of carbohydrate binding sites (per
lectin), resulting in reduced aggregation.
(Final Act. 4).
The issues with respect to these rejection are:
(i) Does a preponderance of the evidence of record support the
Examiner’s conclusion that Narimatsu, Wolf, and Kurokawa render the use
of a dimeric WFA lectin in a detection assay obvious?
(ii) If so, has Appellant provided evidence of unexpected results that,
when weighed with evidence supporting the prima facie case of obviousness,
supports a finding of nonobviousness?
Findings of Fact
1. Narimatsu teaches:
a method for quantitatively determining AGP reacting with the
above lectin “A” by mixing biotinylated lectin “A” prepared by
binding biotin to lectin “A” with a sample, adding magnetic
particles to which streptavidin has been immobilized to the
mixture, so as to form a magnetic particle-lectin “A”-AGP
complex, reacting the complex with a labeled anti-AGP
antibody, so as to form a 2nd complex of magnetic particle-
lectin “A”-AGP-labeled anti-AGP antibody, and then
measuring the amount of the label of the 2nd complex.
(Narimatsu ¶ 102).
2. Narimatsu teaches “[e]xamples of lectin ‘A,’ the reactivity of
which is altered in response to changes in M2BP glycan structure
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accompanying changes in the clinical conditions of the liver, include WFA”
(Narimatsu ¶ 99).
3. Wolf teaches “[m]ost lectins are oligomeric proteins, existing
frequently as tetrameters or dimers” (Wolf 15:65–66).
4. Wolf teaches “ligand should have as few carbohydrate binding
sites as possible, preferably three or fewer. Such a ligand has reduced or
low valency. In preferred embodiments the low valency carbohydrate
binding ligand has a single carbohydrate binding site” (Wolf 15:8–12).
5. Wolf teaches “low valency carbohydrate binding ligand can be
generated from an oligomeric protein, by modification (inactivation) of a
binding site, or by reducing the number of carbohydrate binding site
containing subunits in the molecule. For example, [] a tetramer can be
converted to a dimer or a monomer” (Wolf 18:4–9).
6. Wolf teaches “[r]educed valency ligands are advantageous in
that a lower number of binding sites reduces aggregation. . . . This improves
the performance and sensitivity of the FRET system” (Wolf 19:65–20:3).
7. Wolf teaches: “In preferred embodiments the low valency
carbohydrate binding ligand has a single carbohydrate binding site and is a
monomeric molecule, e.g., a monomeric lectin molecule” (Wolf 15:12–15).
8. Wolf teaches “[e]xamples of some naturally occurring lectins
with a valency less than four are shown in boldface in Table I and include
. . . Wistaria floribunda” (Wolf 17:63–66).
9. Kurokawa teaches:
The present results show that the WFA molecule is
composed of two identical subunits, each with a molecular
weight of approximately 32,000. These two subunits are linked
through a single disulfide bond of the 2 half-cystine residues
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present in the WFA molecule. The intact WFA molecule and
two subunits are di- and monovalent, respectively, with respect
to sugar binding.
(Kurokawa 5692, col. 1).
Principles of Law
A prima facie case for obviousness “requires a suggestion of all
limitations in a claim,” CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333,
1342 (Fed. Cir. 2003) and “a reason that would have prompted a person of
ordinary skill in the relevant field to combine the elements in the way the
claimed new invention does.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007).
Prima facie obviousness can be rebutted by presenting evidence of
secondary considerations and when such evidence is submitted, all of the
evidence must be considered anew. In re Piasecki, 745 F.2d 1468, 1472–73
(Fed. Cir. 1984). Secondary considerations include: long-felt but unsolved
needs, failure of others, unexpected results, commercial success, copying,
licensing, and praise. In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998).
Analysis
We agree with the Examiner that the evidence supports a finding of
prima facie obviousness as Narimatsu discloses the method using tetrameric
WFA and Wolf provides reasons to use one of the three reduced valency
WFA formulations, i.e., monomeric, dimeric, and trimeric (FF 6–8).
However, we need not address Appellant’s prima facie case
arguments because we agree with Appellant that the evidence, particularly in
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Figure 2 of the Specification, supports the secondary consideration of
unexpected results. Appellant contends that Figure 2 shows:
when the dimeric WFA immobilized carrier (triangle; Example
I; Inventive Example) was used, high luminescence intensity
was obtained. On the other hand, when the monomeric WFA
immobilized carrier (square; Comparative Example I) or the
tetrameric WFA immobilized carrier was used (circle;
Comparative Example 2), the luminescence intensity was lower
than the inventive Example
(Appeal Br. 7) (emphasis omitted). Figure 2 is reproduced, as annotated by
Appellant, below:

“Fig. 2 is a graph showing the examination result of the relationship between
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the WFA sensitization concentration and the luminescence intensity when
M2BP is used as a target substance in Test Example 2” (Spec. ¶ 24). Figure
7a of the Specification is asserted to show superior relative reactivity for the
dimeric WFA relative to either the monomeric WFA or tetrameric WFA and
Figure 4 is asserted to show superior storage for the dimeric WFA relative to
the tetrameric WFA (see Appeal Br. 9–10).
The Examiner finds “it would not be unexpected that dimeric would
result in superior luminescence, since dimeric is expected to be an
improvement over tetrameric regarding performance and sensitivity” (Ans.
10). The Examiner also finds
monomeric WFA is not recited in the claims nor is it reference
[sic] in the primary reference of the cited prior art (Narimatsu is
teaching the higher valency species of WFA). The argument
that dimeric performs better than monomeric is not particularly
relevant presently since the rejection is not making the case that
it would be obvious to modify monomeric for dimeric.
(Ans. 11).
We do agree with the Examiner that Wolf reasonably suggests that the
lower valencies would be expected to be superior to tetrameric WFA
because Wolf teaches “[r]educed valency ligands are advantageous in that a
lower number of binding sites reduces aggregation. . . . This improves the
performance and sensitivity of the FRET system” (FF 6). However, neither
Narimatsu, Wolf, nor Kurokawa suggest that dimeric WFA would be
expected to be superior to monomeric WFA, and certainly none of these
references suggest that dimeric WFA would be four fold better in
luminescence than monomeric WFA as concentrations increase as shown in
Figure 2 of the Specification. Nor do any of these references suggest that
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relative reactivity would be best for dimeric WFA relative to either
monomeric or tetrameric WFA as shown in Figure 7 of the Specification.
We are not persuaded by the Examiner’s argument that monomeric is
not relevant because Wolf directly teaches that lower numbers of binding
sites improve the performance and sensitivity of the system, yet monomeric
WFA results in lower performance and sensitivity when compared to
dimeric WFA, directly inconsistent with the teachings of Wolf (FF 6). An
obvious combination is what the prior art would have suggested as obvious
and expected to the ordinary artisan, here that “ligand should have as few
carbohydrate binding sites as possible” (FF 4). But Appellant’s evidence
shows that Wolf was not correct for WFA, where the fewest number of sites
possible, monomeric WFA, was significantly inferior to dimeric WFA as
shown in Figures 2 and 7 of the Specification, and is therefore inconsistent
with Wolf. We therefore find that the unexpected results for this narrow
claim, limited to detecting ligands using dimeric WFA lectin on a solid
phase carrier with a label, is unexpected and is commensurate in scope with
the claims.
Conclusions of Law
(i) A preponderance of the evidence of record supports the
Examiner’s conclusion that Narimatsu, Wolf, and Kurokawa render the use
of a dimeric WFA lectin in a detection assay obvious.
(ii) Appellant has, however, provided evidence of unexpected
results that, when weighed with evidence supporting the prima facie case of
obviousness, support a finding of nonobviousness.

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B. Provisional Double Patenting
We decline to reach this provisional rejection. See Ex parte Moncla,
95 USPQ2d 1884, 1885 (BPAI 2010) (precedential). The rejection is
provisional and US Application No. 15/809,160 remains copending and not
allowed; accordingly, the issues are not ripe for decision.

DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
6–11 103 Narimatsu, Wolf,
Kurokawa
6–11
6–11 Provisional
Nonstatutory Double
Patenting Claims 1–
14 of Application No.
15/809,160, Wolf,
Kurokawa5

Overall
Outcome
6–11

REVERSED

5 We decline to reach this rejection as indicated above.