SUMITOMO BAKELITE CO., LTD.

Patent Trials and Appeals Board

Jun 29, 2020

2020002135 (P.T.A.B. Jun. 29, 2020)

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.
15/758,593 03/08/2018 Masaaki TOYODA P171000US00 3229
38834 7590 06/29/2020
WESTERMAN, HATTORI, DANIELS & ADRIAN, LLP
8500 LEESBURG PIKE
SUITE 7500
TYSONS, VA 22182
EXAMINER
MARTIN, PAUL C
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
06/29/2020 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):
patentmail@whda.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MASAAKI TOYODA1
Appeal 2020-002135
Application 15/758,593
Technology Center 1600
Before ERIC B. GRIMES, FRANCISCO C. PRATS, and
ULRIKE W. JENKS, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method for preparing an antibody sugar chain, which have been rejected as
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
“[T]he present invention relates to a method of rapidly preparing a
sugar chain from a glycoprotein.” Spec. ¶ 1. “Specific examples of the

1 Appellant identifies the real party in interest as Sumitomo Bakelite Co.
Ltd. Appeal Br. 2. We use the word Appellant to refer to “applicant” as
defined in 37 C.F.R. § 1.42(a).
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Application 15/758,593

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glycoprotein include . . . an antibody.” Spec. ¶ 16. “In a case where a
glycoprotein [is] an antibody, it is particularly important to analyze a sugar
chain. In this case, it is possible to rapidly isolate a sugar chain that
influences the activity or the like of the antibody.” Spec. ¶ 17.
In an embodiment, “a sugar chain can be extremely rapidly prepared
from a glycoprotein in the form (labeled form) of a sample for analysis by
isolating a sugar chain on a solid phase without eluting a glycoprotein fixed
to the solid phase, and adding a labeling reagent (labeling reaction solution)
to the container without separating the isolated product.” Spec. ¶ 11. “[I]t is
preferable to purify the sugar chain from the mixed solution before the
analysis in a case where the analysis is carried out by means of mass
analysis or the like.” Spec. ¶ 79. “By means of the analysis of the
glycoprotein sugar chain as described . . . it becomes possible to accelerate
research and development of antibody pharmaceutical products.” Spec.
¶ 130.
Claims 23–30 are on appeal.2 Claim 23, reproduced below, is
illustrative:
Claim 23: A method for preparing a glycoprotein sugar chain,
comprising:
an isolation step of acting a sugar chain-isolating enzyme
on a sample which contains a glycoprotein fixed to a solid
phase in a container to obtain an isolated product which
contains a sugar chain; and

2 The Examiner included claim 39 in the rejection but this claim was
canceled in the amendment filed May 20, 2019. The amendment was
entered by the Examiner. See Advisory Action mailed June 7, 2019.

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a labeling step of adding a labeling reagent to the isolated
product without purifying the sugar chain from the isolated
product to obtain a labeled product which contains a labeled
substance of the sugar chain, wherein
the glycoprotein is an antibody, and the solid phase
includes a ligand selected from the group consisting of protein
A, protein G, protein L, protein H, protein D, and protein Arp,
in the surface thereof, and
the amount the glycoprotein is in a range of 0.001 to 500
µg per one container.

The claims stand rejected as follows:
Claims 23–25 and 27–30 under 35 U.S.C. § 103 as being unpatentable
over Tayi3 and Ruhaak (2008)4 (Ans.5 3);
Claims 23–30 under 35 U.S.C. § 103 as being unpatentable over Tayi,
Ruhaak (2008), and Ruhaak (2011)6 (Ans. 7).
OPINION
Obviousness based on Tayi and Ruhaak (2008)
Claims 23–25 and 27–30 stand rejected under 35 U.S.C. § 103 as
being obvious over Tayi and Ruhaak (2008). Final Action 4. The Examiner
finds that Tayi “teaches a method wherein a sugar chain isolating enzyme
(PNGase F) acts on a sample containing a glycoprotein (antibody) fixed to a

3 Tayi et al., “Isolation and quantification of N-glycans from
immunoglobulin G antibodies for quantitative glycosylation analysis,”
Journal of Biological Methods 2(2):1–8 (2015).
4 Ruhaak et al., “Hydrophilic Interaction Chromatography-Based High-
Throughput Sample Preparation Method for N-Glycan Analysis from Total
Human Plasma Glycoproteins,” Anal. Chem. 80:6119–6126 (2008).
5 Examiner’s Answer mailed Nov. 22, 2019.
6 Ruhaak, WO 2011/038873 A1, published April 7, 2011.
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solid phase (bead) including a ligand (protein-A or protein-G) . . . to obtain
an isolated product which contains a sugar chain (N-glycans).” Final Action
4. The Examiner finds that Tayi also teaches “adding a labeling reagent . . .
to the isolated product in a container to obtain a labeled product which
contains a labeled . . . sugar chain.” Id.
The Examiner finds that Tayi “does not teach a method wherein the
labeling step is performed without purifying the sugar chain from the
isolated product.” Final Action 5.7 The Examiner finds that Ruhaak (2008)
“teaches a high throughput method for preparing a glycoprotein sugar chain”
that, like Tayi’s method, treats “a glycoprotein (citrate plasma)” with
PNGase F “to obtain an isolated product which contains a sugar chain (N-
glycans).” Id. The Examiner also finds that Ruhaak (2008) teaches adding a
labeling reagent “to the isolated product without purifying the N-glycans
from the isolated product to obtain a labeled sugar chain.” Id. The
Examiner finds that Ruhaak (2008) “teaches that prior art methods require
purification systems not available to every laboratory or are labor intensive
and time-consuming.” Id.
The Examiner concludes that it would have been obvious to one of
ordinary skill in the art “to modify the method of preparing labeled N-
glycans from antibodies which requires a purification step prior to labeling”
as taught by Tayi with the method of Ruhaak (2008) “for preparing labeled
N-glycans which does not require a purification step prior to labeling as this

7 The Examiner also states that Tayi does not teach 0.001 to 500 μg of
glycoprotein per container. Final Action 5. However, the Examiner later
corrected himself, and noted that “Tayi et al. discloses the addition of 50–
100 μg of antibody (glycoprotein) into a container.” Ans. 11.
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would decrease the preparation time of the method of Tayi et al. by
eliminating a method step, resulting in time and labor savings.” Final
Action 6.
Appellant argues that “there is no correlation between the process of
Ruhaak (i.e. isolating glycoproteins from citrate plasma which were
denatured, subsequently releasing N-glycans using PNGase, and thereafter
labeling the released N-glycans) and the results obtained thereby with the
distinctly different process of the primary reference Tayi.” Appeal Br. 7.
Appellant argues that “the process of Tayi requires that the sugar chain is
purified from an isolated product . . . and a labeling step is performed by
adding a labeling reagent to the purified sugar chain.” Id. Appellant
concludes that “[t]he skilled artisan would not find an expectation of success
[in] removing these steps from Tayi based on the Ruhaak process.” Id.
Appellant states that “the glycoprotein of the present invention has
been limited to an antibody, and the antibody is fixed to a solid phase via a
ligand” that has an affinity for the antibody. Appeal Br. 8. Appellant argues
that “Ruhaak does not provide for limiting a glycoprotein to an antibody,
and does not provide for fixing an antibody to a solid phase via a ligand
having an affinity for the antibody.” Appeal Br. 8–9. Appellant concludes
that “the skilled artisan has no manner of deriving to simply remove the
purification step taught by Tayi as an obvious modification based on Ruhaak
when the processes of each are completely different in their approach to
isolating and labeling.” Appeal Br. 9.
We agree with the Examiner that the claimed method would have
been obvious to a person of ordinary skill in the art based on Tayi and
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Ruhaak (2008). Tayi discloses a “method of isolating N-glycans from
Immunoglobulin G based antibodies for glycosylation analysis” consisting
of “purification of antibodies from biological solution and release of N-
glycans with peptide-N-glycosidase F in a single consolidated process using
a mini affinity ligand column.” Tayi, Abstract. “The isolated glycans can
be labeled with 2-aminobenzamide (2-AB) or 2-Aminobenzoic acid (2-
AA).” Id. at 4.
Ruhaak (2008) similarly discloses a procedure wherein “N-glycans
are released from glycoproteins and subsequently labeled with 2-AA without
prior purification.” Ruhaak (2008), Abstract. Ruhaak (2008) states that its
method is a “high-throughput procedure for rapid preparation of 2-
aminobenzoic acid (2-AA) labeled N-glycans from . . . human plasma.” Id.
Thus Tayi, like Ruhaak (2008), enzymatically releases N-glycans
from a protein. The Examiner relies upon Ruhaak (2008) only to show that
the isolated N-glycans are effectively labeled without purifying them after
they are released from glycoproteins. “The combination of familiar
elements according to known methods is likely to be obvious when it does
no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550
U.S. 398, 416 (2007). Here, a skilled artisan would have considered it
obvious to modify Tayi’s method by labeling cleaved glycans without
purifying them, because Ruhaak (2008) teaches that pre-labeling purification
is unnecessary.
Appellant states that in Tayi, “after an isolation step is performing
[sic] . . . a sugar chain is purified from an isolated product (see Tayi, page 3,
PROCEDURE 2, item 2.7 ‘Filter the glycans through 10K filter and collect
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the filtrate into 1.5 ml micro-centrifuge tube’, etc.), and a labeling step is
performed by adding a labeling reagent to the purified sugar chain.” Appeal
Br. 5. Appellant has not, however, provided any evidence to indicate that
eliminating the filtration step of Tayi (as suggested by Ruhaak (2008))
would prevent effective labeling of the N-glycans.
Appellant argues that the method of claim 23 “has unexpected
remarkable effects and therefore demonstrates criticality pursuant to
M.P.E.P §2144.05.III.” Appeal Br. 4. Appellant states,
[f]or example, when a sugar chain isolation and a sugar labeling
were performed on Protein A-binding monolith silica (see,
Example 2), the time taken for all steps was approximately 3
hours. On the other hand, when a sugar chain isolation using a
deglycosylation promoter and a sugar chain labeling were
performed after a sugar chain purification were performed on
Protein A-binding monolith silica (see, Reference Example 1),
the time taken for all steps was 7 hours.
Id.
“[W]hen unexpected results are used as evidence of nonobviousness,
the results must be shown to be unexpected compared with the closest prior
art.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). In
this case, Tayi’s sugar chain purification method differs from the sugar chain
purification method disclosed in Reference Example 1 of the Specification.
As noted by Appellant, in Tayi’s method, a sugar chain is purified by
filtering the glycans through a filter and collecting the filtrate, after which a
labeling step is performed. Appeal Br. 5.
By contrast, in the sugar chain purification method disclosed by
Reference Example 1, “[t]he isolated sugar chain was captured by bringing
the separate liquid into contact with sugar chain purification kit BlotGlyco
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(registered trademark) beads (manufactured by Sumitomo Bakelite Co.,
Ltd.), and then re-isolation (purification of the isolated sugar chain) of the
captured sugar chain and labeling with 2-aminobenzamide (2AB) were
performed.” Spec. ¶ 180. The isolated sugar chain purification step by
filtration disclosed by Tayi is distinct from the isolated sugar chain
purification step by capture upon purification beads followed by re-isolation
disclosed by Reference Example 1. Thus, Appellant’s comparison of
Example 2 with Reference Example 1 is not sufficient to demonstrate that
the claimed method is unexpectedly superior when compared with the
closest prior art (Tayi).
In any event, Appellant has not persuasively explained why
eliminating the sugar chain purification step described in Reference Example
1 would not be expected to result in a shorter processing time as described in
Example 2. As the Examiner pointed out, modifying Tayi’s method as
suggested by Ruhaak (2008) “would decrease the preparation time of the
method of Tayi et al. by eliminating a method step, resulting in time and
labor savings.” Final Action 6.
With respect to the amount of glycoprotein per container recited in
claim 23, Appellant argues that “the amount is critical in that isolating and
labeling such a small amount is extremely useful when limited sample size is
available. . . . [T]he Examiner has not identified in the primary reference
Tayi, or any other prior art, a process which isolates and labels a sample size
within this claimed range.” Appeal Br. 9–10.
This argument is unpersuasive. As noted above, Examiner found that
“[w]ith regard to the amount of glycoprotein in a range of 0.001-500 µg per
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one container” Tayi discloses “the addition of 50-100 µg of antibody
(glycoprotein) into a container (column) (see Pg. 3, Procedure, Line 8).”
Ans. 11.
We conclude that the rejection of claims 23–25 and 27–30 under 35
U.S.C. § 103(a) based on Tayi and Ruhaak (2008) is supported by a
preponderance of the evidence, and we therefore affirm it.

Obviousness based on Tayi, Ruhaak (2008), and Ruhaak (2011)
Claims 23–30 stand rejected under 35 U.S.C. § 103 as being obvious
over Tayi, Ruhaak (2008), and Ruhaak (2011). Final Action 7.
The Examiner finds that Tayi and Ruhaak (2008) are silent with
respect to “a method wherein the reducing agent is picoline borane,” but
Ruhaak (2011) teaches that the sodium cyanoborohydride used by Ruhaak
(2008) “may be too strong a reducing agent” and “2-picoline borane/2-PB is
particularly effective for reductive amination of carbohydrate.” Final Action
8. The Examiner concludes that it would have been obvious to modify the
method of Tayi and Ruhaak (2008) “for preparing a labeled glycoprotein
sugar chain comprising the use of the reducing agent sodium cyanoboro-
hydride to use the 2-PB reducing agent as taught by Ruhaak [(2011)]
because the reference teaches that they are art-recognized equivalent
reducing agents.” Id. We agree with the Examiner’s fact-finding and
conclusion.
Appellant argues that Ruhaak (2011) “does not provide for and is not
relied upon in regard to the isolating and labeling steps of claim 23.” Appeal
Br. 10. We find this argument unpersuasive for the reasons discussed above.
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
23–25, 27–
30
103 Tayi, Ruhaak (2008) 23–25, 27–
30

23–30 103 Tayi, Ruhaak (2008),
Ruhaak (2011)
23–30
Overall
Outcome
23–30
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