JAPAN AS REPRESENTED BY DIRECTOR GENERAL OF NATIONAL INSTITUTE OF INFECTIOUS DISEASES et al.

Patent Trials and Appeals Board

Apr 1, 2021

2020005864 (P.T.A.B. Apr. 1, 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.
16/200,233 11/26/2018 Hideki HASEGAWA 08279.1794USD1 6257
52835 7590 04/01/2021
HAMRE, SCHUMANN, MUELLER & LARSON, P.C.
45 South Seventh Street
Suite 2700
Minneapolis, MN 55402-1683
EXAMINER
BLUMEL, BENJAMIN P
ART UNIT PAPER NUMBER
1648
NOTIFICATION DATE DELIVERY MODE
04/01/2021 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):
PTOMail@hsml.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte HIDEKI HASEGAWA, TADAKI SUZUKI, AKIRA AINAI,
TAIZOU KAMISHITA, and TAKASHI MIYAZAKI

Appeal 2020-005864
Application 16/200,233
Technology Center 1600
____________

Before DONALD E. ADAMS, RYAN H. FLAX, and
RACHEL H. TOWNSEND, 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 11–17 (see Appeal Br. 1). 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 “JAPAN AS
REPRESENTED BY DIRECTOR GENERAL OF NATIONAL
INSTITUTE OF INFECTIOUS DISEASES of Tokyo, Japan and TOKO
YAKUHIN KOGYO KABUSHIKI KAISHA of Osaka, Japan” (Appellant’s
March 16, 2020, Appeal Brief (Appeal Br.) 2).
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STATEMENT OF THE CASE
Appellant’s disclosure “relates to an influenza vaccine composition
for spray-administration to nasal mucosa” (Spec.2 ¶ 1). Appellant’s claim 11
is reproduced below:
11. A method for preventing influenza in a human subject,
comprising:
nasally administering to the human subject an influenza
vaccine composition comprising:
(i) an inactivated whole influenza virion; and
(ii) a gel base material comprising carboxy vinyl polymer
that is prepared by treating the gel base material by adding an
outside shearing force with a high-speed spinning-type
emulsifying device, a colloidal mill-type emulsifying device, a
high-pressure emulsifying device, a roll mill-type emulsifying
device, an ultrasonic-type emulsifying device or a membrane-
type emulsifying device to add spray-performance, and then
mixing the resulting gel base material with a virus stock
solution comprising an inactivated whole influenza virion
homogeneously without stress,
wherein the influenza vaccine composition does not
comprise an adjuvant,
by spraying the influenza vaccine composition from a
spray device that can spray a viscous formulation from naris to
intranasal mucosa of the human subject.
(Appeal Br. 12.)3

2 Appellant’s November 26, 2018, Specification.
3 Appellant states that its “[c]laims 12-17 are considered to stand or fall with
independent claim 11 for purposes of this appeal” (Appeal Br. 4).
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Claims 11–17 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of Kamishita4 and Oka.5
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Kamishita
relates to a preparation for nasal drop, and an administration
system of the preparation using a nasal spray wherein the
preparation can be intranasally sprayed, optionally setting the
administration direction of the spray container, in order to
disperse and hold the gel preparation in a broad area of nasal
cavity.
(Kamishita ¶ 1; see id. ¶ 24 (Kamishita discloses its gel-type skin/mucosa-
adhesive preparation contains carboxy vinyl polymer); see also Ans.6 5.)
FF 2. Kamishita discloses that its
gel base material may be controlled by (1) adjusting the
viscosity of the formulation by adding an outside shearing force
to carboxy vinyl polymer, or (2) adjusting the viscosity of the
formulation by adding a viscosity modulating agent and an
outside shearing force to carboxy vinyl polymer, so that the
spray spreading-angle of the spray container and the spray
spread can be set to meet the desired treatment[, wherein] . . .
the shearing force herein can be carried out via a method known
by a skilled person, wherein for example, a high-speed
spinning-type emulsifying device, a colloidal mill-type
emulsifying device, a high-pressure emulsifying device, a roll
mill-type emulsifying device, an ultrasonic-type emulsifying

4 Kamishita, US 2009/0275668 A1, published Nov. 5, 2009.
5 Oka et al., Influenza Vaccine: Enhancement of Immune Response by
Application of Carboxy-Vinylpolymer, 8 Vaccine 573–576 (1990).
6 Examiner’s June 8, 2020, Answer.
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device and a membrane-type emulsifying device can be used as
a device giving shearing force.
(Kamishita ¶¶ 64–65; see also Ans. 5.)
FF 3. Kamishita discloses “a vaccine such as influenza HA vaccine”
“dissolved in the gel base material,” as “[t]he ‘active pharmaceutical
ingredient’” for administration “to the area of skin and/or mucosa”
(Kamishita ¶ 70; see also Ans. 5).
FF 4. Examiner finds that, with respect to Appellant’s claim 11,
“Kamishita does not teach the use of an inactivated whole influenza virion”
(Ans. 5).
FF 5. Oka discloses the “application of carboxy vinylpolymer (CVP) to
influenza vaccine for the improvement of immune response” (Oka Abstr.
(emphasis omitted); see id. at 573 (Oka discloses formulations comprising
CVP in combination with inactivated whole virus (CVP-whole virus)
vaccine or HA (CVP-HA) vaccine); see also Ans. 5).
FF 6. Oka discloses that “CVP-coupled influenza vaccine is most effective
when applied intranasally” (Oka 576; see generally Ans. 5–6).
FF 7. Oka discloses high titres of HI (hemagglutination inhibiting)
antibody and IgA antibody 3 weeks after intranasal administration of CVP-
HA or CVP-whole virus vaccines, whereas no significant production of HI
antibody or IgA was produced in HA or inactivated whole virus vaccines in
the absence of CVP (Oka 575; see id. (Oka discloses that “high titres of
virus neutralization were detected only in mice administered the CVP-HA
vaccine and CVP-whole virus vaccine intranasally”); id. at Table 2 (Oka
discloses that the CVP-whole virus vaccine resulted in a 3.5-fold higher (796
units) ELISA titre of IgA antibody than CVP-HA vaccine (223 units)); see
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also id. at 575 (Oka discloses an ELISA method of measuring IgA
antibody); see generally Ans. 5–6).
ANALYSIS
Based on the combination of Kamishita and Oka, Examiner concludes
that, at the time Appellant’s invention was made, it would have been prima
facie obvious
to modify the methods taught by Kamishita in order to combine
an inactivated whole influenza virus . . . [with CVP] . . . and
spray the inactivated virus into a human subject’s nasal passage
with a device that can spray from the naris to the intranasal
mucosa. One would have been motivated to do so, given the
suggestion by Kamishita that influenza HA vaccines can be
combined with the CVP gel formulations and that the resulting
immunogenic composition can be administered via spray to a
human. There would have been a reasonable expectation of
success, given the knowledge that inactivated whole influenza
virion has been previously taught as being used . . . with a CVP
gel and sprayed into the nasal passages of mice, as taught by
Oka.
(Ans. 6–7.)
Appellant contends that the results achieved by Appellant’s claimed
invention “could not be expected from the [combined] disclosures” of
Kamishita and Oka (Appeal Br. 7). In support of this contention Appellant
directs attention to comparisons of their claimed invention to various
vaccine compositions that lack “a gel base material comprising carboxy
vinyl polymer that has been subjected to an outside shearing force” (Appeal
Br. 7–8 (citing Spec. 23–27)). These comparisons, however, do not address
the closest prior art on this record, which are directed to influenza vaccines
comprising CVP and are, therefore, not persuasive. See In re Huai-Hung
Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011) (In order to be persuasive of non-
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obviousness, “[e]vidence of secondary considerations must be reasonably
commensurate with the scope of the claims.”).
Appellant provided
additional experimental comparisons . . . using different
combinations of whole or split influenza virion with a gel base
material comprising carboxy vinyl polymer that has been
subjected to an outside shearing force (“treated base material”)
or a gel base material comprising carboxy vinyl polymer that
has not been subjected to an outside shearing force as used in
Oka (“untreated base material”).
(Appeal Br. 8 (citing Miyazaki Decl.7).) Appellant contends that Miyazaki’s
comparisons demonstrate that “[b]oth the whole antigen and the split antigen
showed increased effectiveness when used in a composition with the treated
base material instead of the untreated base material, as might be expected
from the teachings of Kamishita” (Appeal Br. 8 (emphasis added); see also
Miyazaki Decl. ¶¶ 7–8). We agree.
Appellant further contends that Miyazaki’s comparisons demonstrate
that “the level of increase in the effectiveness seen for the treated base
material with the whole antigen over the untreated base material with the
whole antigen was significantly higher than the level of increase in the
effectiveness seen for the treated base material with the split antigen over the
untreated base material with the split antigen” (Appeal Br. 8–9; see also
Miyazaki Decl. ¶¶ 7–8). According to Appellant, “[n]either Kamishita nor
Oka provides any reason to expect that the increase in effectiveness seen
when administering compositions using the treated base material could be so
much larger when the whole antigen is used with the treated base material
instead of the split antigen” (Appeal Br. 9). Stated differently, Appellant

7 Declaration of Takashi Miyazaki, signed January 5, 2018.
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contends that it was surprising that a vaccine comprising inactivated whole
influenza antigen and CVP produced a more robust response than a vaccine
comprising influenza HA (i.e., split antigen) and CVP. We are not
persuaded.
On this record, Oka establishes that, three weeks (i.e., 21 days) after
vaccination, inactivated whole influenza virus and CVP (CVP-whole virus
vaccine) produced more robust IgA response than a vaccine comprising
influenza HA (i.e., split antigen) and CVP (CVP-HA) (see FF 7; see also
Appeal Br. 9 (Appellant contends that “[b]oth the treated base material and
the untreated base material showed increased effectiveness when used in a
composition with the whole antigen instead of the split antigen”)). Thus, the
evidence of record establishes that those of ordinary skill in this art would
have reasonably expected a more robust response with CVP-whole virus
vaccine than a CVP-HA (i.e., split antigen) vaccine (FF 7).
The evidence of record further supports a finding that those of
ordinary skill in this art would have reasonably expected that Oka’s vaccine
could have been improved by, inter alia, adjusting the viscosity of the
vaccine formulation by adding an outside shearing force to the carboxy vinyl
polymer component of the vaccine (see FF 2). Appellant has conceded this
fact (see Appeal Br. 8 (Appellant contends that “[b]oth the whole antigen
and the split antigen showed increased effectiveness when used in a
composition with the treated base material instead of the untreated base
material, as might be expected from the teachings of Kamishita”) (emphasis
added); see also Ans. 11 (Examiner finds that “Kamishita teaches that
exposing CVP based compositions to an outside shearing force, including
those presently claimed, would improve the intranasal delivery of droplets
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upon spraying into a nose because the droplet size is more uniform”)). Thus,
we are not persuaded by Appellant’s contention that those of ordinary skill
in this art would have found it unexpected, or surprising, to obtain a more
robust response with inactivated whole virus vaccine formulated with CVP
that was treated with an outside shearing force relative to a HA (i.e., split
antigen) vaccine with or without CVP that was, or was not, treated with an
outside shearing force (cf. Appeal Br. 9 (Appellant contends that “[n]othing
in either reference provides any reason to expect the increase in
effectiveness for compositions using the whole antigen could be so much
greater with the treated base material instead of the untreated base
material”); Reply Br. 2 (Appellant contends “there is nothing in Kamishita
that explains why the combination of the whole antigen with the treated gel
base material significantly outperformed the split antigen with the treated gel
base material relative to the untreated gel base material.”)).
Further, Oka observed a 3.5-fold increase in IgA response using a
CVP-whole antigen vaccine compared to a CVP-HA vaccine 3 weeks (i.e.,
21 days) post-vaccination (see FF 7). In contrast, Miyazaki reported a
nominal increase in IgA response between the two vaccines (3.0 for an
untreated CVP-whole antigen vaccine compared to < 2 for a untreated CVP-
HA vaccine or 4.0 for a treated CVP-whole antigen vaccine compared to 3.0
for a treated CVP-HA vaccine) during the same time period (see Miyazaki
Decl. ¶ 7). It was not until Miyazaki extended its work past the post-
vaccination period tested by Oka and included additional vaccinations that
Miyazaki observed an increased IgA response using a CVP-whole antigen
vaccine instead of a CVP-HA vaccine (see Miyazaki Decl. ¶¶ 6–7). We find
no evidence on this record to support a conclusion that Oka would not have
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obtained a further increase in response had Oka continued its experiment
past 21-days post vaccination with additional vaccinations, as reported by
Miyazaki, or that this increase would not have been expected to be further
amplified by using CVP treated with outside shearing force as disclosed by
Kamishita (see Miyazaki Decl. ¶ 7; see also Appeal Br. 8 (Appellant
conceded that those of ordinary skill in this art would have expected
increased effectiveness with whole antigen over split antigen when used in a
composition with the treated base material instead of the untreated base
material); cf. Ans. 10 (Examiner finds that “[i]f Oka . . . administered their
vaccines at two additional intervals, one of ordinary skill in the art would
expect that Hi and IgA titers would have been even higher than their 21 day”
results)).
We are not persuaded by Appellant’s contention that “Oka’s testing
was conducted on mice. The work of the Declaration was conducted on
monkeys. Nothing in the present record provides any reason for expecting
that the results of work from these two very different subjects should be
directly compared” (Reply Br. 3; see id. (Appellant contends that “[n]othing
in the present record establishes how mice are expected to respond to a
multiple dose vaccination protocol, nor that [the] multiple dose vaccination
protocol for mice would simply carry out a single dose protocol multiple
times instead of being modified taking into account the multiple dosages”)).
We find no persuasive argument or evidence on this record to support a
conclusion that those of ordinary skill in this art would not have found the
results obtained in the prior art’s mouse study comparable to the results
Appellant obtained in its monkey study. See In re Pearson, 494 F.2d 1399,
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1405 (CCPA 1974) (“Attorney’s argument in a brief cannot take the place of
evidence.”).
Taken as a whole we are not persuaded by Appellant’s evidence of
unexpected results (see Appeal Br. 7–10; see also Reply Br. 1–4; Miyazaki
Decl. ¶¶ 6–9). Instead, we agree with Examiner’s conclusion that
Appellant’s invention:
[F]unctions as it was intended to function and one of ordinary
skill in the art would expect that a single administration of the
vaccines used by Oka . . . following outside shearing force
treatment suggested by Kamishita would be sufficient to induce
neutralizing antibodies at a level at least similar to appellants,
thereby achieving the claimed method of preventing influenza
in a human subject.
(Ans. 11.)
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claim 11 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Kamishita and Oka is
affirmed. Claims 12–17 are not separately argued and fall with claim 11.
DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
11–17 103(a) Kamishita, Oka 11–17
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).

AFFIRMED