Hsu, Stephen et al.

Patent Trials and Appeals Board

Nov 27, 2019

14333279 - (D) (P.T.A.B. Nov. 27, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/333,279 07/16/2014
25461 7590 01/16/2020
SMITH, GAMBRELL & RUSSELL
SUITE 3100, PROMENADE II
1230 PEACHTREE STREET, N.E.
ATLANTA, GA 30309-3592
FIRST NAMED INVENTOR
Stephen Hsu
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
064466.037 4306
EXAMINER
ALAWADI, SARAH
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
01/16/2020 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):
docketing@sgrlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte STEPHEN HSU, LEE H. LEE, and TIN-CHUN CHU
Appeal 2018-008685 1
Application 14/333,279
Technology Center 1600
BEFORE FRANCISCO C. PRATS, RACHEL H. TOWNSEND, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.
HARDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for killing spores using certain esterified catechins. We heard oral argument
on October 22, 2019. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 In this Decision we use the word "Appellant" to refer to "Applicant" as
defined in 37 C.F.R. § l.42(a). Appellant identifies the real parties in
interest as Augusta University Research Institute, Inc., Seton Hall
University, and Montclair State University. Appeal Br. 2.
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Application 14/333,279
STATEMENT OF THE CASE
The claims at issue are directed to a method for killing spores. Claim
1, reproduced below, is illustrative of the claimed subject matter:
1. A method for killing spores comprising contacting the spores
with an effective amount of an anti-spore composition
comprising (-)-epigallocatechin-3-gallate (EGCG) esterified at
the 4' position with a fatty acid having a hydrocarbon chain
length of between 14 and 22 to kill the spores.
Appeal Br. 11 (Claims Appendix).
Claims 1, 4, 6-8, 19, and 26-29 are on appeal. Non-Final Act. 2. The
claims stand rejected as follows:
Claims 1, 4, 19, and 29 are rejected under 35 U.S.C. § 103 as
unpatentable over Fukami,2 Kudo,3 and Hsu.4 Non-Final Act. 4.
Claim 28 is rejected under 35 U.S.C. § 103 as unpatentable over
Fukami, Kudo, Hsu, Baugh,5 and Keynan.6 Non-Final Act. 7.
Claims 6-8 and 26 are rejected under 35 U.S.C. § 103 as unpatentable
over Fukami, Kudo, Hsu, and Walker. 7 Non-Final Act. 8.
Claim 27 is rejected under 35 U.S.C. § 103 as unpatentable over
Fukami, Kudo, Hsu, and Hara. 8 Non-Final Act. 10-11.
2 Fukami et al., EP 1849779 Al, published Oct. 31, 2007 ("Fukami").
3 Hara-Kudo et al., Antibacterial Action on Pathogenic Bacterial Spore by
Green Tea Catechins, 85(14) J. Sci. Food Agric. 2354-61 (2005) ("Kudo").
4 Hsu, US 2012/0172423 Al, published July 5, 2012 ("Hsu").
5 Baugh et al., US 6,656,919 Bl, Dec. 2, 2003 ("Baugh").
6 Keynan et al., Activation of Bacterial Endospores, 88(2) J. Bacteriol. 313-
18 ( 19 64) ("Keynan").
7 Walker, US 7,192,601 B2, issued Mar. 20, 2007 ("Walker").
8 Hara, JP 02276562 A, published Nov. 13, 1990 ("Hara").
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DISCUSSION
"[T]he examiner bears the initial burden ... of presenting a prima
facie case ofunpatentability. If that burden is met, the burden of coming
forward with evidence or argument shifts to the applicant." In re Oetiker,
977 F.2d 1443, 1445 (Fed. Cir. 1992). We have considered those arguments
made by Appellant in the Appeal Brief and properly presented in the Reply
Brief; arguments not so presented in Appellant's briefs are waived. See 37
C.F.R. § 41.37(c)(l)(iv) (2015); see also Ex Parte Borden IV, 93 USPQ2d
14 73, 14 7 4 (BP AI 2010) (informative) ("Any bases for asserting error,
whether factual or legal, that are not raised in the principal brief are
waived.").
Rejection of Claims 1, 4, 19, and 29 as Obvious Over Fukami, Kudo, and
Hsu
The Examiner found that Fukami teaches catechins modified with
medium chain fatty acids having between 8-12 carbon atoms at positions
including the 4' hydroxyl group. Non-Final Act. 4 (citing Fukami ,-J 20,
claims 8, 23). According to the Examiner, Fukami discloses that these
catechins can suppress spore formation. Non-Final Act. 4 (citing Fukami
Abstract, Examples 6-10, claim 10, ,-J 32). The Examiner further found that
Fukami contacted spores with the modified catechins overnight, and that it
would have been obvious to adjust the contact time "in order to provide
sufficient and complete antibacterial killing." Non-Final Act. 5.
The Examiner additionally found that Kudo teaches that catechins
such as epigallocatechin gallate ("EGCG") damage bacterial spore
membranes, thus killing spores. Non-Final Act. 4-5 ( citing Kudo at
Abstract, 2360-61 (last paragraph)). According to the Examiner, because
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Kudo "discloses that catechins damage and thus kill spore membranes," the
modified catechins in Fukami must also "necessarily act[] to kill spores."
Non-Final Act. 4-5.
The Examiner further found that Hsu teaches EGCG esterified at the
4' position with stearic acid (i.e., "EGCG stearate"). Non-Final Act. 6
( citing Hsu at claim 2). The Examiner acknowledged, however, that Hsu
teaches use of this compound as an antiviral agent, not as a sporicide. Id.
The Examiner found that a person of ordinary skill in the art would
have been motivated to substitute the medium chain fatty acid ester of
Fukami with stearic acid because "homo logs ( compounds differing regularly
by the successive addition of the same chemical group, e.g., by -CH2-
groups) are generally of sufficiently close structural similarity that there is a
presumed expectation that such compounds possess similar properties."
Non-Final Act. 6. The Examiner found that there would have been a
reasonable expectation of success because "Fukami already teaches
esterified epigallocatechin gallates with fatty acids." Non-Final Act. 7.
We agree with the Examiner's factual findings and conclusion that the
subject matter of claims 1, 4, 19, and 29 would have been obvious to one of
ordinary skill in the art in view of Fukami, Kudo, and Hsu. We address
Appellant's arguments below.
Appellant argues that the asserted combination of prior art does not
teach or suggest the claimed method because Fukami discloses a method of
inhibiting the growth of spore-forming bacteria rather than killing spores;
Kudo "does not teach or suggest a method of contacting spores with an
esterified catechin;" and Hsu does not teach a method of contacting spores.
Appeal Br. 6; see also Reply Br. 2-3 (arguing that Fukami does not teach
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Application 14/333,279
killing spores). We are not persuaded by this argument, which attacks the
references individually for each failing to teach all of the claimed
limitations. The test for obviousness is not whether the claimed invention is
expressly identified in any one or all of the references, but whether the
claimed subject matter would have been obvious to one of ordinary skill in
the art in light of the combined teachings of the prior art. See In re Keller,
642 F.2d 413, 425 (CCPA 1981). As discussed above, we agree with the
Examiner that the references collectively teach the claimed subject matter,
because Fukami teaches that esterified catechins inhibit spore growth (see,
e.g., Fukami abstract), Kudo teaches that catechins kill spores (see, e.g.,
Kudo abstract), and Hsu teaches EGCG stearate, an esterified catechin
compound that falls within the scope of claims 1, 4, 19, and 29 (see, e.g.,
Hsu claim 2).
Appellant further argues that a person of ordinary skill in the art
would not have been motivated to carry out the claimed method because
Fukami and Kudo suggest that it would not have been successful. Appeal
Br. 7. Specifically, Appellant asserts that Fukami's modified catechins
provide the strongest growth inhibition on spore-forming Bacillus species,
yet Kudo suggests that catechins "are not effective at reducing the number of
Bacillus cereus spores over a course of 12 weeks," and could not inhibit
enterotoxin production by Bacillus cereus. Appeal Br. 7. Appellant further
argues that Fukami's teaching that "esterifying catechins at the 4' position
with medium chain fatty acids confers weak antibacterial activity on
vegetative bacteria," in view of Kudo's teaching that "catechins require long
incubation periods to affect spores," would have undermined any motivation
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or reasonable expectation of success in carrying out the claimed method.
Reply Br. 3-4.
We are not persuaded by these arguments. First, Appellant focuses on
Kudo's results relating to minimal efficacy on B. cereus spores, while
ignoring its results relating to decreasing C. botulinum and C. butyricum
spores to undetectable levels. As indicated in Kudo, catechins at 1000 µg/ml
and 500 µg/ml each decreased C. botulinum spores to undetectable levels
after 12 weeks (Figure l(a)); catechins at 1000 µg/ml decreased C.
butyricum spores to undetectable levels after 2 weeks (Figure 1 (b) ); and
catechins at 500 and 250 µg/ml each decreased C. butyricum spores to
undetectable levels after 4 weeks (Figure l(b)). Kudo 2355 (Figure 1), 2356
(Results and Discussion). Kudo further indicates that catechins damage not
only the bacterial vegetative membrane, but the spore membrane as well.
Kudo 2361.
Accordingly, at a minimum, Kudo demonstrates that catechins kill
spores of at least C. botulinum and C. butyricum. See also Non-Final Act. 5
("Kudo [] discloses that catechins damage and thus kill spore membranes.");
Ans. 7 ("Kudo et al. [] teaches that catechins damage bacterial spore
membranes of spore-forming bacterial pathogens, [ and] thus function in
killing spores, see last paragraph."). Indeed, Appellant conceded that Kudo
teaches killing spores, stating: "The only cited prior art reference that
explicitly discusses a method of killing spores is Kudo et al." Appeal Br. 8.
Moreover, even though B. cereus spores did not reach undetectable
levels in Kudo' s experiment (Kudo Figure 1 ( c) ), Kudo does note that "the
decrease in spores was significant at [a] concentration of greater than 250
µg/ml." Kudo 2358. Kudo further notes that "[t]he effect of crude catechins
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on C botulinum, C butyricum and B cereus depended on the concentration of
the former" (Kudo 2358), thus suggesting that catechins kill spores in a
concentration-dependent manner. Accordingly, Kudo also demonstrates that
catechins killed at least some B. cereus spores, and suggests that an
increased concentration of catechins would increase the number of spores
killed. See also Ans. 7 (noting Kudo's teaching that decrease in B. cerus
spores was concentration-dependent).
Accordingly, we find that the prior art provides a reasonable
expectation of success that catechins modified at the 4' position with a long
chain fatty acid would kill spores. Appellant's reliance on Fukami's
statement about relatively weak antibacterial activity for catechins modified
at the 4' position, and Kudo's teaching that catechins require long incubation
periods, is unavailing. Claims 1, 4, 19, and 29 are broadly directed to killing
"spores" ( or "bacterial spores" in claim 29) using "an effective amount" of
the claimed modified catechins, e.g. EGCG stearate. The claims do not
recite an upper limit on the amount of modified catechins that can be used,
nor are they limited to killing any specific species of spores. The claims also
do not recite a time component shorter than the experiments disclosed in
Kudo, which lasted up to twelve weeks. See, e.g., Kudo Fig. 1. (Claim 19
does recite a time component, which includes "months" and "years.") The
claims also do not recite any specific degree of "killing," and thus killing
even a minimal number of spores falls within the claim. In view of the
scope of the claims and the teachings of the prior art as discussed above, we
determine that the combination of Kudo, Fukami, and Hsu would have
provided a person of ordinary skill in the art with a reasonable expectation of
success that catechins modified at the 4' position with a fatty acid having a
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hydrocarbon chain length of between 14 and 22 would kill spores, as recited
in claims 1, 4, 19, and 29.
Relying on a declaration submitted by inventor Dr. Hsu,9 Appellant
argues that the claimed subject matter demonstrates unexpected results.
Appeal Br. 8-9. Specifically, Appellant asserts that the claimed compounds
"showed a significant inhibition of germination for B. cereus when the
endospores were treated for 5 minutes with esterified polyphenol," and a
"complete inhibition (100%) [] when treated for 15 minutes." Appeal Br. 8
( quoting Hsu Declaration ,i 7). Appellant further argues that in contrast to
Kudo which teaches that "it takes up to 12 weeks to achieve maximal growth
inhibition of spores," "[t]he method of [the] pending claims has been shown
to kill over 90% of spores within 30 minutes of application of the esterified
EGCG." Appeal Br. 8-9.
We are not persuaded that Appellant's data demonstrate unexpected
results. Appellant must prove a nexus between the alleged unexpected
results and the merits of the claimed invention. See In re GPAC Inc., 57
F.3d 1573, 1580 (Fed. Cir. 1995). Here, however, Figure 1 in the Hsu
Declaration demonstrates inhibition of endospore germination, which as
Appellant itself has argued, is distinct from the claimed method of "killing
spores." See, e.g., Appeal Br. 6; Reply Br. 3 ("It is understood in the art that
growth inhibition and cell death (killing) are not one in the same.").
Further, unexpected 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). Neither Figure 1 nor Figure 3 in the Hsu
9 Declaration Under 37 C.F.R. § 1.132, submitted by Stephen Hsu, dated
October 6, 2016 ("Hsu Declaration").
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Declaration compare the claimed compounds to the closest prior art, which
the Examiner identified as Fukami's EGCG esterified with lauric acid. See,
e.g., Ans. 10-13. Figure 1 compares EGCG stearate to L TP, which is
catechins randomly modified at multiple sites with 18-carbon lipid chains.
See Hr'g Tr. 4:24-5:12; see also Spec. 52 (discussing LTP). Figure 3
compares EGCG stearate to EGCG, not to EGCG esterified with lauric acid.
Because the record is lacking a comparison of the spore-killing effects
of the claimed compounds with the closest prior art, we determine that on
this record, Appellant has not demonstrated unexpected results sufficient to
outweigh the evidence of obviousness presented in the Examiner's prima
facie case.
Rejection of Claim 28 as Obvious Over Fukami, Kudo, Hsu, Baugh, and
Keynan
Claim 28 depends from claim 1, and further specifies that "the spores
are contacted for 5 minutes, 10 minutes, 15 minutes, 30 minutes, or one
hour." Appeal Br. 12 (Claims Appendix). The Examiner found that a
person of ordinary skill in the art would have been motivated "to provide the
modified Fukami's composition in contact with spores for 15 minutes, 30
minutes or an hour" because Baugh teaches that "generally spores need to be
exposed [ to sporicides] for a time of about 15 minutes to 60 minutes in order
to achieve a useful level of spore reduction." Non-Final Act. 7-8 ( citing
Baugh 4: 1-22).
We adopt the Examiner's findings of fact with respect to this
rejection, and agree that claim 28 would have been obvious over Fukami,
Kudo, Hsu, Baugh, and Keynan.
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In response to this rejection, Appellant relies on the arguments it
presented in response to the previously-addressed rejection. Appeal Br. 9.
Our prior analysis applies with equal force here.
Appellant additionally argues that "[ e Jven though Baugh teaches a
method of killing spores in an hour or less, one of skill in the art would not
have been motivated to use the method of the pending claims for less than an
hour because the combination of Fukami, Kudo, and Hsu suggests that it
takes weeks to kill bacterial spores." Appeal Br. 9. We are not persuaded
by this argument. As noted above, Kudo teaches that higher concentrations
of catechins reduced the number of C. botulinum and C. butyricum spores to
undetectable levels more quickly than lower concentrations. See, e.g., Kudo
Fig. l(a) and (b). In view of this teaching and Baugh's statement that spores
need to be exposed to sporicides for 15-60 minutes in order to achieve a
useful level of spore reduction, we agree with the Examiner that it would
have been prima facie obvious to contact spores for the periods of time
recited in claim 28. We note that like the claims discussed above, claim 28
also does not recite any upper limit on the amount of modified catechins that
can be used in the claimed method. Nor does claim 28 require any specific
degree of "killing," and thus even killing a minimal number of spores within
the recited time periods falls within the claims.
Finally, Appellant again alleges unexpected results. Appeal Br. 9.
For the reasons discussed above, we determine that on this record, Appellant
has not demonstrated unexpected results.
Accordingly, we affirm the rejection of claim 28 as obvious over
Fukami, Kudo, Hsu, Baugh, and Keynan.
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Rejection of Claims 6---8 and 26 as Obvious Over Fukami, Kudo, Hsu, and
Walker; Rejection of Claim 27 as Obvious Over Fukami, Kudo, Hsu, and
Hara
The Examiner rejected claims 6-8 and 26 as obvious over Fukami,
Kudo, Hsu, and Walker. According to the Examiner, Walker teaches
"germicidal compositions that kill spores wherein the composition
comprises antibacterial agents inclusive of phenolic compounds in
combination with other antibacterial agents." Non-Final Act. 9 (citing
Walker 2:5-35).
The Examiner rejected claim 27 as obvious over Fukami, Kudo, Hsu,
and Hara. According to the Examiner, Hara teaches "that green tea
polyphenols can be added as an antibacterial agent to prevent food from
being contaminated with bacteria including Staphylococcus." Non-Final
Act. 9 ( citing Hara, first paragraph).
We adopt the Examiner's findings of fact with respect to these
rejections, and agree that claims 6-8 and 26 would have been obvious over
Fukami, Kudo, Hsu, and Walker, and that claim 27 would have been
obvious over Fukami, Kudo, Hsu, and Hara.
In response to these rejections, Appellant argues that one of ordinary
skill in the art would not have been motivated to combine the cited
references because the combination would not have been successful in
killing spores. Appeal Br. 7-8. For the same reasons discussed above with
respect to the first-addressed rejection, we are not persuaded by Appellant's
argument. Accordingly, we affirm the rejection of claims 6-8 and 26 over
Fukami, Kudo, Hsu, and Walker, and the rejection of claim 27 over Fukami,
Kudo, Hsu, and Hara.
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CONCLUSION
We affirm the rejection of claims 1, 4, 19 and 29 under 35 U.S.C.
§ 103 as being unpatentable over Fukami, Kudo, and Hsu.
We affirm the rejection of claim 28 under 35 U.S.C. § 103 as being
unpatentable over Fukami, Kudo, Hsu, Baugh, and Keynan.
We affirm the rejection of claims 6-8 and 26 under 35 U.S.C. § 103
as being unpatentable over Fukami, Kudo, Hsu, and Walker.
We affirm the rejection of claim 27 under 35 U.S.C. § 103 as being
unpatentable over Fukami, Kudo, Hsu, and Hara.
DECISION SUMMARY
In summary:
1, 4, 19 103 Fukami, Kudo, and 1, 4, 19 and
and29 Hsu 29
28 103 Fukami, Kudo, Hsu, 28
Bau h, and Ke nan
6-8,26 103 Fukami, Kudo, Hsu, 6-8,26
and Walker
27 103 Fukami, Kudo, Hsu, 27
and Hara
Overall 1, 4, 6-8, 19,
Outcome and 26-29
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. § l .136(a). See 37 C.F.R.
§ l.136(a)(l )(iv).
AFFIRMED
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