Rashtchian, Ayoub et al.

Patent Trials and Appeals Board

Jun 12, 2020

10633629 - (D) (P.T.A.B. Jun. 12, 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.
10/633,629 08/05/2003 Ayoub Rashtchian 17104.0047U2 6375
23859 7590 06/12/2020
Ballard Spahr LLP
SUITE 1000
999 PEACHTREE STREET
ATLANTA, GA 30309-3915
EXAMINER
POPA, ILEANA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
06/12/2020 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):
USpatentmail@ballardspahr.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte AYOUB RASHTCHIAN and DAVID M. SCHUSTER

_________________

Appeal 2019-005017
Application 10/633,629
Technology Center 1600
_________________

Before DEBORAH KATZ, JOHN G. NEW, and RYAN H. FLAX,
Administrative Patent Judges.

KATZ, Administrative Patent Judge.

DECISION ON APPEAL

Appellant1 seeks our review,2 under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 43–49, 52, 53, and 56–64. We have
jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party-in-interest as Qiagen Beverly, Inc. (Appeal Br. 1.)
2 We consider the Final Office Action issued December 28, 2017 (“Final
Act.”), the Appeal Brief filed July 27, 2018 (“Appeal Br.”), the Examiner’s
Answer issued on April 12, 2019 (“Ans.”), the Reply Brief filed June 12,
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The Examiner rejects claims 43–47, 52, 56–61, 63, and 64 under 35
U.S.C. § 103(a) over Li,3 McMillan,4 Lopez Garcia,5 Durmowicz,6 and
Kyle.7 (Ans. 4–6.)
The Examiner also rejects claims 43–48, 52, and 56–64 under 35
U.S.C. § 103(a) over Li, McMillan, Lopez Garcia, Durmowicz, Kyle, and
Blaschke.8 (See Ans. 6.)
The Examiner entered a new ground of rejection for claims 49 and 53
under 35 U.S.C. § 103 over Li, McMillan, Lopez Garcia, Durmowicz, Kyle,
and Wierenga.9 (Ans. 7–8.)10

2019 (“Reply Br.”) and the oral argument held on May 6, 2020, in reaching
our decision.
3 Li and Wang, “Application of real-time polymerase chain reaction for the
quantitation of interleukin-I~ mRNA upregulation in brain ischemic
tolerance,” Brain Research Protocols, 5:211-217 (2000).
4 McMillan et al., “Methods for Quantitative Analysis of Nucleic Acid
Amplification Reaction,” U.S. Patent No. 6,783,934B1, issued August 31,
2004.
5 Lopez Garcia et al., “Use of Flow Injection Flame Atomic Absorption
Spectrometry-for Slurry Atomization. Determination of Copper, Manganese,
Chromium and Zinc in Iron Oxide Pigments, Analyst 116:517–20 (1991).
6 Durmowicz, et al., “Detection of Neisseria Gonorrhoeae by Amplification
and Detection of Its Nucleic Acid,” US Patent No. 5,962,273, issued
October 5, 1999.
7 Kyle, “Arachidonic Acid and Methods for the Production and Use
Thereof,” US Patent No. 5,658,767, issued August 19, 1997.
8 Blaschke et al., “Rapid quantitation of proinflammatory and
chemoattractant cytokine expression in small tissue samples and monocyte-
derived dendritic cells: validation of a new real-time RT-PCR technology,”
J. Immunol. Methods, 246:79–90 (2000).
9 Wierenga, US Patent 5,968,889, issued October 19, 1999.
10 In the Answer, the Examiner stated that the instant method is not enabled
with respect to using antifoam O-30 because antifoam O-30 was
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Appellant’s Specification is directed to methods of real-time nucleic
acid amplification that use anti-foam reagents. (Spec. 1:12–15.) Appellant
explains that analysis of real-time polymerase chain reaction (“RT-PCR”)
involves quantifying how much template the polymerase produces by
measuring a fluorescent signal incorporated into the template with each
amplification cycle. (See id. at 3:9–16.) According to Appellant,
determining baseline fluorescence is a major problem in the analysis of RT-
PCR data because the baseline varies for each reaction, increasing and
decreasing without relation to amplification of the template. (See id. at
3:29–30.) Appellant’s Specification states that “[t]hese problems are often
exacerbated by bubbles in the reaction that interfere with optical
measurements” and are likely caused by non-ionic polymeric detergents,
which are, nevertheless, a necessary component of the amplification
reaction. (Id. at 3:33–4:2.)
The Specification states that the anti-foam reagents decrease variation
in the fluorescence background in enzyme assays, “by reducing optical
interference from bubbles that would otherwise change the fluorescent signal
in a manner that is not dependent on the concentration of the desired nucleic
acid product.” (Spec. 5:9–15.)
Appellant’s claim 43 recites:
A method for detecting a target nucleic acid in a sample,
comprising the steps of amplifying the target nucleic acid using
a real-time quantitative polymerase chain reaction and detecting

discontinued. (See Ans. 3.) The Examiner did not formalize a rejection
based on 35 U.S.C. § 112, first paragraph. Thus, we do not consider the
claims to be rejected on that basis and do not consider Appellant’s
arguments in response to such a rejection. (See Reply Br. 17–19.)
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the product of said polymerase chain reaction by optical
detection,
wherein said real-time quantitative polymerase chain
reaction is carried out in the presence of:
a thermostable DNA polymerase suitable for temperature
cycling between high and low temperatures;
a detergent;
and at least one anti-foam reagent at a concentration of
less than 0.01%, wherein said anti-foam reagent is selected
from the group consisting of 1520-US, AF, FG-10, O-30, SE-
15, and Antifoam B.

(Appeal Br. 77.) Appellant’s claim 52 is also independent and recites a
composition for quantifying a target nucleic acid by real-time PCR,
including, inter alia, “(e) at least one anti foam reagent at a concentration of
less than 0.01%, wherein said anti-foam reagent is selected from the group
consisting of 1520-US, AF, FG-10, O-30, SE-15, and Antifoam B.” (Id. at
78.)
Examiner’s Rejection of claims 43–47, 52, 56–61, 63, and 64 under
35 U.S.C. § 103(a) over Li, McMillan, Lopez Garcia, Durmowicz, and Kyle

We begin our review of the Examiner’s rejection and Appellant’s
arguments by focusing on independent claim 43. The Examiner cites Li for
its teaching of TaqMan hot-start RT-PCR for quantitation of mRNA. (See
Ans. 4, citing Li abstract.) Li teaches including the detergent Tween 20 in
the “TaqMan PCR core reagents.” (See Li 212; see Ans. 4.) As the
Examiner notes, Li does not teach including an anti-foam agent in the
reactions. (See Ans. 4.)
The Examiner cites McMillan for its teaching that air bubbles can
have a negative effect on optical detection in amplification reactions such as
RT-PCR. (See Ans. 4, citing McMillan 3:57–4:11 and 35:54–57.) The
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Examiner further cites Lopez Garcia for its teaching that abundant foam
from surfactant can create reproducibility problems because of bubbles
trapped in the sample loop in a procedure for determining copper,
manganese, chromium, and zinc in slurries of commercial iron oxide
pigment using spectrometry. (See Ans. 4, citing Lopez Garcia 518.) Lopez
Garcia teaches further that “this problem could be overcome by adding
several drops of antifoaming agent . . . to the slurry,” but that because
detergent decreased the absorption signal for copper, the surfactant was
eliminated instead. (Lopez Garcia 518.)
The Examiner cites Durmowicz for its teaching to include anti-foam
reagents in a polymerase reaction for optical detection of an amplified
nucleic acid. (See Ans. 4, citing Durmowicz abstract, 26:20.) Durmowicz
teaches strand displacement amplification (“SDA”) assays, which are
distinct from PCR reactions and use a different polymerase. (See
Durmowicz abstract.)
The Examiner cites Kyle for its teaching of the use of silicone-based
anti-foaming agent 1520-US in a fermentation reaction. (See Ans. 5, citing
Kyle 11:53–54.)
As the Examiner finds, the prior art teaches detecting target nucleic
acid in a sample using RT- PCR and detecting the product of the reaction by
optical detection. (See Li abstract.) The prior art also teaches that this
reaction includes a detergent, but that bubbles can have a negative effect on
optical detection of the amplification products of RT-PCR. (See Li 212,
McMillan 3:57–4:11 and 35:54–57.) Although the Examiner does not cite to
the use of anti-foam reagent in RT-PCR specifically, anti-foam was known
to have been used with a different polymerase. (See Durmowicz abstract,
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26:20.) The prior art also shows that at least one of the anti-foams recited in
claim 43 was known in the art. (See Kyle 11:53–54.)
The Examiner determines that it would have been obvious to one of
ordinary skill in the art to modify the method of Li by further including an
anti-foam agent in a concentration of up to 0.015% in the master mix to
improve optical detection in real-time PCR. (See Ans. 5.) The Examiner
notes that although the prior art does not specifically teach the range of
0.01% or less anti-foam reagent, one of ordinary skill would have found it
obvious, requiring only routine experimentation, to vary the anti-foam
concentration with the intent of optimizing the PCR reaction. (See id.; see
also id. at 9–10, 35–36.)
Appellant’s Evidence of Unexpected Results
We turn to Appellant’s evidence of unexpected results in order to
review the substantive record as a whole. See In re Packard, 751 F.3d 1307,
1312 (Fed. Cir. 2014) (“The ‘prima facie case’ determination is a purely
procedural device that operates at the examiner level to clarify how the
interaction process proceeds. Thereafter any final rejection by the examiner,
and any review of the rejection, whether by the Board or through appeal to
the courts, turns on the substantive question of the merits of the rejection.”);
see also In re Rinehart, 531 F.2d 1048, 1052 (CCPA 1976) (“When prima
facie obviousness is established and evidence is submitted in rebuttal, the
decision-maker must start over. . . . An earlier decision should not, as it was
here, be considered as set in concrete, and applicant’s rebuttal evidence then
be evaluated only on its knockdown ability. . . . [A] final finding of
obviousness may of course be reached, but such finding will rest upon
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evaluation of all facts in evidence, uninfluenced by any earlier conclusion
reached . . . .”)
Appellant argues that the method of the rejected claims improves the
efficiency, accuracy, and precision of the RT-PCR reaction when compared
to RT-PCR without an anti-foam reagent. (See Appeal Br. 46–55.)
Appellant asserts that improving optical detection and improving RT-PCR
efficiency are distinct outcomes and that the claimed method unexpectedly
accomplishes the later as well. (See id. at 49.)
Appellant cites to Examples I, II, and III of the Specification to show
that the efficiency of RT-PCR with anti-foam reagents is higher than in
samples without anti-foam reagent and points to Examples IV and VI11 to
show the RT-PCR with anti-foam reagent has improved precision and
accuracy. (See Appeal Br. 49–50.) Appellant refers to Example V, as well.
(See id. at 52–53.)
Appellant also cites to the Declaration of inventor David Schuster,
submitted under 37 C.F.R. § 1.132 on December 4, 2017 (“Schuster Decl.”)
to support these arguments. (See Appeal Br. 53.) Mr. Schuster states that he
reviewed the prior art cited by the Examiner in the Office Action mailed
May 11, 2016. (See Schuster Decl. ¶ 9.) The rejections in that Office
Action do not cite McMillan or Durmowicz. Accordingly, Mr. Schuster’s

11 Appellant does not provide specific argument about Example VI. The
description of Example VI in Appellant’s Specification appears to be a copy
of the description of Example IV. (Compare Spec. 27–28 with Spec. 28–
30.) Thus, even though Appellant refers to Example VI in the Appeal Brief,
we do not review the results it presents separately from those of Example
IV.
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declaration does not address the current rejection of Appellant’s claims. We
review Mr. Schuster’s testimony to the extent it is relevant to the current
rejection.
The results of many of the experiments in Appellant’s Specification
are reported as “Ct” values. Appellant explains that “Ct” is the intersection
between an amplification curve and a threshold line and is a relative measure
of the concentration of target in the PCR reaction. (See Appeal Br. 50.)
Appellant reports that many factors impact the absolute value of Ct besides
the concentration of the target so that “Ct values from PCR reactions run
under different conditions or with different reagents cannot be compared
directly.” (Id.) It is not clear what impact this statement has on the
comparisons of Ct values from different PCR performed under different
conditions that are presented in the examples of Appellant’s Specification.
Appellant argues that Example I shows “the effect of antifoam reagent
1520-US at concentrations of at least 0.01%, 0.001% and 0.0001% increase
the PCR efficiency from 91.1% (no antifoam reagent; 0%) to 96.5%, 98.5%
and 97.7%, respectively.” (Appeal Br. 50.) The results of the experiments
in Example I are reported in Table 1 of Appellant’s Specification, which is
reproduced below.
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Table 1 provides “PCR efficiency” determinations for different
concentrations of 1520-US, including 0% as a control. We note that no
measure of statistical error is reported in Table 1.
The Specification discusses these results, wherein:
Results demonstrated that the inclusion of anti-foam in
PCR does not inhibit the kinetics of DNA amplification or
interfere with optical detection of the 5'-nuclease TaqMan
assay. Linear regression analysis of the log of DNA copy input
versus Ct number indicated that inclusion of anti-foam at all
concentrations that were tested, improved PCR efficiency.
Concentrations of as low as 0.001%, were sufficient to
eliminate bubbles in the reaction cocktail and improve its liquid
handling properties. However, anti-foam concentrations of
0.1% or 0.01% imparted a cloudy appearance to the reaction.
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Therefore, optimal concentration of a given anti-foam
compound must be determined empirically and is a balance
between the cloud point, the efficacy of the compound to
eliminate bubbles from surfactants, and any potential adverse
effect on DNA amplification.

(Spec. 24:31–25:7.) We agree that Table 1 shows PCR efficiency is higher
for each concentration of anti-foam reagent 1520-US than it is for 0%,
although it is not clear that this result is statistically significant.
Appellant argues that Table 1 shows that “regardless of the effect on
bubbles or the appearance of the reaction mixture in which a cloudy
appearance may have a negative effect on optical detection, the PCR
efficiency is still improved for the claimed concentrations tested.” (Appeal
Br. 51.) According to Appellant, because reactions with higher
concentrations of anti-foam are cloudy, yet still yield increased PCR
efficiency, the higher efficiency is not due to reducing bubbles. (See id.)
Appellant’s argument makes the assumption that cloudiness is caused
by bubbles and that a cloudy solution must have significant bubbles. But
Appellant does not direct us to evidence of the cause of cloudiness either in
the Specification or elsewhere to support this argument. We note that
Mr. Schuster testifies that in Exhibit A of his declaration, the addition of
anti-foam at low concentrations “yielded a clear solution, lacking any visible
precipitate . . . .” (Schuster Decl. ¶ 17.) Thus, clouding may be caused by
precipitate instead of bubbles. If the cloudiness of reactions with higher
concentrations of anti-foam is due to precipitate and not to bubbles,
Appellant’s argument that the higher efficiency cannot be due to the lack of
bubbles is unsupported.
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In general, both Appellant and Mr. Schuster fail to sufficiently explain
the interaction between the known optical interference caused by bubbles
(see McMillan 35:55–56), cloudiness (which could be due to bubbles or
precipitate), and the measurements required to determined PCR efficiency.
Appellant’s Specification states:
Ideally, the basal fluorescence of a real-time reaction
should be invariant from cycle to cycle until the accumulation
of PCR product is sufficient to produce signal above
background. Surfactants present in PCR and Taq DNA
polymerase preparations, however, can result in bubbles when
reactants are mixed. Failure to clear reactions of bubbles prior
to PCR cycling can distort optical signals and skew background
fluorescence readings.

(Spec. 27:23–28.) Because Appellant describes Ct measurements as “the
intersection between an amplification curve and a threshold line (see, for
example, Li, Figure 2)” (Appeal Br. 50), it is not clear to us that bubbles,
which can skew background fluorescence readings, would not also impact Ct
measurements. It is not clear that bubbles have no impact on Appellant’s
efficiency calculations, which are based on Ct measurements.
Appellant argues that the increased efficiency of reactions including
anti-foam shown in Example I and Table 1 of the Specification are “not
identified as being tied to optical detection” and that the Examiner makes an
unsupported assumption that optical detection is involved. (Appeal Br. 50–
51.) In light of the statement in the Specification and teachings in
McMillian that bubbles can distort optical signals and, thus skew
background fluorescence readings, we are not persuaded that a link between
efficiency and optical detection is completely unsupported. Appellant fails
to present sufficient evidence to persuade us that one of ordinary skill in the
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art would have considered the increased efficiency reported in Table 1 to
have nothing to do with a reduction in bubbles caused by the addition of
anti-foam. Appellant does not direct us to evidence of increased efficiency
that is based on a parameter independent of optical detection.
Appellant argues further that Examples II and III of the Specification
demonstrate different anti-foam reagents at a concentration of less than
0.01% improve PCR efficiency relative to control reactions without anti-
foam reagent in both real-time TaqMan and SYBR Green I PCR reactions.
(See Appeal Br. 51.) The results of Examples II and III are reported in
Tables 2 and 3, respectively, which indicate PCR efficiency as apparently
determined from Ct values obtained from reactions the included anti-foam
reagent and a control reaction without anti-foam reagent.
We agree that Tables 2 and 3 report higher PCR efficiency for
reactions including each anti-foam than for the control reaction without anti-
foam. We also note that no measure of statistical error was reported for the
PCR efficiency determinations in either Table 2 or 3.
Inventor Schuster analyzed the results of Example III, stating that
“mean Ct values for amplification of low (e.g., 100) copy samples of at least
1520-US (33.321) and O-30 (33.267) are one cycle lower than control
(34.271), providing evidence that anti-foam reagents 1520-US and O-30
improve efficacy of low copy nucleic acid analytes in PCR.” (Schuster Decl.
¶ 13 (emphasis added).) The numbers that Mr. Schuster reports are a mean
of the three Ct values reported for the control, 1520-US, and O-30 at 1 x 102
copies of target DNA. Mr. Schuster does not provide a measure of statistical
error for these numbers. Furthermore, it is not clear what Mr. Schuster
means by “improved efficacy.” Mr. Schuster does not discuss the PCR
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efficiency values reported in Table 3. Nor does Mr. Schuster state that the
“improved efficacy” obtained with 1520-US and Sigma O-30 was
unexpected. Mr. Schuster does not state that any of the anti-foams tested in
Example III other than 1520-US and Sigma O-30 improve the efficacy of
low copy analytes in PCR.
Mr. Schuster’s testimony does not persuade us that the results
reported in Tables 2 and 3 demonstrate the method Appellant’s claim 43
produces unexpected results because Mr. Schuster fails to explain why any
improvement in efficacy would have been unexpected or why the increase in
efficiency reported was statistically significant. Thus, even if the results
with DOW 1520-US were unexpected, the evidence is not commensurate
with the full scope of claim 43.
Appellant argues further that Example IV demonstrates anti-foam
reagents improve precision and reliability of low copy RT-PCR. (See
Appeal Br. 52.) Appellant reports that anti-foam 1520-US resulted in an
average Ct of 32.62 with a standard deviation of 0.87 compared with the
control, which had an average Ct of 33.41 with a standard deviation of 1.29.
(See id.) Although the Specification and Mr. Schuster support Appellant’s
argument, we are not persuaded that these results demonstrate anything
unexpected about a method of real-time PCR in the presence of 1520-US or
any other anti-foam recited in Appellant’s claim 43. (See Spec. 27:14–16;
see Schuster Decl. ¶ 14.) Neither the Specification nor Mr. Schuster
provides an analysis of the statistical significance of these results. Appellant
states that “[r]eporting the standard deviation is the most common measure
of precision” (Appeal Br. 50), but it is unclear if the standard deviations
reported for Example IV indicates a significant difference in the results for
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reactions with and without 1520-US. Neither Appellant nor Mr. Schuster
explains why there is a significant and unexpected difference.
Appellant argues that Example V provides a nexus between the
claimed method and the reportedly unexpected results because it
demonstrates that not any anti-foam at any concentration will improve a
PCR reaction. (See Appeal Br. 52.) According to Appellant, anti-foam at a
concentration of 0.1% inhibited PCR amplification, whereas anti-foam
below 0.01% did not. Appellant reports that 1520 US, Antifoam C,
Antifoam B, and O-30 were effective. (See id. at 53, citing Spec. 28:22–30.)
Data supporting these results are not show in the Specification. (See Spec.
28:22–28.)
Appellant’s declarant, Mr. Schuster, states that the results provided in
the Specification are
evidence that the addition of the claimed antifoam reagents
including Dow 1520-US, AF, FG-10, O-30, SE-15, and
Antifoam B at concentrations less than 0.01% result in an
increased sensitivity of the amplification reactions as evidenced
by lower Ct values and higher precision. These results were
unexpected and surprising at the time the instant application
was filed.

(Schuster Decl. ¶ 15.) We are not persuaded by this statement because
Mr. Schuster does not explain why any observed result of adding the anti-
foam agents recited would have been unexpected or surprising, given their
effects on optical interference. It is not clear what “increased sensitivity”
and “higher precision” are and whether they relate to the “PCR Efficiency”
reported in Tables 1–3.
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Mr. Schuster presents results in Exhibits A and B to his declaration to
support his assertion that the method of claim 43 produced results that would
have been considered unexpected. (See Schuster Decl. ¶¶ 16–19.)
Mr. Schuster reports that Exhibit A shows that each of the anti-foam agents
failed to produce a solution with a visible precipitate at concentrations less
than 0.01%. (See Schuster Decl. ¶ 17.) According to Mr. Schuster, these
results would have been unexpected and surprising because they
demonstrate that “the claimed antifoam reagents at concentrations less than
0.01% are sufficient to eliminate bubbles without adversely effecting PCR
amplification.” (Schuster Decl. ¶ 17.)
This statement is not persuasive because Mr. Schuster fails to explain
why it would have been unexpected that adding anti-foam would produce a
clear solution lacking visible precipitate. Mr. Schuster’s determination may
reflect his statement that “[i]t was generally believed that anti-foam reagents
were incompatible in polymerase reactions” (Schuster Decl. ¶ 12), but this
statement is not supported by the prior art cited by the Examiner.
Specifically, the current rejection cites Durmowicz, which teaches including
0.015% anti-foam reagent in a polymerase reaction. (See Durmowicz 26:20,
Example 14; see Final Act. 4.) Mr. Schuster did not consider Durmowicz in
his declaration. (See Schuster Decl. ¶ 9.)
Mr. Schuster reports that Exhibit B shows that the anti-foam reagents
recited in claim 43 “demonstrate identical efficiency and sensitivity across
all concentrations tested” and that this is an unexpected and surprising result
showing that “antifoam reagents at concentrations less than 0.01% provide
reliable and reproducible PCR amplification.” (Schuster Decl. ¶ 18.)
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Exhibit B provides Ct values for anti-foam reagents at concentrations from
0.1% to 0.0001% with 1 x 102 to 1 x 108 target copies.
Again, we are not persuaded that the claimed method would produce
results unexpected by one of ordinary skill in the art. Mr. Schuster does not
explain why one of ordinary skill would have expected less anti-foam
reagent to produce unreliable results. Mr. Schuster does not direct us to
evidence of the ability of each anti-foam reagent to reduce bubbles at the
concentrations tested in Exhibit B or the expectation of those in the art. For
example, if it was known that anti-foam reagents can reduce bubbles at
0.0001%, it might not have been unexpected that using anti-foam at this
concentration in the claimed method would have produced the similar results
as adding anti-foam reagent at 0.01%.
In summary, we are not persuaded by any of the evidence Appellant
cites that adding the anti-foam reagents recited in claim 43 produced results
that would have been surprising or unexpected to those of ordinary skill in
the art. We are not persuaded that higher PCR efficiency would have been
unexpected given that it was known in the art that bubbles cause optical
interference and PCR efficiency is based on Ct values, which are determined
by detecting optical signals.
Appellant’s Arguments in Regard to the Prima Facie Case
Appellant raises many arguments against the Examiner’s prima facie
case for obviousness. (See, inter alia, Appeal Br. 10–47.) Many of these
arguments address the merits of prior art references individually, but without
consideration of their combination with the other cited references. For
example, Appellant argues that Li fails to teach anti-foam reagent, McMillan
fails to teach any component in a reaction mixture that can be used in RT-
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PCR, Durmowicz fails to teach a thermostable DNA polymerase or
detergent, and Kyle fails to teach a DNA polymerase. (See id. at 25.) “Non-
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Appellant attacks the Examiner’s finding that McMillan would have
provided a motivation to modify the method taught in Li, arguing that
McMillan presents a mechanical solution to the problem of bubbles instead
of by adding anti-foam reagent. (Appeal Br. 10, 31.) Appellant argues that
McMillan fails to teach adding additional components to a reaction mixture.
(See id. at 20.) We are not persuaded by these arguments because
McMillian was not cited for teaching a solution to the problem of bubbles in
RT-PCR, but rather to show that those of ordinary skill would have known
that bubbles were a problem. (See Ans. 4 (“McMillan et al. teach that air
bubbles could have a negative effect on optical detection in amplification
reactions such as RT-PCR (column 3, lines 57 through column 4, line 11;
column 35, lines 54-57).”)
Similarly, Appellant argues that Li presents no motivation to modify
its own teachings because it fails to cite any problems with reproducibility
using optical detection. (See Appeal Br. 12.) This argument is unpersuasive
because it fails to acknowledge that McMillan teaches the negative effects of
air bubbles on optical detection. Whether or not this negative effect was
recognized in Li, those of ordinary skill would have been aware of it from at
least McMillan.
Appellant argues that Durmowicz fails to teach a protocol combining
a detergent, a thermostable polymerase and an anti-foam reagent in RT-PCR
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and also fails to specify which anti-foam reagent it used for the reaction
described. (See Appeal Br. 16.) Durmowicz was cited only to show that
anti-foam reagents had been used with a polymerase in the art. (See Ans. 4–
5 (“Durmowicz et al. teach that antifoam agents in concentration of 0.015%
could be successfully used in conjunction with polymerases, i.e., antifoams
are not inhibitory (Example 14).”).) Durmowicz was not cited for teaching
anti-foam reagent in an RT-PCR solution and was not cited for teaching
specific types of anti-foam reagents that were known in the art at the time.
Thus, Appellant’s argument is unpersuasive. Appellant’s argument that
Durmowicz fails to teach why using an anti-foam reagent is necessary is
similarly unpersuasive in light of the Examiner’s citation of McMillan. (See
Appeal Br. 17.)
Appellant argues further that the Examiner inappropriately relied on
Durmowicz for a teaching of the concentration of anti-foam reagent recited
in claim 43 because the reaction in Durmowicz is different from a PCR
reaction. (See Appeal Br. 17.) Although the Examiner noted the
concentration of anti-foam reagent recited in Durmowicz (0.015%), which is
similar to that recited in claim 43 (less than 0.01%), the rejection is based on
the ability of one of ordinary skill in the art to determine the claimed
concentration based on routine experimentation. (See Ans. 5.) Accordingly,
Appellant’s argument is not persuasive.
In the Reply Brief, Appellant argues that the Examiner failed to
establish that the claimed combination of components in a RT-PCR was
recognized to be a result-effective variable because it was not recognized as
improving amplification efficiency of RT-PCR. (See Reply Br. 16.) We are
not persuaded by this argument, first, because Appellant has not persuaded
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us that anti-foam reagent at added to RT-PCR at less than 0.01% improves
amplification efficiency. We are also not persuaded because even if
amplification efficiency is improved, one of skill in the art need only have
optimized the concentration of anti-foam reagent to reduce bubbles. Claim
43 does not recite a limit on amplification efficiency.
We are similarly not persuaded by Appellant’s argument that those of
ordinary skill in the art would not have been motivated by Durmowicz to
select an anti-foam for use in RT-PCR because Durmowicz teaches using a
different polymerase, which is not thermostable and does not require
detergent. (See Appeal Br. 18.) We are not persuaded by Appellant’s
argument because Durmowicz was cited only for its teaching that it was
known to use anti-foam with a DNA polymerase. We agree with the
Examiner that this teaching would have provided the suggestion it might be
useful with other DNA polymerases, such as the DNA polymerases used in
RT-PCR. We are not persuaded that Durmowicz must have taught the exact
conditions of the method of claim 43 for it to contribute to the obviousness
of the method. “[I]f a technique has been used to improve one device, and a
person of ordinary skill in the art would recognize that it would improve
similar devices in the same way, using the technique is obvious unless its
actual application is beyond his or her skill.” KSR Int'l Co. v. Teleflex Inc.,
550 U.S. 398, 417 (2007). Adding anti-foam reagent to RT-PCR would not
have been beyond the skill of those in the art and Durmowicz relates to
polymerases in the same category as the DNA polymerase used in RT-PCR.
Thus, we are not persuaded that Durmowicz fails to provide a suggestion to
use anti-foam reagent with other DNA polymerases.
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Appellant argues that the Examiner improperly relied on Kyle because
Kyle relates to fermentation and does not teach a protocol that combines
detergent, a thermostable polymerase, and anti-foam reagent suitable for RT-
PCR. (See Appeal Br. 21.) According to Appellant, the Examiner fails to
provide a basis for selecting the anti-foam reagent taught in Kyle. Kyle was
cited to demonstrate the knowledge in the art of at least one of the anti-foam
reagents recited in claim 43. (See Ans. 5 (“Kyle et al. teach the 1520-US as
a suitable silicone-based antifoaming agent (column 11, Example 3).”) We
are not persuaded by Appellant’s argument because McMillan and
Durmowicz provide a basis for including an anti-foam reagent in RT-PCR.
By arguing that Kyle alone fails to teach all of these aspects of the prior art,
Appellant fails to consider the entire rejection presented by the Examiner.
Appellant complains that the Examiner cites five separate references
to describe “disparate elements” of the claimed method (see Appeal Br. 23),
but the number of references cited does not indicate non-obviousness. “The
criterion . . . is not the number of references, but what they would have
meant to a person of ordinary skill in the field of the invention.” In re
Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991). “[F]amiliar items may have
obvious uses beyond their primary purposes, and in many cases a person of
ordinary skill will be able to fit the teachings of multiple patents together
like pieces of a puzzle.” KSR, 550 U.S. at 420. The Examiner provides a
sufficient explanation why one of ordinary skill in the art would have
combined the knowledge of RT-PCR components, with the knowledge of
the problems caused by bubbles and the knowledge that anti-foams can be
used with other DNA polymerases and would have considered it obvious to
add a known anti-foam reagent to the RT-PCR solve the problem.
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Appellant presents several arguments against the citation of Lopez
Garcia, asserting that it is not analogous to the subject matter of the claimed
method and should not have been considered. (See Appeal Br. 10, 33–44.)
A reference is analogous art to the claimed invention if the reference is
either in the same field of endeavor or if it is reasonably pertinent to the
problem faced by the inventor. See In re Oetiker, 977 F.2d 1443, 1447 (Fed.
Cir. 1992). For example, prior art teaching sealing arrangements in
pressurized carbonated beverages systems have been held to be analogous to
claimed cartridges for low pressure liquid chromatography because both
allow easy access and variation of the cartridge’s contents without
destroying its ability to be sealed. See Sci. Plastic Prod., Inc. v. Biotage AB,
766 F.3d 1355, 1359 (Fed. Cir. 2014).
Appellant argues that “the problem faced by the inventors was not
simply how to eliminate bubbles in RT-PCR for optical detection – it was, in
fact, minimizing or reducing baseline fluorescence drift in data analysis of
optical measurements in PCR amplification that use detergents to stabilize
thermostable DNA polymerase (¶ [0009] of the published application).”
(Appeal Br. 38.) The cited paragraph states that the problem solved by the
method of claim 43 is the interference of bubbles in optical measurements
when automating PCR data analysis. (See Spec. 3:29–4:2.)
Lopez Garcia teaches using atomic absorption spectrometry to
determine the amount of elements in slurries of commercial iron oxide
pigments. (See Lopez Garcia abstract.) Lopez Garcia teaches that atomic
absorption measurement involves introduction of solid samples into a flame
and that flow injection (“FI”) methods could be a suitable way of avoiding
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clogging problems when introducing a suspension into the flame. (Lopez
Garcia 517.) Lopez Garcia reports that
[w]hen the surfactant concentration was higher than about
0.20%, the slurries gave rise to abundant foam and small air
bubbles were trapped in the sample loop of the FI manifold,
making reproducibility worse. Although this problem could be
overcome by adding several drops of antifoaming agent
[‘Antifoam A’ (Fluka)] to the slurry, it was also noted that
Triton X-100 decreased the absorption signal of copper, both
for aqueous solutions and for slurries, and hence this surfactant
was not employed.

(Lopez Garcia 518.) Thus, the problem addressed by adding anti-foam
reagents in Lopez Garcia were bubbles in the FI manifold. This problem is
not reasonably pertinent to the problem of optical detection as described in
Appellant’s Specification because introducing samples through an FI
manifold to a flame is not related to optical detection of a fluorescent signal
in liquid reaction mixture.
Although we are not persuaded by Appellant’s arguments that Lopez
Garcia is non-analogous art because it does not teach measurements of
polymerase, or any other enzyme, activity, we are persuaded that it is non-
analogous because it is not pertinent to the problems of bubble interference
in the optical detection of a fluorescent signal in RT-PCR. Accordingly, we
are persuaded that Lopez Garcia does not contribute to the obviousness of
the method recited in Appellant’s claim 43.
In affirming an obviousness rejection, the Board may rely upon fewer
than all the references cited by the Examiner. See In re May, 574 F.2d 1082,
1090 (CCPA 1978); In re Kronig, 539 F.2d 1300, 1304 (CCPA 1976).
Despite the inappropriateness of the citation to Lopez Garcia, we are not
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persuaded that the Examiner erred in rejecting claim 43 because McMillan
provides a sufficient teaching of the problem addressed by the recited
method – interference of bubbles caused by detergents in optical
measurements for PCR data analysis. The Examiner finds that one of
ordinary skill in the art would have readily understood that bubbles interfere
with optical detection in RT-PCR from the teachings of McMillan and thus,
“[t]he motivation to use an antifoam is provided by the combined teachings
of McMillan et al. and Lopez Garcia et al.” (Ans. 13.) Thus, we are
persuaded that even if Lopez Garcia does not provide a reason why one of
ordinary skill in the art would have modified, the method taught in Li,
McMillan does.
Appellant argues that ordinarily skilled artisans would not have been
motivated to add additional components to RT-PCR reactions because at the
time of filing, the general state of the art was to simplify reactions by
reducing the number of components in RT-PCR based on the asserted
known sensitivity of these reactions. (See Appeal Br. 15–16.) Appellant
cites to Higuchi12 in support of this argument. Higuchi was cited by the
Examiner in a prior Office Action to show that it was known that bubbles
interfere with optical detection in real-time RT-PCR. (See Office Action of
January 3, 2017, 8, citing Higuchi 6 (“Small air bubbles trapped under the
oil overlay will expand and contract during thermal cycling and can cause
signal variations.”), 8, 16–17.) Appellant argues that Higuchi’s teaching to
centrifuge the reaction mixture to remove problematic air bubbles, instead of

12 Higuchi and Watson, Kinetic PCR Analysis Using a CCD-camera and
without Using Oligonucleotide Probes, PCR Methods Manual, 1–24 (1999).
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adding another component to the reaction mixture, demonstrates the
motivation in the art to simplify reaction mixtures. (See Appeal Br. 15–16.)
We are not persuaded by this argument because Appellant fails to
direct us to evidence that actually cautions against adding additional
components to a PCR reaction mixture to remove bubbles or for any other
reason. That Higuchi, and McMillan, teach other remedies for the problems
caused by air bubbles does not indicate that the claimed remedy would not
have also been obvious.
Appellant argues further there would not have been a reasonable
expectation of success in adding anti-foam reagent to RT-PCR assays. (See
Appeal Br. 26–33.) Appellant argues, first, that Lopez Garcia does not
provide an expectation of success because the anti-foam reagent worsened
the reaction being tested and was ultimately not chosen as the solution to the
problem caused by bubbles. (See id. at 27–28.) As discussed above, we are
not persuaded that Lopez Garcia contributes to the prima facie case for
obviousness because the problem caused by bubbles in that reference is not
pertinent to the problem of Appellant’s claimed method. We are similarly
not persuaded that even if Lopez Garcia ultimately relied on a different way
to reduce bubbles, those of ordinary skill in the art would not have
reasonably expected anti-foam to solve problems caused by bubbles in RT-
PCR by similarly reducing bubbles because the methods and problems of
Lopez Garcia are not analogous to the claimed methods.
Appellant argues further that there would not have been a reasonable
expectation of success in adding anti-foam to one system when it had been
added to what Appellant characterizes as a completely different system.
(See Appeal Br. 28.) Appellant argues that the thermal strand displacement
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amplification (“SDA”) assay of Durmowicz uses different conditions and
amplification processes than PCR. (See id., citing Durmowicz, cols. 10–11
(comparing strand displacement amplification and PCR.) According to
Appellant, because Durmowicz uses the polymerase Bst in SDA assays,
which is known to be thermally unstable under PCR conditions, and
conducts these assays without a detergent, one of ordinary skill in the art
would have known that the components of SDA and PCR assays could not
be interchanged with a reasonable expectation of success. (See Appeal Br.
28–29.) Appellant argues that one of ordinary skill in the art would have not
have had a reasonable expectation of success using the conditions of
thermolabile polymerase with a thermostable polymerase. (See id.)
We are not persuaded by this argument because “[o]nly a reasonable
expectation of success, not absolute predictability, is necessary for a
conclusion of obviousness.” In re Longi, 759 F.2d 887, 897 (Fed. Cir.
1985). Appellant focuses on the differences between the Bst polymerase of
Durmowicz and the thermostable polymerases used in PCR, but both
enzymes are DNA polymerases and carry out similar functions in
presumably similar ways.
Appellant argues that components used with SDA were known to be
incompatible with PCR, specifically the acetylated BSA included in
Example 14 of Durmowicz, which had been shown to be inhibitory to PCR.
(See Appeal Br. 29–30, citing Kreader.13) The rejection is not based on

13 Kreader, “Relief of Amplification Inhibition in PCR with Bovine Serum
Albumin or T4 Gene 32 Protein,” Applied Environmental Microbiology,
1102–06 (1996).
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using all of the components of SDA as taught in Durmowicz, but rather on
the suggestion that anti-foam reagents could be used successfully with the
polymerase in RT-PCR.
The test for obviousness is not whether the features of a
secondary reference may be bodily incorporated into the
structure of the primary reference; nor is it that the claimed
invention must be expressly suggested in any one or all of the
references. Rather, the test is what the combined teachings of
the references would have suggested to those of ordinary skill
in the art.

In re Keller, 642 F.2d 413, 425 (CCPA 1981).
The facts before us are similar to those in In re Droge, 695 F.3d 1334,
1337–38 (Fed. Cir. 2012), where a reasonable expectation of success of a
method mediating sequence specific recombination of DNA in eukaryotic
cells with a modified enzyme was found because the normal enzyme had
previously been used to mediate similar recombination. Although one of
ordinary skill in the art would not have known that the modified enzyme
would work in the same way as the normal enzyme, the fact that both
enzymes shared structural and functional similarities, indicated a reasonable
expectation of success. Similarly, because the Bst polymerase of
Durmowicz and the thermostable polymerases of the claimed RT-PCR
methods ultimately achieve the same goal in generally the same way –
polymerization of DNA templates by covalent linkage of nucleic acids –
there would have been a sufficient basis for one of ordinary skill to have
expected success.
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
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the known options within his or her technical grasp. If this leads
to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that it was obvious under § 103.

KSR, 550 U.S. at 421.
Appellant also argues that Example V of the Specification is evidence
that substances that inhibit enzyme activity can limit the use of RT-PCR and
that it is not as simple as choosing any anti-foam reagent at any
concentration to improve a PCR reaction itself. (See Appeal Br. 52–53; see
Reply Br. 7.) Example V states: “Anti-foam concentration of 0.1% was
inhibitory to PCR amplification with the selected set of anti-foam
compounds resulting in either no amplification or delayed threshold cycle
for product detection. Anti-foam concentrations of 0.01% or lower did not
inhibit PCR amplification.” (Spec. 28:22–24.)
Although we agree with Appellant that it would not be absolutely
predictable that anti-foam reagent could be successfully added to RT-PCR,
because it was successful with at least one DNA polymerase, one of ordinary
skill in the art would have had a reasonable expectation of success to at least
try anti-foam reagent in PCR. Furthermore, as the Examiner indicates,
routine optimization is not considered inventive and Example V
demonstrates that selecting the antifoams and determining their optimal
concentrations require nothing more than routine experimentation. (Ans.
27.) Appellant’s Specification states: “One skilled in the art will recognize
that selection of an anti-foam reagent and choice of appropriate
concentration for in vitro enzymatic reactions as described in the present
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invention may require some routine experimentation.” (Spec. 18:27–29
(emphasis omitted).)
Appellant argues that because McMillan does not teach or suggest
adding anti-foam reagent, even though it recognizes the problems bubbles
can present, those of ordinary skill in the art would have understood that RT-
PCR is a complex reaction that is unpredictable and would not have known
whether thermostable polymerases and anti-foam agents were compatible.
(See Appeal Br. 31.) We are not persuaded by this argument because
McMillan’s alternative solution to the problem of bubbles (using a diamond-
shaped chamber, see McMillan 19:34–37) says nothing about whether an
anti-foam solution would also have been expected to succeed. McMillan
need not have presented every solution to the problem it discusses for any
one solution to have been reasonably expected to succeed.
Appellant argues that Lopez Garcia provides evidence that the
combination of an anti-foam reagent and detergent is unpredictable and
unsuitable at least in slurry flame atomic absorption spectrometry reactions.
(See Appeal Br. 14, 32.) We are not persuaded that the ultimate
determination in Lopez Garcia to remove the foaming detergent from sample
is a teaching that anti-foam would not have been reasonably expected to
address the problems created by bubbles in RT-PCR. Lopez Garcia states:
Although this problem [of trapped bubbles] could be overcome
by adding several drops of antifoaming agent [‘Antifoam A’
(Fluka)] to the slurry, it was also noted that Triton X-100
decreased the absorption signal of copper, both for aqueous
solutions and for slurries and hence this surfactant was not
employed.

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(Lopez Garcia 518.) Thus, Lopez Garcia expressly teaches that a problem
caused by bubbles could be solved with anti-foam reagent. One of ordinary
skill in the art would have known that removing detergent is not an option
for RT-PCR. (See Spec. 3:34–4:1 (“The bubbles likely are caused by the
presence of non-ionic polymeric detergents, which are a necessary
component of the amplification reaction.”).) Thus, to the extent that Lopez
Garcia is relevant to the issues of obviousness of the method of claim 43, we
are not persuaded that it is evidence that using anti-foam in RT-PCR would
have been unpredictable. Instead, Lopez Garcia teaches that anti-foam is a
reliable way to reduce bubbles.
Appellant argues that the rejection is based on impermissible
hindsight because
[n]owhere in any of the cited references is there any teaching
that combines a thermostable polymerase enzyme with a
detergent and an antifoam reagent in RTQPCR for optical
detection wherein the combination of reagents and a method
that would in fact lead to not only an improvement in the
accuracy of optical detection of nucleic acids, but also result in
an improvement in the kinetics of transcription by the
thermostable polymerase.

(Appeal Br. 45.) As discussed above, we are persuaded that one of ordinary
skill in the art would have modified the RT-PCR assay of Li by adding anti-
foam reagent to reduce the negative effects of bubbles on optical detection
taught in McMillan. We are not persuaded that the method of claim 43 is
not obvious because the Examiner has not cited a single reference that
teaches including anti-foam reagent with a thermostable polymerase in RT-
PCR. We are also not persuaded that any effects of adding anti-foam
reagent, such as any improvement in the kinetics of transcription, would
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have been unexpected and therefore would indicate that the claimed method
is not obvious.
In summary, Appellant’s arguments do not persuade us that the
method claim 43 produces results that would have been unexpected by one
of ordinary skill in the art at the time of filing. Nor do Appellant’s
arguments persuade us that adding anti-foam reagent to RT-PCR when it
was known that bubbles present a problem would not have been obvious
over the teachings of the prior art or that there are any errors in the
Examiner’s prima facie case for obviousness. Accordingly, we are not
persuaded that the Examiner erred in rejecting claim 43.
Appellant does not raise separate arguments against the rejection of
independent claim 52 or of the claims that depend on claim 43 or 52.
Accordingly, we are not persuaded that the Examiner erred in rejecting these
claims.
Examiner’s rejection of claims 49 and 53 under 35 U.S.C. § 103 over
Li, McMillan, Lopez Garcia, Durmowicz, Kyle, and Wierenga

After withdrawing the rejection of claims 43–47, 49, 52, 53, 56–61,
62, and 64 as being obvious over Li, McMillan, Lopez Garcia, Durmowicz,
and Kyle (see Ans. 6–7), the Examiner entered a new ground of rejection
under 35 U.S.C. § 103 over Li, McMillan, Lopez Garcia, Durmowicz, Kyle,
and Wierenga that applies to claims 49 and 53. (See id. at 7–8.)
Claim 49 recites: “The method according to claim 43, wherein said
polymerase chain reaction is carried out in the presence of an effective
amount of at least two anti-foam reagents.” (Appeal Br. 78.) Claim 53
depends on claim 52 and recites a composition comprising at least two anti-
foam reagents. (See id.)
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As the Examiner finds, Wierenga teaches that silicone-based anti-
foam reagents are not that effective and that the addition of organic anti-
foam reagents results in a synergistic anti-foaming combination. (See
Wierenga 1:38–51, 1:66–2:3; see Ans. 8.) Wierenga teaches that
carboxylated poly(oxyalkylated) alcohol cosurfactants have anti-foaming
properties and act synergistically to inhibit foam formation. (See Wierenga
4:1–16; see Ans. 34.) The Examiner finds that it would have been obvious
to combine the anti-foam reagent 1520-US with a second organic anti-foam
reagent because of the synergistic combination taught in Wierenga. (See
Ans. 8.)
Appellant first argues that the Examiner erred by first pointing to the
failure of the Sigma Catalog to teach organic anti-foam reagents. (See
Appeal Br. 56–58.) Because the Examiner’s new ground of rejection does
not rely on the Sigma Catalog, we are not persuaded by these arguments and
do not address them.
Appellant argues that Wierenga does not teach a combination of anti-
foams, but teaches the combination of silicone anti-foaming agent and a
carboxylated linear alkoxylated alcohol, referred to as CS-I, which Appellant
argues is not an anti-foam reagent. (See Appeal Br. 58.) Appellant does not
address the teaching in Wierenga that carboxylated poly(oxyalkylated)
alcohol cosurfactants have anti-foaming properties and act synergistically
with silicone anti-foaming reagents. (See Wierenga 4:1–16.) Accordingly,
we are unpersuaded by Appellant’s argument.
Appellant raises other arguments against the rejection of claims 49
and 53 that are similar to the arguments addressed above made in regard to
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the rejection of claim 43. (See Appeal Br. 62–65.) For the reasons
discussed above, we are not persuaded by these arguments.
The Examiner’s rejection of claims 43–48, 52, and 56–66 over Li,
McMillan, Lopez Garcia, Durmowicz, Kyle, and Blaschke

Appellant’s claim 48 recites: “The method according to claim 43,
comprising detecting said product using a fluorescent nucleic acid-binding
dye.” (Appeal Br. 78.) Claim 62 similarly recites the composition of claim
59 comprising detection by fluorescent nucleic acid binding dye. (See id. at
80.)
The Examiner finds that Blaschke teaches real-time RT-PCR
performed with either TaqMan probes or nucleic acid-binding dyes. (See
Ans. 6, citing Blaschke 80 (“Recently, real-time PCR has become available,
using either labelled sequence-specific probes (e.g., TaqMan®, Heid et al.,
1996) or a fluorescent dye (e.g., SYBR Green, ethidium bromide, Higuchi et
al. 1992) to monitor the formation of PCR products.”).) Appellant does not
contest this finding.
Appellant argues that Blaschke fails to cure the alleged deficiencies of
the other cited prior art. (See Appeal Br. 66–74.) Because we do not agree
that the prior art cited by the Examiner is deficient, we are not persuaded by
Appellant’s arguments, as discussed above.
Conclusion
Upon consideration of the record and for the reasons given, we affirm
the Examiner’s rejection.

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In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
43–47, 52,
56–61, 63,
64
103 Li, McMillan, Lopez
Garcia, Durmowicz,
Kyle
43–47, 52,
56–61, 63,
64

43–48, 52,
56–64
103 Li, McMillan, Lopez
Garcia, Durmowicz,
Kyle, Blaschke
43–48, 52,
56–64

49, 53 103 Li, McMillan, Lopez
Garcia, Durmowicz,
Kyle, Wierenga
49, 53
Overall
Outcome
43–49, 52,
53, 56–64

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED