Wisconsin Alumni Research Foundation et al.

Patent Trials and Appeals Board

Mar 2, 2021

2020002244 (P.T.A.B. Mar. 2, 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.
14/485,119 09/12/2014 David C. Schwartz 960296.01763.P140056US02 5439
27114 7590 03/02/2021
WARF/MKE/QUARLES & BRADY LLP
ATTN: IP DOCKET
411 E. WISCONSIN AVENUE
SUITE 2350
MILWAUKEE, WI 53202-4428
EXAMINER
SCHMIEDEL, EDWARD
ART UNIT PAPER NUMBER
1726
NOTIFICATION DATE DELIVERY MODE
03/02/2021 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):
pat-dept@quarles.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte DAVID C. SCHWARTZ,
KRISTY KOUNOVSKY-SHAFER
JUAN HERNANDEZ-ORTIZ, THEO ODIJK,
JUAN DEPABLO, and KYUBONG JO

Appeal 2020-002244
Application 14/485,119
Technology Center 1700
____________

Before KAREN M. HASTINGS, JAMES C. HOUSEL, and
MICHAEL G. McMANUS, Administrative Patent Judges.

McMANUS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 seeks review of the
Examiner’s decision to reject claims 11–21. 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 parties in interest as Wisconsin
Alumni Research Foundation, University of Leiden, and University of
Chicago. Appeal Brief dated June 20, 2019 (“Appeal Br.”) 2.
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CLAIMED SUBJECT MATTER
The present application generally relates to a microfluidic device and
a method of stretching a nucleic acid molecule. Specification dated Sept. 12,
2014 (“Spec.”) ¶ 7. The Specification teaches that stretching nucleic acid
molecules facilitates inspection of the molecules by various techniques. Id.
¶ 3. Certain stretching techniques are known but each has certain
disadvantages. Id. ¶¶ 5–6. The Specification asserts that the claimed
microfluidic device overcomes the disadvantages of the prior art. Id. ¶ 7.
The Specification teaches a microfluidic device that includes a first
microchannel, a second microchannel, a nanoslit, a nucleic acid molecule,
and an ionic buffer. Id. ¶ 8. This is depicted in an excerpt from the
Drawings reproduced below.

Figure 4 of the Drawings schematically depicts two microchannels
connected by a nanoslit. Id. ¶¶ 14, 99.
The Specification teaches that the Debye length2 may affect the
degree of stretching that occurs within the nanoslit. Id. ¶¶ 8, 99, 100. The
Specification further teaches that the “ionic strength of the ionic buffer and
electrostatic or hydrodynamic properties of the nanoslit and the nucleic acid

2 The Debye length “controls the range of the electrostatic interaction in
ionic solutions.” Kim 6.
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molecule can combine to provide a summed Debye length.” Id. ¶ 8
(emphasis added).
The Specification explains the effects of the strength of the ionic
buffer and nanoslit size as follows:
[D]ecrease of ionic strength [of the buffer] may beneficially
increase chain persistence lengths and enhanced effective
confinement, which is induced by the increased Debye length of
the micro-fluidic device’s surface (itself also enhanced by
appropriately low ionic strength). For example, reduced ionic
strength and appropriately configured nanoslits may result in
the Debye lengths of the device and/or the persistence length of
the molecule being comparable (or equal) to nanoslit height
(e.g., ~ 100 nm, for the device described above).

Spec. ¶ 41. Similarly, the Specification teaches that “[n]otably, the lower
ionic strength buffer (e.g., 0.11 mM), in combination with the appropriately
scaled nanoslits and the elastic forces generated by the induced dumbbell
configuration, may greatly enhance DNA elongation.” Id. ¶ 43.
Claim 11 is illustrative of the subject matter on appeal and is
reproduced below with certain limitations bolded for emphasis:
11. A method of stretching a nucleic acid molecule in
an ionic buffer, the method comprising:
positioning the nucleic acid molecule such that a central
portion of the nucleic acid molecule occupies a nanoslit, a first
end portion of the nucleic acid molecule occupies a first cluster
region adjacent to a first end of the nanoslit, and a second end
portion of the nucleic acid molecule occupies a second cluster
region adjacent to a second end of the nanoslit,
the nanoslit, the first cluster region, and the second
cluster region including the ionic buffer,
the nucleic acid molecule having a contour length that is
greater than the length of the nanoslit, and
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the ionic buffer having an ionic strength and a buffer
temperature, the nanoslit having nanoslit electrostatic or
hydrodynamic properties and the nucleic acid molecule having
molecule electrostatic or hydrodynamic properties, the ionic
strength, the buffer temperature, and the nanoslit
electrostatic or hydrodynamic properties configured in view
of the molecule electrostatic or hydrodynamic properties to
provide a summed Debye length that is greater than or
equal to a nanoslit height or a nanoslit width, wherein the
nanoslit height or nanoslit width is the smallest physical
dimension of the nanoslit.
Appeal Br. 20 (Claims App.) (emphasis added).

REFERENCES
The Examiner relies upon the following prior art:
Name Reference Date
Cao et al. (“Cao”) US 2008/0242556 A1 Oct. 2, 2008
Han et al. (“Han”) US 2011/0114486 Al May 19, 2011
K. Jo et al., A single-molecule barcoding system using nanoslits for DNA
analysis, 104 PNAS 2673–2678 (Feb. 20, 2007) (“Jo”)
Y. Kim et al., Nanochannel Confinement: DNA Stretch Approaching Full
Contour Length, NIH Public Access Author Manuscript, published as Lab
Chip. 2011 May 21; 11(10): 1721-1729 (“Kim”)
REJECTIONS
The Examiner maintains the following rejections:
1. Claims 11–15 and 19–21 are rejected under 35 U.S.C. § 103
as being unpatentable over Cao in view of Kim as evidenced
by Han and Jo. Final Office Action dated Sept. 20, 2018
(“Final Act.”) 3–10.
2. Claims 16–18 are rejected under 35 U.S.C. § 103 as being
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unpatentable over Cao in view of Kim and Jo. Id. at 10–12.
DISCUSSION
Rejection 1. The Examiner rejects claims 11–15 and 19–21 as
obvious over Cao in view of Kim as evidenced by Han and Jo. Final Act. 3–
10. In support of the rejection the Examiner finds that Cao teaches a method
of stretching a nucleic acid molecule in an ionic buffer. Id. at 3. The
Examiner relies, in part, on Figure 1A of Cao, reproduced below.

Figure 1A (annotations in original) “illustrates detection of a macro-
molecule flowing through a nanochannel device.” Cao ¶ 31.
The Examiner further finds that Cao teaches that “the ionic strength,
the buffer temperature, and the nanoslit electrostatic or hydrodynamic
properties [are] configured in view of the molecule electrostatic or
hydrodynamic properties to provide a summed Debye length that is greater
than or equal to a nanoslit height or a nanoslit width.” Final Act. 5. The
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Examiner looks to Paragraph 27 of the Specification which teaches that “[i]n
certain embodiments, the ionic buffer can have an ionic strength that
suitably combines with the nanoslit and nucleic acid molecule to provide a
summed Debye length that is greater than or equal to a nanoslit height or a
nanoslit width.” Spec. ¶ 27; Final Act. 5. The Examiner further finds that
several of the conditions taught by Cao overlap those taught by the
Specification. Final Act. 5–6. More specifically, the Examiner finds that
the buffer type, macromolecule, and nanoslit dimensions taught by Cao
overlap those taught by the Specification. Id. The Examiner concludes that
“these proffered examples have properties of ionic strength, nucleic acid
molecule properties, and nanoslit properties which combine to yield the
claimed summed Debye length which is greater than the nanoslit
height/width.” Id. at 6.
The Examiner further finds that “Cao is silent [as] to the ionic buffer
having a sufficiently low ionic strength to combine with the nucleic acid
molecule properties and nanoslit properties and yield the claimed summed
Debye length being greater than the nanoslit height/width.” Id. In this
regard, the Examiner looks to Kim. Id. at 6–7.
The Examiner finds that Kim teaches that greater DNA stretching is
achieved using lower ionic strength buffers. Id. at 6 (citing Kim, Fig. 2B).
The Examiner further finds that strength of the ionic buffer is a result-
effective variable that is known to alter the degree of DNA stretching
achieved. Id. at 6–7.
The Examiner determines that one of skill in the art would have had
reason “to modify the method of Cao and use a low ionic strength buffer,
such as 0.12 mM or 0.62 mM, in order to achieve a higher degree of DNA
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stretching.” Id. at 7. The Examiner further determines that lowering “the
strength of the ionic buffer to determine an optimal concentration for
achieving stretch of the DNA molecule and arrive upon the disclosed low
ionic strength buffer” would require “nothing more than routine
experimentation.” Id.
The Examiner concludes that the method taught by the hypothetical
combination would necessarily result in the same nucleic acid molecule with
a sufficiently low ionic strength buffer and overlapping nanochannel
width/height dimensions. Id. Accordingly, the Examiner determines, the
combination would necessarily have the same properties as the claimed
method. Id.

Result-Effective Variables
Appellant argues that the rejection is in error in several respects.
Appeal Br. 3–16. First, Appellant argues that the Examiner does not
properly apply the law regarding result-effective variables. Id. at 6–7.
Appellant argues that, in order for the rejection to be well-founded,
the prior art would have to teach that the summed Debye length is a result-
effective parameter. Id. at 6. Appellant asserts that the ionic strength of the
buffer is only one of several components that together form the summed
Debye length. Id. at 6–7. That is, Appellant argues that even if Kim teaches
that the ionic strength of the buffer is a result-effective variable, this is
insufficient to teach that the summed Debye length (the sum of several
inputs) is a result-effective variable. Id. at 7.
In the Answer, the Examiner explains that the rejection does not rely
upon optimizing the ionic strength of the buffer and then subsequently
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optimizing the summed Debye length. Examiner’s Answer dated Nov. 27,
2019 (“Ans.”) 16. Rather, the Examiner asserts, the rejection relies only
upon optimizing the ionic buffer strength and combining such optimized
value with the other properties taught by Cao. Id. The Examiner determines
that because those properties taught by Cao match those taught by the
Specification, they would combine with the optimized buffer to achieve the
claimed summed Debye length being greater than the smallest dimension of
the nanoslit. Id. (citing Final Act. 8–13).
In its Reply Brief, Appellant asserts that the summed Debye length
varies according to its constituent components. Reply Brief dated Jan. 27,
2020 (“Reply Br.”) 3. Appellant contends that the Examiner merely selected
isolated values of ionic strength and nanoslit dimensions from the prior art
without computing the summed Debye length. Id. Appellant asserts that
“the Examiner's specific example of 0.75 mM [ionic buffer strength] and 50
nm [nanoslit width] . . . fails to meet the claimed summed Debye length
limitation, because the summed Debye length of ~46 nm does not exceed the
minimum size dimension of 50 nm.” Id.
We find Appellant’s arguments not to be persuasive. Kim gives clear
guidance that low ionic strength buffer yields increased DNA stretching.
See Kim, Fig. 2. Kim further teaches that “we boosted DNA stretch . . . in
nanoslits (1000 nm x 100 nm) by decreasing ionic strength of loading
buffer.” Kim 3. This shows a relationship between buffer strength and
DNA stretch. The greatest stretch obtained by Kim was achieved at a buffer
strength of 0.12 mM. Id. The primary reference, Cao, teaches several
possible nanochannel widths including “less than 50 nm.” Cao ¶ 133; see
also id. at 12 (claim 16). Kim teaches that “it is naturally expected that
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DNA elongation can be accomplished by reducing dimensions of
nanoconfinement” (Kim 2), thus, suggesting the use of nanochannels of
reduced dimensions. Cao and Kim both teach the analysis of λ DNA. Cao ¶
157; Kim 3.
Accordingly, the Examiner’s conclusion that the method taught by the
hypothetical combination would necessarily result in the same nucleic acid
molecule with a sufficiently low ionic strength buffer and overlapping
nanochannel width/height dimensions as required by the claim is reasonable.
Appellant’s argument that “the Examiner’s specific example of 0.75
mM and 50 nm . . . fails to meet the claimed summed Debye length
limitation, because the summed Debye length of ~46 nm does not exceed the
minimum size dimension of 50 nm” is not persuasive of error. The
Examiner does not find that the hypothetical combination would employ a
buffer strength of 0.75 mM. Final Act. 7. Rather, the Examiner notes that
the ionic buffer strength values taught by Kim are “under the 0.75 mM
concentration of the instant specification.” Id. Nor does the Examiner have
an obligation to independently calculate a summed Debye length. See
Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1329–30 (Fed.
Cir. 2020) (explaining that “the work of the inventor or the patentee can be
used as the evidence of inherency,” which, in the context of obviousness,
may demonstrate that a claimed feature is “the natural result of the
combination of elements explicitly disclosed by the prior art.”).
In view of the foregoing, we determine that Appellant’s arguments
regarding result-effective variables are not persuasive of error.

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Failure of the Kim Authors
Second, Appellant argues that the failure of the Kim authors to
discover the claimed method indicates that it is not obvious. Appeal Br. 7–
9. Appellant argues that “the authors had all of the information that the
Examiner bases the obviousness rejection upon available to them, yet they
did not recognize the criticality of the claimed summed Debye length nor did
they identify the corresponding surprising result.” Id. at 7. Appellant argues
that the Examiner engages in impermissible hindsight to achieve a result
“that the inventors themselves failed to make prior to the present invention.”
That is, Appellant argues that the failure of others to discover the claimed
method suggests the nonobviousness of the method.
This is not persuasive of error. Cao was published Oct. 2, 2008 (Cao,
code (43)) while Kim was published May 21, 2011 (Kim 1). Thus, the
present rejection is predicated, in part, on a 2011 publication. That is, under
the Examiner’s theory, only after such information was known would the
claimed method be obvious.
The present application claims priority to provisional application No.
61/877,570, filed Sep. 13, 2013. Spec. ¶ 1. Thus, the inventors came upon
the claimed method relatively soon after Kim’s publication. Appellant does
not submit evidence of any persons, in possession of the teachings of Cao
and Kim, who attempted, but failed, to achieve the claimed method.
Accordingly, Appellant has not shown error on this basis.

Unexpected Results
Third, Appellant argues that any prima facie case of obviousness is
rebutted because the claimed method yields unexpected results. Appeal Br.
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9–12. Appellant contends that the Specification shows that the claimed
method “approaches or achieves stretch levels in the ‘Odijk’ regime.” Id. at
9–10. Appellant asserts that the “plateau of the Odijk regime represents a
complete elongation of a nucleic acid molecule, which represents a
difference relative to the prior art of kind and not simply of degree.” Id. at
10.
Appellant further discusses the teachings of the Specification and
concludes that “it should be apparent that appropriately scaled nanoslits and
appropriately low ionic strength buffers is directing the person having
ordinary skill in the art to produce the claimed summed Debye length which
Appellant explained was lacking in the prior art.” Id. at 11.
In general, an applicant may overcome a prima facie case of
obviousness by establishing “that the [claimed] range is critical, generally
by showing that the claimed range achieves unexpected results relative to the
prior art range.” In re Geisler, 116 F.3d 1465, 1469–70 (Fed. Cir. 1997)
(alteration in original) (citation omitted). “Although it is well settled that
comparative test data showing an unexpected result will rebut a prima facie
case of obviousness, the comparative testing must be between the claimed
invention and the closest prior art.” In re Fenn, 639 F.2d 762, 765 (CCPA
1981). Moreover, “[i]t is well settled that unexpected results must be
established by factual evidence. Mere argument or conclusory statements in
the specification does not suffice.” In re De Blauwe, 736 F.2d 699, 705
(Fed. Cir. 1984), quoted with approval in In re Soni, 54 F.3d 746, 750 (Fed.
Cir. 1995).
The burden of establishing unexpected results rests on Appellants.
Appellants may meet this burden by establishing that the difference between
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the claimed invention and the closest prior art was an unexpected difference.
See In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972).
Here, there is no clear evidence that the cited result is unexpected.
Appellant summarizes the teachings of the Specification to be that “it should
be apparent that appropriately scaled nanoslits and appropriately low ionic
strength buffers is directing the person having ordinary skill in the art to
produce the claimed summed Debye length which Appellant explained was
lacking in the prior art.” Appeal Br. 11. This is similar to Kim’s teaching
that “we interpret our experimental findings as a function of channel
dimensions and ionic strengths.” Kim, Abstract.
Appellant does not offer any affidavit indicating that one of skill in
the art would have found the result in question to be surprising. Ans. 28.
Appellant argues that “all of the evidence necessary to establish this
surprising result is present in Appellant’s specification.” Reply 11. This
may refer to the Specification’s teaching that “[o]ur results indicate that the
‘Odijk regime’ is achieved once the persistence length is equal to the
effective confinement (including electrostatic considerations), in apparent
contradiction to other theories that suggested that the effective DNA
diameter is the relevant parameter for the de Gennes-Odijk transition.”
Spec. ¶ 47. Absent adequate explanation, this is insufficient to show that the
difference between the claimed invention and the closest prior art was an
unexpected difference.
Further, Appellant refers us to only a single test result that achieves a
stretch greater than one: a stretch of 1.06. Appeal Br. 9, 11; Spec. ¶ 97; Fig.
3. This was achieved using a buffer having an ionic strength of .11 mM
which corresponds to a Debye length of 30 nm. Spec. ¶¶ 70, 97. Appellant,
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however, does not clearly direct us to the channel length used in obtaining
this result. Accordingly, the ratio of summed Debye length to smallest
channel dimension is unclear. Further, Figure 3 appears to include other
results exhibiting stretch of less than one.
In this instance, a single result is insufficient to demonstrate
unexpected results commensurate in scope with the claim. The claims
encompass various nanochannel dimensions and ionic buffer strengths. An
appellant is obliged to offer evidence of unexpected results from which one
may reasonably conclude that the result would be applicable throughout the
full range of the claims. In re Clemens, 622 F.2d 1029, 1036 (CCPA 1980).
In this case, a single value that achieves a stretch in the “Odijk regime” is
insufficient.
Accordingly, Appellant has not shown evidence of unexpected results
commensurate with the scope of the claims sufficient to rebut the
Examiner’s prima facie case of obviousness.

Unsatisfactory for Intended Purpose
Fourth, Appellant argues that the Examiner’s proposed modification
of Cao (to include the use of a low ionic strength buffer) would render it
unsatisfactory for its intended purpose. Appeal Br. 12–15. Appellant cites
to various teachings of Cao and argues that each is an intended purpose of
Cao and that modification would render Cao unfit for such purposes. Id.
The first of these stated intended purposes is “efficient determination
of the sizes and composition of fragments of DNA or other macromolecules
by linearizing and analyzing such molecules.” Id. (citing Cao ¶ 21).
Appellant argues that linearizing and measurement of a molecule would be
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disrupted by modification because linear length would vary when the end
portions of the molecule are within the nanoslit rather than forming the ends
of a “dumbbell” shape. Id. at 13.
The Examiner determines that the proposed modification would not
disrupt the measurement and analysis of molecules of Cao. Ans. 35–36.
The Examiner determines that “the clustered configuration shown in Cao
Figs. 1A–6B is not contrary to Cao’s own intended purpose, as the molecule
is detected and analyzed through the nanoslit/nanochannel and is clearly
shown in the clustered configuration in the drawings” with the ends of the
molecule in the microchamber. Id.
In its Reply Brief, Appellant reiterates that the molecule under
analysis would have a different stretch depending upon the location of the
leading and trailing edges of the DNA molecule. Reply Br. 13. Appellant
argues that such discrepancy would disrupt measurement and analysis. Id.
Appellant’s argument is not persuasive as it is not supported by
evidence of record. See, e.g., Gemtron Corp. v. Saint-Gobain Corp., 572
F.3d 1371, 1380 (Fed. Cir. 2009) (“[U]nsworn attorney argument . . . is not
evidence and cannot rebut . . . other admitted evidence . . . .”); Estee Lauder,
Inc. v. L’Oréal, S.A., 129 F.3d 588, 595 (Fed. Cir. 1997) (Argument made by
counsel in a brief does not substitute for evidence lacking in the record).
Further, Appellant does not address Cao’s numerous teachings regarding
elongation. See, e.g., Cao ¶ 24 (“at least one of the fluidic nanochannel
segments is capable of containing and elongating at least a portion of a
macromolecule residing within at least a portion of the fluidic nanochannel
segment.”). Appellant has not shown why the elongation of the Examiner’s
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proposed combination would have an effect that differs significantly from
the elongation taught by Cao.
Appellant argues that Cao’s second intended purpose is “the nature of
fluidic flow in a nanoscale environment precludes turbulence and many of
the shear forces that would otherwise fragment long DNA molecules.”
Appeal Br. 12 (citing Cao ¶ 59). Appellant argues that it is “clear that the
intended purpose of Cao is to flow macromolecules through their
nanochannels, not to achieve the claimed elongation using the claimed
molecule orientation and summed Debye length.” Id. at 13.
In the Answer, the Examiner determines that Cao teaches fluidic flow
as one means of translocation. Ans. 36. The Examiner finds that Cao also
teaches other methods, including electrokinetic force as required by claim
13. Id. (citing Cao ¶ 96); see also Spec. ¶ 26. Accordingly, we determine
that fluidic flow is not an “intended purpose” of Cao but is rather one of
several alternative teachings.
Appellant argues that Cao’s third intended purpose is “entropic
confinement.” Appeal Br. 12 (citing Cao ¶¶ 62, 64). Appellant argues that
“Cao clearly identified its conf[ine]ment mechanism as entropic
confinement, as opposed to the claimed electrostatic and hydrodynamic
effects.” Id. at 13. In the Answer, the Examiner cites to Paragraph 37 of the
Specification which provides that “[s]uch presentation of DNA, in
accordance with this disclosure, may take advantage of entropic, elastic and
hydrodynamic forces to stretch the DNA.” Spec. ¶ 37.
Entropic forces and entropic confinement are complex and fact-
specific. Appellant presents very limited argument in support of its
contention. Appeal Br. 13, 14. Appellant does not address what entropic
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confinement occurs in the claimed method and how modifying Cao to use a
low strength ionic buffer would affect its entropic confinement. Indeed,
Appellant does not clearly direct us to any source stating that buffer strength
does or does not affect entropic confinement. Accordingly, we determine
that Appellant has not shown error in this regard.
Appellant argues that Cao’s fourth intended purpose is
characterizing one or more macromolecules . . . [including]
translocating at least a portion of at least one region of the
macromolecule through a fluidic nanochannel segment . . .
monitoring . . . one or more signals related to the translocation
of one or more region of the macromolecule through the
nanochannel . . . .
Appeal Br. 12. Appellant argues that Cao teaches moving molecules
through nanochannels and recording signals related to the movement. Id. at
13. Appellant cites to Cao’s teaching the size of a DNA molecule may be
determined by correlating the speed at which DNA moves past the detection
slit to the length of time that a signal is detected. Id. Appellant argues that
this would be frustrated by modification of Cao. Appellant does not offer an
explanation as to why such determination would be frustrated (id.) but we
infer that Appellant relies on the same reasoning as with regard to its first
stated intended purpose (size determination by linearizing and analyzing).
As with Appellant’s first argument, the present argument is insufficiently
supported by citation to evidence of record and fails to address Cao’s
teachings regarding elongation.
Accordingly, Appellant’s argument that use of a low strength ionic
buffer as taught by Kim would render the method of Cao unsuitable for its
intended purpose fails to persuade us of reversible error.
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Principle of Operation
Appellant additionally argues that the Examiner’s proposed
modification would change the principles of operation of Cao. Appeal Br.
15–16. Appellant argues that Cao’s principles of operation overlap its
intended purposes (discussed above). Id. at 15. Specifically, Appellant
identifies “the fluidic flow, entropic confinement, and movement through
channels” as Cao’s principles of operation. Id.
Appellant argues that the “principles of fluidic flow and movement
through the channels would need to be eliminated in favor of the stable
dumbbell configuration of the present claims.” Id.
This argument is not supported by citation to record evidence.
Further, Appellant does not address Cao’s teaching regarding signal
monitoring that, “[i]n some embodiments, at least a portion of the
macromolecule is stationary during the monitoring.” Cao ¶ 102; see also id.
at 14 (claim 71). Accordingly, Appellant has not shown that a stationary
configuration is contrary to the principles of operation of Cao.
Appellant also briefly argues that “[t]he principle of entropic
conf[ine]ment would need to be eliminated in favor of the electrostatic and
hydrodynamic effect of the present claims.” Appeal Br. 15.
As above, entropic forces and entropic confinement are complex and
fact-specific. Appellant makes statements that Cao relies on entropic
confinement while the present application employs electrostatic and
hydrodynamic effects. Id. Appellant, however, does not persuasively
establish that entropic forces have no effect in the practice of the claimed
method nor that electrostatic and hydrodynamic effects have no effect upon
Cao’s process. Nor does Appellant address the overlap in size of the
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nanoslits and similarity of the buffers taught by Cao and the Specification.
In short, Appellant does not persuasively show how use of a weaker ionic
buffer changes Cao’s principle of operation in this regard.
Accordingly, we determine that Appellant has not shown that the
Examiner’s hypothetical combination changes Cao’s principles of operation.

Rejection 2. The Examiner rejects claims 16–18 as obvious over Cao
in view of Kim and Jo. Final Act. 10–12. Claims 16–18 depend from claim
11. Appeal Br. 21 (Claims App.). The Examiner relies on the same
reasoning discussed above in finding that Cao and Kim teach the limitations
of claim 11. Final Act. 10. Appellant relies on the same arguments
discussed above on appeal of claims 16–18. Appeal Br. 16. As we have
found such arguments not to be persuasive, we determine that Appellant has
not shown error with respect to the rejection of claims 16–18.

CONCLUSION
The Examiner’s rejections are affirmed.
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
11-15, 19-
21
103 Cao, Kim, Han, Jo 11-15, 19-
21

16-18 103 Cao, Kim, Jo 16-18
Overall
Outcome
11-21

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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