Ex Parte Mendel-Hartvig et al

Patent Trial and Appeal Board

Jan 30, 2014

10244265 (P.T.A.B. Jan. 30, 2014)

UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
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Ex parte IB MENDEL-HARTVIG,
RUNE BJORKMAN, and GERD RUNDSTROM1
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Appeal 2012-006958
Application 10/244,265
Technology Center 1600
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Before TONI R. SCHEINER, JOHN G. NEW, and
SUSAN L.C. MITCHELL, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 The real party-in-interest is Phadia AB of Uppsala, Sweden. App. Br. 1.
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SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1, 2, and 4-29.2 Specifically, claims
1, 4-8, 10-l3, 16-20, 22, 23, 26, 27, and 29 stand rejected under 35 U.S.C. §
103(a) as being obvious over the combination of Hubscher et al. (US
6,528,325 B1, March 4, 2003)(“Hubscher”), Klepp et al. (US 6,703,196 B1,
March 9, 2004) (“Klepp”), and Kline et al. (US 5,459,078, October 17,
1995) (“Kline”).
Claims 2 and 14 stand rejected under 35 U.S.C. § 103(a) as being
obvious over the combination of Hubscher, Klepp, Kline, and Gordon et al.
(US 5,486,452, January 23, 1996) (“Gordon ’452”).
Claims 9, 15, 21, and 28 stand rejected under 35 U.S.C.
§ 103(a) as being obvious over the combination of Hubscher, Klepp, Kline,
and Gordon et al. (US 6,100,099, August 8, 2000) (“Gordon ’099”).
Claims 24 and 25 stand rejected under 35 U.S.C. § 103(a) as being
obvious over Hubscher, Klepp, Kline, Gordon ’099, and Rundstrom (US
2007/0020768, May 23, 2006) (“Rundstrom”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellants’ invention is directed to a solid phase assay device
comprising a multi-spot detection zone, and the use thereof in
immunochromatographic assays. The invention relates to a device for

2 Claim 3 has been canceled. App. Br. 2.
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determining analytes in an aqueous sample comprising: an elongate flow
matrix allowing lateral transport of fluid therethrough, wherein said matrix
comprises a sample application zone and downstream thereof, a detection
zone having immobilized capture agents capable of directly or indirectly
binding to said analytes, wherein said analytes are detected by allowing a
labeled second binding agent to bind directly or indirectly to the analytes.
The immobilized capture agents are distributed in the detection zone of the
device as a plurality of small spots, thereby permitting multi-analyte and/or
multi-specificity detection. Abstract.

GROUPING OF CLAIMS

Appellants group together claims 1, 4-8, 10-13, 16-20, 22, 23, 26, 27,
and 29. App. Br. 5. We select claim 1 as representative of this group.
Claim 1 recites:
1. A device for determining analytes in an aqueous
sample, comprising:

(i) an elongate flow matrix allowing lateral transport of
fluid therethrough, wherein said matrix comprises a sample
application zone and downstream thereof, a detection zone
having immobilized capture agents capable of directly or
indirectly binding to said analytes, wherein at least some of the
capture agents have cross-reacting analytes, and (ii) a labeled
second binding agent arranged in the device to bind directly or
indirectly to the analytes once the analytes have been
immobilized in the detection zone, wherein said analytes are
detectable by allowing the labeled second binding agent to bind
directly or indirectly to the analytes, and further wherein A) the
immobilized capture agents are distributed in the detection zone
as a plurality of spots, thereby permitting multi-analyte and/or
multi-specificity detection, B) the capture agents are anchored
to the matrix via immobilized particles, C) the number of spots
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per flow matrix is more than 10, and D) some of the spots
function as positive control(s) and/or internal calibrator(s) and
include a control agent capable of binding to the labeled second
binding agent.

App. Br. 20.
Appellants group together claims 2 and 14. App Br. 13. We select
claim 2 as representative of this group. Claim 2 recites:
2. A device according to claim 1, wherein the spots
are smaller than 1 mm in diameter.

Id.
Appellants group together claims 9, 15, 21, and 28. App Br. 14. We
select claim 9 as representative of this group. Claim 9 recites:
9. A device according to claim 1, wherein the capture
agents are DNA/RNA or DNA/RNA like structures.

App. Br. 21.
Appellants group together claims 24 and 25. App Br. 18. We select
claim 24 as representative of this group. Claim 24 recites:
24. A device according to claim 21, wherein at least
some of the capture agents comprise different allergens having
cross-reacting IgE.

App. Br. 22.

ISSUES AND ANALYSES
A. Claim 1

Issue 1
Appellants argue that the Examiner erred in finding that a person of
ordinary skill in the art would have been motivated to modify the device of
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Hubscher with the teachings of Klepp. App. Br. 8. We therefore address
the issue of whether the Examiner so erred.

Analysis
Appellants argue that an artisan of ordinary skill would not have been
motivated to change the device taught by Hubscher by depositing the
labeled second binding agent upstream from the sample application zone as
taught by Klepp. App. Br. 8. Appellants dispute the Examiner’s finding
that this is a mere alternative, and functionally equivalent, configuration
and that the same expected labeling of analyte would have been obtained.
Id.
According to Appellants, Klepp teaches a device which incorporates
two pairs of specific binding partners, neither of which is an analyte, but
one of which is labeled (labeled partner 1 of the specific binding pair 2) and
may be located at different sites of the device. App. Br. 8. Therefore,
argue Appellants, although the labeled partner 1 of Klepp is a specific
binding agent to partner 2 (which is not an analyte) of the binding pair 2,
the labeled second binding agent in the device of claim 1 is arranged to bind
directly or indirectly to the analytes. Id. Appellants contend that the
various configurations taught by Klepp are not functionally equivalent to
those taught by Hubscher. Id. Specifically, Appellants argue that Klepp’s
teaching of a number of capture spots for cross-reacting analytes and
positioning the second binding agent upstream from the sample application
zone (rather than downstream as taught by Hubscher) is not functionally
equivalent to the structure taught by Hubscher. Id.
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Appellants argue further that the device recited in claim 1 provides a
significant improvement that is neither taught nor suggested by Hubscher.
App. Br. 9. Appellants argue that, in their device, the second binding agent
is arranged to bind with all immobilized analytes, but avoids interference
with the analyte-immobilizing reactions because the second binding agent is
arranged in the device to bind directly or indirectly to the analytes once the
analytes have been immobilized in the detection zone. Id. Appellants
contend that, in view of the teachings of Hubscher, one of ordinary skill in
the art would have expected the Examiner’s asserted modification to
provide equivalent detection results, but as Applicants have recognized,
depositing the labeled second binding agent upstream of the sample
application provides a device for significantly improved analyte
determination. Id. Appellants also argue that because the capture agents
may have cross-reacting analytes, the arrangement as presently claimed is
in fact not equivalent to that of Hubscher and that the arrangement claimed
in the present device provides improvement. App. Br. 9.
The Examiner finds that Hubscher teaches a flow matrix having a
labeled reagent zone that is arranged downstream from the sample
application zone. Ans. 14-15. The Examiner finds that Klepp teaches that,
in a flow matrix, a labeled reagent zone can be positioned either upstream
or downstream from the sample application zone while retaining the ability
to label analyte immobilized in a detection zone. App. Br. 15. The
Examiner also finds that Hubscher teaches that allergens are one type of
analyte. Ans. 12. The Examiner finds one of ordinary skill in the art would
recognize that positioning a labeling reagent upstream or downstream from
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a sample application zone could be used in the device taught by Hubscher.
Ans. 15.
The Examiner finds further that an artisan of ordinary skill would not
expect that the number of spots or cross-reaction of analyte taught by
Hubscher would affect the ability to label analyte by altering the
arrangement of the labeled reagent as suggested by Klepp. Ans. 15. The
Examiner finds that, despite Appellants’ assertion that depositing labeled
second binding agent upstream of the sample application zone provides
significantly improved and unexpected analyte determination, Appellants
have not provided any demonstration or results that indicate the
modification of arranging the second binding results in such improved
detection.
We are persuaded by the Examiner’s reasoning. Klepp explicitly
teaches that:
The labelled [sic] partner 1 of the specific binding pair 2
can be located at different sites of the analytical element
according to the invention. This depends for example on the
intended reaction procedure, on the amount of available sample
or depends on the analyte concentration if the analytical
element is for the determination of liquid samples.
Thus the labelled [sic] partner 1 of the specific binding
pair 2 can be located in the sample application zone, it can be
arranged downstream of the sample application zone between
the sample application zone and the detection zone or can also
be located upstream of the sample application zone.

Klepp, col. 5-6, ll. 64-11 (emphasis added). Klepp thus teaches that the
second labeled binding agent can be positioned either upstream or
downstream of the application zone. We agree with the Examiner that it
would be within the ordinary skill of an artisan to combine the known
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teachings of Klepp with those of Hubscher so as to reposition the second
binding agent upstream of the sample application zone, as required by
claim 1.
With respect to Appellants’ arguments that repositioning the second
binding agent upstream of the sample application zone produces
significantly improved binding of cross-reacting analytes that would not
have been predictable from the teachings of the cited prior art references,
we find that Appellants adduce no data or other evidence to demonstrate
that such is the case. Appellants’ assertions, therefore, amount to no more
than attorney argument, and we accord them no probative weight. See In re
De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) (Arguments and
conclusions unsupported by factual evidence carry no evidentiary weight).
We consequently affirm the Examiner’s rejection of claim 1.

Issue 2
Appellants argue separately with respect to dependent claim 7.
Claim 7 recites:
7. A device according to claim 1, wherein the capture
agents are allergens or an immunoactive fragment thereof.

App. Br. 20. Appellants argue that the Examiner erred because Hubscher
provides no teaching, suggestion or recognition for avoiding false positive
testing of particular allergens based on reaction with labeled reagent. App.
Br. 11. We address the issue of whether the Examiner so erred.

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Analysis
Appellants argue that one of ordinary skill in the art would appreciate
that allergens typically have some degree of cross-reactivity and therefore
react with the same IgEs. App. Br. 11 (citing Spec., p. 2, ll. 1-3).
According to Appellants, the problem of cross-reactivity is greater when the
number of capture spots is high (greater than 10) as required by claim 7.
App. Br. 11. However, argue Appellants, Hubscher provides no teaching,
suggestion or recognition for avoiding false positive testing of particular
allergens based on reaction with labeled reagent, and is directed only to
distinguishing between IgG, IgA, IgM, and IgE based on the amount of the
respective immunoglobulins in a sample. Id. Therefore, Appellants
contend, Hubscher does not provide any suggestion to one of ordinary skill
in the art to modify the disclosed device to result in a device as recited in
claim 7, or to provide improved testing accuracy. Id.
We are not persuaded by Appellants’ reasoning. Although we agree
with Appellants that cross-reactivity is known in the art, a method of
avoiding false positive testing of particular allergens based on reaction with
labeled reagent is not within the scope of claim 7, which is directed to a
device and not to a method. Moreover, limitations from Appellants’
Specification cannot be read into the language of the claim. See In re Van
Geuns, 988 F.2d 1181, 1185 (Fed. Cir. 1993) (Although the claims are
interpreted in light of the specification, limitations from the specification
may not be read into the claims). We therefore affirm the Examiner’s
rejection of claim 7.

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Issue 3
Appellants argue separately with respect to dependent claims 26, 27,
and 29. Claim 26 recites:
26. A device according to claim 1, wherein the number
of spots per flow matrix is more than 100.

App. Br. 23. Appellants argue that the Examiner erred in finding that the
cited prior art references teach or suggest a number of spots that are as great
as 100. App. Br. 11-12.

Analysis
Appellants argue that Hubscher provides no teaching, suggestion or
recognition for avoiding false positive testing allergens with such a high
number of capture agents and at least some of the capture agents have
cross-reacting analytes. App. Br. 12. According to Appellants, Hubscher is
only directed to distinguishing between IgG, IgA, IgM and IgE based on the
amount of the respective immunoglobulins in a sample. Id. Thus,
Hubscher does not provide any suggestion to one of ordinary skill in the art
to modify the disclosed device to result in a device as recited in claims 26,
27, and 29 or to provide improved testing accuracy in a device having such
a high number of spots.
The Examiner responds that the discovery of an optimum value of a
result-effective variable in a known process is ordinarily within the skill of
the art. Ans. 8-9. The Examiner finds that Appellants have not disclosed
that the specific limitations recited in instant claim 26 are for any particular
purpose or solve any stated problem, and that the prior art teaches that the
number of spots may be varied depending on the desired number of
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analytes to be tested. Ans. 9. The Examiner therefore finds that, absent
unexpected results, it would have been obvious for one of ordinary skill to
discover the optimum workable ranges of the methods disclosed by the
prior art by normal optimization procedures known in the microarray art.
Id.
We agree with the Examiner that it has long been settled to be no
more than routine experimentation for one of ordinary skill in the art to
discover an optimum value for a result effective variable. See In re Aller,
220 F.2d 454, 456 (C.C.P.A. 1955) (“No invention is involved in
discovering optimum ranges of a process by routine experimentation”); see
also Aller, 220 F.2d at 458 (“[W]here the general conditions of a claim are
disclosed in the prior art, it is not inventive to discover the optimum or
workable ranges by routine experimentation”). Appellants adduce no data
or other evidence to demonstrate unexpected or unpredictable results arising
from the limitations of claims 26, 27, and 29. We therefore affirm the
Examiner’s rejection of these claims.

B. Claim 2
Issue
Appellants argue that the Examiner erred in finding that an artisan of
ordinary skill in the art would have combined the microdots employed in
the liquid systems of Gordon ’452 to be successfully employed in a flow
matrix as taught by Hubscher, Klepp, and Kline. App. Br. 13. We
therefore address whether the Examiner so erred.

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Analysis
Appellants argue that there is no teaching or suggestion by Gordon
’452 relating to a flow device or providing any apparent reason for one of
ordinary skill in the art to have modified any of the teachings of Hubscher
to arrive at the presently claimed devices. App. Br. 13. To the contrary,
argue Appellants, the microdots of Gordon ’452 are applied to a support
which is immersed in the liquid to be analyzed and then dipped into a
diluted solution or suspension of an indicator antibody. Id. (citing Gordon
’452, col. 8, ll. 33-44). Appellants contend that Gordon ’452 does not
suggest the use of microdots in a flow matrix as defined by the present
claims or in a flow matrix as taught by Hubscher and argue that one of
ordinary skill in the art would have had no apparent reason for expecting
the microdots employed in the liquid systems of Gordon ’452 to be
successfully employed in a flow matrix. App. Br. 13.
The Examiner responds that Gordon ’452 teaches a device
comprising a plurality of small spots for multi-analyte detection in which
the spots have a diameter of less than 0.5 mm, in order to crowd the
maximum number of antigens onto a single strip. (col. 6, ll. 47-50; ll. 17-
27). Ans. 10. The Examiner concludes that it would have been obvious to
a person of ordinary skill in the contemporary art to shape the lines
containing capture agents of the device taught by Hubscher into spots that
are circular in shape and have a diameter of less than 0.5 mm, as taught by
Gordon ’452, as a means to provide for detection of a large number of
analytes detected on a single test strip. Ans. 10-11.
We agree with the Examiner’s reasoning. It is not necessary for
Gordon ’452 to teach a flow device if the other cited prior art references do
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so. All elements of each prior art reference need not read on the claimed
invention, rather, the proper test for obviousness is what the combined
teachings would have suggested to a person of ordinary skill in the art. See
In re Kotzab, 217 F.3d 1365, 1370 (Fed. Cir. 2000). What is essential to the
determination of obviousness is whether a person of ordinary skill in the art
would have been motivated to combine the teachings of the prior art. We
find that the Examiner has articulated reasoning with some rational
underpinning to support the legal conclusion of obviousness, viz., an artisan
of ordinary skill would have been motivated to combine the microdots of
Gordon ’452 with the lateral flow system of Hubscher as a means for
detecting a large number of analytes on a single strip. See KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 418 (2007). We consequently affirm the
Examiner’s rejection of claims 2 and 14.

C. Claim 9
Issue 1
Appellants argue that the Examiner erred in combining the teachings
of Gordon ’099 with the teachings of Hubscher, Klepp, and Kline. App. Br.
15. We therefore address whether the Examiner so erred.

Analysis
Appellants argue that although Gordon ’099 teaches the use of a strip
for immersion in a reaction solution with various different capture reagents,
Appellants can find no teaching by Gordon ’099 of a device as recited in
claim 1 from which claim 9 depends. App. Br. 14-15. Appellants argue
that Gordon ’099 discloses only a complicated solution system which
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further uses unique detectable labels associated with each probe set. App.
Br. 15. According to Appellants, the fact that Gordon ’099 employs DNA
capture agents does not provide any motivation to modify the teachings of
Hubscher along the lines necessary to result in a flow matrix device as
required by claims 9. Id. Appellants also argue that Gordon does not
remedy the deficiencies of the prior art references cited with respect to
claim 1. Id.
The Examiner responds that Gordon ’099 is not relied upon for
teaching specific labels, but is rather relied upon for teaching specific
capture agents and the number and pattern of spots on the flow matrix.
Ans. 20. The Examiner finds that Gordon ’099 teaches a test strip of
porous material with immobilized capture agents in the form of circular
spots, in which a different capture agent is immobilized in each spot, in
order to provide multiplex ligase chain reaction (“LCR”). Ans. 10 (citing
Gordon ’099, col. 4, ll. 26-30; ll. 30-41; cols. 4-5, ll. 64-5; col. 9, ll. 23-27;
Fig. 1). The Examiner concludes that it would have been obvious to one
having ordinary skill in the art at the time the invention was made to
arrange the lines of the device of Hubscher, Klepp, and Kline into a circular
spot, wherein each circular spot contains a single type of immobilized
capture agent, as taught by Gordon ’099, as a means of preventing label
from accumulating in the first capture spot and allows for all spots to
readily develop signals. Ans. 10 (citing Gordon ’099, col. 9, lines 33-46).
We are persuaded by the Examiner’s reasoning. Gordon ’099 teaches
the use of DNA probes in capture reactions. Gordon ’099, col. 5, ll. 6-17.
We have related supra our reasons for finding that claim 1 is obvious over
the cited prior art references, and we find that the Examiner has articulated
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sufficient reasons why an artisan of ordinary skill would be motivated to
combine those references with Gordon ’099. We therefore affirm the
Examiner’s rejection of claim 9.

Issue 2
Appellants argue separately with respect to dependent claim 21.
Appellants argue that the Examiner erred in finding that the cited prior art
references teach or suggest the limitation of claim 21 reciting “whereby
spots of capture agents having cross-reacting analytes are not arranged in
the same flow line of liquid.” App. Br. 16. We therefore address the issue
of whether the Examiner so erred.

Analysis
Appellants argue that Gordon ’099 does not teach or suggest a flow
matrix with more than 10 spots arranged in a pattern that allows for
detection of cross reactive analytes or specificities, whereby spots of
capture agents having cross-reacting analytes are not arranged in the same
flow line of liquid, as required by claim 21. App Br. 16.
We are not persuaded by Appellants’ assertion. We have related
supra our reasoning with respect to our findings and conclusion concerning
claim 1. With respect to Appellants’ argument concerning the disputed
limitation supra, Appellants’ brief provides nothing more than a recitation
of the disputed claim language and an assertion that Gordon ’099 does not
teach the limitation. That in itself is insufficient to be accorded any
evidentiary weight. See In re Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011)
(“[W]e hold that the Board reasonably interpreted Rule 41.37 to require
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more substantive arguments in an appeal brief than a mere recitation of the
claim elements and a naked assertion that the corresponding elements were
not found in the prior art”). This issue was discussed at oral argument,
however, fleshing out an argument that was not made in Appellants’ brief
will not remedy the deficiency of the brief. Nevertheless, we find that
Gordon ’099’s teaching of staggered capture spots, would lead a person of
ordinary skill in the art to position the spots so that they could be located in
separate flow lines. We consequently affirm the Examiner’s rejection of
claim 21.

Issue 3
Appellants argue separately with respect to dependent claim 28.
Claim 28 recites:
28. A device according to claim 1, wherein the number
of spots per flow matrix is more than 100, the spots comprising
capture agents having cross-reacting analytes are not arranged
in the same flow line of liquid, and the capture agents comprise
allergens or autoantigens, or immunofragments thereof.

App. Br. 23. Appellants argue that the Examiner erred in finding that
Gordon ’099 teaches or suggests a flow matrix with more than 100 spots
arranged in a pattern that allows for detection of cross reactive analytes or
specificities, whereby spots of capture agents having cross-reacting analytes
are not arranged in the same flow line of liquid, as required by claim 28.
App. Br. 17. We therefore address the issue of whether the Examiner so
erred.

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Analysis
Appellants’ brief does little more than state that Gordon ’099 does
not teach the flow matrix with more than 100 spots. As we have related
supra, a recitation of the disputed claim language and an assertion that the
limitation is not taught by the reference is insufficient to be accorded any
evidentiary weight. In re Lovin, 652 F.3d at 1357. We have also related
supra our reasoning as to why we are not persuaded by Appellants’
argument that “having more than 100 spots” and “are not arranged in the
same flow line of liquid” are nonobvious over the prior art. We
consequently affirm the Examiner’s rejection.

D. Claim 24
Issue
Appellants submit that the Examiner improperly relied upon
Rundstrom as prior art in this rejection. App. Br. 18. We therefore address
whether the Examiner so erred.

Analysis
Appellants argue that whereas Rundstrom may be cited to show that
the analytes of Hubscher cross-reacting, Rundstrom cannot be relied upon
to show motivation for one of ordinary skill in the art to make the
combination of Hubscher and Klepp because Rundstrom has an effective
date as prior art well subsequent to the effective priority date of the present
claims. App. Br. 18.
Appellants argue that Hubscher provides no teaching or suggestion
for avoiding false positive testing of particular allergens based on reaction
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with labeled reagent and is only directed to distinguishing between IgG,
IgA, IgM and IgE based on the amount of the respective immunoglobulins
in a sample. App. Br. 18-19. Therefore, Appellants argue, Hubscher does
not provide any suggestion to one of ordinary skill in the art to modify the
disclosed device to result in a device as recited in claims 24 and 25.
The Examiner responds that, the availability of Rundstrom as prior
art notwithstanding, the claims as written do not require avoidance of false
positive testing. Ans. 23. The Examiner finds that no demonstration of
evidence or results have been provided in the Specification or otherwise, to
show unexpected success attributed to the claimed arrangement of
disposing a labeled binding reagent upstream from a sample application
zone. Id. The Examiner also finds that the combination of prior art
references teaches the claimed structural limitations and therefore reads on
the claimed invention. Ans. 24.
We agree with the Examiner. As we have related supra with respect
to claim 7, claim 24 is directed to a device, and not to a method, and
avoiding false positive results is not within the scope of the invention
recited in claim 24. For the reasons we have recited supra, we affirm the
Examiner’s rejection of claim 24.

DECISION
The Examiner’s rejection of claims 1, 2, and 4-29 under 35 U.S.C. §
103(a) is affirmed.

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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED

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