Ex Parte Alocilja et al

Board of Patent Appeals and Interferences

Feb 23, 2009

10074499 (B.P.A.I. Feb. 23, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte EVANGELYN C. ALOCILJA,
and ZARINI MUHAMMAD-TAHIR
__________

Appeal 2009-1754
Application 10/074,499
Technology Center 1600
__________

Decided:1 February 23, 2009
__________

Before DONALD E. ADAMS, ERIC GRIMES, and
LORA M. GREEN, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an
immunoassay device, which the Examiner has rejected as obvious. We have

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).
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Application 10/074,499

jurisdiction under 35 U.S.C. § 6(b). We affirm.

STATEMENT OF THE CASE
This application was the subject of an earlier appeal to this board
(Appeal 2006-2198, decided Sept. 18, 2006). In that appeal, we affirmed
rejections of the then-pending claims for obviousness. The claims have
since been amended and the rejections now on appeal have a different basis
than the rejections previously affirmed. The earlier decision therefore has
no bearing on whether the present claims are patentable over the evidence
relied on by the Examiner in this appeal.
Claims 1-3, 7-10, 14-16, 18, 19, 21, 22, 24, and 26 are pending and on
appeal. The claims subject to each rejection have not been argued separately
and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii). Claims 1
and 22 are representative and read as follows:
1. A biosensor device which comprises:

a strip of a substrate having at least two zones wherein a

(1) first of the zones contains a first capture reagent bound to
the substrate in a defined area between electrodes on different sides of
the defined area for providing an electrical bias to the defined area;
and

(2) a second of the zones containing a fluid transfer medium for
supplying a fluid to the first zone, wherein the second zone comprises
a second defined area containing a second capture reagent directly
bound to an electrically conductive polymer formed by oxidative
polymerization of monomers and the polymer has been mixed to react
with the second capture reagent to form a conjugate, wherein there is
an absence of electrically conductive particles, wherein when a fluid
sample containing an analyte is bound by the second capture reagent
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to form a complex, the complex migrates to the first zone in the
medium and the analyte is bound by the first capture reagent thereby
altering a conductivity or resistance of the defined area in the first
zone as measured between the electrodes to detect the analyte.

22. The device of Claim 1 or 2, wherein the biosensor device is a multi-
array device comprising:

a plurality of first zones on the single strip of substrate, each of the
first zones having a first capture reagent with a different specificity bound to
the single strip of substrate between electrodes to immobilize one of multiple
analytes on the single strip of substrate so that each of the multiple analytes
can be detected simultaneously from the same sample on the single strip of
substrate of the multi-array biosensor device.

The claims stand rejected under 35 U.S.C. § 103(a) as follows:
• Claims 1, 2, 7-9, 14-16, 18, 19, and 21 as obvious in view of Kim;2
and
• Claims 3, 10, 22, 24, and 26 as obvious in view of Kim and
Roberts.3
OBVIOUSNESS BASED ON KIM
The Issue
The Examiner has rejected claims 1, 2, 7-9, 14-16, 18, 19, and 21 as
obvious in view of Kim. The Examiner’s position is that Kim’s
immunoassay device meets all the limitations of claim 1 except that it
includes electrically conductive gold particles, and Kim suggests omitting

2 Kim et al., “Conductimetric membrane strip immunosensor with
polyaniline-bound gold colloids as signal generator,” 14 Biosensors &
Bioelectronics 907-915 (2000).
3 Roberts et al., U.S. Patent 5,958,791, issued Sept. 28, 1999.
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the gold particles, albeit in an unpreferred embodiment, thereby making
obvious the device of claim 1 (Answer 4-5).
Appellants contend that Kim’s disclosure would not have suggested
omitting the gold particles from its immunocomplexes and in fact teaches
away from doing so (see, e.g., Appeal Br. 11, 19).
The issue with respect to this rejection is: Did the Examiner err in
concluding that Kim suggests omitting gold particles from its immunoassay
device?
Findings of Fact
1. Kim discloses that, in a conventional sandwich immunoassay, “an
aqueous medium containing analyte was absorbed by the capillary action
from the bottom end of the strip system. . . . [T]he antigen-antibody
reactions formed the sandwich complex containing gold particles, and a
colored signal detectable by the naked eye was generated” (Kim 910, right-
hand col.; Fig. 1).
2. Kim discloses that “[a]s an alternative method to colorimetry, the
density of particulate gold, electron-rich metal, can be determined by
measuring electric conduction” (id. at 911, left-hand col.).
3. Kim discloses an immunoassay (biosensor) device comprising a
first zone that contains bound antibody in an area between two electrodes
and a second zone that contains a second antibody conjugated to a gold
particle (id. at Fig. 3).
4. Kim discloses that, when antibody/gold particle complexes were
used in the disclosed system, “the electric conduction mediated by the gold
colloids in the complex was proportional to the tracer concentration,” but the
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signal was weak and the maximum signal-to-noise ratio was half what could
be achieved by photometry (id. at 911, right-hand col.).
5. Kim discloses that the poor performance of plain gold tracer
could result from an impaired transfer of electrons along the
gold particles. . . . The particles are surrounded with protein
molecules, i.e. immunoglobulin and casein as blocking agent
. . . that render an ionic polymer shell on the outside of the gold.
This may interfere with electron hopping, a dominant process
of charge-transfer between conducting mediators.
(Id. at 913, paragraph bridging the columns.)
6. Kim discloses that “[i]n an attempt to resolve the electronic barrier
surrounding the gold, [they] introduced, on the surface, polymeric conductor
molecules that may bridge the neighboring particles or at least bring them
closer to improve the charge-transfer state” (id. at 913, right-hand col.).
7. Kim discloses that the conducting polymer used was a “water-
soluble polyaniline . . . synthesized by oxidative polymerization of aniline
monomer . . . incorporated onto the surface of gold particles . . . after
immobilizing the antibody” (id. at 911, right-hand col.).
8. Kim discloses that polyaniline is an example of an organic polymer
that “exhibit[s] metallic conductivity” and that “polyaniline is highly
conductive upon protonation” (id. at 913, right-hand col.).
9. Kim discloses that the “protrusion degree of the polymer strands,
acting as a wire (i.e. molecular wires) for electrical connection . . . mainly
depends on the polymer concentration applied and the molecular dimension”
(id.).
10. Kim concludes:
An additional labeling agent comprising a conducting polymer
to colloidal gold-antibody conjugates facilitated electric
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conduction between gold particles captured via antigen-
antibody binding. This strategy for conductimetric detection
could be a better approach than direct labeling of the antibody
with the polymer by chemical reaction because, in such a case,
the protein molecule itself does not contain available sites for
electron relay.
(Id. at 914, right-hand col., emphasis added.)
Principles of Law
The test of obviousness is “whether the teachings of the prior art,
taken as a whole, would have made obvious the claimed invention.” In re
Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991).
“Obviousness is determined from the vantage point of a hypothetical
person having ordinary skill in the art to which the patent pertains.” In re
Rouffet, 149 F.3d 1350, 1357 (Fed. Cir. 1998).
“Under 35 U.S.C. § 103, a reference must be considered not only for
what it expressly teaches, but also for what it fairly suggests. . . . [W]e
reiterate that ‘all disclosures of the prior art, including unpreferred
embodiments, must be considered’ in determining obviousness.” In re
Burckel, 592 F.2d 1175, 1179 (CCPA 1979).
“The fact that the motivating benefit comes at the expense of another
benefit. . . should not nullify its use as a basis to modify the disclosure of
one reference with the teachings of another. Instead, the benefits, both lost
and gained, should be weighed against one another.” Medichem S.A. v.
Rolabo S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006).
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Analysis
The Examiner has found, and Appellants do not dispute, that Kim
discloses a device that meets all the limitations of claim 1 except for the
requirement of “an absence of electrically conductive particles.” The
dispositive issue is whether the missing limitation is suggested by Kim’s
conclusion that a labeling agent comprising a conducting polymer together
with a gold-antibody conjugate “could be a better approach than direct
labeling of the antibody with the polymer by chemical reaction.”
The Examiner interprets the above-quoted statement to mean “that
such a direct labeling between the antibody and the conductive polymer was
well known in the art at the time the invention was made” and concludes that
it would have been obvious to directly label the antibody with polyaniline, in
the absence of gold particles (Answer 5).
We agree with the Examiner’s reasoning and conclusion. Kim
discloses that polyaniline is a highly conductive polymer that overcomes the
poor performance of plain gold particles as labels because it bridges the
neighboring particles or brings them closer together. We agree with the
Examiner that, when viewed in the context of its disclosure as a whole,
Kim’s statement that polyaniline/gold/antibody conjugates “could be a better
approach the direct labeling of the antibody with the polymer” would have
been understood to mean that direct labeling of the antibody with polyaniline
would also have been expected to work in the disclosed assay, even if it had
some disadvantages compared to labeling with gold plus polyaniline.
Appellants argue that “one skilled in the art reading Kim et al. would
be directed away from eliminating the metal (gold) particles since Kim et al.
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teaches that direct labeling of the antibody with the polymer would not have
the electron relay sites on the antibody protein molecule which are necessary
for conduction” (Appeal Br. 19).
We disagree. Appellants have pointed to nothing in Kim to show that
electron relay sites on the antibodies are necessary for conduction. Although
Kim’s statement is somewhat ambiguous, we agree with the Examiner that it
is most reasonably interpreted as saying that direct labeling of antibody with
polyaniline would have been expected to work in the disclosed assay, even if
it did not work as well in some respects as the polyaniline-plus-gold
combination. That is, Kim’s statement that polyaniline-plus-gold “could be
a better approach” than polyaniline alone does not mean that polyaniline
would not work, only that polyaniline-plus-gold might be expected to work
better.
A prior art reference does not teach away from a particular approach
just because it teaches that another approach has certain advantages; every
alternative approach to a problem entails trade-offs. Kim reasonably
suggests that direct labeling of antibody with polyaniline would work in its
assay and therefore suggests the only limitation that distinguishes the device
of claim 1 from the prior art device.

OBVIOUSNESS BASED ON KIM AND ROBERTS
The Issue
The Examiner has rejected claims 3, 10, 22, 24, and 26 as obvious in
view of Kim and Roberts. The Examiner finds that Roberts teaches “a test
device that includes multiple sets of interdigitated electrode arrays . . . in
order to perform simultaneous multiple analyte detection” (Answer 7) and
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concludes that it would have been obvious to modify Kim’s device to
include the multiple sets of electrode arrays taught by Roberts, in order to
allow detection of multiple analytes simultaneously (id.).
Appellants contend that Roberts would not have suggested the
claimed device because the device taught by Roberts requires separate
competitive binding portions and measurement portions to avoid cross-over
signals (Appeal Br. 21-23).
The issue with respect to this rejection is: Did the Examiner err in
concluding that Roberts would have suggested modifying Kim’s device to
comprise a plurality of electrode arrays to allow testing for multiple analytes
simultaneously?
Additional Findings of Fact
11. Kim’s Figure 3 is reproduced below:

The figure shows a schematic diagram of Kim’s immunoassay device.
12. Roberts’ Figure 1 is reproduced below:
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The figure shows a schematic diagram of one embodiment of Roberts’
device (Roberts, col. 8, ll. 41-43).
13. Roberts discloses that the device is “divided into two channels,
namely, control channel D and test channel E” (id. at col. 15, ll. 6-7).
14. Roberts discloses that the device includes an electrochemical
measurement portion that comprises fingers (140, 142) of a first conductor
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(130, 134) interdigitated with fingers (144, 146) of a second conductor (132,
136).
15. Roberts discloses that the “electrochemical detection system . . .
comprises an interdigitated set of microelectrodes and, optionally, a
reference electrode” (id. at col. 23, ll. 28-30).
16. Roberts discloses that “the test device . . . may be modified for
simultaneous multiple analyte detection or determination” (id. at col. 18, ll.
53-55).
17. Roberts discloses that “[w]ith the test devices and methods of the
invention, one may also assay a test sample for a plurality of analytes . . . or
screen for one or more of a plurality of analytes. In one embodiment, the
test device includes multiple sets of interdigitated electrode arrays.” (Id. at
col. 25, ll. 16-20.)
Principles of Law
“[A]n implicit motivation to combine exists not only when a
suggestion may be gleaned from the prior art as a whole, but when the
‘improvement’ is technology-independent and the combination of references
results in a product or process that is more desirable, for example because it
is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more
efficient.” Dystar Textilfarben Gmbh & Co. Deutschland KG v. C.H.
Patrick Co., 464 F.3d 1356, 1368 (Fed. Cir. 2006).
Analysis
Claim 22 is directed to the device of claim 1, having a plurality of
“first zones,” at which are bound capture reagents with different
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specificities. Kim would have made obvious the device of claim 1, for the
reasons discussed above. Roberts discloses a similar device, also for
electrochemical detection of analytes, that can comprise a plurality of
electrochemical measurement portions with interdigititated microelectrodes.
Roberts also discloses that the device can be modified to have multiple sets
of interdigitated electrode arrays to screen for a plurality of analytes.
We agree with the Examiner that the combined teachings of Kim and
Roberts would have made obvious the device of claim 22. Specifically, it
would have been obvious to modify Kim’s device to comprise a plurality of
signal generation zones – containing an electrode array and different
immobilized antibodies – in order to screen for a plurality of analytes
simultaneously, because Roberts discloses a device for electrochemical
detection of multiple analytes in a single assay and, as the Examiner noted
(Answer 7), performing multiple tests at once is more efficient.
Appellants argue that “Roberts et al. does not teach a single multiple
array as taught by Applicants as illustrated in Figure 3” (Appeal Br. 21).
Appellants also argue that Roberts’ device “would not suggest to a person of
ordinary skill in the art the single multiple array as taught by Applicants,
since the nature of the immunoassay and test device taught by Roberts et al.
requires separate competitive binding portions 104 and measurement
portions 106” (id. at 21-22).
This argument is not persuasive. The Examiner’s rejection does not
depend on modifying Kim’s device to carry out the assay method disclosed
by Roberts; the rejection is based on using Kim’s assay to detect multiple
analytes simultaneously by modifying Kim’s device to have a plurality of
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first zones comprising electrodes and capture reagents. (See Answer 13-14:
“[T]he combination of Kim et al. in view of Roberts et al. . . . results in the
device lay-out of Kim et al., wherein multiple electrode arrays (i.e. first
zones) are included on the single substrate in order to perform simultaneous
multiple analyte detection . . . as taught by Roberts et al.”)

CONCLUSIONS OF LAW
The Examiner did not err in concluding that Kim suggests omitting
gold particles from its immunoassay device, or that Roberts would have
suggested modifying Kim’s device to comprise a plurality of electrode
arrays to allow testing for multiple analytes simultaneously.

SUMMARY
We affirm the rejection of claims 1, 2, 7-9, 14-16, 18, 19, and 21
under 35 U.S.C. § 103(a) based on Kim and the rejection of claims 3, 10, 22,
24, and 26 under 35 U.S.C. § 103(a) based on Kim and Roberts.

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

AFFIRMED

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dm

IAN C. MCLEOD, P.C.
2190 COMMONS PARKWAY
OKEMOS, MI 48864

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