Ex Parte Wei et al

Board of Patent Appeals and Interferences

Oct 16, 2009

10325429 (B.P.A.I. Oct. 16, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte NING WEI, YANBIN HUANG, XUEDONG SONG, and
ROSANN KAYLOR
____________

Appeal 2009-003621
Application 10/325,429
Technology Center 1600
____________

Decided: October 16, 2009
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Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the patent applicants’ appeal from the patent
examiner’s rejection of claims 41-62 and 78 under 35 U.S.C. §§ 102(b) and
103(a). The Board’s jurisdiction for this appeal is under 35 U.S.C. § 6(b).
The rejections are affirmed-in-part.

Appeal 2009-003621
Application 10/325,429

STATEMENT OF THE CASE
The claims are directed to a flow-through assay device for detecting
the presence or quantity of an analyte in a test sample. The device can be
utilized to detected antibodies, hormones, or proteins in a biological sample,
such as blood or urine (Spec. 4-5).
Claims 41-62 and 78 are pending and appealed. All the pending
claims stand rejected by the Examiner as follows:
1. Claims 41, 45, 49-55, 58, 59, and 62 under 35 U.S.C. § 102(b) as
anticipated by Brooks et al. (US 5,753,517, issued May 19, 1998) as
evidenced by Swerdlow et al. (Keyhole Limpet Hemocyanin: Structural and
Functional Characterization of Two Different Subunits and Multimers, 113B
COMP. BIOCHEM. PHYSIOL 537-548 (1996)) and Wikipedia
(http://en.wikipedia.org/wiki/Polyelectrolyte) (Ans. 4);
2. Claims 41-43 under 35 U.S.C. § 103(a) as obvious over Brooks, as
evidenced by Swerdlow and Wikipedia, in view of Szoka, Jr. et al. (US
5,661,025, issued Aug. 26, 1997) (Ans. 9);
3. Claims 41 and 44 under 35 U.S.C. § 103(a) as obvious over Brooks,
as evidenced by Swerdlow and Wikipedia, in view of Boguslawski et al. (US
4,689,294, issued Aug 25, 1987) (Ans. 12);
4. Claims 41, 46, and 57 under 35 U.S.C. § 103(a) as obvious over
Brooks, as evidenced by Swerdlow and Wikipedia, in view of Keogh (US
5,928,916, issued Jul. 27, 1999) (Ans. 16);
5. Claims 41, 47, and 48 under 35 U.S.C. § 103(a) as obvious over
Brooks, as evidenced by Swerdlow and Wikipedia, in view of Simon (US
4,251,631, issued Feb. 17, 1981) (Ans. 19);
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6. Claims 41, 55, 56, and 61 under 35 U.S.C. § 103(a) as obvious over
Brooks, as evidenced by Swerdlow and Wikipedia, in view of Ching et al.
(EP 0 462 376 A2, published Dec. 27, 1991) (Ans. 23);
7. Claims 41, 58, and 60 under 35 U.S.C. § 103(a) as obvious over
Brooks, as evidenced by Swerdlow and Wikipedia, in view of Empedocles et
al. (WO 01/61040 A1, published Aug. 23, 2001) (Ans. 27); and
8. Claims 41 and 78 under 35 U.S.C. § 103(a) as obvious over
Brooks, as evidenced by Swerdlow and Wikipedia, in view of Osikowicz et
al. (US 5,075,078, issued Dec. 24, 1991) (Ans. 31).
Claim 41 is only the independent claim on appeal. Claim 41 is
representative and reads as follows:
41. A flow-through assay device capable of detecting the presence or
quantity of an analyte in a test sample, the flow-through assay device
comprising a porous membrane in communication with detection probes
conjugated with a specific binding member, and said porous membrane
being in communication with calibration probes, wherein the porous
membrane defines a first discrete zone for receiving a test sample, the
porous membrane defining a second discrete zone spaced apart from said
first discrete zone to which said test sample flows from said first discrete
zone and within which both a capture reagent and polyelectrolyte are
substantially non-diffusively immobilized, wherein the capture reagent is
configured to bind with the conjugated detection probes or complexes
thereof to generate a detection signal in the second discrete zone, and further
wherein the polyelectrolyte differs from the capture reagent and is
configured to bind with the calibration probes to generate a calibration signal
in the second discrete zone such that said second discrete zone is a detection
and calibration zone.

ANTICIPATION BY BROOKS
Claims 41, 45, 49-55, 58, 59, and 62 stand rejected under 35 U.S.C. §
102(b) as anticipated by Brooks as evidenced by Swerdlow and Wikipedia
(Ans. 4).
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Statement of Issue
The Examiner contends that Brooks’ description of a control reaction
zone 32 and detection zone 16 meet the limitation of the claimed “second
discrete zone” which is “a detection and calibration zone.” Appellants
contend that the Brooks apparatus contains two distinct zones not a single
discrete zone as recited in claim 41. They contend that the Examiner
improperly interpreted the claimed “second discrete zone” to read on a
region containing two zones as in the Brooks apparatus. Thus, the principle
issue in this appeal is whether Appellants established that the Examiner
improperly interpreted the phrase “second discrete zone” as recited in claim
41.
Claim interpretation
1. According to the Specification, conventional assay systems typically
utilize a calibration zone and a detection zone (Spec. 2:9-14).
2. In the Summary of the Invention, the Specification describes the
inventive assay device as comprising a porous membrane that defines “a
detection/calibration zone” which is “capable of generating a[n analyte]
detection and calibration signal so that the amount of the analyte is capable
of determination from the detection signal as calibrated by the calibration
signal.” (Id. at 2:33 to 3:2.) The zone contains a “polyelectrolyte capture
reagent” to bind calibration probes and a “second capture reagent” to bind
analyte in order to produce the calibration and detection signals, respectively
(id. at 2:29-33; 14:14-21).
3. The Specification characterizes the invention as an assay device that
“employs the use of a single detection/calibration zone defined by a porous
membrane of the assay.” (Id. at 5:27-29; emphasis added.)
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4. The Specification states that “[c]onducting signal detection and internal
calibration at the same time [in the single detection/calibration zone] can
greatly increase the detection reliability and reproducibility.” (Id. at 5:29-
30.)
5.
Regardless of the technique used to measure the signal
intensity of the probes 41 and 43, it has been discovered that the
use of a single detection/calibration zone 31 can enable the
detection and calibration probes 41 and 43 to be measured at
the same location of the device 20. This “single measurement
location” approach provides a simple and attractive approach
for users of the assay device, particularly those targeted for
home and point-of-care applications.
(Spec. 16: 24-30.)
6. Figure 1 of the Specification is said to contain a “detection/calibration
zone 31” which “generally provides a single distinct detection/calibration
region (e.g., a line, dot, etc.) so that a user can accurately determine the
concentration of a particular analyte within a test sample at one location
along the device.” (Id. at 10:17-22.)
7. In the examples, the Specification describes measuring the detection and
calibration signals at a detection/calibration line (id. at 22:6-26).

Claim 41
Claim 41 is to a “flow-through assay device capable of detecting the
presence or quantity of an analyte in a test sample.” The device has a
“porous membrane” with the following elements:
• “a first discrete zone for receiving a test sample”; and
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• “a second discrete zone spaced apart from said first discrete zone . . .
within which both a capture reagent and polyelectrolyte are
substantially non-diffusively immobilized.”
The “capture reagent” binds “conjugated detection probes or
complexes thereof to generate a detection signal in the second discrete zone”
and the “polyelectrolyte” binds “calibration probes to generate a calibration
signal in the second discrete zone.” The claim also refers to the “second
discrete zone” as “a detection and calibration zone.”
As described in the Specification, the “detection and calibration zone”
– the “second discrete zone” – is “one location” in the assay device where
calibration and detection signals are determined (FF6). The Specification
specifically refers to the detection and calibration zone as a “single zone”
which generates both signal and calibration signals (FF2, 3, & 5). In
contrast, a conventional assay system is characterized in the Specification to
have a calibration zone and a detection zone (FF1), i.e., two zones, rather
than one. A single zone is stated by the Specification to be advantageous
because “[c]onducting signal detection and internal calibration at the same
time can greatly increase the detection reliability and reproducibility.”
(FF4.)
In sum, in light of the Specification, the phrase “second discrete zone”
would be understood by persons of ordinary skill in the art to mean a single
zone or region which contains both the capture reagent and polyelectrolyte
in the same location.
A “polyelectrolyte” is described in the Specification as a reagent
which binds probes “through ionic interaction.” (Spec. 11:12-14.) It can
have a net positive or negative charge, or be generally neutral (id. at 11:16-
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17; 12:1-4). Examples include and polylysine and polyamines (id. at 11:15-
20).
Findings of Fact
The Brooks patent
8. Brooks describes an apparatus for use in a quantitative
immunochromatographic assay to detect an analyte of interest in a fluid
sample (col. 1, ll. 45-48).
9. The apparatus comprises a membrane strip having an application point, a
contact region, and a detection region, where the contact region is between
the application point and detection region (col. 1, ll. 54-56).
10. Figure 1, reproduced below, shows an apparatus for performing the
assay:

The Figure 1 apparatus contains the following elements: membrane 10;
application point 12; contact region 14; control reaction zone 32; and
detection zone 16.
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11. The application point 12 is the position on the membrane where the
fluid sample is applied (col. 4, ll. 24-25).
12. Imbedded in the contact region 14, adjacent to the application point 12,
is a population of particles which are coated with antibodies that specifically
bind the analyte of interest (col. 4, ll. 49-67; col. 5, ll. 18-34).
13. The detection zone 16 refers to “a point on the membrane strip [10] at
which a ‘detection reagent’ is immobilized.” (Col. 5, ll. 35-38.) The
detection reagent can be the analyte of interest or an antibody against the
analyte (col. 5, ll. 39-42).
14. To compensate for variations in the membrane properties from assay to
assay, the apparatus can include an internal control region 32 (col. 5, ll. 49-
50). The internal control reaction zone 32 can comprise internal control
particles coated with antibodies directed against a “control detection
reagent,” such as Keyhole Limpet Hemocyanin (col. 5, ll. 53-65). The
control detection reagent is immobilized in the control reaction zone 32 (col.
5, l. 65 to col. 6, l. 1).

Swerdlow
15. Swerdlow teaches that the both KLH-A and KLH-B comprise charged
amino acids, such as lysine residues (p. 540; Ans. 42:1-5).
16. Since KLH is made of charged residues, logically the molecule as a
whole would also be charged.

Analysis
This rejection turns on claim interpretation. The Examiner found that
the region of the Brooks apparatus between contact zone 14 and wicking pad
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28, as shown in Figure 1 (FF10), formed a single zone that would have been
interpreted by persons of ordinary skill in the art to meet the claimed
limitation of a “second discrete zone” with a capture reagent and
polyelectrolyte (Ans. 5). This region comprised zones 32 and 16 (FF13-14)
which the Examiner found constituted a single discrete zone as required by
the claim. Appellants challenge this interpretation.
During patent examination, claim terms are given “the broadest
reasonable meaning . . . in their ordinary usage as they would be understood
by one of ordinary skill in the art, taking into account whatever
enlightenment by way of definitions or otherwise that may be afforded by
the written description contained in the applicant's specification.” In re
Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997). In this case, it would be
understood from the Specification that the claimed “second discrete zone”
which acts as “detection and calibration zone” is a single region containing
the capture reagent and polyelectrolyte at the same location. The
Specification consistently refers to the use of a “single . . . zone” (FF3)
which contains the polyelectrolyte and capture reagent in the same zone to
generate the calibration and detection signals at the same location (FF2-7).
The Examiner’s interpretation of the “second discrete zone” to read on the
two zoned configuration described in the Brooks patent is not reasonable
when the claim is interpreted in the context of the Specification as it should
have been.
In Brooks, the “detection reagent” (“capture reagent” as in instant
claim 41) is in a detection zone 16 (FF13) and the “control detection
reagent” (polyelectrolyte as in claim 41) is in a control reaction zone 32
(FF14). Brooks describes zones 16 and 32 as physically separated regions
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(FF10), not a single “discrete” zone as in claim 41. The “detection reagent”
and “control detection reagent” are in zones 16 and 32, respectively, and
therefore are not immobilized at the same location as the properly
interpreted claim 41 would require.
Because the Examiner erred in interpreting claim 41, we are
compelled to reverse the rejection of claim 41, and dependent claims 45, 49-
55, 58, 59, and 62, as anticipated by Brooks.

OBVIOUSNESS REJECTIONS 2-7
2. Claims 41-43 stand rejected under 35 U.S.C. § 103(a) as obvious
over Brooks, as evidenced by Swerdlow and Wikipedia, in view of Szoka
(Ans. 9).
3. Claims 41 and 44 stand rejected under 35 U.S.C. § 103(a) as
obvious over Brooks, as evidenced by Swerdlow and Wikipedia, in view of
Boguslawski (Ans. 12).
4. Claims 41, 46, and 57 stand rejected under 35 U.S.C. § 103(a) as
obvious over Brooks, as evidenced by Swerdlow and Wikipedia, in view of
Keogh (Ans. 16).
5. Claims 41, 47, and 48 stand rejected under 35 U.S.C. § 103(a) as
obvious over Brooks, as evidenced by Swerdlow and Wikipedia, in view of
Simon (Ans. 19).
6. Claims 41, 55, 56, and 61 stand rejected under 35 U.S.C. § 103(a)
as obvious over Brooks, as evidenced by Swerdlow and Wikipedia, in view
of Ching (Ans. 23).
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7. Claims 41, 58, and 60 stand rejected under 35 U.S.C. § 103(a) as
obvious over Brooks, as evidenced by Swerdlow and Wikipedia, in view of
Empedocles (Ans. 27).
In the obviousness rejections listed above, the Examiner relied on
secondary references to meet certain limitations in dependent claims which
were said to be missing from the Brooks patent. As these secondary
references were not cited for teaching a “second discrete zone” as required
by claim 41, we are compelled to reverse the rejections because such
element is lacking from Brooks (see above).

OBVIOUSNESS REJECTION 8
8. Claims 41 and 78 stand rejected under 35 U.S.C. § 103(a) as
obvious over Brooks, as evidenced by Swerdlow and Wikipedia, in view of
Osikowicz (Ans. 31).
Findings of Fact
17. Osikowicz describes a method for testing for human chorionic
gonadotropin (hCG) utilizing an anti-Beta hCG antibody conjugated to a
reddish pink colored selenium conjugate (col. 8, ll. 44-55).
18. The assay uses two rectangular bars, a procedural control bar and a test
bar (shown as intersecting bars 62 and 64 in Figure 6; col. 7, ll. 36-57; col. 8,
ll. 41-48). The two bars are arranged in a cross or plus sign, with the
procedural control bar containing immobilized hCG/anti-Beta hCG complex
and the test bar containing immobilized anti-Beta HCG antibody (id.).
Immobilized complex and antibody are present in the intersecting region of
bars 62 and 64 (see Figure 6).
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19. If the patient sample does not contain hCG, the reddish pink colored
selenium conjugate binds to only the procedural control bar and forms a pink
minus sign to show that the “test is functioning properly” (col. 8, ll. 54-60).
Thus the bound selenium conjugate functions as a calibration signal.
20. If the patent sample also contains hCG, then the reddish pink colored
selenium conjugate binds to the anti-hCG antibody in the test bar and an
image of a pink plus sign is formed from the intersecting procedural and test
bars (col. 8, ll. 61-68). Thus, the bound selenium conjugate functions as a
detection signal.
21. The calibration and detection signals occur in the region of overlap
between bars 62 and 64 and therefore are present in the same discrete zone.

Analysis
Claim 78 is dependent on claim 41 and further recites that
a detection signal generated from a conjugated detection probe
bound to the capture reagent and a simultaneous calibration
signal generated from a calibration probe bound to the
polyelectrolyte are intermingled.
The Examiner found that Osikowicz describes a flow through assay
device with intermingled signals emanating from the intersection of the
procedural and test bars (FF19-21; Ans. 33). The Examiner found that
Osikowicz teaches “the known technique of having overlapping reagents,
and consequently overlapping signals, from two different signaling reagents
that overlap in a single discrete zone.” (Ans. 33; FF21.) The Examiner
found:
The ordinary artisan would have been motivated to make such a
modification because the modification would have resulted in a
device having the added advantage of providing an easily
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readable positive assay signal, in the form of a plus sign as
explicitly taught by Osikowicz et al (column 8, lines 35-67). In
addition, it would have been obvious to the ordinary artisan that
the known technique of using the overlapping reagents, and
consequently overlapping signals, from two different signaling
reagents that overlap in a single discrete zone Osikowicz et al
could have been applied to the device of Brooks et al with
predictable results because the overlapping reagents, and
consequently overlapping signals, from two different signaling
reagents that overlap in a single discrete zone Osikowicz et al
predictably result in an easily readable detection signal.
(Ans. 34.)
Appellants contend that the Examiner erred. They argue that neither
reference describes a calibration and detection zone and that Osikowicz,
alone, does not disclose a calibration zone or calibration probes (App. Br.
39). They assert that the “overlapping area [where the procedural test bar
overlaps the patient test bar] does not even produce a detection signal, as this
area will form a detectable signal as long as the device is working properly”
and “provides no information with regard to either detection or calibration”
(id. at 40). They also maintain that Osikowicz “does not intermingle two
different signals, as is required in claim 78” (id. at 41).
Appellants’ arguments do not persuade us that the Examiner erred.
As to the contention about lack of calibration probes, the Examiner
responded that Osikowicz was relied upon for two signaling reagents (a
calibration and detection signals) overlapping in the same zone (Ans. 64).
The calibration probe element was therefore not found by the Examiner to
have been taught by Osikowicz, but rather by the Brooks patent. Moreover,
Osikowicz, in fact, describes signals that arise from the control and when
hCG is present in the test sample, serving as calibration and detection
signals, respectively (FF19-20).
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Claim 78 recites that the detection and calibrations signals are
“intermingled.” In Osikowicz, signals from test and procedural control bars
are intermingled where the bars intersect (FF18, 21). The signals arise from
the same reporter molecule (selenium conjugate) (FF17), but at the same
location and from binding to different immobilized entities (FF19-21).
The claim does not require signals from the reporter molecule to be
different, as asserted by Appellants. The claim simply states that a detection
and calibration signal are generated, without specifying that the signals,
themselves, are different. To the extent that a “calibration” and “detection”
signals would require different immobilized probes, Osikowicz teaches that
the signals from the test and procedural control bars arise from binding
different immobilized entities (FF18). Moreover, the Examiner relied upon
Brooks for teaching the detection and calibration signals (FF13-14), and
provided a reason as to why the skilled worker would have had reason to
utilize Brooks assay reagents in the Osikowicz format (see above).
Appellants have not identified a defect in the Examiner’s reasoning.
Claim 41 is a product claim and does not require that the signals
provide calibration or detection information (see App. Br. 40).
Nonetheless, as a signal would be detected from both the test and procedural
control bars in the intersecting region of the cross, a detection signal from
both bars would be observed in the overlapping area.
Appellants also contend that the Examiner did not establish that KLH,
as taught in the Brook patent, is a “polyelectrolyte” as required by the
claims.
Appellants respectfully submit that Wikipedia is an invalid
evidentiary reference and cannot properly be utilized in
rejection of patent application claims. As described by the
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source itself (see,
http://en.wikipedia.org/wiki/Wikipedia:About) articles can be
edited by anyone with access to the internet and articles
frequently contain significant misinformation.
(App. Br. 12.)
For the reasons stated by Appellants (App. Br. 12-13), we agree that
Wikipedia is not a sufficient evidentiary source in this case to establish that
the KLH would have been considered a polyelectrolyte. However, we do
not agree that no evidence has been put forth to establish that KLH is a
polyelectrolyte. According to the Specification, a polyelectrolyte is a
charged molecule that binds probe through ionic interactions (Spec. 11:12-
17). The Examiner cited Swerdlow for disclosing that KLH comprises
charged amino acids (FF15). KLH is therefore a charged molecule (FF16),
meeting the definition in the Specification.
As Appellants did not challenge the Examiner’s finding that KLH
comprises charged amino acids, we conclude that the evidence when
considered as a whole supports the Examiner’s finding that KLH is a
polyelectrolyte.

CONCLUSION OF LAW AND SUMMARY
The Examiner erred in finding that the Brooks patent taught an assay
device with “a second discrete element . . . within which both a capture
reagent and polyelectrolyte are substantially non-diffusively immobilized.”
The anticipation and obviousness rejections 1) through 7) of claims 41-62
are reversed.
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The Examiner did not err in concluding that claims 41 and 78 were
obvious in view of the teachings of Brooks, as evidenced by Swerdlow, and
Osikowicz. The obviousness rejection of claims 41 and 78 is affirmed.

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-IN-PART

cdc

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