Sam Kavusi et al.

Patent Trials and Appeals Board

Jul 27, 2021

2020005171 (P.T.A.B. Jul. 27, 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.
12/688,193 01/15/2010 Sam Kavusi 1576-0265 3073
28078 7590 07/27/2021
MAGINOT, MOORE & BECK, LLP
One Indiana Square, Suite 2200
INDIANAPOLIS, IN 46204
EXAMINER
GROSS, CHRISTOPHER M
ART UNIT PAPER NUMBER
1639
MAIL DATE DELIVERY MODE
07/27/2021 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte SAM KAVUSI, DANIEL ROSER,
CHRISTOPH LANG, and
AMIRALI HAJ HOSSEIN TALASAZ1
____________

Appeal 2020-005171
Application 12/688,193
Technology Center 1600
____________

Before ULRIKE W. JENKS, JOHN G. NEW, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies Robert Bosch GmbH and Robert
Bosch Tool Corp. as the real parties-in-interest. App. Br. 2.

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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1–6, 10, 11, and 19–27. Specifically,
claims 1, 2, 11, 19, 20, 21, 26, and 27 stand rejected as unpatentable under
35 U.S.C. § 103(a) as being obvious over the combination of Fong et al.
(WO 2008/073393 A1, June 19, 2008) (“Fong”), G. Serpa et al., Evaluation
of Immobilized Metal Membrane Affinity Chromatography for Purification
of an Immunoglobulin G1 Monoclonal Antibody, 816 J. CHROMATOGR. B
259–68 (2005) (“Serpa”), and/or T. Vitha et al., Complexes of DOTA-
Bisphosphonate Conjugates: Probes for Determination of Adsorption
Capacity and Affinity Constants of Hydroxyapatite, 24 LANGMUIR 1952–58
(2008) (“Vitha”).
Claims 1–6, 10, 11, and 19–27 stand rejected as unpatentable under 35
U.S.C. § 103(a) as being obvious over the combination of Fong, Serpa,
Vitha, and Sosnowski et al. (US 2007/0178516 A1, August 2, 2007)
(“Sosnowski”).2
We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

2 Claims 1–6, 10, 11, and 19–27 were also rejected by the Examiner as being
unpatentable under 35 U.S.C. § 112, first paragraph, for failing to comply
with the written description requirement. Final Act. 10. This rejection has
been withdrawn by the Examiner. See Ans. 7–8.
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NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to diagnostic tests and, more
specifically, to affinity based diagnostic tests. Spec. ¶ 1.

REPRESENTATIVE CLAIM
Independent claim 1 is representative of the claims on appeal and
recites:
Claim 1. A method of determining a number of a solution
constituent comprising:

determining a first percentage of a first solution
constituent of interest that will be bound at a first affinity assay
test location based upon a first affinity constant associated with
the first affinity assay test location and a probe density of the first
affinity assay test location;

determining a second percentage of a second solution
constituent that will be bound at the first affinity assay test
location based upon a second affinity constant associated with
the first affinity assay test location and the probe density of the
first affinity assay test location;

introducing a first number of solution constituents to the
first affinity assay test location;

creating a first residual number of solution constituents by
binding with a plurality of identical probe molecules a first
plurality of solution constituents at the first affinity assay test
location wherein the first plurality of solution constituents
includes a first portion of the first solution constituent of interest
and a first portion of the second solution constituent;

creating a second residual number of solution constituents
by binding a second plurality of solution constituents from the
first residual number of solution constituents wherein the second
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plurality of solution constituents includes a second portion of the
first solution constituent of interest and a second portion of the
second solution constituent;

obtaining a first signal associated with the bound first
plurality of solution constituents;

obtaining a second signal associated with the bound
second plurality of solution constituents; and

determining a second number of the first solution
constituent of interest based upon the determined first
percentage, the determined second percentage, the obtained first
signal and the obtained second signal, wherein the obtained first
signal and the obtained second signal are used to compensate for
the second solution constituent.

App. Br. 36–37.

ISSUES AND ANALYSIS
We decline to agree with, or adopt, the Examiner’s findings,
reasoning, and conclusion that the claims are obvious over the teachings and
suggestions of the combined cited prior art.

A. Claims 1, 2, 11, 19, 20, 21, 26, and 27

Issue
Appellant argues that the Examiner erred by finding that the
combination of Fong, Serpa, and Vitha teach or suggest all of the limitations
of the claims. App. Br. 14.

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Analysis
The Examiner finds that Fong teaches methods of measuring the
amount of two or more analytes in a fluid sample with a lateral flow solid
phase apparatus. Final Act. 3 (citing Fong Summary). More particularly the
Examiner finds that Fong teaches providing such a sample with multiple
analytes and a support surface with multiple capture zones (affinity test
locations) bearing, for example, monoclonal antibodies. Id. (citing Fong 21–
24, 14). The Examiner finds that Fong teaches that each analyte sample
flows from one zone to the next (plus a control zone), and further teaches
obtaining signals at each zone and the control. Id. The Examiner finds that
Fong also teaches one or more background areas in the passages. Id.
The Examiner finds that this “lateral flow technique appears to
inherently provide all elements from the ‘introducing a first number . . .’ step
to the ‘obtaining a second signal …’ step” of claims 1and 20, as well as
meeting the limitations of claims 2, 11, 21, and 26. Ans. 3; Final Act. 3.
The Examiner finds that Fong does not expressly teach determining a
percentage of a particular solution constituent that will bind at a particular
affinity assay test location based upon it’s affinity constant and probe
density for each constituent of each location such as set forth in the
manner(s) of the first two steps of claim and first four steps of claim 20.
Ans. 4; Final Act. 3. However, the Examiner finds that both Vitha and
Serpa teach the Langmuir equation, which explains how to determine the
mole fraction (percentage) of a binding species bound to a support versus the
residual which remains in solution based upon the maximum binding
capacity of a support surface and the analyte’s affinity constant (Ka) for the
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surface. Final Act. 4 (citing Vitha 1954 (equation (1)), Serpa 262 (equations
2, 3)).
The Examiner concludes that it would have been prima facie obvious
to a person of ordinary skill in the art to determine the mole fraction of each
analyte that will bind each support capture zone and/or background area(s),
as taught by Fong, and the fraction that will remain in solution as a function
of Ka and the maximum binding capacity (or probe density) of each region
as taught by Vitha or Serpa. Final Act. 4. The Examiner reasons that the
combination of Vitha and/or Serpa with Fong would have suggested to the
skilled artisan to use the Langmuir equation to determine the mole fraction
of each of the multiple analytes that will bind at particular surface regions
and the proportion that will remain in solution. Id.
The Examiner also reasons that a person of ordinary skill in the art
would have been motivated to combine the teachings of the references in
this manner to obtain the benefit of deconvoluting signals from antibodies
with overlapping specificity, such as for influenza A and B, due to common
epitopes. Final Act. 5 (citing Fong 33). The Examiner also finds that a
skilled artisan would have been motivated to combine the teachings of the
references to correct for artifacts, especially in the instance of lot-to-lot
variation in materials or reagents. Id. (citing Fong 29–30).
Alternatively, the Examiner finds, a person of ordinary skill in the art
would have been motivated to model the amount of bound and free analytes
at each surface in order to establish the dynamic range of the assay and not
to waste rare samples. Final Act. 5 (citing MPEP § 2141 III (C); KSR Int’l
Co. v. Teleflex Inc., 550 U.S. 398 (2007)).
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The Examiner also reasons that a person of ordinary skill in the art
would have had a reasonable expectation of success in applying the
Langmuir equation of Vitha or Serpa with a view to characterizing the solid
phase apparatus of Fong, because fitting experimental data to the model(s)
would have been well within the grasp of the skilled artisan. Final Act. 5
(citing Vitha 1954, Serpa 262).
Having reviewed the evidence of record, we are not persuaded that the
Examiner has established a prima facie case of obviousness. “[T]he
examiner bears the initial burden … of presenting a prima facie case of
unpatentability….” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
We agree with the Examiner that the Langmuir equation, as taught by
both Serpa and Vitha, teaches or suggests the limitations reciting, e.g.:
[D]etermining a first percentage of a first solution constituent of
interest that will be bound at a first affinity assay test location
based upon a first affinity constant associated with the first
affinity assay test location and a probe density of the first affinity
assay test location

and

determining a second percentage of a second solution constituent
that will be bound at the first affinity assay test location based
upon a second affinity constant associated with the first affinity
assay test location and the probe density of the first affinity assay
test location….

Because we agree with the Examiner that these passages of Serpa and Vitha
teach the limitations in question, the principal question before us, then, is
whether Fong teaches the remaining limitations of the claims.
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We conclude that it does not. Fong is directed to “methods of
measuring the amount of two or more analytes of interest in a fluid sample,
using a solid phase assay (e.g., a sandwich immunoassay or an inhibition
immunoassay), in which an analyte of interest and a capture reagent are used
as part of a specific binding pair….” Fong 1. Specifically, Fong teaches
that:
The methods of the invention utilize a solid phase apparatus,
such as a lateral flow solid phase apparatus or a capillary flow
apparatus. In representative methods of the invention, the solid
phase apparatus includes an application point, two or more
sample capture zones (one corresponding to each analyte of
interest) and a control capture zone; the sample capture zones
and the control capture zone can be sequentially (with respect to
the flow of liquid by capillary action) located on the solid phase
apparatus; alternatively, the sample capture zones and the
control capture zone can be approximately equidistant from the
application point.

Id. at 2 (emphasis added). Fong further teaches that:
The amount of an analyte of interest in the fluid sample is then
determined. For example, the amount of an analyte of interest in
the fluid sample can be determined as a ratio between 1) the
amount of analyte binding particles that are arrested in the
sample capture zone corresponding to that analyte of interest,
and 2) the sum of the amount of analyte binding particles in all
of the sample capture zones and in the control capture zone. In
another embodiment, if desired, a detected background amount
is subtracted from the detected amount of particles in each of the
sample capture zones and in the control capture zone prior to
determining the ratios.

Id. at 3 (emphasis added). Fong thus teaches that a sample containing
multiple analytes is passed over “sample capture zones,” and each capture
zone contains binding particles specific to one of the analytes. Appellant’s
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claim 1 recites only a single “affinity assay location.” And, although
dependent claim 2 and its dependents recite “transporting the first residual
number of solution constituents from the first affinity assay test site to a
second affinity assay test site,” unlike the individualized capture zones of
Fong, the Specification makes clear that such test sites may contain the same
probe as the first affinity test sites. See Spec. ¶ 26.
Just as importantly, Fong teaches that the amount of a given analyte in
a system can be determined by effectively measuring the strength of the
signal at the capture zone in which the probes are specific for the analyte in
question, and measuring the sum of the amount of analyte binding particles
in all of the sample capture zones and in the control capture zone.
Fong also teaches competitive or inhibition type assays, in which
the buffered, mixed fluid sample is applied to the application
point of the solid phase apparatus. The solid phase apparatus is
then maintained under conditions which are sufficient to allow
capillary action of fluid to transport analyte coated particles to
and through the sample capture zones, and to and through the
control capture zone, where they bind to the control capture
reagent. The sample capture reagents interact with analyte
coated particles; interaction of sample capture reagents and
analyte coated particles results in arrest of analyte coated
particles in the sample capture zones. Because of competition
between the analyte coated particles and analyte (if present) in
the sample for binding sites on the sample capture reagents in the
sample capture zones, the amount of analyte coated particles
arrested in the sample capture zones is inversely proportional to
the amount of the analytes in the sample. The amount of analyte
coated particles that are arrested in the sample capture zones, and
in the control capture zone, are then determined.

Fong, 4–5.
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Neither of these embodiments is comparable to Appellant’s claimed
invention. Claim 1, by way of example, recites:
obtaining a first signal associated with the bound first plurality
of solution constituents;

obtaining a second signal associated with the bound second
plurality of solution constituents; and

determining a second number of the first solution constituent of
interest based upon the determined first percentage, the
determined second percentage, the obtained first signal and the
obtained second signal, wherein the obtained first signal and the
obtained second signal are used to compensate for the second
solution constituent.

App. Br. 37–38 (emphasis added). The claimed invention, as in Fong,
requires passing an analyte-bearing solution over multiple capture zones.
However, it is in the italicized portion of the quoted limitations that a critical
difference between Fong and the claimed invention resides. Specifically, the
claimed invention requires using “the obtained first signal and the obtained
second signal are used to compensate for the second solution constituent.”
To construe the meaning of this limitation, we turn to Appellant’s
Specification. See Phillips v. AWH Corp., 415 F.3d 1303, 1316 (Fed. Cir.
2005) (holding that the Board “determines the scope of claims in patent
applications not solely on the basis of the claim language, but upon giving
claims their broadest reasonable construction ‘in light of the specification as
it would be interpreted by one of ordinary skill in the art.’” (quoting In re
Am. Acad. of Sci. Tech Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004))).
Appellant’s Specification discloses that:
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Typically, affinity assays are limited by the fact that each set of
capture molecules usually yields only a single data point. A
single data point is generally insufficient for computing an
accurate result, especially when there are unknowns in the
system. Such unknowns can be the presence of cross reactive
molecules, molecules different from the analyte of interest which
nonetheless bind to the capture molecules, thus rendering
quantitative results useless and causing false positives.

Spec. ¶ 4. Appellant’s Specification thus recognizes that cross-binding of
additional analytes can be a problem in affinity assays, and recognizes a
need to account for such binding, i.e., to a need to “compensate for the
second solution constituent,” as recited in claim 1. To achieve this end, the
Specification discloses:
Calculation of the number of one or more analytes of interest is
possible since the signal obtained by the sensor 116 for a
particular one of the selected set of test sites 124 is the
summation of the contributors to the signal including the
molecule of interest, and each of the noise sources such as
interfering molecules. The relative proportion of the signal
attributable to each of the contributors is dependent upon the
amount of the particular contributor, the amount of the other
contributors, and the relative affinity to the initially deposited
capturing probes of each of the contributors. The relationship is
reflected in the following equation:

wherein

S1 is the signal associated with the bound probes 160 in the test
site 1241,

a1-1 is the percentage of an analyte (1 through x) which binds to
the probes 160 in the test site 1241, and

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n1-1 is the number in the sample of the identified analyte (1
through x) at the test site 1241.

Similarly, the relationship of the signal at the test site 1242 is
reflected in the following equation:

wherein

S2 is the signal associated with the bound probes 160 in the test
site 1242,

a2-1 is the percentage of an analyte (1 through x) which binds to
the probes 160 in the test site 1242, and

n2-1 is the number in the sample of the identified analyte (1
through x) at the test site 1242.

Since the number of the analytes at the test site 1242 is equal to
the original number of analytes in the test sample less the number
of analytes that were bound at the test site 1241, the equation for
the signal at the test site 1242 may be rewritten as:

The foregoing equations, for the case of two analytes, can be
resolved to:

Accordingly, because the number of probe molecules is
controlled, the percentage of bound analytes can be determined
for each of the analytes as a function of the affinity constant and
probe density. Thus, the number of each of the analytes in the
initial test solution 150 can be determined.

Spec. ¶¶ 32–36.
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The Specification further discloses that:
The equation set forth above in paragraph 44 [sic] is also useful
in scenarios wherein an interfering analyte is present in the
solution. In this scenario, the signals obtained from a test
solution (S1) and a residual solution (S2) are determined
according to the following equations:

Thus, for scenarios wherein the percentage of analyte molecules
which bind to capture molecules is not known, the number of
analytes in a solution including an interfering species can be
determined according to the equation:

Spec. ¶ 53 (emphasis added). In other words, a solution containing at least
two analytes of interest is exposed to an initial capture zone consisting of
identical probes. After exposure, the analytes that are not bound constitute
the “residual number of solution constituents,” which is then bound again in
the first capture zone:
[C]reating a second residual number of solution constituents by
binding a second plurality of solution constituents from the first
residual number of solution constituents wherein the second
plurality of solution constituents includes a second portion of the
first solution constituent of interest and a second portion of the
second solution constituent.

App. Br. 37. A signal is then obtained from each of the bound analytes on
the first and second capture zones, and then the practitioner:
[D]etermin[es] a second number of the first solution constituent
of interest based upon the determined first percentage, the
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determined second percentage, the obtained first signal and the
obtained second signal, wherein the obtained first signal and the
obtained second signal are used to compensate for the second
solution constituent.

Id. at 38 (emphasis added). Appellant’s Specification thus discloses the
meaning of compensating for the second solution constituent, as recited in
claim 1.
This is entirely different from the teachings of Fong, which teaches
quantifying an analyte by “determin[ing…] a ratio between 1) the amount of
analyte binding particles that are arrested in the sample capture zone
corresponding to that analyte of interest, and 2) the sum of the amount of
analyte binding particles in all of the sample capture zones and in the control
capture zone.” Fong 3. The Examiner points to no teaching or suggestion of
Fong, nor can we discern any, by which “the obtained first signal and the
obtained second signal, wherein the obtained first signal and the obtained
second signal are used to compensate for the second solution constituent,”
i.e., to compensate for cross binding of a second analyte that effectively
interferes with obtaining an accurate assay of a first analyte. Absent any
such teaching or suggestion in the cited prior art, we conclude that the
Examiner has failed to establish a prima facie case of obviousness, and we
reverse the Examiner’s rejection of claims 1, 2, 11, 19, 20, 21, 26, and 27.

B. Claims 1–6, 10, 11, and 19–27
The Examiner incorporates the findings and conclusions with respect
to Fong, Serpa, and Vitha, and further finds that Sosnowski teaches active
programmable electronic matrix (“APEX”) devices. Final Act. 8 (citing
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Sosnowski generally, Abstr., and Figs. 3, 9). The Examiner finds that
Sosnowski teaches that such devices can both release and transport
hybridized and mismatched nucleic acid analytes via electrical charge from
one particular microlocation to another. Id. The Examiner finds that
Sosnowski teaches hybridization/dehybridization stringency as a function of
temperature and the concentration of salt, pH, and chaotropic agents in a
solution, as recited in claims 5, 6, 23, and 24. Id. (citing Sosnowski ¶¶ 31,
38).
The Examiner concludes that it would have been prima facie obvious
for a person of ordinary skill in the art to use the APEX device of Sosnowski
in a nucleic acid assay, as taught by Fong in view of Serpa and/or Vitha.
Final Act. 9. The Examiner reasons that a skilled artisan would have been
motivated to utilize the APEX device of Sosnowski for a nucleic acid assay
as taught by Fong, in view of Serpa and/or Vitha, to obtain the benefits of
such a device, including simpler sample processing and single base pair
discrimination, as taught by Sosnowski. Id. (citing Sosnowski ¶¶ 32–38).
Furthermore, the Examiner concludes, a person of ordinary skill in the
art would have had a reasonable expectation of success in applying the
APEX device of Sosnowski to the combined teachings of Fong, Vitha,
and/or Serpa in light of the excellent results taught by Sosnowski. Id. (citing
Sosnowski Fig. 15).
We find that the teachings of Sosnowski do not cure the deficiencies
of the combination of Fong, Serpa, and/or Vitha that we have explained
above. We incorporate our reasoning with respect to claims 1, 2, 11, 19, 20,
21, 26, and 27 with respect to claims 1–6, 10, 11, 19–27 and, for those same
reasons, we reverse the Examiner’s rejection of these claims.
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CONCLUSION
The rejection of claims 1–6, 10, 11, and 19–27 as unpatentable under
35 U.S.C. § 103(a) is reversed.

REVERSED

Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 2, 11, 19, 20,
21, 26, 27
103(a) Fong, Serpa, Vitha, 1, 2, 11,
19, 20, 21,
26, 27
1–6, 10, 11, 19–
27
103(a) Fong, Serpa, Vitha,
Sosnowski
1–6, 10,
11, 19–27
Overall
Outcome
1–6, 10,
11, 19–27