Ex Parte Lang et al

Patent Trial and Appeal Board

Feb 27, 2017

12580113 (P.T.A.B. Feb. 27, 2017)

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.
12/580,113 10/15/2009 Christoph Lang 1576-0264 9675
28078 7590 02/28/2017
MAGINOT, MOORE & BECK, LLP
One Indiana Square, Suite 2200
INDIANAPOLIS, IN 46204
EXAMINER
CRAWFORD, ERIK B
ART UNIT PAPER NUMBER
1677
MAIL DATE DELIVERY MODE
02/28/2017 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 CHRISTOPH LANG, SAM KAVUSI,
DANIEL ROSER, and AMIRALI HAJ HOSSEIN TALASAZ
__________

Appeal 2014-001444
Application 12/580,113
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and
JACQUELINE T. HARLOW, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a method
of detecting a biomarker. The Examiner rejected the claims as anticipated
and as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

Statement of the Case
Background
“Diagnostic tests that can be performed at the point of care of an
individual, such as at the bedside of a patient . . . are becoming increasingly
popular. Diagnostic tests include tests directed to identifying biomarkers

1 Appellants identify the Real Party in Interest as Robert Bosch GmbH (see
App. Br. 1).
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such as Nucleic Acid, protein, and small molecules” (Spec. ¶ 2). A “need
exists for low cost assays including multiplexed assays, protein arrays,
lateral flow devices, sandwich assays, competitive assays, or bead based
arrays which provide accurate results and a method of using such arrays”
(Spec. ¶ 12).
The Claims
Claims 1–11 are on appeal. Claim 1 is representative and reads as
follows:
1. A method of detecting a biomarker comprising:
identifying a quantity of biomolecule types in a sample;
exposing the sample to a plurality of test sites, wherein
the number of test sites in the plurality of test sites is equal to or
greater than the identified quantity of biomolecule types;
establishing, for each of the plurality of test sites, a
respective test environment, wherein the test environment for
each of the plurality of test sites is different from the test
environment for each of the other of the plurality of test sites,
and each of the plurality of test sites is configured to capture
each of the biomolecule types;
obtaining a detection signal associated with each of the
plurality of test sites; and
determining the concentration of one of the biomolecule
types based upon the obtained detection signals.

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The Issues
A. The Examiner rejected claims 1, 4, 5, and 11 under 35 U.S.C.
§ 102(b) as anticipated by Dufva2 (Final Act. 2–3).
B. The Examiner rejected claim 2 under 35 U.S.C. § 103(a) as obvious
over Dufva and Xie3 (Final Act. 4–5).
C. The Examiner rejected claim 3 under 35 U.S.C. § 103(a) as obvious
over Dufva, Xie, and Dowd4 (Final Act. 5–6).
D. The Examiner rejected claims 6–9 under 35 U.S.C. § 103(a) as
obvious over Dufva and Banerjee5 (Final Act. 6–8).
E. The Examiner rejected claim 10 under 35 U.S.C. § 103(a) as obvious
over Dufva, Banerjee, and Matson6 (Final Act. 8–9).

A. 35 U.S.C. § 102(b) over Dufva
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the Dufva anticipates claim
1?
Findings of Fact
1. Dufva teaches “on one and the same solid support it is possible
to quantitatively compare e.g. pairs of mutant versus wild type genes
representing both very strong and very [weak] spots, just in different spatial

2 Dufva et al., WO 2007/062666 A1, published June 7, 2007 (“Dufva”).
3 Xie et al., US 7,087,373 B2, issued Aug. 8, 2006 (“Xie”).
4 Dowd et al., US 2009/0061535 A1, published Mar. 5, 2009 (“Dowd”).
5 Banerjee et al., US 7,892,854 B2, issued Feb. 22, 2011 (“Banerjee”).
6 Matson et al., US 2003/0198967 A1, published Oct. 23, 2003 (“Matson”).
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positions of the array corresponding to different washing conditions” (Dufva
17:4–8).
2. Dufva teaches “an easy and flexible platform for conducting an
assay of chemical entities and determining optimum assay parameters” that
operates “[b]y varying the assay conditions (parameters) within the one or
more chambers the chemical entities on the solid support can be exposed to a
range of assay conditions” (Dufva 10:4–25).
3. Figure 24 of Dufva is reproduced below:

“Fig. 24 shows possible locations of subarrays of chemical entitites (41) on
an asymetric solid support (40). The chambers (21) of the device should be
located in such a way that the subarrays can be subjected to different
conditions” (Dufva 42:5–8).
4. Figure 25 of Dufva is reproduced below:
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Fig. 25 shows the combination of a chemical gradient and
thermal gradient where the chemical gradient is created on each
slide and the respective solid support (40) is treated with
different temperatures . . . we can investigate the chemical
gradient at up to twelve different temperatures provided that
each temperature block (500) can be controlled individually.
The figure shows a device that can investigate eight different
chemical conditions at two different temperatures.

(Dufva 43:4–17).
5. Dufva teaches “the device is formed in a way and from a
material which makes it possible to detect a signal, and the device
furthermore includes means for detecting a signal” (Dufva 23:1–3).
6. Dufva teaches that after capture and washing, there is “analysis
of the locations and amount of the remaining bound analyte on the solid
support” (Dufva 19:23–24).
7. Dufva teaches the “type and amount of analyte
present in the sample is then determined by detecting the location and
amount of specific binding on the microarray spots” (Dufva 2:8–10).
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8. Dufva teaches:
It is for example possible to determine the IC50 dose for
various interacting chemical entities such as a drug-target
interaction. The IC50 represents the efficacy of a drug or
inhibitor, where IC50 is the concentration required to produce
50% inhibition. In this case, a dilution series of the drug is
created with which the target molecules attached to the solid
support are in functional contact.

(Dufva 17:21–26).
9. Figure 16 of Dufva is reproduced below:

“Figure 16 shows images of fluorescently labelled DNA microarray after
stringent washing at different temperatures provided by the device” (Dufva
24:29–30).
Principles of Law
Anticipation under 35 U.S.C. § 102 requires that “‘each and every
element as set forth in the claim is found, either expressly or inherently
described, in a single prior art reference.”’ In re Robertson, 169 F.3d 743,
745 (Fed. Cir. 1999).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 2–3; FF 1–9) and agree that
claim 1 is anticipated by Dufva. We address Appellants’ arguments below.
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Appellants contend that “[n]one of the passages or figures identified
by the Examiner disclose a method for calculating the concentration of a
biomolecule type, in a sample having an unknown concentration of the
biomolecule which is exposed to multiple test environments, using detection
signals obtained from the multiple test sites” (App. Br. 4; cf. App. Br. 5–7,
9–14). Appellants specifically contend “[t]here is no disclosure, however, of
any calculations. Generally obtaining a signal from a capture probe is not
the same as calculating the concentration of a biomolecule type” (App. Br.
8).
We begin our analysis with the claim language because the “name of
the game is the claim.” In re Hiniker Co., 150 F.3d 1362, 1369 (Fed. Cir.
1998). Claim 1 includes no limitations requiring either a “calculating” step
or a sample with an “unknown concentration.” While we read the claims in
light of the Specification, “limitations are not to be read into the claims from
the specification.” In re Van Geuns, 988 F.2d 1181, 1184 (Fed. Cir. 1993).
The Specification does not define the “determining the concentration”
step as requiring calculations and claim 1 does not recite that the
concentration must be determined by calculation rather than observation of a
dilution series or other approaches. Therefore, we do not find Appellants’
argument persuasive that the claim requires a “calculating” step. See In re
Self, 671 F.2d 1344, 1348 (CCPA 1982) (“[A]ppellant’s arguments fail from
the outset because . . . they are not based on limitations appearing in the
claims.”) We interpret the claim as simply requiring “determining the
concentration” by some process that need not include calculation.
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The Specification teaches an example using known concentrations of
AB diamond antibody (Spec. ¶ 55), and provides no definition that requires
the concentration of the target to be unknown (cf. Reply Br. 4
acknowledging “it is theoretically possible to start with a known
concentration” for “validation of the Appellants’ disclosed process”). Claim
1 also lacks a limitation that requires the analyte to have an “unknown
concentration.” In re Self, 671 F.2d at 1348. Therefore, we interpret claim 1
to encompass analysis of both known and unknown concentrations.
Applying these interpretations to Dufva’s disclosure, Dufva teaches to
“quantitatively compare” biomarkers (FF 1) by conducting assays on the
samples (FF 2) including exposing the samples to multiple test sites with
multiple different test environments (FF 2–4), obtaining detection signals
(FF 5) to obtain information on the “amount of the remaining bound analyte
on the solid support” (FF 6).
Dufva further teaches the “determining the concentration” step by
testing a dilution series to determine an IC50 concentration (FF 8). Dufva
specifically teaches that “IC50 is the concentration required to
produce 50% inhibition” (FF 8). Thus, when Dufva performs the assay as
disclosed to obtain an IC50 value, Dufva determines a concentration, the
IC50 concentration, of the drug based upon the signals, reasonably satisfying
the “determining the concentration” limitation of claim 1. See In re Zletz,
893 F.2d 319, 321 (Fed. Cir. 1989) (“[D]uring patent prosecution when
claims can be amended, ambiguities should be recognized, scope and
breadth of language explored, and clarification imposed.”)
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We recognize, but find unpersuasive, Appellants’ contention that a
“determination that is based upon a single signal as alleged by the Examiner
to be present in the prior art, is not the same as a determination based upon
at least two signals as required by claim 1” (Reply Br. 2). Whether the
dilution series (FF 8) or visual changes shown in Figure 16 (FF 9), multiple
signals are used. In the case of the dilution series, the word “series” as a
plural teaches multiple signals. In Figure 16, each hybridization has two
signals for wildtype and two for mutant (FF 9, cf. FF 1). This is shown, for
example, by the top row in Figure 16 of CD8/9 at the first temperature
condition of 22 °C, 24 °C, 26 °C, where there are two wildtype
hybridizations and two mutant hybridizations that both give signal, with a
reduced signal for the mutants at 28 °C, and where the two mutant signals do
not appear in the 30 °C, 32 °C, and 34 °C temperature conditions (FF 9).
We also recognize, but find unpersuasive, Appellants contention that
“the Examiner has failed to identify any disclosure in Dufva of establishing
a concentration using at least two detection signals. For example, in the
newly proffered ‘visual examination’, only one color at a time is compared
to the color scale” (Reply Br. 5). Dufva teaches comparing pairs of mutant
and pairs of wildtype signals quantitatively, thereby expressly teaching the
use of two detection signals (FF 1; cf. FF 9).
Conclusion of Law
The evidence of record support the Examiner’s conclusion that Dufva
anticipates claim 1.
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B. 35 U.S.C. § 103(a) over Dufva and Xie
Appellants contend “Xie discloses using a single binding affinity Kd.
A method which uses a single binding affinity in calculating a concentration
of an analyte is not the same as a method which uses two different binding
efficiencies for the analyte in calculating a concentration of an analyte”
(App. Br. 16).
The Examiner responds:
Dufva et al. (WO 2007/062666 A1) discloses a method for
determining the amount of a biomolecule type in a sample
which is exposed to multiple test environments, using signals
obtained from the multiple test sites. Xie et al. (US 7,087,373
B2) is relied upon for teaching that quantification of the
concentration of an analyte may be performed by direct
measurement of binding affinity of the analyte and calculating
the concentration based on said binding affinity. Thus, one of
ordinary skill in the art would recognize that upon determining
the binding affinity of an analyte for each respective test
environment in the method of Dufva et al. it would be
beneficial to determine the concentration of an analyte based on
each determined binding affinity in order to provide a
redundancy in the concentration calculation that improves
confidence in the obtained results.

(Ans. 22).
We find that the Examiner has the better position. As already noted,
Dufva teaches “to quantitatively compare e.g. pairs of mutant versus wild
type genes” (FF 1), while Xie teaches “quantification of the concentration of
protease inhibitor in free form maybe performed by direct measurement of
binding affinity Kd using isothermal titration calorimetry; and calculating the
concentration” (Xie 6:66 to 7:2). We agree with the Examiner that, given
Dufva’s express teaching to use pairs of data points for quantitative
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comparison and Xie’s teaching to calculate the concentration based on
quantitation information, the ordinary artisan would have found it obvious to
use both data points for “improve[d] confidence in the obtained
[concentration] results” (Ans. 22).
C.-E. 35 U.S.C. § 103(a)
Appellants do not separately argue these obviousness rejections,
instead relying upon their arguments to overcome Dufva or Dufva and Xie
(see App. Br. 17–18). The Examiner provides sound fact-based reasoning
for combining Dufva and Xie with Dowd, Banerjee, and Matson (see Final
Act. 5–9). Having affirmed the anticipation rejection of claim 1 over Dufva
and the obviousness rejection of claim 2 over Dufva and Xie for the reasons
given above, we also find that the further combinations render the rejected
claims obvious for the reasons given by the Examiner.

SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 102(b) as anticipated by Dufva. Claims 4, 5, and 11 fall with claim 1.
We affirm the rejection of claim 2 under 35 U.S.C. § 103(a) as
obvious over Dufva and Xie.
We affirm the rejection of claim 3 under 35 U.S.C. § 103(a) as
obvious over Dufva, Xie, and Dowd.
We affirm the rejection of claims 6–9 under 35 U.S.C. § 103(a) as
obvious over Dufva and Banerjee.
We affirm the rejection of claim 10 under 35 U.S.C. § 103(a) as
obvious over Dufva, Banerjee, and Matson.
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED