Siemens Healthcare Diagnostics Inc.

Patent Trials and Appeals Board

Nov 23, 2020

2020003186 (P.T.A.B. Nov. 23, 2020)

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.
15/128,479 09/23/2016 Jay J. LI 2014P07114WOUS 4069
28524 7590 11/23/2020
SIEMENS CORPORATION
IP Dept - Mail Code INT-244
3850 Quadrangle Blvd
Orlando, FL 32817
EXAMINER
LAM, ANN Y
ART UNIT PAPER NUMBER
1641
NOTIFICATION DATE DELIVERY MODE
11/23/2020 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
ipdadmin.us@siemens.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte JAY J. LI, DAVID J. LEDDEN,
ERIC SCOTT COWDEN, and DONGLAI LU
__________

Appeal 2020-003186
Application 15/128,479
Technology Center 1600
__________

Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and
TAWEN CHANG, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134 involving claims to a kit
containing a chemiluminescent detection system for a specific analyte. The
Examiner rejected the claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the Real Party in Interest as Siemens
Healthcare Diagnostics Inc. (see Appeal Br. 1).
2 We have considered the Specification of Sept. 23, 2016 (“Spec.”); Final
Office Action of May 1, 2019 (“Final Action”); Appeal Brief of Oct. 25,
2019 (“Appeal Br.”); Examiner’s Answer of Jan. 30, 2020 (“Ans.”); and
Reply Brief of Mar. 25, 2020 (“Reply Br.”).
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Statement of the Case
Background
“Immunoassay technologies are widely used in the field of medical
diagnostics. One example of a commercially used immunoassay is . . . the
LOCI® Luminescent Oxygen Channeling Immunoassay technology” (Spec.
¶ 3). “The sensitivity of an analyte detection immunoassay is dependent on
the affinity of one or more anti-analyte antibodies employed in the assay
architecture: the higher the affinity of the antibody, the higher the sensitivity
of the immunoassay” (id. ¶ 5).
The Claims
Claims 1–10 are on appeal.3 Claim 1 is the sole independent claim, is
representative and reads as follows:
1. A kit containing a chemiluminescent detection system for
a specific analyte, the kit comprising:
(a) a first composition comprising a singlet-oxygen
activatable chemiluminescent compound and a first
antibody or binding fragment thereof associated
therewith, wherein the first antibody or binding
fragment thereof is a detection antibody that
specifically binds to a first epitope of the analyte
whereby the singlet-oxygen activatable
chemiluminescent compound is capable of indirectly
binding to the analyte via the first antibody or binding
fragment thereof;
(b) a second composition comprising a singlet-oxygen
activatable chemiluminescent compound and a second
antibody or binding fragment thereof associated
therewith, wherein the second antibody or binding
fragment thereof is a detection antibody that
specifically binds to a second epitope of the analyte

3 Claims 11–15 were withdrawn from prosecution.
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whereby the singlet-oxygen activatable
chemiluminescent compound is capable of indirectly
binding to the analyte via the second antibody or
binding fragment thereof, and wherein the first and
second epitopes at least partially overlap such that the
first and second antibodies or binding fragments
thereof cannot both bind to a single analyte molecule,
and wherein the first and second epitopes are not
identical; and
(c) a third composition comprising a third antibody or
binding fragment thereof, the third antibody or
binding fragment thereof being a capture antibody
that specifically binds to a third epitope of the analyte
that does not overlap with the first and second
epitopes, whereby a single analyte molecule can bind
the third antibody or binding fragment thereof and one
of the first and second antibodies or binding
fragments thereof, and wherein the third antibody or
binding fragment thereof is capable of association
with a sensitizer capable of generating singlet oxygen
in its excited state, whereby association of the third
antibody or binding fragment thereof with the
sensitizer allows for the indirect binding of the
sensitizer to the analyte.

The Rejections
A. The Examiner rejected claims 1 and 2 under U.S.C. § 103(a) as
obvious over Pedersen4 and Singh5 (Final Act. 2–4).
B. The Examiner rejected claim 3 under U.S.C. § 103(a) as obvious over
Pedersen, Singh, and Ullman6 (Final Act. 5–6).

4 Pedersen et al., US 8,414,896 B2, issued Apr. 9, 2013.
5 Singh et al., US 6,703,248 B1, issued Mar. 9, 2004.
6 Ullman et al., EP 0984282 A2, published Mar. 8, 2000.
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C. The Examiner rejected claim 4 under U.S.C. § 103(a) as obvious over
Pedersen, Singh, and Zweig7 (Final Act. 6).
D. The Examiner rejected claim 5 under U.S.C. § 103(a) as obvious over
Pedersen, Singh, Zweig, and Manneh8 (Final Act. 7).
E. The Examiner rejected claim 6–10 under U.S.C. § 103(a) as obvious
over Pedersen, Singh, and Yager9 (Final Act. 8–9).

A. U.S.C. § 103(a) over Pedersen and Singh
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner’s conclusion that Pedersen and
Singh render the claims obvious?
Findings of Fact
1. Pedersen teaches:
the invention is directed to diagnostic kits. Kits according to
the present invention comprise an anti-EGFR antibody
composition prepared according to the invention which protein
may be labeled with a detectable label or non-labeled for non-
label detection. The kit may be used to identify individuals
inflicted with cancer associated with overexpression of EGFR.
(Pedersen 38:21–27).
2. Pedersen teaches, in a treatment context, a “composition
comprises two antibodies binding different but overlapping epitopes”
(Pedersen 18:8–9).

7 Zweig, S., US 2006/0263907 A1, published Nov. 23, 2006.
8 Manneh, V., US 2016/0320415 A1, published Nov. 3, 2016.
9 Yager et al, US 2012/0288961 A1, published Nov. 15, 2012.
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3. Pedersen teaches an:
antibody composition comprising antibodies directed against
three non-overlapping epitopes may thus comprise four, five or
six distinct antibody molecules so that two antibodies bind two
overlapping epitopes or the same first epitope, two other
antibodies bind two other overlapping epitopes or the same
second epitope, and two antibodies bind two further other
overlapping epitopes or the same third epitope.
(Pedersen 18:15–22).
4. Pedersen teaches “the invention relates to a recombinant
antibody composition comprising at least 3 distinct anti-EGFR antibody
molecules, wherein the antibodies bind distinct first, second and third
epitopes of EGFR” (Pedersen 3:66 to 4:2).
5. Pedersen teaches:
Antibodies capable of competing with each other for binding to
the same antigen may bind the same or overlapping epitopes or
may have a binding site in the close vicinity of one another, so
that competition is mainly caused by steric hindrance. Methods
for determining competition between antibodies are described.
(Pedersen 9:52–57).
6. Pedersen teaches “individually fluorescent labelled antibodies”
(Pedersen 10:51–52) and teaches:
The non-overlapping nature of the antibodies is preferably
determined using differently labelled antibodies in a FACS
analysis with EGFR expressing cells or by using Surface
Plasmon Resonance using EGFR antigen captured or
conjugated to a flow cell surface. ELISA based methods as
described in the examples may also be used.
(Pedersen 16:57–63).
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7. Singh teaches an exemplary assay where:
A chemiluminescent particle composition of the present
invention is attached to a specific binding reagent (for example:
antibody, oligonucleotide, receptor, etc.) that is complementary
to the analyte. A sensitizer particle is attached to a second
specific binding reagent that is complementary to the analyte.
In a sandwich assay format the analyte brings both the
sensitizer and chemiluminescer particles in close proximity.
Activation of sensitizer particles with light results in the
formation of singlet oxygen, which is channeled to the particle
label reagent.
(Singh 22:41–52).
Principles of Law
The Examiner has the initial burden of establishing a prima facie case
obviousness under 35 U.S.C. § 103. In re Oetiker, 977 F.2d 1443, 1445
(Fed. Cir. 1992). It is important to provide “a reason that would have
prompted a person of ordinary skill in the relevant field to combine the
elements in the way the claimed new invention does.” KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
We adopt the Examiner’s findings of fact and conclusion of law (see
Final Act. 2–4; FF 1–7). We agree that Pedersen and Singh render claim 1
obvious to the person of ordinary skill. We address Appellant’s arguments
below.
Appellant contends:
the Examiner has not identified any teaching or suggestion in
the prior art for a chemiluminescent detection system that
utilizes three articles/beads that include two “chemibeads”
associated with two different detection antibodies and that are
used in combination with a single “sensibead.” As such, the
Examiner has clearly failed to identify in the prior art the
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presence of an essential element that is required to establish a
prima facie rejection (i.e., the third particle in the form of a
second “chemibead” with a second, different detection antibody
associated therewith).
(Appeal Br. 15–16).
We find this argument unpersuasive for two reasons. First, Pedersen
and Singh render each element of claim 1 obvious. Pedersen teaches
diagnostic kits (FF 1) that may be composed of two antibodies “binding
different but overlapping epitopes” of an antigen (FF 2, 6) as required by the
antibodies of elements (a) and (b) of claim 1 as well as additional antibodies
binding still other epitopes of the antigen as required by element (c) of claim
1 (FF 3–4). Pedersen expressly teaches competitive antibodies (FF 5). And
while Pedersen does not teach the use of the well-known singlet oxygen
chemiluminescent label, Singh teaches an antibody sandwich assay where
the antibodies are labeled using this system (FF 7). The Examiner
reasonably finds this combination obvious “since it is a known type of label
for analyte detection . . . it would have been predictable by one skilled in the
art that the third antibody be associated with a sensitizer in order to form the
sandwich assay which brings both the sensitizer and chemiluminescent
particles in close proximity as taught by Singh” (Final Act. 4).
That is, the Examiner relies upon the KSR reasoning that “[i]f a person
of ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” KSR, 550 U.S. at 417. And “if a technique has been used to
improve one device, and a person of ordinary skill in the art would recognize
that it would improve similar devices in the same way, using the technique is
obvious unless its actual application is beyond his or her skill.” Id.
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As applied here, we agree with the Examiner that selecting the
chemiluminescent label of Singh (FF 7) for use as labels in the kits of
Pedersen (FF 1, 6) is a predictable variation using known technologies.
Second, claim 1 is drawn to a kit, not a chemiluminescent detection
process. While we do find that Pedersen suggests the use of two equally
labeled competitive antibodies for detection of epitopes (FF 5) and Singh
suggests that bound antibodies could be detected using another labeled
antibody with the singlet oxygen chemiluminescent label in a sandwich
assay (FF 7), reasonably suggesting the use of two “chemibeads” with a
single “sensibead”, we need not rely upon this determination because claim
1 is drawn to a product, not a process. And Pedersen clearly teaches the use
of three antibodies as required that may be labeled and Singh teaches the
singlet oxygen chemiluminescent labeling system is a known equivalent (FF
1–7).
Therefore, with regard to the intended use of detection, a “mere
statement of a new use for an otherwise old or obvious composition cannot
render a claim to the composition patentable.” In re Zierden, 411 F.2d 1325,
1328 (CCPA 1969). Moreover, the preamble only recites an intended use of
the kit and “the patentability of apparatus or composition claims depends on
the claimed structure, not on the use or purpose of that structure.” Catalina
Mktg. Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir.
2002).
Appellant contends:
Pedersen et al. do not disclose whether the “protein” that is
labeled with a detectable label is a single antibody or multiple
antibodies. Further, Pedersen et al. only disclose the use of “a
detectable label” and clearly do not disclose or enable the use of
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multiple detectable labels, more less [sic] labeling multiple
antibodies with multiple detectable labels.
(Appeal Br. 16).
We find this argument unpersuasive because Pedersen expressly
teaches “using differently labelled antibodies” in ELISA assays (FF 6).
Thus, Pedersen expressly rebuts Appellant’s argument. Beyond that, “[i]t is
well settled that the mere duplication of parts has no patentable significance
unless a new and unexpected result is produced.” In re Harza, 274 F.2d
669, 671 (CCPA 1960). Appellant provides no evidence or persuasive
argument that following the guidance of Pedersen to label multiple
antibodies as recited in claim 1 results in any unexpected result relative to
Pedersen’s labeled antibodies.
Appellant contends:
The presently claimed invention is directed to an unpredictable
art, and a person having ordinary skill in the art would clearly
recognize that not all antibodies are amenable for use in every
type of diagnostic immunoassay architecture; rather, antibodies
must be carefully selected for use based upon the architecture
employed by the immunoassay.
(Appeal Br. 16).
We find this argument unpersuasive. Pedersen expressly teaches that
two different antibodies to overlapping epitopes can be generated (FF 2–3)
and that a third antibody to different epitopes can be generated (FF 4).
Appellant provides no evidence, as opposed to argument, that the antibody
selection would not be predictable. An “obviousness finding was
appropriate where the prior art ‘contained detailed enabling methodology for
practicing the claimed invention, a suggestion to modify the prior art to
practice the claimed invention, and evidence suggesting that it would be
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successful.”’ In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re
O’Farrell, 853 F.2d 894, 902 (Fed. Cir. 1988)). Kubin stated that
“[r]esponding to concerns about uncertainty in the prior art influencing the
purported success of the claimed combination, this court [in O’Farrell]
stated: ‘[o]bviousness does not require absolute predictability of success . . .
all that is required is a reasonable expectation of success.”’ Kubin, 561 F.3d
at 1360 (citing In re O’Farrell, 853 F.2d at 903–904).
Appellant “submits that Pedersen et al. is clearly not the closest prior
art to the claims, and as such, is an improper primary reference for
utilization in an obviousness rejection of the claims of the subject
application” (Appeal. Br. 17).
We find this argument unpersuasive because the Examiner does not
necessarily need to find the closest prior art, but rather prior art sufficient to
demonstrate that the claim at issue is obvious. Indeed, it stands to reason
that if distant prior art is sufficient to render a claim obvious, then a fortiori
closer prior art would render the claim obvious as well. We agree with the
Examiner that Pedersen and Singh render claim 1 obvious for the reasons
given above.
Conclusion of Law
A preponderance of the evidence of record supports the Examiner’s
conclusion that Pedersen and Singh render claim 1 obvious.

B. U.S.C. § 103(a) over Pedersen, Singh, and Ullman
Appellant substantively relies upon overcoming the rejection over
Pedersen and Singh (see Appeal Br. 18), which we find unpersuasive for the
reasons given above.
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Appellant acknowledges that Ullman teaches “the use of fluorescent
molecules in combination with chemiluminescent compounds in particles”
but contends Ullman does not disclose “the modification of a typical LOCI®
assay architecture that includes two compositions/particles/beads to the
novel and non-obvious claimed assay architecture that includes three
compositions/particles/beads” (Appeal Br. 18).
We remain unpersuaded by this argument because Singh teaches the
LOCI assay architecture in a sandwich assay and Pedersen teaches the use of
three labeled antibodies, two of which may be overlapping, as well as the
use of antibodies to other epitopes (FF 1–7).

C. U.S.C. § 103(a) over Pedersen, Singh, and Zweig
Appellant does not substantively separately argue this obviousness
rejection, instead relying upon their arguments to overcome Pedersen and
Singh. The Examiner provides sound fact-based reasoning for combining
these references with Zweig (see Final Act. 6). Having affirmed the
obviousness rejection of claim 1 over Pedersen and Singh for the reasons
given above, we also find that the further combination with Zweig renders
the rejected claim obvious for the reasons given by the Examiner.

D. U.S.C. § 103(a) over Pedersen, Singh, Zweig, and Manneh
Appellant relies in part upon overcoming the rejection over Pedersen
and Singh (see Appeal Br. 20), which we find unpersuasive for the reasons
given above.
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Appellant also asserts, specific to claim 5, that:
Manneh only discloses the use of excipients in the formulation
of a liquid reagent that will subsequently be lyophilized.
Manneh does NOT disclose an excipient that is utilized to
reconstitute a lyophilized reagent. In other words, Manneh
teaches use of an excipient prelyophilization, whereas claim 5
recites the use of an excipient post-lyophilization. These are
two completely separate and independent phenomenon that
utilize two completely separate and independent
reagents/excipients.
(Appeal Br. 22).
We find this argument unpersuasive because claim 5 simply requires
that the kit include “an excipient for the reconstitution of the lyophilized
reagent.” In the context of this composition claim, the timing of the use of
the excipient is not relevant, because that timing represents an intended use
of the product and imposes no structural limitation on the product. Catalina,
289 F.3d at 809. Appellant identifies no structural difference between the
excipients disclosed by Manneh and those encompassed by claim 5.

E. U.S.C. § 103(a) over Pedersen, Singh, and Yager
Appellant does not substantively separately argue this obviousness
rejection, instead relying upon their arguments to overcome Pedersen and
Singh. The Examiner provides sound fact-based reasoning for combining
these references with Yager (see Final Act. 8–9). Having affirmed the
obviousness rejection of claim 1 over Pedersen and Singh for the reasons
given above, we also find that the further combination with Yager renders
the rejected claims obvious for the reasons given by the Examiner.

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SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 2 103 Pedersen, Singh 1, 2
3 103 Pedersen, Singh,
Ullman
3
4 103 Pedersen, Singh,
Zweig
4
5 103 Pedersen, Singh,
Zweig, Manneh
5
6–10 103 Pedersen, Singh,
Yager
6–10
Overall
Outcome
1–10

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