Ex Parte Labgold et al

Patent Trial and Appeal Board

Sep 9, 2015

11703103 (P.T.A.B. Sep. 9, 2015)

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.
11/703,103 02/07/2007 Marc R. Labgold SIOM-0003-UTI 5872
80308 7590 09/09/2015
Steven B. Kelber
12005 Sunrise Valley Drive, Suite 203
Reston, VA 20191
EXAMINER
CROW, ROBERT THOMAS
ART UNIT PAPER NUMBER
1634
MAIL DATE DELIVERY MODE
09/09/2015 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 MARC R. LABGOLD, GEORGE G. JOKHADZE, I-MIN M. JEN,
NAIPING SHEN, MARK T. KOZLOWSKI,
CHANDRAMOHAN V. AMMINI, DAVID A. SUHY,
MICHAEL C. NORRIS, and PETER E. LOBBAN
__________

Appeal 2013-001248
Application 11/703,1031
Technology Center 1600
__________

Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
ROBERT A. POLLOCK, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
STATEMENT OF CASE
According to the Specification, pages 7–8,
Methods for detecting one or more target agents in a
sample are taught. In preferred embodiments, target agents in
the sample are “captured” by a capture moiety conjugated to an
oligonucleotide, wherein the oligonucleotide serves as a proxy
for presence of the target agent in the sample, for example, by

1 According to Appellants, the real party in interest is Antara Biosciences,
Inc. App. Br. 2.
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detectably hybridizing to a complementary oligonucleotide.
The oligonucleotides employed in the methods herein can be of
many lengths and sequences, but preferably have lengths and
sequences that inhibit non-specific hybridization. Such
methods typically allow for rapid and accurate detection
without the need for nucleic acid purification and/or
amplification. In certain preferred embodiments, the target
agents are detected using electrochemical, fluorescent,
magnetic, or other detection methods known in the art. In
certain other embodiments, target nucleic acid sequences can be
directly detected electrochemically utilizing structural changes
and binding changes that arise when the target and its
complement bind.

A biosensor for use in the method is also taught.

The following claim is representative.
143. A biosensor comprising:
An electrode which comprises a conductive detection
surface, said electrode further comprising a mixed monolayer
comprising electrode-associated oligos bound to said detection
surface and diluent groups bound to said detection surface
which diluent groups serve as insulators on said detection
surface of said electrode;
Capture agents each of which comprises a capture moiety
conjugated to a capture-oligo which hybridizes to said
electrode-associated oligo under stringent hybridization
conditions, said capture moiety comprising an antigen-binding
region of an antibody which binds preferentially to a target;
wherein
said capture moiety binds preferentially to any target
present in a sample it is combined with to produce a sample
mixture, and upon removal of all capture agents comprising
capture moieties not bound to said target in said sample
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mixture, said capture oligos hybridize to said electrode-
associated oligos upon admixture therewith.

Cited Reference
Blackburn et al. US 2005/0003399 A1 Jan. 6, 2005
(“Blackburn”)

FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Answer at pages
5–11. The following facts of record are highlighted.
1. Figure 5 of the Specification is reproduced below.

Figure 5 shows a schematic diagram demonstrating the
detection of a target agent (530) using an immobilized binding
partner (550) for isolation of a reacted capture-associated oligo
complex (540). Step A comprises exposure of a capture-associated
oligo (510) conjugated to a capture moiety (520) to a sample
comprising target agent (530) to create reacted capture-associated
oligo complex (540). Step B comprises exposing reacted capture-
associated oligo complex (540) to immobilized binding partner
(550), which specifically binds to a different epitope of target
agent (530) than does capture moiety (520) to create immobilized
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reacted capture-associated oligo complex (560). Step C comprises
exposing immobilized reacted capture-associated oligo complex
(560) to electrode-associated oligos (570) on oligo chip (580). The
binding of the immobilized reacted capture-associated oligo
complex (560) comprising capture-associated oligo (510) to a
complementary electrode-associated oligo (570) generates a signal
in an electrochemical detection device.

Spec. 65–66.

2. Fig 6B of Blackburn is reproduced below.

Fig. 6B of Blackburn shows the electrode 105, linker, 106,
electrode associated oligonucleotides 100, capture binding moiety
200, capture binding portion 201, target 205.
3. Blackburn teaches a biosensor (paragraph 39) comprising an
electrode 105 (paragraph 30 and Figure 6B).
4. Blackburn teaches that the electrode is a conductive surface
(paragraph 58), and further comprises a mixed monolayer
(paragraph 30) comprising electrode associated oligonucleotides
(i.e., nucleic acids) 100 and passivation agents 107, which are
insulators (paragraph 23).
5. The Blackburn biosensor comprises capture binding ligand having
a capture moiety 200 and a capture binding portion 201 (30).
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6. The Blackburn capture moiety 200 binds to target 205 (paragraph
30 and Figure 6B).
7. Blackburn discloses that
It should also be noted that a number of
electrophoretic steps may be used: for example, the
components of the system may be added sequentially, with
an electrophoresis step after each addition to transport the
reagents down to the detection electrode. Similarly,
electrophoresis may be used to effect “washing” steps,
wherein excess reagents (non-bound target molecules or
non-bound extra binding ligand components, etc.) are driven
away from the detection electrode. Thus any combination of
electrophoresis steps may be used. In addition, the time of
the electrophoretic steps may be altered.
(Blackburn ¶ 86.)
8. Blackburn states that
Generally, the capture binding ligand allows the
attachment of a target analyte to the detection electrode, for
the purposes of detection. As is more fully outlined below,
attachment of the target analyte to the capture binding ligand
may be direct (i.e. the target analyte binds to the capture
binding ligand) or indirect (one or more capture extender
ligands may be used).
(Blackburn ¶ 210.)
9. Blackburn discloses that the target sequence 120 may be attached
to a capture extender probe 110 that has a sequence that will
hybridize to the capture probe 100 which may be used with any of
the embodiments of Figs 4, 5, 6. Blackburn ¶ 23.
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10. Figure 3B of Blackburn is reproduced below.

Figure 3B of Blackburn shows the use of a capture extender 110
having a first portion 111 that will hybridize with a portion of the
target sequence and a second portion 112 that will hybridize with
the capture probe 100, and target sequence 120.
11. Blackburn discloses that

Generally, the methods are as follows. In a preferred
embodiment, the target is initially driven down to the
vicinity of the detection probe using anyone of the methods
outlined above. In general, two methods may be employed;
the assay complexes as described below are formed first (i.e.
all the soluble components are added together, either
simultaneously or sequentially, including capture extender
probes, label probes, amplification probes, label extender
probes, etc.), including any hybridization accelerators, and
then the complex is added to the surface for binding to a
detection electrode. Alternatively, the target may be added,
hybridization acceleration occurs to allow the target to bind
the capture binding ligand and then additional components
are added to form the assay complex. The latter is described
in detail below, but either procedure may be followed.
Similarly, some components may be added, electrophoresed,
and other components added; for example, the target analyte
may be combined with any capture extender probes and then
transported, etc. In addition, as outlined herein,
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electrophoretic steps may be used to effect “washing” steps,
wherein excess reagents (non-bound analytes, excess probes,
etc.) can be driven from the surface.
(Blackburn ¶ 365 (emphasis added).)
12. Blackburn discloses that, “As will be appreciated by those in the
art, any two molecules that will associate, preferably specifically,
may be used, either as the analyte or the binding ligand.”
Blackburn¶ 212.

PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office). 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.’” Phillips v. AWH
Corp., 415 F.3d 1303, 1316 (Fed. Cir. 2005) (quoting In re Am. Acad. of Sci.
Tech. Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004).
“The patentability of a product does not depend on its method of
production. If the product in a product-by-process claim is the same as or
obvious from a product of the prior art, the claim is unpatentable even
though the prior product was made by a different process.” In re Thorpe,
777 F.2d 695, 697 (Fed. Cir. 1985) (citation omitted).

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Grounds of Rejection
Claims 143–146 are rejected under 35 U.S.C. § 102(b) as being
anticipated by Blackburn.
ISSUE
The issue is: Does the cited prior art support the Examiner’s finding
that the claimed subject matter is anticipated, teaching each element
claimed?
ANALYSIS
We do not find that the Examiner has provided a well articulated
statement of rejection to support a prima facie case of anticipation on this
record. We summarily reverse the Examiner’s anticipation rejection and we
enter a new ground of rejection of the claims under 37 C.F.R. § 41.50(b) for
obviousness over Blackburn.

Obviousness Blackburn
Claim 143 is newly rejected under 35 U.S.C. § 103(a) for obviousness
in view of Blackburn.
Comparing Figure 5 of the Specification, with the figures of
Blackburn (primarily Figs. 5 and 6), we find the following equivalencies
between the devices of the Appellants’ Specification (Fig. 5) and that of
Blackburn (Figs. 5 and 6B).
1. Appellants’ electrode 580 corresponds to Blackburn’s electrode
105.
2. Appellants’ oligo 570 corresponds to Blackburn’s oligo 100.
3. Appellants’ linker corresponds to Blackburn’s linker 106.
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4. Appellants’ capture moiety 520 corresponds to Blackburn’s
capture moiety 200.
5. Appellants’ capture agent portion 510 corresponds to Blackburn’s
capture portion 201.
6. Appellants’ hybrid species 510/570 corresponds to Blackburn’s
hybrid species 201/100.
7. Appellants’ target 530 corresponds to Blackburn’s target 205.

Appellants contend that
The capture agent of the claims comprises a capture moiety
which is conjugated with a capture oligo, but not conjugated to
the electrode. Indeed, it must be separate from the electrode
because it is designed to be combined with a sample, bind
target in the sample, and then, after removal of capture agents
with no target bound, hybridize with the electrode-associated
oligo - this is not a process recital, it is an express and structural
requirement of the claims. In contrast, the capture moiety of
Blackburn is specifically bound to the electrode! “FIG. 6A
utilizes a capture binding ligand 200 linked to the electrode 105
by an attachment linker 106.” [0030]. The capture ligand of
Blackburn is discussed in more detail beginning at [0209] and
is clearly set forth as part of the detection electrode (“the
detection electrode further comprises a capture binding ligand,
preferably covalently attached”). The “attachment linker” that
holds the capture moiety in fact is covalently attached to the
electrode itself - [0218]. See, in particular, Structure 17 at
[0220].
There is a simple but dramatic difference between the
claimed invention and the prior art. Blackburn presents a
detection electrode with a capture moiety conjugated directly
with it. There is no separate electrode associated oligo and
“free” “capture oligo”. In the claimed invention, to provide for
flexibility and sensitivity, the “capture agent” is not covalently
bound to the detection electrode at all. It is instead a binding
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ligand conjugated with an oligo. The capture agent is thus an
agent that is mixed with a sample suspected of comprising
target. If target is present, it is bound by the “binding ligand”
of the capture agent - typically an antibody. See Claim 145.
After unbound sample is removed, and capture agent without
target bound is removed, the capture agent with the binding
ligand bound to target is admixed with the detection reagent
bearing the electrode-associated oligos. It is the hybridization
between the two oligos that is detected and conveys the
concentration of the target present in the sample, by the strength
and degree of hybridization. In Blackburn, the sample is
combined directly with the detection electrode, the target is
concentrated in the region of the electrode through, e.g.,
electrophoresis, and it is the binding of the target by the ligand
attached to the electrode that is detected. Different reactions
and different detection schemes. It is unnecessary to
characterize one as good and the other as not as good - it is
sufficient that they are clearly different.

App. Br. 14–15. To summarize, Appellants argue that the capture agent of
the claims is not initially conjugated to the electrode until, upon removal of
all capture agents comprising capture moieties not bound to said target in
said sample mixture, the capture oligos hybridize to the electrode-associated
oligos upon admixture therewith. Appellants further argue that, “The
presentation of a biosensor which comprises a capture moiety that is not
linked to the electrode before admixture with the sample is of patentable
dimension, and taught away from by the reference.” Reply Br. 7.
We are not persuaded by Appellants’ argument. The problem here is
that Appellants claim a product, e.g., a biosensor having a specific structure.
Appellants chose to claim the conformation of the biosensor with the capture
agent, not without the capture agent. It is well settled that “[t]he
patentability of a product does not depend on its method of production. If
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the product in a product-by-process claim is the same as or obvious from a
product of the prior art, the claim is unpatentable even though the prior
product was made by a different process.” In re Thorpe, 777 F.2d at 697
(internal citation omitted). In addition, “[t]he test of obviousness vel non is
statutory. It requires that one compare the claim’s ‘subject matter as a
whole’ with the prior art ‘to which said subject matter pertains.’” In re
Ochiai, 71 F.3d 1565, 1569 (Fed. Cir. 1995) (quoting 35 U.S.C. § 103).
As we interpret claim 143, the claim requires two structural elements:
an electrode with a mixed monolayer comprising electrode-associated oligos
and diluent groups (elements 106 and 108 in figure 6B of Blackburn (FF 2));
and capture agents with a capture moiety that comprises an antigen binding
region (element 200 and 201 in figure 6B of Blackburn (FF 2). The final
requirement for “removal of all capture agents” is a process requirement
that, at best, results in a product based on that particular order of process
steps.
In the present case, Blackburn teaches the same final product structure
as Appellants’ biosensor and Blackburn meets all of the structural
limitations of the claims. Blackburn additionally teaches that different orders
of process steps may be performed, specifically teaching that the assay
complexes can be formed first (i.e. all the soluble components are added
together, either simultaneously or sequentially, including capture extender
probes, label probes, amplification probes, label extender probes, etc.),
including any hybridization accelerators. Then the complex is added to the
surface for binding to a detection electrode. FF11. Thus it would
reasonably appear that at some point in the fabrication of the assay
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components, the complexes are formed and then bind to the detection
electrode.
Alternatively, the target may be added, hybridization
acceleration occurs to allow the target to bind the capture
binding ligand and then additional components are added to
form the assay complex. The latter is described in detail below,
but either procedure may be followed. Similarly, some
components may be added, electrophoresed, and other
components added; for example, the target analyte may be
combined with any capture extender probes and then
transported, etc. In addition, as outlined herein, electrophoretic
steps may be used to effect “washing” steps, wherein excess
reagents (non-bound analytes, excess probes, etc.) can be driven
from the surface.
FF11 (citing Blackburn ¶ 365).
Blackburn further discloses that, “[a]s will be appreciated by those in
the art, any two molecules that will associate, preferably specifically, may be
used, either as the analyte or the binding ligand.” FF12. In addition, any
capture extender probe may first attach to the target in a sample and then
attach to an anchored second capture probe portion (Blackburn, Fig. 3B.)
Therefore, it would have been obvious to one of ordinary skill at the
time of the present invention reading Blackburn that the assay components
could be added either simultaneously or sequentially, first allowing the
complexes to form, and then adding the complexes to the surface for binding
to a detection electrode. Since Blackburn teaches that it is appreciated by
those of ordinary skill in the art at the time of the invention that any two
molecules that will specifically associate may be used, either as the target
analyte or the binding ligand, it would have been obvious to one of ordinary
skill in the art that Blackburn’s hybridization reaction of the target at
201/100 could occur after 201 complexes with the target. Even if the order
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of steps were different, “[t]here is no merit in the point here in the absence
of any proof in the record that the order of performing the steps produces
any new and unexpected results.” In re Burhans, 154 F.2d 690, 692 (CCPA
1946).
Moreover, the final product of Appellants’ biosensor and that of
Blackburn would reasonably appear to be similar, and Blackburn’s capture
moiety is capable of preferentially binding to any target present in a sample
it is combined with to produce a sample mixture, and upon removal of all
capture agents comprising capture moieties not bound to said target in said
sample mixture, the capture oligos are capable of hybridizing to and with the
electrode-associated oligos upon admixture therewith.
Upon return of the application to the Examiner for further
prosecution, the Examiner should address the subject matter of any
remaining claims.

CONCLUSION OF LAW
The pending anticipation rejection over Blackburn is reversed in favor
of a new ground of rejection of claim 143 for obviousness in view of
Blackburn.

TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides that “[a] new ground of
rejection . . . shall not be considered final for judicial review.”
37 C.F.R. § 41.50(b) also provides that the Appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
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the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment of the claims so
rejected or new evidence relating to the claims so rejected, or both, and have
the matter reconsidered by the examiner, in which event the proceeding will
be remanded to the examiner. . . .
(2) Request rehearing. Request that the proceeding be reheard under § 41.52
by the Board upon the same record. . . .

REVERSED and
NEW GROUND UNDER 37 C.F.R. § 41.50(B)
bar