Ex Parte Oliver

Patent Trial and Appeal Board

Jun 7, 2017

12732870 (P.T.A.B. Jun. 7, 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.
12/732,870 03/26/2010 John S. Oliver NAB-004 4044
51414 7590 06/09/2017
GOODWIN PROfTFR T T P
EXAMINER
PATENT ADMINISTRATOR BROWN, MINDY G
100 Northern Avenue
BOSTON, MA 02210 ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
06/09/2017 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):
PATENTBOS @GOODWINPROCTER.COM
PSOUSA-ATWOOD@GOODWINPROCTER.COM
GLENN.WILLIAMS@GOODWINPROCTER.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHN S. OLIVER1
Appeal 2015-007210
Application 12/732,870
Technology Center 1600
Before JOHN G. NEW, RYAN H. FLAX, and RACHEL H. TOWNSEND,
Administrative Patent Judges.
NEW, Administrative Patent Judge.
1 Appellant states the real party-in-interest is Nabsys, Inc. App. Br. 3.
Appeal 2015-007210
Application 12/732,870
DECISION ON APPEAL
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1—3, 5, 7, 8, 10—23, 26—32, 34, 36, 37,
39-53, 56-48, 76, and 77. Specifically, claims 1—3, 5, 7, 8, 10-14, 18, 21—
23, 26, 28, and 76 stand rejected as unpatentable under 35 U.S.C. § 102(b)
as being anticipated by Ling et al. (US 2007/0190542 Al, August 16, 2007)
(“Ling”)-
Claims 15 and 16 stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Ling and R. Rapley,
Enhancing PCR Amplification and Sequencing Using DNA-Binding
Proteins, 2 Molecular Biotechnology 295-98 (1994) (“Rapley”).
Claims 17 and 19 stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Ling and P.V. Riccelli et
al., Hybridization of Single-stranded DNA Targets to Immobilized
Complementary DNA probes: Comparison of Hairpin versus Linear Capture
Probes, 29(4) Nucleic Acids Research, 996-1004 (2001) (“Riccelli”).
Claim 20 stands rejected as unpatentable under 35 U.S.C. § 103(a) as
being obvious over the combination of Ling and A. Bourdoncle et al.,
Quadruplex-BasedMolecular Beacons as Tunable DNA Probes, 128 J. Am.
Chem. Soc., 11094—105 (20006) (“Bourdoncle”).
Dependent claim 27 stands rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Ling and E. Lennon et al.,
Evaporative Pumping of Liquid in Nanochannel for Electrical Measurement
of a Single Biomolecule in Nanofluidic Format, Proc. 7th IEEE Int’l Conf.
on Nanotechnology, 562-65 (2007) (“Lennon”).
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Claim 28 stands rejected as unpatentable under 35 U.S.C. § 103(a) as
being obvious over the combination of Ling and M. Margulies et al.,
Genome Sequencing in Microfabricated High-density Picolitre Reactors,
437 Nature 376-80 (2005) (“Margulies”).2
Claim 29 stands rejected as unpatentable under 35 U.S.C. § 103(a) as
being obvious over the combination of Ling and Drmanac et al. (US
5,202,231, April 13, 1993) (“Drmanac”).
Claims 30-32, 34, 36, 37, 39-44, 51—53, 56, 57, and 77 stand rejected
as unpatentable under 35 U.S.C. § 103(a) as being obvious over the
combination of Ling and Drmanac.
Claims 45 and 46 stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of Ling, Drmanac, and
Rapley.
Dependent claims 47, 48, and 49 stand rejected as unpatentable under
35 U.S.C. § 103(a) as being obvious over the combination of Ling,
Drmanac, and Riccelli.
Claim 50 stands rejected as unpatentable under 35 U.S.C. § 103(a) as
being obvious over the combination of Ling, Drmanac, and Bourdoncle.
Claim 58 stands rejected as unpatentable under 35 U.S.C. § 103(a) as
being obvious over the combination of Ling, Drmanac, and Lennon.
Claims 1-3, 5, 7, 8, 10-23, 26-32, 34, 36, 37, 39-53, 56-58, 76, and
77 also stand rejected as unpatentable on the ground of nonstatutory
obviousness-type double patenting. Those rejections are based on two
different commonly assigned patents each having a common inventor with
2 Also over M. Margulies et al., Genome Sequencing in Microfabricated
High-density Picolitre Reactors, 441 Nature 120 (2006) (Corrigendum).
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the application on appeal. Specifically, claims 1, 16, 21, 26, 29, 30, 46, 51,
and 56 stand rejected as unpatentable over claims 1—18 of Oliver et al. (US
8,262,879 B2, September 11, 2012) (“Oliver ’879”) and Rapley.
Claims 2, 3, 5, 7, 8, 10-15, 18, 22, 23, 31, 32, 34, 36, 37, 39, 45, 48,
52, 53, and 57 stand rejected as unpatentable over claims 1—18 of Oliver
’879, Rapley, and Ling.
Claims 17, 19, 47, and 49 stand rejected as unpatentable over claims
1—18 of Oliver ’879, Rapley, Ling, and Riccelli.
Claims 20 and 50 stand rejected as unpatentable over claims 1—18 of
Oliver ’879, Rapley, Ling, and Bourdoncle.
Claims 27 and 58 stand rejected as unpatentable over claims 1—18 of
Oliver ’879, Rapley, and Lennon.
Claim 28 stands rejected as unpatentable over claims 1—18 of Oliver
’879, Rapley, and Margulies.
Claims 1, 16, 21, 26, 29, 30, 46, 51, and 56 also stand rejected as
unpatentable over claims 16—50 of Ling et al. (US 8,882,980 B2, November
11, 2014) (“Ling ’980”) and Rapley.3
Claims 2, 3, 5, 7, 8, 10-15, 18, 22, 23, 31, 32, 34, 36, 37, 39, 45, 48,
52, 53, and 57 stand rejected as being unpatentable over claims 16—50 of
Ling ’980, Rapley, and Ling.
Claims 17, 19, 4 7, and 49 stand rejected as being unpatentable over
claims 16—50 of Ling ’980, Ling, and Riccelli.
3 The Examiner provisionally rejected these claims over, inter alia,
Appellant’s 12/553,667 application, which has since issued as US 8,882,980
B2.
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Claims 20 and 50 stand rejected as being unpatentable over claims
16—50 of Ling ’980, Ling, and Bourdoncle.
Claims 27 and 58 stand rejected as being unpatentable over claims
16—50 of Ling ’980, Rapley, and Lennon.
Claim 28 stands rejected as being unpatentable over claims 16—50 of
Ling ’980, Rapley, and Margulies
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellant’s invention is directed to devices and methods for
sequencing biomolecules, which include improving signal-to-noise ratio of
the detection of relative positions of probes hybridized to a biomolecule by
coating at least a portion of the biomolecule with a protein prior to its
translocation through a structure defining a nanopore, microchannel or
nanochannel. Abstract.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method for mapping a target biomolecule, the
method comprising the steps of:
a) providing a single-stranded or double-stranded target
biomolecule;
b) providing an apparatus comprising first and second
fluid chambers in fluid communication with one another,
wherein the first and second fluid chambers are separated by a
structure defining a member selected from the group consisting
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of a nanopore and a fluidic channel having a width of 1
micrometer or less, and wherein the apparatus comprises at least
one pair of electrodes defining at least one detector volume
within the structure;
c) providing at least one probe set, said probe set
comprising a first plurality of identical probes that selectively
hybridize to complementary regions on the target biomolecule;
d) hybridizing the probes to the target biomolecule to
provide a partially hybridized biomolecule having probes
hybridized to complementary regions thereon;
e) coating at least a portion of the partially hybridized
biomolecule with one or more proteins to increase a diameter of
the partially hybridized biomolecule;
f) translocating the partially hybridized biomolecule
through the at least one detector volume;
g) monitoring, as a function of time, changes in an
electrical property detected by the at least one pair of electrodes
defining the at least one detector volume as the partially
hybridized biomolecule translocates therethrough; and
h) differentiating between hybridized and non-hybridized
regions of the target biomolecule based at least in part on the
detected changes in the electrical property in the at least one
detector volume, thereby mapping at least a portion of the target
biomolecule,
wherein the increased diameter of the partially hybridized
biomolecule slows a translocation rate of the partially hybridized
biomolecule, and increases a signal-to-noise ratio of the detected
electrical property.
App. Br. 22—23.
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ISSUES AND ANALYSES
Except as otherwise indicated herein, we agree with the Examiner’s
findings and conclusions that the appealed claims are anticipated by, or
obvious over, the combined cited prior art under 35 U.S.C. §§ 102(b) and
103(a). We address the arguments raised by Appellant below.
I. Rejection of claims 1—3, 5, 7, 8,10-14,18, 21—23, 26, 28, and 76 as
unpatentable under 35 U.S.C. § 102(b)
Issue
Appellant argues the Examiner erred because Ling does not disclose
the limitation of claim 1 reciting “coating at least a portion of a partially
hybridized biomolecule.” App. Br. 6.
Analysis
Appellant points to paragraph [0050] of Ling, which Appellant
contends states only that it may be difficult to prevent a long single-stranded
molecule from self-hybridizing during sequencing, and that this can be
prevented. App. Br. 6. According to Appellant, Ling does not enable
coating at least a portion of a hybridized biomolecule by, e.g., incubating a
hybridized biomolecule with a protein or enzyme that binds to the
biomolecule to form at least a partial coating along the biomolecule, as
taught by Appellant’s Specification. Id. Appellant asserts that the single
sentence of Ling in paragraph [0050] cited by the Examiner4 is not an
4 “Alternatively, or in addition, single-stranded binding proteins can be used
to keep the molecule single-stranded.” Ling | 50.
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enabling disclosure for coating a partially hybridized biomolecule, as
required by claim 1. Id. (also citing Declaration of John S. Oliver, || 11—15,
October 9, 2013 (the “Oliver Declaration”)). Appellant points to the Oliver
Declaration, in which Dr. Oliver states that Ling “provides no guidance as to
i) how single-stranded binding proteins can be used to keep a molecule
single stranded, ii) what specific proteins may be used to achieve this effect,
or, iii) what process conditions may be used to utilize such proteins.” Id. at
6—7 (quoting Oliver Decl. 113). Appellant notes that Dr. Oliver opines
further that Ling “does not provide an enabling disclosure for the use of
single-stranded binding protein to keep a molecule single-stranded.” Id. at 7
(quoting Oliver Decl. 114).
Appellant argues further that Ling refers to binding proteins only in
that “they can be used to keep the molecule single-stranded.” App. Br. 7.
Appellant contends Ling does not state how the binding proteins are used,
and does not state that the proteins are used to coat at least a portion of a
partially hybridized biomolecule. Id. According to Appellant, one cannot
conclude from Ling’s statement about the use of binding proteins that
partially hybridized biomolecules are to be at least partially coated, as
required by claim 1, as opposed to “using binding proteins” with
unhybridized biomolecules, an interpretation that may, Appellant contends,
be reasonably inferred from Ling’s statement. Id.
Appellant also argues that Ling does not disclose coating at least a
portion of a partially hybridized biomolecule to increase the diameter of the
biomolecule, by which the increased diameter slows the translocation rate of
the biomolecule and increases the signal-to-noise ratio of a detected
electrical property, as required by claim 1. App. Br. 7. Appellant maintains
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that, to the extent Ling mentions binding proteins at all, they are intended to
only keep the molecule single-stranded. Id. Appellant argues that Ling is
silent with respect to increasing the diameter of the biomolecule to slow its
translocation rate nor does the reference provide an enabling disclosure for
coating a partially hybridized biomolecule to provide the benefit recited in
claim 1. Id.
The Examiner acknowledges that Ling discloses “single-stranded
binding proteins can be used to keep the molecule single-stranded,” but does
not see that teaching as leading to the conclusion that the claimed method
steps are not met. Ans. 26 (quoting Ling | 50). The Examiner finds that is
so because this step is taught to be not only an “[alternative” step, which
admittedly, can prevent a long-single-stranded molecule from self-
hybridizing during sequencing, but “in addition to” to “placing a “hybridized
biomolecule into a nano-channel that is coupled to a nanopore such that the
nano-channel holds the molecule in a relatively straight position until it
passes through the nanopore.” Id. Thus, the Examiner finds the claimed
coating step and the translocating step through a nanopore with a detector
volume to be met by Ling.
The Examiner finds, the addition of a binding protein to a partially
hybridized biomolecule will necessarily increase the diameter of the partially
hybridized biomolecule if even only a single binding protein is added. Ans.
28. The Examiner notes that the limitation reciting “slows a translocation
rate of the partially hybridized biomolecule, and increases a signal-to-noise
ratio of the detected electrical property” are therefore inherent qualities of
increasing the diameter of the partially hybridized biomolecule. Id. The
Examiner therefore finds that, although Ling does not expressly disclose
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these qualities resulting from hybridizing binding proteins to a partially
hybridized biomolecule; the properties are necessarily inherent. Id.
The Examiner acknowledges that Ling does not teach a specific
method to bind the single-stranded binding proteins as disclosed in
paragraph [0050]. Ans. 27. However, the Examiner observes, the claims on
appeal require, in this respect, only “coating at least a portion of the partially
hybridized biomolecule with one or more proteins to increase diameter of
the partially hybridized biomolecule” and, therefore, that features upon
which applicant relies (i.e., how the protein coating is accomplished) are not
recited in the claims. Id. (noting that limitations cannot be imported from
Appellant’s Specification into the claims (citing In re Van Geuns, 988 F.2d
1181, 1184 (Fed. Cir. 1993)).
The Examiner also finds that it was well known in the art at the time
of invention that single-stranded binding proteins such as recA can bind to
single-stranded and double-stranded DNA (“ssDNA” and “dsDNA,”
respectively). Ans. 27 (citing, e.g., as evidence, K. McEntee et al., Binding
of the RecA Protein of Escherichia coli to Single- and Double-stranded
DNA, 256(16) J. Biol. Chem. 8835—44 (1981) (“McEntee”). The Examiner
finds McEntee discloses methods of binding recA to both ssDNA and
dsDNA along with ideal conditions for performing such methods. Id. The
Examiner therefore finds that, at the time of the invention, it was well known
in the art both that binding proteins will bind to ssDNA and dsDNA, and
how to perform those methods. Id.
We agree with the Examiner. Paragraph [0050] of Ling discloses:
It is also possible that when sequencing long lengths of
single-stranded strands of interest or strands of RNA, it may be
difficult to prevent the molecule from self-hybridizing, i.e.
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folding back and hybridizing along their own lengths. This can
be prevented by placing the hybridized biomolecule into a nano­
channel that is coupled to a nanopore such that the nano-channel
holds the molecule in a relatively straight position until it passes
through the nanopore. Alternatively, or in addition, single-
stranded binding proteins can be used to keep the molecule
single-stranded.
(Emphasis added). Ling thus expressly discloses binding single-stranded
binding proteins to a partially hybridized molecule that is also to be
translocated through a nano-channel. Furthermore, we agree with the
Examiner that although the claims do not recite the specific type of binding
proteins to be bound to the partially hybridized molecule nor recite how they
are to be bound, the evidence of McEntee demonstrates that single-stranded
binding proteins, such as those contemplated by Ling, would have been well
known to a person of ordinary skill in the art at the time of invention.
In reply, Appellant contends that McEntee discloses that binding of
recA to DNA produces (1) duplex regions several thousand base pairs in
length and (2) joint molecules or D-loops in which the single-stranded DNA
is base-paired to its complementary strand in the duplex. Reply Br. 4.
Therefore, Appellant asserts, a person of ordinary skill in the art would not
have relied upon recA, as taught by McEntee, to prevent self-annealing of a
long, partially-hybridized biomolecule, as disclosed by Ling. Id.
We are not persuaded by Appellant’s arguments. The Examiner cites
McEntee not for the specific functional properties of recA, but rather as
evidence demonstrating that single- and double-stranded nucleic acid
binding proteins, of the type disclosed by Ling, were well known to a person
of ordinary skill in the art at the time of invention. See Continental Can Co.
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v. Monsanto Co., 948 F.2d 1264, 1269 (Fed. Cir. 1991) (Anticipation
requirement that every element of a claim appears in a single reference
accommodates situations where the common knowledge of “technologists”
is not recorded in a reference, i.e., where technical facts are known to those
in the field of the invention.).
Finally, we agree with the Examiner that binding of proteins to a
partially hybridized biomolecule would necessarily increase the diameter of
the biomolecule and therefore inherently “slow[] a translocation rate of the
partially hybridized biomolecule, and increase [] a signal-to-noise ratio of the
detected electrical property,” as recited in the claims. A reference may
anticipate inherently if a claim limitation that is not expressly disclosed “is
necessarily present, or inherent, in the single anticipating reference.”
Verizon Servs. Corp. v. CoxFibernet Va., Inc., 602 F.3d 1325, 1337 (Fed.
Cir. 2010). In the instant appeal, it is the increased diameter of the partially
hybridized biomolecule at the nanopore that necessarily slows the
translocation rate of the partially hybridized biomolecule, and increases the
signal-to-noise ratio of the detected electrical property, as expressly
acknowledged in the claims (“wherein the increased diameter of the partially
hybridized biomolecule slows a translocation rate of the partially hybridized
biomolecule, and increases a signal-to-noise ratio of the detected electrical
property”).
We consequently affirm the Examiner’s rejection of the claims on this
ground.
II. Rejection of claims 15-17,19, 20, 27-32, 34, 36, 37, 39-53, 56-58,
and 77 as unpatentable under 35 U.S.C. § 103(a)
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A. Claims 15 and 16
Appellant argues claims 15 and 16 separately. App. Br. 8. Appellant
repeats the argument discussed, supra, with respect to the teachings of Ling
and further argues that Rapley fails to cure the alleged deficiencies of Ling.
Id.
Appellant also argues that Rapley describes a Sanger sequencing
method (referred to as chain termination sequencing), which employs a
denaturant (such as dimethyl sulfoxide (DMSO)) and a protein (such as a
single-stranded binding protein or RecA). App. Br. 9. According to
Appellant, Rapley teaches that both the DMSO and the protein are used
during the hybridization process. Id. Appellant asserts claims 15 and 16
explicitly require that the coating be applied to a partially hybridized
biomolecule, (and, in claim 15, to a detectable tag). As such, Appellant
contends, the present claims require that the protein be applied after
hybridization, rather than during that step as disclosed by Rapley. Id. (also
citing Oliver Decl. 17—19).
We are not persuaded. The Examiner cites Rapley solely for the
purpose of teaching the use of recA as a binding protein, as required by
claim 16. See Ans. 30. The exact manner of hybridization taught by Rapley
need not necessarily be combinable with the method taught by Ling. See In
re Sneed, 710 F.2d 1544, 1550 (Fed. Cir. 1983) (“[I]t is not necessary that
the inventions of the references be physically combinable to render obvious
the invention under review.”). We have already explained why we agree
with the Examiner that Fing teaches binding of a binding protein to a
partially hybridized biomolecule and that binding proteins (including recA)
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were well known in the art at the time of invention. We consequently affirm
the Examiner’s rejection of the claims.
B. Claims 17 and 19
Appellant argues claims 17 and 19 separately. App. Br. 8. Appellant
repeats the argument presented supra with respect to the teachings of Ling
and argues that Riccelli fails to cure the alleged deficiencies of Ling. Id.
Appellant also argues that that a skilled artisan would not have been
motivated to combine the teachings of Ling and Riccelli, because Ling and
Riccelli are directed to different problems, and the probes of Riccelli are
incompatible for use with the method of Ling. Id. at 8—9. Appellant
contends that, unlike Ling, Riccelli discloses hairpin capture probes fixed to
a solid support for use in a microtiter-based assay system. Id. at 9 (citing
Riccelli Abstr.). Appellant argues that the use of a hairpin probe fixed to a
solid support would be incompatible with the method of Ling, in which
nucleic acid strands of interest must be in solution so that they can
translocate across a nanopore. Id.
The Examiner responds that Ling and Riccelli are analogous art,
because both Ling and Riccelli employ probes to detect a nucleic acid
sequence. Ans. 30. The Examiner finds Riccelli teaches that probes with a
hairpin structure display generally higher rates of hybridization. Id.
Therefore, the Examiner finds, although Ling and Riccelli disclose nucleic
acid probes employed in different methods, they both disclose binding
probes to nucleic acids and to allow for the detection of nucleic acid
sequences. Id. at 30-31.
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We are not persuaded by Appellant’s arguments. We have already
explained why Appellant’s arguments with respect to Ling are not
persuasive. Furthermore, we agree with the Examiner that Ling, Riccelli,
and Appellant’s claimed invention are analogous art because they are all
directed to solving the same problem, that is, hybridization of a probe to a
biomolecule of interest (albeit, with respect to Riccelli, via a somewhat
different method), and are in the same field of endeavor, viz., detection of
specific nucleic acid sequences via the binding of a probe. See In re Bigio,
381 F.3d 1320, 1325 (Fed. Cir. 2004) (The test for analogous art inquires not
only whether the references address the same problem as the claimed
invention, but also whether they are both from the same field of endeavor as
the claimed invention.).
Furthermore, we agree with the Examiner that Riccelli teaches that
probes with a hairpin structure display generally higher rates of
hybridization. See Riccelli, Abstr. (“Hairpin probes displayed higher rates
of hybridization and larger equilibrium amounts of captured targets than
linear probes. At 25 and 45 °C, rates of hybridization were better than twice
as great for the hairpin compared with the linear capture probes.”). We
consequently agree with the Examiner that a person of ordinary skill would
be motivated to combine the teachings of Ling and Riccelli to obtain
improved rates of hybridization of the probe to the targeted biomolecule.
We therefore affirm the rejection of the claims.
C. Claims 20, 27, and 28
Appellant argues each of these claims separately. App. Br. 10-11.
However, the arguments are not substantively different from those regarding
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the alleged deficiencies of claim 1. In particular, Appellant argues that the
teachings of Bourdoncle, Lennon, and Margulies fail to remedy the alleged
deficiencies of Ling with respect to claims 20, 27, and 28, respectively. Id.
We are not persuaded by Appellant’s arguments. We have already
explained, supra, why we conclude that Appellant’s arguments with respect
to Ling are not persuasive. We consequently affirm the Examiner’s
rejection of the claims.
D. Claims 29. 30-32. 34. 36. 37. 39-44, 51-53. 56. 57. and 77
Appellant argues claim 29 separately and further argues claims 29,
30—32, 34, 36, 37, 39-44, 51—53, 56, 57, and 77 together as a group, but
makes substantially identical arguments with respect to all of the claims.
App. Br. 12—14. Appellant repeats the argument presented supra with
respect to the teachings of Ling and argues further that Drmanac fails to cure
the alleged deficiencies of Ling. Id.
Appellant also argues that that a skilled artisan would have had no
reason to apply a set of overlapping sequencing probes, as taught by
Drmanac, to Ling’s method for using a nanopore in a manner that allows the
detection of the positions of nucleic acid probes hybridized onto a single-
stranded nucleic acid molecule of interest. App. Br. 12; 13—14.
According to Appellant, Drmanac describes a sequencing method in
which “[t]he sequence of a given DNA fragment is read by the hybridization
and assembly of positively hybridizing probes through overlapping
portions.” App. Br. 12; 13 (quoting Drmanac, Abstr.). Appellant asserts
Drmanac’s method uses “simultaneous hybridization of DNA molecules
applied as dots and bound onto a filter, representing single-stranded phage
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vector with the cloned insert, with about 50,000 to 100,000 groups of
probes.” Id. Appellant argues Drmanac teaches the shorter subcloned
sequences are later assembled to provide the longer desired sequence. Id.
Appellant contends Drmanac’s method does not provide positional
information, however, so when an overlapping 10-mer is repeated in a
subclone, assembly of the sequence is interrupted. Id. at 12; 14 (citing
Drmanac col. 2,11. 37—39). Appellant therefore argues that Drmanac teaches
that “fragments of subclone sequence (SF) cannot always be ordered in an
unambiguous linear order without additional information.” Id. (citing
Drmanac, col. 2,11. 42-45). Appellant contrasts these teachings with those
of Ling discussed, supra.
The Examiner responds that Drmanac teaches a method of sequencing
biomolecules wherein probes are hybridized to the biomolecule in an
overlapping fashion. See Final Act. 27, April 10, 2013 (citing Drmanac
Abstr.). The Examiner therefore concludes that, at the time of invention, it
would have been prima facie obvious to one of ordinary skill in the art to
modify the method of hybridization and identification taught by Ling with
the teachings of Drmanac so as to include hybridization probes that overlap.
Id. The Examiner finds that a person of ordinary skill would have realized
that inclusion of the overlapping probes taught by Drmanac would achieve
the predictable result of providing a method that gives a more complete and
accurate picture of the biomolecule of interest, because the overlapping
probes provide more information when a portion of the data is repeated. Id.
We are not persuaded by Appellant’s argument. The exact manner of
hybridization taught by Drmanac need not necessarily be combinable with
the method taught by Ling. See Sneed, 710 F.2d at 1550. Appellant has
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advanced no argument that directly addresses, or overcomes, the Examiner’s
findings and conclusions other than arguing that the general methods of Ling
and Drmanac are not the same. See Ans. 32. The test of obviousness is
“whether the teachings of the prior art, taken as a whole, would have made
obvious the claimed invention.” In re Gorman, 933 F.2d 982, 986 (Fed. Cir.
1991). Appellants’ argument that the general methods of Ling and Drmanac
are not the same is insufficient to overcome the Examiner’s prima facie
conclusion of obviousness, and we affirm the Examiner’s rejection of the
claim.
E. Claims 45 and 46
Concerning claims 45 and 46, Appellant repeats the arguments
presented with respect to claims 17 and 19 discussed supra. We find them
no more persuasive with respect to claims 45 and 46, and we affirm the
Examiner’s rejection of the claims.
F. Claims 47-49
Concerning claims 47-49, Appellant repeats the arguments presented
with respect to claims 15 and 16 discussed supra. Again, we find them no
more persuasive with respect to claims 47-49 and we affirm the Examiner’s
rejection of the claims.
G. Claims 50 and 58
Appellant argues claims 50 and 58 separately. App. Br. 10-11.
Appellant argues that Drmanac and Bourdoncle or Drmanac and Lennon fail
to remedy the alleged deficiencies of Ling with respect to claims 50 and 58,
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respectively. We are not persuaded by Appellant’s arguments. We have
already explained supra why Appellant’s arguments with respect to Ling are
not persuasive. We consequently affirm the Examiner’s rejection of the
claims.
III. Rejection of claims 1—3, 5, 7, 8,10-23, 26-32, 34, 36, 37, 39—53,
56—58, 76, and 77 as unpatentable under the judicially-created doctrine
of nonstatutory obviousness-type double patenting
Issue
Appellant argues the Examiner erred because the claims of Oliver
’879 and Ling ’980 fail to teach or suggest that the binding protein coating
be applied to a partially hybridized biomolecule. App. Br. 20.
Analysis
Appellant points out that the Examiner acknowledges that the claims
of Oliver ’879 and Ling ’980 “do not include coating the hybridized
biopolymer with a binding protein.” App. Br. 20 (quoting Non-Final Act.
88, 116, November 7, 2012). Appellant contends the claims of Oliver
’879 and Ling ’980 also fail to teach or suggest that the coating be applied to
a partially hybridized biomolecule. Id.
Claims 2, 3, 5, 7, 8, 10-15, 18, 22, 23, 31, 32, 34, 36, 37, 39, 45, 48,
52, 53, and 57 stand rejected over either Oliver ’879 or Ling ’980, in
combination with Rapley and Ling. Claims 17, 19, 47, and 49 stand rejected
over the combination of either Oliver ’879 or Ling ’980, Rapley, Ling, and
Riccelli. Claims 20 and 50 stand rejected over the combination of either
Oliver ’879 or Ling ’980, Rapley, Ling, and Bourdoncle. Claims 27 and 58
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stand rejected over the combination of either Oliver ’879 or Ling ’980,
Rapley, and Lennon. Claim 28 stands rejected over the combination of
either Oliver ’879 or Ling ’980, Rapley, and Margulies.
Appellant repeats the arguments we discussed as being not persuasive
with respect to claims 15 and 16 supra. App. Br. 20. Appellant also argues
that a person of ordinary skill in the art would have no reason to modify the
invention defined by each of the claims of Oliver ’879 or Ling ’980 to coat a
partially hybridized biomolecule, or have any reasonable expectation that it
would be possible to do so. Id. at 21. Furthermore, argues Appellant, based
on the claims of Oliver ’879 and Ling ’980, a person of ordinary skill in the
art would have had no reason to believe that it would be possible to coat a
partially hybridized biomolecule to increase a diameter of the partially
hybridized biomolecule, wherein the increased diameter of the partially
hybridized biomolecule slows a translocation rate of the partially hybridized
biomolecule, and increases a signal-to-noise ratio of the detected electrical
property. Id.
We are not persuaded. For those claims (2, 3, 5, 7, 8, 10—15, 17—20,
22, 23, 31, 32, 34, 36, 37, 39, 45, 47—50, 52, 53, and 57) rejected over the
combination of at least either Oliver ’879 or Ling ’980 and Ling, we have
explained our reasoning supra, with respect to claims 15 and 16, as to why
we agree with the Examiner’s finding that Ling teaches that a binding
protein coating can be applied to a partially hybridized biomolecule.
Moreover, Appellant adduces no evidence to support their arguments that a
person of ordinary skill in the art would have no reason modify the claims of
Oliver ’879 or Ling ’980 or reason to believe that it would not be possible to
coat a partially hybridized biomolecule to increase a diameter of the partially
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hybridized biomolecule. As we have explained, binding a protein to a
partially-hybridized biomolecule necessarily increases the diameter of the
molecule and also slows the translocation rate of the partially hybridized
biomolecule and increases a signal-to-noise ratio of the detected electrical
property. See Ans. 28. Consequently, we agree that these properties are
inherent in the combined cited prior art references. Moreover, in the
absence of any citation to evidence of record in support of their contentions,
Appellant’s contentions are mere attorney argument to which we accord
little probative value. See In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir.
1984) (Arguments and conclusions unsupported by factual evidence carry no
evidentiary weight). We consequently affirm the Examiner’s rejection of
these claims.
With respect to those claims (1, 16, 21, 26—29, 30, 46, 51, 56, and 58)
rejected over the combination of at least either Oliver ’879 or Ling ’980 and
Rapley, but not Ling, the Examiner finds Rapley teaches a method of
coating a biomolecule with DNA binding protein to enhance sequencing
methods. See Non-Final Rej. 35—36, 38—39, November, 11, 2012 (citing
Rapley 295). Specifically, the Examiner finds Rapley teaches a method of
using a single-stranded binding protein or recA protein to increase the
resolution of sequencing. Id. Furthermore, Rapley suggests that the
inclusion of a DNA-binding protein prevents or reduces formation of any
DNA secondary structures. Id. (citing Rapley at 298). Therefore, the
Examiner concludes, at the time of the invention it would have been prima
facie obvious to one of ordinary skill in the art to try a DNA-binding protein
that prevents or reduces the formation of secondary structures in a method
that detects electrical
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We are not persuaded by the Examiner’s conclusion with respect to
these claims. Specifically, the Examiner relies upon Ling as teaching
“coating the partially hybridized biomolecule results in maintaining the
conformation of the biomolecule so that it can remain single-stranded while
passing through the nano-channel” and relies upon Rapley for teaching “the
use of a specific binding protein and for teaching that it was known in the art
that RecA (a single-stranded binding protein) binds to nucleic acids.” See
Ans. 34. However, the Examiner’s stated obviousness-type double
patenting rejection of these claims does not include citation to or reliance on
Ling as a reference. Ans. 22. Because the Examiner does not employ Ling
as a reference in the combination to reject these claims or explain how the
cited references of the rejection teach the claimed “coating at least a portion
of the partially hybridized biomolecule” limitation, we cannot see how the
Examiner finds the cited combination of references render claims 1, 16,21,
26—29, 30, 46, 51, 56, and 58 unpatentable under the judicially-created
doctrine of nonstatutory obviousness-type double patenting . See Ans. 22,
24. Consequently we reverse the Examiner’s rejection of claims 1, 16, 21,
26—29, 30, 46, 51, 56, and 58 on this ground.
DECISION
The Examiner’s rejection of claims 1—3, 5, 7, 8, 10-14, 18, 21—23, 26,
28, and 76 as unpatentable under 35 U.S.C. § 102(b) is affirmed.
The Examiner’s rejection of claims 15—17, 19, 20, 27—32, 34, 36, 37,
39-53, 56—58, and 77 as unpatentable under 35 U.S.C. § 103(a) is affirmed.
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The Examiner’s rejection of claims 2, 3, 5, 7, 8, 10-15, 17—20, 22, 23,
31, 32, 34, 36, 37, 39, 45, 47—50, 52, 53, and 57as unpatentable under the
nonstatutory doctrine of obviousness-type double patenting is affirmed.
The Examiner’s rejection of claims 1, 16, 21, 26—29, 30, 46, 51, 56,
and 58 as unpatentable under the nonstatutory doctrine of obviousness-type
double patenting is reversed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(l)(iv).
AFFIRMED
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