Sampson, Jeffrey R. et al.

Patent Trials and Appeals Board

Apr 27, 2020

14486346 - (D) (P.T.A.B. Apr. 27, 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.
14/486,346 09/15/2014 Jeffrey R. Sampson 20140090-02 6386
22878 7590 04/27/2020
Agilent Technologies, Inc.
Global IP Operations
5301 Stevens Creek Blvd
Santa Clara, CA 95051
EXAMINER
KAUP, SAHANA S
ART UNIT PAPER NUMBER
1639
NOTIFICATION DATE DELIVERY MODE
04/27/2020 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):
Agilentdocketing@cpaglobal.com
ipopsadmin@agilent.foundationip.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JEFFREY R. SAMPSON and NICHOLAS M. SAMPAS
____________

Appeal 2019-003853
Application 14/486,346
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and
JOHN G. NEW, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1, 2 under 35 U.S.C. § 134(a) involving claims to an
apparatus for high-throughput gene assembly in droplets. The Examiner
rejected the claims as anticipated or 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 Agilent
Technologies, Inc. (see Appeal Br. 2).
2 We have considered and herein refer to the Specification of Sept. 15, 2014
(“Spec.”); Final Office Action of May 17, 2018 (“Final Act.”); Appeal Brief
of Nov. 13, 2018 (“Appeal Br.”); Examiner’s Answer of Feb. 14, 2019
(“Ans.”); and Reply Brief of Apr. 15, 2019 (“Reply Br.”).
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Statement of the Case
Background
“High-throughput synthesis and assembly of DNA constructs is an
integral part of synthetic biology” (Spec. 1:10–11). “Many high-throughput
methods are performed in micro-titer plates using automated robotic
systems. While these systems reduce the cost of labor, the reagent costs,
including the starting oligonucleotides, are still considerable given the
number and the volume of the various reactions required for the assembly”
(id. at 1:18–21).
The Specification discloses a microarray assembly, exposed to an
aqueous “solution comprising a buffer, Type II restriction endonuclease,
DNA ligase, and ATP,” as an alternative to a micro-titer plate (see id. at
19:10–18). “Because of the hydrophobic-hydrophilic boundary between the
microarray features and the interstitial substrate, the aqueous solution will
form small droplets over the hydrophilic features containing the DNA
thereby isolating each assembly reaction defined by the microarray feature”
(id. at 19:14–18).
The Claims
Claims 17–24 and 31–36 are on appeal.3 Independent claim 17 is
representative and reads as follows:
17. An apparatus comprising:

(a) a planar support comprising a plurality of
oligonucleotide features, wherein each of said features
comprises a different surface-tethered oligonucleotide,

3 Claims 1–16 and 25–30 are cancelled (Appeal Br. 10–11).
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(b) a plurality of spatially distinct droplets on a surface of
the planar support, and

(c) an immiscible liquid covering the droplets, wherein:

the apparatus comprises a plurality of reaction
chambers defined by the droplets,

the boundary of each droplet is defined by the
boundary of an oligonucleotide feature, and

each reaction chamber comprises a plurality of
different oligonucleotides that are bound to the planar support
via a surface-tethered oligonucleotide.

(Appeal Br. 10).

The Issues
The Examiner rejected claims 17–22, 24, and 31–36 under 35 U.S.C.
§ 102(a)(1) as anticipated by Jacobson (Ans. 3–12).4
The Examiner rejected claim 23 under 35 U.S.C. § 103 as obvious
over Jacobson and Pollack (Ans. 12–14).5
Because both of these rejections rely on Jacobson, we will consider
these rejections together.
The Examiner finds Jacobson teaches an addressable array including
discrete features having a plurality of surface-bound oligonucleotides (Ans.
4). The Examiner finds Jacobson discloses hydrating the discrete features to
form droplet reaction chambers (id. at 4–5). The Examiner finds Jacobson
discloses the droplets may contain reagents to facilitate amplifying and

4 Jacobson et al., US 2012/0220497 A1, published Aug. 30, 2012.
5 Pollack et al., US 2010/0291578 A1, published Nov. 18, 2010.
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ligating nucleic acids within the droplets (id. at 5–6). The Examiner also
finds Jacobson teaches the array of droplets may be overlaid with an
immiscible liquid, including an alkane hydrocarbon (id. at 5). The Examiner
finds Pollack teaches analyzing target nucleic acids in aqueous droplets
surrounded by an immiscible fluid containing an alkane (id. at 14).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s findings that the prior art renders the claims
anticipated and/or obvious?
Findings of Fact (“FF”)
1. Jacobson discloses “devices for conducting sub-microvolume
specified reactions within a droplet” (Jacobson ¶ 11).
2. Jacobson discloses devices with a support or substrate that may
include an array, which refers to:
an arrangement of discrete features for storing, routing,
amplifying and releasing oligonucleotides or complementary
oligonucleotides for further reactions. In a preferred
embodiment, the support or array is addressable: the support
includes two or more discrete addressable features at a particular
predetermined location (i.e., an “address”) on the support.
Therefore, each oligonucleotide molecule of the array is
localized to a known and defined location on the support. The
sequence of each oligonucleotide can be determined from its
position on the support.
(Jacobson ¶ 62).
3. Jacobson discloses a substrate with “a plurality of surface-
bound single-stranded oligonucleotides at discrete features . . . each
oligonucleotide has a predefined sequence different from the predefined
sequence of the oligonucleotide bound to a different feature” (Jacobson
¶ 11).
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4. Jacobson discloses “a set of predefined features may be
selectively hydrated, thereby providing hydrated nucleotides” (Jacobson
¶ 11).
5. Jacobson discloses “the hydrated oligonucleotides are exposed
to further processing within a droplet volume. In some embodiments, the
oligonucleotides are subjected to amplification. As each feature can
selectively be hydrated, amplification will take place only at specific
features comprising a droplet. In some embodiments, the droplet acts as a
virtual reaction chamber” (Jacobson ¶ 11).
6. Jacobson discloses “[i]n some embodiments, at least one
plurality of oligonucleotides is synthesized in a chain extension reaction on a
first feature of the support by template-dependent synthesis” (Jacobson
¶ 13).
7. Jacobson discloses “the droplets can be overlaid with a non-
miscible liquid thereby preventing water evaporation of the solution. . . . In
some exemplary embodiments, the non-miscible liquid is a solvent or
mineral oil” (Jacobson ¶ 11).
8. Jacobson discloses the non-miscible fluid may be applied
uniformly over the surface of the array thereby trapping the droplets. “The
non-miscible solution includes, but is not limited to, mineral oil, vegetable
oil, silicone oil, paraffin oil, natural or synthetic wax, organic solvent that is
immiscible in water or any combination thereof. . . . Paraffin is an alkane
hydrocarbon with the general formula CnH2n+2” (Jacobson ¶ 86).
9. Jacobson discloses “addressable supports or arrays enable the
direct control of individual isolated volumes such as droplets. The size of
the defined feature can be chosen to allow formation of a microvolume
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droplet on the feature, each droplet being kept separate from each other”
(Jacobson ¶ 62).
10. Jacobson discloses “features are typically . . . separated by
interfeature spaces to ensure that droplets between two adjacent features do
not merge. Interfeatures will typically not carry any oligonucleotide on their
surface and will correspond to inert space. . . . features and interfeatures may
differ in their hydrophilicity or hydrophobicity properties” (Jacobson ¶ 62).
11. Jacobson discloses:
[T]he reagents in the reaction volumes promote oligonucleotide
or polynucleotide assembly. . . . [T]he reaction volumes may
contain two or more populations of single-stranded
oligonucleotides having predefined sequences in solution. The
populations of oligonucleotides can hybridize to a single-
stranded oligonucleotide attached to the wetted surface thereby
forming double-stranded hybrids or duplexes attached to the
surface. . . . [T]he double-stranded hybrids contain breaks and
gaps in the phosphodiester backbone, formed at the junctions of
different oligonucleotide populations. . . . [A] polymerase and
dNTPs and other necessary components are added to fill the gaps
in the backbone. . . . [A] ligase and other necessary components
are added to mend breaks in the backbone.
(Jacobson ¶ 98).
12. Pollack discloses a droplet microactuator for droplet-based
nucleic acid sequencing (Pollack ¶ 12).
13. Pollack discloses the droplet microactuator includes a liquid-
liquid interface where “chemistry is performed in the primary (droplet)
phase, and the secondary phase serves as a filler fluid separating the droplets
from each other. . . . Where the secondary phase includes a liquid, the liquid
is sufficiently immiscible with the primary liquid phase to permit the droplet
microactuator to conduct one of more droplet operations” (Pollack ¶ 395).
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14. Pollack discloses the “filler fluid may be any fluid in which the
droplet microactuator can, under the right conditions, conduct one or more
droplet operations. . . . Examples of suitable liquid filler fluids include, . . .
hydrocarbons, including for example, alkanes, such as decane, undecane,
dodecane, tridecane, tetradecane, pentadecane, hexadecane; [and] aliphatic
and aromatic alkanes” (Pollack ¶ 399).

Principles of Law
“[A] reference need not always include an express discussion of the
actual combination to anticipate. Instead, a reference may still anticipate if
that reference teaches that the disclosed components or functionalities may
be combined and one of skill in the art would be able to implement the
combination.” Blue Calypso, LLC v. Groupon, Inc., 815 F.3d 1331, 1344
(Fed. Cir. 2016) (internal citations omitted).

Analysis
We adopt the Examiner’s findings of fact and conclusions of law
(Ans. 3–14; FF 1–14) and agree that the claims are anticipated by Jacobson
or would have been obvious over the combination of Jacobson and Pollack.
We address Appellant’s arguments below.
Appellant contends “Jacobson does not disclose the same apparatus
which is being claimed” (Appeal Br. 4). Appellant argues that Jacobson
does not disclose all elements of the claim arranged in the same way as the
claim (id. (citing Net MoneyIN, Inc. v. Verisign, Inc., 545 F.3d 1359, 1369
(Fed. Cir. 2008)).
Appellant contends “Jacobson’s apparatus is fundamentally different”
from the claimed invention because “droplets are added to a substrate so that
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each droplet covers one or more features. The boundary of each droplet is
not defined by the boundary of a feature” (id. at 5). Appellant cites Figure
4A of Jacobson for illustrating an embodiment of moving droplets to a
selected location of the substrate thereby merging droplets together (id. at 6
(citing Jacobson ¶¶ 123, 124)). Appellant argues “Jacobson’s substrate
permits the droplets to move along the surface,” and, therefore, cannot
include a boundary of a nucleotide feature that prevents droplet movement
(id. at 6–7 (citing Jacobson ¶¶ 79, 121)). Appellant also cites Figure 12 of
Jacobson to argue “that Jacobson does not contemplate an apparatus having
reaction chambers which are defined by spatially distinct droplets, and an
immiscible liquid covering the droplets” (Reply Br. 6).
We find this argument unpersuasive. We recognize Appellant’s
contention that Jacobson discloses embodiments in which the droplet
reaction chambers are moved to merge with other droplets. However, as
noted by the Examiner, Appellant highlights embodiments that were not
relied on in the Examiner’s rejection (see Ans. 15). In the embodiments
cited by the Examiner, Jacobson discloses an array with “discrete features”
that are selectively hydrated so that amplification will take place only at
“specific features comprising a droplet” (FF 3–5). Jacobson further
discloses features sized so that the droplets are kept separate from each
other, including “interfeature spaces to ensure that droplets between two
adjacent features do not merge” (FF 9–10). Contrary to Appellant’s
argument, Jacobson expressly discloses the claim 1 elements of “spatially
distinct droplets” wherein “the boundary of each drop is defined by the
boundary of an oligonucleotide feature” when teaching oligonucleotide
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arrays (FF 2) that enable “individual isolated volumes such as droplets” with
“each droplet being kept separate from each other” (FF 9)
Moreover, Jacobson teaches that the disclosed components and
functionalities may be combined, and one of skill in the art would be able to
implement the combination. See Blue Calypso, 815 F.3d at 1344.
Specifically, Jacobson states “[v]arious aspects of the present invention may
be used alone, in combination, or in a variety of arrangements not
specifically discussed in the embodiments described in the foregoing . . .
aspects described in one embodiment may be combined in any manner with
aspects described in other embodiments” (Jacobson ¶ 150). Accordingly,
“[t]his case is distinguishable from Net MoneyIN because, in contrast to the
reference in that case, [Jacobson] explicitly contemplates the combination of
the disclosed functionalities.” 815 F.3d at 1343.
Appellant further contends that Jacobson’s paragraph 0011 “does not
disclose that ‘each of said features comprising a different surface-tethered
oligonucleotide’” (Appeal Br. 7).
We find this argument unpersuasive. Jacobson’s paragraph 0011
discloses “each oligonucleotide has a predefined sequence different from the
predefined sequence of the oligonucleotide bound to a different feature” (FF
3). Accordingly, each feature includes an oligonucleotide with a different
sequence, i.e., a different surface-tethered oligonucleotide.
Appellant also contends Jacobson does not disclose an “immiscible
liquid covering the droplets. Jacobson teaches that its droplets must be
free to merge for subsequent reactions to be conducted, suggesting that a
non-miscible is not laid over those droplets. Instead Jacobson teaches that
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the droplets are overlaid with a non-miscible liquid to prevent water
evaporation” (Reply Br. 6).
We do not find this argument persuasive. Appellant argues that the
intended use of a non-miscible liquid in the claimed apparatus is distinct
from the intended use and purpose of the non-miscible liquid in Jacobson.
However, “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). Jacobson expressly teaches the identical structure with the identical
components, i.e., an immiscible alkane covering aqueous droplets (FF 7–8).
Appellant’s alleged discovery of a previously unappreciated benefit of
covering the droplets with an immiscible liquid other than preventing
evaporation does not render the old composition patentably new to the
discoverer. See Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347 (Fed.
Cir. 1999). Accordingly, we agree with the Examiner that Jacobson
anticipates claim 17. Because Appellant does not separately argue the
dependent claims, we sustain the Examiner’s anticipation rejection of claims
17–22, 24, and 31–36.
Appellant does not provide separate arguments against the
combination of Jacobson and Pollack, arguing that “Pollack fails to provide
what Jacobson lacks” (Appeal Br. 8). Because, we agree with the Examiner
that Jacobson anticipates claims 17–22, 24, and 31–36, we also agree that
claim 23 would have been obvious over Jacobson and Pollack for the
reasons given by the Examiner.

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Conclusion of Law
A preponderance of the evidence of record support the Examiner’s
conclusion that claims 17–24 and 31–36 are unpatentable over Jacobson or
the combination of Jacobson and Pollack.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
17–22, 24,
31–36
102(a)(1) Jacobson 17–22, 24,
31–36

23 103 Jacobson, Pollack 23
Overall
Outcome
17–24, 31–36

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