HandyLab, Inc.

Patent Trials and Appeals Board

Jul 14, 2020

IPR2019-00488 (P.T.A.B. Jul. 14, 2020)

Trials@uspto.gov Paper 52
571-272-7822 Date: July 14, 2020

1030UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

QIAGEN NORTH AMERICAN HOLDINGS, INC.,
Petitioner,
v.
HANDYLAB, INC.,
Patent Owner.

IPR2019-004881
Patent 7,998,708 B2

Before JO-ANNE M. KOKOSKI, CHRISTOPHER G. PAULRAJ, and
JULIA HEANEY, Administrative Patent Judges.
KOKOSKI, Administrative Patent Judge.

JUDGMENT
Final Written Decision
Determining No Challenged Claims Unpatentable
35 U.S.C. § 318(a)
Dismissing Patent Owner’s Motion to Exclude
37 C.F.R. § 42.64(c)

1 IPR2019-01493 has been joined with this proceeding.
IPR2019-00488
Patent 7,998,708 B2
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I. INTRODUCTION
We have jurisdiction to conduct this inter partes review under
35 U.S.C. § 6, and this Final Written Decision is issued pursuant to
35 U.S.C. § 318(a). For the reasons that follow, we determine that QIAGEN
North American Holdings, Inc. (“Petitioner”) has not shown by a
preponderance of the evidence that claims 1–33 of U.S. Patent
No. 7,998,708 B2 (“the ’708 patent,” Ex. 1002) are unpatentable.
A. Procedural History
Petitioner filed a Petition (“Pet.”) to institute an inter partes review of
claims 1–33 of the ’708 patent. Paper 1. HandyLab, Inc. (“Patent Owner”)
filed a Preliminary Response. Paper 5. Pursuant to 35 U.S.C. § 314(a), we
instituted an inter partes review of claims 1–33 on all grounds advanced in
the Petition. Paper 8 (“Dec. on Inst.” or “Institution Decision”), 7, 20.
After institution of trial, Patent Owner filed a Patent Owner Response
(“PO Resp.,” Paper 24), Petitioner filed a Reply (“Pet. Reply,” Paper 31),
and Patent Owner filed a Sur-Reply (“PO Sur-Reply,” Paper 43). Patent
Owner filed a Motion to Exclude Exhibits 1030 and 1032. Paper 44.
Petitioner filed an Opposition (Paper 46), and Patent Owner filed a Reply
(Paper 47).
Patent Owner also filed a Motion to Strike certain portions of
Petitioner’s Reply. Paper 38. Petitioner filed an Opposition. Paper 39. We
granted Patent Owner’s Motion to Strike in part, striking the arguments in
Section II.B.ii from Petitioner’s Reply. Paper 42, 6–8, 13. We did not
consider those arguments in the course of preparing this Final Written
Decision.
An oral hearing was held on April 21, 2020, and a transcript is
included in the record. Paper 51.
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B. Related Proceedings
Petitioner indicates that there are no related matters. Pet. 1. Patent
Owner identifies QIAGEN North American Holdings, Inc. v. HandyLab,
Inc., IPR2019-00490, concerning U.S. Patent No. 8,323,900 (which is a
continuation of the ’708 patent) as a related matter. Paper 3, 1.
C. The ’708 Patent
The ’708 patent, titled “Microfluidic System for Amplifying and
Detecting Polynucleotides in Parallel,” is directed to “a system and related
methods for amplifying, and carrying out diagnostic analyses on,
polynucleotides (e.g., a DNA, RNA, mRNA, or rRNA) from biological
samples.” Ex. 1002, code (54), 3:64–67. The claimed system “includes a
disposable microfluidic cartridge containing multiple sample lanes in
parallel and a reusable instrument platform (a PCR analyzer apparatus) that
can actuate on-cartridge operations” and “can detect (e.g., by fluorescence
detection) and analyze the products of the PCR amplification in each of the
lanes separately, in all simultaneously, or in groups simultaneously.” Id.
at 4:7–13. The system optionally “can display the results on a graphical user
interface.” Id. at 4:13–15.
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The ’708 patent’s Figure 1 is reproduced below.

Figure 1 is “a perspective view of an exemplary apparatus 100” described by
the ’708 patent. Id. at 4:33–34. Apparatus 100 includes read head 300 “that
contains detection apparatus for reading signals from cartridge 200.” Id.
at 4:35–37. Apparatus 100 “is able to carry out real-time PCR on a number
of samples in cartridge 200 simultaneously.” Id. at 4:38–40. Cartridge 200
contains multiple sample lanes, and the ’708 patent explains that
“[p]referably the number of samples is 12 samples, as illustrated with
exemplary cartridge 200,” although other numbers of samples can be
present. Id. at 4:34–35, 4:40–43.
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The ’708 patent’s Figure 3 is reproduced below.

Figure 3 is a “schematic overview of a system 981 for carrying out the
analyses described” in the ’708 patent. Id. at 4:54–55. Processor 980 “is
configured to control functions of various components of the system,” such
as receiving data about a sample to be analyzed from sample reader 990,
“which may be a barcode reader, an optical character reader, or an RFID
scanner (radio frequency tag reader).” Id. at 4:59–65. Processor 980 can
also be configured to accept user instructions from input 984, to
communicate with optional display 982, to transmit analysis results to an
output device, and to control various aspects of sample diagnostics. Id. at
4:67–5:19, 6:1–3.
System 981 “is configured to operate in conjunction with a
complementary cartridge 994, such as a microfluidic cartridge.” Id. at 6:3–
5. Cartridge 994 is itself configured “to receive one or more samples 996
containing one or more polynucleotides in a form suitable for amplification
and diagnostic analysis,” and “has dedicated regions within which
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amplification, such as by PCR, of the polynucleotides is carried out when
the cartridge is situated in the apparatus.” Id. at 6:5–11. Receiving bay 992
is “configured to selectively receive the cartridge,” and “is in
communication with a heater unit 998 that itself is controlled by processor
980 in such a way that specific regions of the cartridge, such as individual
sample lanes, are independently and selectively heated at specific times
during amplification and analysis.” Id. at 6:12–13, 6:33–37.
Processor 980 “is also configured to receive signals from and control
a detector 999 configured to detect a polynucleotide in a sample in one or
more individual sample lanes, separately or simultaneously.” Id. at 7:31–34.
Detector 999 can be “an optical detector that includes a light source that
selectively emits light in an absorption band of a fluorescent dye, and a light
detector that selectively detects light in an emission band of the fluorescent
dye, wherein the fluorescent dye corresponds to a fluorescent polynucleotide
probe.” Id. at 7:41–46.
The ’708 patent explains that system 981 “is configured so that a
cartridge with capacity to receive multiple samples can be acted upon by the
system to analyze multiple samples—or subsets thereof—simultaneously, or
to analyze the samples consecutively.” Id. at 7:64–67. According to
the ’708 patent, this system is self-contained and therefore “is advantageous
at least because it does not require locations within the system suitably
configured for storage of reagents,” and does not “require inlet or outlet
ports that are configured to receive reagents from, e.g., externally stored
containers such as bottles, canisters, or reservoirs.” Id. at 8:4–11.
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Claims 1 and 33 are the only independent claims, and are reproduced
below.
1. An apparatus, comprising:
a multi-lane microfluidic cartridge, each lane comprising a
PCR reaction zone;
a receiving bay configured to receive the microfluidic
cartridge;
each PCR reaction zone comprising a separately controllable
heat source thermally coupled thereto, wherein the
heat source maintains a substantially uniform
temperature throughout the PCR reaction zone and
thermal cycles the PCR reaction zone to carry out PCR
on a polynucleotide-containing sample in the PCR
reaction zone;
a detector configured to detect the presence of an
amplification product in the respective PCR reaction
zone; and
a processor coupled to the detector and the heat source,
configured to control heating of one or more PCR
reaction zones by the heat sources.
Ex. 1002, 46:5–22.
33. A method of carrying out PCR on a plurality of
samples, the method comprising:
introducing the plurality of samples into a multi-lane
microfluidic cartridge, wherein each lane comprises a
PCR reaction zone configure to permit thermal cycling
of a sample independently of the other samples;
moving the plurality of samples into the respective plurality
of PCR reaction zones; and
amplifying polynucleotides contained with the plurality of
samples in the PCR reaction zones while thermal
cycling the PCR reaction zones, at least one PCR
reaction zone separately thermally controllable from
another PCR reaction zone.
Id. at 48:28–40.
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D. Prior Art and Asserted Grounds
Petitioner asserts that claims 1–33 of the ’708 patent are unpatentable
on the following grounds:
References 35 U.S.C. § Claim(s) Challenged
Zou I2, McNeely3 or
Pease4
103 1–6, 9, 10, 18–20, 23–25, 28,
30–33
Zou I, McNeely or
Pease, Hsieh5
103 7, 8
Zou I, McNeely or
Pease, Zou II6
103 11–17
Zou I, McNeely 103 21, 22
Zou I, McNeely or
Pease, Duong7
103 26, 27
Zou I, McNeely or
Pease, Chow8
103 29

Petitioner relies on the Declaration of Bruce K. Gale, Ph.D. (“First Gale
Declaration,” Ex. 1001) and the Second Declaration of Bruce K. Gale, Ph.D.
(“Second Gale Declaration,” Ex. 1026) (collectively, “Gale Declarations”).
Patent Owner relies on the Declaration of Allen Northrup, Ph.D. (“Northrup
Declaration,” Ex. 2036).

2 U.S. Patent No. 6,509,186 B1, issued Jan. 21, 2003 (Ex. 1008).
3 U.S. Patent App. Pub. No. US 2004/0037739 A1, published Feb. 26, 2004
(Ex. 1009).
4 U.S. Patent App. Pub. No. US 2004/0151629 A1, published Aug. 5, 2004
(Ex. 1010).
5 U.S. Patent No. 7,122,799 B2, issued Oct. 17, 2006 (Ex. 1012).
6 U.S. Patent No. 6,762,049 B2, issued July 13, 2004 (Ex. 1011).
7 WO 01/54813 A2, published Aug. 2, 2001 (Ex. 1013).
8 U.S. Patent No. 5,955,028, issued Sept. 21, 1999 (Ex. 1014).
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II. ANALYSIS
A. Level of Ordinary Skill in the Art
Petitioner contends that a person having ordinary skill in the art
(“POSA”) would have had “a degree in Mechanical Engineering,
Bioengineering, or a similar field, and three years of experience with
microfluidic devices or systems relating to biochemical reactions/analysis,
such as PCR,” or “an advanced degree in a similar field with at least one
year of related experience.” Pet. 5. Patent Owner argues that Petitioner’s
proposed definition “is not narrowly drawn to experience in ‘microfluidic
systems that carry out PCR,’” and contends that a POSA “would have had a
degree in Mechanical Engineering, Bioengineering, or a similar field, and
three years of experience with microfluidic devices that carry out PCR, or
would have an advanced degree in a similar field with at least one year of
related experience.” PO Resp. 9 (citing Ex. 2036 ¶¶ 25–26). Patent
Owner’s declarant Dr. Northrup states that, although he disagrees with
Petitioner’s proposed definition of a POSA, his “opinions would not change
under” that definition. Ex. 2036 ¶ 28.
We agree with the parties that a POSA would have had an engineering
background and experience with microfluidic devices, which is consistent
with the level of ordinary skill in the art at the time of the invention as
reflected in the prior art in this proceeding. See Okajima v. Bourdeau, 261
F.3d 1350, 1355 (Fed. Cir. 2001) (explaining that specific findings regarding
ordinary skill level are not required “where the prior art itself reflects an
appropriate level and a need for testimony is not shown” (quoting Litton
Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d 158, 163 (Fed. Cir.
1985))). Our determination regarding the patentability of the challenged
claims does not turn on the differences between Petitioner’s and Patent
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Owner’s definitions, and we note that our conclusions would be the same
under either assessment.
B. Claim Construction
For petitions such as this one, filed after November 13, 2018, we
apply the same claim construction standard “used in the federal courts, in
other words, the claim construction standard that would be used to construe
the claim in a civil action under 35 U.S.C. [§] 282(b), which is articulated
in” Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) (en banc).
83 Fed. Reg. 51,340, 51,343 (Oct. 11, 2018). Under the Phillips standard,
the “words of a claim ‘are generally given their ordinary and customary
meaning,’” which is “the meaning that the term would have to a person of
ordinary skill in the art in question at the time of the invention, i.e., as of the
effective filing date of the patent application.” Phillips, 415 F.3d at 1312–
13. Only those terms in controversy need to be construed, and only to the
extent necessary to resolve the controversy. See Nidec Motor Corp. v.
Zhongshan Broad Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017)
(“[W]e need only construe terms ‘that are in controversy, and only to the
extent necessary to resolve the controversy.’”) (quoting Vivid Techs., Inc. v.
Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)).
In its Petition, Petitioner proposes a construction for the term “contact
heat source” in dependent claims 10–17. Pet. 4–5. Patent Owner proposes a
construction for the term “multi-lane microfluidic cartridge” in independent
claims 1 and 33. PO Resp. 11–15. For purposes of the Institution Decision,
we determined that no term required explicit construction. Dec. on Inst. 9.
Based on our review of the complete record and the claim construction
arguments raised by the parties, for purposes of this Final Written Decision
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we determine it is necessary to expressly construe “multi-lane microfluidic
cartridge.”
Patent Owner proposes that we construe “multi-lane microfluidic
cartridge” to mean “a microfluidic cartridge comprising a plurality of sample
lanes with separate sample inlets and microfluidic networks.” PO Resp. 11
(citing Ex. 2036 ¶¶ 51–58). In support of its construction, Patent Owner
contends that “the specification makes clear that the claimed ‘multi-lane
microfluidic cartridge’ has a plurality of samples lanes,” and “defines that, in
the context of the ’708 patented invention, a ‘sample lane’ or ‘lane’ has
certain specific characteristics,” such as a sample inlet and certain
microfluidic components. Id. at 11–12 (citing Ex. 1002, 12:66–13:15,
13:24–36; Ex. 2036 ¶¶ 53–54). Patent Owner further contends that the
specification states that the sample inlet and the microfluidic network are
separate from one another and unique to each lane. Id. at 12 (citing
Ex. 1002, 12:64–65, 13:34–36, 14:64–67). According to Patent Owner, the
disclosures in the specification “confirm the basic design of the ’708
patented invention: the disclosed cartridge has separate sample lanes that
can process multiple different samples independently.” Id. at 13 (citing
Ex. 1002, 13:21–23, 13:38–42).
Petitioner argues in its Reply that the claims “do not recite a ‘sample
inlet’ associated with each lane, much less a ‘separate sample inlet,’” and,
therefore, “‘[m]ulti-lane microfluidic cartridge’ should be given its ordinary
meaning,” which is “a cartridge with multiple microfluidic channels.”
Pet. Reply 2 (citing Ex. 1026 ¶¶ 10, 12–13). Petitioner also argues that
Patent Owner’s construction improperly relies on the specification’s use of
the term “sample lane” to import a separate sample inlet into the claims,
because “the claims say ‘lane,’ not ‘sample lane,’” and also “say what each
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‘lane’ must include: ‘each lane comprising a PCR reaction zone.’” Id. at 2–3
(citing Ex. 1002, claims 1 and 33; Ex. 1026 ¶¶ 13–14). Petitioner further
contends that the “claims should not be limited to the embodiments in the
specification,” and, “[h]ere[,] the specification confirms that the disclosed
cartridges are only ‘exemplary’ and that the purported invention includes
‘[o]ther configurations of inlets though not explicitly described or
depicted.’” Id. at 3 (citing Ex. 1002, 2:55–56, 13:5–6, 17:15–20, 17:65–67).
Petitioner also contends that Patent Owner added the term “multi-lane” to
the claims during prosecution to distinguish over a prior art reference, and in
doing so “expressly equat[ed] ‘lane’ to ‘flow channel,’” which is “more
evidence that the term ‘lane’ is used according to its ordinary meaning.” Id.
at 3–4 (citing Ex. 1005, 7–8; Ex. 1026 ¶ 21).
We have considered, but are not persuaded by, Petitioner’s claim
arguments regarding the construction of the term “multi-lane microfluidic
cartridge.” The claim language requires that “each lane” of the multi-lane
microfluidic cartridge comprises a separately controllable PCR reaction
zone. While this much is apparent from the plain language of the claims, the
issue is what constitutes a “lane.” For guidance, we turn to the specification.
See Phillips, 415 F.3d at 1315 (the specification is “the single best guide to
the meaning of a disputed term”) (citing Vitronics Corp. v. Conceptronic,
Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996).
As an initial matter, we are not persuaded by Petitioner’s implicit
argument that, as used in the ’708 patent specification, a “lane” is something
different from a “sample lane.” See Pet. Reply 2–3. The specification
consistently uses the terms “lane” and “sample lane” interchangeably to
refer to the structure in which the polynucleotide analysis occurs. For
example, the specification explains that “[o]ne aspect of the present
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technology relates to a microfluidic cartridge having two or more sample
lanes arranged so that analyses can be carried out in two or more of the lanes
in parallel, for example simultaneously, and wherein each lane is
independently associated with a given sample.” Ex. 1002, 12:61–65
(emphasis added); see also id. at 4:7–14 (describing the apparatus as
including “a disposable microfluidic cartridge containing multiple sample
lanes in parallel” with an instrument platform that can analyze the PCR
amplification products “in each of the lanes” separately or simultaneously),
13:34–42 (“The multi-lane cartridge comprises at least a first sample lane
having a first microfluidic network and a second lane having a second
microfluidic network . . .”), 13:55–61 (describing a microfluidic cartridge
containing “twelve independent sample lanes” in which “each lane” is
“configured to carry out amplification”). Petitioner does not direct us to, nor
do we discern, anything in the specification that indicates that a “lane” is
something different than a “sample lane.” See Phillips, 415 F.3d at 1313
(“[T]he person of ordinary skill in the art is deemed to read the claim term
not only in the context of the particular claim in which the disputed term
appears, but in the context of the entire patent, including the specification.”).
We also agree with Patent Owner that the specification defines the
structure of the sample lane. PO Resp. 12. The specification states:
A sample lane is an independently controllable set of elements
by which a sample can be analyzed, according to methods
described herein as well as others known in the art. A sample
lane comprises at least a sample inlet, and a microfluidic network
having one or more microfluidic components as further described
herein.
Ex. 1002, 12:66–13:4. The embodiments described in the specification
include sample inlets associated with each of the sample lanes. See, e.g., id.
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at 14:34–45, Figs. 10A, 10B (describing an exemplary microfluidic cartridge
depicted in Figures 10A and 10B as showing “[m]ore than one inlet 202 . . .
wherein one inlet operates in conjunction with a single sample lane”),
17:55–60, Fig. 13 (describing and depicting a 48-sample cartridge with
separate inlets 602 for each sample lane). In contrast, when describing other
elements (such as inlet ports and valves) that may be included in a sample
lane, the specification clearly conveys that these other elements are optional.
Id. at 13:5–12 (“In various embodiments, a sample lane can include a
sample inlet port or valve, and a microfluidic network that comprises, in
fluidic communication one or more components selected from the group
consisting of” certain specified valves, vents, pumps, and chambers.
(emphasis added)).
That each sample lane must be associated with a separate, dedicated
inlet is further supported by the ’708 patent specification’s teaching that
[a] multi-lane cartridge is configured to accept a number of
samples in series or in parallel, simultaneously or consecutively,
in particular in embodiments [of] 12 samples, wherein the
samples include at least a first sample and a second sample,
wherein the first sample and the second sample each contain one
or more polynucleotides in a form suitable for amplification. The
polynucleotides in question may be the same as, or different from
one another, in different samples and hence in different lanes of
the cartridge.
Ex. 1002, 13:21–29; see also id. at 13:38–42 (“[T]he first microfluidic
network is configured to amplify polynucleotides in the first sample, and . . .
the second microfluidic network is configured to amplify polynucleotides in
the second sample.”). The ’708 patent specification further teaches that the
“sample inlets of adjacent lanes are reasonably spaced apart from one
another to prevent any contamination of one sample inlet from another
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sample when a user introduces a sample into any one cartridge,” and
describes an embodiment where “the sample inlets are configured so as to
prevent inadvertent introduction of sample into a given lane after sample has
already been introduced into that lane.” Id. at 14:64–15:3.
Taken as a whole, these disclosures indicate that the multi-lane
microfluidic cartridge claimed in the ’708 patent is capable of analyzing a
distinct sample in each lane, such that multiple different samples can be
processed in the cartridge at the same time. This is achieved by associating
a separate sample inlet with each sample lane.
Moreover, Petitioner’s proposed construction merges the meaning of
“channel” with “sample lane” or “lane” as those terms are used in the ’708
patent. As Patent Owner notes, in the ’708 patent specification, the terms
“channel” and “sample lane” or “lane” are not used interchangeably, and
instead refer to separate structures. PO Sur-Reply 3. In particular, the ’708
patent specification teaches that a channel is an element of a microfluidic
network, which in turn is an element of the sample lane. See Ex. 1002,
18:55–57 (“Channels of a microfluidic network in a lane of [a] cartridge
typically have at least one sub-millimeter cross-sectional dimension.”); see
also id. at 14:48–52 (“Also shown [in Figs. 10A and 10B] is an ultrafast
PCR reactor 210, which, as further described herein, is a microfluidic
channel in a given sample lane that is long enough to permit PCR to amplify
polynucleotides present in a sample.”).
Finally, Petitioner’s argument that Patent Owner equated “lane” and
“flow channel” to overcome prior art during prosecution of the ’708 patent is
not persuasive. Petitioner directs us to an amendment in which the
applicants added the phrase “multi-lane” to modify “microfluidic cartridge”
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in the pending claims in response to a rejection over a reference called
Wilding. Ex. 1005, 2–5. In that amendment, the applicants argued:
The amplification device disclosed in Wilding is a single lane
(flow channel) amplification device for conducting PCR. See,
e.g., Wilding, paragraph [0039] and Figures 2 and 5. Thus,
Wilding fails to disclose a “multi-lane microfluidic cartridge,
each lane comprising a PCR reaction zone” as required by Claim
1. Furthermore, Wilding teaches a PCR reaction chamber with
multiple sections, and if the two chambers are interpreted to be
the same reaction zone, the device fails to satisfy the claim
limitations that “the heat source maintains substantially uniform
temperature throughout the PCR reaction zone” and that it
“thermal cycles the PCR reaction zone.”
Id. at 7.
The Federal Circuit has cautioned that “prosecution history comments
cannot trump the plain language of the claims and the direct teaching of the
specification.” Telecordia Techs., Inc. v. Cisco Sys., Inc., 612 F.3d 1365,
1375 (Fed. Cir. 2010) (citation omitted). As set forth above, the direct
teaching of the specification here establishes that “lane” and “channel” refer
to different structures. On its face, the applicants appear to use the phrase
“single lane (flow channel)” only to characterize the device used in Wilding,
which is consistent with Patent Owner’s representation that the applicants
were “simply using the terminology that Wilding itself uses (‘flow channel’)
as short-hand for discussing the relevant features of the Wilding reference.”
PO Sur-Reply 3–4.9 Furthermore, the applicants did not distinguish Wilding
on the basis that a lane and a flow channel are actually the same structures,
but instead argued that the number of such lanes or flow channels in the
Wilding device did not satisfy the claim requirement of a “multi-lane

9 A complete copy of the prosecution history, including Wilding, is not of
record in this proceeding.
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microfluidic cartridge.” Accordingly, we find that, on this record, the
applicants’ remarks regarding Wilding are insufficient to overcome the
direct teaching of the ’708 patent, namely, that a “lane” and a “channel” are
different structures.
In view of the foregoing, we construe the phrase “multi-lane
microfluidic cartridge” to mean “a microfluidic cartridge comprising a
plurality of sample lanes, each sample lane comprising a separate sample
inlet and microfluidic network.” The express language of the claims further
requires that each lane also comprise a PCR reaction zone. Ex. 1002, 46:6–7
(“a multi-lane microfluidic cartridge, each lane comprising a PCR reaction
zone”), 48:30–32 (“a multi-lane microfluidic cartridge, wherein each lane
comprises a PCR reaction zone”).
C. Claims 1–6, 9, 10, 18–20, 23–25, 28, and 30–33
Petitioner asserts that claims 1–6, 9, 10, 18–20, 23–25, 28, and 30–33
would have been obvious over the combined teachings of Zou I and
McNeely or Pease, and relies on the Gale Declarations to support its
assertions. Pet. 28–63; Pet. Reply 4–27. Patent Owner disagrees with
Petitioner’s assertions, and relies on the Northrup Declaration.
PO Resp. 29–76; PO Sur-Reply 1–31.
1. Overview of Zou I
Zou I is directed to “a thermal cycler which permits simultaneous
treatment of multiple individual samples in independent thermal protocols,
so as to implement large numbers of DNA experiments simultaneously in a
short time.” Ex. 1008, at [57]. Zou I explains that “[t]he basic principle that
governs the present invention is that the thermally conductive cycler
chamber is thermally isolated from its surroundings except for one or more
heat transfer members through which all heat that flows in and out of the
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chamber passes,” and “by placing at least one heating element in each
transfer area, heat lost from the chamber can be continuously and precisely
replaced, as needed.” Id. at 3:55–62. Zou I teaches that “[t]his is achieved
by placing, within the chamber, at least one temperature sensor per heating
element and locating this sensor close to the heating elements,” and, further,
that the chamber can be rapidly cooled “by connecting the heat transfer areas
to a heat sink through a high thermal conductance path.” Id. at 3:62–67.
Figure 1a of Zou I is reproduced below.

Figure 1a is a “plan view of a first embodiment of the invention” described
in Zou I. Id. at 3:14–15. Chamber 11 “is connected at both ends to silicon
frame 1 through monocrystalline silicon beams 10,” with heaters 5 “at each
end inside the heat transfer areas.” Id. at 4:19–22. Each chamber also
“contains at least one heat temperature sensor 4 for each heating element 5.”
Id. at 4:24–27. “Fluid bearing channels dispense fluid into and remove fluid
from the chamber 11” through silicon beams 10. Id. at 4:28–30.
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“[U]nprocessed fluid is stored in common reservoir 7, and is directed to
chamber 11 through fluid bearing channel 31.” Id. at 4:31–33.
Figure 4 of Zou I is reproduced below.

Figure 4 depicts “an example of several chambers integrated to form a single
multi-sample recycling unit.” Id. at 5:4–6. “[I]ndividual chambers 11 are
positioned inside the interior open area of silicon frame 1 and are connected
to it through silicon beams 10,” and, “except for these beams, the chamber is
always thermally isolated from the frame by open space 3.” Id. at 5:6–11.
2. Overview of McNeely
McNeely is directed to devices for processing microarray slides used
in detection reactions involving biomolecules. Ex. 1009 ¶ 2. In particular,
McNeely states that “the invention relates to a novel device for interfacing
with a microarray slide to provide for the controlled delivery of fluids to
selected regions of the slide surface as well as an instrument for performing
simultaneous processing of a plurality of microarray slides,” each of which
is used in combination with an interface device. Id. McNeely teaches that
the “microarray interface device can be connected to a substrate bearing a
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microarray of spots made up of DNA, RNA, oligonucleotides, proteins, or
other biomolecules,” and “is adapted to for interfacing with glass
microscope slides and similar planar substrates.” Id. ¶ 17. “The interface
device provides for the delivery of sample, reagents, rinses, and so forth, to
selected portions of the array in a controlled manner.” Id. According to
McNeely, “[o]ne of the advantages of the inventive system is that it can be
configured for use in processing a single slide, or it can be multiplexed to
handle the processing of multiple slides.” Id. ¶ 139.
Figure 1 of McNeely is reproduced below.

Figure 1 “is a perspective view of an exemplary embodiment of a slide
processing device” described by McNeely. Id. ¶ 35. Instrument 600
includes multiple bays 602, each of which is adapted to receive reaction
device 604. Id. ¶ 82. Reaction device 604 “is made up of a microarray slide
in combination with a microarray interface device.” Id. “Bays 602 are
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located in base 603 on heat block 606,” and bays 602 and base 603 “are in
thermal communication with heat block 606.” Id. Sample, reagent, and
wash liquids are introduced into each reaction device 604 via inlet hole 612,
and air or liquid exits reaction device 604 through outlet hole 614. Id. “Inlet
hole 612 and outlet hole 614 are formed in interface device 616, and are in
fluid communication with a reaction chamber on the surface of the
microarray slide.” Id. Instrument 600 may “also include opaque lid 624 to
keep the microarray slides from being exposed to light.” Id. Lid 624 may
also provide thermal insulation. Id.
McNeely Figures 5 and 6 are reproduced below.

Figure 5 is a perspective view of an interface device and microarray
structure described by McNeely, and Figure 6 is a top view of the
microarray structure depicted in Figure 5. Id. ¶¶ 39–40. In Figure 5, closed
interface channels 39 are formed “when interface surface 13 is pressed
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against surface 7 of microarray slide 1” and “grooves 25 are closed or
covered by surface 7.” Id. ¶ 95. Each interface channel 39 contains column
11 of spots 5. Id. “Interface inlets 31 and interface outlets 35 in interface
device 3 provide access to interface channels 39.” Id. The top view of
interface device 3 shown in Figure 6 shows “spots 5 on microarray slide 1,
interface channels 39, inlet channels 33, outlet channels 37, interface inlets
31, and interface outlets 35.” Id. ¶ 96. In this embodiment, fluid samples
may enter interface inlets 31, travel through interface channels 39 and over
spots 5, and exit the interface device through interface outlets 35. Id.
McNeely teaches that the embodiment shown in Figures 5 and 6
“permits column 11 of spots 5 to be accessed individually,” and
“[c]ontinuous flow of samples, reagents, or other reactants may be provided
to each column of spots.” Id. ¶ 97. “Inlet channels 33 and outlet channels
37 may be closed channels formed in the interior of interface device 3,” and
“[i]t would also be possible to form inlet channels 33 and outlet channels 37
as open grooves in interface surface 13 of interface device 3, continuous
with grooves 25, which would similarly form closed channels when interface
device 3 was sealed to microarray slide 1.” Id. McNeely further teaches
that the interface device may include various types of sensors, including
“optical sensors for real time detection of reactions occurring in the interface
device.” Id. ¶ 138. The interface device may also include “heating elements
or other mechanism for regulating reaction conditions,” and that such
“heating elements may be used to perform thermo-cycling during PCR.” Id.
3. Overview of Pease
Pease describes systems, including methods and apparatus, “for
microfluidic processing of samples using a microfluidic device having an
array of thin-film electronic devices.” Ex. 1010 ¶ 35. Pease teaches that
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“the array may include an arrangement of thermal control devices and
associated thermal control features that enables independent temperature
control of closely spaced regions of fluid disposed adjacent the array.” Id.
¶ 40. Pease also teaches that thermal control zones “are isolated so that each
zone may be adjusted independently to a different temperature,” and “may
correspond to regions under different fluid chambers and/or to different
regions under one fluid chamber.” Id. ¶ 48.
Pease describes an embodiment of a microfluidic system “for
processing and analysis of samples, particularly samples containing nucleic
acids.” Id. ¶ 71. The system includes a control apparatus and an integrated
cartridge that is configured to be electrically coupled to the control
apparatus. Id. Figure 15 of Pease is reproduced below.

Figure 15 is a schematic view of the cartridge and control apparatus,
“illustrating movement of fluid, sample, electricity, digital information, and
detected signals” in one of Pease’s embodiments. Id. ¶ 19. In order to
control processing in the cartridge, “[c]ontrol apparatus 312 is configured to
send and receive control signals to cartridge 314.” Id. ¶ 72. Cartridge 314
can include detection electronics, which allows control apparatus 312 to
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receive signals from cartridge 314 that are utilized to determine the assay
result. Id. Additionally, control apparatus 312 “may include one or more
optical, mechanical, and/or fluid interfaces with cartridge 314.” Id. ¶ 76.
For example, optical interface 336 may send light to and/or receive light
from cartridge 314, and “may act as a detection mechanism having one or
more emitters and detectors to receive optical information from” cartridge
314. Id.
“Assay portion 344 is configured for further processing of nucleic
acid in fluid network 348 after nucleic acid isolation in fluid-handling
portion 342,” and “relies on electronics or electronic circuitry 358, which
may include thin-film electronic devices to facilitate controlled processing of
[the] nucleic acids.” Id. ¶ 84. Amplification chamber 366 may be used to
copy one or more target nucleic acids from among the concentrated nucleic
acids, using an amplification reaction. Id. ¶ 90. Pease explains that
“amplification may involve thermal cycling (for example, polymerase chain
reaction (PCR) or ligase chain reaction (LCR)).” Id. Optical interface 366
“may measure sample processing at any suitable position of assay portion
344,” and “may include separate emitter-detector pairs for monitoring
amplification of nucleic acids in amplification chamber 366, and for
detecting binding and/or position of amplified nucleic acids after processing
in assay chamber 368.” Id. ¶ 92.
4. Analysis
Petitioner contends that “Zou I discloses much of the purported
invention,” and that “[t]he remaining elements, such as a detector, a
processor coupled to the detector, and a receiving bay configured to receive
a microfluidic cartridge, were standard features of integrated machines used
for performing biochemical reactions such as PCR.” Pet. 28 (citing
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Ex. 1001 ¶¶ 49, 52–58, 115, 116). Petitioner contends that “[s]uch
apparatuses were common by March of 2006,” and that McNeely and Pease
“disclosed two such machines.” Id. Petitioner further contends that “a
POSA would have been motivated to combine the multiplexing PCR unit of
Zou I with a conventional integrated machine such as in McNeely or Pease,
with a high expectation of success,” and provides a number of reasons why a
POSA would have been motivated to do so. Id. at 28–33.
Patent Owner argues in response that Zou I does not disclose a “multi-
lane microfluidic cartridge, each lane comprising a PCR reaction zone.” PO
Resp. 30–35. Patent Owner also argues that “Petitioner fails to show a
motivation to combine the references to teach or suggest” a “cartridge,”
“receiving bay,” or “detector configured to detect the presence of an
amplification product in the respective PCR reaction zone” as recited in
claim 1, and that Petitioner does not explain “why or how the teachings [of
the prior art] would have or could have been successfully combined.” Id.
at 38–55. We address these arguments in turn below.
a) multi-lane microfluidic cartridge, each lane comprising a PCR
reaction zone
Each of the challenged claims requires a “multi-lane microfluidic
cartridge, each lane comprising a PCR reaction zone” (Ex. 1002, 46:1–
48:40), which we interpret to mean “a microfluidic cartridge comprising a
plurality of sample lanes, each sample lane comprising a separate sample
inlet and microfluidic network” and a PCR reaction zone (see supra § II.B).
Petitioner contends that “Zou I discloses a multi-lane microfluidic unit”
wherein “[e]ach lane includes an inlet, a PCR reaction chamber 11, and an
exit reservoir 9.” Pet. 34 (citing Ex. 1008, 4:28–5:21, Figs. 3 and 4;
Ex. 1001 ¶ 129). Petitioner contends that “Zou I further teaches that PCR
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can be carried out in each chamber 11.” Id. (citing Ex. 1008, Abstract, 1:12–
20, 2:49–54, 5:51–55, 8:30–35; Ex. 1001 ¶ 130).
Petitioner uses an annotated version of Zou I’s Figure 4, shown
below, to depict its contentions:

Id. (citing Ex. 1001 ¶ 130). Figure 4 depicts “several chambers integrated to
form a single multi-sample recycling unit” (Ex. 1008, 5:4–6), with
Petitioner’s annotations in the form of green shading to delineate the claimed
PCR reaction zone, and arrows pointing to the features Petitioner contends
comprise each lane of the claimed “multi-lane microfluidic cartridge,”
namely, the PCR reaction chambers, inlets, and exit reservoirs. Pet. 34.
Petitioner further contends that, “[t]o the extent that Zou I doesn’t
expressly disclose a cartridge, each of McNeely and Pease does.” Pet. 35;
see also Pet. Reply 8 n. 5 (Stating that “Zou I could be considered a
cartridge itself” without explaining how or why, but that “Pease and
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McNeely disclose cartridges.” (emphasis added)). According to Petitioner,
“McNeely discloses a multilane microfluidic cartridge that can be used to
perform PCR on samples in the cartridge, with inlets and outlets for each
lane” (Pet. 35 (citing Ex. 1009 ¶¶ 96, 97, 138, Figs. 5, 6; Ex. 1001 ¶ 131)),
and “Pease also discloses a multilane microfluidic cartridge that can be used
to perform PCR on samples in a cartridge, with plural separate fluid
channels and chambers” (id. (citing Ex. 1010, Abstract et. seq.; Ex. 1001
¶ 132)).
In response, Patent Owner argues that “Zou I does not disclose
multiple separate microfluidic networks, but a single microfluidic network.”
PO Resp. 32 (emphasis omitted). In particular, Patent Owner argues that
“Zou I has a single ‘common reservoir 7’ that directs fluid to individual
chambers (11) through single channel (31).” Id. (emphasis omitted).
Patent Owner further argues that “Zou I does not disclose multiple
lanes with separate inlets, but instead multiple chambers that share a single
inlet.” PO Resp. 33 (emphasis omitted). Patent Owner argues that
reservoir 7 shown in Zou I’s Figure 4 is “the inlet for all three chambers, as
fluid is dispensed from that reservoir into each chamber.” Id. at 34. Patent
Owner also argues that “Petitioner offers no explanation or justification for
why it identifies multiple inlets to chambers 11,” when Zou I uses the term
“inlet” to refer to “reservoir 7.” Id. at 35 (citing Ex. 1008, 4:36, 6:12–15).
According to Patent Owner, “an ‘inlet’ is a common term in both the ’708
patent and Zou I, and would have been understood to refer to a location
where sample is input.” Id. (citing Ex. 2036 ¶ 173).
Petitioner argues in its Reply that “Zou I describes element 7 as ‘inlet
fluid source reservoir 7,’” and a “POSA would understand reservoir 7 is the
source of the fluid for the inlets, not the inlet itself.” Pet. Reply 5 (citing
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Ex. 1008, 4:4; Ex. 1026 ¶ 25) (emphasis omitted). Patent Owner contends in
its Sur-Reply that “Petitioners’ so-called ‘inlets’ (valve 8 and channel 31)
are within the chip in Zou I,” and, “[c]onversely, a sample inlet in the ’708
patent is ‘a location where the sample is input into the cartridge.’” PO Sur-
Reply 8 (citing Ex. 1008, 4:1–6, Figs. 3 & 4; Ex. 2036 ¶¶ 376–378;
Ex. 1027, 156:2–9; Ex. 1002, 14:64–67) (emphasis omitted).
We have considered the arguments and evidence of record and
determine that Zou I does not teach a multi-lane microfluidic unit under the
proper claim construction. In particular, we find that Zou I does not teach a
plurality of sample lanes wherein each sample lane comprises a separate
sample inlet. We agree with Patent Owner that Zou I teaches that all of the
lanes are associated with a single sample inlet, namely, common reservoir 7.
PO Resp. 32–35; PO Sur-Reply 7–10. Patent Owner’s annotated version of
Figure 4 of Zou I is shown below:

PO Resp. 33 (citing Ex. 1008, Fig. 4, 4:30–33). Patent Owner annotates the
“several chambers integrated to form a single multi-sample recycling unit”
shown in Zou I’s Figure 4 above by using red shading to show that “the PCR
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reaction zones (chambers 11) and the common reservoir are in fluid
communication with one another as a single fluidic network.” Id. (citing
Ex. 1008, 4:1–6).
Patent Owner’s annotated Figure 4 is consistent with the teachings of
Zou I. Zou I teaches “a fully integrated fluid dispensing and retrieval
system” that “allows multiple chambers to share both a common heat sink as
well as an inlet fluid source reservoir with both fluid flow and temperature
being separately and independently controllable.” Ex. 1008, 4:1–6. Zou I
further teaches that “unprocessed fluid is stored in common reservoir 7 and
is directed to chamber 11 through fluid-bearing channel 31,” and that
pressure valves 8 (not shown) “are placed at both ends of the chamber” in
order to “prevent unintended entry of fluid into the chamber.” Id. at 4:30–
35, 4:43–45. We credit Dr. Northrup’s testimony that
[a]n “inlet” is a common term used in the ’708 patent, Zou I, and
understood in the art to refer to a location where sample is input.
In Zou I, as the Zou I authors expressly stated, the “inlet” is a
common reservoir that dispenses fluid to multiple chambers;
Zou I Figure 4 does not include multiple inlets, each of which is
associated with a separate lane.
Ex. 2036 ¶ 101 (emphasis omitted).
Moreover, Petitioner does not direct us to, nor do we discern, any
teaching in Zou I that its microfluidic unit is capable of analyzing a distinct
sample in each lane, such that multiple different samples can be processed in
the cartridge at the same time. In that regard, we also credit Dr. Northrup’s
testimony that
Zou I could not effectively function to analyze multiple separate
samples independently. When a nucleic acid sample passes
through a channel or container, it will contaminate that receptacle
by leaving some nucleic acid behind. As illustrated in the further
annotated Figure 4 of Zou [I] below, any second sample (pink)
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that passed through the common reservoir 7 of Figure 4 would
be contaminated by the residue left by a first sample (blue),
resulting in a mixture of both samples.

A POSA would have understood that such cross-contamination
would render the Figure 4 device unreliable, if not inoperable
for its purpose.
Id. ¶¶ 104–105 (citing Ex. 1008, Figure 4 (depicting “several chambers
integrated to form a single multi-sample recycling unit”)).
We note that, in its Reply, Petitioner argues that “Zou I’s Figure 5
shows an embodiment with at least four physically distinct fluid input
locations.” Pet. Reply 5–6 (citing Ex. 1008, Figure 4; Ex. 2012, 185:18–
186:3; Ex. 1026 ¶ 28). In support of this argument, Dr. Gale testifies that
[b]ased on the layout of the reaction chambers in Fig. 5 of Zou I
and the layout of each reaction chamber from Fig. 4 of Zou I,
there would be a maximum of 24 reaction chambers connected
to one fluid reservoir if the reaction chambers were mirrored
across the fluid reservoir, leading to a minimum of 4 physically
distinct input ports.
Ex. 1026 ¶ 28. This argument is unpersuasive. Zou I does not discuss
Figure 5 other than to say it “shows a full population of cycling chambers
covering an entire wafer,” and that it “shows how the sub-structure shown in
FIG. 4 appears when full wafer 66 of silicon has been used to form multiple
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chambers.” Ex. 1008, 3:24–25, 5:11–13. In light of these limited
disclosures in Zou I, Dr. Gale does not sufficiently explain why or how
Zou I’s Figure 5 discloses separate sample inlets for each sample lane, or
that each sample lane in Figure 5 is associated with a separate sample inlet,
as required by the claims of the ’708 patent.
Petitioner also argues in its Reply that “it would have been obvious to
modify Zou I’s Figure 4” to have “physically distinct exterior sample input
locations.” Pet. Reply 7. In support of this argument, Dr. Gale testifies that
drilling access holes in the glass cover of Zou I’s microfluidic chip would
have been “a common technique by March 2006,” and “it would have been
trivial for a POSA to drill individual ports through the glass cover of Zou I
in order to provide physically distinct ports into each of Zou I’s microfluidic
lanes.” Ex. 1026 ¶ 30. Neither Petitioner nor Dr. Gale sufficiently explain,
however, why a POSA would have been motivated to make this
modification, or how this modification would affect how Zou I’s
microfluidic chip functions. For example, neither Petitioner nor Dr. Gale
address how such access holes would interact, if at all, with Zou I’s common
reservoir. See PO Sur-Reply 10 (citing Ex. 1008, 4:1–11, 4:30–32; Ex. 2036
¶¶ 101–105; PO Resp. 32–33).
In an obviousness analysis, a sufficient reason must be shown as to
why a POSA would have thought of combining or modifying the prior art to
achieve the patented invention. See Innogenetics, N.V. v. Abbott Labs., 512
F.3d 1363, 1374 (Fed. Cir. 2008). Here, Petitioner offers only the general
proposition that drilling access holes into the glass cover of Zou I’s
microfluidic chip was a “common technique,” but this does not provide a
reason why a POSA would have been motivated to modify Zou I’s
microfluidic chip. Pet. Reply 7. Petitioner’s argument and Dr. Gale’s
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testimony with respect to the modification of Zou I leaves an analytical gap
that does not apprise us of why a POSA would have modified Zou I with
access holes that would operate as separate sample inlets for each sample
lane as required by the claims of the ’708 patent.
Here, Petitioner attempts to imbue a POSA with the knowledge of the
claimed invention, when no prior art reference, references of record, or other
evidence conveys or suggests that knowledge. Petitioner’s argument that a
POSA would have modified Zou I in this way appears to be premised on
Petitioner’s knowledge of the ’708 patent disclosure. This is improper
hindsight reasoning. Petitioner needed to explain what would have led a
POSA at the time of the invention to consider modifying Zou I to include a
separate sample inlet with each sample lane. Petitioner failed to provide
such an explanation. See W.L. Gore & Assoc., Inc. v. Garlock, Inc., 721
F.2d 1540, 1553 (Fed. Cir. 1983) (In an obviousness analysis, we must “cast
the mind back to the time the invention was made” and “occupy the mind of
one skilled in the art who is presented only with the references, and who is
normally guided by the then-accepted wisdom in the art.”).
For these reasons, after considering Petitioner’s and Patent Owner’s
positions, as well as their supporting evidence, we are not persuaded that
Petitioner has demonstrated that Zou I teaches or suggests a multi-lane
microfluidic unit. Petitioner does not rely on McNeely or Pease to remedy
this deficiency in Zou I. Accordingly, we find that Petitioner has not
established that the combined teachings of Zou I and McNeely or Pease
teaches a “multi-lane microfluidic cartridge, each lane comprising a PCR
reaction zone” as required by the challenged claims.
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b) Motivation to Combine
Petitioner contends that a POSA “would have been motivated to
combine the multiplexing PCR unit of Zou I with a conventional integrated
machine such as in McNeely or Pease,” with a reasonable expectation of
success. Pet. 28–33. Petitioner characterizes Zou I as teaching a
microfluidic PCR “unit,” or “chip,” but not a cartridge. See, e.g., Pet. 29
(“Zou I suggests that its chip may be ‘used in current macro thermal cycler
machines’”), 34 (“Zou I discloses a multi-lane microfluidic unit”);
Pet. Reply 11 (“a multi-lane microfluidic unit or chip like Zou I”), 13 (“use
[Zou I’s] chip with ‘current macro thermal cycler machines’”), 15 (“Zou I’s
fully functional multi-lane microfluidic unit, virtually unaltered”). Thus,
Petitioner does not dispute Patent Owner’s assertion that Zou I discloses “a
‘thermal cycler chip,’ not a ‘cartridge’ – nor does it contain any reference to
a cartridge.” PO Sur-Reply 6 (citing Ex. 1008, 7:51–62, 8:45–63; PO Resp.
15–16, 30–31; Ex. 2036 ¶¶ 97–100, 165–166).
As to the cartridge requirement of the challenged claims, Petitioner
relies on McNeely and Pease as teaching a cartridge as part of a
“conventional integrated machine.” Pet. 28–29. Specifically, Petitioner
argues that “McNeely discloses a multilane microfluidic cartridge that can
be used to perform PCR on samples in the cartridge” (id. at 35 (citing
Ex. 1009 ¶¶ 96, 97, 138, Figs. 5, 6; Ex. 1001 ¶¶ 79–80, 131)), and that
“Pease also discloses a multilane microfluidic cartridge that can be used to
perform PCR on samples in a cartridge, with plural separate fluid channels
and chambers” (id. (citing Ex. 1010, Abstract et. seq.; Ex. 1001 ¶ 132)).
Petitioner argues that “a POSA would have been motivated to combine the
multiplexing PCR unit of Zou I with a conventional integrated machine as in
McNeely or Pease, with a high expectation of success,” because: (1) Zou I
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“teaches combining its microfluidic unit into existing machines suitable for
performing biochemical reactions” (id. at 29 (citing Ex. 1001 ¶¶ 36–46,
118–121)); (2) “the combination would have provided the known benefit of
integrating detection with the amplification reaction process” (id. at 29–30
(citing Ex. 1001 ¶¶ 50–53, 122); (3) the combination “would have
predictably provided the necessary interfacing with the outside world” (id. at
30–31 (citing Ex. 1001 ¶¶ 123–124)); (4) “the combination would have
predictably improved reproducibility, reliability, and safety” (id. at 31–32
(citing Ex. 1001 ¶¶ 125–126)); and (5) “combining Zou I to be operated by a
standard machine such as disclosed by McNeely or Pease would have been
no more than applying known techniques to yield predictable results” (id. at
32–33 (citing Ex. 1001 ¶¶ 88, 127)).
In its Reply, Petitioner further argues that a POSA would have had a
reasonable expectation of success in combining the teachings of Zou I and
McNeely or Pease because the level of ordinary skill in the art was high, the
art was relatively advanced, and “[t]he combinations are straightforward –
Zou I’s fully functional multi-lane microfluidic unit, virtually unaltered and
maintaining its ‘basic principles of operation,’ with Pease or McNeely’s
cartridge-based systems.” Pet. Reply 15. Petitioner also argues that “using a
microfluidic PCR chip like Zou I with a cartridge was routine and
predictable by March 2006.” Id. at 16 (citing Ex. 1026 ¶ 66; Ex. 1030, 846–
847).
Patent Owner responds that Petitioner’s arguments regarding
motivation and reasonable expectation of success are conclusory and
contradicted by the record evidence. PO Sur-Reply 17. Patent Owner
asserts that “[t]he state of the art was early and aspirational” (id. (citing
Ex. 2036 ¶¶ 25–42; Ex. 2018, 2121)), neither McNeely nor Pease teach how
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to interface a generic chip with a cartridge, and “both experts agree that the
proposed combinations would ‘have to be designed’ to ‘match each other,’
including design of ‘the right interfaces,’ ‘heat sinks’ and other components”
(id. at 18 (citing Ex. 2068, 149:4–150:13; Ex. 2057, 170; Ex. 2002, 245–
248, 259–261; Ex. 2058, 536; Ex. 2036 ¶ 99)). Patent Owner further asserts
that “skilled artisans reported challenges in seeking to interface a PCR chip
within a cartridge” with regard to placement of heaters and temperature
uniformity. Id. (citing Ex. 1030, 845; Ex. 2002, 252; Ex. 2001, 16.5.1;
Ex. 2023, 346–353). Patent Owner also argues that specific features of
Zou I’s chip do not support a motivation to combine, namely, the fragility of
the monocrystalline silicon beams that connect each of Zou I’s PCR reaction
chambers to the frame. PO Resp. 41–42 (citing Ex. 1008, 4:17–21, Figs. 1B,
4; Ex. 2012, 44:18–22; Ex. 2036 ¶¶ 499–500); PO Sur-Reply 18–19 (citing
Ex. 1031, 421–422; Ex. 2068, 180:19–181:10, 182:3–19, 284:18–286:22).
Having considered the complete trial record, we determine that
Petitioner has failed to sufficiently demonstrate that the combination of
Zou I and McNeely or Pease teaches multi-lane microfluidic cartridges,
because Petitioner has failed to establish by a preponderance of the evidence
that a POSA would reasonably have expected to be successful in combining
Zou I’s microfluidic chip with a cartridge as taught by McNeely or Pease. In
order to demonstrate that the challenged claims are obvious, a petitioner
must demonstrate “that a skilled artisan would have been motivated to
combine the teachings of the prior art references to achieve the claimed
invention, and that the skilled artisan would have had a reasonable
expectation of success in doing so.” ActiveVideo Networks, Inc. v. Verizon
Commc’ns, Inc., 694 F.3d 1312, 1327 (Fed. Cir. 2012) (quoting Pfizer, Inc.
v. Apotex, Inc., 480 F.3d 1348, 1361 (Fed. Cir. 2007)). A petitioner must
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articulate “[1] how specific references could be combined, [2] which
combination(s) of elements in specific references would yield a predictable
result, or [3] how any specific combination would operate or read on the
asserted claims.” Id. at 1327–28.
Focusing on the parties’ arguments pertaining to how Zou I and
McNeely or Pease could be combined, which combination of elements in the
references would yield a predictable result, and how the combination would
operate or read on the challenged claims, we determine that the evidence on
this record is not sufficient to show that a POSA could have had a
reasonable expectation of success in attempting to combine the teachings of
Zou I with McNeely or Pease. Although the Petition sets forth various
rationales for why a person of ordinary skill would have had reason to
combine the teachings of Zou I and McNeely or Pease, the rationales are
general in nature and do not address any specific modification to either of
the references. Pet. 28–33. The Petition includes a single reference to
reasonable expectation of success, in a conclusory statement that “a POSA
would have been motivated to combine the multiplexing PCR unit of Zou I
with a conventional integrated machine such as in McNeely or Pease, with a
high expectation of success.” Id. at 28–29. The First Gale Declaration is
similarly conclusory as to how Zou I and McNeely or Pease could be
combined and does not elaborate on reasonable expectation of success. See
Ex. 1001 ¶¶ 116–127. Such conclusory assertions, lacking factual
substantiation, are insufficient for evaluating reasonable expectation of
success as part of an obviousness determination. Wasica Fin. GmbH v.
Cont’l Auto. Sys., Inc., 853 F.3d 1272, 1286 (Fed. Cir. 2017).
As discussed above, Petitioner in its Reply argues that Pease teaches
“a microfluidic ‘chip’ with multiple chambers for performing PCR, used in
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cartridge 314,” and that “McNeely shows various options combining its
‘interface device’ with a glass slide to create a cartridge 604.” Pet. Reply 16
(citing Ex. 1010 ¶ 78; Ex. 1009, ¶¶ 82, 126–129,Figs. 2, 23–24, 30, 32;
Ex. 1026 ¶ 65). Petitioner’s assertion that “using a microfluidic PCR chip
like Zou I as a cartridge was routine and predictable by March 2006,”
however, is based on Exhibit 1030, which Petitioner did not submit with the
Petition. Id. (citing Ex. 1026 ¶ 66; Ex. 1030, 846–847).
Moreover, we find persuasive Patent Owner’s argument that the
development of microfluidic PCR devices was not routine and predictable
by March 2006, but rather a very complex endeavor that presented
challenges with regard to uniform heating, detection of small volume
reactions, contamination, design and configuration of a microfluidic
network, and functionally interfacing the reaction instrument with control
machinery. PO Resp. 4–6, 50–55. Dr. Northrup provides factual support for
Patent Owner’s arguments, with reference to numerous contemporaneous
publications in the field (see, e.g., Ex. 2036 ¶¶ 29–47, 771–786; Exs. 2001,
2002, 2023, 2026, 2032, 2033), and persuasively explains that “[w]here PCR
microfluidic devices are designed as chips, connecting these chips to heat
sources or detection mechanisms, can be a complex task, particularly in view
of the need to ensure that other functionalities (e.g. uniform temperature,
optical detection, multiple reaction chambers, etc.) are not adversely
affected.” Ex. 2036 ¶ 39. Therefore, we credit Dr. Northrup’s testimony
that, in light of the state of the art in March 2006, a POSA would not
reasonably have expected a combination of Zou I and McNeely or Pease to
be successful, because of the particular challenges listed above. Ex. 2036
¶¶ 771–786. Dr. Gale’s testimony that interfacing a PCR chip with a
cartridge, such as Zou I with McNeely and Pease, would require that they be
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designed to match with each other, also supports that conclusion. Ex. 2068,
149:4–150:13.
Dr. Northrup also credibly explains why Zou I’s teaching relating to
integration into a micro total analysis system does not support the
combination of Zou I’s unit with the integrated machines described in
McNeely and Pease. Ex. 2036 ¶¶ 507–511. In particular, Dr. Northrup
explains that Zou I does not describe integrating its chip into a “total-
analysis” cartridge-based system as asserted by Petitioner, but rather
describes the possibility of integrating Zou I’s PCR unit into a total analysis
system on a single chip, i.e. combining Zou I’s chip with another chip
capable of providing other functionalities. Id. Additional evidence
corroborates Dr. Northrup’s opinion, which is unrebutted on this point.
Ex. 2001.
Furthermore, we disagree with Petitioner’s assertions that combining
Zou I and McNeely or Pease to arrive at the claimed invention would have
been “straightforward,” and that “each of Zou I, Pease, and McNeely already
disclosed functional cartridge devices for performing PCR” (Pet. Reply 15–
17), because Dr. Northrup’s credible testimony and the evidence of record
contradicts those assertions as discussed above. We also find that Dr. Gale’s
opinions in the Second Gale Declaration that “a POSA would expect to be
able to combine Zou I’s microfluidic unit, virtually unaltered and including
its thermally-isolated chamber structure” into a cartridge system (Ex. 1026
¶¶ 67, 70) to be conclusory and not supported by the evidence of record. In
particular, we note that Dr. Gale’s statement that “Zou I’s unit is more or
less a cartridge itself” and “all that would be required to combine into Pease
or McNeely would be potentially the addition of a basic cartridge housing”
is unsupported by sufficient analysis or objective evidence. Id. ¶ 70. It is
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also inconsistent with Dr. Gale’s testimony that a POSA would have
combined “Zou I’s multi-sample PCR unit with a cartridge configured for an
integrated machine,” and his consistent usage of “unit” or “chip” (instead of
“cartridge”) to describe Zou I’s device. Ex. 1001 ¶ 133; see also id. ¶¶ 76
(“Zou I further provides examples of a multi-lane microfluidic unit for
conducting PCR on multiple samples.”), 123 (“the cartridges of McNeely or
Pease, would have predictably provided beneficial interfacing of the
microfluidic chip of Zou I with the outside world”); 129 (“Zou I discloses a
multi-lane microfluidic unit”); 137 (“Zou I discloses a unit with multiple
PCR reaction zones 11”); Ex. 1026 ¶ 66 (“using a microfluidic PCR chip
like Zou I with cartridge-based machines was routine and predictable by
March 2006”). Furthermore, Dr. Gale does not address the evidence
supporting Dr. Northrup’s testimony regarding the complexity of connecting
PCR microfluidic chips to heat sources or detection mechanisms discussed
above. Thus, we would remain unpersuaded that Petitioner met its
evidentiary burden of providing sufficient evidence to support its proposed
combination even if the evidence and arguments from Petitioner’s Reply had
been set forth properly in the Petition.
Accordingly, after considering Petitioner’s and Patent Owner’s
positions, as well as their supporting evidence, we are not persuaded that
Petitioner has demonstrated that a POSA would have been motivated to
combine the teachings of Zou I with McNeely or Pease as Petitioner
contends, with a reasonable expectation of success in doing so.
c) Conclusion
For the foregoing reasons, we conclude that Petitioner has not
demonstrated by a preponderance of the evidence that claims 1–6, 9, 10, 18–
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20, 23–25, 28, 30–33 of the ’708 patent would have been obvious over the
combined teachings of Zou I and McNeely or Pease.10
D. Claims 7, 8, 11–17, 21, 22, 26, 27, and 29
Petitioner argues that: (1) claims 7 and 8 would have been obvious
over the combined teachings of Zou I, McNeely or Pease, and Hsieh; (2)
claims 11–17 would have been obvious over the combined teachings of
Zou I, McNeely or and Zou II; (3) claims 21 and 22 would have been
obvious over the combined teachings of Zou I and McNeely; (4) claims 26
and 27 would have been obvious over the combined teachings of Zou I ,
McNeely or Pease, and Duong; and (5) claim 29 would have been obvious
over the combined teachings of Zou I, McNeely or Pease, and Chow.
Pet. 3–4, 63–86. Each of claims 7, 8, 11–17, 21, 22, 26, 27, and 29 depend,
directly or indirectly, from independent claim 1, and, therefore, require a
“multi-lane microfluidic cartridge.” Ex. 1002, 46:44–53, 46:60–47:21,
47:31–35, 48:6–11, 48:17–20. Thus, for the same reasons given above with
respect to Petitioner’s challenge of claim 1, we also conclude that Petitioner
has not demonstrated by a preponderance of the evidence that 7, 8, 11–17,
21, 22, 26, 27, and 29 would have been obvious over the asserted prior art.
III. PATENT OWNER’S MOTION TO EXCLUDE
Patent Owner moves to exclude Exhibits 1030 and 1032. Paper 44.
We do not reach the merits of Patent Owner’s Motion to Exclude because

10 Patent Owner argues that objective indicia (namely, commercial success)
support the nonobviousness of the challenged claims. PO Resp. 74–77.
Because we find that Petitioner has not demonstrated that the claims would
have been obvious over the asserted prior art, we need not address Patent
Owner’s evidence regarding objective indicia of nonobviousness.
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Patent 7,998,708 B2
41
our Decision does not rely on Exhibits 1030 and 1032. Accordingly, we
dismiss Petitioner’s Motion to Exclude as moot.
IV. CONCLUSION
For the reasons given, we are not persuaded that Petitioner has shown
by a preponderance of the evidence that claims 1–33 of the ’708 patent
would have been unpatentable based on the challenges presented in the
Petition.
In summary:

Claims

35
U.S.C. §
Reference(s)/Basis Claims
Shown
Unpatentable
Claims
Not shown
Unpatentable
1–6, 9,
10, 18–
20, 23–
25, 28,
30–33
103 Zou I, McNeely or
Pease
1–6, 9, 10,
18–20, 23–25,
28, 30–33
7, 8 103 Zou I, McNeely or
Pease, Hsieh
7, 8
11–17 103 Zou I, McNeely or
Pease, Zou II
11–17
21, 22 103 Zou I, McNeely 21, 22
26, 27 103 Zou I, McNeely or
Pease, Duong
26, 27
29 103 Zou I, McNeely or
Pease, Chow
29
Overall
Outcome
1–33
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V. ORDER
In consideration of the foregoing, it is hereby:
ORDERED that Petitioner has not shown by a preponderance of the
evidence that claims 1–33 of the ’708 patent are unpatentable;
FURTHER ORDERED that Patent Owner’s Motion to Exclude
(Paper 44) is dismissed; and
FURTHER ORDERED that, because this is a Final Written Decision,
parties to the proceeding seeking judicial review of the Decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.

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FOR PETITIONER:
Gary Speier
J. Derek Vandenburgh
Jonathan D. Carpenter
CARLSON, CASPERS, VANDENBURGH & LINDQUIST
gspeier@carlsoncaspers.com
dvandenburgh@carlsoncaspers.com
jcarpenter@carlsoncaspers.com

FOR PATENT OWNER:
Heather M. Petruzzi
Barish Ozdamar, Ph.D.
Christopher M. Cherry
WILMER CUTLER PICKERING HALE AND DORR LLP
Heather.Petruzzi@wilmerhale.com
Barish.Ozdamar@wilmerhale.com
Chris.Cherry@wilmerhale.com

Kerry S. Taylor
Maria V. Stout
Benjamin B. Anger
KNOBBBE, MARTENS, OLSON & BEAR, LLP
2kst@knobbe.com
2mvs@knobbe.com
2bba@knobbe.com