HandyLab, Inc.

Patent Trials and Appeals Board

Jul 14, 2020

IPR2019-00490 (P.T.A.B. Jul. 14, 2020)

Trials@uspto.gov Paper 51
571-272-7822 Date: July 14, 2020

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

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

IPR2019-004901
Patent 8,323,900 B2

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

JUDGMENT
Final Written Decision
Determining No Challenged Claims Unpatentable
35 U.S.C. § 318(a)

1 IPR2019-01494 has been joined with this proceeding.
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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 1–22 of U.S. Patent
No. 8,323,900 B2 (“the ’900 patent,” Ex. 1003) are unpatentable.
A. Procedural History
Petitioner filed a Petition (“Pet.”) to institute an inter partes review of
claims 1–22 of the ’900 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 1–22 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 42).
Patent Owner filed a Motion to Strike certain portions of Petitioner’s
Reply. Paper 37. Petitioner filed an Opposition. Paper 38. We denied
Patent Owner’s Motion to Strike. Paper 41. Patent Owner also filed a
Motion to Exclude Exhibits 1030 and 1032. Paper 43. Petitioner filed an
Opposition (Paper 45), and Patent Owner filed a Reply (Paper 46).
An oral hearing was held on April 21, 2020, and a transcript is
included in the record. Paper 50 (“Tr.”).
B. Related Proceedings
Petitioner indicates that there are no related matters. Pet. 3. Patent
Owner identifies QIAGEN North American Holdings, Inc. v. HandyLab,
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Inc., Case IPR2019-00488, which concerns U.S. Patent No. 7,998,708 (“the
’708 patent”), as a related matter. Paper 3, 1.2
C. The ’900 Patent
The ’900 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. 1003, code (54), 4:4–7. 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
4:14–20. The system optionally “can display the results on a graphical user
interface.” Id. at 4:20–21.

2 Petitioner indicates that the ’900 patent issued from the same application
as the ’708 patent. Pet. 7.
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The ‘900 patent’s Figure 1 is reproduced below.

Figure 1 is “a perspective view of an exemplary apparatus 100” described by
the ’900 patent. Id. at 4:33–34. Apparatus 100 includes read head 300 “that
contains detection apparatus for reading signals from cartridge 200.” Id. at
4:42–43. Apparatus 100 “is able to carry out real-time PCR on a number of
samples in cartridge 200 simultaneously.” Id. at 4:43–45. Cartridge 200
contains multiple sample lanes, and the ’900 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 4:40–41, 4:45–46.

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The ’900 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 ’900 patent. Id. at 4:59–62. 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 4:64–5:3. 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
5:5–19, 6:6–7.
System 981 “is configured to operate in conjunction with a
complementary cartridge 994, such as a microfluidic cartridge.” Id. at 6:8–
10. 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 6:12–17. 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 6:18–19, 6:39–43.
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 of the individual sample lanes, separately or simultaneously.” Id. at
7:36–39. 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 7:45–50.
The ’900 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 8:1–4. According to the ’900
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 8:9–15.
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D. Challenged Claims
Petitioner challenges claims 1–22 (“the challenged claims”) of
the ’900 patent. Claims 1, 7, and 20 are independent. Claim 1 is
representative and is reproduced below.
1. An apparatus, comprising:
a plurality of multi-lane microfluidic cartridges, each lane
comprising a PCR reaction zone;
a plurality of receiving bays, each receiving bay configured
to receive one of the plurality of the microfluidic
cartridges;
each PCR reaction zone comprising a separately controllable
heat source thermally coupled thereto, wherein the
heat source thermal cycles the PCR reaction zone to
carry out PCR on a polynucleotide-containing sample
in the PCR reaction zone and maintains a substantially
uniform temperature throughout the PCR reaction
zone during each cycle;
a detector configured to detect the presence of an
amplification product in one or more PCR reaction
zones; and
a processor coupled to the detector and the heat sources,
configured to control heating of one or more PCR
reaction zones by the heat sources.
Ex. 1003, 46:4–20.
E. Prior Art and Asserted Grounds
Petitioner challenges the patentability of claims 1–22 of the ’900
patent on the following grounds:
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Claim(s) Challenged 35 U.S.C. §3 Reference(s)/Basis
1–8, 12, 14, 15, 17,
19–22
103(a) Zou I4 and McNeely5 or
Pourahmadi6
9–11, 13 103(a) Zou I, McNeely or Pourahmadi,
and Zou II7
18 103(a) Zou I, McNeely, or
Pourahmadi, and Chow8
16 103(a) Zou I, McNeely, or
Pourahmadi, and Duong9

Petitioner relies on the Declaration of Bruce K. Gale, Ph.D. (“Gale
Declaration,” Ex. 1001) and the second Declaration of Bruce K. Gale, Ph.D.
(“Second Gale Declaration,” Ex. 1026) in support of its contentions. Patent
Owner relies on the Declaration of Allen Northrup, Ph.D. (“Northrup
Declaration,” Ex. 2036).
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,

3 The Leahy-Smith America Invents Act (“AIA”) included revisions to 35
U.S.C. § 103 that became effective on March 16, 2013. Because the ’900
patent issued from an application filed before March 16, 2013, we apply the
pre-AIA versions of the statutory bases for unpatentability.
4 U.S. Patent No. 6,509,186 B1, issued Jan. 21, 2003 (Ex. 1008).
5 U.S. Patent App. Pub. No. US 2004/0037739 A1, published Feb. 26, 2004
(Ex. 1009).
6 U.S. Patent App. Pub. No. US 2002/0055167 A1, published May 9, 2002
(Ex. 1015).
7 U.S. Patent No. 6,762,049 B2, issued July 13, 2004 (Ex. 1011).
8 U.S. Patent No. 5,955,028, issued Sept. 21, 1999 (Ex. 1014).
9 WO 01/54813 A2, published Aug. 2, 2001 (Ex. 1013).
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such as PCR,” or “an advanced degree in a similar field with at least one
year of related experience.” Pet. 7. 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. 8 (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
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
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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) (now codified at 37 C.F.R.
§ 42.100(b) (2019)). 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)).
1. “multi-lane microfluidic cartridges”
Patent Owner argues that “multi-lane microfluidic cartridges” should
be construed to mean “microfluidic cartridges each comprising a plurality of
sample lanes with separate sample inlets and microfluidic networks.” PO
Resp. 10 (citing Ex. 2036 ¶ 51). Patent Owner argues that “the specification
makes clear that the claims ‘multi-lane microfluidic cartridge’ has a plurality
of samples lanes,” and “defines that in the context of the ’900 patented
invention, a ‘sample lane’ or ‘lane’ has certain specific characteristics,” such
as (1) a sample inlet and (2) certain microfluidic components. Id. at 10–11
(citing Ex. 1003, 13:4–20, 39–47; Ex. 2036 ¶¶ 53–54). Patent Owner further
argues that the specification states that the sample inlet and the microfluidic
network are separate from one another and unique to each lane. Id. at 11
(citing Ex. 1003, 13:2–3, 13:39–41, 15:4–7). According to Patent Owner,
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the disclosures in the specification “confirm the basic design of the ’900
patented invention: the disclosed cartridge has separate sample lanes that
can process multiple different samples independently.” Id. at 12 (citing Ex.
1003, 13:26–28, 13:38–42).
Petitioner argues that the claims “do not recite a ‘sample inlet’
associated with each lane, much less a ‘separate sample inlet,’” or a “sample
lane.” Pet. Reply 2–3.10 Petitioner argues that Patent Owner improperly
imports the specification’s description of a “sample lane” into the claim term
“lane” in order to impose the additional requirement of a sample inlet
associated with each lane, which is contrary to the claim language which
requires only that each “lane” must include a PCR reaction zone. Id.
Petitioner further argues that “multi-lane microfluidic cartridge” should be
given its ordinary meaning, i.e., “a cartridge with multiple microfluidic
channels,” and “should not be limited to the embodiments in the
specification” because “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. 1003, 2:59–60, 13:26–28, 17:22–26, 18:2–4).
We have considered, but are not persuaded by Petitioner’s claim
construction arguments for “multi-lane microfluidic cartridges.” 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

10 Petitioner’s Reply does not have numbered pages. In this decision, we
refer to page numbers of Petitioner’s Reply starting from the page titled
“Introduction” as page one.
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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).
We 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. 1003, 13:4–9. The embodiments described in the specification include
sample inlets associated with each of the sample lanes. See, e.g., id. at
14:41–52, 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”),
17:60–64, 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 13:10–13 (“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” 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 ’900 patent specification’s teaching that
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[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. 1003, 13:26–34; see also id. at 13:43–47 (“[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 ’900 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
sample when a user introduces a sample into any 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 15:4–10.
Taken as a whole, these disclosures indicate that the multi-lane
microfluidic cartridge claimed in the ’900 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.
We are not persuaded by Petitioner’s argument that a “lane” in the
’900 patent specification is something different from a “sample lane.” See
Pet. Reply 2–3. The specification uses the terms “lane” and “sample lane”
interchangeably, e.g., “[o]ne aspect of the present technology relates to a
microfluidic cartridge having two or more sample lanes arranged so that
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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. 1003, 12:66–13:3 (emphasis added); see also id.
at 4:14–19 (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 lane”
separately or simultaneously), 13:39–42 (“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 . . .”), 13:61–63
(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.”).
Moreover, we are not persuaded to adopt Petitioner’s proposed
construction, i.e., “a cartridge with multiple microfluidic channels,” because
it refers to “channels” in a different sense than the term is used in the ’900
patent. In the ’900 patent specification the terms “channel” and “sample
lane” or “lane” are not used interchangeably, and instead refer to separate
structures. See PO Sur-Reply 3. In particular, the ’900 patent specification
describes channels as elements of a microfluidic network, which in turn is an
element of the sample lane. See Ex. 1003, 18:59–61 (“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 14:55–59 (“Also
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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. See Pet. Reply 4 (citing Ex. 1005, 7–8; Ex. 1026 ¶ 21).
Petitioner directs us to an amendment in which the applicants added the
phrase “multi-lane” to modify “microfluidic cartridge” in the pending claims
in response to a rejection over the Wilding reference. 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
specification uses “lane” and “channel” to refer to different structures. In
the prosecution history relied upon by Petitioner, the applicants appear to
use the phrase “single lane (flow channel)” only to characterize the device
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used in Wilding. This 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 3–4.11 Further, the applicants did not
distinguish Wilding on the basis that a lane and a flow channel are actually
the same structures, but instead only argued that the number of such lanes or
flow channels in the Wilding device did not satisfy the claim requirement of
a “multi-lane microfluidic cartridge.”. Accordingly, we find that the
applicants’ remarks regarding Wilding are insufficient to overcome the
direct teaching of the ’900 patent, namely, that a “lane” and a “channel” are
different structures.
In view of the foregoing, we construe the term “multi-lane
microfluidic cartridges” to mean “microfluidic cartridges each comprising a
plurality of sample lanes with separate sample inlets and microfluidic
networks.” The express language of the claims further requires that each
lane also comprise a PCR reaction zone. Ex. 1003, 46:5–6 (“a plurality of
multi-lane microfluidic cartridges, each lane comprising a PCR reaction
zone”).
C. Obviousness over Zou I and McNeely or Pourahmadi
Petitioner contends that the combined teachings of Zou I and
Pourahmadi teach or suggest each limitation of claims 1–8, 12, 14, 15, 17,
and 19–22. Pet. 33–65.

11 A complete copy of the prosecution history, including Wilding, is not of
record in this proceeding.
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1. Overview of Zou I (Ex. 1008)
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
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 each 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.

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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 chamber 11 through silicon beams 10. Id. at 4:28–30. Unprocessed
fluid is stored in common reservoir 7, and then directed to chamber 11
through fluid bearing channel 31. Id. at 4:31–33. Chamber 11 is
sandwiched between glass plate 2 and silicon membrane 12 (shown in
Figure 1c), which keeps the chamber volume below 100 microliters and
minimizes thermal capacitance of the chamber. Id. at 5:14–20.
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. Individual chambers 11 are
positioned inside the interior open area of silicon frame 1 and are connected
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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 Pourahmadi (Ex. 1015)
Pourahmadi describes an instrument with multiple microfluidic
cartridges for performing various operations, such as PCR, on a fluid
sample. Ex. 1015 ¶¶ 21, 43, 48. Pourahmadi teaches that the instrument
may include a processor for controlling the operation of each cartridge, and
that the processor is connected to various sensors in the cartridge, such as
temperature sensors. Id. ¶ 64. The processor is programmed to receive and
record temperature data, and provides thermal control of the sample to
achieve the desired temperature for a particular stage of reaction. Id. ¶¶ 125,
129. Alternatively, thermal control may be achieved by transferring the
sample among different reaction regions having different, constant
temperatures. Id. ¶ 125. The processor “will typically include programming
for instructing the delivery of appropriate current for raising and lowering
the temperature” of cartridge regions in order to carry out “predetermined
time/temperature profiles, e.g., thermal cycling for PCR, and the like.” Id.
¶ 129. Pourahmadi further teaches:
In addition to sensors for monitoring temperature, the cartridge
may contain sensors to monitor the progress of one or more of
the operations of the device. For example, optical sensors and
pressure sensors may be incorporated into one or more regions
to monitor the progress of the various reactions, or within flow
channels to monitor the progress of fluids or detect
characteristics of the fluids ….
Id. ¶ 130.
Figure 2 of Pourahmadi is reproduced below.
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Figure 2 depicts an example of a cartridge according to an embodiment of
Pourahmadi. Id. ¶ 48. The cartridge is designed to process a fluid sample
and amplify nucleic acids, such as by PCR, and includes a sample flow path
extending from inlet port 103 through reagent mixing chamber 107 and
lysing chamber 119. Id. ¶¶ 48–49. The sample flow path also includes
flow-through component 122 which Pourahmadi describes as a
microfabricated chip comprising an array of columns for capturing analyte
as the sample flows through the chip. Id. ¶ 50. Following capture in the
flow-through component, the analyte is released into elution fluid that flows
through reagent chamber 141 which contains PCR reagents, and then flows
into reaction chamber 143 for PCR amplification. Id. ¶¶ 53–54.
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3. Overview of McNeely (Ex. 1009)
McNeely is directed to an interface device to provide for controlled
delivery of fluids to selected regions of microarray slides used in a detection
reaction, and an instrument for simultaneous processing of the microarray
slides. Ex. 1009 ¶ 2. McNeely teaches that its interface device “can be
connected to a substrate bearing a microarray of spots made up of DNA,
RNA, oligonucleotides, proteins, or other biomolecules” and “provides for
the delivery of sample, reagents, rinses, and so forth, to selected portions of
the array in a controlled manner.” Id. ¶ 17.
McNeely’s instrument is shown in Figure 1, reproduced below.

Figure 1 illustrates reaction devices 604 received by bays 602 in instrument
600. Ex. 1009 ¶ 82. The instrument includes multiple bays that are each
adapted to receive a reaction device, which is a combination of a microarray
slide and microarray interface device. Id. McNeely describes “[o]ne of the
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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.
McNeely further describes each interface device with reference to
Figures 5 and 6 below.

Figure 5, shown above, is a perspective view of interface device 3; Figure 6,
shown above, is a top view of the interface device. Id. ¶¶ 39–40. In the
interface device, closed interface channels 39 are formed when interface
surface 13 is pressed against surface 7 of microarray slide 1 and grooves 25
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are closed or covered by surface 7. Id. ¶ 95. Fluid samples may enter the
interface channels through interface inlets 31, travel over columns of spots 5,
and exit through outlets 35. Id. ¶ 96. 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, and 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 elements for regulating reaction
conditions,” and that such “heating elements may be used to perform
thermo-cycling during PCR.” Id.
4. Analysis of Claims 1–8, 12, 14, 15, 17, and 19–22
Petitioner contends that Zou I teaches a multi-lane microfluidic unit
that includes most of the elements of the challenged claims, and that “[t]he
remaining elements, such as a detector, a processor coupled to the detector,
multiple microfluidic cartridges, and a plurality of receiving bays each
configured to receive one of the cartridges, were standard features of
integrated machines used for performing biochemical reactions such as
PCR.” Pet. 26 (citing Ex. 1001 ¶¶ 116, 313–315, 319–321), 33 (citing Ex.
1008, 2:50-60, 5:4-20, Figs. 4, 5, 16; Ex. 1001 ¶ 333.) Petitioner contends
that “such integrated machines with multiple cartridges were common by
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March of 2006” and that McNeely and Pourahmadi disclose two such
machines. Id. at 26. Petitioner also contends that a person of ordinary skill
in the art would have been motivated to combine Zou I’s unit with a
conventional integrated machine such as in Pourahmadi or McNeely, with a
reasonable expectation of success. Pet. 27–32.
Patent Owner argues in response that Zou I does not disclose a multi-
lane microfluidic unit with each lane comprising a PCR reaction zone. PO
Resp. 29–32. Patent Owner also argues that Petitioner fails to show a
motivation to combine the references to teach or suggest cartridges,
receiving bays, or a detector configured to detect the presence of an
amplification product in one or more respective PCR reaction zones 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 39–51. We address these arguments in turn below.
a) “a plurality of multi-lane microfluidic cartridges,
each lane comprising a PCR reaction zone”
Each of the challenged claims includes this limitation. Ex. 1003,
46:4–48:37. As discussed above, we have construed the term “multi-lane
microfluidic cartridges” to mean “microfluidic cartridges each comprising a
plurality of sample lanes with separate sample inlets and microfluidic
networks.” Petitioner argues that even under this construction, Zou I
discloses a multi-lane microfluidic unit because “[e]ach lane includes an
inlet, a PCR reaction chamber 11, and an exit reservoir 9” which serve as
“separate sample inlets and microfluidic networks” for each lane. Pet. Reply
4–5 (citing Pet. 33, 14). Petitioner further argues that “Zou I further teaches
that PCR can be carried out in each chamber 11.” Pet. 34 (citing Ex. 1008,
Abstract, 1:12–20, 2:49–54, 5:51–55, 8:30–35; Ex. 1001 ¶ 130). Petitioner
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explains its contentions by reference to an annotated version of Zou I’s
Figure 4, reproduced below.

Pet. Reply 5. Figure 4 illustrates a multi-sample unit as described in Zou I
(Ex. 1008, 5:4–6); in the annotated version of Figure 4 above, Petitioner
shades in green and labels the parts of Zou I that purportedly correspond to
each lane of the claimed “multi-lane microfluidic cartridge,” i.e., inlets, PCR
reaction chambers 11, and exit reservoirs 9. Id. Petitioner contends that Zou
I’s valve 8 and channel 31 together comprise a “separate sample inlet” as
shown in detail in Figure 3. Id. (citing Ex. 1008, 4:43–47; Ex. 1026 ¶¶ 22–
23).
Patent Owner argues that “Zou I does not disclose multiple separate
microfluidic networks, but a single microfluidic network” because “Zou I
has a single ‘common reservoir 7’ that directs fluid to individual chambers
(11) through a single channel (31).” PO Resp. 30. Patent Owner explains its
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contention by reference to an annotated version of Figure 4, reproduced
below.

Id. In the annotated version of Figure 4 above, Patent Owner’s pink shading
shows that “the PCR reaction zones (chambers 11) and the common
reservoir are in fluid communication with one another and are part of a
single fluidic network.” Id. (citing Ex. 1008, 4:1–6). Patent Owner further
argues that “Zou I is clear that reservoir 7 is its ‘inlet fluid source reservoir;”
(id. at 31 (citing Ex. 1008, 4:36, 6:12–15)) and reservoir 7 “is the inlet for all
three chambers, as fluid is dispensed from that reservoir into each chamber
... Zou I discloses multiple reaction chambers that share a common inlet, as
opposed to distinct, independent inlets for the network associated with each
chamber ….” Id. (citing Ex. 2036 ¶ 171). 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
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“reservoir 7.” Id. at 32 (citing Ex. 1008, 4:36, 6:12–15). According to
Patent Owner, “an ‘inlet’ is a term common in both the ’900 patent and Zou
I, and would have been understood to refer to a location where sample is
input.” Id. (citing Ex. 2036 ¶¶ 172–173).
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 5–6 (citing
Ex. 1008, 4:4; Ex. 1026 ¶ 25). 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 ’900 patent is ‘a location
where the sample is input into the cartridge.’” Sur-Reply 8 (citing Ex. 1008,
4:1–6, Figs. 3 & 4; Ex. 2036 ¶¶ 376–378; Ex. 1027, 156:2–9; Ex. 1003,
15:4–7) (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 our
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. 31–32; Reply 7–10. As shown in Patent Owner’s annotation of
Zou I’s Figure 4 supra, “the PCR reaction zones (chambers 11) and the
common reservoir are in fluid communication with one another as a single
fluidic network.” Id. at 30 (citing 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
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unintended entry of fluid into the chamber.” Ex. 1008, 4:30–35, 4:43–45.
We credit Dr. Northrup’s testimony that
[a]n “inlet” is a common term used in the [’900] 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.
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 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) 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.
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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).
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.” Reply 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
chambers.” Ex. 1008, 3:24–25, 5:11–13. In light of these disclosures in
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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 ’900 patent.
Petitioner further argues in its Reply that it would have been obvious
to drill a fluid access hole in the glass cover of Zou I for each lane, because a
person of ordinary skill in the art “would have (i) been motivated to provide
physically distinct sample input ports, to avoid sample contamination, and
(ii) had a reasonable expectation of success in doing so, via the known
option of simply drilling fluid access holes in the glass cover.” Id. at 7–8
(citing Ex. 2036 ¶ 57; Ex. 1027, 166:12–167:1, 168:10–170:4; Ex. 1015
¶ 174; Ex. 1026 ¶ 30; Ex. 1008, 7:17–21). 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 person of ordinary skill would
have been motivated to make this modification, or how this modification
would have affected 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).
Patent Owner also raises issues with the newly introduced fluid flowing back
into the common reservoir and intermixing with other samples (id. at 11–12
(citing Ex. 2068, 256:18–257:14; Ex. 2036 ¶¶ 102–105, 375–378)), and
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evaporation of fluid samples resulting from the drilled access holes. Id. at
12 (citing Ex. 2021, 123). Petitioner does not rebut these points.
In an obviousness analysis, a sufficient reason must be shown as to
why a person of ordinary skill in the art 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 would have been a common technique
Pet. Reply 7. Petitioner’s argument and Dr. Gale’s testimony with respect to
the modification of Zou I leaves an analytical gap that does not apprise us of
why a person of ordinary skill 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 ’900 patent.
Here, Petitioner attempts to imbue a person of ordinary skill with the
knowledge of the claimed invention, when no prior art reference of record or
other evidence conveys or suggests that knowledge. Without such evidence,
Petitioner’s argument that a person of ordinary skill would have modified
Zou I in this way appears to be premised on Petitioner’s knowledge of the
’900 patent disclosure. This is improper hindsight reasoning. Petitioner
needed to explain what would have led a person of ordinary skill 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.”).
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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 discloses a multi-lane microfluidic
unit. We also note Petitioner’s contention that to the extent Zou I does not
expressly disclose a multi-lane microfluidic cartridge, “McNeely discloses at
least four multilane microfluidic cartridges, each of which can be used to
perform PCR on samples in the cartridge, with inlets and outlets for each
lane.” Pet. 34–35 (citing Ex. 1001 ¶¶ 79–80, 335; Ex. 1009 ¶¶ 96, 97, 138,
Figs. 5, 6). Patent Owner argues that the Petition did not present sufficient
evidence to support a contention that McNeely alone teaches this limitation
of the challenged claims (Tr. 75–76), and also disputes that McNeely
discloses multiple microfluidic lanes for performing reactions in parallel.
PO Resp. 20. After considering the complete trial record, we determine that
Petitioner also has not established by a preponderance of the evidence that
McNeely discloses this limitation of the challenged claims. Petitioner
presents no argument or evidence in support of its contention, other than the
single sentence of the Petition quoted above, which also appears in the Gale
Declaration. This conclusory assertion, without further explanation, fails to
meet Petitioner’s burden to demonstrate invalidity by a preponderance of the
evidence.
Accordingly, we find that Petitioner has not established that the
combination of Zou I and McNeely or Pourahmadi teaches a “multi-lane
microfluidic cartridge, each lane comprising a PCR reaction zone” as
required by the challenged claims.
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b) Combination of Zou I and McNeely or
Pourahmadi
Petitioner contends that a person of ordinary skill in the art would
have been motivated to combine Zou I’s PCR unit with a conventional
integrated machine such as in Pourahmadi or McNeely, with a reasonable
expectation of success. Pet. 27–32.
Petitioner relies on Zou I as teaching a microfluidic PCR “unit,” or
“chip,” but not a cartridge. E.g. Pet. 27 (“the PCR unit of Zou I;” Zou I’s
“microfluidic chip”), 28 (“Zou I’s multi-sample PCR unit”); Pet. Reply 10
(“a multi-lane microfluidic unit like Zou I”), 12–13 (“use Zou I’s chip with
current macro thermal cycler machines”), 14–15 (“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 7 (citing Ex. 1008, 7:51–62, 8:45–63; PO Resp. 14–15, 30–
31; Ex. 2036 ¶¶ 97–100, 537–538; Ex. 2068, 114:2–11; Ex. 2012, 179:21–
180:5, 184:3–188:9, 220:5–221:15).
As to the cartridge requirement of the challenged claims, Petitioner
relies on Pourahmadi or McNeely as teaching a cartridge as part of a “multi-
cartridge integrated machine.” Pet. 27. Specifically, Petitioner argues that
Pourahmadi “discloses at least four microfluidic cartridges, each of which
can be used to perform PCR on samples in the cartridge” id. at 35 (citing Ex.
1001 ¶ 335; e.g. Ex. 1015 ¶¶ 13, 48, 54, 76, 77, 123, 129), and that
“McNeely discloses at least four multilane microfluidic cartridges, each of
which can be used to perform PCR on samples in the cartridge, with inlets
and outlets for each lane.” Id. at 34–35 (citing Ex. 1001 ¶ 79–80, 335; Ex.
1009 ¶¶ 96, 97, 138, Figs. 5, 6). The Petition does not point to any teaching
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in Pourahmadi of using a microfluidic unit or chip with Pourahmadi’s
cartridge. In the Reply, however, Petitioner argues Pourahmadi “teaches
various known ways a POSA could generally ‘incorporate[]’ microfluidic
chips into cartridges – for example, ‘silicon glue,’ ‘fused or welded,’ or
‘recessed regions’ that are ‘dimensioned’ to accept the microfluidic chip.”
Pet. Reply 17 (citing Ex. 1015 ¶¶ 176–181; Ex. 1026 ¶¶ 119, 121).
Petitioner presents various reasons why a person of ordinary skill
would have been motivated to combine Zou I with Pourahmadi or McNeely.
Pet. 27–32. Several of these reasons relate specifically to the combination of
Zou I’s microfluidic unit with a cartridge, such as: “Zou I itself expressly
teaches combining its microfluidic chip into existing machines” such as
Pourahmadi or McNeely (id. at 27 (citing Ex. 1001 ¶¶ 118, 318; Ex. 1008,
1:62–65, 8:15–17)); “inclusion of Zou I’s multi-sample PCR unit in multiple
cartridges of a single machine would be a workload or throughput
multiplier” (id. at 28); “the cartridges of McNeely or Pourahmadi, would
have predictably provided the necessary interfacing with the outside world”
(id. at 30 (citing Ex. 1001 ¶¶ 123–124, 325)); “a POSA would have known
that one needed to ‘package’ or ‘interface’ the microfluidic chip in a way
that allowed an operator to quickly and efficiently interact with it” (id.
(citing e.g. Ex. 1009, Abstract, ¶¶ 24, 82, 138–140)); and “incorporating the
Zou I unit into a cartridge to be operated on by a machine ... would have
provided the well-known benefit of better and more consistent control on the
conditions to which the sample was exposed ... [i]t would also have reduced
the potential for contamination of the sample, or for the sample to
contaminate the laboratory working area ... would also have been expected
to improve safety ....” (id. at 31 (citing Ex. 1001 ¶ 329–330; Ex. 1009 ¶ 9;
Ex. 1020, 16:17–22)). In its Reply, Petitioner argues “a POSA would have
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had a reasonable expectation of success” because the level of ordinary skill
was high, the art was relatively advanced, and “the combinations are
straightforward – Zou I’s fully functional multi-lane microfluidic unit,
virtually unaltered and maintaining its ‘basic principles of operation,’ into
Pourahmadi or McNeely’s cartridge-based systems.” Pet. Reply 14–15.
Petitioner argues that “using a microfluidic PCR chip like Zou I as a
cartridge was routine and predictable by March 2006.” Id. at 18 (citing Ex.
1026 ¶¶ 119–121; 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 this is “a very complex field” (id. at 18 (citing Ex. 2036 ¶¶ 32–
42; Ex. 2018, 2121)), “the state of the art was early and aspirational” (id. at
17 (citing Ex. 2036 ¶¶ 25–42; Ex. 2018, 2121)), none of the references teach
how to interface a generic chip with a cartridge, “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. (citing Ex. 2068, 149:4–150:13; Ex. 2057, 170; Ex. 2002, 245–248,
259–261; Ex. 2058, 536; Ex. 2036 ¶ 99)), and “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. 1003,
845; Ex. 2001, 16.5.1; Ex. 2023, 346–353)). Patent Owner further argues
that specific features of Zou I’s chip do not support a motivation to combine,
e.g. fragility of the monocrystalline silicon beams that connect each of Zou
I’s PCR reaction chambers to the frame (PO Resp. 37–38 (citing Ex. 1008,
4:17–21, Figs. 1B, 4; Ex. 2012, 44:18–22)); PO Sur-Reply 18–19 (citing Ex.
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1026 ¶¶ 51–52; 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 Pourahmadi teaches multi-lane microfluidic
cartridges, because Petitioner has failed to establish by a preponderance of
the evidence that a person of ordinary skill in the art would reasonably have
expected to be successful in combining Zou I’s microfluidic chip with a
cartridge as taught by McNeely or Pourahmadi. 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,
1327–28 (Fed. Cir. 2012) (quoting Pfizer, Inc. v. Apotex, Inc., 480 F.3d
1348, 1361 (Fed. Cir. 2007). A petitioner must 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.
Focusing on the parties’ arguments pertaining to how Zou I and
McNeely or Pourahmadi 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 person having
ordinary skill in the art would have had a reasonable expectation of success
in attempting to combine the teachings of Zou I with McNeely or
Pourahmadi. Although the Petition sets forth various rationales for why a
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person of ordinary skill would have had reason to combine the teachings of
Zou I and McNeely or Pourahmadi (Pet. 27–32), the rationales are general in
nature and do not address any specific modification to either of the
references. Further, 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 PCR unit of Zou I with a multi-cartridge
integrated machine such as in McNeely or Pourahmadi, with a high
expectation of success.” Pet. 27. The Gale Declaration is similarly
conclusory as to how Zou I and McNeely or Pourahmadi could have been
combined by the ordinary artisan, and does not elaborate on the artisan’s
reasonable expectation of success. 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). Thus,
Petitioner did not make out its obviousness case based on combining Zou I
and McNeely or Pourahmadi, in the Petition. 35 U.S.C. § 312(a)(3).
As discussed above, Petitioner in its Reply identifies teachings in
Pourahmadi regarding “known ways a POSA could generally ‘incorporate[]’
microfluidic chips into cartridges.” Pet. Reply 17 (citing Ex. 1015 ¶¶ 176–
181; Ex. 1026 ¶¶ 119–121), and also relies on McNeely as teaching “various
options for clamping its ‘interface device’ to a glass slide to create a
cartridge 604.” Id. (citing Ex. 1009, Figs. 2, 23–24, 30, 32, ¶¶ 82, 126–129;
Ex. 1026 ¶ 120). Petitioner’s assertion that “using a microfluidic PCR chip
like Zou I as a cartridge was routine and predictable by March 2006” (Pet.
Reply 18), however, is based on Exhibit 1030, which Petitioner did not
submit with the Petition.
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Moreover, we find persuasive Patent Owner’s arguments that
microfluidic PCR was not routine and predictable by March 2006, but rather
a very complex field 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. Dr. Northrup provides factual
substantiation for Patent Owner’s arguments, with reference to numerous
contemporaneous publications in the field (Exs. 2001, 2002, 2023, 2026,
2032, 2033) that persuasively explain why “[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 person of ordinary skill would not
reasonably have expected a combination of Zou I and McNeely or
Pourahmadi to be successful, because of the particular challenges listed
above. Ex. 2036 ¶¶ 811–825. Dr. Gale’s testimony that interfacing a PCR
chip with a cartridge, such as Zou I with McNeely or Pourahmadi, would
require that they be 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 combination
of Zou I’s unit with Pourahmadi’s cartridge. Ex. 2036 ¶¶ 753–759. As Dr.
Northrup explains, 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
IPR2019-00490
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39
system on a single chip, i.e. combining Zou I’s chip with another chip
capable of providing other functionalities. Id. Additional evidence (Ex.
2001) corroborates Dr. Northrup’s opinion, which is unrebutted on this
point.
We disagree with Petitioner’s assertions that combining Zou I and
McNeely or Pourahmadi to arrive at the claimed invention would have been
“straightforward” and that “each of Zou I, Pourahmadi, and McNeely
already disclosed functional microfluidic cartridge devices for performing
PCR” (Pet. Reply 15, 17), because the evidence presented by Patent Owner
and Dr. Northrup’s testimony, as discussed above, contradicts those
assertions. 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, and that “Zou I’s unit is more or
less a cartridge itself” (Ex. 1026 ¶¶ 67, 70, 105) are conclusory and not
supported by the evidence of record. In particular, we note that Dr. Gale’s
statements that Zou I’s unit “would have been easily combined, virtually
unaltered, into Pourahmadi or McNeely’s cartridge-based systems” and that
“[a]t most, a POSA would have to attach Zou I’s multi-lane microfluidic unit
to a very basic cartridge housing sized to fit the receiving bay of Pourahmadi
or McNeely” are unsupported by sufficient analysis or objective evidence.
Id. ¶ 114. They are also inconsistent with Dr. Gale’s testimony that a POSA
would have combined “Zou I’s multi-sample 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 ¶ 312;
see also id. ¶¶ 76 (“Zou I further provides examples of a multi-lane
microfluidic unit for conducting PCR on multiple samples.”), 322
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(“implementing Zou I’s multi-sample PCR unit in each of the four cartridges
of McNeely. . . . Zou I’s multi-sample PCR unit in each of the multiple
cartridges of a machine such as disclosed by McNeely or Pourahmadi”); 329
(“incorporating the Zou I unit into a cartridge configured to be operated on a
machine such as McNeely or Pourahmadi”); 331 (“Zou I discloses multi-
lane microfluidic units”); Ex. 1026 ¶ 119 (“using a microfluidic PCR chip-
like unit like Zou I, in a cartridge-based machine such as Pourahmadi or
McNeely, was common and routine by March 2006”). Furthermore, Dr.
Gale does not address the evidence supporting Dr. Northrup’s testimony
regarding the complexity of connecting microfluidic chips to heat sources or
detectors, as discussed above. Thus, we would remain unpersuaded that
Petitioner met its evidentiary burden of showing particular evidence that
supports its proposed combination even if the evidence and arguments from
Petitioner’s Reply had been set forth properly in the Petition.
c) Conclusion
For the foregoing reasons, we conclude that Petitioner has not
demonstrated by a preponderance of the evidence that claims 1–8, 12, 14,
15, 17, and 19–22 of the ’900 patent would have been obvious over the
combined teachings of Zou I and McNeely or Pourahmadi.12
D. Claims 9–11, 13, 16, and 18
Petitioner argues that: (1) claims 9–11 and 13 would have been
obvious over the combined teachings of Zou I, McNeely or Pourahmadi, and

12 Patent Owner argues that objective indicia (namely, commercial success)
support the nonobviousness of the challenged claims. PO Resp. 62–64.
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 8,323,900 B2
41
Zou II; (2) claim 18 would have been obvious over the combined teachings
of Zou I, McNeely or Pourahmadi, and Chow; and (3) claim 16 would have
been obvious over the combined teachings of Zou I and McNeely or
Pourahmadi, and Duong. Pet. 65–80. Each of claims 9–11, 13, 16, and 18
depend, directly or indirectly, from independent claim 1 or 7, and, therefore,
require “multi-lane microfluidic cartridges, each lane comprising a PCR
reaction zone.” Ex. 1003, 47:5–48:9. Thus, for the same reasons given
above with regard to Petitioner’s challenge of claim 1, we conclude that
Petitioner has not demonstrated by a preponderance of the evidence that 9–
11, 13, 16, and 18 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 under Federal
Rules of Evidence 402 and 403. Paper 43. We have not considered either of
these exhibits in reaching our decision, and therefore Patent Owner’s motion
is dismissed as moot.
IV. CONCLUSION
Petitioner has not shown by a preponderance of the evidence that
claims 1–22 are unpatentable under 35 U.S.C. § 103(a) in view of the
various proposed combinations of prior art references.
V. ORDER
In consideration of the foregoing, it is hereby:
ORDERED that Petitioner has not shown by a preponderance of the
evidence that claims 1–22 of the ’900 Patent are unpatentable;
FURTHER ORDERED that Patent Owner’s Motion to Exclude is
dismissed as moot; and
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Patent 8,323,900 B2
42
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.

In summary:

Claims

35
U.S.C.
§
Reference(s)/Basis Claims
Shown
Unpatentable
Claims
Not shown
Unpatentable
1–8, 12,
14, 15, 17,
19–22
103 Zou I and
McNeely or
Pourahmadi
1–8, 12, 14,
15, 17, 19–22
9–11, 13 103 Zou I, McNeely or
Pourahmadi, and
Zou II
9–11, 13
18 103 Zou I, McNeely or
Pourahmadi, and
Chow
18
16 103 Zou I, McNeely or
Pourahmadi, and
Duong
16
Overall
Outcome
1–22
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Patent 8,323,900 B2
43
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